FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Jones, SB
Thomas, GA
Hesselsweet, SD
Alvarez-Reeves, M
Yu, H
Irwin, ML
AF Jones, Sara B.
Thomas, Gwendolyn A.
Hesselsweet, Sara D.
Alvarez-Reeves, Marty
Yu, Herbert
Irwin, Melinda L.
TI Effect of Exercise on Markers of Inflammation in Breast Cancer
Survivors: The Yale Exercise and Survivorship Study
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID C-REACTIVE PROTEIN; RANDOMIZED CONTROLLED-TRIAL; TYPE-2
DIABETES-MELLITUS; CORONARY-HEART-DISEASE; INDUCED WEIGHT-LOSS;
POSTMENOPAUSAL WOMEN; PHYSICAL-ACTIVITY; ADIPOSE-TISSUE; CIRCULATING
INTERLEUKIN-6; AEROBIC EXERCISE
AB Physical activity is associated with improved breast cancer survival, but the underlying mechanisms, possibly including modification of the inflammatory state, are not well understood. We analyzed changes in interleukin (IL)-6, C-reactive protein (CRP), and TNF-alpha in a randomized controlled trial of exercise in postmenopausal breast cancer survivors. Seventy-five women, recruited through the Yale-New Haven Hospital Tumor Registry, were randomized to either a six-month aerobic exercise intervention or usual care. Correlations were calculated between baseline cytokines, adiposity, and physical activity measures. Generalized linear models were used to assess the effect of exercise on IL-6, CRP, and TNF-alpha. At baseline, IL-6 and CRP were positively correlated with body fat and body mass index (BMI) and were inversely correlated with daily pedometer steps (P < 0.001). We found no significant effect of exercise on changes in inflammatory marker concentrations between women randomized to exercise versus usual care, though secondary analyses revealed a significant reduction in IL-6 among exercisers who reached 80% of the intervention goal compared with those who did not. Future studies should examine the effect of different types and doses of exercise and weight loss on inflammatory markers in large-scale trials of women diagnosed with breast cancer. Cancer Prev Res; 6(2); 109-18. (C)2012 AACR.
C1 [Jones, Sara B.; Thomas, Gwendolyn A.; Hesselsweet, Sara D.; Yu, Herbert; Irwin, Melinda L.] Yale Univ, Sch Publ Hlth, New Haven, CT 06520 USA.
[Alvarez-Reeves, Marty] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Irwin, ML (reprint author), Yale Univ, Sch Publ Hlth, POB 208034, New Haven, CT 06520 USA.
EM melinda.irwin@yale.edu
FU American Cancer Society [MRSG 04 006 01 CPPB]; Susan G. Komen Breast
Cancer Foundation [BCTR0201916]; General Clinical Research Center grant
from the National Center of Research Resources, NIH [M01-RR00125];
National Institute of Nursing Research [T32 NR008346]
FX This study was supported by American Cancer Society (MRSG 04 006 01
CPPB) and the Susan G. Komen Breast Cancer Foundation (BCTR0201916).
Supported in part by a General Clinical Research Center grant from the
National Center of Research Resources, NIH (grant # M01-RR00125) awarded
to Yale University School of Medicine and the National Institute of
Nursing Research (Research Training: Self and Family Management Research
T32 NR008346).
NR 64
TC 20
Z9 21
U1 3
U2 13
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1940-6207
J9 CANCER PREV RES
JI Cancer Prev. Res.
PD FEB
PY 2013
VL 6
IS 2
BP 109
EP 118
DI 10.1158/1940-6207.CAPR-12-0278
PG 10
WC Oncology
SC Oncology
GA 086IF
UT WOS:000314676600006
PM 23213072
ER
PT J
AU Adam, M
Huang, HD
Shahzad, SA
Kar, B
Virani, SS
Rogers, PA
Paniagua, D
Bozkurt, B
Palacios, I
Kleiman, NS
Jneid, H
AF Adam, Mahboob
Huang, Henry D.
Shahzad, Saima A.
Kar, Biswajit
Virani, Salim S.
Rogers, Paul A.
Paniagua, David
Bozkurt, Biykem
Palacios, Igor
Kleiman, Neal S.
Jneid, Hani
TI Percutaneous Coronary Intervention vs. Coronary Artery Bypass Graft
Surgery for Unprotected Left Main Coronary Artery Disease in the
Drug-Eluting Stents Era - An Aggregate Data Meta-Analysis of 11,148
Patients
SO CIRCULATION JOURNAL
LA English
DT Article
DE Coronary artery bypass grafting; Meta-analysis; Percutaneous coronary
intervention; Unprotected left main coronary artery
ID LONG-TERM OUTCOMES; AGED GREATER-THAN-OR-EQUAL-TO-75 YEARS; BARE-METAL
STENTS; SURGICAL REVASCULARIZATION; SYNTAX TRIAL; TASK-FORCE; FOLLOW-UP;
STENOSIS; REGISTRY; IMPLANTATION
AB Background: Patients with unprotected left main coronary artery (LMCA) disease are increasingly treated with percutaneous coronary intervention (PCI) using drug-eluting stents (DES), but its benefits compared with coronary artery bypass grafting (CABG) remain controversial. We hypothesized that PCI with DES for unprotected LMCA disease is safe and effective compared with CABG.
Methods and Results: We performed aggregate data meta-analyses of clinical outcomes [death; non-fatal myocardial infarction (MI); stroke; repeat revascularization; and major adverse cardiac and cerebrovascular events (MACCE)] in studies comparing PCI with DES vs. CABG in patients with LMCA disease. A comprehensive literature search (01/01/2003 to 12/01/2011) identified 27 studies comparing PCI and CABG (11,148 patients). Summary odds ratios (OR) were calculated using a random-effects model. At 30 days, PCI for unprotected LMCA disease was associated with lower MACCE [odds ratio (OR) 0.57, 95% confidence interval (CI) 0.36-0.89) and stroke rates (OR 0.22, 95% CI 0.11-0.44) compared with CABG. At 12 months, the PCI group experienced higher rates of repeat revascularization (OR 3.72, 95% CI 2.75-5.03), but lower rates of stroke (OR 0.25, 95% CI 0.14-0.44) and all-cause death (OR 0.69, 95% CI 0.49-0.97). At the longest follow-up of 60 months, PCI was associated with equivalent mortality, lower rates of stroke (OR 0.42, 95% CI 0.28-0.62) and higher rates of MACCE (OR 1.30, 95% CI 1.10-1.55) and repeat revascularization (OR 3.54, 95% CI 2.75-4.54).
Conclusions: In the DES era, PCI for unprotected LMCA disease is associated with equivalent mortality and MI, lower stroke rates and higher rates of repeat revascularization compared with CABG. (Circ J 2013; 77: 372-382)
C1 [Adam, Mahboob; Huang, Henry D.; Shahzad, Saima A.; Rogers, Paul A.; Paniagua, David; Bozkurt, Biykem; Jneid, Hani] Baylor Coll Med, Houston, TX 77030 USA.
[Shahzad, Saima A.] Al Noor Specialist Hosp, Mecca, Saudi Arabia.
[Kar, Biswajit; Virani, Salim S.; Paniagua, David; Bozkurt, Biykem; Jneid, Hani] Michael E DeBakey VA Med Ctr, Houston, TX USA.
[Palacios, Igor] Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA.
[Palacios, Igor] Harvard Univ, Sch Med, Boston, MA USA.
[Kleiman, Neal S.] Methodist DeBakey Heart & Vasc Ctr, Houston, TX USA.
[Kleiman, Neal S.] Weill Cornell Med Coll, New York, NY USA.
RP Jneid, H (reprint author), Baylor Coll Med, Michael E DeBakey VA Med Ctr, 2002 Holcombe Blvd 3C-300A, Houston, TX 77030 USA.
EM jneid@bcm.edu
OI Virani, Salim/0000-0001-9541-6954
FU Department of Veterans Affairs Health Services Research and Development
Service (HSR&D) Career Development Award [CDA-09-028]
FX Dr Virani is supported by a Department of Veterans Affairs Health
Services Research and Development Service (HSR&D) Career Development
Award (CDA-09-028).
NR 49
TC 0
Z9 0
U1 0
U2 8
PU JAPANESE CIRCULATION SOC
PI KYOTO
PA KINKI INVENTION CENTER, 14 YOSHIDA KAWAHARACHO, SAKYO-KU, KYOTO,
606-8305, JAPAN
SN 1346-9843
J9 CIRC J
JI Circ. J.
PD FEB
PY 2013
VL 77
IS 2
BP 372
EP 382
DI 10.1253/circj.CJ-12-0747
PG 11
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 080SG
UT WOS:000314263000019
ER
PT J
AU Lochhead, P
Chan, AT
AF Lochhead, Paul
Chan, Andrew T.
TI Statins and Colorectal Cancer
SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
LA English
DT Article
DE Statin; Colon; Rectum; Adenoma; Chemoprevention
ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; MORPHOGENETIC PROTEIN PATHWAY;
RANDOMIZED CONTROLLED-TRIAL; AVERAGE CHOLESTEROL LEVELS; LOWERING LDL
CHOLESTEROL; A REDUCTASE INHIBITORS; LONG-TERM USE; COLON-CANCER;
FOLLOW-UP; CARDIOVASCULAR-DISEASE
AB The 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, more commonly referred to as statins, comprise a family of lipid-lowering drugs that are prescribed on a global scale on account of their proven safety and efficacy in reducing mortality from cardiovascular disease. Beyond their potent pharmacologic inhibition of cholesterol biosynthesis, statins appear to have pleiotropic effects, including modulation of cell growth, apoptosis, and inflammation. Through modulation of these pathways, statins have the potential to influence a wide range of disease processes, including cancer. Much attention has focused on the association between statins and colorectal cancer, raising the prospect that these well-tolerated compounds could form the basis of future chemopreventive strategies. Herein, we review the epidemiologic, clinical, and preclinical data relevant to statins and colorectal neoplasia, and discuss the current status and future potential of statins as chemopreventive agents.
C1 [Lochhead, Paul] Univ Aberdeen, Inst Med Sci, Gastrointestinal Res Grp, Div Appl Med, Aberdeen, Scotland.
[Lochhead, Paul] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA.
[Chan, Andrew T.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA.
[Chan, Andrew T.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
RP Chan, AT (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, GRJ 722,55 Fruit St, Boston, MA 02114 USA.
EM achan@partners.org
FU Clinical Academic Fellowship from the Chief Scientist Office of the
Scottish Government; Damon Runyon Clinical Investigator award
FX Supported by a Clinical Academic Fellowship from the Chief Scientist
Office of the Scottish Government (P.L.), and a Damon Runyon Clinical
Investigator award (A.C.).
NR 101
TC 23
Z9 23
U1 1
U2 20
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1542-3565
J9 CLIN GASTROENTEROL H
JI Clin. Gastroenterol. Hepatol.
PD FEB
PY 2013
VL 11
IS 2
BP 109
EP 118
DI 10.1016/j.cgh.2012.08.037
PG 10
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 086RU
UT WOS:000314705400006
PM 22982096
ER
PT J
AU Kentsis, A
Shulman, A
Ahmed, S
Brennan, E
Monuteaux, MC
Lee, YH
Lipsett, S
Paulo, JA
Dedeoglu, F
Fuhlbrigge, R
Bachur, R
Bradwin, G
Arditi, M
Sundel, RP
Newburger, JW
Steen, H
Kim, S
AF Kentsis, Alex
Shulman, Andrew
Ahmed, Saima
Brennan, Eileen
Monuteaux, Michael C.
Lee, Young-Ho
Lipsett, Susan
Paulo, Joao A.
Dedeoglu, Fatma
Fuhlbrigge, Robert
Bachur, Richard
Bradwin, Gary
Arditi, Moshe
Sundel, Robert P.
Newburger, Jane W.
Steen, Hanno
Kim, Susan
TI Urine proteomics for discovery of improved diagnostic markers of
Kawasaki disease
SO EMBO MOLECULAR MEDICINE
LA English
DT Article
DE biomarker; Kawasaki disease; mass spectrometry; vasculitis; urinary
proteome
ID CORONARY-ARTERY INVOLVEMENT; AMERICAN-HEART-ASSOCIATION;
MASS-SPECTROMETRY; SERUM INTERLEUKIN-6; NATIONWIDE SURVEY;
RHEUMATIC-FEVER; CHILDREN; BIOMARKERS; EXPRESSION; ANEURYSMS
AB Kawasaki disease (KD) is a systemic vasculitis of unknown etiology. Absence of definitive diagnostic markers limits the accuracy of clinical evaluations of suspected KD with significant increases in morbidity. In turn, incomplete understanding of its molecular pathogenesis hinders the identification of rational targets needed to improve therapy. We used high-accuracy mass spectrometry proteomics to analyse over 2000 unique proteins in clinical urine specimens of patients with KD. We discovered that urine proteomes of patients with KD, but not those with mimicking conditions, were enriched for markers of cellular injury such as filamin and talin, immune regulators such as complement regulator CSMD3, immune pattern recognition receptor muclin, and immune cytokine protease meprin A. Significant elevations of filamin C and meprin A were detected in both the serum and urine in two independent cohorts of patients with KD, comprised of a total of 236 patients. Meprin A and filamin C exhibited superior diagnostic performance as compared to currently used markers of disease in a blinded case-control study of 107 patients with suspected KD, with receiver operating characteristic areas under the curve of 0.98 (95% confidence intervals [CI] of 0.971 and 0.951, respectively). Notably, meprin A was enriched in the coronary artery lesions of a mouse model of KD. In all, urine proteome profiles revealed novel candidate molecular markers of KD, including filamin C and meprin A that exhibit excellent diagnostic performance. These disease markers may improve the diagnostic accuracy of clinical evaluations of children with suspected KD, lead to the identification of novel therapeutic targets, and allow the development of a biological classification of Kawasaki disease.
C1 [Kentsis, Alex] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Oncol,Dept Pediat Oncol,Boston Childr, Boston, MA 02115 USA.
[Shulman, Andrew; Dedeoglu, Fatma; Fuhlbrigge, Robert; Sundel, Robert P.; Kim, Susan] Harvard Univ, Sch Med, Div Immunol, Rheumatol Program,Boston Childrens Hosp, Boston, MA USA.
[Ahmed, Saima; Paulo, Joao A.; Steen, Hanno] Harvard Univ, Sch Med, Dept Pathol, Prote Ctr,Boston Childrens Hosp, Boston, MA 02115 USA.
[Brennan, Eileen; Bradwin, Gary] Harvard Univ, Sch Med, Dept Lab Med, Boston Childrens Hosp, Boston, MA USA.
[Monuteaux, Michael C.; Lipsett, Susan; Bachur, Richard] Harvard Univ, Sch Med, Boston Childrens Hosp, Div Emergency Med, Boston, MA USA.
[Arditi, Moshe] Cedars Sinai Med Ctr, Dept Pediat, Infect & Immunol Dis Res Ctr, Los Angeles, CA 90048 USA.
[Newburger, Jane W.] Harvard Univ, Sch Med, Dept Cardiol, Boston Childrens Hosp, Boston, MA USA.
RP Steen, H (reprint author), Harvard Univ, Sch Med, Dept Pathol, Prote Ctr,Boston Childrens Hosp, Boston, MA 02115 USA.
EM hanno.steen@childrens.harvard.edu; susan.kim@childrens.harvard.edu
OI Kentsis, Alex/0000-0002-8063-9191; Sundel, Robert/0000-0002-0083-5695;
Bachur, Richard/0000-0001-8831-014X
FU Boston Children's Hospital Division of Immunology Pilot Grant;
Translational Research Program Pilot Grant; Boston Children's Hospital
Clinical Research Program; Harvard Catalyst; Harvard Clinical and
Translational Science Center [UL1 RR 025758]; National Institutes of
Health [U01 HL068285, RR 02172, U01 HL068270, U01 HL068269, U01
HL068292, U01 HL068290, U01 HL068288, U01 HL068281, U01 HL068279];
[NIH-K08CA160660]
FX We thank the staff of the Boston Children's Hospital Rheumatology and
Cardiology Programs for help with patient recruitment. This research was
funded by the Boston Children's Hospital Division of Immunology Pilot
Grant, Translational Research Program Pilot Grant and supported by the
Boston Children's Hospital Clinical Research Program and Harvard
Catalyst. The Harvard Clinical and Translational Science Center (UL1 RR
025758). Collection of sera by the Pediatric Heart Network centres was
supported by U01 HL068285, RR 02172, U01 HL068270, U01 HL068269, U01
HL068292, U01 HL068290, U01 HL068288, U01 HL068281 and U01 HL068279 from
the National Institutes of Health. AK is supported by the
NIH-K08CA160660.
NR 45
TC 29
Z9 31
U1 0
U2 14
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1757-4676
J9 EMBO MOL MED
JI EMBO Mol. Med.
PD FEB
PY 2013
VL 5
IS 2
BP 210
EP 220
DI 10.1002/emmm.201201494
PG 11
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 086CW
UT WOS:000314661800008
PM 23281308
ER
PT J
AU Desai, A
Bekelis, K
Thadani, VM
Roberts, DW
Jobst, BC
Duhaime, AC
Gilbert, K
Darcey, TM
Studholme, C
Siegel, A
AF Desai, Atman
Bekelis, Kimon
Thadani, Vijay M.
Roberts, David W.
Jobst, Barbara C.
Duhaime, Ann-Christine
Gilbert, Karen
Darcey, Terrance M.
Studholme, Colin
Siegel, Alan
TI Interictal PET and ictal subtraction SPECT: Sensitivity in the detection
of seizure foci in patients with medically intractable epilepsy
SO EPILEPSIA
LA English
DT Article
DE Epilepsy surgery; Seizure localization; Epilepsy imaging
ID TEMPORAL-LOBE EPILEPSY; POSITRON-EMISSION-TOMOGRAPHY;
COMPUTED-TOMOGRAPHY; FDG-PET; MRI; SURGERY; ABNORMALITIES; EEG;
LATERALIZATION; PATHOLOGY
AB Purpose: Interictal positron emission tomography (PET) and ictal subtraction single photon emission computed tomography (SPECT) of the brain have been shown to be valuable tests in the presurgical evaluation of epilepsy. To determine the relative utility of these methods in the localization of seizure foci, we compared interictal PET and ictal subtraction SPECT to subdural and depth electrode recordings in patients with medically intractable epilepsy. Methods: Between 2003 and 2009, clinical information on all patients at our institution undergoing intracranial electroencephalography (EEG) monitoring was charted in a prospectively recorded database. Patients who underwent preoperative interictal PET and ictal subtraction SPECT were selected from this database. Patient characteristics and the findings on preoperative interictal PET and ictal subtraction SPECT were analyzed. Sensitivity of detection of seizure foci for each modality, as compared to intracranial EEG monitoring, was calculated. Key Findings: Fifty-three patients underwent intracranial EEG monitoring with preoperative interictal PET and ictal subtraction SPECT scans. The average patient age was 32.7years (median 32years, range 160years). Twenty-seven patients had findings of reduced metabolism on interictal PET scan, whereas all 53 patients studied demonstrated a region of relative hyperperfusion on ictal subtraction SPECT suggestive of an epileptogenic zone. Intracranial EEG monitoring identified a single seizure focus in 45 patients, with 39 eventually undergoing resective surgery. Of the 45 patients in whom a seizure focus was localized, PET scan identified the same region in 25 cases (56% sensitivity) and SPECT in 39 cases (87% sensitivity). Intracranial EEG was concordant with at least one study in 41 cases (91%) and both studies in 23 cases (51%). In 16 (80%) of 20 cases where PET did not correlate with intracranial EEG, the SPECT study was concordant. Conversely, PET and intracranial EEG were concordant in two (33%) of the six cases where the SPECT did not demonstrate the seizure focus outlined by intracranial EEG. Thirty-three patients had surgical resection and >2years of follow-up, and 21 of these (64%) had Engel class 1 outcome. No significant effect of imaging concordance on seizure outcome was seen. Significance: Interictal PET and ictal subtraction SPECT studies can provide important information in the preoperative evaluation of medically intractable epilepsy. Of the two studies, ictal subtraction SPECT appears to be the more sensitive. When both studies are used together, however, they can provide complementary information.
C1 [Desai, Atman; Bekelis, Kimon; Roberts, David W.] Dartmouth Hitchcock Med Ctr, Neurosurg Sect, Lebanon, NH 03756 USA.
[Thadani, Vijay M.; Jobst, Barbara C.; Gilbert, Karen; Darcey, Terrance M.] Dartmouth Hitchcock Med Ctr, Dept Neurol, Lebanon, NH 03756 USA.
[Duhaime, Ann-Christine] Massachusetts Gen Hosp, Sect Pediat Neurosurg, Boston, MA 02114 USA.
[Studholme, Colin] Univ Washington, Dept Bioengn, Seattle, WA 98195 USA.
[Siegel, Alan] Dartmouth Hitchcock Med Ctr, Dept Radiol, Lebanon, NH 03756 USA.
RP Desai, A (reprint author), Dartmouth Hitchcock Med Ctr, Neurosurg Sect, 1 Med Ctr Dr, Lebanon, NH 03756 USA.
EM atman.desai@hitchcock.org
NR 31
TC 24
Z9 27
U1 0
U2 13
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0013-9580
J9 EPILEPSIA
JI Epilepsia
PD FEB
PY 2013
VL 54
IS 2
BP 341
EP 350
DI 10.1111/j.1528-1167.2012.03686.x
PG 10
WC Clinical Neurology
SC Neurosciences & Neurology
GA 087GT
UT WOS:000314750200018
PM 23030361
ER
PT J
AU Heinz, AJ
Peters, EN
Boden, MT
Bonn-Miller, MO
AF Heinz, Adrienne J.
Peters, Erica N.
Boden, Matthew T.
Bonn-Miller, Marcel O.
TI A Comprehensive Examination of Delay Discounting in a Clinical Sample of
Cannabis-Dependent Military Veterans Making a Self-Guided Quit Attempt
SO EXPERIMENTAL AND CLINICAL PSYCHOPHARMACOLOGY
LA English
DT Article
DE marijuana; Cannabis; cessation; delay discounting; impulsivity; relapse
ID ADULTS SEEKING TREATMENT; SUBSTANCE-USE DISORDERS; ALCOHOL-USE
DISORDERS; TIMELINE FOLLOW-BACK; MARIJUANA USE; BEHAVIORAL ECONOMICS;
TREATMENT SEEKERS; MONEY MANAGEMENT; DRUG-DEPENDENCE; REPORTED USE
AB Delay discounting (DD), an index of impulsivity, reflects individuals' preference for smaller immediate rewards to larger delayed rewards. The current study examined (a) relations between DD and quantity, frequency, and severity of Cannabis use, as well as several other measures of co-occurring substance use and clinical severity, and (b) whether DD predicted Cannabis-cessation outcomes. Cannabis-dependent United States (U. S.) veterans (N = 72; 95% male) who were interested in making serious self-quit attempts were evaluated prior to their cessation attempts, during which they completed a computerized DD task, and were followed throughout six months postattempt. Results indicated that higher DD was significantly correlated with higher compulsive craving for Cannabis (rho = .29, p < .05), younger age of first Cannabis use (r = -.32, p < .01), earlier commencement of regular Cannabis smoking (r = -.25, p < .05), and seeking professional help for a previous Cannabis quit attempt (rho = -.27, p < .05). DD did not significantly predict any Cannabis-cessation outcomes in the first week postattempt or during the 6-month follow-up. These results add to the literature on DD, which has focused on users of tobacco, alcohol, opioids, and cocaine, by demonstrating that DD is sensitive to developmental trajectories of Cannabis dependence, but does not reliably predict cessation outcomes. Results also suggest that DD may carry less relevance for Cannabis than for other substances of abuse.
C1 [Heinz, Adrienne J.; Boden, Matthew T.; Bonn-Miller, Marcel O.] Vet Affairs Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat, Palo Alto, CA USA.
[Heinz, Adrienne J.] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
[Peters, Erica N.] Friends Res Inst, Baltimore, MD USA.
[Peters, Erica N.] Yale Univ, Sch Med, New Haven, CT 06520 USA.
[Bonn-Miller, Marcel O.] Vet Affairs Palo Alto Hlth Care Syst, Natl Ctr Posttraumat Stress Disorder, Palo Alto, CA USA.
[Bonn-Miller, Marcel O.] Philadelphia Vet Affairs Med Ctr, Ctr Excellence Subst Abuse Treatment & Educ, Philadelphia, PA USA.
RP Heinz, AJ (reprint author), 795 Willow Rd,MPD 152, Menlo Pk, CA 94025 USA.
EM aheinz@stanford.edu
FU United States Department Veterans Affairs (VA); VA Health Services
Research and Development Service funds
FX Support for this research was provided by a United States Department
Veterans Affairs (VA) Clinical Science Research and Development Career
Development Award, Level 2, granted to Dr. Bonn-Miller, and VA Health
Services Research and Development Service funds were provided to Dr.
Heinz. These funding sources played no roles other than financial
support. The expressed views do not necessarily represent those of the
VA. The authors thank Neha Mitragotri, Johnna Medina, Meggan Bucossi,
Nicole Short, and Jessica Galang for their assistance with data
collection and management. All authors contributed in a significant way
to the manuscript and all authors have read and approved the final
manuscript.
NR 91
TC 13
Z9 13
U1 6
U2 27
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 1064-1297
EI 1936-2293
J9 EXP CLIN PSYCHOPHARM
JI Exp. Clin. Psychopharmacol.
PD FEB
PY 2013
VL 21
IS 1
BP 55
EP 65
DI 10.1037/a0031192
PG 11
WC Psychology, Biological; Psychology, Clinical; Pharmacology & Pharmacy;
Psychiatry
SC Psychology; Pharmacology & Pharmacy; Psychiatry
GA 084KG
UT WOS:000314537400007
PM 23379614
ER
PT J
AU Pekcec, A
Yigitkanli, K
Jung, JE
Pallast, S
Xing, CH
Antipenko, A
Minchenko, M
Nikolov, DB
Holman, TR
Lo, EH
van Leyen, K
AF Pekcec, Anton
Yigitkanli, Kazim
Jung, Joo Eun
Pallast, Stefanie
Xing, Changhong
Antipenko, Alexander
Minchenko, Maria
Nikolov, Dimitar B.
Holman, Theodore R.
Lo, Eng H.
van Leyen, Klaus
TI Following experimental stroke, the recovering brain is vulnerable to
lipoxygenase-dependent semaphorin signaling
SO FASEB JOURNAL
LA English
DT Article
DE eicosanoid; 12-HPETE; cortex; axon growth; second messenger
ID ENDOTHELIAL GROWTH-FACTOR; TRANSIENT FOCAL ISCHEMIA;
CEREBRAL-BLOOD-FLOW; UP-REGULATION; TUMOR ANGIOGENESIS; PERIINFARCT
CORTEX; NEUROVASCULAR UNIT; ARACHIDONIC-ACID; GENE-EXPRESSION; CONE
COLLAPSE
AB Recovery from stroke is limited, in part, by an inhibitory environment in the postischemic brain, but factors preventing successful remodeling are not well known. Using cultured cortical neurons from mice, brain endothelial cells, and a mouse model of ischemic stroke, we show that signaling from the axon guidance molecule Sema3A via eicosanoid second messengers can contribute to this inhibitory environment. Either 90 nM recombinant Sema3A, or the 12/15-lipoxygenase (12/15-LOX) metabolites 12-HETE and 12-HPETE at 300 nM, block axon extension in neurons compared to solvent controls, and decrease tube formation in endothelial cells. The Sema3A effect is reversed by inhibiting 12/15-LOX, and neurons derived from 12/15-LOX-knockout mice are insensitive to Sema3A. Following middle cerebral artery occlusion to induce stroke in mice, immunohistochemistry shows both Sema3A and 12/15-LOX are increased in the cortex up to 2 wk. To determine whether a Sema3A-dependent damage pathway is activated following ischemia, we injected recombinant Sema3A into the striatum. Sema3A alone did not cause injury in normal brains. But when injected into postischemic brains, Sema3A increased cortical damage by 79%, and again, this effect was reversed by 12/15-LOX inhibition. Our findings suggest that blocking the semaphorin pathway should be investigated as a therapeutic strategy to improve stroke recovery.-Pekcec, A., Yigitkanli, K., Jung, J. E., Pallast, S., Xing, C., Antipenko, A., Minchenko, M., Nikolov, D. B., Holman, T. R., Lo, E. H., van Leyen, K. Following experimental stroke, the recovering brain is vulnerable to lipoxygenase-dependent semaphorin signaling. FASEB J. 27, 437-445 (2013). www.fasebj.org
C1 [Pekcec, Anton; Yigitkanli, Kazim; Jung, Joo Eun; Pallast, Stefanie; Xing, Changhong; Lo, Eng H.; van Leyen, Klaus] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroprotect Res Lab,Dept Radiol, Charlestown, MA USA.
[Antipenko, Alexander; Minchenko, Maria; Nikolov, Dimitar B.] Sloan Kettering Inst, Dept Biol Struct, New York, NY USA.
[Holman, Theodore R.] Univ Calif Santa Cruz, Dept Chem & Biochem, Santa Cruz, CA 95064 USA.
RP van Leyen, K (reprint author), Massachusetts Gen Hosp, Neuroprotect Res Lab, 149 13th St,R 2401, Charlestown, MA 02129 USA.
EM klaus_vanleyen@hms.harvard.edu
RI van Leyen, Klaus/C-9126-2013
FU U.S. National Institutes of Health [NS049430, NS069939, NS048372,
GM056062]
FX The authors thank Dr. Emiri Mandeville for help with the injection
experiments. This work was supported by U.S. National Institutes of
Health grants NS049430 and NS069939 to K. V. L., NS048372 to D.B.N., and
GM056062 to T.R.H.
NR 66
TC 16
Z9 18
U1 0
U2 9
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD FEB
PY 2013
VL 27
IS 2
BP 437
EP 445
DI 10.1096/fj.12-206896
PG 9
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 081YG
UT WOS:000314358000005
PM 23070608
ER
PT J
AU Zhang, JP
Valianou, M
Simmons, H
Robinson, MK
Lee, HO
Mullins, SR
Marasco, WA
Adams, GP
Weiner, LM
Cheng, JD
AF Zhang, Jiping
Valianou, Matthildi
Simmons, Heidi
Robinson, Matthew K.
Lee, Hyung-Ok
Mullins, Stefanie R.
Marasco, Wayne A.
Adams, Gregory P.
Weiner, Louis M.
Cheng, Jonathan D.
TI Identification of inhibitory scFv antibodies targeting fibroblast
activation protein utilizing phage display functional screens
SO FASEB JOURNAL
LA English
DT Article
DE serine protease; single-chain variable fragment
ID TUMOR STROMAL FIBROBLASTS; SERINE-PROTEASE; EXTRACELLULAR-MATRIX;
EPITHELIAL CANCERS; MOLECULAR-CLONING; DIFFERENTIAL EXPRESSION;
OVARIAN-CANCER; COLON-CANCER; PHASE-I; CELLS
AB Fibroblast activation protein (FAP) is a serine protease selectively expressed on tumor stromal fibroblasts in epithelial carcinomas and is important in cancer growth, adhesion, and metastases. As FAP enzymatic activity is a potent therapeutic target, we aimed to identify inhibitory antibodies. Using a competitive inhibition strategy, we used phage display techniques to identify 53 single-chain variable fragments (scFvs) after three rounds of panning against FAP. These scFvs were expressed and characterized for binding to FAP by surface plasmon resonance and flow cytometry. Functional assessment of these antibodies yielded an inhibitory scFv antibody, named E3, which could attenuate 35% of FAP cleavage of the fluorescent substrate Ala-Pro-7-amido-4-trifluoromethylcoumarin compared with nonfunctional scFv control. Furthermore, a mutant E3 scFv was identified by yeast affinity maturation. It had higher affinity (4-fold) and enhanced inhibitory effect on FAP enzyme activity (3-fold) than E3. The application of both inhibitory anti-FAP scFvs significantly affected the formation of 3-dimensional FAP-positive cell matrix, as demonstrated by reducing the fibronectin fiber orientation from 41.18% (negative antibody control) to 34.06% (E3) and 36.15% (mutant E3), respectively. Thus, we have identified and affinity-maturated the first scFv antibody capable of inhibiting FAP function. This scFv antibody has the potential to disrupt the role of FAP in tumor invasion and metastasis.-Zhang, J., Valianou, M., Simmons, H., Robinson, M. K., Lee, H.-O., Mullins, S. R., Marasco, W. A., Adams, G. P., Weiner, L. M., Cheng, J. D. Identification of inhibitory ScFv antibodies targeting fibroblast activation protein utilizing phage display functional screens. FASEB J. 27, 581-589 (2013). www.fasebj.org
C1 [Valianou, Matthildi; Lee, Hyung-Ok; Mullins, Stefanie R.; Cheng, Jonathan D.] Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19111 USA.
[Zhang, Jiping; Simmons, Heidi; Robinson, Matthew K.; Adams, Gregory P.] Fox Chase Canc Ctr, Dev Therapeut Program, Philadelphia, PA 19111 USA.
[Marasco, Wayne A.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
[Weiner, Louis M.] Georgetown Lombardi Comprehens Canc Ctr, Dept Oncol, Washington, DC USA.
RP Cheng, JD (reprint author), Fox Chase Canc Ctr, Dept Med Oncol, 333 Cottman Ave, Philadelphia, PA 19111 USA.
EM j_cheng@fccc.edu
FU U.S. National Institutes of Health [CA090468, CA103991-01, CA09035-28];
Frank Strick Foundation; Bernard A. and Rebecca S. Bernard Foundation
FX This study was supported by U.S. National Institutes of Health grants
CA090468, CA103991-01, and CA09035-28; the Frank Strick Foundation; the
Bernard A. and Rebecca S. Bernard Foundation; and an appropriation from
the Commonwealth of Pennsylvania and the American Cancer Society.
NR 38
TC 7
Z9 7
U1 0
U2 19
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD FEB
PY 2013
VL 27
IS 2
BP 581
EP 589
DI 10.1096/fj.12-210377
PG 9
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 081YG
UT WOS:000314358000017
PM 23104982
ER
PT J
AU Furuya, H
Wada, M
Shimizu, Y
Yamada, PM
Hannun, YA
Obeid, LM
Kawamori, T
AF Furuya, Hideki
Wada, Masayuki
Shimizu, Yoshiko
Yamada, Paulette M.
Hannun, Yusuf A.
Obeid, Lina M.
Kawamori, Toshihiko
TI Effect of sphingosine kinase 1 inhibition on blood pressure
SO FASEB JOURNAL
LA English
DT Article
DE sphingolipids; cardiovascular functions; chemoprevention; prostacyclin;
COX-2; mPGES-1
ID PROSTAGLANDIN-E SYNTHASE-1; II-INDUCED HYPERTENSION; ANGIOTENSIN-II;
CYCLOOXYGENASE-2 INHIBITOR; COLON CARCINOGENESIS; OXIDATIVE STRESS;
ENDOTHELIAL-CELLS; E-2 PROTECTS; TNF-ALPHA; 1-PHOSPHATE
AB Accumulating evidence suggests that sphingosine kinase 1 (SphK1) plays a key role in carcinogenesis by regulating cyclooxygenase-2 (COX-2) expression. Recent clinical studies have revealed that COX-2 inhibitors cause adverse cardiovascular side effects, likely due to inhibition of prostacyclin (PGI(2)). In this work, we investigated the roles of SphK1 inhibition on blood pressure (BP). The results show that lack of SphK1 expression did not exacerbate angiotensin II (Ang II)-induced acute hypertension, whereas celecoxib, a COX-2 inhibitor, augmented and sustained higher BP in mice. Interestingly, SphK1-knockout mice inhibited prostaglandin E-2 (PGE(2)) but not PGI(2) production in response to Ang II, whereas celecoxib blocked both PGE(2) and PGI(2) production. Mechanistically, SphK1 down-regulation by siRNA in human umbilical vein endothelial cells decreased cytokine-induced PGE(2) production primarily through inhibition of microsomal PGE synthase-1 (mPGES-1), not COX-2. SphK1 downregulation also decreased MKK6 expression, which phosphorylates and activates P38 MAPK, which, in turn, regulates early growth response-1 (Egr-1), a transcription factor of mPGES-1. Together, these data indicate that SphK1 regulates PGE(2) production by mPGES-1 expression via the p38 MAPK pathway, independent of COX-2 signaling, in endothelial cells, suggesting that SphK1 inhibition may be a promising strategy for cancer chemoprevention with lack of the adverse cardiovascular side effects associated with coxibs.-Furuya, H., Wada, M., Shimizu, Y., Yamada, P. M., Hannun, Y. A., Obeid, L. M., Kawamori, T. Effect of sphingosine kinase 1 inhibition on blood pressure. FASEB J. 27, 656-664 (2013). www.fasebj.org
C1 [Furuya, Hideki; Shimizu, Yoshiko; Yamada, Paulette M.; Kawamori, Toshihiko] Univ Hawaii, Ctr Canc, Honolulu, HI 96813 USA.
[Furuya, Hideki; Wada, Masayuki; Kawamori, Toshihiko] Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA.
[Hannun, Yusuf A.; Obeid, Lina M.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA.
[Obeid, Lina M.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA.
[Shimizu, Yoshiko; Kawamori, Toshihiko] Univ Hawaii Manoa, Dept Mol Biosci & Bioengn, Honolulu, HI 96822 USA.
[Obeid, Lina M.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA.
RP Kawamori, T (reprint author), Univ Hawaii, Ctr Canc, 651 Ilalo St,BSB 222H, Honolulu, HI 96813 USA.
EM kawamori@cc.hawaii.edu
OI obeid, lina/0000-0002-0734-0847
FU U.S. National Institutes of Health (NIH) [R01CA124687, P20RR17677,
P01CA97132]; Hollings Cancer Center, MUSC; NIH Extramural Research
Facilities Program of the National Center for Research Resources
[C06RR015455]
FX The authors thank the Lipidomics Core Facility and Animal Carcinogenesis
Core, Hollings Cancer Center, Medical University of South Carolina
(MUSC), and Animal Carcinogenesis Shared Resource, University of Hawaii
Cancer Center. This work was supported by U.S. National Institutes of
Health (NIH) grants (R01CA124687 and P20RR17677 to T. K., P01CA97132 to
T. K., Y.A.H., and L.M.O.) and a seed grant to T. K. from the Hollings
Cancer Center, MUSC. This work was conducted in a facility constructed
with support from the NIH Extramural Research Facilities Program of the
National Center for Research Resources (C06RR015455).
NR 52
TC 9
Z9 9
U1 0
U2 4
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
EI 1530-6860
J9 FASEB J
JI Faseb J.
PD FEB
PY 2013
VL 27
IS 2
BP 656
EP 664
DI 10.1096/fj.12-219014
PG 9
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 081YG
UT WOS:000314358000024
PM 23109673
ER
PT J
AU Liu, CH
Yang, JS
Ren, JQ
Liu, CM
You, ZR
Liu, PK
AF Liu, Christina H.
Yang, Jinsheng
Ren, Jia Q.
Liu, Charng-Ming
You, Zerong
Liu, Philip K.
TI MRI reveals differential effects of amphetamine exposure on neuroglia in
vivo
SO FASEB JOURNAL
LA English
DT Article
DE drug delivery; molecular MR imaging; nanomedicine; gliogenesis
ID BLOOD-BRAIN-BARRIER; METHAMPHETAMINE-INDUCED NEUROTOXICITY; FIBRILLARY
ACIDIC PROTEIN; IRON-OXIDE PARTICLES; GENE-EXPRESSION; STEM-CELLS;
MESSENGER-RNA; SEROTONIN NEUROTOXICITY; TRANSGENIC MICE; LIVING BRAINS
AB How amphetamine affects the neuroglia in living brains is not well understood. In an effort to elucidate this effect, we investigated neuroglia in response to amphetamine exposure using antisense (AS) or sense (S) phosphorothioate-modified oligodeoxynucleotide (sODN) sequences that correspond to glial fibrillary acidic protein (GFAP) mRNA (AS-gfap or S-gfap, respectively) expression. The control is a random-sequence sODN (Ran). Using cyanine 5.5-super-paramagnetic iron oxide nanoparticle (Cy5.5-SPION) labeling and fluorescent microscopy, we demonstrated that living neural progenitor cells (PC-12.1), as well as the cells in fresh brain slices and intact brains of male C57BL6 mice, exhibited universal uptake of all of the sODNs but rapidly excluded all sODN-Ran and most S-gfap. Moreover, transmission electron microscopy revealed electron-dense nanoparticles only in the neuroglia of normal or transgenic mice [B6;DBA-Tg(Fos-tTA, Fos-EGFP*)1MmayTg(tetO-lacZ,tTA*)1Mmay/J] that had been administered AS-gfap or Cy5.5-SPION-gfap. Subtraction R2* maps from mice with acute and chronic amphetamine exposure demonstrated, validated by postmortem immunohistochemistry, a reduction in striatal neuroglia, with gliogenesis in the subventricular zone and the somatosensory cortex in vivo. The sensitivity of our unique gene transcript targeted MRI was illustrated by a positive linear correlation (r(2) = 1.0) between in vivo MRI signal changes and GFAP mRNA copy numbers determined by ex vivo quantitative RTPCR. The study provides direct evidence for targeting neuroglia by antisense DNA-based SPION-gfap that enables in vivo MRI of inaccessible tissue with PCR sensitivity. The results enable us to conclude that amphetamine induces toxicity to neuroglia in vivo, which may cause remodeling or reconnectivity of neuroglia.-Liu, C. H., Yang, J., Ren, J. Q., Liu, C.-M., You, Z., Liu, P. K. MRI reveals differential effects of amphetamine exposure on neuroglia in vivo. FASEB J. 27, 712-724 (2013). www.fasebj.org
C1 [Liu, Christina H.; Yang, Jinsheng; Ren, Jia Q.; Liu, Charng-Ming; Liu, Philip K.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA USA.
[You, Zerong] Massachusetts Gen Hosp, Dept Pediat, Charlestown, MA USA.
RP Liu, PK (reprint author), CNY149 2301 13th St, Charlestown, MA 02129 USA.
EM philipl@nmr.mgh.harvard.edu
OI Liu, Christina/0000-0002-5723-177X
FU American Heart Association [2060416]; U.S. National Institutes of Health
(NIH) [AT004974, DA026108, DA029889, EB013768, NS045776]; NIH [DK43351,
DK57521]
FX The authors thank Ms. N. Eusemann for help with editing. This project
was supported by grants from the American Heart Association
(09Grant2060416) and the U.S. National Institutes of Health (NIH;
AT004974 to J.Q.R.; DA026108, DA029889, and EB013768 to P. K. L.; and
NS045776 to the Massachusetts General Hospital Neuroscience Center). The
9.4-T MR system used for this work was funded in part by an NIH Shared
Instrumentation grant awarded to the Athinoula A. Martinos Center for
Biomedical Imaging. The authors appreciate the help of M. McKee with
TEM, and the availability of the Microscopy Core (which is supported by
NIH DK43351 and DK57521). Author contributions: C. H. L. contributed to
MRI acquisition and data analysis and wrote the initial draft of the
manuscript; J.Y. contributed to qRT-PCR and TaqMan analysis; J.Q.R.
established brain slice cultures, delivered SPION-gfap, and contributed
to histology and TEM; C.-M. L. synthesized and modified sODN and carried
out PC-12.1 culture studies; Z.Y. contributed to immunohistology; P. K.
L. coordinated and provided overall oversight for the project, designed
and prepared SPION-sODN, carried out time-lapse microscopy, and
supervised the various phases of revision of the manuscript.
NR 61
TC 6
Z9 6
U1 2
U2 15
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD FEB
PY 2013
VL 27
IS 2
BP 712
EP 724
DI 10.1096/fj.12-220061
PG 13
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 081YG
UT WOS:000314358000030
PM 23150521
ER
PT J
AU Ho, L
Ferruzzi, MG
Janle, EM
Wang, J
Gong, B
Chen, TY
Lobo, J
Cooper, B
Wu, QL
Talcott, ST
Percival, SS
Simon, JE
Pasinetti, GM
AF Ho, Lap
Ferruzzi, Mario G.
Janle, Elsa M.
Wang, Jun
Gong, Bing
Chen, Tzu-Ying
Lobo, Jessica
Cooper, Bruce
Wu, Qing Li
Talcott, Stephen T.
Percival, Susan S.
Simon, James E.
Pasinetti, Giulio Maria
TI Identification of brain-targeted bioactive dietary
quercetin-3-O-glucuronide as a novel intervention for Alzheimer's
disease
SO FASEB JOURNAL
LA English
DT Article
DE polyphenol bioavailability; cognitive deterioration; neuroplasticity
ID LONG-TERM POTENTIATION; RED WINE; TRANSGENIC MICE; MOUSE MODEL; IN-VIVO;
LIQUID-CHROMATOGRAPHY; VARIETAL DIFFERENCES; SYNAPTIC PLASTICITY;
OXIDATIVE STRESS; VITIS-VINIFERA
AB Epidemiological and preclinical studies indicate that polyphenol intake from moderate consumption of red wines may lower the relative risk for developing Alzheimer's disease (AD) dementia. There is limited information regarding the specific biological activities and cellular and molecular mechanisms by which wine polyphenolic components might modulate AD. We assessed accumulations of polyphenols in the rat brain following oral dosage with a Cabernet Sauvignon red wine and tested brain-targeted polyphenols for potential beneficial AD disease-modifying activities. We identified accumulations of select polyphenolic metabolites in the brain. We demonstrated that, in comparison to vehicle-control treatment, one of the brain-targeted polyphenol metabolites, quercetin-3-O-glucuronide, significantly reduced the generation of beta-amyloid (A beta\) peptides by primary neuron cultures generated from the Tg2576 AD mouse model. Another brain-targeted metabolite, malvidin-3-O-glucoside, had no detectable effect on A beta generation. Moreover, in an in vitro analysis using the photo-induced cross-linking of unmodified proteins (PICUP) technique, we found that quercetin-3-O-glucuronide is also capable of interfering with the initial protein-protein interaction of A beta(1-40) and A beta(1-42) that is necessary for the formation of neurotoxic oligomeric A beta species. Lastly, we found that quercetin-3-O-glucuronide treatment, compared to vehicle-control treatment, significantly improved AD-type deficits in hippocampal formation basal synaptic transmission and long-term potentiation, possibly through mechanisms involving the activation of the c-Jun N-terminal kinases and the mitogen-activated protein kinase signaling pathways. Brain-targeted quercetin-3-O-glucuronide may simultaneously modulate multiple independent AD disease-modifying mechanisms and, as such, may contribute to the benefits of dietary supplementation with red wines as an effective intervention for AD.-Ho, L., Ferruzzi, M. G., Janle, E. M., Wang, J., Gong, B., Chen, T.-Y., Lobo, J., Cooper, B., Wu, Q. L., Talcott, S. T., Percival, S. S., Simon, J. E., Pasinetti, G. M. Identification of brain-targeted bioactive dietary quercetin-3-O-glucuronide as a novel intervention for Alzheimer's disease. FASEB J. 27, 769-781 (2013). www.fasebj.org
C1 [Ho, Lap; Wang, Jun; Gong, Bing; Pasinetti, Giulio Maria] Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA.
[Pasinetti, Giulio Maria] James J Peters Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, Bronx, NY USA.
[Ferruzzi, Mario G.; Lobo, Jessica] Purdue Univ, Dept Food Sci, W Lafayette, IN 47907 USA.
[Ferruzzi, Mario G.; Janle, Elsa M.; Chen, Tzu-Ying] Purdue Univ, Dept Nutr Sci, W Lafayette, IN 47907 USA.
[Cooper, Bruce] Purdue Univ, Bindley Biosci Ctr, W Lafayette, IN 47907 USA.
[Wu, Qing Li; Simon, James E.] Rutgers State Univ, Dept Plant Biol & Plant Pathol, New Brunswick, NJ 08903 USA.
[Talcott, Stephen T.] Texas A&M Univ, Dept Nutr & Food Sci, College Stn, TX USA.
[Percival, Susan S.] Univ Florida, Dept Food Sci & Human Nutr, Gainesville, FL USA.
RP Pasinetti, GM (reprint author), Mt Sinai Sch Med, Dept Neurol, 1468 Madison Ave,Annenberg Bldg,Rm 20-02, New York, NY 10029 USA.
EM giulio.pasinetti@mssm.edu
FU U.S. National Institutes of Health [National Center for Complementary
and Alternative Medicine (NCCAM)] [PO1 AT004511]
FX These studies were supported by the U.S. National Institutes of Health
[grant PO1 AT004511; National Center for Complementary and Alternative
Medicine (NCCAM) Project 1 to L. H. and Project 3 to G. M. P.]. The
authors thank Dr. Kenjiro Ono (Kanazawa University Graduate School of
Medical Science, Takara-Machi, Kanazawa, Japan), for valuable assistance
and support with the PICUP analysis.
NR 80
TC 52
Z9 55
U1 1
U2 50
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD FEB
PY 2013
VL 27
IS 2
BP 769
EP 781
DI 10.1096/fj.12-212118
PG 13
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 081YG
UT WOS:000314358000035
PM 23097297
ER
PT J
AU Manabe, Y
Gollisch, KSC
Holton, L
Kim, YB
Brandauer, J
Fujii, NL
Hirshman, MF
Goodyear, LJ
AF Manabe, Yasuko
Gollisch, Katja S. C.
Holton, Laura
Kim, Young-Bum
Brandauer, Josef
Fujii, Nobuharu L.
Hirshman, Michael F.
Goodyear, Laurie J.
TI Exercise training-induced adaptations associated with increases in
skeletal muscle glycogen content
SO FEBS JOURNAL
LA English
DT Article
DE exercise; glycogen synthase; glycogen synthase kinase 3 (GSK-3); rat;
skeletal muscle
ID PROTEIN PHOSPHATASE 1; GLUCOSE-TRANSPORT; SYNTHASE KINASE-3; INSULIN
SENSITIVITY; TARGETING SUBUNIT; PHOSPHORYLASE; METABOLISM; ACTIVATION;
ACCUMULATION; EXPRESSION
AB Chronic exercise training results in numerous skeletal muscle adaptations, including increases in insulin sensitivity and glycogen content. To understand the mechanism leading to increased muscle glycogen, we studied the effects of exercise training on glycogen regulatory proteins in rat skeletal muscle. Female Sprague Dawley rats performed voluntary wheel running for 1, 4 or 7 weeks. After 7 weeks of training, insulin-stimulated glucose uptake was increased in epitrochlearis muscle. As compared with sedentary control rats, muscle glycogen did not change after 1 week of training, but increased significantly after 4 and 7 weeks. The increases in muscle glycogen were accompanied by elevated glycogen synthase activity and protein expression. To assess the regulation of glycogen synthase, we examined its major activator, protein phosphatase 1 (PP1), and its major deactivator, glycogen synthase kinase (GSK)-3. Consistent with glycogen synthase activity, PP1 activity was unchanged after 1 week of training but significantly increased after 4 and 7 weeks of training. Protein expression of RGL(GM), another regulatory PP1 subunit, significantly decreased after 4 and 7 weeks of training. Unlike PP1 activity, GSK-3 phosphorylation did not follow the pattern of glycogen synthase activity. The 40% decrease in GSK-3a phosphorylation after 1 week of exercise training persisted until 7 weeks, and may function as a negative feedback mechanism in response to elevated glycogen. Our findings suggest that exercise training-induced increases in muscle glycogen content could be regulated by multiple mechanisms, including enhanced insulin sensitivity, glycogen synthase expression, allosteric activation of glycogen synthase, and PP1 activity.
C1 [Manabe, Yasuko; Gollisch, Katja S. C.; Holton, Laura; Brandauer, Josef; Fujii, Nobuharu L.; Hirshman, Michael F.; Goodyear, Laurie J.] Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA 02215 USA.
[Kim, Young-Bum] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol Diabet & Metab,Dept Med, Boston, MA 02215 USA.
RP Goodyear, LJ (reprint author), Joslin Diabet Ctr, Sect Integrat Physiol & Metab, 1 Joslin Pl, Boston, MA 02215 USA.
EM laurie.goodyear@joslin.harvard.edu
RI Fujii, Nobuharu/J-2724-2014
OI Fujii, Nobuharu/0000-0002-0974-3033
FU National Institutes of Health [AR45670, AR42338, T32DK07260-29]; Japan
Society for the Promotion of Science [KAKENHI 24700700, KAKENHI
21240063]; Cabinet Office, Government of Japan [LS102]; German Academic
Exchange Service DAAD
FX This work was supported by the National Institutes of Health (Grants
AR45670 and AR42338 to L. J. Goodyear and Training Grant T32DK07260-29
to J. Brandauer), by the Japan Society for the Promotion of Science
(KAKENHI 24700700 to Y. Manabe and KAKENHI 21240063 to N. L. Fujii), by
the Cabinet Office, Government of Japan (Funding Program for Next
Generation World-Leading Researchers, LS102 to N. L. Fujii), and by a
fellowship within the Postdoc Program of the German Academic Exchange
Service DAAD (to K. S. C. Gollisch.). We thank Drs A. Saltiel
(University of Michigan) and M. Brady (University of Chicago) for
providing the RGL(GM) and PTG/R5 antibodies.
NR 44
TC 8
Z9 9
U1 0
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1742-464X
J9 FEBS J
JI FEBS J.
PD FEB
PY 2013
VL 280
IS 3
BP 916
EP 926
DI 10.1111/febs.12085
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 079JT
UT WOS:000314167100011
PM 23206309
ER
PT J
AU Zou, L
AF Zou, Lee
TI Four pillars of the S-phase checkpoint
SO GENES & DEVELOPMENT
LA English
DT Article
DE DNA replication; cell cycle checkpoint; 9-1-1; ATR; ATM
ID REPLICATION-PROTEIN-A; DNA-DAMAGE CHECKPOINT; CELL-CYCLE CHECKPOINT;
ESSENTIAL IN-VIVO; C-TERMINAL TAIL; SACCHAROMYCES-CEREVISIAE;
END-RESECTION; GENOME STABILITY; BUDDING YEAST; HOMOLOG MEC1
AB The yeast Mec1 kinase is a key regulator of the DNA damage response (DDR). In this issue of Genes & Development, Kumar and Burgers (pp. 313-321) report that Ddc1, Dpb11, and Dna2 function in concert to activate Mec1 during S phase of the cell cycle. Furthermore, the Tel1 kinase also contributes to the DDR in S phase when Mec1 activation is compromised.
C1 [Zou, Lee] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Charlestown, MA 02129 USA.
[Zou, Lee] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
RP Zou, L (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Charlestown, MA 02129 USA.
EM zou.lee@mgh.harvard.edu
FU NIH [GM076388]; MGH/NCI Proton Program
FX I apologize to the colleagues whose work is not cited due to space
constraints. Work in my laboratory is supported by grants from NIH
(GM076388) and the MGH/NCI Proton Program. I am a Jim and Ann Orr MGH
Research Scholar and a Scholar of the Ellison Medical Foundation.
NR 55
TC 11
Z9 11
U1 0
U2 8
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 FEB 1
PY 2013
VL 27
IS 3
BP 227
EP 233
DI 10.1101/gad.213306.113
PG 7
WC Cell Biology; Developmental Biology; Genetics & Heredity
SC Cell Biology; Developmental Biology; Genetics & Heredity
GA 088BS
UT WOS:000314809400001
PM 23388823
ER
PT J
AU Wu, J
Cohen, P
Spiegelman, BM
AF Wu, Jun
Cohen, Paul
Spiegelman, Bruce M.
TI Adaptive thermogenesis in adipocytes: Is beige the new brown?
SO GENES & DEVELOPMENT
LA English
DT Review
DE brown fat; beige fat; obesity; adaptive thermogenesis; UCP1
ID WHITE ADIPOSE-TISSUE; DIET-INDUCED OBESITY; ACTIVATED RECEPTOR-GAMMA;
MITOCHONDRIAL UNCOUPLING-PROTEIN; GROWTH-FACTOR-BETA;
ENERGY-EXPENDITURE; SKELETAL-MUSCLE; INSULIN-RESISTANCE; PPAR-GAMMA;
GENE-EXPRESSION
AB One of the most promising areas in the therapeutics for metabolic diseases centers around activation of the pathways of energy expenditure. Brown adipose tissue is a particularly appealing target for increasing energy expenditure, given its amazing capacity to transform chemical energy into heat. In addition to classical brown adipose tissue, the last few years have seen great advances in our understanding of inducible thermogenic adipose tissue, also referred to as beige fat. A deeper understanding of the molecular processes involved in the development and function of these cell types may lead to new therapeutics for obesity, diabetes, and other metabolic diseases.
C1 [Wu, Jun; Cohen, Paul; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Wu, Jun; Cohen, Paul; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
[Cohen, Paul] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc,Dept Med, Boston, MA 02115 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 NIH [1K01DK094824, DK31405, DK90861]; American Heart Association
[11FTF7510004]; JPB Foundation
FX We thank M. Khandekar for helpful discussions. We apologize to those
whom we were unable to reference due to space limitations. J.W. is
supported by an NIH grant (1K01DK094824). P. C. is supported by a grant
from the American Heart Association (11FTF7510004). This work is funded
by the JPB Foundation and NIH grants (DK31405 and DK90861) to B.M.S.
NR 203
TC 239
Z9 242
U1 9
U2 88
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
EI 1549-5477
J9 GENE DEV
JI Genes Dev.
PD FEB 1
PY 2013
VL 27
IS 3
BP 234
EP 250
DI 10.1101/gad.211649.112
PG 17
WC Cell Biology; Developmental Biology; Genetics & Heredity
SC Cell Biology; Developmental Biology; Genetics & Heredity
GA 088BS
UT WOS:000314809400002
PM 23388824
ER
PT J
AU Dai, N
Christiansen, J
Nielsen, FC
Avruch, J
AF Dai, Ning
Christiansen, Jan
Nielsen, Finn C.
Avruch, Joseph
TI mTOR complex 2 phosphorylates IMP1 cotranslationally to promote IGF2
production and the proliferation of mouse embryonic fibroblasts
SO GENES & DEVELOPMENT
LA English
DT Article
DE mTOR complex 2; IMP1; cotranslational phosphorylation; mRNA translation;
IGF2; embryonic growth
ID II MESSENGER-RNA; PROTEIN-KINASE INHIBITORS; BINDING PROTEINS; GROWTH;
TRANSLATION; EXPRESSION; EMBRYOGENESIS; RIBOSOME; FAMILY; TARGET
AB Lack of IGF2 in mice results in diminished embryonic growth due to diminished cell proliferation. Here we show that mouse embryonic fibroblasts lacking the RNA-binding protein IMP1 (IGF2 mRNA-binding protein 1) have defective splicing and translation of IGF2 mRNAs, markedly reduced IGF2 polypeptide production, and diminished proliferation. The proliferation of the IMP1-null fibroblasts can be restored to wild-type levels by IGF2 in vitro or by re-expression of IMP1, which corrects the defects in IGF2 RNA splicing and translation. The ability of IMP1 to correct these defects is dependent on IMP1 phosphorylation at Ser181, which is catalyzed cotranslationally by mTOR complex 2 (mTORC2). Phosphorylation strongly enhances IMP1 binding to the IGF2-leader 3 5' untranslated region, which is absolutely required to enable IGF2-leader 3 mRNA translational initiation by internal ribosomal entry. These findings uncover a new mechanism by which mTOR regulates organismal growth by promoting IGF2 production in the mouse embryo through mTORC2-catalyzed cotranslational IMP1/IMP3 phosphorylation. Inasmuch as TORC2 is activated by association with ribosomes, the present results indicate that mTORC2-catalyzed cotranslational protein phosphorylation is a core function of this complex.
C1 [Dai, Ning; Avruch, Joseph] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
[Dai, Ning; Avruch, Joseph] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA.
[Dai, Ning; Avruch, Joseph] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
[Christiansen, Jan] Univ Copenhagen, Rigshosp, Dept Biol, DK-2100 Copenhagen, Denmark.
[Nielsen, Finn C.] Univ Copenhagen, Rigshosp, Dept Clin Biochem, DK-2100 Copenhagen, Denmark.
RP Avruch, J (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
EM avruch@molbio.mgh.harvard.edu
RI Christiansen, Jan/L-3312-2014
OI Christiansen, Jan/0000-0001-8624-4601
FU NIH [DK17776, CA73818, DK057521]
FX We thank E. Jacinto and colleagues for advice regarding the analysis of
cotranslational phosphorylation. The work was supported by NIH grants
DK17776, CA73818, and DK057521 (to J.A.) and by institutional funds.
NR 29
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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 FEB 1
PY 2013
VL 27
IS 3
BP 301
EP 312
DI 10.1101/gad.209130.112
PG 12
WC Cell Biology; Developmental Biology; Genetics & Heredity
SC Cell Biology; Developmental Biology; Genetics & Heredity
GA 088BS
UT WOS:000314809400007
PM 23388827
ER
PT J
AU Campos, SM
Penson, RT
Matulonis, U
Horowitz, NS
Whalen, C
Pereira, L
Tyburski, K
Roche, M
Szymonifka, J
Berlin, S
AF Campos, Susana M.
Penson, Richard T.
Matulonis, Ursula
Horowitz, Neil S.
Whalen, Christin
Pereira, Lauren
Tyburski, Karin
Roche, Maria
Szymonifka, Jackie
Berlin, Suzanne
TI A phase II trial of Sunitinib malate in recurrent and refractory
ovarian, fallopian tube and peritoneal carcinoma
SO GYNECOLOGIC ONCOLOGY
LA English
DT Article
DE Ovarian cancer; Tyrosine kinase inhibitors; Angiogenic biomarkers;
Targeted therapy
ID ENDOTHELIAL GROWTH-FACTOR; TYROSINE KINASE INHIBITOR; RENAL-CELL
CARCINOMA; EPITHELIAL OVARIAN; BREAST-CANCER; BEVACIZUMAB; THERAPY;
CYCLOPHOSPHAMIDE; POLYMORPHISMS; EXPRESSION
AB Objective. Ovarian cancer is a highly angiogenic tumor and a model for antiangiogenic research. The tyrosine kinase receptor inhibitors target several receptors allowing for the pharmacological disruption of several independent pathways. Sunitinib malate (R) is a multitargeted tyrosine kinase inhibitor. A phase II study utilizing a modified dosing schedule was conducted to assess the efficacy and safety of Sunitinib in recurrent ovarian, fallopian tube and peritoneal carcinoma.
Methods. A nonrandomized-phase II study was modeled as a two-stage Simon design initially enrolling 17 evaluable participants in stage one and 18 patients in stage two. Patients received the study drug at 37.5 mg every day over a 28 day treatment cycle until clinical or radiological evidence of progressive disease. Disease was evaluated radiographically and best overall response was defined using the RECIST 1.0 criteria. The primary objective of this study was to define the response rate (defined a complete response and partial response) while the secondary objectives included both the progression free rate as well as the safety of this agent in this patient population.
Results. The response rate (PR+CR) was 8.3% (95% confidence interval: 1.8%, 22.5%). The 16-week and 24 week progression-free survival estimate was 36% (95% confidence interval and 19.2%), respectively. The median progression-free survival estimate was 9.9 weeks. Hypertension and gastrointestional events were the most common toxicities noted.
Conclusions. A modest response rate of 8.3% was achieved with Sunitinib malate (R). This phase II study adds to the body of literature of VEGFR inhibitors and further underscores the need of defining a genetic angiogenic signature. (C) 2012 Published by Elsevier Inc.
C1 [Campos, Susana M.; Matulonis, Ursula; Berlin, Suzanne] Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02115 USA.
[Penson, Richard T.; Roche, Maria] Massachusetts Gen Hosp, Dept Med, Div Gynecol Oncol, Boston, MA 02114 USA.
[Horowitz, Neil S.] Brigham & Womens Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, Boston, MA 02115 USA.
[Campos, Susana M.; Whalen, Christin; Pereira, Lauren; Tyburski, Karin] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Szymonifka, Jackie] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Campos, SM (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02115 USA.
EM scampos@partners.org; rtpenson@partners.org; umatulonis@partners.org;
nhorowitz@partners.org; cwhalen@partners.org; lpereira@partners.org;
ktyburski@partners.org; maria.roche@kadman.com;
jszymonifka@partners.org; sberlin@partners.org
FU Genentech
FX Susana Campos: Genentech: research funding; consultant to Pfizer (breast
cancer). Richard Penson: Genentech: research funding. Otherwise there
are no additional financial conflicts of interest.
NR 40
TC 18
Z9 21
U1 0
U2 5
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD FEB
PY 2013
VL 128
IS 2
BP 215
EP 220
DI 10.1016/j.ygyno.2012.07.126
PG 6
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 083EK
UT WOS:000314445300013
PM 22885865
ER
PT J
AU Winer, I
Mahdi, H
Bandyopadhyay, S
Semaan, A
Van de Vijver, KK
Nucci, MR
Abdul-Karim, F
Hussein, Y
Qureshi, F
Hayek, K
Alosh, B
Schulz, D
Cote, M
Munkarah, A
Morris, R
Oliva, E
Ali-Fehmi, R
AF Winer, I.
Mahdi, H.
Bandyopadhyay, S.
Semaan, A.
Van de Vijver, K. K.
Nucci, M. R.
Abdul-Karim, F.
Hussein, Y.
Qureshi, F.
Hayek, K.
Alosh, B.
Schulz, D.
Cote, M.
Munkarah, A.
Morris, R.
Oliva, E.
Ali-Fehmi, R.
TI Correlation of tumor size with other prognostic factors in uterine
serous carcinoma: A large multi-institutional study
SO GYNECOLOGIC ONCOLOGY
LA English
DT Article
DE Uterine serous carcinoma (USC); Staging; Tumor size; Prognostic factors
ID LYMPH-NODE METASTASIS; ENDOMETRIAL CANCER; STAGE-I; FOLLOW-UP; SURVIVAL;
ADENOCARCINOMA; RECURRENCE; PREDICTORS; DISEASE; SPREAD
AB Objective. Uterine serous carcinoma (USC) constitutes 10% of uterine cancers but similar to 40% of deaths. Tumor size is a known prognostic factor in other solid tumors. In endometriod cancers it is one element used to identify the need for complete staging, while its significance in USC is debated. Therefore tumor size was examined as an independent prognostic factor.
Methods. Clinical and pathologic variables were recorded for 236 institutional patients, and those patients in the SEER database with USC. Chi-square and Fisher exact t-tests were utilized and survival data generated via Kaplan-Meier method; multivariate analysis was performed via cox-regression.
Results. The patients' mean age was 67.2 years (range 40-91). Survival ranged from 0 to 184 months (mean 42.8). We used a tumor size cut-off of 1 cm and noted significant associations with myometrial invasion (p < 0.0001), angiolymphatic invasion (p < 0.0001), peritoneal washings (p = 0.03), stage (p = 0.015) and positive lymph nodes (p = 0.05). Furthermore, recurrence was associated with larger tumors (p = 0.03). In multivariate analysis, extra-uterine disease was the only factor associated with both recurrence and survival. Review of the SEER database noted association of larger tumors with lymph node involvement and a significant survival advantage with tumors <1 cm in both univariate and multivariate analysis.
Conclusions. Treatment options for USC are often predicated on the surgical stage and therefore components of the staging are vitally important. The I cm tumor-size cut-off should be studied prospectively as a prognostic indicator of survival and recurrence in USC and considered for inclusion in USC staging. (c) 2012 Published by Elsevier Inc.
C1 [Winer, I.; Semaan, A.; Morris, R.] Wayne State Univ, Div Gynecol Oncol, Dept OB GYN, Detroit, MI USA.
[Winer, I.; Semaan, A.; Morris, R.] Karmanos Canc Inst, Detroit, MI USA.
[Mahdi, H.] Univ Washington, Med Ctr, Dept OB GYN, Seattle, WA 98195 USA.
[Bandyopadhyay, S.; Hussein, Y.; Qureshi, F.; Hayek, K.; Alosh, B.; Ali-Fehmi, R.] Wayne State Univ, Dept Pathol, Detroit, MI 48202 USA.
[Van de Vijver, K. K.; Nucci, M. R.] Harvard Univ, Brigham & Womens Hosp, Dept Pathol, Sch Med, Boston, MA 02115 USA.
[Abdul-Karim, F.] Cleveland Clin Fdn, Dept Anat Pathol, Cleveland, OH 44195 USA.
[Schulz, D.] Henry Ford Hlth Syst, Dept Pathol, Detroit, MI USA.
[Cote, M.] Karmanos Canc Inst, Dept Epidemiol, Detroit, MI USA.
[Munkarah, A.] Henry Ford Hlth Syst, Div Gynecol Oncol, Dept OB GYN, Detroit, MI USA.
[Oliva, E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA.
RP Ali-Fehmi, R (reprint author), Harper Univ Hosp, Dept Pathol, 3990 John R, Detroit, MI 48201 USA.
EM rali@med.wayne.edu
NR 41
TC 4
Z9 4
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 0090-8258
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD FEB
PY 2013
VL 128
IS 2
BP 316
EP 321
DI 10.1016/j.ygyno.2012.10.027
PG 6
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 083EK
UT WOS:000314445300029
PM 23138135
ER
PT J
AU Lim, D
Wang, WL
Lee, CH
Dodge, T
Gilks, B
Oliva, E
AF Lim, D.
Wang, W. L.
Lee, C. H.
Dodge, T.
Gilks, B.
Oliva, E.
TI Old versus new FIGO staging systems in predicting overall survival in
patients with uterine leiomyosarcoma: A study of 86 cases
SO GYNECOLOGIC ONCOLOGY
LA English
DT Article
DE Leiomyosarcoma; FIGO; Staging; Uterus; Survival
ID GYNECOLOGIC-ONCOLOGY-GROUP; SMOOTH-MUSCLE TUMORS; PROGNOSTIC-FACTORS;
TREATMENT MODALITIES; ADJUVANT THERAPY; LYMPH-NODE; SARCOMA; UTERUS;
CANCER; EXPERIENCE
AB Objectives. Uterine leiomyosarcoma (uLMS) was staged using the FIGO system for endometrial cancers. The new FIGO system takes into consideration tumor size disregarding myometrial and cervical involvement. We aimed to compare the two systems and gee Which more accurately predicts overall survival (OS).
Methods. 86 patients with uLMS (1984-2010) Were retrospectively staged using both FIGO systems. Mean OS rates were estimated using the Kaplan-Meier method.
Results. More patients had stage-I disease by the new FIGO system (42 versus 33). Five versus 18 and 27 versus 5 had old and new stage-II and III diseases respectively. Five and 4 patients with old stage II and III uLMS respectively were downstaged to stage I while 18 with old stage III were downstaged to stage II. Median follow-up was 23.5 months with a median OS of 114 (95% CI, 61-166) months. Although patients with stage I tumors had a higher mean OS rate compared to those with higher stage disease by either system, patients with old stage II-IV disease showed similar mean OS rates, with stage III-IV patients having a slightly better mean OS and a similar trend was observed with the new system. Patients with new FIGO stage III had a higher mean OS rate than those with stage II or IV disease (37.6 versus 28.1 and 34.3 months). Nonetheless, no statistical significant differences were seen in OS according to stage using either system (p = 0.786 and p = 0.400 respectively).
Conclusion. Neither FIGO staging system is ideal in classifying patients into four clinically significant stages. (c) 2012 Elsevier Inc. All rights reserved.
C1 [Lim, D.] Natl Univ Hlth Syst, Dept Pathol, Singapore, Singapore.
[Wang, W. L.] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA.
[Lee, C. H.; Dodge, T.; Gilks, B.] Vancouver Gen Hosp, Dept Pathol, Vancouver, BC V5Z 1M9, Canada.
[Oliva, E.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
RP Oliva, E (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 2,55 Fruit St, Boston, MA 02114 USA.
EM eoliva@partners.org
NR 56
TC 5
Z9 5
U1 0
U2 2
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD FEB
PY 2013
VL 128
IS 2
BP 322
EP 326
DI 10.1016/j.ygyno.2012.11.009
PG 5
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 083EK
UT WOS:000314445300030
PM 23153591
ER
PT J
AU Safren, SA
O'Cleirigh, CM
Skeer, M
Elsesser, SA
Mayer, KH
AF Safren, Steven A.
O'Cleirigh, Conall M.
Skeer, Margie
Elsesser, Steven A.
Mayer, Kenneth H.
TI Project Enhance: A Randomized Controlled Trial of an Individualized HIV
Prevention Intervention for HIV-Infected Men Who Have Sex With Men
Conducted in a Primary Care Setting
SO HEALTH PSYCHOLOGY
LA English
DT Article
DE MSM; HIV prevention; AIDS/HIV; high-risk sexual behavior; depression
ID BEHAVIORAL INTERVENTION; ANTIRETROVIRAL THERAPY; TRANSMISSION RISK;
UNITED-STATES; POSITIVE MEN; MSM; CHALLENGES; DEPRESSION; ADHERENCE;
COMMUNITY
AB Objective: Men who have sex with men (MSM) are the largest group of individuals in the U. S. living with HIV and have the greatest number of new infections. This study was designed to test a brief, culturally relevant prevention intervention for HIV-infected MSM, which could be integrated into HIV care. Method: HIV-infected MSM who received HIV care in a community health center (N = 201), and who reported HIV sexual transmission-risk behavior (TRB) in the prior 6 months, were randomized to receive the intervention or treatment as usual. The intervention, provided by a medical social worker, included proactive case management for psychosocial problems, counseling about living with HIV, and HIV TRB risk reduction. Participants were followed every 3 months for one year. Results: Participants, regardless of study condition, reported reductions in HIV TRB, with no significant differential effect by condition in primary intent-to-treat analyses. When examining moderators, the intervention was differentially effective in reducing HIV TRB for those who screened in for baseline depression, but this was not the case for those who did not screen in for depression. Conclusions: The similar level of reduction in HIV TRB in the intervention and control groups, consistent with other recent secondary prevention interventions, speaks to the need for new, creative designs, or more potent interventions in secondary HIV prevention trials, as the control group seemed to benefit from risk assessment, study contact, and referrals provided by study staff. The differential finding for those with depression may suggest that those without depression could reap benefits from limited interventions, but those with a comorbid psychiatric diagnosis may require additional interventions to modify their sexual risk behaviors.
C1 [Safren, Steven A.; O'Cleirigh, Conall M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA.
[Safren, Steven A.; O'Cleirigh, Conall M.] Fenway Hlth, Boston, MA USA.
[Skeer, Margie; Elsesser, Steven A.; Mayer, Kenneth H.] Fenway Hlth, Fenway Inst, Boston, MA USA.
[Mayer, Kenneth H.] Brown Univ, Miriam Hosp, Providence, RI 02912 USA.
RP Safren, SA (reprint author), 1 Bowdoin Sq, Boston, MA 02114 USA.
EM ssafren@partners.org
FU NIMH [5R01MH068746-05]
FX This study was supported by NIMH grant 5R01MH068746-05 awarded to
Kenneth H. Mayer and Steven A. Safren. The authors would like to thank
the following individuals for their hard work that made the study
possible: Daniel Aguilar, Jeremy Hobsen, Robert Knauz, Rodney
VanDerwarker, Benjamin Capistrant, Jessica Ripton, Danielle Dang, Liz
Salomon, Bonnie Kissler, Alex Weissman, Adam Sussman, Dhana Perry,
Christopher Sterling, William O'Brien, Brett Goshe, the medical
providers at Fenway Community Health, and the Fenway Community Advisory
Board. We also thank Drs. Margaret Chesney and Ronald Stall for their
consultation about the project. Finally, and most importantly, we thank
the study participants.
NR 34
TC 19
Z9 19
U1 0
U2 10
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0278-6133
J9 HEALTH PSYCHOL
JI Health Psychol.
PD FEB
PY 2013
VL 32
IS 2
BP 171
EP 179
DI 10.1037/a0028581
PG 9
WC Psychology, Clinical; Psychology
SC Psychology
GA 084JT
UT WOS:000314535900007
PM 22746262
ER
PT J
AU Hoogeveen-Westerveld, M
Ekong, R
Povey, S
Mayer, K
Lannoy, N
Elmslie, F
Bebin, M
Dies, K
Thompson, C
Sparagana, SP
Davies, P
van Eeghen, AM
Thiele, EA
van den Ouweland, A
Halley, D
Nellist, M
AF Hoogeveen-Westerveld, Marianne
Ekong, Rosemary
Povey, Sue
Mayer, Karin
Lannoy, Nathalie
Elmslie, Frances
Bebin, Martina
Dies, Kira
Thompson, Catherine
Sparagana, Steven P.
Davies, Peter
van Eeghen, Agnies M.
Thiele, Elizabeth A.
van den Ouweland, Ans
Halley, Dicky
Nellist, Mark
TI Functional Assessment of TSC2 Variants Identified in Individuals with
Tuberous Sclerosis Complex (vol 34, pg 167, 2013)
SO HUMAN MUTATION
LA English
DT Correction
C1 [Hoogeveen-Westerveld, Marianne; van den Ouweland, Ans; Halley, Dicky; Nellist, Mark] Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands.
[Ekong, Rosemary; Povey, Sue] UCL, Res Dept Genet Evolut & Environm, London, England.
[Mayer, Karin] Ctr Human Genet & Lab Med, Martinsried, Germany.
[Lannoy, Nathalie] Ctr Human Genet, Brussels, Belgium.
[Elmslie, Frances] St George Hosp, Dept Med Genet, London, England.
[Bebin, Martina] Univ Alabama Birmingham, Dept Neurol, Birmingham, AL 35294 USA.
[Dies, Kira] Childrens Hosp Boston, Dept Neurol, Boston, MA USA.
[Thompson, Catherine; Sparagana, Steven P.] Texas Scottish Rite Hosp Children, Dept Neurol, Dallas, TX 75219 USA.
[Sparagana, Steven P.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Davies, Peter] Cardiff Univ, Inst Med Genet, Cardiff CF10 3AX, S Glam, Wales.
[Thiele, Elizabeth A.] Massachusetts Gen Hosp, Dept Neurol, Herscot Ctr Tuberous Sclerosis Complex, Boston, MA 02114 USA.
RP Hoogeveen-Westerveld, M (reprint author), Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands.
NR 1
TC 0
Z9 0
U1 1
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1059-7794
J9 HUM MUTAT
JI Hum. Mutat.
PD FEB
PY 2013
VL 34
IS 2
BP 409
EP 410
DI 10.1002/humu.22256
PG 2
WC Genetics & Heredity
SC Genetics & Heredity
GA 083PP
UT WOS:000314477700021
ER
PT J
AU Aganj, I
Yeo, BTT
Sabuncu, MR
Fischl, B
AF Aganj, Iman
Yeo, Boon Thye Thomas
Sabuncu, Mert R.
Fischl, Bruce
TI On Removing Interpolation and Resampling Artifacts in Rigid Image
Registration
SO IEEE TRANSACTIONS ON IMAGE PROCESSING
LA English
DT Article
DE Aliasing; image registration; image resampling; interpolation artifacts
ID MUTUAL-INFORMATION; SUBPIXEL REGISTRATION; MRI DATA; MAXIMIZATION;
DESIGN; RECONSTRUCTION; CONVOLUTION; ROTATIONS; SERIES; SIGNAL
AB We show that image registration using conventional interpolation and summation approximations of continuous integrals can generally fail because of resampling artifacts. These artifacts negatively affect the accuracy of registration by producing local optima, altering the gradient, shifting the global optimum, and making rigid registration asymmetric. In this paper, after an extensive literature review, we demonstrate the causes of the artifacts by comparing inclusion and avoidance of resampling analytically. We show the sum-of-squared-differences cost function formulated as an integral to be more accurate compared with its traditional sum form in a simple case of image registration. We then discuss aliasing that occurs in rotation, which is due to the fact that an image represented in the Cartesian grid is sampled with different rates in different directions, and propose the use of oscillatory isotropic interpolation kernels, which allow better recovery of true global optima by overcoming this type of aliasing. Through our experiments on brain, fingerprint, and white noise images, we illustrate the superior performance of the integral registration cost function in both the Cartesian and spherical coordinates, and also validate the introduced radial interpolation kernel by demonstrating the improvement in registration.
C1 [Aganj, Iman; Yeo, Boon Thye Thomas; Sabuncu, Mert R.; Fischl, Bruce] Harvard Univ, Athinoula A Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp, Sch Med, Charlestown, MA 02129 USA.
[Aganj, Iman] MIT, Lab Informat & Decis Syst, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA.
[Yeo, Boon Thye Thomas] Duke NUS Grad Med Sch, Dept Neurosci & Behav Disorders, Singapore, Singapore.
[Sabuncu, Mert R.; Fischl, Bruce] MIT, Comp Sci & Artificial Intelligence Lab, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA.
[Fischl, Bruce] MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
RP Aganj, I (reprint author), Harvard Univ, Athinoula A Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp, Sch Med, Charlestown, MA 02129 USA.
EM iman@nmr.mgh.harvard.edu; ythomas@csail.mit.edu; msabuncu@csail.mit.edu;
fischl@nmr.mgh.harvard.edu
OI Yeo, B.T. Thomas/0000-0002-0119-3276
FU National Center for Research Resources [P41-RR14075]; NCRR BIRN
Morphometric Project [BIRN002, U24RR021382]; National Institute for
Biomedical Imaging and Bioengineering [R01EB006758]; National Institute
on Aging [AG022381]; National Center for Alternative Medicine [RC1
AT005728-01]; National Institute for Neurological Disorders and Stroke
[R01NS052585-01, 1R21NS072652-01, 1R01NS070963]; Shared Instrumentation
Grant [1S10RR023401, 1S10RR019307, 1S10RR023043]; Ellison Medical
Foundation; NIH Blueprint for Neuroscience Research [5U01-MH093765];
multi-institutional Human Connectome Project; Harvard Catalyst; Harvard
Clinical and Translational Science Center under NIH [1KL2RR025757-01];
Harvard University; NIH [NIBIB 1K25EB013649-01]
FX This work was supported in part by the National Center for Research
Resources (P41-RR14075 and the NCRR BIRN Morphometric Project BIRN002,
U24RR021382), the National Institute for Biomedical Imaging and
Bioengineering (R01EB006758), the National Institute on Aging
(AG022381), the National Center for Alternative Medicine (RC1
AT005728-01), the National Institute for Neurological Disorders and
Stroke (R01NS052585-01, 1R21NS072652-01, 1R01NS070963), the Shared
Instrumentation Grant 1S10RR023401, Grant 1S10RR019307, and Grant
1S10RR023043, the Autism and Dyslexia Project funded by the Ellison
Medical Foundation, and the NIH Blueprint for Neuroscience Research
(5U01-MH093765), part of the multi-institutional Human Connectome
Project. The work of M. R. Sabuncu was supported in part by Harvard
Catalyst, under the KL2 Medical Research Investigator Training (MeRIT)
Grant, the Harvard Clinical and Translational Science Center under NIH
Grant 1KL2RR025757-01 and financial contributions from Harvard
University and its affiliated academic health care centers, and the NIH
K25 Grant NIBIB 1K25EB013649-01. The associate editor coordinating the
review of this manuscript and approving it for publication was Prof.
Marios S. Pattichis.
NR 71
TC 6
Z9 6
U1 0
U2 30
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 1057-7149
J9 IEEE T IMAGE PROCESS
JI IEEE Trans. Image Process.
PD FEB
PY 2013
VL 22
IS 2
BP 816
EP 827
DI 10.1109/TIP.2012.2224356
PG 12
WC Computer Science, Artificial Intelligence; Engineering, Electrical &
Electronic
SC Computer Science; Engineering
GA 086VW
UT WOS:000314717800033
PM 23076044
ER
PT J
AU Singh, KK
Wang, Y
Gray, KP
Farhad, M
Brummel, S
Fenton, T
Trout, R
Spector, SA
AF Singh, Kumud K.
Wang, Yan
Gray, Kathryn P.
Farhad, Mona
Brummel, Sean
Fenton, Terence
Trout, Rodney
Spector, Stephen A.
TI Genetic Variants in the Host Restriction Factor APOBEC3G are Associated
With HIV-1-Related Disease Progression and Central Nervous System
Impairment in Children
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE APOBEC3G; polymorphisms; HIV-1; children; disease progression; CNS
impairment
ID RNA-EDITING ENZYME; HIV-1 VIF; ANTIVIRAL ACTIVITY; POLYMORPHISMS;
DEGRADATION; INFECTION; AIDS; PROTEASOME; DIDANOSINE; ZIDOVUDINE
AB Background: Apolipoprotein B mRNA editing catalytic polypeptide 3G (APOBEC3G) protein is incorporated into nascent virus particles and mediates cytidine deamination (C-to-U) of first-strand reverse transcripts of HIV-1 in target cells resulting in G-to-A hypermutation of the coding strand and premature degradation. We investigated the effects of APOBEC3G genetic variants on HIV-1-related disease in children.
Methods: APOBEC3G variants were detected using real-time polymerase chain reaction in HIV-1-infected children from Pediatric AIDS Clinical Trials Group (PACTG) protocols P152 and P300 that evaluated the effectiveness of 3 mono-or dual-nucleoside reverse transcriptase inhibitor treatments.
Results: Of the 1049 children evaluated, 60% were non-Hispanic black, 26% Hispanic, 13% non-Hispanicwhite, and1% other or unknown race/ethnicity. Age ranged from 42 days to 18 years; 45% were males. APOBEC3G-H186R homozygous G/G genotype was associated with more rapid HIV-1 disease progression [hazard ratio (HR): 1.69; P = 0.01] and central nervous system (CNS) impairment (HR: 2.00; P = 0.02) compared with the wild-type A/A or heterozygous A/G genotype in a recessive model. In both additive and dominant models, APOBEC3G-F119F-C allele was associated with protection against disease progression (HR [additive]: 0.69; P = 0.002 and HR [dominant]: 0.60; P = 0.001, respectively) and CNS impairment (HR [additive]: 0.65; P = 0.02 and HR [dominant]: 0.54; P = 0.007, respectively). These associations remained significant in multivariate analyses controlling for baseline characteristics or previously identified genetic variants known to alter HIV-1-related disease in this cohort of children.
Conclusions: APOBEC3G-H186R and F119F variants are associated with altered HIV-1-related disease progression and CNS impairment in children.
C1 [Singh, Kumud K.; Trout, Rodney; Spector, Stephen A.] Univ Calif San Diego, Dept Pediat, Div Infect Dis, La Jolla, CA 92093 USA.
[Wang, Yan; Gray, Kathryn P.; Farhad, Mona; Brummel, Sean; Fenton, Terence] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA.
[Gray, Kathryn P.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Spector, Stephen A.] Rady Childrens Hosp San Diego, San Diego, CA USA.
RP Spector, SA (reprint author), Univ Calif San Diego, Dept Pediat, 9500 Gilman Dr, La Jolla, CA 92093 USA.
EM kusingh@ucsd.edu; saspector@ucsd.edu
FU International Maternal Perinatal Adolescent AIDS Clinical Trials
(IMPAACT) Network; National Institute of Allergy and Infectious Diseases
(NIAID) [U01 AI068632]; Eunice Kennedy Shriver National Institute of
Child Health and Human Development (NICHD); National Institute of Mental
Health (NIMH) [AI068632]; Statistical and Data Analysis Center at
Harvard School of Public Health under the National Institute of Allergy
and Infectious Diseases [5 U01 AI41110]; Pediatric AIDS Clinical Trials
Group (PACTG); IMPAACT Group [U01 AI068616]; National Institute of
Allergy and Infectious Diseases (NIAID); NICHD International and
Domestic Pediatric and Maternal HIV Clinical Trials Network; NICHD
[N01-DK-9-001/HHSN267200800001C]; National Institute of Health
[1R01NS077874, 5R01MH085608]
FX This research was supported in part by the International Maternal
Perinatal Adolescent AIDS Clinical Trials (IMPAACT) Network. Overall
support for the International Maternal Pediatric Adolescent AIDS
Clinical Trials Group (IMPAACT) was provided by the National Institute
of Allergy and Infectious Diseases (NIAID) [U01 AI068632], the Eunice
Kennedy Shriver National Institute of Child Health and Human Development
(NICHD), and the National Institute of Mental Health (NIMH) [AI068632].
The content is solely the responsibility of the authors and does not
necessarily represent the official views of the NIH. This work was
supported by the Statistical and Data Analysis Center at Harvard School
of Public Health, under the National Institute of Allergy and Infectious
Diseases cooperative agreement #5 U01 AI41110 with the Pediatric AIDS
Clinical Trials Group (PACTG) and U01 AI068616 with the IMPAACT Group.
Support of the sites was provided by the National Institute of Allergy
and Infectious Diseases (NIAID) and the NICHD International and Domestic
Pediatric and Maternal HIV Clinical Trials Network funded by NICHD
(contract number N01-DK-9-001/HHSN267200800001C), and supported by
National Institute of Health. 1R01NS077874 (S. A. S.) and 5R01MH085608
(K.K.S.).
NR 33
TC 18
Z9 18
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD FEB 1
PY 2013
VL 62
IS 2
BP 197
EP 203
DI 10.1097/QAI.0b013e31827ab612
PG 7
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 083JM
UT WOS:000314459500016
PM 23138837
ER
PT J
AU Barbeau, EB
Soulieres, I
Dawson, M
Zeffiro, TA
Mottron, L
AF Barbeau, Elise B.
Soulieres, Isabelle
Dawson, Michelle
Zeffiro, Thomas A.
Mottron, Laurent
TI The Level and Nature of Autistic Intelligence III: Inspection Time
SO JOURNAL OF ABNORMAL PSYCHOLOGY
LA English
DT Article
DE autism; Asperger syndrome; perception; processing speed; Raven
Progressive Matrices
ID CHILDREN; SPEED; DISORDER; SPECTRUM; INDIVIDUALS; PERFORMANCE;
ABILITIES; SAVANT; FMRI; IQ
AB Across the autism spectrum, level of intelligence is highly dependent on the psychometric instrument used for assessment, and there are conflicting views concerning which measures best estimate autistic cognitive abilities. Inspection time is a processing speed measure associated with general intelligence in typical individuals. We therefore investigated autism spectrum performance on inspection time in relation to two different general intelligence tests. Autism spectrum individuals were divided into autistic and Asperger subgroups according to speech development history. Compared to a typical control group, mean inspection time for the autistic subgroup but not the Asperger subgroup was significantly shorter (by 31%). However, the shorter mean autistic inspection time was evident only when groups were matched on Wechsler IQ and disappeared when they were matched using Raven's Progressive Matrices. When autism spectrum abilities are compared to typical abilities, results may be influenced by speech development history as well as by the instrument used for intelligence matching.
C1 [Barbeau, Elise B.; Soulieres, Isabelle; Mottron, Laurent] Univ Montreal, Fernand Seguin Res Ctr, CET EDUM, Montreal, PQ, Canada.
[Barbeau, Elise B.; Mottron, Laurent] Univ Montreal, Dept Psychiat, Montreal, PQ H3C 3J7, Canada.
[Soulieres, Isabelle] Univ Montreal, Dept Psychol, Montreal, PQ H3C 3J7, Canada.
[Zeffiro, Thomas A.] Massachusetts Gen Hosp, Neural Syst Grp, Boston, MA 02114 USA.
RP Mottron, L (reprint author), Hop Riviere Des Prairies, 7070 Blvd Perras, Montreal, PQ H1E 1A4, Canada.
EM mottronl@uniserve.com
FU Canadian Institutes of Health Research
NR 44
TC 21
Z9 21
U1 7
U2 44
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0021-843X
J9 J ABNORM PSYCHOL
JI J. Abnorm. Psychol.
PD FEB
PY 2013
VL 122
IS 1
BP 295
EP 301
DI 10.1037/a0029984
PG 7
WC Psychology, Clinical; Psychology, Multidisciplinary
SC Psychology
GA 085VD
UT WOS:000314641500032
PM 23088375
ER
PT J
AU Goldvasser, D
Marchie, A
Bragdon, LK
Bragdon, CR
Weidenhielm, L
Malchau, H
AF Goldvasser, Dov
Marchie, Anthony
Bragdon, Louisa K.
Bragdon, Charles R.
Weidenhielm, Lars
Malchau, Henrik
TI Incidence of Osteolysis in Total Knee Arthroplasty Comparison Between
Radiographic and Retrieval Analysis
SO JOURNAL OF ARTHROPLASTY
LA English
DT Article
DE total knee arthroplasty; polyethylene; wear; radiograph; Computed
tomography
ID POLYETHYLENE TIBIAL INSERTS; TOTAL HIP-ARTHROPLASTY; WEAR; PROSTHESES;
COMPONENT; REPLACEMENT; THICKNESS; FAILURE; JOINT
AB Detection of polyethylene wear and osteolysis in total knee arthroplasty using radiographs is imprecise. To correlate radiographic findings with retrieved tibial component analysis, we reviewed knee revision cases. A joint registry was used to identify all knee revisions. Radiographic scoring systems were developed. Radiographs were analyzed for osteolysis and implant alignment. Polyethylene liner retrievals were visually and optically graded for surface damage. Statistical analyses that included correlation analysis and Mann-Whitney U test were used. When osteolysis was found, radiographic scores and delamination score were significantly higher (P = .047 and P = .014, respectively). Delamination is a good indicator for polyethylene wear and osteolysis. There is a need to develop in vivo methods to identify polyethylene changes and thereby prevent severe clinical outcomes.
C1 [Goldvasser, Dov; Marchie, Anthony; Bragdon, Louisa K.; Bragdon, Charles R.; Malchau, Henrik] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Goldvasser, Dov; Weidenhielm, Lars] Karolinska Inst, Sect Orthopaed & Sport Med, Dept Mol Med & Surg, Stockholm, Sweden.
RP Goldvasser, D (reprint author), Massachusetts Gen Hosp, Harris Orthopaed Labs, 55 Fruit St, Boston, MA 02114 USA.
OI Malchau, Henrik/0000-0002-4291-2441
NR 22
TC 5
Z9 5
U1 0
U2 12
PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS
PI PHILADELPHIA
PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA
SN 0883-5403
J9 J ARTHROPLASTY
JI J. Arthroplast.
PD FEB
PY 2013
VL 28
IS 2
BP 201
EP 206
DI 10.1016/j.arth.2012.06.008
PG 6
WC Orthopedics
SC Orthopedics
GA 083CP
UT WOS:000314440600001
PM 22868074
ER
PT J
AU Saunders, JE
Beeson, CC
Schnellmann, RG
AF Saunders, Janet E.
Beeson, Craig C.
Schnellmann, Rick G.
TI Characterization of functionally distinct mitochondrial subpopulations
SO JOURNAL OF BIOENERGETICS AND BIOMEMBRANES
LA English
DT Article
DE Mitochondria; Heterogeneity; Flow cytometry; Kidney; Subpopulations
ID SKELETAL-MUSCLE MITOCHONDRIA; FLOW-CYTOMETRIC ANALYSIS; RAT
CARDIAC-MUSCLE; INTERMYOFIBRILLAR MITOCHONDRIA;
OXIDATIVE-PHOSPHORYLATION; PERMEABILITY TRANSITION; LIVER-MITOCHONDRIA;
LIGHT SCATTER; INTERFIBRILLAR MITOCHONDRIA; HEART-MITOCHONDRIA
AB Mitochondrial stress results in changes in mitochondrial function, morphology and homeostasis (biogenesis, fission/fusion, mitophagy) and may lead to changes in mitochondrial subpopulations. While flow cytometric techniques have been developed to quantify features of individual mitochondria related to volume, Ca2+ concentration, mtDNA content, respiratory capacity and oxidative damage, less information is available concerning the identification and characterization of mitochondrial subpopulations, particularly in epithelial cells. Mitochondria from rabbit kidneys were stained with molecular probes for cardiolipin content (nonyl acridine orange, NAO) and membrane potential (tetramethylrhodamine, TMRM) and analyzed using flow cytometry. We validated that side scatter was a better indicator of volume and that as side scatter (SSC) decreased mitochondrial volume increased. Furthermore, those mitochondria with the highest NAO content had greater side scattering and were most highly charged. Mitochondria with average NAO content were of average side scattering and maintained an intermediate charge. Those mitochondria with low NAO content had minimal side scattering and exhibited minimal charge. Upon titration with the uncoupler carbonylcyanide-4-(trifluoromethoxy)-phenylhydrazone (FCCP), it was found that the high NAO content subpopulations were more resistant to uncoupling than lower NAO content populations. Ca2+-induced swelling of mitochondria was evaluated using probability binning (PB) analyses of SSC. Interestingly, only 30 % of the mitochondria showed changes in response to Ca2+, which was blocked by cyclosporine A. In addition, the small, high NAO content mitochondria swelled differentially in response to Ca2+ over time. Our results demonstrate that flow cytometry can be used to identify mitochondrial subpopulations based on high, mid and low NAO content and/or volume/complexity. These subpopulations showed differences in membrane potential, volume, and responses to uncoupling and Ca2+-induced swelling.
C1 [Saunders, Janet E.; Beeson, Craig C.; Schnellmann, Rick G.] Med Univ S Carolina, Dept Pharmaceut & Biomed Sci, Ctr Cell Death Injury & Regenerat, Charleston, SC 29425 USA.
[Beeson, Craig C.] Med Univ S Carolina, Dept Pharmaceut & Biomed Sci, Charleston, SC 29425 USA.
[Schnellmann, Rick G.] Ralph Johnson VA Med Ctr, Charleston, SC 29401 USA.
RP Beeson, CC (reprint author), Med Univ S Carolina, Dept Pharmaceut & Biomed Sci, 280 Calhoun St,MSC140, Charleston, SC 29425 USA.
EM beesonc@musc.edu
FU NIH [GM 084147, C06 RR-015455]; NIM/NIEHS [T32ES012878-05]; NIH/NHLBI
[T32HL007260-34]; Department of Veterans Affairs
FX This study was supported by NIH Grant GM 084147, the NIM/NIEHS Training
Program in Environmental Stress Signaling T32ES012878-05 and NIH/NHLBI
Training to Improve Cardiovascular Therapies T32HL007260-34, and by the
Biomedical Laboratory Research and Development Program of the Department
of Veterans Affairs. Animal facilities were funded by NIH grant C06
RR-015455
NR 43
TC 6
Z9 6
U1 0
U2 22
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0145-479X
J9 J BIOENERG BIOMEMBR
JI J. Bioenerg. Biomembr.
PD FEB
PY 2013
VL 45
IS 1-2
BP 87
EP 99
DI 10.1007/s10863-012-9478-4
PG 13
WC Biophysics; Cell Biology
SC Biophysics; Cell Biology
GA 089GR
UT WOS:000314899500008
PM 23080405
ER
PT J
AU Perron, NR
Beeson, C
Rohrer, B
AF Perron, Nathan R.
Beeson, Craig
Rohrer, Barbel
TI Early alterations in mitochondrial reserve capacity; a means to predict
subsequent photoreceptor cell death
SO JOURNAL OF BIOENERGETICS AND BIOMEMBRANES
LA English
DT Article
DE Mitochondrial respiration; Cell death; Photoreceptors; Retinitis
pigmentosa
ID RETINAL MULLER CELLS; ACID PROTEIN ASSAY; OXIDATIVE STRESS;
BICINCHONINIC ACID; ENERGY-METABOLISM; ROD PHOTORECEPTORS; DEGENERATION;
CALCIUM; SUPEROXIDE; MECHANISMS
AB Although genetic and environmental factors contribute to neurodegenerative disease, the underlying etiology common to many diseases might be based on metabolic demand. Mitochondria are the main producer of ATP, but are also the major source of reactive oxygen species. Under normal conditions, these oxidants are neutralized; however, under environmental insult or genetic susceptibility conditions, oxidative stress may exceed cellular antioxidant capacities, leading to degeneration. We tested the hypothesis that loss in mitochondrial reserve capacity plays a causative role in neuronal degeneration and chose a cone photoreceptor cell line as our model. 661W cells were exposed to agents that mimic oxidant stress or calcium overload. Real-time changes in cellular metabolism were assessed using the multi-well Seahorse Biosciences XF24 analyzer that measures oxygen consumption (OCR) and extracellular acidification rates (ECAR). Cellular stress resulted in an early loss of mitochondrial reserve capacity, without affecting basal respiration; and ECAR was increased, representing a compensatory shift of ATP productions toward glycolysis. The degree of change in energy metabolism was correlated with the amount of subsequent cell death 24-hours post-treatment, the concentration-dependent loss in mitochondrial reserve capacity correlated with the number of live cells. Our data suggested first, that loss in mitochondrial reserve capacity is a major contributor in disease pathogenesis; and second, that the XF24 assay might represent a useful surrogate assay amenable to the screening of agents that protect against loss of mitochondrial reserve capacity. In future experiments, we will explore these concepts for the development of neuroprotective agents.
C1 [Rohrer, Barbel] Med Univ S Carolina, Dept Ophthalmol, Charleston, SC 29425 USA.
[Perron, Nathan R.; Beeson, Craig] Med Univ S Carolina, Dept Pharmaceut Sci, Charleston, SC 29425 USA.
[Rohrer, Barbel] Ralph H Johnson VA Med Ctr, Dept Res Serv, Charleston, SC 29425 USA.
[Beeson, Craig] Med Univ S Carolina, Coll Pharm Pharmaceut & Biomed Sci, Charleston, SC 29425 USA.
RP Rohrer, B (reprint author), Med Univ S Carolina, Dept Ophthalmol, 167 Ashley Ave,SEI 511, Charleston, SC 29425 USA.
EM beesonc@musc.edu; rohrer@musc.edu
FU National Institutes of Health [EY013520, EY019320]; Department for
Veterans Affairs [RX000444]; Foundation Fighting Blindness; Research to
Prevent Blindness (RPB), New York, NY
FX This work was supported in part by National Institutes of Health grant
EY013520, EY019320 (B.R.), a Department for Veterans Affairs merit award
RX000444 (B.R.), the WG-TRAP award by Foundation Fighting Blindness
(B.R. and C.B.), and an unrestricted grant to MUSC from Research to
Prevent Blindness (RPB), New York, NY. B.R. is a RPB Olga Keith Wiess
Scholar.
NR 56
TC 11
Z9 11
U1 0
U2 16
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0145-479X
J9 J BIOENERG BIOMEMBR
JI J. Bioenerg. Biomembr.
PD FEB
PY 2013
VL 45
IS 1-2
BP 101
EP 109
DI 10.1007/s10863-012-9477-5
PG 9
WC Biophysics; Cell Biology
SC Biophysics; Cell Biology
GA 089GR
UT WOS:000314899500009
PM 23090843
ER
PT J
AU Hoffmann, U
Sukhotinsky, I
Eikermann-Haerter, K
Ayata, C
AF Hoffmann, Ulrike
Sukhotinsky, Irma
Eikermann-Haerter, Katharina
Ayata, Cenk
TI Glucose modulation of spreading depression susceptibility
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Article
DE animal models; electrophysiology; glucose; migraine; spreading
depression
ID CORTICAL DEPRESSION; BRAIN GLUCOSE; RAT-BRAIN; PERIINFARCT
DEPOLARIZATIONS; ONLINE MICRODIALYSIS; MIGRAINE PROPHYLAXIS;
CEREBRAL-ISCHEMIA; REGIONAL CHANGES; BLOOD-FLOW; CORTEX
AB Spreading depression of Leao is an intense spreading depolarization (SD) wave associated with massive transmembrane ionic, water, and neurotransmitter shifts. Spreading depolarization underlies migraine aura, and occurs in brain injury, making it a potential therapeutic target. While susceptibility to SD can be modulated pharmacologically, much less is known about modulation by systemic physiological factors, such as the glycemic state. In this study, we systematically examined modulation of SD susceptibility by blood glucose in anesthetized rats under full physiological monitoring. Hyperglycemia and hypoglycemia were induced by insulin or dextrose infusion (blood glucose similar to 40 and 400 mg/dL, respectively). Spreading depolarizations were evoked by direct cortical electrical stimulation to determine the intensity threshold, or by continuous topical KCI application to determine SD frequency. Hyperglycemia elevated the electrical SD threshold and reduced the frequency of KCI-induced SDs, without significantly affecting other SD properties. In contrast, hypoglycemia significantly prolonged individual and cumulative SD durations, but did not alter the electrical SD threshold, or SD frequency, amplitude or propagation speed. These data show that increased cerebral glucose availability makes the tissue resistant to SD. Journal of Cerebral Blood Flow & Metabolism (2013) 33, 191-195; doi:10.1038/jcbfm.2012.132; published online 12 September 2012
C1 [Hoffmann, Ulrike; Sukhotinsky, Irma; Eikermann-Haerter, Katharina; Ayata, Cenk] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurovasc Res Lab,Dept Radiol, Charlestown, MA USA.
[Hoffmann, Ulrike] Tech Univ Munich, Klinikum Rechts Isar, Klin Anaesthesiol, D-80290 Munich, Germany.
[Ayata, Cenk] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke Serv, Charlestown, MA USA.
[Ayata, Cenk] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurosci Intens Care Unit,Dept Neurol, Charlestown, MA USA.
RP Ayata, C (reprint author), Neurovasc Res Lab, 149 13th St,Room 6408, Charlestown, MA 02129 USA.
EM cayata@partners.org
FU National Institutes of Health [NS055104, NS061505]
FX This study was supported by the National Institutes of Health (NS055104;
NS061505).
NR 32
TC 10
Z9 12
U1 0
U2 14
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0271-678X
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD FEB
PY 2013
VL 33
IS 2
BP 191
EP 195
DI 10.1038/jcbfm.2012.132
PG 5
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA 087CT
UT WOS:000314739600006
PM 22968322
ER
PT J
AU Zhang, R
Huynh, A
Whitcher, G
Chang, J
Maltzman, JS
Turka, LA
AF Zhang, Ruan
Huynh, Alexandria
Whitcher, Gregory
Chang, JiHoon
Maltzman, Jonathan S.
Turka, Laurence A.
TI An obligate cell-intrinsic function for CD28 in Tregs
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID REGULATORY T-CELLS; TRANSPLANTATION TOLERANCE; CUTTING EDGE;
CD4(+)CD25(+); FOXP3; HOMEOSTASIS; CTLA-4; COMPARTMENTALIZATION;
DIFFERENTIATION; COSTIMULATION
AB Tregs expressing the transcription factor FOXP3 are critical for immune homeostasis. The costimulatory molecule CD28 is required for optimal activation and function of naive T cells; however, its role in Treg function has been difficult to dissect, as CD28 is required for thymic Treg development, and blockade of CD28-ligand. interactions has confounding effects in trans on nonregulatory cells. To address this question, we created Treg-specific Cd28 conditional knockout mice. Despite the presence of normal numbers of FOXP3(+) cells, these animals accumulated large numbers of activated T cells, developed severe autoimmunity that primarily affected the skin and lungs, and failed to appropriately resolve induced experimental allergic encephalomyelitis. This in vivo functional impairment was accompanied by dampened expression of CTLA-4, PD-1, and CCR6. Disease occurrence was not due to subversion of Cd28-deficient Tregs into pathogenic cells, as complementation with normal Tregs prevented disease occurrence. Interestingly, in these "competitive" environments, Cd28-deficient Tregs exhibited a pronounced proliferative/survival disadvantage. These data demonstrate clear postmaturational roles for CD28 in FOXP3(+) Tregs and provide mechanisms which we believe to be novel to explain how interruption of CD28-ligand interactions may enhance immune responses independent of effects on thymic development or on other cell types.
C1 [Zhang, Ruan; Huynh, Alexandria; Whitcher, Gregory; Chang, JiHoon; Turka, Laurence A.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Transplant Inst,Dept Med, Boston, MA 02215 USA.
[Maltzman, Jonathan S.] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA.
RP Turka, LA (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, MGH E,Bldg 149-9019,13th St, Boston, MA 02129 USA.
EM lturka@partners.org
FU NIH [AI-037691, AI-085160]
FX We thank Terry Strom, Arlene Sharpe, Christophe Benoist, and members of
the Turka, Strom, and Maltzman laboratories for many helpful discussions
and Eva Csizmadia and Weihua Gong for technical assistance. This work
was funded by NIH grants AI-037691 and AI-085160.
NR 39
TC 77
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U1 0
U2 6
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
J9 J CLIN INVEST
JI J. Clin. Invest.
PD FEB
PY 2013
VL 123
IS 2
BP 580
EP 593
DI 10.1172/JCI65013
PG 14
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 084QG
UT WOS:000314553600015
PM 23281398
ER
PT J
AU Lotinun, S
Kiviranta, R
Matsubara, T
Alzate, JA
Neff, L
Luth, A
Koskivirta, I
Kleuser, B
Vacher, J
Vuorio, E
Horne, WC
Baron, R
AF Lotinun, Sutada
Kiviranta, Riku
Matsubara, Takuma
Alzate, Jorge A.
Neff, Lynn
Lueth, Anja
Koskivirta, Ilpo
Kleuser, Burkhard
Vacher, Jean
Vuorio, Eero
Horne, William C.
Baron, Roland
TI Osteoclast-specific cathepsin K deletion stimulates S1P-dependent bone
formation
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID DEFICIENT MICE; SPHINGOSINE 1-PHOSPHATE; PARATHYROID-HORMONE; TRANSGENIC
MICE; HOMEOSTASIS; RESORPTION; EXPRESSION; MASS; PYCNODYSOSTOSIS;
OSTEOPETROSIS
AB Cathepsin K (CTSK) is secreted by osteoclasts to degrade collagen and other matrix proteins during bone resorption. Global deletion of Ctsk in mice decreases bone resorption, leading to osteopetrosis, but also increases the bone formation rate (BFR). To understand how Ctsk deletion increases the BFR, we generated osteoclast- and osteoblast-targeted Ctsk knockout mice using floxed Ctsk alleles. Targeted ablation of Ctsk in hematopoietic cells, or specifically in osteoclasts and cells of the monocyte-osteoclast lineage, resulted in increased bone volume and BFR as well as osteoclast and osteoblast numbers. In contrast, targeted deletion of Ctsk in osteoblasts had no effect on bone resorption or BFR, demonstrating that the increased BFR is osteoclast dependent. Deletion of Ctsk in osteoclasts increased their sphingosine kinase 1 (Sphk1) expression. Conditioned media from Ctsk-deficient osteoclasts, which contained elevated levels of sphingosine-l-phosphate (S1P), increased alkaline phosphatase and mineralized nodules in osteoblast cultures. An S1P(1,3) receptor antagonist inhibited these responses. Osteoblasts derived from mice with Ctsk-deficient osteoclasts had an increased RANKL/OPG ratio, providing a positive feedback loop that increased the number of osteoclasts. Our data provide genetic evidence that deletion of CTSK in osteoclasts enhances bone formation in vivo by increasing the generation of osteoclast-derived S1P.
C1 [Lotinun, Sutada; Kiviranta, Riku; Matsubara, Takuma; Alzate, Jorge A.; Neff, Lynn; Horne, William C.; Baron, Roland] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA.
[Kiviranta, Riku; Koskivirta, Ilpo] Univ Turku, Dept Med Biochem, Turku, Finland.
[Kiviranta, Riku; Koskivirta, Ilpo; Vuorio, Eero] Univ Turku, Dept Genet & Med, Turku, Finland.
[Lueth, Anja; Kleuser, Burkhard] Univ Potsdam, Inst Nutr Sci, Dept Nutr Toxicol, Bergholz Rehbrucke, Germany.
[Vacher, Jean] Univ Montreal, Fac Med, Clin Res Inst Montreal, Montreal, PQ H3C 3J7, Canada.
[Baron, Roland] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02115 USA.
RP Baron, R (reprint author), Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, 188 Longwood Ave,REB 310, Boston, MA 02115 USA.
EM roland_baron@hsdm.harvard.edu
FU Procter Gamble
FX We thank Kei Yamana for providing PCR primer sequences. We also thank
Nicholas Brady, Chantel Lester, and Antonios Aliprands for mu CT
analysis. Confocal analysis was performed at the Harvard NeuroDiscovery
Center (Boston, Massachusetts, USA). This work was supported in part by
Procter & Gamble.
NR 54
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U2 29
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
J9 J CLIN INVEST
JI J. Clin. Invest.
PD FEB
PY 2013
VL 123
IS 2
BP 666
EP 681
DI 10.1172/JCI64840
PG 16
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 084QG
UT WOS:000314553600023
PM 23321671
ER
PT J
AU Tzatsos, A
Paskaleva, P
Ferrari, F
Deshpande, V
Stoykova, S
Contino, G
Wong, KK
Lan, F
Trojer, P
Park, PJ
Bardeesy, N
AF Tzatsos, Alexandros
Paskaleva, Polina
Ferrari, Francesco
Deshpande, Vikram
Stoykova, Svetlana
Contino, Gianmarco
Wong, Kwok-Kin
Lan, Fei
Trojer, Patrick
Park, Peter J.
Bardeesy, Nabeel
TI KDM2B promotes pancreatic cancer via Polycomb-dependent and -independent
transcriptional programs
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID REGULATES CELL-PROLIFERATION; GENE-EXPRESSION SIGNATURE; ZESTE HOMOLOG
2; DUCTAL ADENOCARCINOMA; HISTONE DEMETHYLASE; EMBRYONIC FIBROBLASTS;
PATHWAY; MOUSE; TRANSFORMATION; TUMORIGENESIS
AB Epigenetic mechanisms mediate heritable control of cell identity in normal cells and cancer. We sought to identify epigenetic regulators driving the pathogenesis of pancreatic ductal adenocarcinoma (PDAC), one of the most lethal human cancers. We found that KDM2B (also known as Ndy1, FBXL10, and JHDM1B), an H3K36 histone demethylase implicated in bypass of cellular senescence and somatic cell reprogramming, is markedly overexpressed in human PDAC, with levels increasing with disease grade and stage, and highest expression in metastases. KDM2B silencing abrogated tumorigenicity of PDAC cell lines exhibiting loss of epithelial differentiation, whereas KDM2B overexpression cooperated with Kras(G12D) to promote PDAC formation in mouse models. Gain- and loss-of-function experiments coupled to genome-wide gene expression and ChIP studies revealed that KDM2B drives tumorigenicity through 2 different transcriptional mechanisms. KDM2B repressed developmental genes through cobinding with Polycomb group (PcG) proteins at transcriptional start sites, whereas it activated a module of metabolic genes, including mediators of protein synthesis and mitochondrial function, cobound by the MYC oncogene and the histone demethylase KDM5A. These results defined epigenetic programs through which KDM2B subverts cellular differentiation and drives the pathogenesis of an aggressive subset of PDAC.
C1 [Tzatsos, Alexandros; Paskaleva, Polina; Stoykova, Svetlana; Contino, Gianmarco; Bardeesy, Nabeel] Massachusetts Gen Hosp Canc Ctr, Boston, MA USA.
[Tzatsos, Alexandros; Wong, Kwok-Kin; Bardeesy, Nabeel] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Ferrari, Francesco; Park, Peter J.] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA USA.
[Deshpande, Vikram] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Deshpande, Vikram] Harvard Univ, Sch Med, Boston, MA USA.
[Wong, Kwok-Kin] Dana Farber Harvard Canc Ctr, Dept Med Oncol, Boston, MA USA.
[Lan, Fei; Trojer, Patrick] Constellat Pharmaceut, Cambridge, MA USA.
RP Tzatsos, A (reprint author), 185 Cambridge St, Boston, MA 02114 USA.
EM Tzatsos.Alexandros@mgh.harvard.edu; Bardeesy.Nabeel@mgh.harvard.edu
RI Ferrari, Francesco/H-5007-2012;
OI Ferrari, Francesco/0000-0002-9811-3753; Contino,
Gianmarco/0000-0001-5874-0405; wong, kwok kin/0000-0001-6323-235X
FU Waxman Foundation; NCI [P01 CA117969-06, P50 CA127003, 1 R01
CA133557-01]; Andrew Warshaw Institute; Lynda J. Verville Foundation;
Nestora fund; NIH [K99 CA158582]; Massachusetts Biomedical Research
Corporation Tosteson Fellowship Award
FX We are grateful to Nick Dyson, Mo Motamedi, Leif Ellisen, and Rushika
Perera for critical reading of the manuscript and to members of the
Bardeesy lab for helpful discussions throughout the course of these
studies. This work was supported by grants from the Waxman Foundation,
the NCI (P01 CA117969-06, P50 CA127003, and 1 R01 CA133557-01), the
Andrew Warshaw Institute, and the Lynda J. Verville Foundation to N.
Bardeesy. A. Tzatsos is supported by the Nestora fund, NIH grant K99
CA158582, and the Massachusetts Biomedical Research Corporation Tosteson
Fellowship Award.
NR 48
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U1 0
U2 25
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
J9 J CLIN INVEST
JI J. Clin. Invest.
PD FEB
PY 2013
VL 123
IS 2
BP 727
EP 739
DI 10.1172/JCI64535
PG 13
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 084QG
UT WOS:000314553600027
PM 23321669
ER
PT J
AU Seo, JH
Miyamoto, N
Hayakawa, K
Pham, LDD
Maki, T
Ayata, C
Kim, KW
Lo, EH
Arai, K
AF Seo, Ji Hae
Miyamoto, Nobukazu
Hayakawa, Kazuhide
Pham, Loc-Duyen D.
Maki, Takakuni
Ayata, Cenk
Kim, Kyu-Won
Lo, Eng H.
Arai, Ken
TI Oligodendrocyte precursors induce early blood-brain barrier opening
after white matter injury
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID RAT-BRAIN; STROKE; CELLS; ACTIVATION; PROLIFERATION; REGENERATION;
REPERFUSION; ASTROCYTES; PLASTICITY; ISCHEMIA
AB Oligodendrocyte precursor cells (OPCs) are thought to maintain homeostasis and contribute to long-term repair in adult white matter; however, their roles in the acute phase after brain injury remain unclear. Mice that were subjected to prolonged cerebral hypoperfusion stress developed white matter demyelination over time. Prior to demyelination, we detected increased MMP9 expression, blood-brain barrier (BBB) leakage, and neutrophil infiltration in damaged white matter. Notably, at this early stage, OPCs made up the majority of MMP9-expressing cells. The standard MMP inhibitor GM6001 reduced the early BBB leakage and neutrophil infiltration, indicating that OPC-derived MMP9 induced early BBB disruption after white matter injury. Cell-culture experiments confirmed that OPCs secreted MMP9 under pathological conditions, and conditioned medium prepared from the stressed OPCs weakened endothelial barrier tightness in vitro. Our study reveals that OPCs can rapidly respond to white matter injury and produce MMP9 that disrupts the BBB, indicating that OPCs may mediate injury in white matter under disease conditions.
C1 [Seo, Ji Hae; Miyamoto, Nobukazu; Hayakawa, Kazuhide; Pham, Loc-Duyen D.; Maki, Takakuni; Lo, Eng H.; Arai, Ken] Massachusetts Gen Hosp, Dept Radiol, Neuroprotect Res Lab, Boston, MA 02114 USA.
[Seo, Ji Hae; Miyamoto, Nobukazu; Hayakawa, Kazuhide; Pham, Loc-Duyen D.; Maki, Takakuni; Lo, Eng H.; Arai, Ken] Massachusetts Gen Hosp, Dept Neurol, Neuroprotect Res Lab, Boston, MA 02114 USA.
[Seo, Ji Hae; Miyamoto, Nobukazu; Hayakawa, Kazuhide; Pham, Loc-Duyen D.; Maki, Takakuni; Ayata, Cenk; Lo, Eng H.; Arai, Ken] Harvard Univ, Sch Med, Boston, MA USA.
[Seo, Ji Hae; Kim, Kyu-Won] Seoul Natl Univ, Coll Pharm, NeuroVasc Coordinat Res Ctr, Seoul, South Korea.
[Ayata, Cenk] Massachusetts Gen Hosp, Dept Radiol, Neurovasc Res Lab, Boston, MA 02114 USA.
[Kim, Kyu-Won] Seoul Natl Univ, Grad Sch Convergence Sci & Technol, Dept Mol Med & Biopharmaceut Sci, Seoul, South Korea.
[Kim, Kyu-Won] Seoul Natl Univ, Dept Internal Med, Seoul, South Korea.
[Kim, Kyu-Won] Seoul Natl Univ, Innovat Res Inst Cell Therapy, Seoul, South Korea.
RP Arai, K (reprint author), Neuroprotect Res Lab, MGH E 149-2401, Charlestown, MA 02129 USA.
EM lo@helix.mgh.harvard.edu; karai@partners.org
FU Deane Foundation; American Heart Association; NIH; National Research
Foundation of Korea; World Class University Program; Global Research
Laboratory Program
FX This work was supported in part by the Deane Foundation, the American
Heart Association, the NIH, the National Research Foundation of Korea,
the World Class University Program, and the Global Research Laboratory
Program.
NR 25
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U1 0
U2 16
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
J9 J CLIN INVEST
JI J. Clin. Invest.
PD FEB
PY 2013
VL 123
IS 2
BP 782
EP 786
DI 10.1172/JCI65863
PG 5
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 084QG
UT WOS:000314553600031
PM 23281396
ER
PT J
AU Hassan, S
Karpova, Y
Baiz, D
Yancey, D
Pullikuth, A
Flores, A
Register, T
Cline, JM
D'Agostino, R
Danial, N
Datta, SR
Kulik, G
AF Hassan, Sazzad
Karpova, Yelena
Baiz, Daniele
Yancey, Dana
Pullikuth, Ashok
Flores, Anabel
Register, Thomas
Cline, J. Mark
D'Agostino, Ralph, Jr.
Danial, Nika
Datta, Sandeep Robert
Kulik, George
TI Behavioral stress accelerates prostate cancer development in mice
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID PROTEIN-KINASE-A; ANDROGEN RECEPTOR; GROWTH-FACTOR; PHOSPHATIDYLINOSITOL
3-KINASE; BETA(2)-ADRENERGIC RECEPTOR; BAD PHOSPHORYLATION; DISEASE
PROGRESSION; GENE-EXPRESSION; CELLS; SURVIVAL
AB Prostate cancer patients have increased levels of stress and anxiety. Conversely, men who take beta blockers, which interfere with signaling from the stress hormones adrenaline and noradrenaline, have a lower incidence of prostate cancer; however, the mechanisms underlying stress-prostate cancer interactions are unknown. Here, we report that stress promotes prostate carcinogenesis in mice in an adrenaline-dependent manner. Behavioral stress inhibited apoptosis and delayed prostate tumor involution both in phosphatase and tensin homolog-deficient (PTEN-deficient) prostate cancer xenografts treated with PI3K inhibitor and in prostate tumors of mice with prostate-restricted expression of c-MYC (Hi-Myc mice) subjected to androgen ablation therapy with bicalutamide. Additionally, stress accelerated prostate cancer development in Hi-Myc mice. The effects of stress were prevented by treatment with the selective beta(2)-adrenergic receptor (ADRB2) antagonist ICI118,551 or by inducible expression of PKA inhibitor (PKI) or of BCL2-associated death promoter (BAD) with a mutated PKA phosphorylation site (BAD(S112A)) in xenograft tumors. Effects of stress were also blocked in Hi-Myc mice expressing phosphorylation-deficient BAD (BAD(3SA)). These results demonstrate interactions between prostate tumors and the psychosocial environment mediated by activation of an adrenaline/ADRB2/PKA/BAD antiapoptotic signaling pathway. Our findings could be used to identify prostate cancer patients who could benefit from stress reduction or from pharmacological inhibition of stress-induced signaling.
C1 [Hassan, Sazzad; Karpova, Yelena; Baiz, Daniele; Yancey, Dana; Pullikuth, Ashok; Flores, Anabel; Kulik, George] Wake Forest Univ, Bowman Gray Sch Med, Dept Canc Biol, Winston Salem, NC 27157 USA.
[Register, Thomas; Cline, J. Mark] Wake Forest Univ, Bowman Gray Sch Med, Dept Pathol, Winston Salem, NC 27157 USA.
[Register, Thomas; Cline, J. Mark; D'Agostino, Ralph, Jr.; Kulik, George] Wake Forest Univ, Bowman Gray Sch Med, Ctr Comprehens Canc, Winston Salem, NC 27157 USA.
[Danial, Nika] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Datta, Sandeep Robert] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA.
RP Kulik, G (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Dept Canc Biol, Med Ctr Blvd, Winston Salem, NC 27157 USA.
EM gkulik@wakehealth.edu
RI Dagostino Jr, Ralph/C-4060-2017;
OI Dagostino Jr, Ralph/0000-0002-3550-8395; Pullikuth,
Ashok/0000-0002-0041-3310
FU Department of Defense [PC073548]; National Cancer Institute
[R01CA118329]; Wake Forest University Health Sciences; Research
Supplement to Promote Diversity in Health-Related Research
FX The authors are grateful to Anil Sood and Karen Klein for critical
reading and helpful suggestions; to Dina Yamaleeva, Michael Mangiapani,
and Michael Conlin for assistance with image analysis; to John Olson for
MRI imaging; and to Michael Thomas for mass spectrometry detection of
noradrenaline. This work was supported by federal grants PC073548 from
the Department of Defense and R01CA118329 from the National Cancer
Institute and by institutional grants from Wake Forest University Health
Sciences to G. Kulik. D. Yancey was supported in part by Research
Supplement to Promote Diversity in Health-Related Research.
NR 61
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Z9 59
U1 1
U2 21
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
J9 J CLIN INVEST
JI J. Clin. Invest.
PD FEB
PY 2013
VL 123
IS 2
BP 874
EP 886
DI 10.1172/JCI63324
PG 13
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 084QG
UT WOS:000314553600040
PM 23348742
ER
PT J
AU Broder, JS
Hamedani, AG
Liu, SW
Emerman, CL
AF Broder, Joshua S.
Hamedani, Azita G.
Liu, Shan W.
Emerman, Charles L.
TI EMERGENCY DEPARTMENT CONTRAST PRACTICES FOR ABDOMINAL/PELVIC COMPUTED
TOMOGRAPHY-A NATIONAL SURVEY AND COMPARISON WITH THE AMERICAN COLLEGE OF
RADIOLOGY APPROPRIATENESS CRITERIA (R)
SO JOURNAL OF EMERGENCY MEDICINE
LA English
DT Article
DE emergency department; abdominal/pelvic CT(computed tomography);
contrast; guidelines
AB Background: Controversy exists regarding the need for contrast agents for emergency abdominal computed tomography (CT). Objectives: We surveyed United States (US) academic Emergency Departments (EDs) to document national practice. We hypothesized variable contrast use for abdominal/pelvic CT, including variance from the American College of Radiology's (ACR) Appropriateness Criteria (R), an evidence-based guideline. Methods: A survey was sent to physician leaders of US academic EDs, defined as primary site of an Emergency Medicine residency program. Respondents were asked about their institutions' use of oral, intravenous (i.v.), and rectal contrast for various abdominal/ pelvic CT indications. Responses were compared with the approach given the highest appropriateness rating by the American College of Radiology. Results: One hundred and six of 152 (70%) surveys were completed. Intravenous contrast was the most frequently cited contrast. At least 90% of respondents reported using i.v. contrast in 12 of 18 indications. Oral contrast use was more variable. In no indication did >= 90% of respondents indicate use of oral contrast, and in only two indications did >= 90% avoid its use. Rectal contrast was rarely used. The most common indications for which no contrast agent was used were suspected renal colic (79%), viscus perforation (19%), penetrating abdominal trauma (18%), and blunt abdominal trauma (15%). Conclusions: Contrast practices for abdominal/pelvic CT vary nationally, according to a survey of US academic EDs. For multiple indications, the contrast practices of a substantial number of respondents deviated from those recommendations given the highest clinical appropriateness rating by the American College of Radiology. (c) 2013 Elsevier Inc.
C1 [Broder, Joshua S.] Duke Univ, Med Ctr, Dept Surg, Div Emergency Med, Durham, NC 27710 USA.
[Hamedani, Azita G.] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Div Emergency Med, Madison, WI USA.
[Liu, Shan W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA.
[Emerman, Charles L.] Case Western Reserve Univ, Dept Emergency Med, Cleveland, OH 44106 USA.
RP Broder, JS (reprint author), Duke Univ, Med Ctr, Dept Surg, Div Emergency Med, Box 3096, Durham, NC 27710 USA.
OI Broder, Joshua/0000-0001-8030-2831
NR 20
TC 8
Z9 8
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0736-4679
J9 J EMERG MED
JI J. Emerg. Med.
PD FEB
PY 2013
VL 44
IS 2
BP 423
EP 433
DI 10.1016/j.jemermed.2012.08.027
PG 11
WC Emergency Medicine
SC Emergency Medicine
GA 086EC
UT WOS:000314665400063
PM 23164558
ER
PT J
AU Gonen, L
Binder, WD
Nadel, ES
Brown, DFM
AF Gonen, Liza
Binder, William D.
Nadel, Eric S.
Brown, David F. M.
TI EOSINOPHILIA AND RASH
SO JOURNAL OF EMERGENCY MEDICINE
LA English
DT Editorial Material
ID CHURG-STRAUSS-SYNDROME; ADRENAL INSUFFICIENCY; INFECTIONS
C1 [Gonen, Liza; Binder, William D.; Nadel, Eric S.; Brown, David F. M.] Harvard Univ, Sch Med, Div Emergency Med, Boston, MA USA.
[Binder, William D.; Nadel, Eric S.; Brown, David F. M.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.
[Nadel, Eric S.] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA.
RP Brown, DFM (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 55 Fruit St,Founders 114, Boston, MA 02114 USA.
NR 11
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 0736-4679
J9 J EMERG MED
JI J. Emerg. Med.
PD FEB
PY 2013
VL 44
IS 2
BP 469
EP 471
PG 3
WC Emergency Medicine
SC Emergency Medicine
GA 086EC
UT WOS:000314665400071
PM 23103066
ER
PT J
AU Neuhaus, V
Badri, O
Ferree, S
Bot, AGJ
Ring, DC
Mudgal, CS
AF Neuhaus, Valentin
Badri, Omar
Ferree, Steven
Bot, Arjan G. J.
Ring, David C.
Mudgal, Chaitanya S.
TI Radiographic Alignment of Unstable Distal Radius Fractures Fixed With 1
or 2 Rows of Screws in Volar Locking Plates
SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME
LA English
DT Article
DE Distal radius fracture; DVR plate; secondary displacement; volar tilt
ID FIXATION; OSTEOSYNTHESIS; MODEL
AB Purpose We tested the null hypothesis that there is no difference in the change in volar tilt of the articular surface of the distal radius on lateral radiographs obtained before suture removal and 3 months or more after surgical fracture fixation when 1 or 2 rows of screws are used in the distal part of a volar locked plate.
Methods We retrospectively identified 364 consecutive patients with a distal radius fracture treated by 2 surgeons with open reduction and volar locked plate fixation between 2007 and 2011 at our institution. A manually case-matched design with one-to-one matching of 2 different strategies for screws in the distal part of the plate (1 row versus 2 rows) on the basis of sex, AO type, presence of dorsal comminution, ulna fracture, mechanism of injury, and age (+/- 8 y) resulted in a group of 34 pairs, 68 total fractures. Radiographic alignment was measured before suture removal and 3 months or more after surgery.
Results The change in volar tilt of the articular surface was -1.2 degrees in the. 1-row group and -0.9 degrees in the 2-row group, which was not significantly different. The secondary displacement of radial inclination and ulnar variance were likewise small and not statistically significant.
Conclusions We found no advantage of 2 rows of distal screws over a single row of screws with respect to maintenance of achieved restoration of volar angulation after volar locked plate fixation of AO type A and C fractures of the distal radius. (J Hand Surg 2013;38A:297-301. Copyright (C) 2013 by the American Society for Surgery of the Hand. All rights reserved.)
C1 [Neuhaus, Valentin; Badri, Omar; Ferree, Steven; Bot, Arjan G. J.; Ring, David C.; Mudgal, Chaitanya S.] Massachusetts Gen Hosp, Orthopaed Hand Serv, Boston, MA 02114 USA.
RP Ring, DC (reprint author), Massachusetts Gen Hosp, Orthopaed Hand Serv, Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA.
EM dring@partners.org
OI Neuhaus, Valentin/0000-0003-4012-5628
NR 19
TC 3
Z9 3
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 0363-5023
J9 J HAND SURG-AM
JI J. Hand Surg.-Am. Vol.
PD FEB
PY 2013
VL 38A
IS 2
BP 297
EP 301
DI 10.1016/j.jhsa.2012.10.040
PG 5
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA 087CR
UT WOS:000314739400010
PM 23267755
ER
PT J
AU ten Berg, PWL
Mudgal, CS
Leibman, MI
Belsky, MR
Ruchelsman, DE
AF ten Berg, Paul W. L.
Mudgal, Chaitanya S.
Leibman, Matthew I.
Belsky, Mark R.
Ruchelsman, David E.
TI Quantitative 3-Dimensional CT Analyses of Intramedullary Headless Screw
Fixation for Metacarpal Neck Fractures
SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME
LA English
DT Article
DE Hand fracture; headless screw; intramedullary fixation; metacarpal neck
ID DISTAL RADIUS FRACTURES; K-WIRE FIXATION; CAPITELLAR FRACTURES;
INTERNAL-FIXATION; PLATE FIXATION; OPEN REDUCTION; COMPLICATIONS; WRIST;
HAND
AB Purpose Fixation countersunk beneath the articular surface is well accepted for periarticular fractures. Limited open intramedullary headless compression screw (HCS) fixation offers clinical advantages over Kirschner wire and open techniques. We used quantitative 3-dimensional computed tomography to assess the articular starting point, surface area, and subchondral volumes used during HCS fixation of metacarpal neck fractures.
Methods We simulated retrograde intramedullary insertion of 2.4- and 3.0-mm HCS and 1.1-mm Kirschner wires for metacarpal neck fracture fixation in 3-dimensional models from 16 adults. We used metacarpal head articular surface area (mm(2)) and subchondral volumes (mm(3)) and coronal and sagittal plane arcs of motion, during which we analyzed the center and rim of the articular base of the proximal phalanx engaging the countersunk entry site.
Results Mean metacarpal head surface area mated to the proximal phalangeal base in neutral position was 93 mm(2); through the coronal plane arc (45 degrees) was 129 mm(2), and through the sagittal plane arc (120 degrees) was 265 mm(2) The mean articular surface area used by countersunk HCS threads was 12%, 8%, and 4%, respectively, in each of these arcs. The 1.1-mm Kirschner wire occupied 1.2%, 0.9%, and 0.4%, respectively. Mean metacarpal head volume was 927 mm(3). Mean subchondral volume occupied by the countersunk portion was 4%. The phalangeal base did not overlap the dorsally located countersunk entry site through most of the sagittal plane arc. During coronal plane motion in neutral extension, the center of the base never engaged the dorsally located countersunk entry site.
Conclusions Metacarpal head surface area and subchondral head volume occupied by HCS were minimal. Articular surface area violation was least during the more clinically relevant sagittal plane arc of motion.
Clinical relevance The dorsal articular starting point was in line with the medullary canal and avoided engaging the center of the articular base through most of the sagittal plane arc. Three-dimensional computed tomography data support the use of an articular starting point for these extra-articular fractures. (J Hand Surg 2013;38A:322-330. Copyright (C) 2013 by the American Society for Surgery of the Hand. All rights reserved.)
C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Hand & Upper Extrem Surg Serv, Boston, MA USA.
Tufts Univ, Sch Med, Newton Wellesley Hosp, PC, Newton, MA USA.
Acad Med Ctr, Amsterdam, Netherlands.
RP Ruchelsman, DE (reprint author), Newton Wellesley Hosp, PC, 2000 Washington St,Blue Bldg,Suite 201, Newton, MA 02462 USA.
EM druchelsman@partners.org
NR 30
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Z9 8
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 0363-5023
J9 J HAND SURG-AM
JI J. Hand Surg.-Am. Vol.
PD FEB
PY 2013
VL 38A
IS 2
BP 322
EP 330
DI 10.1016/j.jhsa.2012.09.029
PG 9
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA 087CR
UT WOS:000314739400014
PM 23200214
ER
PT J
AU Peters, F
Vranceanu, AM
Elbon, M
Ring, D
AF Peters, F.
Vranceanu, A. -M.
Elbon, M.
Ring, D.
TI Ganglions of the hand and wrist: determinants of treatment choice
SO JOURNAL OF HAND SURGERY-EUROPEAN VOLUME
LA English
DT Article
DE Depression; ganglions; pain catastrophizing; patient satisfaction;
surgery
ID PAIN CATASTROPHIZING SCALE; IDIOPATHIC ARM PAIN; VALIDATION; SYMPTOMS
AB The aim of this study was to determine whether psychological factors (depression, catastrophic thinking, and pain anxiety) and pain intensity are associated with choice of operative treatment. Ninety new patients with a ganglion cyst on their hand or wrist completed psychological questionnaires (Pain Catastrophizing Scale, Pain Anxiety Symptoms Scale, and Center for the Epidemiological Study of Depression instrument) and an ordinal measure of pain intensity. After a minimum of 4 months, patients were contacted to determine if they chose operative treatment, to rate their pain intensity, and to complete the Disabilities of the Arm, Shoulder, and Hand questionnaire. Younger patients were more likely to choose operative treatment. Psychological factors were associated with pain intensity at enrolment, but not with treatment choice. Operative treatment did not result in less pain intensity or disability, or higher satisfaction compared with non-operative treatment.
C1 [Peters, F.; Elbon, M.; Ring, D.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA.
[Vranceanu, A. -M.] Massachusetts Gen Hosp, Dept Behav Med, Boston, MA 02114 USA.
RP Ring, D (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA.
EM dring@partners.org
FU Wright; Biomet; Skeletal Dynamics
FX David Ring MD PhD is a consultant for and has contracted royalties with
Wright, Biomet, and Skeletal Dynamics.
NR 18
TC 0
Z9 0
U1 0
U2 4
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1753-1934
J9 J HAND SURG-EUR VOL
JI J. Hand Surg.-Eur. Vol.
PD FEB
PY 2013
VL 38E
IS 2
BP 151
EP 157
DI 10.1177/1753193412442468
PG 7
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA 085BX
UT WOS:000314586800007
PM 22508801
ER
PT J
AU Hu, J
Wen, PY
Abrey, LE
Fadul, CE
Drappatz, J
Salem, N
Supko, JG
Hochberg, F
AF Hu, Jethro
Wen, Patrick Y.
Abrey, Lauren E.
Fadul, Camilo E.
Drappatz, Jan
Salem, Nadia
Supko, Jeffrey G.
Hochberg, Fred
TI A phase II trial of oral gimatecan for recurrent glioblastoma
SO JOURNAL OF NEURO-ONCOLOGY
LA English
DT Article
DE Gimatecan; Glioblastoma; Clinical trial; Camptothecin; Brain tumor;
Glioma
ID ADVANCED SOLID TUMORS; MALIGNANT GLIOMA; CAMPTOTHECIN GIMATECAN;
EPITHELIAL OVARIAN; CLINICAL-TRIALS; STRAND BREAKS; IRINOTECAN; CANCER;
ADULTS; ST1481
AB Gimatecan is a lipophilic oral camptothecin analogue with preclinical activity in glioma models. We conducted a multicenter phase II trial to evaluate the efficacy of gimatecan in adults with recurrent glioblastoma. Eligibility criteria included a parts per thousand currency sign1 prior treatment for recurrent disease, age a parts per thousand yen18, Eastern Cooperative Oncology Group performance status 0-1, and normal organ function. Patients taking enzyme-inducing anti-seizure medications were excluded. Gimatecan 1.22 mg/m(2) was given orally once daily for 5 consecutive days during each 28-day cycle. The primary endpoint was progression-free survival at 6 months. A Simon 2-stage optimal design was used in which 19 patients were evaluated in the 1st stage, with an additional 36 patients accrued if > 4 patients in stage 1 achieved PFS at 6 months. 29 patients were enrolled in the study, with median age of 58 years (range, 25-77 years); 58.6 % female. All patients received prior surgery, radiation therapy, and at least one chemotherapy regimen. The daily dose was reduced to 1.0 mg/m(2) after four of the first 10 patients experienced grade 4 hematologic toxicity. Treatment-related grade 3/4 toxicities included thrombocytopenia (17.2 %), leukopenia (17.2 %) and neutropenia (10.3 %). None of the 19 patients treated at 1.0 mg/m(2)/day experienced grade 4 hematologic toxicity. One patient had a partial radiographic response by modified Macdonald criteria. Only 3 patients (12 %) were progression-free at 6 months. Median time to progression was 12.0 weeks (7.0, 17.0).Treatment with gimatecan 1.0 mg/m(2)/day for 5 days, repeated every 28-days showed minimal efficacy.
C1 [Hu, Jethro] Johnnie L Cochran Jr Brain Tumor Ctr, Los Angeles, CA 90048 USA.
[Wen, Patrick Y.] Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02215 USA.
[Abrey, Lauren E.] Univ Zurich, Dept Neurol, Zurich, Switzerland.
[Fadul, Camilo E.] Dartmouth Hitchcock Med Ctr, Norris Cotton Canc Ctr, Lebanon, NH 03756 USA.
[Drappatz, Jan] UPMC Canc Pavil, Pittsburgh, PA 15232 USA.
[Salem, Nadia] Sigma Tau Pharmaceut Inc, Gaithersburg, MD 20878 USA.
[Supko, Jeffrey G.] Massachusetts Gen Hosp, Clin Pharmacol Lab, Boston, MA 02114 USA.
[Hochberg, Fred] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Stephen E & Catherine Pappas Ctr Neurooncol,Canc, Boston, MA 02114 USA.
RP Hu, J (reprint author), Johnnie L Cochran Jr Brain Tumor Ctr, 8631 W 3rd St,Suite 410E, Los Angeles, CA 90048 USA.
EM jethro.hu@gmail.com
FU Sigma-Tau Research
FX Grant support from Sigma-Tau Research.
NR 30
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Z9 8
U1 2
U2 8
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-594X
J9 J NEURO-ONCOL
JI J. Neuro-Oncol.
PD FEB
PY 2013
VL 111
IS 3
BP 347
EP 353
DI 10.1007/s11060-012-1023-0
PG 7
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA 086VC
UT WOS:000314715100015
PM 23232808
ER
PT J
AU Ransom, CB
Tao, WC
Wu, YM
Spain, WJ
Richerson, GB
AF Ransom, Christopher B.
Tao, Wucheng
Wu, Yuanming
Spain, William J.
Richerson, George B.
TI Rapid regulation of tonic GABA currents in cultured rat hippocampal
neurons
SO JOURNAL OF NEUROPHYSIOLOGY
LA English
DT Article
DE tonic inhibition; gamma-aminobutyric acid receptor type A;
gamma-aminobutyric acid transporter type 1; seizure
ID CEREBELLAR GRANULE CELLS; ACTIVITY-DEPENDENT DISINHIBITION; CHLORIDE
ACCUMULATION; DENTATE GYRUS; DELTA-SUBUNIT; MOUSE MODEL; IONIC BASIS;
RECEPTORS; INHIBITION; TRANSPORTER
AB Ransom CB, Tao W, Wu Y, Spain WJ, Richerson GB. Rapid regulation of tonic GABA currents in cultured rat hippocampal neurons. J Neurophysiol 109: 803-812, 2013. First published October 31, 2012; doi:10.1152/jn.00460.2012.-Subacute and chronic changes in tonic GABAergic inhibition occur in human and experimental epilepsy. Less is known about how tonic inhibition is modulated over shorter time frames (seconds). We measured endogenous tonic GABA currents from cultured rat hippocampal neurons to evaluate how they are affected by 1) transient increases in extracellular GABA concentration ([GABA]), 2) transient postsynaptic depolarization, and 3) depolarization of presynaptic cells. Transient increases in [GABA] (1 mu M) reduced tonic currents; this reduction resulted from GABA-induced shifts in the reversal potential for GABA currents (E-GABA). Transient depolarization of postsynaptic neurons reversed the effects of exogenous GABA and potentiated tonic currents. The voltage-dependent potentiation of tonic GABA currents was independent of E-GABA shifts and represented postdepolarization potentiation (PDP), an intrinsic GABA(A) receptor property (Ransom CB, Wu Y, Richerson GB. J Neurosci 30: 7672-7684, 2010). Inhibition of vesicular GABA release with concanamycin A (ConA) did not affect tonic currents. In ConA-treated cells, transient application of 12 mM K+ to depolarize presynaptic neurons and glia produced a persistent increase in tonic current amplitude. The K+-induced increase in tonic current was reversibly inhibited by SKF89976a (40 mu M), indicating that this was caused by nonvesicular GABA release from GABA transporter type 1 (GAT1). Nonvesicular GABA release due to GAT1 reversal also occurred in acute hippocampal brain slices. Our results indicate that tonic GABA currents are rapidly regulated by GABA-induced changes in intracellular Cl- concentration, PDP of extrasynaptic GABA(A) receptors, and nonvesicular GABA release. These mechanisms may influence tonic inhibition during seizures when neurons are robustly depolarized and extracellular GABA and K+ concentrations are elevated.
C1 [Ransom, Christopher B.; Spain, William J.] Vet Affairs Puget Sound Hlth Care Syst, Epilepsy Ctr Excellence, Seattle, WA USA.
[Ransom, Christopher B.; Spain, William J.] Univ Washington, Dept Neurol, Seattle, WA 98105 USA.
[Tao, Wucheng; Spain, William J.] Univ Washington, Dept Physiol & Biophys, Seattle, WA 98105 USA.
[Wu, Yuanming; Richerson, George B.] Univ Iowa, Dept Neurol, Iowa City, IA 52242 USA.
[Richerson, George B.] Univ Iowa, Dept Mol Physiol & Biophys, Iowa City, IA USA.
RP Ransom, CB (reprint author), Univ Washington, Epilepsy Ctr Excellence, VA Puget Sound Hlth Care Syst, Dept Neurol, Seattle, WA 98105 USA.
EM cbr5@u.washington.edu
FU Department of Veterans Affairs Health Administration; National
Institutes of Health; National Epifellows Foundation
FX This work was supported by the Department of Veterans Affairs Health
Administration (C. B. Ransom, W. J. Spain), the National Institutes of
Health (G. B. Richerson), and the National Epifellows Foundation (C. B.
Ransom).
NR 60
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Z9 10
U1 2
U2 13
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3077
J9 J NEUROPHYSIOL
JI J. Neurophysiol.
PD FEB
PY 2013
VL 109
IS 3
BP 803
EP 812
DI 10.1152/jn.00460.2012
PG 10
WC Neurosciences; Physiology
SC Neurosciences & Neurology; Physiology
GA 085TI
UT WOS:000314636800019
PM 23114210
ER
PT J
AU Gharagouzloo, CA
Madi, S
Seethamraju, RT
Harisinghani, M
Sridhar, S
AF Gharagouzloo, C. A.
Madi, S.
Seethamraju, R. T.
Harisinghani, M.
Sridhar, S.
TI Ultrashort TE imaging with SPIONs: bright prospects for in vivo
applications
SO JOURNAL OF NUCLEAR MEDICINE
LA English
DT Meeting Abstract
CT AACR/SNMMI Conference on State-of-the-Art Molecular Imaging in Cancer
Biology and Therapy
CY FEB 27-MAR 02, 2013
CL San Diego, CA
SP Amer Assoc Canc Res (AACR), Soc Nucl Med & Mol Imaging (SNMMI)
C1 [Gharagouzloo, C. A.; Sridhar, S.] Northeastern Univ, Boston, MA 02115 USA.
[Madi, S.] Bruker BioSpin Corp, Billerica, MA USA.
[Seethamraju, R. T.] Siemens Med Solut USA Inc, Boston, MA USA.
[Harisinghani, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 2
TC 0
Z9 0
U1 0
U2 0
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 FEB 1
PY 2013
VL 54
SU 1
BP 9
EP 9
PG 1
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 086NK
UT WOS:000314691400029
ER
PT J
AU Moore, A
AF Moore, A.
TI Image-guided siRNA and miRNA therapies
SO JOURNAL OF NUCLEAR MEDICINE
LA English
DT Meeting Abstract
CT AACR/SNMMI Conference on State-of-the-Art Molecular Imaging in Cancer
Biology and Therapy
CY FEB 27-MAR 02, 2013
CL San Diego, CA
SP Amer Assoc Canc Res (AACR), Soc Nucl Med & Mol Imaging (SNMMI)
C1 [Moore, A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
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 FEB 1
PY 2013
VL 54
SU 1
BP 33
EP 33
PG 1
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 086NK
UT WOS:000314691400103
ER
PT J
AU Choi, JG
Kim, SY
Perez-Atayde, AR
Padwa, BL
AF Choi, James G.
Kim, Sang Yoon
Perez-Atayde, Antonio R.
Padwa, Bonnie L.
TI Bilateral Coronoid Process Hyperplasia With Pseudocartilaginous Joint
Formation: Jacob Disease
SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY
LA English
DT Article
ID 3-DIMENSIONAL COMPUTED-TOMOGRAPHY; OSTEOCHONDROMA; MANAGEMENT
C1 [Choi, James G.] Univ Penn, Sch Dent Med, Philadelphia, PA 19104 USA.
[Kim, Sang Yoon] Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA.
[Perez-Atayde, Antonio R.] Harvard Univ, Sch Med, Childrens Hosp Boston, Boston, MA USA.
[Padwa, Bonnie L.] Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA.
[Padwa, Bonnie L.] Childrens Hosp Boston, Sect Oral & Maxillofacial Surg, Boston, MA USA.
RP Padwa, BL (reprint author), Childrens Hosp Boston, Dept Plast & Oral Surg, 300 Longwood Ave, Boston, MA 02115 USA.
EM bonnie.padwa@childrens.harvard.edu
OI kim, sang/0000-0002-5860-3491
NR 13
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U1 0
U2 2
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0278-2391
J9 J ORAL MAXIL SURG
JI J. Oral Maxillofac. Surg.
PD FEB
PY 2013
VL 71
IS 2
BP 316
EP 321
DI 10.1016/j.joms.2012.05.029
PG 6
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 086TN
UT WOS:000314710200029
PM 22871308
ER
PT J
AU Kumar, N
Garg, N
Bailey, A
AF Kumar, Nilay
Garg, Neetika
Bailey, Amos
TI Opiate Receptor Antagonists for Treatment of Severe Pruritus Associated
with Advanced Cholestatic Liver Disease
SO JOURNAL OF PALLIATIVE MEDICINE
LA English
DT Letter
ID DOUBLE-BLIND
C1 [Kumar, Nilay] Univ Alabama Birmingham, Dept Internal Med, Birmingham, AL 35294 USA.
[Garg, Neetika] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA.
[Bailey, Amos] Birmingham VA Med Ctr, Div Palliat Care & Hosp Med, Birmingham, AL USA.
RP Kumar, N (reprint author), Univ Alabama Birmingham, Dept Internal Med, BDB 327,1530 3rd Ave S, Birmingham, AL 35294 USA.
EM nkumar@uab.edu
OI Garg, Neetika/0000-0002-7001-2168
NR 6
TC 3
Z9 3
U1 0
U2 1
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1096-6218
J9 J PALLIAT MED
JI J. Palliat. Med.
PD FEB
PY 2013
VL 16
IS 2
BP 122
EP 123
DI 10.1089/jpm.2012.0452
PG 2
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA 088FB
UT WOS:000314818100003
PM 23391399
ER
PT J
AU Goldstein, R
Rimer, KP
AF Goldstein, Richard
Rimer, Kathleen P.
TI Parents' Views of Their Child's End-of-Life Care: Subanalysis of Primary
Care Involvement
SO JOURNAL OF PALLIATIVE MEDICINE
LA English
DT Article
ID PEDIATRIC PALLIATIVE CARE; GENERAL-PRACTITIONERS; LAST YEAR; EDUCATION;
PLACE; DEATH; NEEDS; HOME
AB Background: The medical literature encourages primary care pediatricians (PCPs) to play a role in the care of patients who are dying. Actual involvement has not been investigated.
Objective: Our objective was to explore current involvement of PCPs when their patients face the end of life and bereaved parents' attitudes toward it.
Design: Individual, in-depth, semi-structured interviews were conducted using a focused ethnographic technique. Qualitative analysis was performed on the interviews.
Setting/Subjects: Most (14/16) interviews were conducted in the family's home, involving parents of Massachusetts children who died aged 1 month to 11 years during 2005.
Measurements: Themes identified through thematic analysis of interview transcripts were utilized.
Results: Interviews were thematically analyzed, revealing four categories of themes: 1) the role of individual PCP in decision making and care at end of life; 2) general attitudes about the care provided by the PCP; 3) the impact of practice infrastructure on the PCP's care; and 4) bereavement involvement. From the interviews we hypothesize that PCPs play a supportive and appreciated role while having limited involvement in decision making and care; an involved PCP acting with knowledge of a family may in some cases provide profound guidance, but that kind of involvement is not typical; and although there is an articulated role for the PCP with the parents' and siblings' bereavement, it is not routinely exercised.
Conclusions: The interviews suggest limited involvement by PCPs in care at the end of life and subsequent bereavement. Parents overall seem to accept this role. Further research is needed to examine these observations from the perspective of PCPs.
C1 [Goldstein, Richard] Childrens Hosp, Dana Farber Canc Inst, Pediat Adv Care Team, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA.
[Rimer, Kathleen P.] Beth Israel Deaconess Med Ctr, Dept Pastoral Care & Educ, Boston, MA 02215 USA.
RP Goldstein, R (reprint author), Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, 450 Brookline Ave,SW411, Boston, MA 02215 USA.
EM richard_goldstein@dfci.harvard.edu
FU Cameron and Hayden Lord Foundation
FX This research was supported by a grant from the Cameron and Hayden Lord
Foundation. We also thank Barry Zuckerman, M. D., Susan Block, M. D.,
and Joanne Wolfe, M. D., M. P. H., for their invaluable support for this
project.
NR 26
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U1 0
U2 18
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 FEB
PY 2013
VL 16
IS 2
BP 198
EP 202
DI 10.1089/jpm.2012.0269
PG 5
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA 088FB
UT WOS:000314818100017
PM 23098631
ER
PT J
AU Cheng, JT
Hamade, M
Merchant, SN
Rosowski, JJ
Harrington, E
Furlong, C
AF Cheng, Jeffrey Tao
Hamade, Mohamad
Merchant, Saumil N.
Rosowski, John J.
Harrington, Ellery
Furlong, Cosme
TI Wave motion on the surface of the human tympanic membrane: Holographic
measurement and modeling analysis
SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA
LA English
DT Article
ID TIME-AVERAGED HOLOGRAPHY; MIDDLE-EAR TRANSMISSION; DOPPLER VIBROMETER
LDV; HUMAN TEMPORAL BONES; REFLECTION COEFFICIENT; ENERGY REFLECTANCE;
INPUT IMMITTANCE; SOUND PRESSURE; EARDRUM; IMPEDANCE
AB Sound-induced motions of the surface of the tympanic membrane (TM) were measured using stroboscopic holography in cadaveric human temporal bones at frequencies between 0.2 and 18 kHz. The results are consistent with the combination of standing-wave-like modal motions and traveling-wave-like motions on the TM surface. The holographic techniques also quantified sound-induced displacements of the umbo of the malleus, as well as volume velocity of the TM. These measurements were combined with sound-pressure measurements near the TM to compute middle-ear input impedance and power reflectance at the TM. The results are generally consistent with other published data. A phenomenological model that behaved qualitatively like the data was used to quantify the relative magnitude and spatial frequencies of the modal and traveling-wave-like displacement components on the TM surface. This model suggests the modal magnitudes are generally larger than those of the putative traveling waves, and the computed wave speeds are much slower than wave speeds predicted by estimates of middle-ear delay. While the data are inconsistent with simple modal displacements of the TM, an alternate model based on the combination of modal motions in a lossy membrane can also explain these measurements without invoking traveling waves. (C) 2013 Acoustical Society of America. [http://dx.doi.org/10.1121/1.4773263]
C1 [Cheng, Jeffrey Tao; Hamade, Mohamad; Merchant, Saumil N.; Rosowski, John J.; Furlong, Cosme] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA.
[Harrington, Ellery; Furlong, Cosme] Worcester Polytech Inst, Dept Mech Engn, Ctr Holog Studies & Laser MicromechaTron, Worcester, MA 01609 USA.
[Cheng, Jeffrey Tao; Hamade, Mohamad; Merchant, Saumil N.; Rosowski, John J.; Furlong, Cosme] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA.
[Rosowski, John J.] MIT Harvard Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol Program, Cambridge, MA 02139 USA.
RP Cheng, JT (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA.
EM Tao_Cheng@meei.harvard.edu
FU NIDCD [NRSA 1F32DC009949-01, 1R03DC011617-01, R01-DC008642]
FX The authors thank Diane Jones at the Eaton-Peabody Laboratory of the
Massachusetts Eye and Ear Infirmary (MEEI) for help in acquiring TB
specimens. Dr. Maria del Socorro Hernandez-Montes, Ivo Dobrev, Dr.
Mauricio Flores-Moreno, and Christopher Scarpino from the Center for
Holographic Studies and Laser Mico-mechaTronics at the Worcester
Polytechnic Institute have provided technical assistances in the use of
the holographic interferometry system. We value discussions with Michael
Ravicz, Dr. Heidi Nakajima, Melissa Woods, and Rachelle Horwitz at MEEI
and Jef Aernouts of the University of Antwerp regarding our results. We
also acknowledge the help of the four reviewers, all of whom helped
improve the paper. This work was supported by NRSA 1F32DC009949-01,
1R03DC011617-01, and R01-DC008642 from NIDCD and a donation from L.
Mittal.
NR 54
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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 FEB
PY 2013
VL 133
IS 2
BP 918
EP 937
DI 10.1121/1.4773263
PG 20
WC Acoustics; Audiology & Speech-Language Pathology
SC Acoustics; Audiology & Speech-Language Pathology
GA 080TW
UT WOS:000314267200040
PM 23363110
ER
PT J
AU Nigwekar, SU
Thadhani, RI
AF Nigwekar, Sagar U.
Thadhani, Ravi I.
TI Shining light on vitamin D trials in chronic kidney disease
SO KIDNEY INTERNATIONAL
LA English
DT Editorial Material
ID D THERAPY; INSULIN; CALCITRIOL
AB Vitamin D compounds may have extraskeletal functions. Chronic kidney disease (CKD) offers an opportunity to investigate these actions, as vitamin D deficiency is prevalent in this population and actions of vitamin D such as those on the heart and glucose metabolism are highly relevant. However, recent randomized controlled trials have tempered enthusiasm. We appraise a trial by de Boer et al. that addresses effects of paricalcitol on glucose metabolism in CKD, and offer perspectives on future trials. Kidney International (2013) 83, 198-200. doi:10.1038/ki.2012.415
C1 [Nigwekar, Sagar U.; Thadhani, Ravi I.] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA.
[Nigwekar, Sagar U.] Harvard Univ, Sch Med, Scholars Clin Sci Program, Boston, MA USA.
RP Thadhani, RI (reprint author), Massachusetts Gen Hosp, Bulfinch 127,55 Fruit St, Boston, MA 02114 USA.
EM rthadhani@partners.org
FU NIDDK NIH HHS [K24 DK094872]
NR 12
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U1 0
U2 2
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 FEB
PY 2013
VL 83
IS 2
BP 198
EP 200
DI 10.1038/ki.2012.415
PG 3
WC Urology & Nephrology
SC Urology & Nephrology
GA 085NM
UT WOS:000314621500006
PM 23364588
ER
PT J
AU de Boer, IH
Sachs, M
Hoofnagle, AN
Utzschneider, KM
Kahn, SE
Kestenbaum, B
Himmelfarb, J
AF de Boer, Ian H.
Sachs, Michael
Hoofnagle, Andrew N.
Utzschneider, Kristina M.
Kahn, Steven E.
Kestenbaum, Bryan
Himmelfarb, Jonathan
TI Paricalcitol does not improve glucose metabolism in patients with stage
3-4 chronic kidney disease
SO KIDNEY INTERNATIONAL
LA English
DT Article
DE chronic kidney disease; clinical trial; insulin resistance; metabolism;
vitamin D
ID FIBROBLAST GROWTH FACTOR-23; RANDOMIZED CONTROLLED-TRIAL;
GLOMERULAR-FILTRATION-RATE; FGF23 GENE-EXPRESSION; VITAMIN-D THERAPY;
INSULIN-RESISTANCE; SECONDARY HYPERPARATHYROIDISM;
HEMODIALYSIS-PATIENTS; 1,25-DIHYDROXYVITAMIN D-3; INTRAVENOUS CALCITRIOL
AB Patients with chronic kidney disease are often insulin resistant and glucose intolerant abnormalities that promote cardiovascular disease. Administration of 1,25-dihydroxyvitamin D (calcitriol) has improved glucose metabolism in patients with end-stage renal disease. We conducted a randomized, placebo-controlled clinical trial to test whether paricalcitol, a 1,25-dihydroxyvitamin D analog, changes glucose tolerance in earlier stages of chronic kidney disease. In a crossover design, 22 nondiabetic patients with estimated glomerular filtration rates of stage 3-4 chronic kidney disease and fasting plasma glucose of 100-125 mg/dl were given daily oral paricalcitol for 8 weeks and matching placebo for 8 weeks, separated by an 8-week washout period. The order of interventions was random and blinded to both participants and investigators. Paricalcitol significantly reduced serum concentrations of parathyroid hormone, 1,25-dihydroxyvitamin D, and 25-hydroxyvitamin D while significantly increasing serum concentrations of fibroblast growth factor-23 and 24,25-dihydroxyvitamin D. Paricalcitol, however, had no significant effect on glucose tolerance (the primary outcome measure), insulin sensitivity, beta-cell insulin response, plasma free fatty acid suppression, or urinary F2-isoprostane excretion. Thus, despite substantial effects on vitamin D metabolism, paricalcitol did not improve glucose metabolism in nondiabetic patients with stage 3-4 chronic kidney disease. Kidney International (2013) 83, 323-330; doi:10.1038/ki.2012.311; published online 22 August 2012
C1 [de Boer, Ian H.; Sachs, Michael; Kestenbaum, Bryan; Himmelfarb, Jonathan] Univ Washington, Dept Med, Div Nephrol, Seattle, WA 98104 USA.
[de Boer, Ian H.; Sachs, Michael; Kestenbaum, Bryan; Himmelfarb, Jonathan] Univ Washington, Dept Med, Kidney Res Inst, Seattle, WA 98104 USA.
[de Boer, Ian H.; Kestenbaum, Bryan] Univ Washington, Dept Epidemiol, Seattle, WA 98104 USA.
[Hoofnagle, Andrew N.] Univ Washington, Dept Lab Med, Seattle, WA 98104 USA.
[Utzschneider, Kristina M.; Kahn, Steven E.] VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA USA.
[Utzschneider, Kristina M.; Kahn, Steven E.] Univ Washington, Seattle, WA 98104 USA.
RP de Boer, IH (reprint author), Univ Washington, Dept Med, Div Nephrol, Box 359606,325 9th Ave, Seattle, WA 98104 USA.
EM deboer@u.washington.edu
OI Kahn, Steven/0000-0001-7307-9002
FU Abbott Laboratories; National Institutes of Health [1R01DK087726,
1R01HL096875, 5R01HL070938, 5KL2RR025015, P30DK035816, 5P30DK017047,
UL1RR025014]; Veterans Affairs Puget Sound Health Care System, Seattle,
WA
FX This work was supported by an investigator-initiated grant from Abbott
Laboratories and by grants 1R01DK087726, 1R01HL096875, 5R01HL070938,
5KL2RR025015, P30DK035816, 5P30DK017047, and UL1RR025014 from the
National Institutes of Health. This material is the result of work
supported in part by resources from the Veterans Affairs Puget Sound
Health Care System, Seattle, WA. We thank the study participants for
their generous dedication and Laura Curtin, BS, Alexandra Flynn, MD,
Aparna Lakshman, BA, and the staff of the University of Washington
Investigational Drug Services and Clinical Research Center for their
hard work.
NR 52
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U1 0
U2 4
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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 FEB
PY 2013
VL 83
IS 2
BP 323
EP 330
DI 10.1038/ki.2012.311
PG 8
WC Urology & Nephrology
SC Urology & Nephrology
GA 085NM
UT WOS:000314621500022
PM 22913981
ER
PT J
AU Hardin, C
Fredberg, JJ
Krishnan, R
AF Hardin, Corey
Fredberg, Jeffrey J.
Krishnan, Ramaswamy
TI Real estate of monolayer permeability: location location location
SO LABORATORY INVESTIGATION
LA English
DT Editorial Material
ID COLLECTIVE CELL-MIGRATION; PHYSICAL FORCES
C1 [Hardin, Corey] Massachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02114 USA.
[Fredberg, Jeffrey J.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Krishnan, Ramaswamy] Beth Israel Deaconess Med Ctr, Ctr Vasc Biol, Boston, MA 02215 USA.
RP Fredberg, JJ (reprint author), Harvard Univ, Sch Publ Hlth, 665 Huntington Ave, Boston, MA 02115 USA.
EM jjf@harvard.edu
FU NHLBI NIH HHS [R01 HL107561]
NR 14
TC 0
Z9 0
U1 0
U2 13
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2013
VL 93
IS 2
BP 148
EP 150
DI 10.1038/labinvest.2012.168
PG 3
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 084SF
UT WOS:000314558700001
PM 23361599
ER
PT J
AU Royall, DR
AF Royall, Donald R.
TI Fortress Brain
SO MEDICAL HYPOTHESES
LA English
DT Article
ID SIMPLEX-VIRUS TYPE-1; MILD COGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE;
NEUROFIBRILLARY TANGLES; PARKINSONS-DISEASE; PERINEURONAL NETS;
FOLLOW-UP; EXPRESSION; TAU; DISORDERS
AB Neurodegenerative diseases are associated with neuronal inclusions, comprised of protein aggregates. In Alzheimer's Disease (AD) and Lewy Body Disease (LBD) such lesions are distributed in a hierarchical retrograde transynaptic spatial pattern. This implies a retrograde transynaptic temporal propagation as well. There can be few explanations for this other than infectious agents (prions and viruses). This suggests that AD and LBD (at least) may have infectious origins.
Transynaptic infiltration of the CNS along cranial nerve or other major projections, by one or more infectious agents has important implications. The clinical syndrome and natural history of each neurodegenerative disorder will reflect its portal of entry. There may be a different neurodegenerative syndrome for each cranial nerve or other portal of entry, and not all may manifest as "dementia". Each syndrome may be associated with more than one pathological lesion. Each pathology may be associated with several clinical syndromes.
Host-parasite interactions are species specific. This may explain the rarity of AD-like pathology in most other older mammals. Over evolutionary timescales, the human brain should be adapted to predation by neurotropic agents. Viewed from this perspective, the prion-like pro-inflammatory and pro-apoptotic properties of beta-amyloid and other proteins may be adaptive, and anti-microbial. Reductions in synaptic density may slow the progress of invading pathogens, while perineuronal nets and other structures may guard the gates. This suggests a defense in depth of a structure, the brain, that is inherently vulnerable to invasion along its neural networks. (c) 2012 Elsevier Ltd. All rights reserved.
C1 [Royall, Donald R.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA.
[Royall, Donald R.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA.
[Royall, Donald R.] Univ Texas Hlth Sci Ctr San Antonio, Dept Family & Community Med, San Antonio, TX 78229 USA.
[Royall, Donald R.] S Texas Vet Hlth Syst, Audie L Murphy Div, GRECC, San Antonio, TX USA.
RP Royall, DR (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA.
EM royall@uthscsa.edu
NR 48
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U1 0
U2 9
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 0306-9877
J9 MED HYPOTHESES
JI Med. Hypotheses
PD FEB
PY 2013
VL 80
IS 2
BP 118
EP 121
DI 10.1016/j.mehy.2012.11.005
PG 4
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 083SO
UT WOS:000314485700004
PM 23265350
ER
PT J
AU Cipriani, NA
McLaughlin, PJ
Borger, DR
Nielsen, GP
AF Cipriani, N. A.
McLaughlin, P. J.
Borger, D. R.
Nielsen, G. P.
TI BRAF Mutation in "Sarcomas": A Possible Method To Detect Melanomas
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 102nd Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology (USCAP)
CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 [Cipriani, N. A.; McLaughlin, P. J.; Borger, D. R.; Nielsen, G. P.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
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 FEB
PY 2013
VL 26
SU 2
MA 30
BP 10A
EP 10A
PG 1
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444400031
ER
PT J
AU Cipriani, NA
Kurzawa, P
Mullen, J
Deshpande, V
Ahmad, R
Nielsen, GP
AF Cipriani, N. A.
Kurzawa, P.
Mullen, J.
Deshpande, V.
Ahmad, R.
Nielsen, G. P.
TI Prognostic Value of Subclassification of Pleomorphic Soft Tissue Sarcoma
(STS): Myogenic Versus Non-Myogenic Differentiation
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 102nd Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology (USCAP)
CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Greater Poland Canc Ctr, Poznan, Poland.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2013
VL 26
SU 2
MA 31
BP 10A
EP 11A
PG 2
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444400032
ER
PT J
AU Kerr, DA
Deshpande, V
Kurzawa, P
Nielsen, GP
AF Kerr, D. A.
Deshpande, V.
Kurzawa, P.
Nielsen, G. P.
TI Chondroid Chordoma: A Chordoma Subtype with Worse Prognosis
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 102nd Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology (USCAP)
CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Greater Poland Canc Ctr, Poznan, Poland.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2013
VL 26
SU 2
MA 47
BP 14A
EP 14A
PG 1
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444400048
ER
PT J
AU Lee, YD
Nardi, V
Le, LP
Deshpande, V
Hornicek, FJ
Iafrate, AJ
Nielsen, GP
AF Lee, Y. D.
Nardi, V.
Le, L. P.
Deshpande, V.
Hornicek, F. J.
Iafrate, A. J.
Nielsen, G. P.
TI Array Comparative Genomic Hybridization Analysis of a Conventional
Chordoma and an Adjacent Benign Notochordal Tumor Shows No Direct
Lineage Relationship
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 102nd Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology (USCAP)
CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 [Lee, Y. D.; Nardi, V.; Le, L. P.; Deshpande, V.; Hornicek, F. J.; Iafrate, A. J.; Nielsen, G. P.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
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U1 0
U2 2
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 FEB
PY 2013
VL 26
SU 2
MA 56
BP 16A
EP 17A
PG 2
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444400057
ER
PT J
AU Shah, K
Zhang, Y
Nielsen, GP
Rosenberg, AE
AF Shah, K.
Zhang, Y.
Nielsen, G. P.
Rosenberg, A. E.
TI Primary Myoepithelioma of the Orbit
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 102nd Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology (USCAP)
CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 Univ Miami, Miller Sch Med, Jackson Mem Hosp, Miami, FL 33136 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
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 FEB
PY 2013
VL 26
SU 2
MA 71
BP 20A
EP 20A
PG 1
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444400072
ER
PT J
AU Zhang, Y
Nielsen, GP
Raskin, K
Cipriani, N
Rosenberg, AE
AF Zhang, Y.
Nielsen, G. P.
Raskin, K.
Cipriani, N.
Rosenberg, A. E.
TI Primary Malignant Myoepithelial Tumor of Bone
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 102nd Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology (USCAP)
CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 Univ Miami, Miller Sch Med, Jackson Mem Hosp, Miami, FL 33136 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
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 FEB
PY 2013
VL 26
SU 2
MA 94
BP 25A
EP 25A
PG 1
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444400095
ER
PT J
AU Brachtel, EF
Kerr, SE
Anderson, J
Zhang, Y
Singh, V
Erlander, MG
Carey, B
Highsmith, WE
Schnabel, CA
Dry, SM
Sullivan, PS
AF Brachtel, E. F.
Kerr, S. E.
Anderson, J.
Zhang, Y.
Singh, V.
Erlander, M. G.
Carey, B.
Highsmith, W. E.
Schnabel, C. A.
Dry, S. M.
Sullivan, P. S.
TI Diagnostic Utility of a 92-Gene Classifier in Triple-Negative Breast
Carcinomas
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 102nd Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology (USCAP)
CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
Mayo Clin, Rochester, MN USA.
BioTheranostics Inc, San Diego, CA USA.
Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2013
VL 26
SU 2
MA 121
BP 31A
EP 31A
PG 1
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444400123
ER
PT J
AU Marques, RC
Lerwill, MF
AF Canas Marques, R.
Lerwill, M. F.
TI Incidence of Carcinoma and Atypia in Breast Reduction Mammoplasty
Specimens
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 102nd Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology (USCAP)
CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 EPE, Inst Portugues Oncol Lisboa Francisco Gentil, Lisbon, Portugal.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
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 FEB
PY 2013
VL 26
SU 2
MA 126
BP 32A
EP 32A
PG 1
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444400128
ER
PT J
AU Auger, M
Nayar, R
Khalbuss, WE
Barkan, GA
Benedict, C
Tambouret, R
Schwartz, MR
Howell, L
Souers, R
Hartley, A
Thomas, N
Moriarty, AT
AF Auger, M.
Nayar, R.
Khalbuss, W. E.
Barkan, G. A.
Benedict, C.
Tambouret, R.
Schwartz, M. R.
Howell, L.
Souers, R.
Hartley, A.
Thomas, N.
Moriarty, A. T.
TI Implementation of the Bethesda System for Reporting Thyroid
Cytopathology: Observations from the 2011 Thyroid Supplemental
Questionnaire of the College of American Pathologists
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 102nd Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology (USCAP)
CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 McGill Univ, Montreal, PQ, Canada.
McGill Unvers Hlth Ctr, Montreal, PQ, Canada.
Northwestern Univ, Chicago, IL 60611 USA.
NW Mem Hosp, Chicago, IL 60611 USA.
Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA.
Loyola Univ, Maywood, IL 60153 USA.
Loyola Univ, Med Ctr Bedside Test, Maywood, IL 60153 USA.
DCL Pathol LLC, Indianapolis, IN USA.
Harvard Univ, Boston, MA 02115 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
Methodist Hosp, Phys Org, Houston, TX 77030 USA.
Univ Calif Davis, Sacramento, CA 95817 USA.
Univ Calif Davis, Sch Med, Sacramento, CA 95817 USA.
Coll Amer Pathologists, Northfield, MN USA.
AmeriPath Indiana, Indianapolis, IN USA.
NR 0
TC 0
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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 FEB
PY 2013
VL 26
SU 2
MA 338
BP 83A
EP 83A
PG 1
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444400341
ER
PT J
AU Balassanian, R
Ono, JC
Wool, GD
Olejnik-Nave, J
Mah, MM
Sweeney, BJ
Ljung, BM
Pitman, MB
AF Balassanian, R.
Ono, J. C.
Wool, G. D.
Olejnik-Nave, J.
Mah, M. M.
Sweeney, B. J.
Ljung, B-M
Pitman, M. B.
TI A SuperiorTechnique for Cell Block Preparation for Fine Needle
Aspiration
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 102nd Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology (USCAP)
CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 Univ Calif San Francisco, San Francisco, CA 94143 USA.
Lab Med Consultants, Las Vegas, NV USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 1
Z9 1
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2013
VL 26
SU 2
MA 340
BP 83A
EP 83A
PG 1
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444400343
ER
PT J
AU Linskey, K
Kay, J
Duncan, LM
Nazarian, RM
AF Linskey, K.
Kay, J.
Duncan, L. M.
Nazarian, R. M.
TI Wnt and Hedgehog Signaling Pathway Activation in Cutaneous Fibrosing
Disorders: A Tissue Microarray Study
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 102nd Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology (USCAP)
CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
UMass Mem Med Ctr, Worcester, MA USA.
NR 0
TC 0
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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 FEB
PY 2013
VL 26
SU 2
MA 479
BP 116A
EP 117A
PG 2
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444400482
ER
PT J
AU Mochel, M
Arakaki, R
Wang, G
Kroshinsky, D
Hoang, M
AF Mochel, M.
Arakaki, R.
Wang, G.
Kroshinsky, D.
Hoang, M.
TI A Retrospective Histologic and Histochemical Evaluation of Cutaneous
Calciphylaxis
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 102nd Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology (USCAP)
CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 [Mochel, M.; Arakaki, R.; Wang, G.; Kroshinsky, D.; Hoang, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2013
VL 26
SU 2
MA 482
BP 117A
EP 117A
PG 1
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444400485
ER
PT J
AU Prieto-Granada, CN
Lezcano, C
Piris, A
Scoyler, R
Mihm, M
AF Prieto-Granada, C. N.
Lezcano, C.
Piris, A.
Scoyler, R.
Mihm, M.
TI Lethal Childhood Melanoma: A Clinicopathological Study of 12 Cases
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 102nd Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology (USCAP)
CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 Baystate Med Ctr, Springfield, MA USA.
Brigham & Womens Hosp, Boston, MA 02115 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
Sydney Med Sch, Sydney, NSW, Australia.
NR 0
TC 0
Z9 0
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 FEB
PY 2013
VL 26
SU 2
MA 489
BP 119A
EP 119A
PG 1
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444400492
ER
PT J
AU Cipriani, NA
Faquin, WC
Sadow, PM
AF Cipriani, N. A.
Faquin, W. C.
Sadow, P. M.
TI Clear Cell Variant of Thyroid Carcinoma: A Clinicopathologic Study
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 102nd Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology (USCAP)
CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 [Cipriani, N. A.; Faquin, W. C.; Sadow, P. M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
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 FEB
PY 2013
VL 26
SU 2
MA 542
BP 131A
EP 131A
PG 1
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444400545
ER
PT J
AU Agoston, AT
Zheng, Y
Bueno, R
Lauwers, GY
Odze, RD
Srivastava, A
AF Agoston, A. T.
Zheng, Y.
Bueno, R.
Lauwers, G. Y.
Odze, R. D.
Srivastava, A.
TI Clinicopathologic Predictors of Long Term and Disease-Free Survival in
Esophageal Adenocarcinomas with Complete Pathologic Response to
Neoadjuvant Chemoradiation
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 102nd Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology (USCAP)
CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 Brigham & Womens Hosp, Boston, MA 02115 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
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 FEB
PY 2013
VL 26
SU 2
MA 592
BP 142A
EP 142A
PG 1
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444400595
ER
PT J
AU Arnason, T
Pino, MS
Chung, DC
Sapp, HL
Rayson, D
Deshpande, V
Zukerberg, LR
AF Arnason, T.
Pino, M. S.
Chung, D. C.
Sapp, H. L.
Rayson, D.
Deshpande, V.
Zukerberg, L. R.
TI Loss of Cables Expression in Neuroendocrine Tumors (NETS) of the
Gastrointestinal Tract, Pancreas, and Lung
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 102nd Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology (USCAP)
CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Queen Elizabeth II HSC, Halifax, NS, Canada.
NR 0
TC 0
Z9 0
U1 0
U2 2
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 FEB
PY 2013
VL 26
SU 2
MA 600
BP 143A
EP 144A
PG 2
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444401005
ER
PT J
AU Arnason, T
Brown, I
O'Brien, B
Wilson, C
Winter, H
Lauwers, GY
AF Arnason, T.
Brown, I.
O'Brien, B.
Wilson, C.
Winter, H.
Lauwers, G. Y.
TI Collagenous Gastritis: A Morphologic and Immunohistochemical Study of 27
Cases
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 102nd Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology (USCAP)
CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Royal Brisbane & Womens Hosp, Brisbane, Qld, Australia.
Sullivan Nicolaides Pathol, Brisbane, Qld, Australia.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2013
VL 26
SU 2
MA 601
BP 144A
EP 144A
PG 1
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444401006
ER
PT J
AU Bandla, S
Peters, JH
Ruff, D
Chen, SM
Li, CY
Song, K
Thoms, K
Litle, VR
Watson, T
Chapurin, N
Pennathur, A
Luketich, JD
Peterson, D
Dulak, A
Lin, L
Bass, A
Beer, DG
Godfrey, TE
Zhou, Z
AF Bandla, S.
Peters, J. H.
Ruff, D.
Chen, S-M
Li, C-Y
Song, K.
Thoms, K.
Litle, V. R.
Watson, T.
Chapurin, N.
Pennathur, A.
Luketich, J. D.
Peterson, D.
Dulak, A.
Lin, L.
Bass, A.
Beer, D. G.
Godfrey, T. E.
Zhou, Z.
TI Analysis of Columnar Lined Esophagus Reveals Less Frequent Mutations in
Non-Goblet Cell Metaplasia Than Intestinal Metaplasia
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 102nd Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology (USCAP)
CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 URMC, Rochester, NY USA.
Univ Pittsburgh, Pittsburgh, PA USA.
Life Technol, Foster City, CA USA.
Dana Farber Canc Ctr, Boston, MA USA.
Univ Michigan, Ann Arbor, MI 48109 USA.
NR 0
TC 0
Z9 0
U1 0
U2 4
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2013
VL 26
SU 2
MA 604
BP 145A
EP 145A
PG 1
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444401009
ER
PT J
AU Bledsoe, JR
Kamionek, M
Shvetz, DE
Mino-Kenudson, M
AF Bledsoe, J. R.
Kamionek, M.
Shvetz, D. E.
Mino-Kenudson, M.
TI Loss of Expression of ARID1A and BRG1 in Colorectal Cancer Occurs
Infrequently and Is Associated with BRAF Mutation and Microsatellite
Instability
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 102nd Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology (USCAP)
CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 [Bledsoe, J. R.; Kamionek, M.; Shvetz, D. E.; Mino-Kenudson, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2013
VL 26
SU 2
MA 608
BP 145A
EP 146A
PG 2
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444401013
ER
PT J
AU Bledsoe, JR
Shvetz, DE
Mino-Kenudson, M
AF Bledsoe, J. R.
Shvetz, D. E.
Mino-Kenudson, M.
TI Phosphorylation of EGFR in Colorectal Cancer
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 102nd Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology (USCAP)
CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 [Bledsoe, J. R.; Shvetz, D. E.; Mino-Kenudson, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2013
VL 26
SU 2
MA 607
BP 145A
EP 145A
PG 1
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444401012
ER
PT J
AU Deshpande, A
Deshpande, V
O'Brien, MJ
AF Deshpande, A.
Deshpande, V.
O'Brien, M. J.
TI Interstitial Cells of Cajal in Gastrointestinal Leiomyoma
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 102nd Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology (USCAP)
CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 Boston Med Ctr, Boston, MA USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 1
Z9 1
U1 0
U2 2
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 FEB
PY 2013
VL 26
SU 2
MA 621
BP 149A
EP 149A
PG 1
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444401026
ER
PT J
AU Huang, Q
Shi, J
Sun, Q
Yu, H
Chen, J
Wu, H
Gold, JK
Mashimo, H
Yu, C
Lauwers, GY
AF Huang, Q.
Shi, J.
Sun, Q.
Yu, H.
Chen, J.
Wu, H.
Gold, J. K.
Mashimo, H.
Yu, C.
Lauwers, G. Y.
TI Small (<= 2 cm) Carcinomas in the Proximal Stomach Demonstrate Distinct
Clinicopathologic Features from Those in the Distal and Corpus: A
Proposal for Classification of Gastric Cancer by Location
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 102nd Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology (USCAP)
CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 Nanjing Drum Tower Hosp, Nanjing, Peoples R China.
VA Boston Healthcare Syst, W Roxbury, MA USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 3
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 FEB
PY 2013
VL 26
SU 2
MA 648
BP 155A
EP 155A
PG 1
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444401053
ER
PT J
AU Imamura, Y
Fuchs, C
Ogino, S
AF Imamura, Y.
Fuchs, C.
Ogino, S.
TI KRAS c.35G > T (p.G12V) and c.34G > C (p.G12R) Mutations Predict Shorter
Survival in 1925 Colorectal Cancers
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 102nd Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology (USCAP)
CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 Dana Farber Canc Inst, Boston, MA 02115 USA.
Brigham & Womens Hosp, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
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 FEB
PY 2013
VL 26
SU 2
MA 651
BP 156A
EP 157A
PG 2
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444401056
ER
PT J
AU Kuchiba, A
Lochhead, P
Ogino, S
AF Kuchiba, A.
Lochhead, P.
Ogino, S.
TI Colon Cancer Nodal Staging Score: A Tool To Assess Adequacy of Nodal
Harvesting in Pathology Practice
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 102nd Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology (USCAP)
CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 Dana Farber Canc Inst, Boston, MA 02115 USA.
Brigham & Womens Hosp, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
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 FEB
PY 2013
VL 26
SU 2
MA 672
BP 161A
EP 162A
PG 2
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444401077
ER
PT J
AU Liang, WY
Hsu, CY
Arnason, T
Hawkins, AT
Sylla, P
Lauwers, GY
AF Liang, W. Y.
Hsu, C. Y.
Arnason, T.
Hawkins, A. T.
Sylla, P.
Lauwers, G. Y.
TI Retrospective Evaluation of Elastic Stain in the Assessment of Serosal
Invasion of pT3N0Mx Colorectal Cancers
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 102nd Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology (USCAP)
CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 Vet Gen Hosp, Taipei, Taiwan.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2013
VL 26
SU 2
MA 683
BP 164A
EP 165A
PG 2
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444401088
ER
PT J
AU Liang, WY
Arnason, T
Kelly, P
Genevay, M
Odze, RD
Lauwers, GY
AF Liang, W. Y.
Arnason, T.
Kelly, P.
Genevay, M.
Odze, R. D.
Lauwers, G. Y.
TI Morphology and Natural History of Familial Adenomatous Polyposis
(FAP)-Associated Dysplastic Fundic Gland Polyps (FGPs)
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 102nd Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology (USCAP)
CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Brigham & Womens Hosp, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
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 FEB
PY 2013
VL 26
SU 2
MA 684
BP 165A
EP 165A
PG 1
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444401089
ER
PT J
AU Liao, X
Imamura, Y
Ogino, S
AF Liao, X.
Imamura, Y.
Ogino, S.
TI KRAS Codon 12, 13, 61 and 146 Mutations in 1267 Colorectal Cancers:
Clinicopathological, Molecular, and Survival Analyses
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 102nd Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology (USCAP)
CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 Dana Farber Canc Inst, Boston, MA 02115 USA.
Brigham & Womens Hosp, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
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 FEB
PY 2013
VL 26
SU 2
MA 685
BP 165A
EP 165A
PG 1
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444401090
ER
PT J
AU Lochhead, P
Fuchs, C
Ogino, S
AF Lochhead, P.
Fuchs, C.
Ogino, S.
TI Microsatellite Instability (MSI) and BRAF Mutation Tests Jointly Provide
Useful Prognostic Information in 1861 Colorectal Cancers
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 102nd Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology (USCAP)
CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 Dana Farber Canc Inst, Boston, MA 02115 USA.
Brigham & Womens Hosp, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
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 FEB
PY 2013
VL 26
SU 2
MA 688
BP 166A
EP 166A
PG 1
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444401093
ER
PT J
AU Masia, R
Peyton, S
Lauwers, GY
Brown, I
AF Masia, R.
Peyton, S.
Lauwers, G. Y.
Brown, I.
TI Gastrointestinal Biopsy Findings of Autoimmune Enteropathy - A Review of
20 Cases
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 102nd Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology (USCAP)
CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Pathol Queensland, Herston, Qld, Australia.
NR 0
TC 0
Z9 0
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 FEB
PY 2013
VL 26
SU 2
MA 690
BP 167A
EP 167A
PG 1
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444401095
ER
PT J
AU Nishihara, R
Fuchs, C
Ogino, S
AF Nishihara, R.
Fuchs, C.
Ogino, S.
TI Hereditary Predisposition to LINE-1 Hypomethylated Colorectal Cancer:
Potential Clinical Utility of Tumor LINE-1 Methylation Test for Familial
Cancer Risk Assessment
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 102nd Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology (USCAP)
CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 Dana Farber Canc Inst, Boston, MA 02115 USA.
Brigham & Womens Hosp, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2013
VL 26
SU 2
MA 698
BP 169A
EP 169A
PG 1
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444401103
ER
PT J
AU Ogino, S
Imamura, Y
Fuchs, C
AF Ogino, S.
Imamura, Y.
Fuchs, C.
TI LINE-1 Hypomethylation and Patient Prognosis in 1253 Colorectal Cancers
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 102nd Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology (USCAP)
CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 Brigham & Womens Hosp, Boston, MA 02115 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
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 FEB
PY 2013
VL 26
SU 2
MA 702
BP 170A
EP 170A
PG 1
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444401107
ER
PT J
AU Primiani, A
Shahid, M
Yilmaz, O
Ferrone, CR
Borger, DR
Iafrate, AJ
Zhu, AX
Deshpande, V
AF Primiani, A.
Shahid, M.
Yilmaz, O.
Ferrone, C. R.
Borger, D. R.
Iafrate, A. J.
Zhu, A. X.
Deshpande, V.
TI Microsatellite Instability in Gallbladder Carcinoma
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 102nd Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology (USCAP)
CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 [Primiani, A.; Shahid, M.; Yilmaz, O.; Ferrone, C. R.; Borger, D. R.; Iafrate, A. J.; Zhu, A. X.; Deshpande, V.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2013
VL 26
SU 2
MA 713
BP 172A
EP 173A
PG 2
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444401118
ER
PT J
AU Primiani, A
Shahid, M
Yilmaz, O
Ferrone, CR
Borger, DR
Iafrate, AJ
Zhu, AX
Deshpande, V
AF Primiani, A.
Shahid, M.
Yilmaz, O.
Ferrone, C. R.
Borger, D. R.
Iafrate, A. J.
Zhu, A. X.
Deshpande, V.
TI The PI3K/mTOR Pathway in Gallbladder Carcinoma
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 102nd Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology (USCAP)
CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 [Primiani, A.; Shahid, M.; Yilmaz, O.; Ferrone, C. R.; Borger, D. R.; Iafrate, A. J.; Zhu, A. X.; Deshpande, V.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2013
VL 26
SU 2
MA 715
BP 173A
EP 173A
PG 1
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444401120
ER
PT J
AU Primiani, A
Nazarian, RM
Linskey, K
Doyle, LA
Duncan, LM
Odze, R
Zukerberg, LR
AF Primiani, A.
Nazarian, R. M.
Linskey, K.
Doyle, L. A.
Duncan, L. M.
Odze, R.
Zukerberg, L. R.
TI CK17: An Adjunctive Marker of Invasion in Squamous Neoplastic Lesions of
the Anus
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 102nd Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology (USCAP)
CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Brigham & Womans Hosp, Boston, MA USA.
NR 0
TC 0
Z9 0
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 FEB
PY 2013
VL 26
SU 2
MA 714
BP 173A
EP 173A
PG 1
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444401119
ER
PT J
AU Shen, J
Najarian, RM
Dessauvagie, B
Deshpande, V
Kumarasinghe, MP
Hamilton, M
Shahid, M
Lauwers, G
Odze, RD
Srivastava, A
AF Shen, J.
Najarian, R. M.
Dessauvagie, B.
Deshpande, V.
Kumarasinghe, M. P.
Hamilton, M.
Shahid, M.
Lauwers, G.
Odze, R. D.
Srivastava, A.
TI Isolated Ileitis May Be a Manifestation of Crohn's Disease, but Only in
Symptomatic Patients: A Multi-Institution Study of 131 Cases
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 102nd Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology (USCAP)
CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 Brigham & Womens Hosp, Boston, MA 02115 USA.
Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
PathW & UWA, Perth, WA, Australia.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
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 FEB
PY 2013
VL 26
SU 2
MA 738
BP 179A
EP 179A
PG 1
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444401143
ER
PT J
AU Tse, JY
Riggi, N
Ting, DT
Stone, JH
Rivera, M
Deshpande, V
AF Tse, J. Y.
Riggi, N.
Ting, D. T.
Stone, J. H.
Rivera, M.
Deshpande, V.
TI Diagnosis of IgG4-Related Disease: No Longer an IS(H)-Sue?
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 102nd Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology (USCAP)
CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 [Tse, J. Y.; Riggi, N.; Ting, D. T.; Stone, J. H.; Rivera, M.; Deshpande, V.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
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 FEB
PY 2013
VL 26
SU 2
MA 758
BP 184A
EP 184A
PG 1
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444401163
ER
PT J
AU Ushiku, T
Moran, CJ
Lauwers, GY
AF Ushiku, T.
Moran, C. J.
Lauwers, G. Y.
TI Focally Enhanced Gastritis in Pediatric Inflammatory Bowel Disease:
Patterns, Associations and Significance
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 102nd Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology (USCAP)
CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 [Ushiku, T.; Moran, C. J.; Lauwers, G. Y.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
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 FEB
PY 2013
VL 26
SU 2
MA 760
BP 184A
EP 184A
PG 1
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444401165
ER
PT J
AU Ushiku, T
Ban, S
Arnason, T
Hishima, T
Fukayama, M
Lauwers, GY
AF Ushiku, T.
Ban, S.
Arnason, T.
Hishima, T.
Fukayama, M.
Lauwers, G. Y.
TI Very Well Differentiated Gastric Cancer of Intestinal Metaplasia-Type: A
Systemic Analysis
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 102nd Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology (USCAP)
CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Univ Tokyo, Tokyo, Japan.
Saiseikai Kawaguchi Gen Hosp, Saitama, Japan.
Tokyo Metropolitan Komagome Hosp, Tokyo, Japan.
NR 0
TC 0
Z9 0
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 FEB
PY 2013
VL 26
SU 2
MA 761
BP 185A
EP 185A
PG 1
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444401166
ER
PT J
AU Ananthanarayanan, V
Pan, Y
Kocherginsky, M
Tretiakova, M
Amin, MB
Cheng, L
Epstein, JI
Grignon, DJ
Hansel, DE
Jimenez, RE
McKenney, JK
Montironi, R
Oliva, E
Osunkoya, AO
Rao, P
Reuter, VE
Ro, JY
Shen, SS
Srigley, JR
Tsuzuki, T
Yao, JL
Antic, T
Haber, M
Taxy, JB
Paner, GP
AF Ananthanarayanan, V.
Pan, Y.
Kocherginsky, M.
Tretiakova, M.
Amin, M. B.
Cheng, L.
Epstein, J. I.
Grignon, D. J.
Hansel, D. E.
Jimenez, R. E.
McKenney, J. K.
Montironi, R.
Oliva, E.
Osunkoya, A. O.
Rao, P.
Reuter, V. E.
Ro, J. Y.
Shen, S. S.
Srigley, J. R.
Tsuzuki, T.
Yao, J. L.
Antic, T.
Haber, M.
Taxy, J. B.
Paner, G. P.
TI Influence of Histologic Criteria and Confounding Factors (CFs) in
Staging Equivocal Cases for Microscopic Perivesical Tissue Invasion
(MPVI or pT3a): An Interobserver Study among Expert GU Pathologists
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 102nd Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology (USCAP)
CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 Univ Chicago, Chicago, IL 60637 USA.
Emory Univ, Atlanta, GA 30322 USA.
Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA.
Indiana Univ, Indianapolis, IN 46204 USA.
Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA.
Cleveland Clin, Cleveland, OH 44106 USA.
Mayo Clin, Rochester, MN USA.
Polytech Univ Marche Reg, Ancona, Italy.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
Methodist Hosp, Houston, TX 77030 USA.
McMaster Univ, Hamilton, ON, Canada.
Nagoya Daini Red Cross Hosp, Nagoya, Aichi, Japan.
Univ Rochester, Rochester, NY USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2013
VL 26
SU 2
MA 802
BP 194A
EP 195A
PG 2
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444401206
ER
PT J
AU Dong, F
Ping, Y
Wang, C
Wu, S
Xiao, Y
McDougal, WS
Young, RH
Wu, CL
AF Dong, F.
Ping, Y.
Wang, C.
Wu, S.
Xiao, Y.
McDougal, W. S.
Young, R. H.
Wu, C-L
TI Architectural Heterogeneity and Cribriform Pattern Predict Adverse
Clinical Outcome for Gleason Grade 4 Prostatic Adenocarcinoma
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 102nd Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology (USCAP)
CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 [Dong, F.; Ping, Y.; Wang, C.; Wu, S.; Xiao, Y.; McDougal, W. S.; Young, R. H.; Wu, C-L] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
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 FEB
PY 2013
VL 26
SU 2
MA 852
BP 206A
EP 206A
PG 1
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444401256
ER
PT J
AU Flynn, L
Sheils, O
O'Leary, JJ
Finn, SP
Watson, W
Loda, M
Mucci, L
AF Flynn, L.
Sheils, O.
O'Leary, J. J.
Finn, S. P.
Watson, W.
Loda, M.
Mucci, L.
TI miRNA Signatures of Indolent and Aggressive Prostate Cancer
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 102nd Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology (USCAP)
CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 Dublin City Univ, Trinity Coll, Dublin 9, Ireland.
Univ Coll Dublin, Dublin 2, Ireland.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
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 FEB
PY 2013
VL 26
SU 2
MA 875
BP 211A
EP 211A
PG 1
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444401279
ER
PT J
AU Mason, EF
Sadow, PM
Wagner, AJ
Remillard, SP
Flood, TA
Belanger, EC
Hornick, JL
Barletta, JA
AF Mason, E. F.
Sadow, P. M.
Wagner, A. J.
Remillard, S. P.
Flood, T. A.
Belanger, E. C.
Hornick, J. L.
Barletta, J. A.
TI Identification of Succinate Dehydrogenase-Deficient Bladder
Paragangliomas
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 102nd Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology (USCAP)
CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 Brigham & Womens Hosp, Boston, MA 02115 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Ottawa Hosp, Ottawa, ON, Canada.
NR 0
TC 0
Z9 0
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 FEB
PY 2013
VL 26
SU 2
MA 966
BP 233A
EP 233A
PG 1
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444401370
ER
PT J
AU Ali, RH
Kurihara, S
Endo, M
Rouzbahman, M
Hoang, LN
Melnyk, N
Marino-Enriquez, A
Dal Cin, P
Fletcher, JA
Oliva, E
Huntsman, DG
Oda, Y
Nucci, MR
Lee, CH
AF Ali, R. H.
Kurihara, S.
Endo, M.
Rouzbahman, M.
Hoang, L. N.
Melnyk, N.
Marino-Enriquez, A.
Dal Cin, P.
Fletcher, J. A.
Oliva, E.
Huntsman, D. G.
Oda, Y.
Nucci, M. R.
Lee, C-H
TI Genetic Reclassification of Undifferentiated Endometrial Sarcoma:
Clinical Relevance
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 102nd Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology (USCAP)
CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 Univ British Columbia, Vancouver, BC V5Z 1M9, Canada.
Kyushu Univ, Fukuoka 812, Japan.
Univ Toronto, Toronto, ON, Canada.
Brigham & Womens Hosp, Boston, MA 02115 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada.
NR 0
TC 1
Z9 1
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2013
VL 26
SU 2
MA 1096
BP 263A
EP 263A
PG 1
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444401501
ER
PT J
AU Bandyopadhyay, S
Winer, I
Mert, I
Oliva, E
Nucci, M
Al-Wahab, Z
Guan, H
Arabi, H
Alosh, B
Van de Vijver, KK
Ali-Fehmi, R
AF Bandyopadhyay, S.
Winer, I.
Mert, I.
Oliva, E.
Nucci, M.
Al-Wahab, Z.
Guan, H.
Arabi, H.
Alosh, B.
Van de Vijver, K. K.
Ali-Fehmi, R.
TI Clinical Significance of Lymphovascular Space Invasion in Uterine Serous
Carcinoma
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 102nd Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology (USCAP)
CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 Wayne State Univ, Detroit, MI USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
Brigham & Womens Hosp, Boston, MA 02115 USA.
King Abdul Aziz Med City, Jeddah, Saudi Arabia.
NR 0
TC 0
Z9 0
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 FEB
PY 2013
VL 26
SU 2
MA 1106
BP 266A
EP 266A
PG 1
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444401511
ER
PT J
AU Hoang, LN
McConechy, MK
Koebel, M
Han, G
Rouzbahman, M
Davidson, B
Irving, J
Ali, R
Leung, S
Oliva, E
Nucci, MR
Soslow, RA
Huntsman, DG
Gilks, CB
Lee, CH
AF Hoang, L. N.
McConechy, M. K.
Koebel, M.
Han, G.
Rouzbahman, M.
Davidson, B.
Irving, J.
Ali, R.
Leung, S.
Oliva, E.
Nucci, M. R.
Soslow, R. A.
Huntsman, D. G.
Gilks, C. B.
Lee, C-H
TI Histotype-Genotype Correlation in 36 High-Grade Endometrial Carcinomas
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 102nd Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology (USCAP)
CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 Univ British Columbia, Vancouver, BC V5Z 1M9, Canada.
Univ Calgary, Calgary, AB, Canada.
Univ Toronto, Toronto, ON, Canada.
Norwegian Radium Hosp, Oslo, Norway.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
Brigham & Womens Hosp, Boston, MA 02115 USA.
Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
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 FEB
PY 2013
VL 26
SU 2
MA 1160
BP 278A
EP 278A
PG 1
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444401565
ER
PT J
AU Lee, CH
Hoang, LN
Reyes, C
Saslow, RA
Nucci, MR
Oliva, E
AF Lee, C-H
Hoang, L. N.
Reyes, C.
Saslow, R. A.
Nucci, M. R.
Oliva, E.
TI Frequent Immunohistochemical Expression of KIT in YWHAE-FAM22
Endometrial Stromal Sarcoma
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 102nd Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology (USCAP)
CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 Univ British Columbia, Vancouver, BC V5Z 1M9, Canada.
Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
Brigham & Womens Hosp, Boston, MA 02115 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
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 FEB
PY 2013
VL 26
SU 2
MA 1192
BP 285A
EP 285A
PG 1
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444401597
ER
PT J
AU Wagner, AJ
Remillard, SP
Zhang, YX
Doyle, LA
George, S
Hornick, JL
AF Wagner, Andrew J.
Remillard, Stephen P.
Zhang, Yi-Xiang
Doyle, Leona A.
George, Suzanne
Hornick, Jason L.
TI Loss of expression of SDHA predicts SDHA mutations in gastrointestinal
stromal tumors
SO MODERN PATHOLOGY
LA English
DT Article
DE gastrointestinal stromal tumor; succinate dehydrogenase; SDHA; SDHB;
soft tissue sarcoma; immunohistochemistry
ID V600E BRAF MUTATIONS; GERM-LINE MUTATIONS; SUCCINATE-DEHYDROGENASE;
GENE-MUTATIONS; CARNEY-STRATAKIS; RENAL TUMORS; PHEOCHROMOCYTOMA;
PARAGANGLIOMAS; IMMUNOHISTOCHEMISTRY; ADULTS
AB Gastrointestinal stromal tumors (GISTs) are usually driven by mutations in KIT or PDGFRA, although 15% of GISTs in adults and >90% in children lack such mutations. The majority of gastric KIT/PDGFRA wild-type GISTs show distinctive morphological and clinical features and loss of expression of succinate dehydrogenase (SDH) B. Only a small subset of SDHB-deficient GISTs carries loss-of-function mutations in SDHB, SDHC, or SDHD. Because of the complexity of its locus (15 exons) and the presence of three pseudogenes, SDHA is rarely analyzed. Recently, mutations in SDHA were shown to lead to loss of expression of SDHA in a small group of paragangliomas. We sought to determine whether immunohistochemistry for SDHA could identify GISTs with SDHA mutations. Tumors (n = 33) with pathological features of SDH-deficient GIST were analyzed for expression of SDHA and SDHB by immunohistochemistry, and SDHA exons were sequenced from tumors lacking SDHA expression. Exons harboring somatic mutations were examined in DNA from corresponding normal tissue. All 33 tumors showed loss of SDHB expression. A total of 9 out of 33 (27%) tumors also lacked expression of SDHA. SDHA-deficient GISTs affected five men and four women (median age 38 years). SDHA expression was intact in the 24 remaining tumors, including those with known SDHB (n = 3) or SDHC (n = 2) mutations. Nonsense (n = 8) or missense (n = 1) mutations in SDHA were identified in all SDHA-deficient tumors. Heterozygous mutations were also found in DNA from normal tissues from six patients with available material. Somatic loss of the second allele has been found in seven tumors, five by loss of heterozygosity, one by a 13-bp deletion, and one by a missense mutation. Loss of SDHA expression in GIST reliably predicts the presence of SDHA mutations, which represent a relatively common cause of SDH-deficient GIST in adults. Immunohistochemistry for SDHA can be used to select patients for SDHA-specific genetic testing. Modern Pathology (2013) 26, 289-294; doi:10.1038/modpathol.2012.153; published online 7 September 2012
C1 [Wagner, Andrew J.; Remillard, Stephen P.; Zhang, Yi-Xiang; George, Suzanne] Harvard Univ, Sch Med, Ctr Sarcoma & Bone Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Doyle, Leona A.; Hornick, Jason L.] Harvard Univ, Sch Med, Dept Pathol, Brigham & Womens Hosp, Boston, MA 02115 USA.
RP Hornick, JL (reprint author), Harvard Univ, Sch Med, Dept Pathol, Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.
EM jhornick@partners.org
FU DK Ludwig Fund for Cancer Research
FX We are grateful to Dr Esther Korpershoek (University Medical Center,
Rotterdam) for providing SDHA primer sequences, and to the DK Ludwig
Fund for Cancer Research for support of the Ludwig Center at
Dana-Farber/Harvard.
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DI 10.1038/modpathol.2012.153
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PM 22955521
ER
PT J
AU Zane, NA
Kraft, S
Faquin, W
Stone, JH
Deshpande, V
AF Zane, N. A.
Kraft, S.
Faquin, W.
Stone, J. H.
Deshpande, V.
TI IgG4-Related Disease Is a Rare Cause of Recurrent Mastoiditis and Can Be
Mimicked by Severe Otitis Media
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 102nd Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology (USCAP)
CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 [Zane, N. A.; Kraft, S.; Faquin, W.; Stone, J. H.; Deshpande, V.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
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PD FEB
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VL 26
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MA 1317
BP 315A
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PG 1
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SC Pathology
GA 083EB
UT WOS:000314444401722
ER
PT J
AU Boyer, DF
Lindeman, NI
Harris, NL
Ferry, JA
AF Boyer, D. F.
Lindeman, N. I.
Harris, N. L.
Ferry, J. A.
TI Peripheral T-Cell Lymphomas with Cytotoxic Phenotype in Patients with
Nodal SLL/CLL
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 102nd Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology (USCAP)
CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Brigham & Womens Hosp, Boston, MA 02115 USA.
NR 0
TC 0
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PD FEB
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VL 26
SU 2
MA 1341
BP 321A
EP 321A
PG 1
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444401746
ER
PT J
AU Chen, BJ
Ouyang, J
Xu, ML
Yu, H
Fletcher, CDM
Sun, H
Shipp, MA
Rodig, SJ
AF Chen, B. J.
Ouyang, J.
Xu, M. L.
Yu, H.
Fletcher, C. D. M.
Sun, H.
Shipp, M. A.
Rodig, S. J.
TI Expression of the Immunosuppressive Molecules PD-L1 and Galectin-1 by
EBV+ Lymphoproliferative Disorders: Novel Candidates for Targeted
Immunotherapy
SO MODERN PATHOLOGY
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DT Meeting Abstract
CT 102nd Annual Meeting of the
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CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
DFCI, Boston, MA USA.
Yale Univ, Sch Med, New Haven, CT USA.
UMass Mem Hosp, Worcester, MA USA.
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PD FEB
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VL 26
SU 2
MA 1351
BP 323A
EP 323A
PG 1
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SC Pathology
GA 083EB
UT WOS:000314444401756
ER
PT J
AU Huck, A
Fathi, A
Hasserjian, R
AF Huck, A.
Fathi, A.
Hasserjian, R.
TI Cytopenia Prior to AML Diagnosis Predicts Aggressive Behavior Even in
the Absence of Antecedent MDS: Another Diagnostic Criterion for AML with
Myelodysplasia-Related Changes?
SO MODERN PATHOLOGY
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DT Meeting Abstract
CT 102nd Annual Meeting of the
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CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 [Huck, A.; Fathi, A.; Hasserjian, R.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
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VL 26
SU 2
MA 1395
BP 333A
EP 333A
PG 1
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SC Pathology
GA 083EB
UT WOS:000314444402022
ER
PT J
AU Hwang, DG
Dorfman, DM
Briggs, DA
Silverio, R
Pozdnyakova, O
AF Hwang, D. G.
Dorfman, D. M.
Briggs, D. A.
Silverio, R.
Pozdnyakova, O.
TI Detecting Myelodysplastic Syndromes on Peripheral Blood Using a Machine
Learning Approach To Analyze Multiparameter Hematology Analyzer Data
SO MODERN PATHOLOGY
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CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 Virginia Mason Med Ctr, Seattle, WA 98101 USA.
Brigham & Womens Hosp, Boston, MA 02115 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
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VL 26
SU 2
MA 1399
BP 334A
EP 334A
PG 1
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GA 083EB
UT WOS:000314444402026
ER
PT J
AU Klepeis, V
Hasserjian, RP
AF Klepeis, V.
Hasserjian, R. P.
TI Refractory Anemia with Excess Blasts in Transformation Exhibits
Clinicopathologic Features and Clinical Behavior Similar to AML with >=
30% Blasts
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CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 [Klepeis, V.; Hasserjian, R. P.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
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VL 26
SU 2
MA 1410
BP 336A
EP 336A
PG 1
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444402037
ER
PT J
AU Klepeis, VE
Zukerberg, LR
Hasserjian, RP
AF Klepeis, V. E.
Zukerberg, L. R.
Hasserjian, R. P.
TI Genetic Subtypes of Acute Myeloid Leukemia Are Associated with
Distinctive Features of the Bone Marrow Microenvironment
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CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 [Klepeis, V. E.; Zukerberg, L. R.; Hasserjian, R. P.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
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SU 2
MA 1411
BP 336A
EP 337A
PG 2
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444402038
ER
PT J
AU Nicolae, A
Huppmann, AR
Slack, GW
Ferry, JA
Harris, NL
Pittaluga, S
Jaffe, ES
Hasserjian, RP
AF Nicolae, A.
Huppmann, A. R.
Slack, G. W.
Ferry, J. A.
Harris, N. L.
Pittaluga, S.
Jaffe, E. S.
Hasserjian, R. P.
TI EBV Is Infrequently Expressed in the LP Cells of Nodular Lymphocyte
Predominant Hodgkin Lymphoma (NLPHL) in Both Children and Adults
SO MODERN PATHOLOGY
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CT 102nd Annual Meeting of the
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CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 NCI, Bethesda, MD 20892 USA.
BC Canc Agcy, Vancouver, BC, Canada.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
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PD FEB
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VL 26
SU 2
MA 1473
BP 352A
EP 352A
PG 1
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444402100
ER
PT J
AU O'Malley, DP
Kim, YS
Sohani, A
Weiss, L
Perkins, S
Burke, JS
Fisher, C
Orazi, A
AF O'Malley, D. P.
Kim, Y. S.
Sohani, A.
Weiss, L.
Perkins, S.
Burke, J. S.
Fisher, C.
Orazi, A.
TI Immunohistochemical Characterization of Vascular and Stromal
Proliferations of Spleen
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C1 Clarient Inc GE Healthcare, Aliso Viejo, CA USA.
City Hope Natl Med Ctr, Duarte, CA 91010 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
Univ Utah, Salt Lake City, UT USA.
Alta Bates Med Ctr, Berkeley, CA USA.
Royal Marsden Hosp, London SW3 6JJ, England.
Weill Cornell Med Coll, New York, NY USA.
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VL 26
SU 2
MA 1475
BP 352A
EP 352A
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GA 083EB
UT WOS:000314444402102
ER
PT J
AU O'Malley, DP
Zuckerberg, L
Smith, L
Barry, TS
Gunn, S
Tam, W
Orazi, A
Kim, YS
Weiss, L
AF O'Malley, D. P.
Zuckerberg, L.
Smith, L.
Barry, T. S.
Gunn, S.
Tam, W.
Orazi, A.
Kim, Y. S.
Weiss, L.
TI The Genetics of Interdigitating Dendritic Cell Tumors Shares Some
Changes with Langerhans Cell Histiocytosis in Select Cases
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CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 Clarient Inc GE Healthcare, Aliso Viejo, CA USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
Univ Michigan, Ann Arbor, MI 48109 USA.
Spectrum Pathol, Mission Viejo, CA USA.
PathCentral, Irvine, CA USA.
Weill Cornell Med Ctr, New York, NY USA.
City Hope Natl Med Ctr, Duarte, CA 91010 USA.
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PD FEB
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VL 26
SU 2
MA 1476
BP 353A
EP 353A
PG 1
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444402103
ER
PT J
AU Pozdnyakova, O
Shahsafaei, A
Freeman, G
Dorfman, D
AF Pozdnyakova, O.
Shahsafaei, A.
Freeman, G.
Dorfman, D.
TI A Panel of Follicular Helper T-Cell (T-FH) Immunophenotypic Markers
Identifies and Differentiates T-FH-Derived Neoplasms from Other T-Cell
Neoplasms
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CL Baltimore, MD
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C1 Brigham & Womens Hosp, Boston, MA 02115 USA.
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VL 26
SU 2
MA 1486
BP 355A
EP 355A
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UT WOS:000314444402113
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PT J
AU Rogers, HJ
Vardiman, JW
Anastasi, J
Raca, G
Savage, NM
Cherry, AM
Arber, D
Moore, E
Morrissette, JJD
Bagg, A
Liu, YC
Mathew, S
Orazi, A
Lin, P
Wang, SA
Bueso-Ramos, CE
Foucar, K
Hasserjian, RP
Hsi, ED
AF Rogers, H. J.
Vardiman, J. W.
Anastasi, J.
Raca, G.
Savage, N. M.
Cherry, A. M.
Arber, D.
Moore, E.
Morrissette, J. J. D.
Bagg, A.
Liu, Y-C
Mathew, S.
Orazi, A.
Lin, P.
Wang, S. A.
Bueso-Ramos, C. E.
Foucar, K.
Hasserjian, R. P.
Hsi, E. D.
TI Complex Karyotype but Not Blast Percentage Is Associated with Poor
Survival in Acute Myeloid Leukemia and Myelodysplastic Syndrome with
Inv(3)(q21q26.2)/t(3;3)(q21;q26.2); a Bone Marrow Pathology Group Study
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SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 Cleveland Clin, Cleveland, OH 44106 USA.
Univ Chicago, Chicago, IL 60637 USA.
Stanford Univ, Stanford, CA 94305 USA.
Univ Penn, Philadelphia, PA 19104 USA.
Cornell Univ, Weill Med Coll, New York, NY 10021 USA.
Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
Univ New Mexico, Albuquerque, NM 87131 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
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PD FEB
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VL 26
SU 2
MA 1498
BP 358A
EP 358A
PG 1
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GA 083EB
UT WOS:000314444402125
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PT J
AU Ryan, RJH
Akin, C
Castells, M
Selig, MK
Nielsen, GP
Ferry, JA
Hornick, JL
AF Ryan, R. J. H.
Akin, C.
Castells, M.
Selig, M. K.
Nielsen, G. P.
Ferry, J. A.
Hornick, J. L.
TI Mast Cell Sarcoma: An Aggressive and Potentially Under-Diagnosed
Neoplasm That May Be Responsive to Targeted Therapy
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SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
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PD FEB
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VL 26
SU 2
MA 1501
BP 359A
EP 359A
PG 1
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444402128
ER
PT J
AU Tandon, B
Swerdlow, SH
Hasserjian, RP
Gibson, SE
AF Tandon, B.
Swerdlow, S. H.
Hasserjian, R. P.
Gibson, S. E.
TI Is Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) a
Lymphoma of Mantle Zone B-Cells?
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C1 Univ Pittsburgh, Sch Med, Pittsburgh, PA USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
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VL 26
SU 2
MA 1522
BP 364A
EP 364A
PG 1
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GA 083EB
UT WOS:000314444402149
ER
PT J
AU Yagi, Y
Qureshi, I
Malik, AZ
Wilbur, DC
AF Yagi, Y.
Qureshi, I.
Malik, A. Z.
Wilbur, D. C.
TI Challenges in Establishing the WSI Based Digital Pathology Facility and
Telepathology Network between Pakistna and USA
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CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Holy Family Hosp, Rawalpindi, Pakistan.
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VL 26
SU 2
MA 1598
BP 382A
EP 383A
PG 2
WC Pathology
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GA 083EB
UT WOS:000314444402224
ER
PT J
AU Fazlollahi, L
Dias-Santagata, D
Sahora, K
Morales-Oyarvide, V
Bernardo, LA
Iafrate, AJ
Pitman, MB
Fernandez-del Castillo, C
Mino-Kenudson, M
AF Fazlollahi, L.
Dias-Santagata, D.
Sahora, K.
Morales-Oyarvide, V.
Bernardo, L. A.
Iafrate, A. J.
Pitman, M. B.
Fernandez-del Castillo, C.
Mino-Kenudson, M.
TI GNAS Mutations in Concomitant Pancreatic Ductal Adenocarcinoma: A Pilot
Study
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CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 [Fazlollahi, L.; Dias-Santagata, D.; Sahora, K.; Morales-Oyarvide, V.; Bernardo, L. A.; Iafrate, A. J.; Pitman, M. B.; Fernandez-del Castillo, C.; Mino-Kenudson, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2013
VL 26
SU 2
MA 1765
BP 424A
EP 424A
PG 1
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444402391
ER
PT J
AU Shahid, M
Zukerberg, LR
Deshpande, V
AF Shahid, M.
Zukerberg, L. R.
Deshpande, V.
TI Is Investing Additional Time on Mitotic Counts in Neuroendocrine
Neoplasm Clinically Relevant?
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 102nd Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology (USCAP)
CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 [Shahid, M.; Zukerberg, L. R.; Deshpande, V.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 1
Z9 1
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2013
VL 26
SU 2
MA 1791
BP 430A
EP 430A
PG 1
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444402417
ER
PT J
AU Solus, JF
Sahora, K
Shvetz, D
Fernandez-del-Castillo, C
Pitman, MB
Mino-Kenudson, M
AF Solus, J. F.
Sahora, K.
Shvetz, D.
Fernandez-del-Castillo, C.
Pitman, M. B.
Mino-Kenudson, M.
TI Protein Expression of the SWI/SNF Chromatin Remolding Subunits in
Intraductal Papillary Mucinous Neoplasm (IPMN) and Pancreatic Ductal
Adenocarcinoma (PDAC)
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 102nd Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology (USCAP)
CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 [Solus, J. F.; Sahora, K.; Shvetz, D.; Fernandez-del-Castillo, C.; Pitman, M. B.; Mino-Kenudson, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
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 FEB
PY 2013
VL 26
SU 2
MA 1796
BP 431A
EP 431A
PG 1
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444402422
ER
PT J
AU Wang, JL
Shvetz, D
Sahora, K
Fernandez-del Castillo, C
Pitman, M
Mino-Kenudson, M
AF Wang, J. L.
Shvetz, D.
Sahora, K.
Fernandez-del Castillo, C.
Pitman, M.
Mino-Kenudson, M.
TI Activation of Src and STAT3 in Intraductal Papillary Mucinous Neoplasm
of the Pancreas (IPMN)
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 102nd Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology (USCAP)
CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU 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 FEB
PY 2013
VL 26
SU 2
MA 1800
BP 432A
EP 432A
PG 1
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444402426
ER
PT J
AU Lindeman, NI
MacConaill, LE
Garcia, E
Kuo, FC
Longtine, JA
Hahn, WC
Kantoff, PW
Rollins, BJ
AF Lindeman, N. I.
MacConaill, L. E.
Garcia, E.
Kuo, F. C.
Longtine, J. A.
Hahn, W. C.
Kantoff, P. W.
Rollins, B. J.
TI Profile: Results from Multiplexed Mass Spectrometric Genotyping of 2178
Cancer Patients
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 102nd Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology (USCAP)
CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 Harvard Univ, Sch Med, Boston, MA USA.
Brigham & Womens Hosp, Boston, MA 02115 USA.
Mt Sinai Hosp, New York, NY 10029 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2013
VL 26
SU 2
MA 1816
BP 436A
EP 436A
PG 1
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444402441
ER
PT J
AU Waldron, L
Parmigiani, G
Fuchs, C
Huttenhower, C
Ogino, S
AF Waldron, L.
Parmigiani, G.
Fuchs, C.
Huttenhower, C.
Ogino, S.
TI Expression Profiling and Molecular Classification of Colorectal Cancer:
Meta-Analysis of 8 Independent mRNA Expression Datasets across the Globe
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 102nd Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology (USCAP)
CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 Dana Farber Canc Inst, Boston, MA 02115 USA.
Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
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 FEB
PY 2013
VL 26
SU 2
MA 1830
BP 439A
EP 439A
PG 1
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444402455
ER
PT J
AU Pessarakli, MM
Phan, RT
AF Pessarakli, M. M.
Phan, R. T.
TI Association between Methylenetetrahydrofolate Reductase (MTHFR) Gene
Variants and Hyperhomocysteinemia in United States Veterans
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 102nd Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology (USCAP)
CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 USC, Keck Sch Med, Los Angeles, CA USA.
Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
NR 0
TC 0
Z9 0
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 FEB
PY 2013
VL 26
SU 2
MA 1853
BP 444A
EP 445A
PG 2
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444402478
ER
PT J
AU Kovach, AE
Cheng, GZ
Channick, CL
Channick, R
Gaissert, HA
Muniappan, A
Kradin, RL
AF Kovach, A. E.
Cheng, G. Z.
Channick, C. L.
Channick, R.
Gaissert, H. A.
Muniappan, A.
Kradin, R. L.
TI The Pathology of Pulmonary Vein Radiofrequency Ablation
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 102nd Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology (USCAP)
CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 [Kovach, A. E.; Cheng, G. Z.; Channick, C. L.; Channick, R.; Gaissert, H. A.; Muniappan, A.; Kradin, R. L.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2013
VL 26
SU 2
MA 1901
BP 457A
EP 457A
PG 1
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444402526
ER
PT J
AU Kovach, AE
Morales-Oyarvide, V
Shvetz, DE
Tammireddy, S
Klepeis, V
Mark, EJ
Santagata, DD
Iafrate, AJ
Mino-Kenudson, M
AF Kovach, A. E.
Morales-Oyarvide, V.
Shvetz, D. E.
Tammireddy, S.
Klepeis, V.
Mark, E. J.
Santagata, D. Dias
Iafrate, A. J.
Mino-Kenudson, M.
TI Pathway Interplay: Activation of EGFR, ERK, and AKT in Early-Stage Lung
Adenocarcinomas
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 102nd Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology (USCAP)
CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 [Kovach, A. E.; Morales-Oyarvide, V.; Shvetz, D. E.; Tammireddy, S.; Klepeis, V.; Mark, E. J.; Santagata, D. Dias; Iafrate, A. J.; Mino-Kenudson, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2013
VL 26
SU 2
MA 1900
BP 457A
EP 457A
PG 1
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444402525
ER
PT J
AU Matsubara, O
Miyai, K
Ishikawa, Y
Nakatani, Y
Mark, EJ
AF Matsubara, O.
Miyai, K.
Ishikawa, Y.
Nakatani, Y.
Mark, E. J.
TI Epithelial-Mesenchymal Transition (EMT) in Active Fibroblastic Foci in
IPF/UIP
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 102nd Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology (USCAP)
CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 Natl Def Med Coll, Tokorozawa, Saitama 359, Japan.
Japanese Fdn Canc Res, Inst Canc, Koto Ku, Tokyo 170, Japan.
Chiba Univ, Chiba, Japan.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
NR 0
TC 0
Z9 0
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 FEB
PY 2013
VL 26
SU 2
MA 1911
BP 459A
EP 459A
PG 1
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444402535
ER
PT J
AU Miyamoto, A
Sharma, A
Nishino, M
Mino-Kenudson, M
Mark, EJ
AF Miyamoto, A.
Sharma, A.
Nishino, M.
Mino-Kenudson, M.
Mark, E. J.
TI Acute Exacerbation of Non-Specific Interstitial Pneumonia Compared to
That of Usual Interstitial Pneumonia
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 102nd Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology (USCAP)
CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 Toranomon Gen Hosp, Tokyo, Japan.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2013
VL 26
SU 2
MA 1915
BP 460A
EP 460A
PG 1
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444402540
ER
PT J
AU Nishino, M
Mathai, SK
O'Donnell, WJ
Kradin, RL
AF Nishino, M.
Mathai, S. K.
O'Donnell, W. J.
Kradin, R. L.
TI Intraalveolar Fibrin Is Associated with Poor Outcomes in Cryptogenic
Organizing Pneumonia
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 102nd Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology (USCAP)
CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 [Nishino, M.; Mathai, S. K.; O'Donnell, W. J.; Kradin, R. L.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
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 FEB
PY 2013
VL 26
SU 2
MA 1921
BP 462A
EP 462A
PG 1
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444402546
ER
PT J
AU Setia, N
Janne, PA
Sholl, LM
AF Setia, N.
Janne, P. A.
Sholl, L. M.
TI Long Term Effects of EGFR Tyrosine Kinase Inhibitor Therapy on the
Non-Neoplastic Lung
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 102nd Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology (USCAP)
CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 Brigham & Womens Hosp, Boston, MA 02115 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
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 FEB
PY 2013
VL 26
SU 2
MA 1939
BP 466A
EP 466A
PG 1
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444402564
ER
PT J
AU Sholl, L
Sun, H
Ligon, A
Butaney, M
Janne, PA
Rodig, S
AF Sholl, L.
Sun, H.
Ligon, A.
Butaney, M.
Janne, P. A.
Rodig, S.
TI MET Copy Number by Dual Color Brightfield In Situ Hybridization and
Fluorescence In Situ Hybridization Correlates with Met Protein
Expression in Lung Adenocarcinomas
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 102nd Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology (USCAP)
CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 Brigham & Womens Hosp, Boston, MA 02115 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
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 FEB
PY 2013
VL 26
SU 2
MA 1942
BP 467A
EP 467A
PG 1
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444402567
ER
PT J
AU Sholl, L
Sun, H
Butaney, M
Lee, C
Janne, PA
Rodig, S
AF Sholl, L.
Sun, H.
Butaney, M.
Lee, C.
Janne, P. A.
Rodig, S.
TI ROS Immunohistochemistry Is a Sensitive and Specific Tool for Detection
of ROS Rearrangements in Lung Adenocarcinoma
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 102nd Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology (USCAP)
CY MAR 02-08, 2013
CL Baltimore, MD
SP US & Canadian Acad Pathol (USCAP), Dako, Biocare Med, Leica Biosyst, Integrated Oncol, Definiens, Ventana, Philips, USCAP Fdn, Nephropath, Sakura
C1 Brigham & Womens Hosp, Boston, MA 02115 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
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 FEB
PY 2013
VL 26
SU 2
MA 1943
BP 467A
EP 467A
PG 1
WC Pathology
SC Pathology
GA 083EB
UT WOS:000314444402568
ER
PT J
AU Caretti, V
Hiddingh, L
Lagerweij, T
Schellen, P
Koken, PW
Hulleman, E
van Vuurden, DG
Vandertop, WP
Kaspers, GJL
Noske, DP
Wurdinger, T
AF Caretti, Viola
Hiddingh, Lotte
Lagerweij, Tonny
Schellen, Pepijn
Koken, Phil W.
Hulleman, Esther
van Vuurden, Dannis G.
Vandertop, W. Peter
Kaspers, Gertjan J. L.
Noske, David P.
Wurdinger, Thomas
TI WEE1 Kinase Inhibition Enhances the Radiation Response of Diffuse
Intrinsic Pontine Gliomas
SO MOLECULAR CANCER THERAPEUTICS
LA English
DT Article
ID DNA-DAMAGING AGENTS; BRAIN-STEM GLIOMAS; GENE-EXPRESSION; MITOTIC
CATASTROPHE; TYROSINE KINASE; CHECKPOINT KINASE; CLINICAL-TRIALS;
TUMOR-CELLS; MK-1775; IDENTIFICATION
AB Diffuse intrinsic pontine glioma (DIPG) is a fatal pediatric disease. Thus far, no therapeutic agent has proven beneficial in the treatment of this malignancy. Therefore, conventional DNA-damaging radiotherapy remains the standard treatment, providing transient neurologic improvement without improving the probability of overall survival. During radiotherapy, WEE1 kinase controls the G(2) cell-cycle checkpoint, allowing for repair of irradiation (IR)-induced DNA damage. Here, we show that WEE1 kinase is one of the highest overexpressed kinases in primary DIPG tissues compared with matching non-neoplastic brain tissues. Inhibition of WEE1 by MK-1775 treatment of DIPG cells inhibited the IR-induced WEE1-mediated phosphorylation of CDC2, resulting in reduced G(2)-M arrest and decreased cell viability. Finally, we show that MK-1775 enhances the radiation response of E98-Fluc-mCherry DIPG mouse xenografts. Altogether, these results show that inhibition of WEE1 kinase in conjunction with radiotherapy holds potential as a therapeutic approach for the treatment of DIPG. Mol Cancer Ther; 12(2); 141-50. (C)2012 AACR.
C1 [Caretti, Viola; Hiddingh, Lotte; Lagerweij, Tonny; Schellen, Pepijn; Hulleman, Esther; van Vuurden, Dannis G.; Kaspers, Gertjan J. L.] Vrije Univ Amsterdam, Med Ctr, Dept Pediat Oncol, NL-1081 HV Amsterdam, Netherlands.
[Caretti, Viola; Hiddingh, Lotte; Lagerweij, Tonny; Schellen, Pepijn; Hulleman, Esther; Vandertop, W. Peter; Noske, David P.; Wurdinger, Thomas] Vrije Univ Amsterdam, Med Ctr, Dept Neurosurg, NL-1081 HV Amsterdam, Netherlands.
[Koken, Phil W.] Vrije Univ Amsterdam, Med Ctr, Dept Radiat Oncol, NL-1081 HV Amsterdam, Netherlands.
[Caretti, Viola; Hiddingh, Lotte; Lagerweij, Tonny; Schellen, Pepijn; Hulleman, Esther; van Vuurden, Dannis G.; Noske, David P.; Wurdinger, Thomas] Vrije Univ Amsterdam, Med Ctr, Neurooncol Res Grp, NL-1081 HV Amsterdam, Netherlands.
[Wurdinger, Thomas] Massachusetts Gen Hosp, Dept Neurol, Mol Neurogenet Unit, Boston, MA 02114 USA.
[Wurdinger, Thomas] Harvard Univ, Sch Med, Boston, MA USA.
RP Wurdinger, T (reprint author), Vrije Univ Amsterdam, Med Ctr, CCA Room 3-36,De Boelelaan 1117, NL-1081 HV Amsterdam, Netherlands.
EM t.wurdinger@vumc.nl
OI Lagerweij, Tonny/0000-0003-1043-7452; Van Vuurden,
Dannis/0000-0002-1364-9007
FU Semmy foundation
FX This research was financially supported by the Semmy foundation (G.J.L.
Kaspers).
NR 41
TC 15
Z9 15
U1 0
U2 12
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1535-7163
EI 1538-8514
J9 MOL CANCER THER
JI Mol. Cancer Ther.
PD FEB
PY 2013
VL 12
IS 2
BP 141
EP 150
DI 10.1158/1535-7163.MCT-12-0735
PG 10
WC Oncology
SC Oncology
GA 088NV
UT WOS:000314842700003
PM 23270927
ER
PT J
AU Hart, S
Novotny-Diermayr, V
Goh, KC
Williams, M
Tan, YC
Ong, LC
Cheong, A
Ng, BK
Amalini, C
Madan, B
Nagaraj, H
Jayaraman, R
Pasha, KM
Ethirajulu, K
Chng, WJ
Mustafa, N
Goh, BC
Benes, C
McDermott, U
Garnett, M
Dymock, B
Wood, JM
AF Hart, Stefan
Novotny-Diermayr, Veronica
Goh, Kee Chuan
Williams, Meredith
Tan, Yong Cheng
Ong, Lai Chun
Cheong, Albert
Ng, Bee Kheng
Amalini, Chithra
Madan, Babita
Nagaraj, Harish
Jayaraman, Ramesh
Pasha, Khalid M.
Ethirajulu, Kantharaj
Chng, Wee Joo
Mustafa, Nurulhuda
Goh, Boon Cher
Benes, Cyril
McDermott, Ultan
Garnett, Mathew
Dymock, Brian
Wood, Jeanette M.
TI VS-5584, a Novel and Highly Selective PI3K/mTOR Kinase Inhibitor for the
Treatment of Cancer
SO MOLECULAR CANCER THERAPEUTICS
LA English
DT Article
ID BREAST-CANCER; PI3K PATHWAY; MTOR; RAPAMYCIN; MODELS; TUMORS;
SENSITIVITY; LIMITATIONS; STRATEGIES; GDC-0941
AB Dysregulation of the PI3K/mTOR pathway, either through amplifications, deletions, or as a direct result of mutations, has been closely linked to the development and progression of a wide range of cancers. Moreover, this pathway activation is a poor prognostic marker for many tumor types and confers resistance to various cancer therapies. Here, we describe VS-5584, a novel, low-molecular weight compound with equivalent potent activity against mTOR(IC50 = 37 nmol/L) and all class I phosphoinositide 3-kinase (PI3K) isoforms IC50: PI3K alpha = 16 nmol/L; PI3K beta = 68 nmol/L; PI3K gamma 25 nmol/L; PI3K delta 42 nmol/L, without relevant activity on 400 lipid and protein kinases. VS-5584 shows robust modulation of cellular PI3K/mTOR pathways, inhibiting phosphorylation of substrates downstream of PI3K and mTORC1/2. A large human cancer cell line panel screen (436 lines) revealed broad antiproliferative sensitivity and that cells harboring mutations in PI3KCA are generally more sensitive toward VS-5584 treatment. VS-5584 exhibits favorable pharmacokinetic properties after oral dosing in mice and is well tolerated. VS-5584 induces long-lasting and dose-dependent inhibition of PI3K/mTOR signaling in tumor tissue, leading to tumor growth inhibition in various rapalog-sensitive and -resistant human xenograft models. Furthermore, VS-5584 is synergistic with an EGF receptor inhibitor in a gastric tumor model. The unique selectivity profile and favorable pharmacologic and pharmaceutical properties of VS-5584 and its efficacy in a wide range of human tumor models supports further investigations of VS-5584 in clinical trials. Mol Cancer Ther; 12(2); 151-61. (C)2012 AACR.
C1 [Hart, Stefan; Novotny-Diermayr, Veronica; Goh, Kee Chuan; Williams, Meredith; Tan, Yong Cheng; Ong, Lai Chun; Cheong, Albert; Ng, Bee Kheng; Amalini, Chithra; Madan, Babita; Nagaraj, Harish; Jayaraman, Ramesh; Pasha, Khalid M.; Ethirajulu, Kantharaj; Dymock, Brian; Wood, Jeanette M.] S BIO Pte Ltd, Singapore 117528, Singapore.
[Chng, Wee Joo; Mustafa, Nurulhuda; Goh, Boon Cher] Natl Univ Singapore, Canc Sci Inst Singapore, Singapore 117548, Singapore.
[Chng, Wee Joo] Natl Univ Hlth Syst, Natl Univ Canc Inst Singapore, Dept Haematol Oncol, Singapore, Singapore.
[Benes, Cyril] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA.
[McDermott, Ultan; Garnett, Mathew] Wellcome Trust Sanger Inst, Canc Genome Project, Hinxton, England.
RP Hart, S (reprint author), S BIO Pte Ltd, 1 Sci Pk Rd,05-09 Capricorn, Singapore 117528, Singapore.
EM stefan.sbio@gmail.com
OI Madan, Babita/0000-0003-1065-8589; McDermott, Ultan/0000-0001-9032-4700
FU Astrazeneca
FX C. Benes has a commercial research grant from Astrazeneca and has
honoraria from Speakers Bureau of EMD serono. No potential conflicts of
interest were disclosed by the other authors.
NR 35
TC 14
Z9 16
U1 2
U2 12
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 FEB
PY 2013
VL 12
IS 2
BP 151
EP 161
DI 10.1158/1535-7163.MCT-12-0466
PG 11
WC Oncology
SC Oncology
GA 088NV
UT WOS:000314842700004
PM 23270925
ER
PT J
AU Goss, K
Wells, C
Kao, D
Bahia, A
Salcedo, E
Long, C
Massoudi, F
Fearing, M
Sims, K
Taylor, M
AF Goss, Kendrick
Wells, Cara
Kao, David
Bahia, Amit
Salcedo, Ernesto
Long, Carlin
Massoudi, Fred
Fearing, Marsha
Sims, Katherine
Taylor, Matthew
TI Implementation of direct-to-patient (DPI) dried-blood-spot (DBS)
screening for Fabry disease in adults with unexplained left-ventricular
hypertrophy (LVH)
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Meeting Abstract
CT 9th Annual World Symposium of the Lysosomal-Disease-Network (LDN)
CY FEB 12-15, 2013
CL Orlando, FL
SP Lysosomal Dis Network (LDN)
C1 [Goss, Kendrick; Sims, Katherine] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurogenet Diagnost Lab,Ctr Human Genet Res, Boston, MA USA.
[Goss, Kendrick; Sims, Katherine] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Wells, Cara; Kao, David; Bahia, Amit; Salcedo, Ernesto; Long, Carlin; Massoudi, Fred; Taylor, Matthew] Univ Colorado, Adult Med Genet Program, Aurora, CO USA.
[Fearing, Marsha] Massachusetts Gen Hosp, Genet Unit, Dept Pediat, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
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 1096-7192
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD FEB
PY 2013
VL 108
IS 2
MA 87
BP S45
EP S45
DI 10.1016/j.ymgme.2012.11.101
PG 1
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 086FW
UT WOS:000314670500089
ER
PT J
AU Hopkin, R
Mauer, M
Lemay, R
Ortiz, J
Sims, K
Waldek, S
AF Hopkin, Robert
Mauer, Michael
Lemay, Roberta
Ortiz, Jose
Sims, Kathy
Waldek, Stephen
TI Early initiation of agalsidase beta treatment is associated with fewer
clinical events in women with Fabry disease: Data from the Fabry
Registry
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Meeting Abstract
CT 9th Annual World Symposium of the Lysosomal-Disease-Network (LDN)
CY FEB 12-15, 2013
CL Orlando, FL
SP Lysosomal Dis Network (LDN)
C1 [Hopkin, Robert] Cincinnati Childrens Hosp Med Ctr, Cincninnati, OH USA.
[Mauer, Michael] Univ Minnesota, Div Pediat Nephrol, Minneapolis, MN USA.
[Lemay, Roberta] Genzyme, Biomed Data Sci & Informat, Cambridge, MA USA.
[Ortiz, Jose] Fdn Jimenez Diaz, E-28040 Madrid, Spain.
[Sims, Kathy] Massachusetts Gen Hosp, Dept Neurol, Ctr Human Genet Res, Boston, MA 02114 USA.
[Sims, Kathy] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA.
[Waldek, Stephen] Salford Royal NHS Fdn Trust, Manchester, Lancs, England.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1096-7192
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD FEB
PY 2013
VL 108
IS 2
MA 99
BP S49
EP S49
DI 10.1016/j.ymgme.2012.11.113
PG 1
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 086FW
UT WOS:000314670500101
ER
PT J
AU Pan, J
Caruso, P
Loes, D
Kubilus, K
Hayden, D
Eichler, F
AF Pan, Jessica
Caruso, Paul
Loes, Daniel
Kubilus, Kim
Hayden, Douglas
Eichler, Florian
TI Brain MRI abnormalities in GM2-gangliosidosis
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Meeting Abstract
CT 9th Annual World Symposium of the Lysosomal-Disease-Network (LDN)
CY FEB 12-15, 2013
CL Orlando, FL
SP Lysosomal Dis Network (LDN)
C1 [Pan, Jessica; Caruso, Paul; Eichler, Florian] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Loes, Daniel] Suburban Radiol Consultants, Minneapolis, MN USA.
[Kubilus, Kim] Natl Tay Sachs & Allied Dis Assoc, Boston, MA USA.
[Hayden, Douglas] MGH Biostat Ctr, Boston, MA USA.
[Eichler, Florian] Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA.
NR 0
TC 0
Z9 0
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 1096-7192
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD FEB
PY 2013
VL 108
IS 2
MA 173
BP S71
EP S72
DI 10.1016/j.ymgme.2012.11.187
PG 2
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 086FW
UT WOS:000314670500175
ER
PT J
AU Rost, N
Metterville, DR
Cloonan, LK
Fitzpatrick, KM
Germain, D
Politei, JM
Sims, KB
AF Rost, Natalia
Metterville, Danielle R.
Cloonan, Lisa K.
Fitzpatrick, Kaitlin M.
Germain, Dominique
Politei, Juan M.
Sims, Katherine B.
TI White matter hyperintensity volume assessment in patients with Fabry
disease
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Meeting Abstract
CT 9th Annual World Symposium of the Lysosomal-Disease-Network (LDN)
CY FEB 12-15, 2013
CL Orlando, FL
SP Lysosomal Dis Network (LDN)
C1 [Rost, Natalia; Metterville, Danielle R.; Cloonan, Lisa K.; Fitzpatrick, Kaitlin M.; Sims, Katherine B.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Germain, Dominique] Hop Raymond Poincare, Garches, France.
[Politei, Juan M.] Juan Fernandez Hosp, Buenos Aires, DF, Argentina.
NR 0
TC 1
Z9 1
U1 0
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1096-7192
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD FEB
PY 2013
VL 108
IS 2
MA 198
BP S80
EP S80
DI 10.1016/j.ymgme.2012.11.212
PG 1
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 086FW
UT WOS:000314670500200
ER
PT J
AU Schiffmann, R
Forni, S
Swift, C
Wu, XY
Lockhart, D
Chee, M
Kitaoka, T
Chudin, E
Pond, S
McNeill, N
Sims, K
Benjamin, E
Sweetman, L
AF Schiffmann, Raphael
Forni, Sabrina
Swift, Caren
Wu, Xiaoyang
Lockhart, David
Chee, Mark
Kitaoka, Traci
Chudin, Eugene
Pond, Stephanie
McNeill, Nathan
Sims, Katherine
Benjamin, Elfrida
Sweetman, Lawrence
TI High incidence of GLA variants in a non-selected heart disease patient
population suggests that the Fabry trait is a common cardiovascular
genetic risk factor
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Meeting Abstract
CT 9th Annual World Symposium of the Lysosomal-Disease-Network (LDN)
CY FEB 12-15, 2013
CL Orlando, FL
SP Lysosomal Dis Network (LDN)
C1 [Schiffmann, Raphael; Forni, Sabrina; Swift, Caren; McNeill, Nathan; Sweetman, Lawrence] Baylor Res Inst, Dallas, TX USA.
[Wu, Xiaoyang; Lockhart, David; Benjamin, Elfrida] Amicus Therapeut, Cranbury, NJ USA.
[Chee, Mark; Kitaoka, Traci; Chudin, Eugene; Pond, Stephanie] Prognosys Biosci Inc, La Jolla, CA USA.
[Sims, Katherine] Massachusetts Gen Hosp, Neurogenet DNA Diagnost Lab, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
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 1096-7192
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD FEB
PY 2013
VL 108
IS 2
MA 204
BP S82
EP S82
DI 10.1016/j.ymgme.2012.11.218
PG 1
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 086FW
UT WOS:000314670500206
ER
PT J
AU Andres, PL
English, R
Mendoza, M
Florence, J
Malkus, E
Schierbecker, J
Siener, C
Malspeis, S
Schoenfeld, DA
Munsat, TL
Cudkowicz, ME
AF Andres, Patricia L.
English, Robert
Mendoza, Michelle
Florence, Julaine
Malkus, Elizabeth
Schierbecker, Jeanine
Siener, Catherine
Malspeis, Susan
Schoenfeld, David A.
Munsat, Theodore L.
Cudkowicz, Merit E.
TI Developing normalized strength scores for neuromuscular research
SO MUSCLE & NERVE
LA English
DT Article
DE ALS; neuromuscular; outcomes measures; strength testing; summary scores
ID AMYOTROPHIC-LATERAL-SCLEROSIS; VOLUNTARY ISOMETRIC CONTRACTION;
CLINICAL-TRIALS; ALS; MUSCLE
AB Introduction: The Accurate Test of Limb Isometric Strength (ATLIS) device can reliably measure the strength of 12 muscle groups using a fixed load cell. The purpose of this study was to analyze ATLIS data from healthy adults to calculate an individual's predicted strength scores. Methods: ATLIS data were collected from 432 healthy adults. Linear regression models were developed to predict each muscle group's strength. The R-squared statistic assessed variability accounted for by the models. Results: Simple main effects models stratified by gender were used to establish regression equations for each muscle using factors of age, weight, and height. Conclusions: Normalizing raw strength scores controls for biometric factors, thus enabling meaningful comparisons between subjects and allowing each muscle to contribute equally to a summary score. Normalized scores are easily interpreted for broad clinical uses, and derived summary scores establish individuals' disease progression rates using a common scale, allowing for more efficient clinical trials. Muscle Nerve 47: 177-182, 2013
C1 [Andres, Patricia L.; Cudkowicz, Merit E.] Massachusetts Gen Hosp, Neurol Clin Trials Unit, Charlestown, MA 02129 USA.
[English, Robert] Univ Kentucky, Dept Phys Therapy, Lexington, KY USA.
[Mendoza, Michelle] Calif Pacific Med Ctr, Forbes Norris MDA ALS Res Ctr, San Francisco, CA USA.
[Florence, Julaine; Malkus, Elizabeth; Schierbecker, Jeanine; Siener, Catherine] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA.
[Malspeis, Susan; Schoenfeld, David A.] Massachusetts Gen Hosp, Biostat Ctr, Charlestown, MA 02129 USA.
[Munsat, Theodore L.] Tufts Med Ctr, Dept Neurol, Boston, MA USA.
RP Andres, PL (reprint author), Massachusetts Gen Hosp, Neurol Clin Trials Unit, 149 13th St,Room 2274, Charlestown, MA 02129 USA.
EM pandres1@partners.org
FU ALS Association; Muscular Dystrophy Association; ALS Therapy Alliance;
Northeast ALS Consortium
FX The authors gratefully acknowledge support by the ALS Association,
Muscular Dystrophy Association, the ALS Therapy Alliance, and the
Northeast ALS Consortium.
NR 33
TC 5
Z9 5
U1 1
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0148-639X
J9 MUSCLE NERVE
JI Muscle Nerve
PD FEB
PY 2013
VL 47
IS 2
BP 177
EP 182
DI 10.1002/mus.23516
PG 6
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 078VS
UT WOS:000314128700004
PM 23168880
ER
PT J
AU Khan, LA
Zhang, HJ
Abraham, N
Sun, L
Fleming, JT
Buechner, M
Hall, DH
Gobel, V
AF Khan, Liakot A.
Zhang, Hongjie
Abraham, Nessy
Sun, Lei
Fleming, John T.
Buechner, Matthew
Hall, David H.
Gobel, Verena
TI Intracellular lumen extension requires ERM-1-dependent apical membrane
expansion and AQP-8-mediated flux
SO NATURE CELL BIOLOGY
LA English
DT Article
ID CAENORHABDITIS-ELEGANS; EXCRETORY CELL; WATER CHANNEL; ERM PROTEINS; C.
ELEGANS; IN-VIVO; EZRIN; AQUAPORINS; MORPHOGENESIS; GENE
AB Many unicellular tubes such as capillaries form lumens intracellularly, a process that is not well understood. Here we show that the cortical membrane organizer ERM-1 is required to expand the intracellular apical/lumenal membrane and its actin undercoat during single-cell Caenorhabditis elegans excretory canal morphogenesis. We characterize AQP-8, identified in an ERM-1-overexpression (ERM-1[++]) suppressor screen, as a canalicular aquaporin that interacts with ERM-1 in lumen extension in a mercury-sensitive manner, implicating water-channel activity. AQP-8 is transiently recruited to the lumen by ERM-1, co-localizing in peri-lumenal cuffs interspaced along expanding canals. An ERM-1[++]-mediated increase in the number of lumen-associated canaliculi is reversed by AQP-8 depletion. We propose that the ERM-1/AQP-8 interaction propels lumen extension by translumenal flux, suggesting a direct morphogenetic effect of water-channel-regulated fluid pressure.
C1 [Khan, Liakot A.; Zhang, Hongjie; Abraham, Nessy; Fleming, John T.; Gobel, Verena] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA.
[Khan, Liakot A.; Zhang, Hongjie; Abraham, Nessy; Fleming, John T.; Gobel, Verena] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Buechner, Matthew] Univ Kansas, Dept Mol Biosci, Lawrence, KS 66045 USA.
[Sun, Lei; Hall, David H.] Albert Einstein Coll Med, Ctr C Elegans Anat, Dept Neurosci, Bronx, NY 10461 USA.
RP Gobel, V (reprint author), Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA.
EM gobel@helix.mgh.harvard.edu
FU NIH [GM078653]; Mattina R. Proctor Award
FX We thank D. Bailie (Simon Fraser University, Burnaby, British Columbia,
Canada), M. Futai (Osaka University, Osaka, Japan), M. Labouesse (IGBMC,
France), K. Nehrke (University of Rochester Medical Center, Rochester
New York, USA) and J. Simske (Case Western Reserve University School of
Medicine, Cleveland, Ohio, USA), and the following C. elegans resource
centres: J. Kohara (National Institute of Genetics, Mishima, Japan), S.
Mitani (National Bioresource Project, Tokyo Women's Medical University,
Tokyo, Japan), the International C. elegans Gene Knockout Consortium and
the Caenorhabditis elegans genetic centre (NIH Center for Research
Resources) for providing plasmids and strains. We thank E. Membreno and
D. Fernandez for technical support, A. Sengupta for three-dimensional
graphics, A. Kim for image editing, F. Solomon for critical reading of
the manuscript, and H. Weinstein and A. Walker for ongoing support. This
work was supported by NIH grant GM078653 and a Mattina R. Proctor Award
to V.G.
NR 65
TC 30
Z9 32
U1 0
U2 9
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1465-7392
J9 NAT CELL BIOL
JI Nat. Cell Biol.
PD FEB
PY 2013
VL 15
IS 2
BP 143
EP 156
DI 10.1038/ncb2656
PG 14
WC Cell Biology
SC Cell Biology
GA 088SF
UT WOS:000314856700006
PM 23334498
ER
PT J
AU Liew, CW
Boucher, J
Cheong, JK
Vernochet, C
Koh, HJ
Mallol, C
Townsend, K
Langin, D
Kawamori, D
Hu, J
Tseng, YH
Hellerstein, MK
Farmer, SR
Goodyear, L
Doria, A
Bluher, M
Hsu, SIH
Kulkarni, RN
AF Liew, Chong Wee
Boucher, Jeremie
Cheong, Jit Kong
Vernochet, Cecile
Koh, Ho-Jin
Mallol, Cristina
Townsend, Kristy
Langin, Dominique
Kawamori, Dan
Hu, Jiang
Tseng, Yu-Hua
Hellerstein, Marc K.
Farmer, Stephen R.
Goodyear, Laurie
Doria, Alessandro
Blueher, Matthias
Hsu, Stephen I-Hong
Kulkarni, Rohit N.
TI Ablation of TRIP-Br2, a regulator of fat lipolysis, thermogenesis and
oxidative metabolism, prevents diet-induced obesity and insulin
resistance
SO NATURE MEDICINE
LA English
DT Article
ID HORMONE-SENSITIVE LIPASE; WHITE ADIPOSE-TISSUE; ADIPOCYTE
DIFFERENTIATION; BR FAMILY; MICE; OVEREXPRESSION; TRANSCRIPTION;
INFLAMMATION; COREGULATORS; HOMEOSTASIS
AB Obesity develops as a result of altered energy homeostasis favoring fat storage. Here we describe a new transcription co-regulator for adiposity and energy metabolism, SERTA domain containing 2 (TRIP-Br2, also called SERTAD2). TRIP-Br2 null mice are resistant to obesity and obesity-related insulin resistance. Adipocytes of these knockout mice showed greater stimulated lipolysis secondary to enhanced expression of hormone sensitive lipase (HSL) and beta 3-adrenergic (Adrb3) receptors. The knockout mice also have higher energy expenditure because of increased adipocyte thermogenesis and oxidative metabolism caused by upregulating key enzymes in their respective processes. Our data show that a cell-cycle transcriptional co-regulator, TRIP-Br2, modulates fat storage through simultaneous regulation of lipolysis, thermogenesis and oxidative metabolism. These data, together with the observation that TRIP-Br2 expression is selectively elevated in visceral fat in obese humans, suggests that this transcriptional co-regulator is a new therapeutic target for counteracting the development of obesity, insulin resistance and hyperlipidemia.
C1 [Liew, Chong Wee; Boucher, Jeremie; Vernochet, Cecile; Koh, Ho-Jin; Townsend, Kristy; Kawamori, Dan; Hu, Jiang; Tseng, Yu-Hua; Goodyear, Laurie; Doria, Alessandro; Kulkarni, Rohit N.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA.
[Cheong, Jit Kong] Duke Natl Univ Singapore, Grad Sch Med, Canc & Stem Cell Biol Program, Singapore, Singapore.
[Vernochet, Cecile; Farmer, Stephen R.] Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA.
[Mallol, Cristina] Univ Autonoma Barcelona, Ctr Anim Biotechnol & Gene Therapy, E-08193 Barcelona, Spain.
[Langin, Dominique] Inst Metab & Cardiovasc Dis, Obes Res Lab, INSERM, U1048, Toulouse, France.
[Hellerstein, Marc K.] Univ Calif Berkeley, Dept Nutr Sci & Toxicol, Berkeley, CA 94720 USA.
[Blueher, Matthias] Univ Leipzig, Dept Med, D-04109 Leipzig, Germany.
[Hsu, Stephen I-Hong] Univ Florida, Coll Med, Dept Med, Gainesville, FL USA.
[Hsu, Stephen I-Hong] Univ Florida, Coll Med, Dept Mol Genet & Microbiol, Gainesville, FL USA.
[Liew, Chong Wee] Univ Illinois, Dept Physiol & Biophys, Chicago, IL 60680 USA.
RP Kulkarni, RN (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA.
EM clipcap2148@gmail.com; rohit.kulkarni@joslin.harvard.edu
OI Langin, Dominique/0000-0002-2669-7825
FU US National Institutes of Health (NIH) [RO1 DK 67536]; Joslin Graetz
Bridge Funds; Joslin Diabetes and Endocrinology Research Center
Specialized Assay and Advanced Microscopy Cores [NIH P30 DK36836];
Deutsche Forschungsgemeinschaft Clinical Research group 'Atherobesity'
[KFO152, BL 833/1-1]; US National Institutes of Health Interdisciplinary
training grant [1RL9EB008539-01]; Manpei Suzuki Diabetes Foundation,
Japan; Juvenile Diabetes Research Foundation; Dialysis Center, Inc.;
University of Florida, Division of Nephrology Gatorade Fund; NIH [K99
DK090210, R01 HL073168, DK51586, DK58825]; Clinical Translational
Science Institute at the University of Florida; [R00 DK090210]
FX The authors thank C.R. Kahn (Joslin Diabetes Center) for providing
reagents and discussions, E. Rosen for discussions, E. Morgan and K.
Parlee for excellent assistance in the preparation of this manuscript,
H. Li for assistance with hormone assays, O.P. McGuinness for mouse
metabolic phenotyping, L. Fajas (INSERM) for providing reagents, M. Mori
(Joslin Diabetes Center) for providing samples and R. Zechner for
providing the protocol for triglyceride hydrolase activities. Funds to
generate some reagents used in this research were supported by US
National Institutes of Health (NIH) grant RO1 DK 67536 (R.N.K.) and the
Joslin Graetz Bridge Funds (R.N.K.), NIH grants R01 HL073168 (A.D.), K99
DK090210 (C.W.L.), DK51586 and DK58825 (S.R.F.) and the Joslin Diabetes
and Endocrinology Research Center Specialized Assay and Advanced
Microscopy Cores (NIH P30 DK36836). The human studies were supported by
a grant of the Deutsche Forschungsgemeinschaft Clinical Research group
'Atherobesity' (KFO152; BL 833/1-1). C.W.L. was supported by a US
National Institutes of Health Interdisciplinary training grant
(1RL9EB008539-01) (SysCODE), K99 DK090210 and R00 DK090210. D.K. is the
recipient of a research fellowship (Manpei Suzuki Diabetes Foundation,
Japan) and a Juvenile Diabetes Research Foundation postdoctoral
Fellowship. S.I.-H.H. and J.K.C. were supported by the R. Glenn Davis
(Dialysis Center, Inc.) Endowed Professorship in Clinical and
Translational Medicine and by the University of Florida, Division of
Nephrology Gatorade Fund. S.I.-H.H. was supported as a Scholar of the
Clinical Translational Science Institute at the University of Florida.
NR 49
TC 23
Z9 26
U1 4
U2 23
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
J9 NAT MED
JI Nat. Med.
PD FEB
PY 2013
VL 19
IS 2
BP 217
EP 226
DI 10.1038/nm.3056
PG 10
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA 086HY
UT WOS:000314675900030
PM 23291629
ER
PT J
AU Gora, MJ
Sauk, JS
Carruth, RW
Gallagher, KA
Suter, MJ
Nishioka, NS
Kava, LE
Rosenberg, M
Bouma, BE
Tearney, GJ
AF Gora, Michalina J.
Sauk, Jenny S.
Carruth, Robert W.
Gallagher, Kevin A.
Suter, Melissa J.
Nishioka, Norman S.
Kava, Lauren E.
Rosenberg, Mireille
Bouma, Brett E.
Tearney, Guillermo J.
TI Tethered capsule endomicroscopy enables less invasive imaging of
gastrointestinal tract microstructure
SO NATURE MEDICINE
LA English
DT Article
ID OPTICAL COHERENCE TOMOGRAPHY; BARRETTS-ESOPHAGUS; INTESTINAL METAPLASIA;
FEASIBILITY; ENDOSCOPY; DIAGNOSIS
AB Here we introduce tethered capsule endomicroscopy, which involves swallowing an optomechanically engineered pill that captures cross-sectional microscopic images of the gut wall at 30 mu m (lateral) x 7 mu m (axial) resolution as it travels through the digestive tract. Results in human subjects show that this technique rapidly provides three-dimensional, microstructural images of the upper gastrointestinal tract in a simple and painless procedure, opening up new opportunities for screening for internal diseases.
C1 [Gora, Michalina J.; Carruth, Robert W.; Gallagher, Kevin A.; Nishioka, Norman S.; Kava, Lauren E.; Rosenberg, Mireille; Bouma, Brett E.; Tearney, Guillermo J.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.
[Gora, Michalina J.; Sauk, Jenny S.; Carruth, Robert W.; Gallagher, Kevin A.; Nishioka, Norman S.; Kava, Lauren E.; Rosenberg, Mireille; Bouma, Brett E.; Tearney, Guillermo J.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Sauk, Jenny S.; Nishioka, Norman S.] Massachusetts Gen Hosp, Dept Gastroenterol, Boston, MA 02114 USA.
[Suter, Melissa J.] Massachusetts Gen Hosp, Dept Pulmonol, Boston, MA 02114 USA.
[Tearney, Guillermo J.] Harvard MIT Hlth Sci & Technol, Cambridge, MA USA.
[Tearney, Guillermo J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
RP Tearney, GJ (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.
EM gtearney@partners.org
FU US National Institutes of Health [NIH R01DK091923, NIH R01CA103769]
FX We thank B. Puricelli for his valuable assistance in the conduct of the
clinical studies and M. Shishkov for useful discussions pertaining to
device design. This work was supported in part by US National Institutes
of Health grants NIH R01DK091923 (G.J.T.) and NIH R01CA103769 (G.J.T.).
NR 14
TC 63
Z9 63
U1 1
U2 34
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
J9 NAT MED
JI Nat. Med.
PD FEB
PY 2013
VL 19
IS 2
BP 238
EP 240
DI 10.1038/nm.3052
PG 3
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA 086HY
UT WOS:000314675900033
PM 23314056
ER
PT J
AU Vaduganathan, M
Greene, SJ
Ambrosy, AP
Gheorghiade, M
Butler, J
AF Vaduganathan, Muthiah
Greene, Stephen J.
Ambrosy, Andrew P.
Gheorghiade, Mihai
Butler, Javed
TI The disconnect between phase II and phase III trials of drugs for heart
failure
SO NATURE REVIEWS CARDIOLOGY
LA English
DT Review
ID RANDOMIZED INTRAVENOUS TEZOSENTAN; BRAIN NATRIURETIC PEPTIDE; A(1)
RECEPTOR ANTAGONIST; WORSENING RENAL-FUNCTION; COLLEGE-OF-CARDIOLOGY;
DOUBLE-BLIND; CLINICAL-TRIALS; VASOPRESSIN ANTAGONIST; SYSTOLIC
DYSFUNCTION; ORAL TOLVAPTAN
AB Hospitalization for heart failure (HF) is a clinical entity associated with high postdischarge morbidity and mortality, yet few therapies are available to improve outcomes in patients with this condition. In the past debacle, large phase III studies of HF treatments have failed to demonstrate drug efficacy, safety, or both, despite encouraging results from preceding phase II trials. This Review is focused on this disconnect between the results of phase II and phase III trials of drugs for HF and discusses findings from five drug-development programs (for levosimendan, tezosentan, tolvaptan, rolofylline, and nesiritide) to shed light on common themes in clinical trials conducted in patients hospitalized for HF. In particular, the importance of selecting the 'right' patient population, drug, and clinical end points to optimize the trial design is discussed. Areas that require further investigation are highlighted and we suggest possible directions that will help to guide future clinical trials in these patients. Large, expensive phase III trials should not be initiated without adequate phase II evidence or on the basis of overly optimistic interpretation of phase II data. Additionally, drug development programs should be targeted not only to change short-term symptoms, but also to improve the postdischarge event rate. Vaduganathan, M. et al. Nat. Rev. Cardiol. 10, 85-97 (2013); published online 8 January 2013; doi:10.1038/nrcardio.2012.181
C1 [Vaduganathan, Muthiah] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Greene, Stephen J.; Gheorghiade, Mihai] NW Univ Feinberg, Ctr Cardiovasc Innovat, Sch Med, Chicago, IL 60611 USA.
[Ambrosy, Andrew P.] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA.
[Butler, Javed] Emory Univ, Div Cardiol, Atlanta, GA 30322 USA.
RP Gheorghiade, M (reprint author), NW Univ Feinberg, Ctr Cardiovasc Innovat, Sch Med, 645 N Michigan Ave,Suite 1006, Chicago, IL 60611 USA.
EM m-gheorghiade@northwestern.edu
NR 78
TC 34
Z9 34
U1 0
U2 5
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1759-5002
J9 NAT REV CARDIOL
JI Nat. Rev. Cardiol.
PD FEB
PY 2013
VL 10
IS 2
BP 85
EP 97
DI 10.1038/nrcardio.2012.181
PG 13
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 085OD
UT WOS:000314623200007
PM 23296069
ER
PT J
AU Wang, CI
Alekseyenko, AA
LeRoy, G
Elia, AEH
Gorchakov, AA
Britton, LMP
Elledge, SJ
Kharchenko, PV
Garcia, BA
Kuroda, MI
AF Wang, Charlotte I.
Alekseyenko, Artyom A.
LeRoy, Gary
Elia, Andrew E. H.
Gorchakov, Andrey A.
Britton, Laura-Mae P.
Elledge, Stephen J.
Kharchenko, Peter V.
Garcia, Benjamin A.
Kuroda, Mitzi I.
TI Chromatin proteins captured by ChIP-mass spectrometry are linked to
dosage compensation in Drosophila
SO NATURE STRUCTURAL & MOLECULAR BIOLOGY
LA English
DT Article
ID X-CHROMOSOMAL GENES; VIVO CROSS-LINKING; RNA-POLYMERASE-II; MSL COMPLEX;
PWWP DOMAIN; HISTONE H4; ANALYSIS REVEALS; METHYLATION; TRANSCRIPTION;
GENOME
AB X-chromosome dosage compensation by the MSL (male-specific lethal) complex is required in Drosophila melanogaster to increase gene expression from the single male X to equal that of both female X chromosomes. Instead of focusing solely on protein complexes released from DNA, here we used chromatin-interacting protein MS (ChIP-MS) to identify MSL interactions on cross-linked chromatin. We identified MSL-enriched histone modifications, including histone H4 Lys16 acetylation and histone H3 Lys36 methylation, and CG4747, a putative Lys36-trimethylated histone H3 (H3K36me3)-binding protein. CG4747 is associated with the bodies of active genes, coincident with H3K36me3, and is mislocalized in the Set2 mutant lacking H3K36me3. CG4747 loss of function in vivo results in partial mislocalization of the MSL complex to autosomes, and RNA interference experiments confirm that CG4747 and Set2 function together to facilitate targeting of the MSL complex to active genes, validating the ChIP-MS approach.
C1 [Wang, Charlotte I.; Alekseyenko, Artyom A.; Elia, Andrew E. H.; Gorchakov, Andrey A.; Elledge, Stephen J.; Kuroda, Mitzi I.] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA.
[Wang, Charlotte I.; Alekseyenko, Artyom A.; Elia, Andrew E. H.; Gorchakov, Andrey A.; Elledge, Stephen J.; Kuroda, Mitzi I.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA.
[LeRoy, Gary; Britton, Laura-Mae P.; Garcia, Benjamin A.] Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA.
[Elia, Andrew E. H.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Elia, Andrew E. H.; Elledge, Stephen J.] Brigham & Womens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA.
[Gorchakov, Andrey A.] Inst Mol & Cell Biol, Novosibirsk, Russia.
[Kharchenko, Peter V.] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA USA.
[Garcia, Benjamin A.] Univ Penn, Dept Biochem & Biophys, Philadelphia, PA 19104 USA.
RP Kuroda, MI (reprint author), Brigham & Womens Hosp, Dept Med, Div Genet, 75 Francis St, Boston, MA 02115 USA.
EM mkuroda@genetics.med.harvard.edu
RI Gorchakov, Andrey/N-5840-2015
OI Gorchakov, Andrey/0000-0003-2830-4236
FU Bloomington Stock Center and TRIP at Harvard Medical School [NIH/NIGMS
R01-GM084947]; US National Institutes of Health (NIH) [GM45744,
GM101958), K25AG037596, GM44664]; Jane Coffin Childs Foundation;
American Society for Radiation Oncology; US National Science Foundation
Early Faculty CAREER award and NIH award, Office of the Director
[DP20D007447]
FX We thank P. Kaiser (University of California, Irvine, Irvine,
California, USA) for the HTB tag and insightful discussions. We thank G.
Schotta (Ludwig-Maxirnilians Universitat, Munich, Germany) for the
pGS-mw[+] vector. The anti-Z4 antibody was a generous gift from H.
Saumweber (Humboldt University, Berlin, Germany). We thank E. Gerace
from the Moazed lab (Harvard Medical School, Boston, Massachusetts, USA)
for providing the protocol for coupling IgG to magnetic beads. We thank
the Bloomington Stock Center and TRIP at Harvard Medical School
(NIH/NIGMS R01-GM084947) for providing fly stocks used in this study. We
are grateful to M. Gelbart for support and expertise, E. Smith for
technical assistance and A. Ciccia, B. Adamson and A. Plachetka for
critical reading of the manuscript. This work was supported by grants
from the US National Institutes of Health (NIH) to M.I.K. (GM45744 and
GM101958), P.V.K. (K25AG037596) and S.J.E. (GM44664). A.E.H.E. is
supported by fellowships from The Jane Coffin Childs Foundation and The
American Society for Radiation Oncology. B.A.G. is supported by a US
National Science Foundation Early Faculty CAREER award and NIH award
number DP20D007447 from the Office of the Director.
NR 55
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U1 0
U2 22
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1545-9993
J9 NAT STRUCT MOL BIOL
JI Nat. Struct. Mol. Biol.
PD FEB
PY 2013
VL 20
IS 2
BP 202
EP 209
DI 10.1038/nsmb.2477
PG 8
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 085OF
UT WOS:000314623400012
PM 23295261
ER
PT J
AU Mendez, MF
Joshi, A
Tassniyom, K
Teng, E
Shapira, JS
AF Mendez, Mario F.
Joshi, Aditi
Tassniyom, Kanida
Teng, Edmond
Shapira, Jill S.
TI Clinicopathologic differences among patients with behavioral variant
frontotemporal dementia
SO NEUROLOGY
LA English
DT Article
ID CENTER NACC DATABASE; UNIFORM DATA SET; LOBAR DEGENERATION;
ALZHEIMER-DISEASE; DIAGNOSTIC-CRITERIA; CONSORTIUM; CONSENSUS; FEATURES
AB Objective: To characterize the presenting symptoms and signs of patients clinically diagnosed with behavioral variant frontotemporal dementia (bvFTD) and who had different neuropathologic findings on autopsy.
Methods: This study reviewed all patients entered as clinical bvFTD in the National Alzheimer's Coordinating Center's database and who had both clinical and neuropathologic data from 2005 to 2011. Among the 107 patients identified, 95 had unambiguous pathologic findings, including 74 with frontotemporal lobar degeneration (bvFTD-FTLD) and 21 with Alzheimer disease (bvFTD-AD). The patients with bvFTD-FTLD were further subdivided into tau-positive (n = 23) or tau-negative (n = 51) histopathology subgroups. Presenting clinical signs and symptoms were compared between these neuropathologic groups.
Results: The patients with bvFTD-FTLD were significantly more likely than patients with bvFTD-AD to have initially predominant personality changes and poor judgment/decision-making. In contrast, patients with bvFTD-AD were more likely than patients with bvFTD-FTLD to have memory difficulty and delusions/hallucinations and agitation. Within the bvFTD-FTLD group, the tau-positive subgroup had more patients with initial behavioral problems and personality change than the tau-negative subgroup, who, in turn, had more patients with initial cognitive impairment and speech problems.
Conclusion: During life, patients with AD pathology may be misdiagnosed with bvFTD if they have an early age at onset and prominent neuropsychiatric features despite having greater memory difficulties and more intact personality and executive functions than patients with bvFTD-FTLD. Among those with FTLD pathology, patients with tau-positive bvFTD were likely to present with behavior/personality changes. These findings offer clues for antemortem recognition of neuropathologic subtypes of bvFTD. Neurology (R) 2013;80:561-568
C1 [Mendez, Mario F.; Joshi, Aditi; Teng, Edmond; Shapira, Jill S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA.
[Mendez, Mario F.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA.
[Mendez, Mario F.; Teng, Edmond] VA Greater Los Angeles Healthcare Ctr, Los Angeles, CA USA.
[Tassniyom, Kanida] Khon Kaen Univ, Dept Psychiat, Khon Kaen, Thailand.
RP Mendez, MF (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA.
EM mmendez@ucla.edu
FU NIA [R01AG034499-03]; VA Merit Review; Alzheimer's Disease Research
Center Grant [NIA P50 AG-16570]; NACC [UO1 AG016976]
FX Supported by NIA grant #R01AG034499-03 (M.F. Mendez), a VA Merit Review
(A. Joshi, M.F. Mendez), Alzheimer's Disease Research Center Grant NIA
P50 AG-16570 (M.F. Mendez), and the NACC grant (UO1 AG016976).
NR 27
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U1 0
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 FEB
PY 2013
VL 80
IS 6
BP 561
EP 568
DI 10.1212/WNL.0b013e3182815547
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA 086OD
UT WOS:000314693800014
PM 23325909
ER
PT J
AU Dunn, GP
Andronesi, OC
Cahill, DP
AF Dunn, Gavin P.
Andronesi, Ovidiu C.
Cahill, Daniel P.
TI From genomics to the clinic: biological and translational insights of
mutant IDH1/2 in glioma
SO NEUROSURGICAL FOCUS
LA English
DT Article
DE isocitrate dehydrogenase 1; isocitrate dehydrogenase 2; glioblastoma;
low-grade glioma; magnetic resonance spectroscopy
ID ISOCITRATE DEHYDROGENASE 1; ACUTE MYELOID-LEUKEMIA;
MAGNETIC-RESONANCE-SPECTROSCOPY; CODON 132 MUTATION; CELL LUNG-CANCER;
IDH2 MUTATIONS; ONCOMETABOLITE 2-HYDROXYGLUTARATE; INDUCED APOPTOSIS;
MAFFUCCI SYNDROME; OLLIER DISEASE
AB The characterization of the genomic alterations across all human cancers is changing the way that malignant disease is defined and treated. This paradigm is extending to glioma, where the discovery of recurrent mutations in the isocitrate dehydrogenase 1 (IDH1) gene has shed new light on the molecular landscape in glioma and other IDH-mutant cancers. The IDH1 mutations are present in the vast majority of low-grade gliomas and secondary glioblastomas. Rapidly emerging work on the consequences of mutant IDH1 protein expression suggests that its neomorphic enzymatic activity catalyzing the production of the oncometabolite 2-hydroxyglutarate influences a range of cellular programs that affect the epigenome, transcriptional programs, hypoxia-inducible factor biology, and development. In the brief time since its discovery, knowledge of the IDH mutation status has had significant translational implications, and diagnostic tools are being used to monitor its expression and function. The concept of IDH1-mutant versus IDH1-wild type will become a critical early distinction in diagnostic and treatment algorithms. (http://thejns.org/doi/abs/10.3171/2012.12.FOCUS12355)
C1 [Dunn, Gavin P.; Cahill, Daniel P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02114 USA.
[Andronesi, Ovidiu C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA.
RP Cahill, DP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02114 USA.
EM dcahill@partners.org
OI Cahill, Daniel/0000-0003-2552-6546
FU Buroughs-Wellcome Fund Career Award; American Brain Tumor Association;
NIH NINDS [R25]; KL2 Medical Research Investigator Training (MeRIT)
award from the Harvard Catalyst-The Harvard Clinical and Translational
Science Center (National Center for Research Resources); National Center
for Advancing Translational Sciences, NIH Award [8KL2TR000168-05];
National Institute of Biomedical Imaging and Bioengineering (NIBIB) of
the NIH; NIH Shared Instrumentation Grant Program [S10RR021110]; NIH
High-End Instrumentation Grant Program [S10RR021110]
FX This work was supported by the Buroughs-Wellcome Fund Career Award (Dr.
Cahill); the American Brain Tumor Association and the NIH NINDS R25
award (Dr. Dunn); and the KL2 Medical Research Investigator Training
(MeRIT) award from the Harvard Catalyst-The Harvard Clinical and
Translational Science Center (National Center for Research Resources and
the National Center for Advancing Translational Sciences, NIH Award
8KL2TR000168-05) (Dr. Andronesi). The content is solely the
responsibility of the authors and does not necessarily represent the
official views of Harvard Catalyst, Harvard University and its
affiliated academic health care centers, or the NIH.; Imaging research
(Dr. Andronesi) was carried out in part at the Athinoula A. Martinos
Center for Biomedical Imaging at the Massachusetts General Hospital,
using resources provided by the Center for Functional Neuroimaging
Technologies, P41EB015896, a P41 Regional Resource supported by the
National Institute of Biomedical Imaging and Bioengineering (NIBIB) of
the NIH. This work also involved the use of instrumentation supported by
the NIH Shared Instrumentation Grant Program and/or High-End
Instrumentation Grant Program, specifically Grant No. S10RR021110.
NR 102
TC 15
Z9 17
U1 2
U2 19
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 FEB
PY 2013
VL 34
IS 2
AR E2
DI 10.3171/2012.12.FOCUS12355
PG 15
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA 084FD
UT WOS:000314522200003
PM 23373447
ER
PT J
AU Jones, PS
Dunn, GP
Barker, FG
Curry, WT
Hochberg, FH
Cahill, DP
AF Jones, Pamela S.
Dunn, Gavin P.
Barker, Fred G., II
Curry, William T.
Hochberg, Fred H.
Cahill, Daniel P.
TI Molecular genetics of low-grade gliomas: genomic alterations guiding
diagnosis and therapeutic intervention. 11th Annual Frye-Halloran Brain
Tumor Symposium Meeting Report
SO NEUROSURGICAL FOCUS
LA English
DT Article
DE glioma; meeting report; IDH
ID CENTRAL-NERVOUS-SYSTEM; ACUTE MYELOID-LEUKEMIA; IDH2 MUTATIONS;
GLIOBLASTOMA-MULTIFORME; DIFFERENTIATION; CLASSIFICATION; SURVIVAL;
OLIGODENDROGLIOMAS; HYPERMETHYLATION; IDENTIFICATION
AB Object. The authors' goal was to review the current understanding of the underlying molecular and genetic mechanisms involved in low-grade glioma development and how these mechanisms can be targets for detection and treatment of the disease and its recurrence.
Methods. On October 4, 2012, the authors convened a meeting of researchers and clinicians across a variety of pertinent medical specialties to review the state of current knowledge on molecular genetic mechanisms of low-grade gliomas and to identify areas for further research and drug development.
Results. The meeting consisted of 3 scientific sessions ranging from neuropathology of IDH1 mutations; CIC, ATRX, and FUBP1 mutations in oligodendrogliomas and astrocytomas; and IDH1 mutations as therapeutic targets. Sessions consisted of a total of 10 talks by international leaders in low-grade glioma research, mutant IDH1 biology and its application in glioma research, and treatment.
Conclusions. The recent discovery of recurrent gene mutations in low-grade glioma has increased the understanding of the molecular mechanisms involved in a host of biological activities related to low-grade gliomas. Understanding the role these genetic alterations play in brain cancer initiation and progression will help lead to the development of novel treatment modalities than can be personalized to each patient, thereby helping transform this now often-fatal malignancy into a chronic or even curable disease. (http://thejns.org/doi/abs/10.3171/2012.12.FOCUS12349)
C1 [Jones, Pamela S.; Dunn, Gavin P.; Barker, Fred G., II; Curry, William T.; Hochberg, Fred H.; Cahill, Daniel P.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA.
RP Cahill, DP (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, 55 Fruit St,YAW 9E-9026, Boston, MA 02114 USA.
EM dcahill@partners.org
FU The Carolyn Frye-Halloran Brain Tumor Therapy Program
FX The Carolyn Frye-Halloran Brain Tumor Therapy Program sponsored the
symposium.
NR 26
TC 5
Z9 7
U1 0
U2 17
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 FEB
PY 2013
VL 34
IS 2
AR E9
DI 10.3171/2012.12.FOCUS12349
PG 6
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA 084FD
UT WOS:000314522200010
PM 23373454
ER
PT J
AU Park, JW
Piknova, B
Huang, PL
Noguchi, CT
Schechter, AN
AF Park, Ji Won
Piknova, Barbora
Huang, Paul L.
Noguchi, Constance T.
Schechter, Alan N.
TI Effect of Blood Nitrite and Nitrate Levels on Murine Platelet Function
SO PLOS ONE
LA English
DT Article
ID OXIDE SYNTHASE; XANTHINE OXIDOREDUCTASE; DIETARY NITRATE; HYPOXIC
CONDITIONS; RELAXING FACTOR; REDUCTION; ENDOTHELIUM; AGGREGATION;
HUMANS; MICE
AB Nitric oxide (NO) appears to play an important role in the regulation of thrombosis and hemostasis by inhibiting platelet function. The discovery of NO generation by reduction of nitrite (NO2-) and nitrate (NO3-) in mammals has led to increased attention to these anions with respect to potential beneficial effects in cardiovascular diseases. We have previously shown that nitrite anions at 0.1 mu M inhibit aggregation and activation of human platelet preparations in vitro in the presence of red blood cells and this effect was enhanced by deoxygenation, an effect likely due to NO generation. In the present study, we hypothesized that nitrite and nitrate derived from the diet could also alter platelet function upon their conversion to NO in vivo. To manipulate the levels of nitrite and nitrate in mouse blood, we used antibiotics, NOS inhibitors, low nitrite/nitrate (NOx) diets, endothelial NOS knock-out mice and also supplementation with high levels of nitrite or nitrate in the drinking water. We found that all of these perturbations affected nitrite and nitrate levels but that the lowest whole blood values were obtained by dietary restriction. Platelet aggregation and ATP release were measured in whole blood and the results show an inverse correlation between nitrite/nitrate levels and platelet activity in aggregation and ATP release. Furthermore, we demonstrated that nitrite-supplemented group has a prolonged bleeding time compared with control or low NOx diet group. These results show that diet restriction contributes greatly to blood nitrite and nitrate levels and that platelet reactivity can be significantly affected by these manipulations. Our study suggests that endogenous levels of nitrite and nitrate may be used as a biomarker for predicting platelet function and that dietary manipulation may affect thrombotic processes.
C1 [Park, Ji Won; Piknova, Barbora; Noguchi, Constance T.; Schechter, Alan N.] NIDDKD, Mol Med Branch, NIH, Bethesda, MD 20892 USA.
[Huang, Paul L.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Schechter, AN (reprint author), NIDDKD, Mol Med Branch, NIH, Bethesda, MD 20892 USA.
EM alans@intra.niddk.nih.gov
OI Schechter, Alan N/0000-0002-5235-9408
FU National Institue of Diabetes and Digestive and Kidney Diseases
FX This research was supported by grants from the intramural program of the
National Institue of Diabetes and Digestive and Kidney Diseases. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 42
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U1 0
U2 11
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD FEB 1
PY 2013
VL 8
IS 2
AR e55699
DI 10.1371/journal.pone.0055699
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 085EU
UT WOS:000314597900051
PM 23383344
ER
PT J
AU Traeger, L
Penedo, FJ
Benedict, C
Dahn, JR
Lechner, SC
Schneiderman, N
Antoni, MH
AF Traeger, Lara
Penedo, Frank J.
Benedict, Catherine
Dahn, Jason R.
Lechner, Suzanne C.
Schneiderman, Neil
Antoni, Michael H.
TI Identifying how and for whom cognitive-behavioral stress management
improves emotional well-being among recent prostate cancer survivors
SO PSYCHO-ONCOLOGY
LA English
DT Article
DE cancer; oncology; prostate carcinoma; psychosocial intervention; illness
perceptions
ID QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIAL; RADICAL PROSTATECTOMY;
FUNCTIONAL ASSESSMENT; BREAST-CANCER; MEN; THERAPY; OUTCOMES; ILLNESS;
VALIDATION
AB Objective The outcomes of a 10-week cognitive-behavioral stress management (CBSM) group intervention were evaluated in prostate cancer survivors. A model was tested in which CBSM-related improvements in emotional well-being were attained through changes in men's perceptions of their condition, as conceptualized by information processing explanations of self-regulation theory. The model also tested whether life stress and treatment-related side effects moderated intervention effects. Methods Men treated for localized prostate cancer (n=257) within the past 18months were randomized to CBSM or a half-day psycho-educational seminar. At pre-intervention and 12-week follow-up, emotional well-being, illness perceptions, life stress, and sexual and urinary function were assessed using validated questionnaires. Results After controlling for covariates, CBSM participants showed greater improvements in emotional well-being relative to control participants (=0.13, p<0.05). For men reporting higher stress upon study entry, CBSM-related improvements were partially explained by changes in some, but not all, illness perceptions. Sexual and urinary dysfunction did not influence CBSM-related gains. Conclusions Prostate cancer perceptions may be an important target for enhancing emotional well-being, particularly for men experiencing general life stress. However, interventions that explicitly target mental representations of cancer may be needed to modify perceptions of the disease. Copyright (c) 2011 John Wiley & Sons, Ltd.
C1 [Traeger, Lara] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
[Penedo, Frank J.; Benedict, Catherine; Lechner, Suzanne C.; Schneiderman, Neil; Antoni, Michael H.] Univ Miami, Dept Psychol, Coral Gables, FL 33124 USA.
[Dahn, Jason R.] Miami VA Med Ctr, Psychol Serv, Miami, FL USA.
RP Traeger, L (reprint author), Massachusetts Gen Hosp, Behav Med Serv, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA.
EM ltraeger@partners.org
FU NCI NIH HHS [1P50CA84944, U01CA861]
NR 44
TC 12
Z9 12
U1 3
U2 20
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1057-9249
J9 PSYCHO-ONCOLOGY
JI Psycho-Oncol.
PD FEB
PY 2013
VL 22
IS 2
BP 250
EP 259
DI 10.1002/pon.2074
PG 10
WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences,
Biomedical
SC Oncology; Psychology; Biomedical Social Sciences
GA 083VQ
UT WOS:000314493700003
PM 21932396
ER
PT J
AU Herndon, JE
Kornblith, AB
Holland, JC
Paskett, ED
AF Herndon, James E., II
Kornblith, Alice B.
Holland, Jimmie C.
Paskett, Electra D.
TI Effect of socioeconomic status as measured by education level on
survival in breast cancer clinical trials
SO PSYCHO-ONCOLOGY
LA English
DT Article
DE breast cancer; oncology; education; survival; SES
ID LEUKEMIA GROUP-B; AFRICAN-AMERICAN PATIENTS; INTERMEDIATE-DOSE
CHEMOTHERAPY; CELL LUNG-CARCINOMA; QUALITY-OF-LIFE; ADJUVANT
CHEMOTHERAPY; PHASE-III; SOCIAL INEQUALITIES; RACIAL-DIFFERENCES;
PROGNOSTIC-FACTORS
AB Objectives This paper aims to investigate the effect of socioeconomic status, as measured by education, on the survival of breast cancer patients treated on 10 studies conducted by the Cancer and Leukemia Group B. Methods Sociodemographic data, including education, were reported by the patient at trial enrollment. Cox proportional hazards model stratified by treatment arm/study was used to examine the effect of education on survival among patients with early stage and metastatic breast cancer, after adjustment for known prognostic factors. Results The patient population included 1020 patients with metastatic disease and 5146 patients with early stage disease. Among metastatic patients, factors associated with poorer survival in the final multivariable model included African American race, never married, negative estrogen receptor status, prior hormonal therapy, visceral involvement, and bone involvement. Among early stage patients, significant factors associated with poorer survival included African American race, separated/widowed, post/perimenopausal, negative/unknown estrogen receptor status, negative progesterone receptor status, >4 positive nodes, tumor diameter >2cm, and education. Having not completed high school was associated with poorer survival among early stage patients. Among metastatic patients, non-African American women who lacked a high school degree had poorer survival than other non-African American women, and African American women who lacked a high school education had better survival than educated African American women. Conclusions Having less than a high school education is a risk factor for death among patients with early stage breast cancer who participated in a clinical trial, with its impact among metastatic patients being less clear. Post-trial survivorship plans need to focus on women with low social status, as measured by education. Copyright (c) 2011 John Wiley & Sons, Ltd.
C1 [Herndon, James E., II] Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC 27710 USA.
[Kornblith, Alice B.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Holland, Jimmie C.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Paskett, Electra D.] Ohio State Univ, Coll Med, Columbus, OH 43210 USA.
[Paskett, Electra D.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA.
RP Herndon, JE (reprint author), Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Hock Plaza,Suite 802,Box 2717, Durham, NC 27710 USA.
EM james.herndon@duke.edu
FU National Cancer Institute [CA31946, CA33601]; [CA32291]; [CA77651];
[CA77658]
FX The research was supported, in part, by grants from the National Cancer
Institute (CA31946) to the Cancer and Leukemia Group B (Richard L.
Schilsky, MD, Chairman) and to the CALGB Statistical Center (Stephen
George, PhD, CA33601). The authors were also supported by grants (Alice
B. Kornblith, PhD, CA32291; Jimmie C. Holland, MD, CA77651; Electra D.
Paskett, PhD, CA77658). The content of this manuscript is solely the
responsibility of the authors and does not necessarily represent the
official views of the National Cancer Institute.
NR 62
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U1 0
U2 14
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1057-9249
J9 PSYCHO-ONCOLOGY
JI Psycho-Oncol.
PD FEB
PY 2013
VL 22
IS 2
BP 315
EP 323
DI 10.1002/pon.2094
PG 9
WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences,
Biomedical
SC Oncology; Psychology; Biomedical Social Sciences
GA 083VQ
UT WOS:000314493700010
PM 22021121
ER
PT J
AU Varela, VS
Ng, A
Mauch, P
Recklitis, CJ
AF Varela, Veronica Sanchez
Ng, Andrea
Mauch, Peter
Recklitis, Christopher J.
TI Posttraumatic stress disorder (PTSD) in survivors of Hodgkin's lymphoma:
prevalence of PTSD and partial PTSD compared with sibling controls
SO PSYCHO-ONCOLOGY
LA English
DT Article
DE Hodgkin's lymphoma; long-term survivors; posttraumatic stress; survey;
cancer; oncology
ID BONE-MARROW-TRANSPLANTATION; BREAST-CANCER PATIENTS; LONG-TERM
SURVIVORS; CHILDHOOD-CANCER; SYMPTOMS; DIAGNOSIS; SYMPTOMATOLOGY;
CHILDREN; PARENTS; DISEASE
AB Objectives Studies of posttraumatic stress disorder (PTSD) document a significant proportion of cancer survivors reporting severe posttraumatic stress symptoms, even when they do not meet full diagnostic criteria. However, few studies have directly examined the clinical significance of these partial PTSD' symptoms in survivors. This study aimed to investigate the prevalence of PTSD symptoms in a cohort of long-term survivors of Hodgkin's lymphoma (HL) and to explore the clinical relevance of the partial PTSD phenomenon by assessing impairment of function secondary to sub-threshold symptomatology. Methods The Posttraumatic Diagnostic Scale was completed by 105 HL survivors and 101 sibling controls. Survivors' age at time of participation ranged from 24 to 71 years, age at time of diagnosis ranged from 6 to 61 years, and the median time since diagnosis was 16 years (range=734). Results Posttraumatic stress disorder prevalence was not significantly higher in HL survivors (13%) compared with sibling controls (6.9%, p=0.098). However, a significantly larger proportion of survivors (35.2%) met criteria for partial PTSD compared with siblings (17.8%, p=0.004). Moreover, the majority of the survivors with partial PTSD (86.5%) reported experiencing some functional impairment related to these posttraumatic stress symptoms. Conclusions A significant number of HL survivors experience posttraumatic stress symptoms severe enough to result in functional impairment. This finding underscores the importance of future research detailing the psychological and functional outcomes in survivors with partial PTSD and of careful clinical practice that assesses for functional impairment secondary to partial PTSD symptomatology, in male and female survivors, even years after completion of therapy. Copyright (c) 2011 John Wiley & Sons, Ltd.
C1 [Varela, Veronica Sanchez; Recklitis, Christopher J.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Ng, Andrea; Mauch, Peter] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Varela, Veronica Sanchez; Ng, Andrea; Mauch, Peter; Recklitis, Christopher J.] Harvard Univ, Sch Med, Boston, MA USA.
RP Recklitis, CJ (reprint author), Dana Farber Canc Inst, Perini Family Survivors Ctr, Boston, MA 02115 USA.
EM Christopher_Recklitis@dfci.harvard.edu
FU National Cancer Institute [5R03CA134159-02]
FX This research was supported by Grant Number 5R03CA134159-02 to Dr.
Recklitis from the National Cancer Institute. Its contents are solely
the responsibility of the authors and do not necessarily represent the
official views of the National Cancer Institute or NIH.
NR 33
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U1 7
U2 21
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1057-9249
J9 PSYCHO-ONCOLOGY
JI Psycho-Oncol.
PD FEB
PY 2013
VL 22
IS 2
BP 434
EP 440
DI 10.1002/pon.2109
PG 7
WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences,
Biomedical
SC Oncology; Psychology; Biomedical Social Sciences
GA 083VQ
UT WOS:000314493700025
PM 22162210
ER
PT J
AU Fisher, DF
Kondili, D
Williams, J
Hess, DR
Bittner, EA
Schmidt, UH
AF Fisher, Daniel F.
Kondili, Dhimiter
Williams, June
Hess, Dean R.
Bittner, Edward A.
Schmidt, Ulrich H.
TI Tracheostomy Tube Change Before Day 7 Is Associated With Earlier Use of
Speaking Valve and Earlier Oral Intake
SO RESPIRATORY CARE
LA English
DT Article
DE tracheostomy; mechanical ventilation; respiratory failure; outcomes;
safety
ID VENTILATION
AB BACKGROUND: Presence of a tracheostomy tube often decreases the patient's ability to communicate and to tolerate oral intake. The initial tracheostomy tube change is often recommended between day 7 and 14 post insertion. Local guidelines permit tracheostomy tube change 5 days after insertion. OBJECTIVE: We hypothesized that changing tracheostomy tubes before day 7 is associated with earlier use of a speaking valve as well as earlier oral intake, compared to changing tracheostomy tubes after 7 days. METHODS: We prospectively enrolled 130 admitted subjects, after tracheostomy placement to a respiratory care unit between July 2008 and May 2010. Subject data were recorded from the electronic medical record. The primary end point was the time from tracheostomy tube placement to tolerating speaking valve. The secondary end point was the time from tracheostomy tube placement to tolerating oral intake. Complications of tracheostomy tube change were recorded. RESULTS: Thirty-eight subjects had the first tracheostomy tube change before 7 days (early group), and 92 subjects had the first tracheostomy tube change after 7 days (late group). The early group tolerated a speaking valve significantly sooner than the late group (7 d vs 12 d, P = .001). The early group also tolerated oral intake significantly sooner (10 d vs 20 d, P = .04). After change of the tracheostomy tube, the time to tolerating oral feeding was 5.5 days in both groups. There was no significant difference in time to decannulation between the groups. The early group had a shorter respiratory care unit stay (11 d vs 17 d, P = .001) and a shorter hospital stay (P = .05) than the late group. There was no difference in survival. There were no complications associated with tracheostomy tube change. CONCLUSIONS: Tracheostomy tube change before day 7 is associated with earlier ability to tolerate speaking valve and oral intake. In this series, early tracheostomy tube change was not associated with an increased rate of complications.
C1 [Fisher, Daniel F.; Hess, Dean R.; Schmidt, Ulrich H.] Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA.
[Williams, June] Massachusetts Gen Hosp, Dept Speech Language & Swallowing Disorders, Boston, MA 02114 USA.
[Kondili, Dhimiter; Hess, Dean R.; Bittner, Edward A.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
[Hess, Dean R.; Bittner, Edward A.; Schmidt, Ulrich H.] Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA.
[Schmidt, Ulrich H.] Massachusetts Gen Hosp, Surg Intens Care Unit, Boston, MA 02114 USA.
RP Schmidt, UH (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Surg Intens Care Unit, 55 Fruit St,Gray 4, Boston, MA 02114 USA.
EM uschmidt@partners.org
NR 15
TC 4
Z9 5
U1 0
U2 7
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 FEB
PY 2013
VL 58
IS 2
BP 257
EP 263
DI 10.4187/respcare.01714
PG 7
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 084PY
UT WOS:000314552800005
PM 22782273
ER
PT J
AU Wilcox, SR
Richards, JB
AF Wilcox, Susan R.
Richards, Jeremy B.
TI Noninvasive Carbon Monoxide Detection: Insufficient Evidence for Broad
Clinical Use
SO RESPIRATORY CARE
LA English
DT Editorial Material
ID LABORATORY CARBOXYHEMOGLOBIN MEASUREMENT; PULSE COOXIMETER;
EMERGENCY-DEPARTMENT; ICE STORM; OXIMETRY; METHEMOGLOBIN; DIAGNOSIS;
PERFORMANCE; MANAGEMENT
C1 [Wilcox, Susan R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA.
[Wilcox, Susan R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA.
[Richards, Jeremy B.] Beth Israel Deaconess Med Ctr, Dept Med, Div Pulm Crit Care & Sleep Med, Boston, MA 02215 USA.
[Richards, Jeremy B.] Harvard Univ, Sch Med, Boston, MA USA.
RP Wilcox, SR (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA.
EM swilcox1@partners.org
OI Wilcox, Susan/0000-0001-7477-7531
NR 25
TC 1
Z9 1
U1 0
U2 5
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 FEB
PY 2013
VL 58
IS 2
BP 376
EP 379
DI 10.4187/respcare.02288
PG 4
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 084PY
UT WOS:000314552800020
PM 23359727
ER
PT J
AU Gazourian, L
Coronata, AMF
Rogers, AJ
Weinhouse, GL
Soiffer, RJ
Antin, JH
Ritz, J
Ho, VT
Baron, RM
Washko, GR
AF Gazourian, Lee
Coronata, Anna Maria F.
Rogers, Angela J.
Weinhouse, Gerald L.
Soiffer, Robert J.
Antin, Joseph H.
Ritz, Jerome
Ho, Vincent T.
Baron, Rebecca M.
Washko, George R.
TI Airway dilation in bronchiolitis obliterans after allogeneic
hematopoietic stem cell transplantation
SO RESPIRATORY MEDICINE
LA English
DT Article
DE Computed tomography; Bone marrowtransplantation; Bronchiolitis
obliterans syndrome; Airway disease
ID BONE-MARROW-TRANSPLANTATION; HIGH-RESOLUTION CT; THIN-SECTION CT;
OBSTRUCTIVE PULMONARY-DISEASE; VERSUS-HOST-DISEASE; LUNG
TRANSPLANTATION; COMPUTED-TOMOGRAPHY; FLOW OBSTRUCTION; FUNCTION TESTS;
RISK-FACTORS
AB Rationale: Bronchiolitis obliterans syndrome (BOS) is a late, non-infectious pulmonary complication following hematopoietic stem cell transplantation (HSCT). There is minimal data published on quantitative radiologic characterization of airway remodeling in these subjects.
Objectives: To examine quantitative measurements of airway morphology and their correlation with lung function in a cohort of patients who underwent HSCT and developed BOS.
Methods: All adult patients who underwent allogeneic HSCT at the Dana-Farber Cancer Institute/Brigham and Women's Hospital (n = 1854) between January 1st 2000 and June 30th 2010 were screened for the development of BOS. Clinically acquired high resolution CT (HRCT) scans of the chest were collected. For each subjects discrete measures of airway wall area were performed and the square root of wall area of a 10-mm luminal perimeter (Pi 10) was calculated.
Measurements and main results: We identified 88 cases of BOS, and 37 of these patients had available HRCT. On CT scans obtained after BOS diagnosis, the Pi10 decreased (consistent with airway dilation) as compared with pre-BOS values (p < 0.001). After HSCT the Pi10 correlated with FEV1% predicted (r = 0.636, p < 0.0001), and RV/TLC% predicted (r = -0.736, p < 0.0001), even after adjusting for age, sex and total lung capacity (p < 0.0001 for both).
Conclusions: On HRCT scan BOS is characterized by central airway dilation, the degree of which is correlated to decrements in lung function. This is opposite of what has been previously demonstrated in COPD and asthma that quantitative measure of proximal airway wall thickening directly correlate with pulmonary function. Our data suggests that the pathologic process affecting the central airways is different from the pathology observed in the distal airways. Further work is needed to determine if such change can be used as a sensitive and specific tool for the future diagnosis and staging of BOS. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Gazourian, Lee; Coronata, Anna Maria F.; Rogers, Angela J.; Weinhouse, Gerald L.; Baron, Rebecca M.; Washko, George R.] Brigham & Womens Hosp, Dept Med, Div Pulm & Crit Care Med, Boston, MA 02115 USA.
[Rogers, Angela J.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA.
[Soiffer, Robert J.; Antin, Joseph H.; Ritz, Jerome; Ho, Vincent T.] Dana Farber Canc Inst, Dept Med Oncol, Div Hematol Malignancies, Boston, MA 02115 USA.
RP Gazourian, L (reprint author), Brigham & Womens Hosp, Dept Med, Div Pulm & Crit Care Med, 75 Francis St, Boston, MA 02115 USA.
EM lgazourian@partners.org
OI Ritz, Jerome/0000-0001-5526-4669
FU National Institutes of Health [5T32HL007118-35, 5T32HL007680-20,
K23HL089353-04, CA142106, PO1HL070149-02]; Ted and Eileen Pasquarello
Research Fund; Jock and Bunny Adams Education and Research Fund; Parker
B. Francis Foundation
FX This work was supported by the following National Institutes of Health
grants; Dr. Gazourian 5T32HL007118-35, 5T32HL007680-20, Dr. Washko,
K23HL089353-04. The DFCI BMT data repository is supported, in part, by
the Ted and Eileen Pasquarello Research Fund; NIH grants; CA142106, and
PO1HL070149-02; and the Jock and Bunny Adams Education and Research
Fund. Dr. Rogers and Dr. Washko were also supported by an award from the
Parker B. Francis Foundation.
NR 36
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U1 0
U2 5
PU W B SAUNDERS CO LTD
PI LONDON
PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND
SN 0954-6111
J9 RESP MED
JI Respir. Med.
PD FEB
PY 2013
VL 107
IS 2
BP 276
EP 283
DI 10.1016/j.rmed.2012.11.002
PG 8
WC Cardiac & Cardiovascular Systems; Respiratory System
SC Cardiovascular System & Cardiology; Respiratory System
GA 084RE
UT WOS:000314556000015
PM 23195332
ER
PT J
AU Sibila, O
Restrepo, MI
AF Sibila, Oriol
Restrepo, Marcos I.
TI Corticosteroids for pneumonia: Are we there yet?
SO RESPIROLOGY
LA English
DT Editorial Material
DE community-acquired pneumonia; corticosteroid; length of stay; pneumonia
ID COMMUNITY-ACQUIRED PNEUMONIA; CONTROLLED-TRIAL; CLINICAL-COURSE;
GLUCOCORTICOIDS
C1 [Sibila, Oriol] Hosp Santa Creu & Sant Pau, Serv Pneumol, Barcelona, Spain.
[Restrepo, Marcos I.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Restrepo, Marcos I.] S Texas Vet Hlth Care Syst, San Antonio, TX USA.
[Restrepo, Marcos I.] Vet Evidence Based Res Disseminat & Implementat C, San Antonio, TX USA.
RP Sibila, O (reprint author), Hosp Santa Creu & Sant Pau, Serv Pneumol, Barcelona, Spain.
RI Restrepo, Marcos/H-4442-2014
FU NHLBI NIH HHS [K23HL096054, K23 HL096054]
NR 12
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1323-7799
J9 RESPIROLOGY
JI Respirology
PD FEB
PY 2013
VL 18
IS 2
BP 199
EP 200
DI 10.1111/resp.12012
PG 2
WC Respiratory System
SC Respiratory System
GA 078RH
UT WOS:000314116500001
PM 23134329
ER
PT J
AU Bui, E
Rodgers, R
Simon, NM
Jehel, L
Metcalf, CA
Birmes, P
Schmitt, L
AF Bui, Eric
Rodgers, Rachel
Simon, Naomi M.
Jehel, Louis
Metcalf, Christina A.
Birmes, Philippe
Schmitt, Laurent
TI Body Piercings and Posttraumatic Stress Disorder Symptoms in Young
Adults
SO STRESS AND HEALTH
LA English
DT Article
DE traumatic stress/disaster relief operations; group norms; psychological
well-being
ID SENSATION SEEKING; COLLEGE-STUDENTS; ADOLESCENTS; MOTIVATIONS;
POPULATION; PERCEPTION; BEHAVIOR; TATTOOS; ART
AB Body piercing, which is prevalent in young adults, has been suggested to be associated with features usually related to posttraumatic stress disorder (PTSD) such as high-risk behaviours and psychopathological symptoms and might be motivated by a wish to deal with prior traumatic experiences. However, to date, no research has investigated the relationship between this practice and PTSD symptoms. The present research aims to investigate the possible relationship between body piercing and PTSD symptoms in French-speaking young adults. According to our results, having two or more body piercings was associated with a twofold increased risk for scoring above the cut-off score for PTSD on the PTSD checklist. Our findings suggest that two or more body piercings might serve as an identifiable marker for PTSD symptoms and may have important implications for clinical screening. Copyright (c) 2012 John Wiley & Sons, Ltd.
C1 [Bui, Eric; Birmes, Philippe; Schmitt, Laurent] CHU Toulouse, Lab Stress Traumat EA4560, Toulouse, France.
[Bui, Eric; Birmes, Philippe; Schmitt, Laurent] Univ Toulouse, Toulouse, France.
[Bui, Eric; Simon, Naomi M.; Metcalf, Christina A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Rodgers, Rachel] Univ Toulouse Le Mirail, Toulouse, France.
[Rodgers, Rachel] Northeastern Univ, Boston, MA 02115 USA.
[Jehel, Louis] Univ Antilles Guyane, CHU Ft de France, Fort De France, France.
[Jehel, Louis] INSERM, U669, Fort De France, France.
RP Bui, E (reprint author), Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Boston, MA 02114 USA.
EM tebui@partners.org
RI Bui, Eric/J-8347-2015
OI Bui, Eric/0000-0002-1413-6473
FU Traumapsy Association; Centre Hospitalier Universitaire de Toulouse
FX This research was supported by a grant from the Traumapsy Association
and the Centre Hospitalier Universitaire de Toulouse awarded to Eric
Bui.
NR 23
TC 0
Z9 0
U1 4
U2 21
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1532-3005
J9 STRESS HEALTH
JI Stress Health
PD FEB
PY 2013
VL 29
IS 1
BP 70
EP 74
DI 10.1002/smi.2427
PG 5
WC Psychology, Applied; Psychiatry; Psychology
SC Psychology; Psychiatry
GA 083NY
UT WOS:000314472500011
PM 22499241
ER
PT J
AU Kelley, JM
Onderdonk, AB
Kao, G
AF Kelley, James M.
Onderdonk, Andrew B.
Kao, Grace
TI Bacillus cereus septicemia attributed to a matched unrelated bone marrow
transplant
SO TRANSFUSION
LA English
DT Article
ID BACTERIAL-CONTAMINATION; DETECTION SYSTEM; CELL PRODUCTS; COMPONENTS;
PLATELETS; OXYGEN
AB BACKGROUND: Hematopoietic cell transplantation (HCT) is performed in more than 25,000 patients annually. Clinically significant bacterial transmission from HCT products is rare. CASE REPORT: A 36-year-old male of Asian descent with chronic myelogenous leukemia developed sepsis leading to acute renal failure and disseminated intravascular coagulation during infusion of matched unrelated donor bone marrow. This product later tested positive for Bacillus cereus. DISCUSSION: This HCT product traveled 31 hours at room temperature before arriving at the transplant center. Reducing transport times, transporting at 4 degrees C, and enhancing bacterial surveillance of HCT products may increase the ability to detect bacterial proliferation from transport. CONCLUSION: To prevent a similar case in the future, we will begin Gram staining all HCT products in transit more than 24 hours to alert physicians of the need for prophylactic antibiotic therapy.
C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA.
Dana Farber Canc Inst, Cell Manipulat Core Facil, Boston, MA 02215 USA.
RP Kao, G (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,JFB313, Boston, MA 02215 USA.
EM gkao@partners.org
NR 21
TC 2
Z9 2
U1 0
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0041-1132
J9 TRANSFUSION
JI Transfusion
PD FEB
PY 2013
VL 53
IS 2
BP 394
EP 397
DI 10.1111/j.1537-2995.2012.03723.x
PG 4
WC Hematology
SC Hematology
GA 087ST
UT WOS:000314783700022
PM 22624657
ER
PT J
AU Soskin, DP
AF Soskin, David P.
TI Artist's Statement: Puzzled Commentary
SO ACADEMIC MEDICINE
LA English
DT Editorial Material
C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Treatment Resistant Depress,Depress Clin & Re, Boston, MA 02115 USA.
RP Soskin, DP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Treatment Resistant Depress,Depress Clin & Re, Boston, MA 02115 USA.
EM dsoskin@partners.org
NR 4
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 FEB
PY 2013
VL 88
IS 2
BP 215
EP 215
DI 10.1097/01.ACM.0000426356.35520.8c
PG 1
WC Education, Scientific Disciplines; Health Care Sciences & Services
SC Education & Educational Research; Health Care Sciences & Services
GA 081WA
UT WOS:000314351900024
ER
PT J
AU Matthews, LT
Crankshaw, T
Giddy, J
Kaida, A
Smit, JA
Ware, NC
Bangsberg, DR
AF Matthews, Lynn T.
Crankshaw, Tamaryn
Giddy, Janet
Kaida, Angela
Smit, Jennifer A.
Ware, Norma C.
Bangsberg, David R.
TI Reproductive Decision-Making and Periconception Practices Among
HIV-Positive Men and Women Attending HIV Services in Durban, South
Africa
SO AIDS AND BEHAVIOR
LA English
DT Article
DE HIV-serodiscordant couples; HIV prevention; Safer conception; Family
planning; South Africa
ID SUB-SAHARAN AFRICA; SERO-DISCORDANT COUPLES; ANTIRETROVIRAL THERAPY;
INFECTED WOMEN; FERTILITY INTENTIONS; MALE CIRCUMCISION; INVOLUNTARY
CHILDLESSNESS; HIV-1-DISCORDANT COUPLES; PROSPECTIVE COHORT; COMMUNITY
TRIAL
AB Understanding reproductive decisions and periconception behavior among HIV-discordant couples is important for designing risk reduction interventions for couples who choose to conceive. In-depth interviews were conducted to explore reproductive decision-making and periconception practices among HIV-positive women with recent pregnancy (n = 30), and HIV-positive men (n = 20), all reporting partners of negative or unknown HIV-status, and attending HIV services in Durban, South Africa. Transcripts were coded for categories and emergent themes. Participants expressed strong reasons for having children, but rarely knew how to reduce periconception HIV transmission. Pregnancy planning occurred on a spectrum ranging from explicitly intended to explicitly unintended, with many falling in between the two extremes. Male fertility desire and misunderstanding serodiscordance contributed to HIV risk behavior. Participants expressed openness to healthcare worker advice for safer conception and modified risk behavior post-conception, suggesting the feasibility of safer conception interventions which may target both men and women and include serodiscordance counseling and promotion of contraception.
C1 [Matthews, Lynn T.; Bangsberg, David R.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[Matthews, Lynn T.; Bangsberg, David R.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA.
[Matthews, Lynn T.] Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA.
[Crankshaw, Tamaryn; Giddy, Janet] PMTCT, McCord Hosp, Durban, South Africa.
Simon Fraser Univ, Fac Hlth Sci, Vancouver, BC, Canada.
[Smit, Jennifer A.] Univ Witwatersrand, Dept Obstet & Gynaecol, Maternal Adolescent & Child Hlth Div MatCH, Durban, South Africa.
[Ware, Norma C.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA 02115 USA.
[Bangsberg, David R.] Mbarara Univ Sci & Technol, Mbarara, Uganda.
RP Matthews, LT (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 100 Cambridge St,15th Floor, Boston, MA 02114 USA.
EM ltmatthews@partners.org
FU NIMH NIH HHS [K23 MH095655, K24 MH087227, K24 MH090894]; Wellcome Trust
NR 80
TC 32
Z9 33
U1 1
U2 14
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 FEB
PY 2013
VL 17
IS 2
BP 461
EP 470
DI 10.1007/s10461-011-0068-y
PG 10
WC Public, Environmental & Occupational Health; Social Sciences, Biomedical
SC Public, Environmental & Occupational Health; Biomedical Social Sciences
GA 081FL
UT WOS:000314302800002
PM 22038045
ER
PT J
AU Donnell, DJ
Baeten, JM
Hong, T
Lingappa, JR
Mujugira, A
Nakku-Joloba, E
Bangsberg, D
Celum, C
AF Donnell, Deborah J.
Baeten, Jared M.
Hong, Ting
Lingappa, Jairam R.
Mujugira, Andrew
Nakku-Joloba, Edith
Bangsberg, David
Celum, Connie
TI Correlation Between Pill Counts and Biologic Effects in an HIV-1
Prevention Clinical Trial: Implications for Measuring Adherence
SO AIDS AND BEHAVIOR
LA English
DT Article; Proceedings Paper
CT 6th International-AIDS-Society (IAS) Conference on HIV Pathogenesis,
Treatment and Prevention
CY JUL 17-20, 2011
CL Rome, ITALY
SP Int AIDS Soc (IAS)
DE Medication adherence; HIV prevention; Pill count
ID HERPES-SIMPLEX-VIRUS; RECURRENT GENITAL HERPES; PLACEBO-CONTROLLED
TRIAL; ANTIRETROVIRAL ADHERENCE; PROTEASE INHIBITORS; DOUBLE-BLIND;
SUPPRESSION; ACYCLOVIR; THERAPY; WOMEN
AB Clinic-based pill counts of unused study medication are frequently used to measure adherence in HIV-1 prevention trials. Monthly pill count adherence data from the Partners in Prevention HSV/HIV Transmission Study, a double-blind, placebo controlled trial of twice-daily acyclovir suppression of herpes simplex virus type 2 (HSV-2) in HIV-1 infected persons was used to compare changes between 3,381 placebo and active arm participants in two objective biologic measures of acyclovir's drug activity: reduction in plasma HIV-1 RNA and HSV-2 genital ulcer disease (GUD). Higher acyclovir pill count adherence was associated with greater reductions in plasma HIV-1 RNA and GUD, indicating pill count data is strongly correlated with biological effects of adherence. However, when calculated adherence exceeded 102 % (i.e., fewer pills returned than expected) and when pill counts were missing because bottles were not returned, plasma HIV-1 RNA and GUD effects were diminished, likely indicating periods of non-adherence.
C1 [Donnell, Deborah J.; Baeten, Jared M.; Hong, Ting; Lingappa, Jairam R.; Mujugira, Andrew; Nakku-Joloba, Edith; Celum, Connie] Univ Washington, Dept Global Hlth, Seattle, WA 98195 USA.
[Donnell, Deborah J.] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98109 USA.
[Baeten, Jared M.; Lingappa, Jairam R.; Celum, Connie] Univ Washington, Dept Med, Seattle, WA USA.
[Baeten, Jared M.; Celum, Connie] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Lingappa, Jairam R.] Univ Washington, Dept Pediat, Seattle, WA 98195 USA.
[Bangsberg, David] Harvard Univ, Sch Med, Boston, MA USA.
[Bangsberg, David] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Donnell, DJ (reprint author), Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, 1100 Fairview Ave N,M2-200, Seattle, WA 98109 USA.
EM deborah@scharp.org
OI Donnell, Deborah/0000-0002-0587-7480
FU NIMH NIH HHS [R01-MH095507, R01 MH095507]
NR 30
TC 5
Z9 5
U1 1
U2 4
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1090-7165
J9 AIDS BEHAV
JI AIDS Behav.
PD FEB
PY 2013
VL 17
IS 2
BP 632
EP 639
DI 10.1007/s10461-012-0268-0
PG 8
WC Public, Environmental & Occupational Health; Social Sciences, Biomedical
SC Public, Environmental & Occupational Health; Biomedical Social Sciences
GA 081FL
UT WOS:000314302800020
PM 22869103
ER
PT J
AU Ananthakrishnan, AN
Gainer, VS
Perez, RG
Cai, T
Cheng, SC
Savova, G
Chen, P
Szolovits, P
Xia, Z
De Jager, PL
Shaw, SY
Churchill, S
Karlson, EW
Kohane, I
Perlis, RH
Plenge, RM
Murphy, SN
Liao, KP
AF Ananthakrishnan, A. N.
Gainer, V. S.
Perez, R. G.
Cai, T.
Cheng, S-C.
Savova, G.
Chen, P.
Szolovits, P.
Xia, Z.
De Jager, P. L.
Shaw, S. Y.
Churchill, S.
Karlson, E. W.
Kohane, I.
Perlis, R. H.
Plenge, R. M.
Murphy, S. N.
Liao, K. P.
TI Psychiatric co-morbidity is associated with increased risk of surgery in
Crohn's disease
SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS
LA English
DT Article
ID INFLAMMATORY-BOWEL-DISEASE; QUALITY-OF-LIFE; FUNCTIONAL GASTROINTESTINAL
DISORDERS; OBSTRUCTIVE PULMONARY-DISEASE; IONIZING-RADIATION EXPOSURE;
POPULATION-BASED SAMPLE; ULCERATIVE-COLITIS; HEALTH-CARE; PSYCHOLOGICAL
STRESS; DEPRESSIVE SYMPTOMS
AB Background Psychiatric co-morbidity, in particular major depression and anxiety, is common in patients with Crohn's disease (CD) and ulcerative colitis (UC). Prior studies examining this may be confounded by the co-existence of functional bowel symptoms. Limited data exist examining an association between depression or anxiety and disease-specific endpoints such as bowel surgery. Aims To examine the frequency of depression and anxiety (prior to surgery or hospitalisation) in a large multi-institution electronic medical record (EMR)-based cohort of CD and UC patients; to define the independent effect of psychiatric co-morbidity on risk of subsequent surgery or hospitalisation in CD and UC, and to identify the effects of depression and anxiety on healthcare utilisation in our cohort. Methods Using a multi-institution cohort of patients with CD and UC, we identified those who also had co-existing psychiatric co-morbidity (major depressive disorder or generalised anxiety). After excluding those diagnosed with such co-morbidity for the first time following surgery, we used multivariate logistic regression to examine the independent effect of psychiatric co-morbidity on IBD-related surgery and hospitalisation. To account for confounding by disease severity, we adjusted for a propensity score estimating likelihood of psychiatric co-morbidity influenced by severity of disease in our models. Results A total of 5405 CD and 5429 UC patients were included in this study; one-fifth had either major depressive disorder or generalised anxiety. In multivariate analysis, adjusting for potential confounders and the propensity score, presence of mood or anxiety co-morbidity was associated with a 28% increase in risk of surgery in CD (OR: 1.28, 95% CI: 1.031.57), but not UC (OR: 1.01, 95% CI: 0.801.28). Psychiatric co-morbidity was associated with increased healthcare utilisation. Conclusions Depressive disorder or generalised anxiety is associated with a modestly increased risk of surgery in patients with Crohn's disease. Interventions addressing this may improve patient outcomes.
C1 [Ananthakrishnan, A. N.] Massachusetts Gen Hosp, Crohns & Colitis Ctr, Div Gastroenterol, Boston, MA 02114 USA.
[Ananthakrishnan, A. N.; Xia, Z.; De Jager, P. L.; Shaw, S. Y.; Karlson, E. W.; Kohane, I.; Perlis, R. H.; Plenge, R. M.; Murphy, S. N.; Liao, K. P.] Harvard Univ, Sch Med, Boston, MA USA.
[Gainer, V. S.; Perez, R. G.; Murphy, S. N.] Partners HealthCare, Res Comp, Charlestown, MA USA.
[Cai, T.; Cheng, S-C.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Savova, G.; Chen, P.; Kohane, I.] Childrens Hosp, Boston, MA 02115 USA.
[Szolovits, P.] MIT, Cambridge, MA 02139 USA.
[Xia, Z.; De Jager, P. L.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA.
[Shaw, S. Y.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA.
[Churchill, S.; Kohane, I.] Brigham & Womens Hosp, Natl Ctr Biomed Comp i2b2, Boston, MA 02115 USA.
[Karlson, E. W.; Plenge, R. M.; Liao, K. P.] Brigham & Womens Hosp, Div Rheumatol, Boston, MA 02115 USA.
[Perlis, R. H.] Massachusetts Gen Hosp, Psychiat Ctr Expt Drugs & Diagnost, Boston, MA 02114 USA.
[Murphy, S. N.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
RP Ananthakrishnan, AN (reprint author), Massachusetts Gen Hosp, Crohns & Colitis Ctr, Div Gastroenterol, 165 Cambridge St,9th Floor, Boston, MA 02114 USA.
EM aananthakrishnan@partners.org
OI Szolovits, Peter/0000-0001-8411-6403
FU NIH [U54-LM008748, K08 AR060257, K24 AR052403, P60 AR047782, R01
AR049880]; American Gastroenterological Association; US National
Institutes of Health [K23 DK097142]; Katherine Swan Ginsburg Fund; US
National Institutes of Health (NIH) [R01-AR056768, U01-GM092691,
R01-AR059648]; Burroughs Wellcome Fund
FX The study was supported by NIH U54-LM008748. A.N.A is supported by
funding from the American Gastroenterological Association and from the
US National Institutes of Health (K23 DK097142). K.P.L. is supported by
NIH K08 AR060257 and the Katherine Swan Ginsburg Fund. R.M.P. is
supported by grants from the US National Institutes of Health (NIH)
(R01-AR056768, U01-GM092691 and R01-AR059648) and holds a Career Award
for Medical Scientists from the Burroughs Wellcome Fund. E.W.K is
supported by grants from the NIH (K24 AR052403, P60 AR047782, R01
AR049880).
NR 50
TC 20
Z9 21
U1 1
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0269-2813
J9 ALIMENT PHARM THER
JI Aliment. Pharmacol. Ther.
PD FEB
PY 2013
VL 37
IS 4
BP 445
EP 454
DI 10.1111/apt.12195
PG 10
WC Gastroenterology & Hepatology; Pharmacology & Pharmacy
SC Gastroenterology & Hepatology; Pharmacology & Pharmacy
GA 075MW
UT WOS:000313891900009
PM 23289600
ER
PT J
AU Busarla, SVP
Sadruddin, FA
Sohani, AR
AF Busarla, Satya Vara Prasad
Sadruddin, Feroz Allibhoy
Sohani, Aliyah R.
TI Pseudo-Gaucher cells in disseminated mycobacterial infection
SO AMERICAN JOURNAL OF HEMATOLOGY
LA English
DT Editorial Material
C1 [Busarla, Satya Vara Prasad] Aga Khan Hosp, Dept Pathol, Kisumu, Kenya.
[Sadruddin, Feroz Allibhoy] Aga Khan Hosp, Dept Med, Kisumu, Kenya.
[Sohani, Aliyah R.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Sohani, Aliyah R.] Harvard Univ, Sch Med, Boston, MA USA.
RP Sohani, AR (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,WRN 219, Boston, MA 02114 USA.
EM arsohani@partners.org
NR 3
TC 3
Z9 3
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0361-8609
J9 AM J HEMATOL
JI Am. J. Hematol.
PD FEB
PY 2013
VL 88
IS 2
BP 155
EP 155
DI 10.1002/ajh.22269
PG 1
WC Hematology
SC Hematology
GA 079DF
UT WOS:000314149700014
PM 22307983
ER
PT J
AU Kring, AM
Gur, RE
Blanchard, JJ
Horan, WP
Reise, SP
AF Kring, Ann M.
Gur, Raquel E.
Blanchard, Jack J.
Horan, William P.
Reise, Steven P.
TI The Clinical Assessment Interview for Negative Symptoms (CAINS): Final
Development and Validation
SO AMERICAN JOURNAL OF PSYCHIATRY
LA English
DT Article
ID PSYCHIATRIC RATING-SCALE; RESEARCH DOMAIN CRITERIA; ITEM RESPONSE
THEORY; SCHIZOPHRENIA; ANHEDONIA; PERSPECTIVE; DEFICITS; EMOTION;
RELIABILITY; REWARD
AB Objective: A major barrier to developing treatments for negative symptoms has been measurement concerns with existing assessment tools. Fulfilling the top recommendation of the National Institute of Mental Health's Consensus Development Conference on Negative Symptoms, the Clinical Assessment Interview for Negative Symptoms (CAINS) was developed-using an iterative, empirical approach, and includes items assessing motivation, pleasure, and emotion expression. The authors employed multiple analytic techniques to develop the CAINS and here provide final development and validation results.
Method: The CAINS structure, interrater agreement, test-retest reliability, and convergent and discriminant validity were assessed in a large and diverse sample of 162 outpatients with schizophrenia or schizo-affective disorder recruited from four sites.
Results: Three items with poor psychometric properties were removed, resulting in a 13-item CAINS. The CAMS factor structure was replicated, demonstrating two modestly correlated scales: expression (four items) and motivation/pleasure (nine items). The scales demonstrated good internal consistency, test-retest stability, and interrater agreement. Strong convergent validity was demonstrated by linkages with other negative symptom measures, self-report scales of sociality, pleasure, and motivation, and coded facial expressions. Discriminant validity was shown by independence from depression, medication side effects, and cognition. Notably, the CAINS scales were related to real-world vocational, independent living, and social/familial functioning.
Conclusions: The CAINS is an empirically developed and evaluated measure of negative symptoms. Findings indicate that the CAINS is brief yet comprehensive and employable across a wide range of research and clinical contexts. (Am J Psychiatry 2013; 170:165-172)
C1 [Kring, Ann M.] Univ Calif Berkeley, Dept Psychol, Berkeley, CA 94720 USA.
Univ Penn, Perelman Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA.
Univ Maryland, Dept Psychol, College Pk, MD 20742 USA.
Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA.
RP Kring, AM (reprint author), Univ Calif Berkeley, Dept Psychol, 3210 Tolman Hall, Berkeley, CA 94720 USA.
EM akring@berkeley.edu
FU Pfizer; AstraZeneca; NIH [1R01MH082890, 1R01MH082783, 1R01MH082839,
1R01MH082782]
FX Dr. Gur has received investigator-initiated grants from Pfizer and
AstraZeneca. Dr. Blanchard has received honoraria and travel support
from Merck and Genentech for consulting. The other authors report no
competing interests.; Supported in part by NIH grant 1R01MH082890 to Dr.
Kring, grant 1R01MH082783 to Dr. Gur, grant 1R01MH082839 to Dr.
Blanchard, and grant 1R01MH082782 to Dr. Horan.
NR 44
TC 131
Z9 132
U1 4
U2 25
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 FEB
PY 2013
VL 170
IS 2
BP 165
EP 172
DI 10.1176/appi.ajp.2012.12010109
PG 8
WC Psychiatry
SC Psychiatry
GA 079VY
UT WOS:000314201500008
PM 23377637
ER
PT J
AU Fishman, JA
AF Fishman, J. A.
TI Overview: Cytomegalovirus and the Herpesviruses in Transplantation
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Article
DE Epidemiology; herpesvirus; immunosuppression; latency; opportunistic
infection; trans-plantation
ID SARCOMA-ASSOCIATED HERPESVIRUS; KAPOSIS-SARCOMA;
INFECTIOUS-MONONUCLEOSIS; HETEROLOGOUS IMMUNITY; LATENT INFECTION;
GENITAL HERPES; VIRUS; RECIPIENTS; VACCINE; MEMORY
AB Herpesviruses infect most animal species. Infections due to the eight human herpesviruses (HHV) are exacerbated by immunosuppression in organ transplantation. The special features of the herpesvirus life cycle include the ability to establish latent, nonproductive infection and the life-long capacity for reactivation to productive, lytic infection. Interactions between latent virus and the immune system determine the frequency and severity of symptomatic infections. The immunologic and cellular effects of herpesvirus infections contribute to risk for opportunistic infections and graft rejection. Among the most important advances in transplantation are laboratory assays for the diagnosis and monitoring of herpesvirus infections and antiviral agents with improved efficacy in prophylaxis and therapy. For herpes simplex virus, varicella zoster virus and cytomegalovirus, these advances have significantly reduced the morbidity of infection. The syndromes of EBV-associated posttransplant lymphoproliferative disorders (PTLD) and Kaposi's sarcoma remain important complications of immunosuppression. The epidemiology and essential biology of human herpesvirus is reviewed.
C1 [Fishman, J. A.] Massachusetts Gen Hosp, MGH Transplant Ctr, Transplant Infect Dis & Compromised Host Ctr, Boston, MA 02114 USA.
[Fishman, J. A.] Harvard Univ, Sch Med, Boston, MA USA.
[Fishman, J. A.] Massachusetts Gen Hosp, Transplant Ctr, Boston, MA 02114 USA.
RP Fishman, JA (reprint author), Massachusetts Gen Hosp, MGH Transplant Ctr, Transplant Infect Dis & Compromised Host Ctr, Boston, MA 02114 USA.
EM jfishman@partners.org
NR 34
TC 29
Z9 31
U1 0
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1600-6135
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD FEB
PY 2013
VL 13
SU 3
SI SI
BP 1
EP 8
DI 10.1111/ajt.12002
PG 8
WC Surgery; Transplantation
SC Surgery; Transplantation
GA 079DX
UT WOS:000314151600001
PM 23347210
ER
PT J
AU Kotton, CN
AF Kotton, C. N.
TI CMV: Prevention, Diagnosis and Therapy
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Article
DE Cytomegalovirus; diagnostics; infection; prevention; transplant
ID ORGAN TRANSPLANT RECIPIENTS; GANCICLOVIR-RESISTANT CYTOMEGALOVIRUS;
EXTENDED VALGANCICLOVIR PROPHYLAXIS; BRONCHIOLITIS OBLITERANS SYNDROME;
ORTHOTOPIC LIVER-TRANSPLANTATION; CELL IMMUNE RECONSTITUTION;
HEPATIC-ARTERY THROMBOSIS; PREEMPTIVE THERAPY; LUNG TRANSPLANTATION;
DRUG-RESISTANCE
AB Cytomegalovirus (CMV) is the most common infection after organ transplantation and has a major impact on morbidity, mortality and graft survival. Optimal prevention, diagnosis and treatment of active CMV infection enhance transplant outcomes, and are the focus of this section. Methods to prevent CMV include universal prophylaxis and preemptive therapy; each has its merits, and will be compared and contrasted. Diagnostics have improved substantially in recent years, both in type and quality, allowing for more accurate and savvy treatment; advances in diagnostics include the development of an international standard, which should allow comparison of results across different methodologies, and assays for cellular immune function against CMV. Therapy primarily involves ganciclovir, now rendered more versatile by data suggesting oral therapy with valganciclovir is not inferior to intravenous therapy with ganciclovir. Treatment of resistant virus remains problematic, but is enhanced by the availability of multiple novel therapeutic agents.
C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
RP Kotton, CN (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
EM ckotton@partners.org
FU Genentech
FX The author has served as a continuing medical education speaker on the
topic of CMV for Genentech and Viropharma. She led The Transplantation
Society International CMV Consensus Group with an investigator-initiated
independent grant from Roche, now Genentech. She has been a scientific
consultant for Genentech, Roche and CSL Behring.
NR 151
TC 59
Z9 61
U1 1
U2 20
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1600-6135
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD FEB
PY 2013
VL 13
SU 3
SI SI
BP 24
EP 40
DI 10.1111/ajt.12006
PG 17
WC Surgery; Transplantation
SC Surgery; Transplantation
GA 079DX
UT WOS:000314151600003
PM 23347212
ER
PT J
AU Fishman, JA
AF Fishman, J. A.
TI What's New and What's Hot? Basic Science at the American Transplant
Congress 2012
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Article
DE Costimulation; heterologous immunity; infection; immune tolerance;
microbiome; NK cells; Th17 cells
ID NK CELL TRANSCRIPTS; T-CELLS; REJECTION; BIOPSIES; INJURY
AB Application of advanced molecular techniques and novel animal models has provided new insights into basic mechanisms underlying clinical transplantation. Investigations in diverse areas, including graft rejection and tolerance, autoimmunity and infectious diseases, have revealed increasing complexity of the mechanisms controlling immune function, notably at the interface of the innate and adaptive immune systems and within secondary lymphoid organs. New roles have been identified for NK and dendritic cells, B-lymphocytes and for Th17 and regulatory T cells, notably in novel animal models of costimulatory blockade and tolerance. Confirmation of these observations will be needed in normal animals and in humans undergoing organ and cell transplantation. The impact of the microbiome, of vaccines, and of antimicrobial therapies on immune memory and reconstitution after lymphocyte depletion is beginning to be defined.
C1 [Fishman, J. A.] Massachusetts Gen Hosp, Transplant Infect Dis & Compromised Host Program, MGH Transplant Ctr, Boston, MA 02114 USA.
[Fishman, J. A.] Harvard Univ, Sch Med, Boston, MA USA.
RP Fishman, JA (reprint author), Massachusetts Gen Hosp, Transplant Infect Dis & Compromised Host Program, MGH Transplant Ctr, Boston, MA 02114 USA.
EM jfishman@partners.org
NR 34
TC 1
Z9 1
U1 0
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1600-6135
EI 1600-6143
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD FEB
PY 2013
VL 13
IS 2
BP 275
EP 280
DI 10.1111/ajt.12015
PG 6
WC Surgery; Transplantation
SC Surgery; Transplantation
GA 079LE
UT WOS:000314171100008
PM 23279436
ER
PT J
AU Bagchi, A
Eikermann, M
AF Bagchi, Aranya
Eikermann, Matthias
TI Mashed Potatoes and Maize Are the Starches Safe?
SO ANESTHESIOLOGY
LA English
DT Editorial Material
ID HYDROXYETHYL STARCH; INTENSIVE-CARE; SEVERE SEPSIS; FLUID RESUSCITATION;
RENAL-FUNCTION; SALINE
C1 [Bagchi, Aranya; Eikermann, Matthias] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesiol Crit Care & Pain Med, Boston, MA 02115 USA.
[Eikermann, Matthias] Dusiburg Essen Univ, Klin Anaesthesiol & Intens Med, Univ Klinikum Essen, Essen, Germany.
RP Bagchi, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesiol Crit Care & Pain Med, Boston, MA 02115 USA.
EM meikermann@partners.org
NR 20
TC 6
Z9 6
U1 1
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0003-3022
EI 1528-1175
J9 ANESTHESIOLOGY
JI Anesthesiology
PD FEB
PY 2013
VL 118
IS 2
BP 244
EP 247
DI 10.1097/ALN.0b013e31827e5582
PG 4
WC Anesthesiology
SC Anesthesiology
GA 076SH
UT WOS:000313977700003
PM 23340348
ER
PT J
AU Vaz-Luis, I
Winer, EP
Lin, NU
AF Vaz-Luis, I.
Winer, E. P.
Lin, N. U.
TI Human epidermal growth factor receptor-2-positive breast cancer: does
estrogen receptor status define two distinct subtypes?
SO ANNALS OF ONCOLOGY
LA English
DT Review
DE breast cancer; estrogen receptor; human epidermal growth factor
receptor-2; outcomes; subtypes
ID PATHOLOGICAL COMPLETE RESPONSE; POLYMERASE CHAIN-REACTION; PLUS ADJUVANT
CHEMOTHERAPY; STEROID-HORMONE RECEPTORS; GENE-EXPRESSION PATTERNS;
PHASE-II TRIAL; ANDROGEN RECEPTOR; GUIDELINE RECOMMENDATIONS;
NEOADJUVANT CHEMOTHERAPY; PROGESTERONE-RECEPTOR
AB Human epidermal growth factor receptor-2 (HER2) overexpression occurs in similar to 20% of breast cancers and has historically been associated with decreased survival. Despite substantial improvements in clinical outcomes, particularly with the emergence of HER2-targeted therapy, a substantial minority of patients still relapses, and progression is inevitable in metastatic disease. Accumulating data indicate that HER2-positive disease is itself a heterogeneous entity.
In this article, we qualitatively review the data supporting the classification of HER2-positive disease as at least two separate entities, distinguished by estrogen receptor (ER) status. We summarize differences in clinical outcomes, including response to neoadjuvant therapy, timing and patterns of dissemination, efficacy of therapy in the metastatic setting and survival outcomes.
The collective data are sufficiently strong at this point to propose that ER status defines two distinct subtypes within HER2-positive breast cancer, and we highlight the implications of this knowledge in future research, including understanding of the basic biology of HER2-positive breast cancer and the design of future clinical trials.
C1 [Vaz-Luis, I.; Winer, E. P.; Lin, N. U.] Dana Farber Canc Inst, Breast Oncol Ctr, Dept Med Oncol, Boston, MA 02215 USA.
[Vaz-Luis, I.] Inst Mol Med, Clin & Translat Oncol Res Unit, Lisbon, Portugal.
RP Lin, NU (reprint author), Dana Farber Canc Inst, Breast Oncol Ctr, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA.
EM nancy_lin@dfci.harvard.edu
FU Breast Cancer Research Foundation; Fundacao da Ciencia e Tecnologia
[HMSP-ICS/0004/2011]; The Harvard Clinical and Translational Science
Center [UL1 RR025758]
FX Additional support for this work has been provided by the Breast Cancer
Research Foundation (no grant number assigned). IV-L is supported by
Fundacao da Ciencia e Tecnologia (HMSP-ICS/0004/2011) and by the
Scholars in Clinical Science Program of Harvard Catalyst vertical bar
The Harvard Clinical and Translational Science Center (Award No. UL1
RR025758 and contributions from Harvard University and its affiliated
academic health-care centers). The content of this work is solely the
responsibility of the authors and does not necessarily represent the
official views of Harvard Catalyst, Harvard University and its
affiliated academic health-care centers, or the National Institutes of
Health.
NR 91
TC 17
Z9 19
U1 0
U2 10
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0923-7534
EI 1569-8041
J9 ANN ONCOL
JI Ann. Oncol.
PD FEB
PY 2013
VL 24
IS 2
BP 283
EP 291
DI 10.1093/annonc/mds286
PG 9
WC Oncology
SC Oncology
GA 077VM
UT WOS:000314057100004
PM 23022997
ER
PT J
AU Goss, PE
Ingle, JN
Martino, S
Robert, NJ
Muss, HB
Livingston, RB
Davidson, NE
Perez, EA
Chavarri-Guerra, Y
Cameron, DA
Pritchard, KI
Whelan, T
Shepherd, LE
Tu, D
AF Goss, P. E.
Ingle, J. N.
Martino, S.
Robert, N. J.
Muss, H. B.
Livingston, R. B.
Davidson, N. E.
Perez, E. A.
Chavarri-Guerra, Y.
Cameron, D. A.
Pritchard, K. I.
Whelan, T.
Shepherd, L. E.
Tu, D.
TI Impact of premenopausal status at breast cancer diagnosis in women
entered on the placebo-controlled NCIC CTG MA17 trial of extended
adjuvant letrozole
SO ANNALS OF ONCOLOGY
LA English
DT Article
DE adjuvant therapy; aromatase inhibitors; breast cancer; extended therapy;
letrozole; menopausal status
ID ENDOCRINE THERAPY; RANDOMIZED-TRIAL; POSTMENOPAUSAL WOMEN; AROMATASE
INHIBITORS; ESTROGEN-RECEPTOR; TAMOXIFEN THERAPY; UPDATED FINDINGS;
MA.17; SURVIVAL
AB MA17 showed improved outcomes in postmenopausal women given extended letrozole (LET) after completing 5 years of adjuvant tamoxifen.
Exploratory subgroup analyses of disease-free survival (DFS), distant DFS (DDFS), overall survival (OS), toxic effects and quality of life (QOL) in MA17 were performed based on menopausal status at breast cancer diagnosis.
At diagnosis, 877 women were premenopausal and 4289 were postmenopausal. Extended LET was significantly better than placebo (PLAC) in DFS for premenopausal [hazard ratio (HR) = 0.26, 95% confidence interval (CI) 0.13-0.55; P = 0.0003] and postmenopausal women (HR = 0.67; 95% CI 0.51-0.89; P = 0.006), with greater DFS benefit in those premenopausal (interaction P = 0.03). In adjusted post-unblinding analysis, those who switched from PLAC to LET improved DDFS in premenopausal (HR = 0.15; 95% CI 0.03-0.79; P = 0.02) and postmenopausal women (HR = 0.45; 95% CI 0.22-0.94; P = 0.03).
Extended LET after 5 years of tamoxifen was effective in pre- and postmenopausal women at diagnosis, and significantly better in those premenopausal. Women premenopausal at diagnosis should be considered for extended adjuvant therapy with LET if menopausal after completing tamoxifen.
C1 [Goss, P. E.; Chavarri-Guerra, Y.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
[Ingle, J. N.] Mayo Clin, Dept Oncol, Div Med Oncol, Rochester, MN USA.
[Martino, S.] Los Angeles Clin & Res Inst, Breast Canc Div, Santa Monica, CA USA.
[Robert, N. J.] Inova Fairfax Hosp, Virgina Canc Specialists, Fairfax, VA USA.
[Muss, H. B.] Univ N Carolina, Dept Med, Chapel Hill, NC USA.
[Muss, H. B.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
[Livingston, R. B.] Univ Washington, Seattle, WA 98195 USA.
[Davidson, N. E.] Univ Pittsburgh, Sch Med, Inst Canc, Pittsburgh, PA USA.
[Davidson, N. E.] Univ Pittsburgh, Sch Med, UPMC Canc Ctr, Pittsburgh, PA USA.
[Perez, E. A.] Mayo Clin, Ctr Canc, Jacksonville, FL USA.
[Cameron, D. A.] Western Gen Hosp, Edinburgh Breast Unit, Edinburgh EH4 2XU, Midlothian, Scotland.
[Cameron, D. A.] Univ Edinburgh, Edinburgh, Midlothian, Scotland.
[Pritchard, K. I.] Univ Toronto, Sunnybrook Odette Reg Canc Ctr, Toronto, ON, Canada.
[Whelan, T.] McMaster Univ, Dept Oncol, Hamilton, ON, Canada.
[Shepherd, L. E.; Tu, D.] Natl Canc Inst Canada, Clin Trials Grp, Kingston, ON, Canada.
RP Goss, PE (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,Lawrence House,LRH-302, Boston, MA 02114 USA.
EM pgoss@partners.org
RI Whelan, Timothy/D-3185-2017
FU Novartis Pharmaceuticals; Canadian Cancer Society through National
Cancer Institute of Canada [10362]; National Cancer Institute in the
United States [CA31946, CA21115, CA25224, CA38926, CA32102]; Avon
Foundation in New York; Genentech; Sanofi; Novartis; Astra-Zeneca;
Pfizer; Expert Testimony
FX The authors are very grateful to the 5187 extraordinary women who agreed
to participate in this study. The authors also acknowledge the trial
committee; the many hundreds of investigators, pharmacists, and clinical
research associates from the National Cancer Institute of Canada
Clinical Trials Group, the Southwest Oncology Group, the Eastern
Cooperative Oncology Group, the Cancer and Leukemia Group B, the North
Central Cancer Treatment Group, the European Organization for Research
and Treatment of Cancer, the International Breast Cancer Study Group,
and Centers in England, including the Royal Marsden, St. George's, and
Withington Hospitals; the members of the Data Safety Monitoring
Committee: the central office staff of the NCIC Clinical Trials Group
who contributed to the conduct of the trial; and to Novartis
Pharmaceuticals for their support and provision of LET and PLAC. The
authors thank Pedro Liedke for his review of the manuscript.; This work
was supported by the Canadian Cancer Society through National Cancer
Institute of Canada grant (10362) and grants from the National Cancer
Institute in the United States (CA31946, CA21115, CA25224, CA38926, and
CA32102). PEG and YC-G are supported by the Avon Foundation in New
York.; EAP: Research funding: Genentech and Sanofi.; DAC: Consultant or
advisory role: Novartis, Astra-Zeneca and Pfizer; Honoraria: Novartis,
Astra-Zeneca and Pfizer; Research Funding: Novartis, Astra-Zeneca and
Pfizer.; KIP: Consultant or advisory role: Novartis; Honoraria:
Novartis; Research Funding: Novartis: Expert Testimony: Novartis.
NR 20
TC 30
Z9 35
U1 0
U2 8
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0923-7534
J9 ANN ONCOL
JI Ann. Oncol.
PD FEB
PY 2013
VL 24
IS 2
BP 355
EP 361
DI 10.1093/annonc/mds330
PG 8
WC Oncology
SC Oncology
GA 077VM
UT WOS:000314057100014
PM 23028039
ER
PT J
AU Bernhard, J
Aldridge, J
Butow, PN
Zoller, P
Brown, R
Smith, A
Juraskova, I
AF Bernhard, J.
Aldridge, J.
Butow, P. N.
Zoller, P.
Brown, R.
Smith, A.
Juraskova, I.
TI Patient-doctor agreement on recall of clinical trial discussion across
cultures
SO ANNALS OF ONCOLOGY
LA English
DT Article
DE breast cancer; communication skills training; cross-cultural
differences; patient-doctor agreement; shared decision-making
ID SEEKING INFORMED-CONSENT; DECISION-MAKING; CANCER-PATIENTS;
BREAST-CANCER; COMMUNICATION; SATISFACTION; PARTICIPATION; ONCOLOGISTS;
INFORMATION; SCALE
AB The purpose was to investigate patient-doctor agreement on clinical trial discussion cross-culturally.
In the International Breast Cancer Study Group Trial 33-03 on shared decision-making for early breast cancer in Australian/New Zealand (ANZ) and Swiss/German/Austrian (SGA) centers, doctor and patient characteristics plus doctor stress and burnout were assessed. Within 2 weeks post-consultation about treatment options, the doctor and patient reported independently, whether a trial was discussed. Odds ratios of agreement for covariables were estimated by generalized estimating equations for each language cohort, with doctor as a random effect.
In ANZ, 21 doctors and 339 patients were eligible; in SGA, 41 doctors and 427 patients. In cases where the doctor indicated 'no trial discussed', 82% of both ANZ and SGA patients agreed; if the doctor indicated 'trial discussed', 50% of ANZ and 38% of SGA patients agreed, respectively. Factors associated with higher agreement were: low tumor grade and fewer patients recruited into clinical trials in SGA; public institution, patient born in ANZ (versus other), higher doctor depersonalization and personal accomplishment in ANZ.
There is discordance between oncologists and their patients regarding clinical trial discussion, particularly when the doctor indicates that a trial was discussed. Factors contributing to this agreement vary by culture.
C1 [Bernhard, J.; Zoller, P.] Int Breast Canc Study Grp Coordinating Ctr, CH-3008 Bern, Switzerland.
[Bernhard, J.] Univ Hosp Bern, Inselspital, Dept Med Oncol, CH-3010 Bern, Switzerland.
[Aldridge, J.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, IBCSG Stat Ctr, Boston, MA 02115 USA.
[Butow, P. N.; Juraskova, I.] Univ Sydney, Sch Psychol, Ctr Med Psychol & Evidence Based Decis Making CeM, Sydney, NSW 2006, Australia.
[Butow, P. N.; Smith, A.] Univ Sydney, Psychooncol Cooperat Res Grp PoCoG, Sydney, NSW 2006, Australia.
[Brown, R.] Virginia Commonwealth Univ, Sch Med, Dept Social & Behav Hlth, Richmond, VA 23284 USA.
RP Bernhard, J (reprint author), Int Breast Canc Study Grp Coordinating Ctr, Effingerstr 40, CH-3008 Bern, Switzerland.
EM juerg.bernhard@ibcsg.org
OI Smith, Allan 'Ben'/0000-0002-2496-7369
FU National Breast Cancer Foundation of Australia; Oncosuisse/Swiss Cancer
League [OCS-01165-09-2001/KLS-01648-02-2005]; Deutsche Krebshilfe
[106668]; IBCSG; US National Cancer Institute [CA-75362]
FX We thank the National Breast Cancer Foundation of Australia (no grant
number), Oncosuisse/Swiss Cancer League
(OCS-01165-09-2001/KLS-01648-02-2005), Deutsche Krebshilfe (106668), and
IBCSG for funding this trial. The IBCSG Statistical Center (JA) is
partially funded through a grant from the US National Cancer Institute
(CA-75362).
NR 29
TC 1
Z9 1
U1 4
U2 10
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0923-7534
J9 ANN ONCOL
JI Ann. Oncol.
PD FEB
PY 2013
VL 24
IS 2
BP 391
EP 397
DI 10.1093/annonc/mds288
PG 7
WC Oncology
SC Oncology
GA 077VM
UT WOS:000314057100019
PM 23019277
ER
PT J
AU Mattei, PL
Alora-Palli, MB
Kraft, S
Lawrence, DP
Flaherty, KT
Kimball, AB
AF Mattei, P. L.
Alora-Palli, M. B.
Kraft, S.
Lawrence, D. P.
Flaherty, K. T.
Kimball, A. B.
TI Cutaneous effects of BRAF inhibitor therapy: a case series
SO ANNALS OF ONCOLOGY
LA English
DT Article
DE BRAF inhibitor; cutaneous squamous cell carcinoma; MEK inhibitor;
photosensitivity; side effects
ID RENAL-TRANSPLANT RECIPIENTS; HUMAN-PAPILLOMAVIRUS TYPES; NONMELANOMA
SKIN CANCERS; SQUAMOUS-CELL CARCINOMA; IMMUNOCOMPETENT INDIVIDUALS;
SORAFENIB; MUTATIONS; MELANOMA; PATHWAY; SURAMIN
AB The cutaneous effects of rapidly accelerated fibrosarcoma kinase B (BRAF) inhibitors are not well understood. Squamous cell carcinoma (SCC), keratoacanthoma, and photosensitivity have been described in patients taking BRAF inhibitors.
To characterize the timing and frequency of skin lesions in patients receiving BRAF inhibitor therapy, we utilized a retrospective case review of 53 patients undergoing treatment with BRAF inhibitors for 4-92 weeks of therapy. Patients were evaluated at baseline, and then followed at 4- to 12-week intervals. Charts were retrospectively reviewed, and the morphology and timing of cutaneous events were recorded.
Thirty-three of the 53 charts met exclusion/inclusion criteria, 15 were treated with vemurafenib, and 18 were treated with GSK 2118436/GSK 1120212. Of 33 patients treated with BRAF inhibitor, 13 developed photosensitivity (39.4%), 10 developed actinic keratoses (30.3%), 10 developed warts (30.3%), and 6 developed SCC (18.2%).
Multiple cutaneous findings were observed in the 33 patients taking BRAF inhibitors. The previously described association with SCC and photosensitivity was observed in these patients as well. Over half of the observed SCCs were invasive in nature. Photosensitivity continues to be frequent with BRAF inhibitors. Patients taking BRAF inhibitors should have regular full body skin exams. Further studies are necessary to better elucidate the rates of these adverse cutaneous effects.
C1 [Mattei, P. L.; Alora-Palli, M. B.; Kimball, A. B.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA.
[Kraft, S.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Lawrence, D. P.; Flaherty, K. T.] Massachusetts Gen Hosp, Dept Oncol, Boston, MA 02114 USA.
RP Kimball, AB (reprint author), Harvard Univ, Sch Med, Clin Unit Res Trials & Outcomes Skin CURTIS, 50 Staniford St,Suite 240, Boston, MA 02114 USA.
EM harvardskinstudies@partners.org
FU Roche; GlaxoSmithKline; Genentech
FX Roche, GlaxoSmithKline, and Genentech funded the underlying clinical
trials from which these data were derived. Our analysis was unfunded.
NR 46
TC 45
Z9 45
U1 0
U2 6
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0923-7534
EI 1569-8041
J9 ANN ONCOL
JI Ann. Oncol.
PD FEB
PY 2013
VL 24
IS 2
BP 530
EP 537
DI 10.1093/annonc/mds292
PG 8
WC Oncology
SC Oncology
GA 077VM
UT WOS:000314057100038
PM 23035153
ER
PT J
AU Penel, N
Demetri, GD
Blay, JY
Cousin, S
Maki, RG
Chawla, SP
Judson, I
von Mehren, M
Schoffski, P
Verweij, J
Casali, P
Rodenhuis, S
Schutte, HJ
Cassar, A
Gomez, J
Nieto, A
Zintl, P
Pontes, MJ
Le Cesne, A
AF Penel, N.
Demetri, G. D.
Blay, J. Y.
Cousin, S.
Maki, R. G.
Chawla, S. P.
Judson, I.
von Mehren, M.
Schoffski, P.
Verweij, J.
Casali, P.
Rodenhuis, S.
Schuette, H. J.
Cassar, A.
Gomez, J.
Nieto, A.
Zintl, P.
Pontes, M. J.
Le Cesne, A.
TI Growth modulation index as metric of clinical benefit assessment among
advanced soft tissue sarcoma patients receiving trabectedin as a salvage
therapy
SO ANNALS OF ONCOLOGY
LA English
DT Article
DE growth modulation index; sarcoma; time-to-progression ratio; trabectedin
ID GASTROINTESTINAL STROMAL TUMORS; PHASE-II; EUROPEAN ORGANIZATION;
END-POINT; ANTICANCER AGENTS; OVARIAN-CANCER; TRIAL; PROGRESSION;
ECTEINASCIDIN-743; 5-FLUOROURACIL
AB The growth modulation index (GMI) is the ratio of time to progression with the nth line (TTPn) of therapy to the TTPn-1 with the n-1th line. GMI > 1.33 is considered as a sign of activity in phase II trials.
This retrospective analysis evaluated the concordance between the GMI and the efficacy outcomes in 279 patients with advanced soft tissue sarcoma (ASTS) treated with trabectedin 1.5 mg/m superset of (24-h infusion every 3 weeks) in four phase II trials.
One hundred and forty-two (51%) patients received one prior line and 137 >= 2 lines. The median TTPn was 2.8 months (range 0.2-26.8), whereas the median TTPn-1 was 4.0 months (0.3-79.5). The median GMI was 0.6 (0.0-14.4). Overall, 177 patients (63%) had a GMI < 1; 21 (8%) a GMI equal to 1-1.33 and 81 (29%) a GMI > 1.33, which correlated with the median overall survival in those patients (9.1, 13.9 and 23.8 months, respectively, P = 0.0005). A high concordance rate between the GMI and response rate (P < 0.0001) and progression-free survival (PFS, P < 0.0001) was observed. Good performance status (PS) was the only factor associated with GMI > 1.33 (PS = 0; P < 0.04).
A high GMI was associated with favorable efficacy outcomes in patients treated with trabectedin. Further research is needed to assess GMI as an indicator in this setting.
C1 [Penel, N.; Cousin, S.] Ctr Oscar Lambret, Dept Med Oncol, F-59020 Lille, France.
[Demetri, G. D.] Dana Farber Canc Inst, Ludwig Ctr, Dept Med Oncol, Boston, MA 02115 USA.
[Blay, J. Y.] Ctr Leon Berard, Dept Med Oncol, F-69373 Lyon, France.
[Maki, R. G.] Mt Sinai Sch Med, Dept Med Oncol, New York, NY USA.
[Chawla, S. P.] Santa Monica Oncol Ctr Santa Monica, Dept Med Oncol, Santa Monica, CA USA.
[Judson, I.] Royal Marsden Hosp, Dept Med Oncol, London SW3 6JJ, England.
[von Mehren, M.] Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19111 USA.
[Schoffski, P.] Univ Hosp Gasthuisberg, Dept Med Oncol, B-3000 Louvain, Belgium.
[Verweij, J.] Erasmus Univ, Dept Med Oncol, Med Ctr, Rotterdam, Netherlands.
[Casali, P.] Ist Nazl Tumori, Dept Med Oncol, I-20133 Milan, Italy.
[Rodenhuis, S.] Netherlands Canc Inst, Dept Med Oncol, Amsterdam, Netherlands.
[Schuette, H. J.] Marien Hosp, Dept Med Oncol, Dusseldorf, Germany.
[Cassar, A.] Novex Pharma, Sci Liaison Off, Levallois Perret, France.
[Gomez, J.; Nieto, A.; Zintl, P.; Pontes, M. J.] Pharmamar, Dept Stat, Madrid, Spain.
[Gomez, J.; Nieto, A.; Zintl, P.; Pontes, M. J.] Pharmamar, Med Affairs, Madrid, Spain.
[Le Cesne, A.] Inst Gustave Roussy, Dept Med Oncol, Villejuif, France.
RP Penel, N (reprint author), Ctr Oscar Lambret, Dept Gen Oncol, 3 Rue F Combemale, F-59020 Lille, France.
EM n-penel@o-lambret.fr
RI casali, Paolo Giovanni/D-1524-2017; Blay, Jean-Yves/N-3966-2016
OI casali, Paolo Giovanni/0000-0003-4056-8023; Blay,
Jean-Yves/0000-0001-7190-120X
FU PharmaMar SA
FX AC, JG, AN, PZ and MJP are employed by PharmaMar SA. NP, GDD, JYB, RGM,
SPC, IJ, MVM, PS, JV, PC, SR, HJS and ALC are investigators in the
clinical trials funded by PharmaMar SA and have received research grant
from PharmaMar SA.
NR 29
TC 10
Z9 10
U1 0
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0923-7534
J9 ANN ONCOL
JI Ann. Oncol.
PD FEB
PY 2013
VL 24
IS 2
BP 537
EP 542
DI 10.1093/annonc/mds470
PG 6
WC Oncology
SC Oncology
GA 077VM
UT WOS:000314057100039
PM 23117071
ER
PT J
AU Cattaneo, Z
Vecchi, T
Fantino, M
Herbert, AM
Merabet, LB
AF Cattaneo, Zaira
Vecchi, Tomaso
Fantino, Micaela
Herbert, Andrew M.
Merabet, Lotfi B.
TI The effect of vertical and horizontal symmetry on memory for tactile
patterns in late blind individuals
SO ATTENTION PERCEPTION & PSYCHOPHYSICS
LA English
DT Article
DE Symmetry; Tactile; Haptic; Late blind; Spatial memory; Reference frame
ID BILATERAL SYMMETRY; HAPTIC DISCRIMINATION; UNFAMILIAR DISPLAYS; SPATIAL
PROCESSES; PERCEPTION; ORIENTATION; STRATEGIES; IMAGERY; PICTURE; PEOPLE
AB Visual stimuli that exhibit vertical symmetry are easier to remember than stimuli symmetric along other axes, an advantage that extends to the haptic modality as well. Critically, the vertical symmetry memory advantage has not been found in early blind individuals, despite their overall superior memory, as compared with sighted individuals, and the presence of an overall advantage for identifying symmetric over asymmetric patterns. The absence of the vertical axis memory advantage in the early blind may depend on their total lack of visual experience or on the effect of prolonged visual deprivation. To disentangle this issue, in this study, we measured the ability of late blind individuals to remember tactile spatial patterns that were either vertically or horizontally symmetric or asymmetric. Late blind participants showed better memory performance for symmetric patterns. An additional advantage for the vertical axis of symmetry over the horizontal one was reported, but only for patterns presented in the frontal plane. In the horizontal plane, no difference was observed between vertical and horizontal symmetric patterns, due to the latter being recalled particularly well. These results are discussed in terms of the influence of the spatial reference frame adopted during exploration. Overall, our data suggest that prior visual experience is sufficient to drive the vertical symmetry memory advantage, at least when an external reference frame based on geocentric cues (i.e., gravity) is adopted.
C1 [Cattaneo, Zaira] Univ Milano Bicocca, Dept Psychol, Milan, Italy.
[Cattaneo, Zaira; Vecchi, Tomaso] IRCCS Mondino, Brain Connect Ctr, Pavia, Italy.
[Vecchi, Tomaso; Fantino, Micaela] Univ Pavia, Dept Psychol, I-27100 Pavia, Italy.
[Herbert, Andrew M.] Rochester Inst Technol, Dept Psychol, Rochester, NY 14623 USA.
[Merabet, Lotfi B.] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA USA.
RP Cattaneo, Z (reprint author), Univ Milano Bicocca, Dept Psychol, Milan, Italy.
EM zaira.cattaneo@unimib.it
NR 37
TC 5
Z9 5
U1 1
U2 12
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1943-3921
J9 ATTEN PERCEPT PSYCHO
JI Atten. Percept. Psychophys.
PD FEB
PY 2013
VL 75
IS 2
BP 375
EP 382
DI 10.3758/s13414-012-0393-x
PG 8
WC Psychology; Psychology, Experimental
SC Psychology
GA 081BX
UT WOS:000314291700014
PM 23150215
ER
PT J
AU Maramattom, LV
Hari, PN
Burns, LJ
Carreras, J
Arcese, W
Cairo, MS
Costa, LJ
Fenske, TS
Lill, M
Freytes, CO
Gale, RP
Gross, TG
Hale, GA
Hamadani, M
Holmberg, LA
Hsu, JW
Inwards, DJ
Lazarus, HM
Marks, DI
Maloney, DG
Maziarz, RT
Montoto, S
Rizzieri, DA
Wirk, B
Gajewski, JL
AF Maramattom, Leena V.
Hari, Parameswaran N.
Burns, Linda J.
Carreras, Jeanette
Arcese, William
Cairo, Mitchell S.
Costa, Luciano J.
Fenske, Timothy S.
Lill, Michael
Freytes, Cesar O.
Gale, Robert Peter
Gross, Thomas G.
Hale, Gregory A.
Hamadani, Mehdi
Holmberg, Leona A.
Hsu, Jack W.
Inwards, David J.
Lazarus, Hillard M.
Marks, David I.
Maloney, David G.
Maziarz, Richard T.
Montoto, Silvia
Rizzieri, David A.
Wirk, Baldeep
Gajewski, James L.
TI Autologous and Allogeneic Transplantation for Burkitt Lymphoma Outcomes
and Changes in Utilization: A Report from the Center for International
Blood and Marrow Transplant Research
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Article
DE AlloHCT; AutoHCT; Burkitt lymphoma
ID ADULT BURKITT; LEUKEMIA; CHEMOTHERAPY; RADIATION; THERAPY
AB Trends in utilization and outcomes after autologous or allogeneic hematopoietic cell transplantation (HCT) for Burkitt lymphoma were analyzed in 241 recipients reported to the Center for International Blood and Marrow Transplant Research between 1985 and 2007. The autologous HCT cohort had a higher proportion of chemotherapy-sensitive disease, peripheral blood grafts, and HCT in first complete remission (CR1). The use of autologous HCT has declined over time, with only 19% done after 2001. Overall survival at 5 years for the autologous cohort was 83% for those in CR1 and 31% for those not in CR1. Corresponding progression-free survival (PFS) was 78% and 27%, respectively. After allogeneic HCT, overall survival at 5 years was 53% and 20% for the CR1 and non-CR1 cohorts, whereas PFS was 50% and 19%, respectively. The most common cause of death was progressive lymphoma. Allogeneic HCT performed in a higher-risk subset (per National Comprehensive Cancer Network guidelines) resulted in a 5-year PFS of 27%. Autologous HCT resulted in a 5-year PFS of 44% in those undergoing transplantation in the second CR. (C) 2013 American Society for Blood and Marrow Transplantation.
C1 [Maramattom, Leena V.; Hari, Parameswaran N.; Fenske, Timothy S.] Med Coll Wisconsin, Milwaukee, WI 53226 USA.
[Hari, Parameswaran N.; Fenske, Timothy S.] Med Coll Wisconsin, Dept Med, Div Hematol Oncol, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA.
[Burns, Linda J.] Univ Minnesota, Med Ctr, Minneapolis, MN 55455 USA.
[Carreras, Jeanette] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA.
[Arcese, William] Univ Roma Tor Vergata, Rome Transplant Network, Rome, Italy.
[Cairo, Mitchell S.] New York Med Coll, Valhalla, NY 10595 USA.
[Costa, Luciano J.] Med Univ S Carolina, Charleston, SC 29425 USA.
[Lill, Michael] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA.
[Freytes, Cesar O.] S Vet Hlth Care Syst, San Antonio, TX USA.
[Freytes, Cesar O.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Gale, Robert Peter] Celgene Cord Blood Bank, Cedar Knolls, NJ USA.
[Gross, Thomas G.] Nationwide Childrens Hosp, Columbus, OH USA.
[Hale, Gregory A.] Univ S Florida, All Childrens Hosp, St Petersburg, FL 33701 USA.
[Hamadani, Mehdi] W Virginia Univ Hosp Inc, Morgantown, WV USA.
[Holmberg, Leona A.; Maloney, David G.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Hsu, Jack W.; Wirk, Baldeep] Shands HealthCare, Gainesville, FL USA.
[Hsu, Jack W.] Univ Florida, Gainesville, FL USA.
[Inwards, David J.] Mayo Clin Rochester, Rochester, MN USA.
[Lazarus, Hillard M.] Univ Hosp Case Med Ctr, Cleveland, OH USA.
[Marks, David I.] Bristol Childrens Hosp, Bristol, Avon, England.
[Maziarz, Richard T.; Gajewski, James L.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Montoto, Silvia] Queen Mary Univ London, Barts Canc Inst, London, England.
[Rizzieri, David A.] Duke Univ, Med Ctr, Durham, NC USA.
RP Hari, PN (reprint author), Med Coll Wisconsin, POB 26509, Milwaukee, WI 53226 USA.
EM phari@mcw.edu
OI Hamadani, Mehdi/0000-0001-5372-510X; Hari,
Parameswaran/0000-0002-8800-297X
FU Public Health Service from the National Cancer Institute (NCI)
[U24-CA76518]; National Heart, Lung and Blood Institute (NHLBI)
[5U01HL069294]; National Institute of Allergy and Infectious Diseases
(NIAID); NCI; Resources and Services Administration (HRSA/DHHS)
[HHSH234200637015C]; Office of Naval Research [N00014-06-1-0704,
N00014-08-1-0058]; Allos, Inc.; Amgen, Inc.; Angioblast; Anonymous
donation to the Medical College of Wisconsin; Ariad; Be the Match
Foundation; Blue Cross and Blue Shield Association; Buchanan Family
Foundation; CaridianBCT; Celgene Corporation; CellGenix, GmbH;
Children's Leukemia Research Association; Fresenius-Biotech North
America, Inc.; Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.;
Genzyme Corporation; GlaxoSmithKline; HistoGenetics, Inc.; Kiadis
Pharma; Leukemia & Lymphoma Society; Medical College of Wisconsin; Merck
Co, Inc.; Millennium: The Takeda Oncology Co.; Milliman USA, Inc.;
Miltenyi Biotec, Inc.; National Marrow Donor Program; Optum Healthcare
Solutions, Inc.; Osiris Therapeutics, Inc.; Otsuka America
Pharmaceutical, Inc.; RemedyMD; Sanofi; Seattle Genetics; Sigma-Tau
Pharmaceuticals; Soligenix, Inc.; StemCyte, A Global Cord Blood
Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan Biovitrum;
Tarix Pharmaceuticals; Teva Neuroscience, Inc.; THERAKOS, Inc.;
Wellpoint, Inc.
FX The CIBMTR is supported by Public Health Service Grant/Cooperative
Agreement U24-CA76518 from the National Cancer Institute (NCI), the
National Heart, Lung and Blood Institute (NHLBI), and the National
Institute of Allergy and Infectious Diseases (NIAID); a
Grant/Cooperative Agreement 5U01HL069294 from NHLBI and NCI; a contract
HHSH234200637015C with Health Resources and Services Administration
(HRSA/DHHS); two grants N00014-06-1-0704 and. N00014-08-1-0058 from the
Office of Naval Research; and grants from Allos, Inc.; Amgen, Inc.;
Angioblast; Anonymous donation to the Medical College of Wisconsin;
Ariad; Be the Match Foundation; Blue Cross and Blue Shield Association;
Buchanan Family Foundation; CaridianBCT; Celgene Corporation; CellGenix,
GmbH; Children's Leukemia Research Association; Fresenius-Biotech North
America, Inc.; Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.;
Genzyme Corporation; GlaxoSmithKline; HistoGenetics, Inc.; Kiadis
Pharma; The Leukemia & Lymphoma Society; The Medical College of
Wisconsin; Merck & Co, Inc.; Millennium: The Takeda Oncology Co.;
Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor
Program; Optum Healthcare Solutions, Inc.; Osiris Therapeutics, Inc.;
Otsuka America Pharmaceutical, Inc.; RemedyMD; Sanofi; Seattle Genetics;
Sigma-Tau Pharmaceuticals; Soligenix, Inc.; StemCyte, A Global Cord
Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan
Biovitrum; Tarix Pharmaceuticals; Teva Neuroscience, Inc.; THERAKOS,
Inc.; and Wellpoint, Inc. The views expressed in this article do not
reflect the official policy or position of the National Institutes of
Health, the Department of the Navy, the Department of Defense, or any
other agency of the US Government.
NR 14
TC 2
Z9 2
U1 1
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD FEB
PY 2013
VL 19
IS 2
BP 173
EP 179
DI 10.1016/j.bbmt.2012.11.016
PG 7
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA 083DA
UT WOS:000314441700004
PM 23200705
ER
PT J
AU Linsky, A
Simon, SR
AF Linsky, Amy
Simon, Steven R.
TI Medication discrepancies in integrated electronic health records
SO BMJ QUALITY & SAFETY
LA English
DT Article
ID ADVERSE DRUG EVENTS; PATIENT TRANSFER; CARE; SAFETY
AB Introduction Medication discrepancies are associated with adverse drug events. Electronic health records (EHRs) may reduce discrepancies, especially if integrated with pharmacy dispensing. We determined the prevalence of discrepancies within a national healthcare system with EHR-pharmacy linkage to characterise the medications involved and to identify factors associated with discrepancies.
Methods We conducted a retrospective cohort study of ambulatory care patients at Veterans Affairs Boston Healthcare System, April 2010-July 2011. The primary outcome was the presence of any medication discrepancy or specific types of discrepancies: commission-present in the record but not taken by patient; omission-not present in the record; duplication-present more than once; or alteration in dose or frequency-present but taken differently than documented.
Results Sixty-two patients (60%) had at least one medication discrepancy. Prevalence of commissions, omissions, duplications and alterations were 36%, 27%, 11% and 19%, respectively. The involved medications differed by type of discrepancy, but non-opioid analgesics and herbal therapies were common among commissions and omissions. In adjusted analyses, an increasing number of medications was associated with more commissions (OR 1.2; 95% CI 1.1 to 1.3) and duplications (OR 1.2; 95% CI 1.1 to 1.4) and fewer omissions (OR 0.9; 95% CI 0.8 to 1.0).
Discussion In a system with a well established EHR linked to pharmacy dispensing, medication discrepancies occurred in 60% of ambulatory clinic patients. Patients with a greater number of medications were more likely to have errors of commission and duplication, but less likely to have errors of omission. Our findings highlight that relying on EHRs alone will not ensure an accurate medication list and stress the need to review medication taking thoroughly with patients to capitalise on the full potential of EHRs.
C1 [Linsky, Amy; Simon, Steven R.] VA Boston Healthcare Syst, Gen Internal Med Sect, Boston, MA 02130 USA.
[Linsky, Amy; Simon, Steven R.] Boston Med Ctr, Gen Internal Med Sect, Boston, MA USA.
[Linsky, Amy; Simon, Steven R.] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Linsky, Amy; Simon, Steven R.] Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA.
[Linsky, Amy; Simon, Steven R.] Harvard Univ, Sch Med, Boston, MA USA.
RP Linsky, A (reprint author), VA Boston Healthcare Syst, Gen Internal Med Sect, 150 S Huntington Ave,Bldg 9,Room 425 152G, Boston, MA 02130 USA.
EM amy.linsky@va.gov
OI Linsky, Amy/0000-0002-8090-3431
FU Boston Medical Center; Center for Organisation, Leadership, and
Management Research at VA Boston Healthcare System
FX The study was conducted using resources of the VA Boston Healthcare
System. The work was initiated while Dr Linsky was a fellow supported by
Boston Medical Center and the Center for Organisation, Leadership, and
Management Research at VA Boston Healthcare System.
NR 22
TC 9
Z9 9
U1 0
U2 11
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 2044-5415
J9 BMJ QUAL SAF
JI BMJ Qual. Saf.
PD FEB
PY 2013
VL 22
IS 2
BP 103
EP 109
DI 10.1136/bmjqs-2012-001301
PG 7
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA 079ZV
UT WOS:000314211900003
PM 23100547
ER
PT J
AU Moustafa, AA
Gilbertson, MW
Orr, SP
Herzallah, MM
Servatius, RJ
Myers, CE
AF Moustafa, Ahmed A.
Gilbertson, Mark W.
Orr, Scott P.
Herzallah, Mohammad M.
Servatius, Richard J.
Myers, Catherine E.
TI A model of amygdala-hippocampal-prefrontal interaction in fear
conditioning and extinction in animals
SO BRAIN AND COGNITION
LA English
DT Article
DE Fear conditioning; Computational model; Hippocampus; Amygdala;
Ventromedial prefrontal cortex; Extinction
ID IBOTENIC ACID LESIONS; NEURAL-NETWORK MODEL; CONTEXTUAL FEAR; CENTRAL
NUCLEUS; HEART-RATE; BASOLATERAL AMYGDALA; DORSAL HIPPOCAMPUS;
NEUROCOMPUTATIONAL MODEL; BEHAVIORAL EXTINCTION; INTERCALATED NEURONS
AB Empirical research has shown that the amygdala, hippocampus, and ventromedial prefrontal cortex (vmPFC) are involved in fear conditioning. However, the functional contribution of each brain area and the nature of their interactions are not clearly understood. Here, we extend existing neural network models of the functional roles of the hippocampus in classical conditioning to include interactions with the amygdala and prefrontal cortex. We apply the model to fear conditioning, in which animals learn physiological (e.g. heart rate) and behavioral (e.g. freezing) responses to stimuli that have been paired with a highly aversive event (e.g. electrical shock). The key feature of our model is that learning of these conditioned responses in the central nucleus of the amygdala is modulated by two separate processes, one from basolateral amygdala and signaling a positive prediction error, and one from the vmPFC, via the intercalated cells of the amygdala, and signaling a negative prediction error. In addition, we propose that hippocampal input to both vmPFC and basolateral amygdala is essential for contextual modulation of fear acquisition and extinction. The model is sufficient to account for a body of data from various animal fear conditioning paradigms, including acquisition, extinction, reacquisition, and context specificity effects. Consistent with studies on lesioned animals, our model shows that damage to the vmPFC impairs extinction, while damage to the hippocampus impairs extinction in a different context (e.g., a different conditioning chamber from that used in initial training in animal experiments). We also discuss model limitations and predictions, including the effects of number of training trials on fear conditioning. Published by Elsevier Inc.
C1 [Moustafa, Ahmed A.] Univ Western Sydney, Marcs Inst Brain & Behav, Sch Social Sci & Psychol, Sydney, NSW, Australia.
[Moustafa, Ahmed A.; Herzallah, Mohammad M.] Rutgers State Univ, Ctr Mol & Behav Neurosci, Newark, NJ 07102 USA.
[Moustafa, Ahmed A.; Servatius, Richard J.; Myers, Catherine E.] New Jersey Hlth Care Syst, Dept Vet Affairs, E Orange, NJ USA.
[Gilbertson, Mark W.] Manchester VA Med Ctr, Manchester, NH USA.
[Gilbertson, Mark W.; Orr, Scott P.] Harvard Univ, Sch Med, Boston, MA USA.
[Orr, Scott P.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Herzallah, Mohammad M.] Al Quds Univ Abu Dis, Cognit Neurosci Lab, Beit Hanina, Israel.
[Servatius, Richard J.; Myers, Catherine E.] Univ Med & Dent New Jersey, New Jersey Med Sch, Stress & Motivated Behav Inst, Newark, NJ 07103 USA.
[Myers, Catherine E.] Rutgers State Univ, Dept Psychol, Newark, NJ 07102 USA.
RP Moustafa, AA (reprint author), Univ Western Sydney, Sch Psychol, Sydney, NSW, Australia.
EM a.moustafa@uws.edu.au
OI Myers, Catherine/0000-0002-2776-4823
FU NSF/NIH Collaborative Research in Computational Neuroscience (CRCNS)
Program; NIAAA [RO1 AA018737-01]
FX This work was partially supported by the NSF/NIH Collaborative Research
in Computational Neuroscience (CRCNS) Program and by NIAAA (RO1
AA018737-01).
NR 168
TC 21
Z9 21
U1 1
U2 21
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0278-2626
EI 1090-2147
J9 BRAIN COGNITION
JI Brain Cogn.
PD FEB
PY 2013
VL 81
IS 1
BP 29
EP 43
DI 10.1016/j.bandc.2012.10.005
PG 15
WC Neurosciences; Psychology, Experimental
SC Neurosciences & Neurology; Psychology
GA 079BP
UT WOS:000314145500005
PM 23164732
ER
PT J
AU Liu, YH
Malin, JL
Diamant, AL
Thind, A
Maly, RC
AF Liu, Yihang
Malin, Jennifer L.
Diamant, Allison L.
Thind, Amardeep
Maly, Rose C.
TI Adherence to adjuvant hormone therapy in low-income women with breast
cancer: the role of provider-patient communication
SO BREAST CANCER RESEARCH AND TREATMENT
LA English
DT Article
DE Breast cancer; Hormone therapy adherence; Low-income women
ID MEDICALLY UNDERSERVED WOMEN; POSTMENOPAUSAL WOMEN; PHYSICIAN
COMMUNICATION; MEDICATION NONADHERENCE; RACIAL DISPARITIES; TAMOXIFEN
THERAPY; ENDOCRINE THERAPY; OLDER PATIENTS; CARE; DISCONTINUATION
AB To assess the impact of patient-provider communication on adherence to tamoxifen (TAM) and aromatase inhibitors (AIs) 36 months after breast cancer (BC) diagnosis in a low-income population of women. California statewide surveys were conducted among 921 low-income women with BC at 6, 18, and 36 months after BC diagnosis. A subset of 303 women with stage I-III BC who initiated hormone treatment after diagnosis was identified. Bivariate and multivariate logistic regression analyses were performed, and adjusted adherence rates were calculated. The main outcome measure was self-reported hormone use at 36 months after BC diagnosis and the chief independent variables were patient-centered communication after diagnosis by patient report as measured by the Consumer Assessment of Healthcare Providers and Systems (CAHPS) and patients' self-efficacy in patient-physician interactions (PEPPI). Overall adherence to TAM/AI was relatively high (88 %). Adjusted rates of adherence were 59 and 94 % for patients with the lowest versus highest scores on the CAHPS communication scale (AOR = 1.22, P = 0.006) and 72 versus 91 % for patients with the lowest and highest rating of PEPPI (AOR = 1.04, P = 0.04). Having at least one comorbid condition also increased the odds of adherence to hormonal therapy (AOR = 3.14, P = 0.03). Having no health insurance and experiencing side-effects from hormone treatment were barriers for adherence (AOR = 0.12, P = 0.001; AOR = 0.26, P = 0.003, respectively). Patient-centered communication and perceived self-efficacy in patient-physician interaction were significantly associated with patient adherence to ongoing TAM/AI therapy among low-income women with BC. Interventions on patient-provider communication may provide opportunities to improve patient outcomes in this vulnerable population.
C1 [Liu, Yihang; Maly, Rose C.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Family Med, Los Angeles, CA 90024 USA.
[Malin, Jennifer L.] VA Greater Los Angeles Healthcare Syst, Div Hematol Oncol, Los Angeles, CA USA.
[Diamant, Allison L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90024 USA.
[Thind, Amardeep] Univ Western Ontario, Dept Family Med & Epidemiol & Biostat, London, ON, Canada.
RP Maly, RC (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Family Med, 10880 Wilshire Blvd Ste 1800, Los Angeles, CA 90024 USA.
EM rmaly@mednet.ucla.edu
FU American Cancer Society [TURSG-02-081]; California Breast Cancer
Research Program [7PB-0070]; National Cancer Institute
[R01CA119197-01A1, R01CA140481-01A1]
FX This study was funded by the American Cancer Society (# TURSG-02-081),
the California Breast Cancer Research Program (# 7PB-0070), and the
National Cancer Institute (#R01CA119197-01A1). Dr. Maly was additionally
supported by the National Cancer Institute (#R01CA140481-01A1).
NR 58
TC 32
Z9 32
U1 3
U2 21
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-6806
J9 BREAST CANCER RES TR
JI Breast Cancer Res. Treat.
PD FEB
PY 2013
VL 137
IS 3
BP 829
EP 836
DI 10.1007/s10549-012-2387-8
PG 8
WC Oncology
SC Oncology
GA 076GN
UT WOS:000313944600017
PM 23263740
ER
PT J
AU Rosovsky, R
Hong, FX
Tocco, D
Connell, B
Mitsiades, C
Schlossman, R
Ghobrial, I
Lockridge, L
Warren, D
Bradwin, G
Doyle, M
Munshi, N
Soiffer, RJ
Anderson, KC
Weller, E
Richardson, P
AF Rosovsky, Rachel
Hong, Fangxin
Tocco, Deanna
Connell, Brendan
Mitsiades, Constantine
Schlossman, Robert
Ghobrial, Irene
Lockridge, Leslie
Warren, Diane
Bradwin, Gary
Doyle, Mary
Munshi, Nikhil
Soiffer, Robert J.
Anderson, Kenneth C.
Weller, Edie
Richardson, Paul
TI Endothelial stress products and coagulation markers in patients with
multiple myeloma treated with lenalidomide plus dexamethasone: an
observational study
SO BRITISH JOURNAL OF HAEMATOLOGY
LA English
DT Article
DE multiple myeloma; venous thromboembolism; dexamethasone; lenalidomide;
endothelial markers
ID VENOUS THROMBOSIS; COMBINATION THERAPY; THALIDOMIDE; IMMUNOMODULATION;
DEFIBROTIDE; CC-4047; TRIAL
AB In this prospective study of patients with relapsed or relapsed and refractory multiple myeloma (MM) treated with lenalidomide and dexamethasone, relationships between markers of endothelial stress and drug administration and incidence of venous thromboembolism (VTE) were assessed. Of 33 enrolled patients, laboratory and treatment data were available for 32 patients. Of these, 23 received pulsed dexamethasone (40 mg/day on days 1-4, 9-12 and 17-21 of each 28-day cycle) and 9 received weekly dexamethasone (40 mg/day on days 1, 8, 15 and 21 of each cycle). The overall incidence of VTE was 9%. A decreasing trend in markers values was observed with intercellular adhesion molecule (P = 0.05), fibrinogen (P = 0.008), plasminogen activator inhibitor-1 (P < 0.001), homocysteine (P = 0.002) and Pselectin (P < 0.001) during therapy. Compared with weekly dexamethasone, pulsed dexamethasone was associated with significantly greater variation in mean adjusted relative values of fibrinogen, P-selectin and vascular endothelial growth factor (P < 0.001 for all comparisons), although there was no apparent association with VTE incidence. Lenalidomide plus dexamethasone affects endothelial stress marker levels in patients with advanced MM. The higher variation seen with pulsed dexamethasone suggests greater endothelial stress with this approach.
C1 [Rosovsky, Rachel] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Rosovsky, Rachel; Hong, Fangxin; Mitsiades, Constantine; Schlossman, Robert; Ghobrial, Irene; Lockridge, Leslie; Bradwin, Gary; Munshi, Nikhil; Soiffer, Robert J.; Anderson, Kenneth C.; Weller, Edie; Richardson, Paul] Harvard Univ, Sch Med, Boston, MA USA.
[Tocco, Deanna; Connell, Brendan; Mitsiades, Constantine; Schlossman, Robert; Ghobrial, Irene; Lockridge, Leslie; Warren, Diane; Munshi, Nikhil; Soiffer, Robert J.; Anderson, Kenneth C.; Weller, Edie; Richardson, Paul] Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Div Hematol Malignancy, Boston, MA 02115 USA.
[Bradwin, Gary] Childrens Hosp, Boston, MA 02115 USA.
[Doyle, Mary] Instrumentat Lab, Lexington, MA USA.
RP Rosovsky, R (reprint author), Massachusetts Gen Hosp, POB 246,55 Fruit St, Boston, MA 02114 USA.
EM rprosovsky@partners.org
FU Celgene; Rick Corman Multiple Myeloma Research Foundation; Celgene
Corporation
FX Celgene (Advisory Board, Research Support): I. Ghobrial, N. Munshi, K.
C. Anderson and P. Richardson.; Support for this project was provided by
the Rick Corman Multiple Myeloma Research Foundation and Celgene
Corporation. The authors gratefully acknowledge Michelle Maglio for her
extensive administrative support; Jacob Laubach MD for his review of the
manuscript and contributions to the discussions; and the assistance of
the Medical Arts Core, DFCI, Boston, MA, USA.
NR 26
TC 5
Z9 6
U1 0
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0007-1048
J9 BRIT J HAEMATOL
JI Br. J. Haematol.
PD FEB
PY 2013
VL 160
IS 3
BP 351
EP 358
DI 10.1111/bjh.12152
PG 8
WC Hematology
SC Hematology
GA 073MH
UT WOS:000313746600009
PM 23240658
ER
PT J
AU Zwicker, JI
Liebman, HA
Bauer, KA
Caughey, T
Campigotto, F
Rosovsky, R
Mantha, S
Kessler, CM
Eneman, J
Raghavan, V
Lenz, HJ
Bullock, A
Buchbinder, E
Neuberg, D
Furie, B
AF Zwicker, Jeffrey I.
Liebman, Howard A.
Bauer, Kenneth A.
Caughey, Thomas
Campigotto, Federico
Rosovsky, Rachel
Mantha, Simon
Kessler, Craig M.
Eneman, Jonathan
Raghavan, Vidya
Lenz, Heinz-Joseph
Bullock, Andrea
Buchbinder, Elizabeth
Neuberg, Donna
Furie, Bruce
TI Prediction and prevention of thromboembolic events with enoxaparin in
cancer patients with elevated tissue factor-bearing microparticles: a
randomized-controlled phase II trial (the Microtec study)
SO BRITISH JOURNAL OF HAEMATOLOGY
LA English
DT Article
DE microparticles; venous thromboembolic events; cancer associated
thrombosis; low molecular weight heparin
ID FACTOR PROCOAGULANT ACTIVITY; CELL-DERIVED MICROPARTICLES; VENOUS
THROMBOEMBOLISM; THROMBIN GENERATION; FIBRIN FORMATION; FLOW-CYTOMETRY;
COMPETING RISK; P-SELECTIN; IN-VIVO; CHEMOTHERAPY
AB Elevated levels of circulating tissue factor-bearing microparticles (TFMP) have been associated with an increased risk of developing venous thromboembolism (VTE) in cancer patients. We performed a randomized phase II study to evaluate the cumulative incidence of VTE in advanced cancer patients with lower levels of TFMP not receiving thromboprophylaxis and those with higher levels of circulating TFMP randomized to enoxaparin or observation. The cumulative incidence of VTE at 2 months in the higher TFMP group randomized to enoxaparin (N = 23) was 5.6% while the higher TFMP group observation arm (N = 11) was 27.3% (Gray test P = 0.06). The cumulative incidence of VTE in the low TFMP was 7.2% (N = 32). No major haemorrhages were observed in the enoxaparin arm. The median survival for patients with higher levels of TFMP followed by observation was 11.8 months compared with 17.8 months on enoxaparin (P = 0.58). In a prospective randomized trial, increased numbers of circulating TFMP detected by impedance flow cytometry identified cancer patients with a high incidence of VTE. Enoxaparin demonstrated a clear trend towards reducing the rate of VTE in patients with elevated levels of TFMP, with an overall rate of VTE similar in magnitude to the lower TFMP group.
C1 [Zwicker, Jeffrey I.; Bauer, Kenneth A.; Furie, Bruce] Beth Israel Deaconess Med Ctr, Div Hemostasis & Thrombosis, Boston, MA 02215 USA.
[Zwicker, Jeffrey I.; Bullock, Andrea; Buchbinder, Elizabeth] Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA.
[Liebman, Howard A.; Lenz, Heinz-Joseph] Univ So Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Los Angeles, CA 90033 USA.
[Bauer, Kenneth A.] Harvard Univ, Sch Med, Vet Affairs Boston Healthcare Syst, Boston, MA USA.
[Caughey, Thomas; Raghavan, Vidya] Harvard Univ, Sch Med, Mt Auburn Hosp, Cambridge, MA 02138 USA.
[Campigotto, Federico; Neuberg, Donna] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Rosovsky, Rachel] Harvard Univ, Sch Med, Massachusetts Gen Hosp, N Shore Canc Ctr, Danvers, MA USA.
[Mantha, Simon] Lahey Clin Hosp, Burlington, MA USA.
[Kessler, Craig M.] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA.
[Eneman, Jonathan] York Hosp, York, ME USA.
RP Zwicker, JI (reprint author), Beth Israel Deaconess Med Ctr, Div Hemostasis & Thrombosis, 330 Brookline Ave, Boston, MA 02215 USA.
EM jzwicker@bidmc.harvard.edu
OI Zwicker, Jeffrey/0000-0001-5810-6893
FU National Institutes of Health [K23 HL84052, R01 HL095084]; Sanofi
FX This work was supported by grants from the National Institutes of
Health, K23 HL84052 (JIZ) and R01 HL095084 (BF), as well as a research
grant from Sanofi (JIZ). We thank Anita Rodrigues, Marie Mahony RN,
Laurie Hornor RN, Lisa Fabry RN, and Kelly Tammaro PharmD for their
efforts in clinical research coordination; Gus Alban and Leo Puljanowski
and Beckman Coulter for cytometry technical support; Dr. Gary Horowitz
for technical assistance with D-dimer analysis; Dr. Hing Wong at Altor
Biosciences for the gift of humanized tissue factor antibody. We are
indebted to the patients for participating in this trial and acknowledge
the critical roles played by all the participating investigators and
coordinators.
NR 34
TC 56
Z9 58
U1 0
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0007-1048
J9 BRIT J HAEMATOL
JI Br. J. Haematol.
PD FEB
PY 2013
VL 160
IS 4
BP 530
EP 537
DI 10.1111/bjh.12163
PG 8
WC Hematology
SC Hematology
GA 077ZO
UT WOS:000314068100013
PM 23240761
ER
PT J
AU Demay, MB
AF Demay, Marie B.
TI Physiological Insights from the Vitamin D Receptor Knockout Mouse
SO CALCIFIED TISSUE INTERNATIONAL
LA English
DT Article
DE Alopecia; Ligand-independent; Osteomalacia; Rickets
ID MINERAL ION HOMEOSTASIS; VDR-NULL MICE; 1,25-DIHYDROXYVITAMIN D-3;
ABLATED MICE; HYPERTROPHIC CHONDROCYTES; EPIDERMAL DIFFERENTIATION;
CALCIUM-ABSORPTION; HAIRLESS GENE; ANIMAL-MODEL; RICKETS
AB Identification of vitamin D as a potent antirachitic factor almost a century ago prompted investigations aimed at addressing its mechanism of action and key target tissues. Studies in vitamin D deficiency models and in kindreds with impaired hormone activation and function were critical in identifying key steps in the vitamin D signaling pathway. Studies in humans with vitamin D receptor (VDR) mutations provided a tremendous amount of information regarding the role of this receptor in calcium and skeletal homeostasis. The availability of mouse models of VDR ablation provided an important tool for detailed molecular analyses of the pathophysiologic basis for the skeletal, parathyroid and cutaneous phenotypes observed in mice and humans with impaired VDR function. These investigations revealed that a critical action of the liganded receptor is the promotion of intestinal calcium absorption. Bypassing this defect by dietary or transgenic rescue prevents the severe skeletal phenotype of the VDR ablated mice, as well as the development of hyperparathyroidism. In contrast, intestine specific ablation of the receptor results in marked skeletal pathology. Like their human counterparts, VDR knockout mice develop alopecia. Studies in these mice demonstrated that the actions of the VDR required for cyclical regeneration of the hair follicle and prevention of alopecia were shown independent of 1,25-dihydroxyvitamin D demonstrating that the unliganded receptor has an important role in the cutaneous homeostasis.
C1 Harvard Univ, Endocrine Unit, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA.
RP Demay, MB (reprint author), Harvard Univ, Endocrine Unit, Massachusetts Gen Hosp, Sch Med, Thier 11,50 Blossom St, Boston, MA 02115 USA.
EM demay@helix.mgh.harvard.edu
FU National Institutes of Health [R01-DK-46974]
FX This work was supported by a Grant from the National Institutes of
Health R01-DK-46974.
NR 45
TC 12
Z9 13
U1 1
U2 8
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0171-967X
J9 CALCIFIED TISSUE INT
JI Calcif. Tissue Int.
PD FEB
PY 2013
VL 92
IS 2
SI SI
BP 99
EP 105
DI 10.1007/s00223-012-9633-2
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 077RA
UT WOS:000314043900003
PM 22903507
ER
PT J
AU Diyabalanage, HVK
Granda, ML
Hooker, JM
AF Diyabalanage, Himashinie V. K.
Granda, Michael L.
Hooker, Jacob M.
TI Combination therapy: Histone deacetylase inhibitors and platinum-based
chemotherapeutics for cancer
SO CANCER LETTERS
LA English
DT Review
DE Histone deacetylase; Cisplatin; Cancer; Chemotherapy; HDAC inhibitor;
Combination therapy; Platinum drug
ID SUBEROYLANILIDE HYDROXAMIC ACID; T-CELL LYMPHOMA; PHASE-II TRIAL; HDAC
INHIBITORS; OVARIAN-CANCER; VALPROIC ACID; CARCINOMA-CELLS;
CLINICAL-APPLICATIONS; MOLECULAR-MECHANISMS; EPIGENETIC THERAPY
AB One of the most promising strategies to increase the efficacy of standard chemotherapy drugs is by combining them with low doses of histone deacetylases inhibitors (HDACis). Regarded as chemosensitizers, the addition of well-tolerated doses of HDACis to platinum-based chemotherapeutics has been proven in vitro and in vivo in recent studies for many cancer types and stages. In this review, we discuss the most commonly used combinations of histone deacetylase inhibitors and platinum based drugs in the context of their possible mechanisms, efficiency, efficacy, and related drawbacks in preclinical and clinical studies. (c) 2012 Elsevier Ireland Ltd. All rights reserved.
C1 [Diyabalanage, Himashinie V. K.; Granda, Michael L.; Hooker, Jacob M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Boston, MA 02129 USA.
RP Hooker, JM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Boston, MA 02129 USA.
EM hooker@nmr.mgh.harvard.edu
OI Hooker, Jacob/0000-0002-9394-7708
FU NCI NIH HHS [T32 CA009502]; NCRR NIH HHS [S10 RR023385]; NIDA NIH HHS
[R01 DA030321]
NR 120
TC 19
Z9 19
U1 1
U2 45
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0304-3835
J9 CANCER LETT
JI Cancer Lett.
PD FEB 1
PY 2013
VL 329
IS 1
BP 1
EP 8
DI 10.1016/j.canlet.2012.09.018
PG 8
WC Oncology
SC Oncology
GA 078CQ
UT WOS:000314076100001
PM 23032720
ER
PT J
AU Micco, JA
Hirshfeld-Becker, DR
Henin, A
Ehrenreich-May, J
AF Micco, Jamie A.
Hirshfeld-Becker, Dina R.
Henin, Aude
Ehrenreich-May, Jill
TI Content Specificity of Threat Interpretation in Anxious and Non-Clinical
Children
SO COGNITIVE THERAPY AND RESEARCH
LA English
DT Article
DE Content specificity; Threat interpretation; Interpretation bias; Child
anxiety
ID SEPARATION ANXIETY DISORDER; GENERALIZED-ANXIETY; SOCIAL PHOBIA;
INTERPRETATION BIAS; CHILDHOOD ANXIETY; PANIC DISORDER; PERCEPTION
ABNORMALITIES; EMOTIONAL INFORMATION; SOMATIC COMPLAINTS; DEPRESSION
SCALE
AB This study investigated content specificity of children's threat interpretations in a group of 40 clinically anxious (18 boys, 22 girls; ages 7-14 years) and a group of 40 non-clinical children (19 boys, 21 girls; ages 8-14 years). Associations between disorder-specific threat interpretations (in response to situations selected by each child) and each of six DSM-IV anxiety and depressive disorder symptom domains were examined for each group of children through multivariate regression analyses. Supporting theories of cognitive content specificity, results showed that for clinically anxious children, symptoms of social phobia and panic disorder were significantly and specifically predicted by threat interpretation in response to situations that corresponded to each disorder, while symptoms of separation anxiety were predicted by threat perception in situations relevant to separation anxiety and panic disorder. There was little evidence of cognitive content specificity within the non-clinical group of children. Implications for theories of development of interpretation biases associated with child anxiety disorders are discussed.
C1 [Micco, Jamie A.; Hirshfeld-Becker, Dina R.; Henin, Aude] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Cambridge, MA 02138 USA.
[Ehrenreich-May, Jill] Univ Miami, Dept Psychol, Coral Gables, FL 33124 USA.
RP Micco, JA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, 185 Alewife Brook Pkwy,Suite 2000, Cambridge, MA 02138 USA.
EM jmicco@partners.org
NR 49
TC 2
Z9 3
U1 1
U2 10
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0147-5916
J9 COGNITIVE THER RES
JI Cogn. Ther. Res.
PD FEB
PY 2013
VL 37
IS 1
BP 78
EP 88
DI 10.1007/s10608-012-9438-7
PG 11
WC Psychology, Clinical
SC Psychology
GA 077YD
UT WOS:000314064400010
ER
PT J
AU Bui, E
Simon, NM
Robinaugh, DJ
LeBlanc, NJ
Wang, YJ
Skritskaya, NA
Mauro, C
Shear, MK
AF Bui, Eric
Simon, Naomi M.
Robinaugh, Donald J.
LeBlanc, Nicole J.
Wang, Yuanjia
Skritskaya, Natalia A.
Mauro, Christine
Shear, M. Katherine
TI PERILOSS DISSOCIATION, SYMPTOM SEVERITY, AND TREATMENT RESPONSE IN
COMPLICATED GRIEF
SO DEPRESSION AND ANXIETY
LA English
DT Article
DE peritraumatic dissociation; complicated grief; treatment response; drop
out; prediction
ID POSTTRAUMATIC STRESS SYMPTOMS; PERITRAUMATIC DISSOCIATION; CHILDREN
VICTIMS; TRAUMA; INDIVIDUALS; EXPERIENCES; ACCIDENT
AB Background Complicated grief (CG) is a bereavement-specific syndrome characterized by traumatic and separation distress lasting over 6 months. Little is known about the role of dissociation experienced during or immediately after the loss of a loved one (i.e. periloss dissociation [PLD]) in CG. The present study aimed to examine the psychometric properties of the PLD-adapted Peritraumatic Dissociative Experiences Questionnaire and its association with symptom severity, treatment response, and drop-out rate. Methods PLD data collected as part of a randomized controlled trial of two loss-focused psychotherapy approaches for CG were examined. Treatment-seeking individuals with primary CG (n = 193) were assessed for PLD at the initial visit, 95 of whom were randomized and completed at least one treatment session. Results The PLD-adapted Peritraumatic Dissociative Experiences Questionnaire was found to be internally consistent (a = 0.91) with good convergent and divergent validity. After controlling for age, gender, time since loss, and current comorbid psychiatric diagnosis, self-reported PLD was associated with greater CG symptom severity (P < .01). However, contrary to our hypotheses, after controlling for age, baseline symptoms severity, psychiatric comorbidity, and treatment arm, PLD was predictive of better treatment response (P < .05) and lower study discontinuation (P < .01). Conclusions PLD may be useful in identifying individuals at risk for CG and those who might respond to psychotherapy. Additional research should investigate the relationship of PLD with treatment outcome for different treatment approaches, and whether PLD prospectively predicts the development of CG.
C1 [Bui, Eric] Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Boston, MA 02114 USA.
[Bui, Eric; Simon, Naomi M.] Harvard Univ, Sch Med, Boston, MA USA.
[Bui, Eric] Univ Toulouse, Toulouse, France.
[Bui, Eric] CHU Toulouse, Toulouse, France.
[Wang, Yuanjia; Skritskaya, Natalia A.; Mauro, Christine; Shear, M. Katherine] Columbia Univ, New York, NY USA.
RP Bui, E (reprint author), Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, 1 Bowdoin Sq,6th Floor,Suite 650, Boston, MA 02114 USA.
EM tebui@partners.org
RI Bui, Eric/J-8347-2015
OI Bui, Eric/0000-0002-1413-6473
FU American Foundation for Suicide Prevention; Forest Laboratories; NIMH;
DOD; GlaxoSmithKline; NARSAD Sepracor
FX EB has received honoraria from Laboratoires Servier. NMS has research
grants from American Foundation for Suicide Prevention, Forest
Laboratories, NIMH, DOD, GlaxoSmithKline, NARSAD Sepracor and also has
received honoraria for speaking/CME from MGH Psychiatry Academy. MKS has
research grant from American Foundation for Suicide Prevention and NIMH.
All other authors declare that they have no conflicts of interest.
NR 24
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Z9 4
U1 0
U2 20
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1091-4269
J9 DEPRESS ANXIETY
JI Depress. Anxiety
PD FEB
PY 2013
VL 30
IS 2
BP 123
EP 128
DI 10.1002/da.22029
PG 6
WC Psychology, Clinical; Psychiatry; Psychology
SC Psychology; Psychiatry
GA 078QC
UT WOS:000314113300004
PM 23212730
ER
PT J
AU Shah, RR
Koniski, A
Shinde, M
Blythe, SA
Fass, DM
Haggarty, SJ
Palis, J
Klein, PS
AF Shah, Rishita R.
Koniski, Anne
Shinde, Mansi
Blythe, Shelby A.
Fass, Daniel M.
Haggarty, Stephen J.
Palis, James
Klein, Peter S.
TI Regulation of Primitive Hematopoiesis by Class I Histone Deacetylases
SO DEVELOPMENTAL DYNAMICS
LA English
DT Article
DE class I HDACs; hematopoiesis
ID VALPROIC ACID; EMBRYONIC BLOOD; XENOPUS-LAEVIS; MIDBLASTULA TRANSITION;
VENTRAL MESODERM; CELL-DEVELOPMENT; GENE-EXPRESSION; GROWTH-FACTOR;
ZEBRAFISH; GATA-1
AB Background: Histone deacetylases (HDACs) regulate multiple developmental processes and cellular functions. However, their roles in blood development have not been determined, and in Xenopus laevis a specific function for HDACs has yet to be identified. Here, we employed the class I selective HDAC inhibitor, valproic acid (VPA), to show that HDAC activity is required for primitive hematopoiesis. Results: VPA treatment during gastrulation resulted in a complete absence of red blood cells (RBCs) in Xenopus tadpoles, but did not affect development of other mesodermal tissues, including myeloid and endothelial lineages. These effects of VPA were mimicked by Trichostatin A (TSA), a well-established pan-HDAC inhibitor, but not by valpromide, which is structurally similar to VPA but does not inhibit HDACs. VPA also caused a marked, dose-dependent loss of primitive erythroid progenitors in mouse yolk sac explants at clinically relevant concentrations. In addition, VPA treatment inhibited erythropoietic development downstream of bmp4 and gata1 in Xenopus ectodermal explants. Conclusions: These findings suggest an important role for class I HDACs in primitive hematopoiesis. Our work also demonstrates that specific developmental defects associated with exposure to VPA, a significant teratogen in humans, arise through inhibition of class I HDACs. Developmental Dynamics 242:108121, 2013. (c) 2012 Wiley Periodicals,Inc.
C1 [Shah, Rishita R.; Blythe, Shelby A.; Klein, Peter S.] Univ Penn, Cell & Mol Biol Grad Grp, Philadelphia, PA 19104 USA.
[Koniski, Anne; Palis, James] Univ Rochester, Med Ctr, Dept Pediat, Ctr Pediat Biomed Res, Rochester, NY 14642 USA.
[Shinde, Mansi; Klein, Peter S.] Univ Penn, Pharmacol Grad Grp, Philadelphia, PA 19104 USA.
[Fass, Daniel M.; Haggarty, Stephen J.] Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Cambridge, MA USA.
[Fass, Daniel M.; Haggarty, Stephen J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA USA.
[Klein, Peter S.] Univ Penn, Dept Med Hematol Oncol, Philadelphia, PA 19104 USA.
RP Klein, PS (reprint author), Univ Penn, Dept Med Hematol Oncol, Philadelphia, PA 19104 USA.
EM pklein@mail.med.upenn.edu
OI Blythe, Shelby/0000-0003-4986-2579; Haggarty, Stephen
J./0000-0002-7872-168X
FU NIH [1R01GM076621, 1R01HL110806-01, R25 CA101871-07, R01DK09361,
1R01DA028301, R01DK 09361]; NCI [R25 CA101871-07]
FX Contract grant sponsor: NIH; Contract grant numbers: 1R01GM076621;
1R01HL110806-01; R25 CA101871-07; R01DK09361; 1R01DA028301.; We thank
Nancy Speck, Daniel Kessler, Michael May, Judy Meinkoth, and the members
of the Klein Lab for their insights and encouragement. We also thank
Mitch Weiss, Gerd Blobel, and Wei Tong for insightful comments. We thank
Edward Holson for the synthesis of CI-994 and C60. This work was
supported by the following NIH grants: 1R01GM076621 (P.S.K.),
1R01HL110806-01 (P.S.K.); R01DK 09361 (J.P.); and 1R01DA028301 (S.J.H.).
In addition, R.S. was supported by the Cancer Pharmacology Training
Grant R25 CA101871-07 from the NCI.
NR 54
TC 4
Z9 5
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1058-8388
J9 DEV DYNAM
JI Dev. Dyn.
PD FEB
PY 2013
VL 242
IS 2
BP 108
EP 121
DI 10.1002/dvdy.23906
PG 14
WC Anatomy & Morphology; Developmental Biology
SC Anatomy & Morphology; Developmental Biology
GA 076VE
UT WOS:000313986100002
PM 23184530
ER
PT J
AU Saxon, AJ
Ling, W
Hillhouse, M
Thomas, C
Hasson, A
Ang, A
Doraimani, G
Tasissa, G
Lokhnygina, Y
Leimberger, J
Bruce, RD
McCarthy, J
Wiest, K
McLaughlin, P
Bilangi, R
Cohen, A
Woody, G
Jacobs, P
AF Saxon, Andrew J.
Ling, Walter
Hillhouse, Maureen
Thomas, Christie
Hasson, Albert
Ang, Alfonso
Doraimani, Geetha
Tasissa, Gudaye
Lokhnygina, Yuliya
Leimberger, Jeff
Bruce, R. Douglas
McCarthy, John
Wiest, Katharina
McLaughlin, Paul
Bilangi, Richard
Cohen, Allan
Woody, George
Jacobs, Petra
TI Buprenorphine/Naloxone and methadone effects on laboratory indices of
liver health: A randomized trial
SO DRUG AND ALCOHOL DEPENDENCE
LA English
DT Article
DE Liver function; Buprenorphine; Methadone; Treatment outcome
ID OPIOID DEPENDENCE; MAINTENANCE; HEPATITIS; ABUSE
AB Background: Buprenorphine/naloxone (BUP) and methadone (MET) are efficacious treatments for opioid dependence, although concerns about a link between BUP and drug-induced hepatitis have been raised. This study compares the effects of BUP and MET on liver health in opioid-dependent participants.
Methods: This was a randomized controlled trial of 1269 opioid-dependent participants seeking treatment at 8 federally licensed opioid treatment programs and followed for up to 32 weeks between May 2006 and August 2010; 731 participants met "evaluable" criteria defined as completing 24 weeks of medication and providing at least 4 blood samples for transaminase testing. Participants were randomly assigned to receive BUP or MET for 24 weeks. Shift table analysis determined how many evaluable participants moved between categories of low and elevated transaminase levels. Predictors of moving from low to high transaminase levels were identified.
Results: Changes in transaminase levels did not differ by medication condition. Baseline infection with hepatitis C or B was the only significant predictor of moving from low to elevated transaminase levels; 9 BUP and 15 MET participants showed extreme liver test elevations and were more likely than those without extreme elevations to have seroconverted to both hepatitis B and C during the study, or to use illicit drugs during the first 8 weeks of treatment. MET participants were retained longer in treatment than BUP participants.
Conclusions: This study demonstrated no evidence of liver damage during the initial 6 months of treatment in either condition. Physicians can prescribe either medication without major concern for liver injury. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
C1 [Saxon, Andrew J.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA.
[Ling, Walter; Hillhouse, Maureen; Thomas, Christie; Hasson, Albert; Ang, Alfonso; Doraimani, Geetha] Univ Calif Los Angeles, Integrated Subst Abuse Programs, Los Angeles, CA 90025 USA.
[Tasissa, Gudaye; Lokhnygina, Yuliya; Leimberger, Jeff] Duke Clin Res Inst, Durham, NC 27705 USA.
[Bruce, R. Douglas] Yale Univ, Sch Med, New Haven, CT 06510 USA.
[McCarthy, John] Bivalley Med Clin Inc, Carmichael, CA 95838 USA.
[Wiest, Katharina] CODA Inc, Portland, OR 97214 USA.
[McLaughlin, Paul] Hartford Dispensary, Manchester, CT 06040 USA.
[Bilangi, Richard] Connecticut Counseling Ctr, Danbury, CT 06810 USA.
[Cohen, Allan] Bay Area Addict Res & Treatment, Sherman Oaks, CA 91403 USA.
[Woody, George] Univ Penn, Sch Med, Philadelphia, PA 19106 USA.
[Jacobs, Petra] NIDA, Clin Trials Network, Bethesda, MD 20892 USA.
RP Hillhouse, M (reprint author), Univ Calif Los Angeles, Integrated Subst Abuse Programs, 1640 S Sepulveda Blvd,Suite 120, Los Angeles, CA 90025 USA.
EM hillhous@ucla.edu
FU Gilead Sciences, Inc; Merck Co; Bristol Myers Squibb; Boehringer
Ingelheim; Reckitt Benckiser Pharmaceuticals; Abbott Laboratories;
Pfizer, Inc
FX Authors disclosing relevant financial interests, activities,
relationships, and affiliations are: Andrew Saxon: Paid consultant to
Reckitt Benckiser Pharmaceuticals; Walter Ling: Paid consultant to
Reckitt Benckiser Pharmaceuticals; R. Douglas Bruce: Research grant
support from Gilead Sciences, Inc., Merck & Co., Bristol Myers Squibb,
Boehringer Ingelheim, Reckitt Benckiser Pharmaceuticals, Abbott
Laboratories, Pfizer, Inc., and honorarium from Reckitt Benckiser
Pharmaceuticals; Yuliya Lokhnygina: Paid consultant to Johnson &
Johnson. All other authors report no financial or other possible
conflicts of interest.
NR 19
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Z9 25
U1 2
U2 8
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0376-8716
J9 DRUG ALCOHOL DEPEN
JI Drug Alcohol Depend.
PD FEB 1
PY 2013
VL 128
IS 1-2
BP 71
EP 76
DI 10.1016/j.drugalcdep.2012.08.002
PG 6
WC Substance Abuse; Psychiatry
SC Substance Abuse; Psychiatry
GA 081OO
UT WOS:000314331700011
PM 22921476
ER
PT J
AU Schackman, BR
Metsch, LR
Colfax, GN
Leff, JA
Wong, A
Scott, CA
Feaster, DJ
Gooden, L
Matheson, T
Haynes, LF
Paltiel, AD
Walensky, RP
AF Schackman, Bruce R.
Metsch, Lisa R.
Colfax, Grant N.
Leff, Jared A.
Wong, Angela
Scott, Callie A.
Feaster, Daniel J.
Gooden, Lauren
Matheson, Tim
Haynes, Louise F.
Paltiel, A. David
Walensky, Rochelle P.
TI The cost-effectiveness of rapid HIV testing in substance abuse
treatment: Results of a randomized trial
SO DRUG AND ALCOHOL DEPENDENCE
LA English
DT Article
DE Rapid HIV testing; Substance use; Cost-effectiveness
ID HUMAN-IMMUNODEFICIENCY-VIRUS; UNITED-STATES; ANTIRETROVIRAL THERAPY;
INFECTED PERSONS; CLINICAL-TRIALS; CARE; EFFICACY; PREVENTION; HIV/AIDS;
LIFE
AB Background: The President's National HIV/AIDS Strategy calls for coupling HIV screening and prevention services with substance abuse treatment programs. Fewer than half of US community-based substance abuse treatment programs make HIV testing available on-site or through referral.
Methods: We measured the cost-effectiveness of three HIV testing strategies evaluated in a randomized trial conducted in 12 community-based substance abuse treatment programs in 2009: off-site testing referral, on-site rapid testing with information only, on-site rapid testing with risk-reduction counseling. Data from the trial included patient demographics, prior testing history, test acceptance and receipt of results, undiagnosed HIV prevalence (0.4%) and program costs. The Cost-Effectiveness of Preventing AIDS Complications (CEPAC) computer simulation model was used to project life expectancy, lifetime costs, and quality-adjusted life years (QALYs) for HIV-infected individuals. Incremental cost-effectiveness ratios (2009 US $/QALY) were calculated after adding costs of testing HIV-uninfected individuals; costs and QALYs were discounted at 3% annually.
Results: Referral for off-site testing is less efficient (dominated) compared to offering on-site testing with information only. The cost-effectiveness ratio for on-site testing with information is $60,300/QALY in the base case, or $76,300/QALY with 0.1% undiagnosed HIV prevalence. HIV risk-reduction counseling costs $36 per person more without additional benefit.
Conclusions: A strategy of on-site rapid HIV testing offer with information only in substance abuse treatment programs increases life expectancy at a cost-effectiveness ratio <$100,000/QALY. Policymakers and substance abuse treatment leaders should seek funding to implement on-site rapid HIV testing in substance abuse treatment programs for those not recently tested. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
C1 [Schackman, Bruce R.; Leff, Jared A.] Weill Cornell Med Coll, Dept Publ Hlth, New York, NY 10065 USA.
[Metsch, Lisa R.; Feaster, Daniel J.; Gooden, Lauren] Univ Miami, Miller Sch Med, Dept Epidemiol & Publ Hlth, Miami, FL 33136 USA.
[Colfax, Grant N.; Matheson, Tim] San Francisco Dept Publ Hlth, HIV Prevent & Res Sect, San Francisco, CA 94102 USA.
[Wong, Angela; Scott, Callie A.; Walensky, Rochelle P.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA.
[Haynes, Louise F.] Med Univ S Carolina, Div Clin Neurosci, Charleston, SC 29403 USA.
[Paltiel, A. David] Yale Univ, Sch Publ Hlth, Div Hlth Policy & Adm, New Haven, CT 06510 USA.
[Walensky, Rochelle P.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA.
[Walensky, Rochelle P.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
RP Schackman, BR (reprint author), Weill Cornell Med Coll, Dept Publ Hlth, 402 E 67th St, New York, NY 10065 USA.
EM brs2006@med.cornell.edu
RI Feaster, Daniel/I-6079-2013;
OI Walensky, Rochelle P./0000-0002-8795-379X; Feaster,
Daniel/0000-0002-6172-7460
FU National Institute on Drug Abuse [R01 DA027379, R01 DA015612]; National
Drug Abuse Treatment Clinical Trials Network (CTN) [U10 DA013720,
U10DA13720-09S, U10 DA020036, U10DA15815, U10DA13034, U10DA013038, U10
DA013732, U10 DA13036, U10 DA13727, U10DA015833, HHSN271200522081C,
HHSN271200522071C]; National Institute of Mental Health [R01 MH065869];
National Institute of Allergy and Infectious Diseases [R37 A1042006]
FX This research was supported by the National Institute on Drug Abuse (R01
DA027379; R01 DA015612), the National Drug Abuse Treatment Clinical
Trials Network (CTN) (U10 DA013720, U10DA13720-09S, U10 DA020036,
U10DA15815, U10DA13034, U10DA013038, U10 DA013732, U10 DA13036, U10
DA13727, U10DA015833, HHSN271200522081C, HHSN271200522071C); the
National Institute of Mental Health (R01 MH065869), and the National
Institute of Allergy and Infectious Diseases (R37 A1042006). The
contents of this publication are solely the responsibility of the
authors and do not necessarily represent the views of the funding
agencies or the U.S. government.
NR 44
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U1 4
U2 24
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0376-8716
J9 DRUG ALCOHOL DEPEN
JI Drug Alcohol Depend.
PD FEB 1
PY 2013
VL 128
IS 1-2
BP 90
EP 97
DI 10.1016/j.drugalcdep.2012.08.009
PG 8
WC Substance Abuse; Psychiatry
SC Substance Abuse; Psychiatry
GA 081OO
UT WOS:000314331700014
PM 22971593
ER
PT J
AU Ho, JM
Blevins, JE
AF Ho, Jacqueline M.
Blevins, James E.
TI Coming Full Circle: Contributions of Central and Peripheral Oxytocin
Actions to Energy Balance
SO ENDOCRINOLOGY
LA English
DT Review
ID HYPOTHALAMIC PARAVENTRICULAR NUCLEUS; CONDITIONED PLACE PREFERENCE;
RECEPTOR GENE-EXPRESSION; C-FOS EXPRESSION; FOOD-INTAKE; BRAIN-STEM;
GASTRIC DISTENSION; DEFICIENT MICE; NEUROHYPOPHYSEAL HORMONES;
INTRACELLULAR CALCIUM
AB The neuropeptide oxytocin has emerged as an important anorexigen in the regulation of energy balance. Its effects on food intake have largely been attributed to limiting meal size through interactions in key regulatory brain regions such as the hypothalamus and hindbrain. Pharmacologic and pair-feeding studies indicate that its ability to reduce body mass extends beyond that of food intake, affecting multiple factors that determine energy balance such as energy expenditure, lipolysis, and glucose regulation. Systemic administration of oxytocin recapitulates many of its effects when administered centrally, raising the questions of whether and to what extent circulating oxytocin contributes to energy regulation. Its therapeutic potential to treat metabolic conditions remains to be determined, but data from diet-induced and genetically obese rodent models as well as application of oxytocin in humans in other areas of research have revealed promising results thus far. (Endocrinology 154: 589-596, 2013)
C1 [Ho, Jacqueline M.] Vet Affairs Puget Sound Hlth Care Syst, Off Res & Dev, Med Res Serv, Seattle, WA 98108 USA.
Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA.
RP Ho, JM (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Off Res & Dev, Med Res Serv, 1660 S Columbian Way, Seattle, WA 98108 USA.
EM jmh529@uw.edu
FU Office of Research and Development, Medical Research Service, Department
of Veterans Affairs; Department of Veterans Affairs; National Institutes
of Health [T32DK007247-35]
FX This work was supported by resources from the Office of Research and
Development, Medical Research Service, Department of Veterans Affairs,
including the Department of Veterans Affairs Merit Review Research
Program. Funding for this manuscript was provided by the Department of
Veterans Affairs Merit Review Research Program (to J.E.B.) and a Trainee
Fellowship under National Institutes of Health grant T32DK007247-35 (to
J.M.H.).
NR 99
TC 19
Z9 21
U1 2
U2 14
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0013-7227
J9 ENDOCRINOLOGY
JI Endocrinology
PD FEB
PY 2013
VL 154
IS 2
BP 589
EP 596
DI 10.1210/en.2012-1751
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 076ME
UT WOS:000313959800004
PM 23270805
ER
PT J
AU Giubellino, A
Bullova, P
Nolting, E
Turkova, H
Powers, JF
Liu, QS
Guichard, S
Tischler, AS
Grossman, AB
Pacak, K
AF Giubellino, Alessio
Bullova, Petra
Noelting, Svenja
Turkova, Hana
Powers, James F.
Liu, Qingsong
Guichard, Sylvie
Tischler, Arthur S.
Grossman, Ashley B.
Pacak, Karel
TI Combined Inhibition of mTORC1 and mTORC2 Signaling Pathways Is a
Promising Therapeutic Option in Inhibiting Pheochromocytoma Tumor
Growth: In Vitro and In Vivo Studies in Female Athymic Nude Mice
SO ENDOCRINOLOGY
LA English
DT Article
ID MALIGNANT PHEOCHROMOCYTOMA; DIFFERENTIAL EXPRESSION; NEUROENDOCRINE
TUMORS; MAMMALIAN TARGET; KINASE INHIBITOR; ENDOCRINE TUMORS; CANCER;
PARAGANGLIOMA; RAPAMYCIN; THERAPIES
AB Several lines of evidence, including the recent discovery of novel susceptibility genes, point out an important role for the mammalian target of rapamycin (mTOR) signaling pathway in the development of pheochromocytoma. Analyzing a set of pheochromocytomas from patients with different genetic backgrounds, we observed and confirmed a significant overexpression of key mTOR complex (mTORC) signaling mediators. Using selective ATP-competitive inhibitors targeting both mTORC1 and mTORC2, we significantly arrested the in vitro cell proliferation and blocked migration of pheochromocytoma cells as a result of the pharmacological suppression of the Akt/mTOR signaling pathway. Moreover, AZD8055, a selective ATP-competitive dual mTORC1/2 small molecular inhibitor, significantly reduced the tumor burden in a model of metastatic pheochromocytoma using female athymic nude mice. This study suggests that targeting both mTORC1 and mTORC2 is a potentially rewarding strategy and supports the application of selective inhibitors in combinatorial drug regimens for metastatic pheochromocytoma. (Endocrinology 154: 646-655, 2013)
C1 [Giubellino, Alessio; Bullova, Petra; Turkova, Hana; Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Reprod & Adult Endocrinol Program, NIH, Bethesda, MD 20892 USA.
[Noelting, Svenja; Grossman, Ashley B.] Queen Mary Univ London, Barts & London Sch Med, Dept Endocrinol, William Harvey Res Inst, London EC1M 6BQ, England.
[Powers, James F.; Tischler, Arthur S.] Tufts Med Ctr, Dept Pathol, Boston, MA 02111 USA.
[Liu, Qingsong] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA.
[Guichard, Sylvie] AstraZeneca, Oncol iMed, Macclesfield SK10 4TG, Cheshire, England.
[Grossman, Ashley B.] Univ Oxford, Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX3 7LE, England.
RP Giubellino, A (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Reprod & Adult Endocrinol Program, NIH, Bldg 10-CRC,1E-3140,10 Ctr Dr, Bethesda, MD 20892 USA.
EM giubella@mail.nih.gov; karel@mail.nih.gov
OI Giubellino, Alessio/0000-0002-5352-0662; liu, qing
song/0000-0002-7829-2547
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health; Department of Defense
[W81XWH-11-1-0670]
FX This work was supported by the Intramural Research Program of the Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health. J.F.P. and A. S. T. were
supported by Grant W81XWH-11-1-0670 from the Department of Defense.
NR 50
TC 18
Z9 19
U1 0
U2 5
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0013-7227
J9 ENDOCRINOLOGY
JI Endocrinology
PD FEB
PY 2013
VL 154
IS 2
BP 646
EP 655
DI 10.1210/en.2012-1854
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 076ME
UT WOS:000313959800010
PM 23307788
ER
PT J
AU Miao, J
Wang, SB
Wan, ZM
Park, WM
Xia, Q
Wood, K
Li, GA
AF Miao, Jun
Wang, Shaobai
Wan, Zongmiao
Park, Won Man
Xia, Qun
Wood, Kirkham
Li, Guoan
TI Motion characteristics of the vertebral segments with lumbar
degenerative spondylolisthesis in elderly patients
SO EUROPEAN SPINE JOURNAL
LA English
DT Article
DE Lumbar spine; Degenerative spondylolisthesis; Vertebral kinematics; Disc
degeneration; Spinal instability
ID DISC DEGENERATION; DYNAMIC-MOTION; INSTABILITY; SPINE; ORIENTATION;
KINEMATICS; HEIGHT
AB Although some studies have reported on the kinematics of the lumbar segments with degenerative spondylolisthesis (DS), few data have been reported on the in vivo 6 degree-of-freedom kinematics of different anatomical structures of the diseased levels under physiological loading conditions. This research is to study the in vivo motion characteristics of the lumbar vertebral segments with L4 DS during weight-bearing activities.
Nine asymptomatic volunteers (mean age 54.4) and 9 patients with L4 DS (mean age 73.4) were included. Vertebral kinematics was obtained using a combined MRI/CT and dual fluoroscopic imaging technique. During functional postures (supine, standing upright, flexion, and extension), disc heights, vertebral motion patterns and instability were compared between the two groups.
Although anterior disc heights were smaller in the DS group than in the normal group, the differences were only significant at standing upright. Posterior disc heights were significantly smaller in DS group than in the normal group under all postures. Different vertebral motion patterns were observed in the DS group, especially in the left-right and cranial-caudal directions during flexion and extension of the body. However, the range of motions of the both groups were much less than the reported criteria of lumbar spinal instability.
The study showed that lumbar vertebra with DS has disordered motion patterns. DS did not necessary result in vertebral instability. A restabilization process may have occurred and surgical treatment should be planned accordingly.
C1 [Miao, Jun; Wang, Shaobai; Wan, Zongmiao; Park, Won Man; Wood, Kirkham; Li, Guoan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bioengn Lab,Dept Orthopaed Surg, Boston, MA 02114 USA.
[Miao, Jun; Xia, Qun] Tianjin Hosp, Dept Spinal Surg, Tianjin, Peoples R China.
[Wang, Shaobai] MIT, Dept Mech Engn, Cambridge, MA 02139 USA.
[Wan, Zongmiao] Cent S Univ, Xiangya Hosp 2, Changsha, Hunan, Peoples R China.
[Park, Won Man] Kyung Hee Univ, Dept Mech Engn, Yongin, 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@partner.org
FU NIH [R21AR057 989]; China scholarship council
FX This study was supported by NIH (R21AR057 989) and China scholarship
council.
NR 30
TC 8
Z9 12
U1 3
U2 14
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0940-6719
J9 EUR SPINE J
JI Eur. Spine J.
PD FEB
PY 2013
VL 22
IS 2
BP 425
EP 431
DI 10.1007/s00586-012-2428-3
PG 7
WC Clinical Neurology; Orthopedics
SC Neurosciences & Neurology; Orthopedics
GA 077XU
UT WOS:000314063500026
PM 22892705
ER
PT J
AU Drier, Y
Lawrence, MS
Carter, SL
Stewart, C
Gabriel, SB
Lander, ES
Meyerson, M
Beroukhim, R
Getz, G
AF Drier, Yotam
Lawrence, Michael S.
Carter, Scott L.
Stewart, Chip
Gabriel, Stacey B.
Lander, Eric S.
Meyerson, Matthew
Beroukhim, Rameen
Getz, Gad
TI Somatic rearrangements across cancer reveal classes of samples with
distinct patterns of DNA breakage and rearrangement-induced
hypermutability
SO GENOME RESEARCH
LA English
DT Article
ID HUMAN BREAST-CANCER; SEQUENCING REVEALS; GENOME; MUTATIONS;
TRANSLOCATIONS; ARCHITECTURE; IDENTIFICATION; TRANSVERSIONS;
ORGANIZATION; CHROMOSOMES
AB Whole-genome sequencing using massively parallel sequencing technologies enables accurate detection of somatic rearrangements in cancer. Pinpointing large numbers of rearrangement breakpoints to base-pair resolution allows analysis of rearrangement microhomology and genomic location for every sample. Here we analyze 95 tumor genome sequences from breast, head and neck, colorectal, and prostate carcinomas, and from melanoma, multiple myeloma, and chronic lymphocytic leukemia. We discover three genomic factors that are significantly correlated with the distribution of rearrangements: replication time, transcription rate, and GC content. The correlation is complex, and different patterns are observed between tumor types, within tumor types, and even between different types of rearrangements. Mutations in the APC gene correlate with and, hence, potentially contribute to DNA breakage in late-replicating, low %GC, untranscribed regions of the genome. We show that somatic rearrangements display less microhomology than germline rearrangements, and that breakpoint loci are correlated with local hypermutability with a particular enrichment for C <-> G transversions.
C1 [Drier, Yotam] Weizmann Inst Sci, Dept Phys Complex Syst, IL-76100 Rehovot, Israel.
[Drier, Yotam; Lawrence, Michael S.; Carter, Scott L.; Stewart, Chip; Gabriel, Stacey B.; Lander, Eric S.; Meyerson, Matthew; Beroukhim, Rameen; Getz, Gad] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
[Meyerson, Matthew; Beroukhim, Rameen] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
RP Getz, G (reprint author), Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
EM gadgetz@broadinstitute.org
RI Drier, Yotam/K-5208-2012
OI Drier, Yotam/0000-0003-1725-2995
FU NHGRI NIH HHS [U54 HG003067]
NR 54
TC 49
Z9 50
U1 0
U2 18
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 1088-9051
J9 GENOME RES
JI Genome Res.
PD FEB
PY 2013
VL 23
IS 2
BP 228
EP 235
DI 10.1101/gr.141382.112
PG 8
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
GA 081LG
UT WOS:000314323100002
PM 23124520
ER
PT J
AU Yu, ZT
Chen, C
Kling, DE
Liu, B
McCoy, JM
Merighi, M
Heidtman, M
Newburg, DS
AF Yu, Zhuo-Teng
Chen, Ceng
Kling, David E.
Liu, Bo
McCoy, John M.
Merighi, Massimo
Heidtman, Matthew
Newburg, David S.
TI The principal fucosylated oligosaccharides of human milk exhibit
prebiotic properties on cultured infant microbiota
SO GLYCOBIOLOGY
LA English
DT Article
DE bifidobacteria; fucosylated oligosaccharides; human milk; prebiotic
ID IN-VITRO FERMENTATION; REAL-TIME PCR; BIFIDOBACTERIUM-INFANTIS;
ESCHERICHIA-COLI; BREAST-MILK; CONSUMPTION; PROTECTION; BACTERIA;
PRIMERS; SAMPLES
AB Breast-fed infant microbiota is typically rich in bifidobacteria. Herein, major human milk oligosaccharides (HMOS) are assessed for their ability to promote the growth of bifidobacteria and to acidify their environment, key features of prebiotics. During in vitro anaerobic fermentation of infant microbiota, supplementation by HMOS significantly decreased the pH even greater than supplementation by fructooligosaccharide (FOS), a prebiotic positive control. HMOS elevated lactate concentrations, increased the proportion of Bifidobacterium spp. in culture, and through their fermentation into organic acids, decreased the proportion of Escherichia and Clostridium perfringens. Three principal components of HMOS, 2'-fucosyllactose, lactodifucotetraose and 3-fucosyllactose, were consumed in these cultures. These three principal oligosaccharides of human milk were then individually tested as supplements for in vitro growth of four individual representative strains of infant gut microbes. Bifidobacterium longum JCM7007 and B. longum ATCC15697 efficiently consumed oligosaccharides and produced abundant lactate and short-chain fatty acids, resulting in significant pH reduction. The specificity of fermentation differed by microbe species and strain and by oligosaccharide structure. Escherichia coli K12 and C. perfringens did not utilize appreciable fucosylated oligosaccharides, and a typical mixture of organic acid fermentation products inhibited their growth. In summary, 2'-fucosyllactose, lactodifucotetraose, and 3-fucosyllactose, when cultured with B. longum JCM7007 and B. longum ATCC15697, exhibit key characteristics of a prebiotic in vitro. If these bifidobacteria are representative of pioneering or keystone species for human microbiota, fucosylated HMOS could strongly promote colonization and maintenance of a mutualist symbiotic microbiome. Thus, these simple glycans could mediate beneficial effects of human milk on infant health.
C1 [Yu, Zhuo-Teng; Chen, Ceng; Liu, Bo; Newburg, David S.] Harvard Univ, Massachusetts Gen Hosp, Dept Pediat Gastroenterol & Nutr, Sch Med, Boston, MA 02129 USA.
[McCoy, John M.; Merighi, Massimo; Heidtman, Matthew] Glycosyn LLC, Medford, MA 02155 USA.
RP Newburg, DS (reprint author), Boston Coll, Program Glycobiol, Higgins Hall,140 Commonwealth Ave, Chestnut Hill, MA 02467 USA.
EM david.newburg@bc.edu
FU NIH [AI075563, HD013021, HD059140]
FX This investigation was financially supported by the NIH grants AI075563,
HD013021 and HD059140.
NR 35
TC 51
Z9 52
U1 6
U2 74
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0959-6658
J9 GLYCOBIOLOGY
JI Glycobiology
PD FEB
PY 2013
VL 23
IS 2
BP 169
EP 177
DI 10.1093/glycob/cws138
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 079DU
UT WOS:000314151200004
PM 23028202
ER
PT J
AU Nuzzo, E
Shensa, A
Kim, KH
Fine, MJ
Barnett, TE
Cook, R
Primack, BA
AF Nuzzo, Erin
Shensa, Ariel
Kim, Kevin H.
Fine, Michael J.
Barnett, Tracey E.
Cook, Robert
Primack, Brian A.
TI Associations between hookah tobacco smoking knowledge and hookah smoking
behavior among US college students
SO HEALTH EDUCATION RESEARCH
LA English
DT Article
ID HIGH-SCHOOL-STUDENTS; WATER-PIPE; CIGARETTE SMOKERS; CARBON-MONOXIDE;
PREVALENCE; UNIVERSITY; NICOTINE; SUSCEPTIBILITY; CONSEQUENCES;
NONRESPONSE
AB Hookah tobacco smoking is increasing among US college students, including those who would not otherwise use tobacco. Part of hookah's appeal is attributed to the perception that hookah is less harmful than cigarettes. The aims of this study were to assess knowledge of harmful exposures associated with hookah smoking relative to cigarette smoking and to determine associations between this knowledge and hookah smoking outcomes. Students (N = 852) at the University of Florida were randomly sampled via e-mail to obtain information on demographics, hookah smoking behavior and knowledge of five exposures (e.g. tar and nicotine). Multivariable logistic regression models assessed independent associations between knowledge and hookah smoking outcomes. Of the five factual knowledge items asked, 475 (55.8%) of the respondents answered none correctly. In multivariable models, correct responses to any knowledge items were not associated with lower odds of hookah smoking or susceptibility to hookah smoking in the future. Although college students are largely unaware of the toxicant exposures associated with hookah smoking, there is little association between knowledge and hookah smoking behavior.
C1 [Nuzzo, Erin; Shensa, Ariel; Fine, Michael J.; Primack, Brian A.] Univ Pittsburgh, Sch Educ, Dept Med, Div Gen Internal Med, Pittsburgh, PA 15260 USA.
[Kim, Kevin H.] Univ Pittsburgh, Sch Educ, Dept Educ Psychol, Pittsburgh, PA 15260 USA.
[Fine, Michael J.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15213 USA.
[Barnett, Tracey E.] Univ Florida, Dept Behav Sci & Community Hlth, Gainesville, FL 32610 USA.
[Cook, Robert] Univ Florida, Dept Epidemiol, Gainesville, FL 32610 USA.
[Primack, Brian A.] Univ Pittsburgh, Sch Med, Dept Pediat, Div Adolescent Med, Pittsburgh, PA 15213 USA.
RP Primack, BA (reprint author), Univ Pittsburgh, Sch Educ, Dept Med, Div Gen Internal Med, Pittsburgh, PA 15260 USA.
EM bprimack@pitt.edu
FU NCI NIH HHS [K07 CA114315, R01 CA140150, R01-CA140150]
NR 38
TC 22
Z9 22
U1 1
U2 16
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0268-1153
J9 HEALTH EDUC RES
JI Health Educ. Res.
PD FEB
PY 2013
VL 28
IS 1
BP 92
EP 100
DI 10.1093/her/cys095
PG 9
WC Education & Educational Research; Public, Environmental & Occupational
Health
SC Education & Educational Research; Public, Environmental & Occupational
Health
GA 079EF
UT WOS:000314152400009
PM 22987864
ER
PT J
AU Nagler, EM
Pednekar, MS
Viswanath, K
Sinha, DN
Aghi, MB
Pischke, CR
Ebbeling, CB
Lando, HA
Gupta, PC
Sorensen, GC
AF Nagler, Eve M.
Pednekar, Mangesh S.
Viswanath, Kasisomayajula
Sinha, Dhirendra N.
Aghi, Mira B.
Pischke, Claudia R.
Ebbeling, Cara B.
Lando, Harry A.
Gupta, Prakash C.
Sorensen, Glorian C.
TI Designing in the social context: using the social contextual model of
health behavior change to develop a tobacco control intervention for
teachers in India
SO HEALTH EDUCATION RESEARCH
LA English
DT Article
ID DIRECTIONS-SMALL-BUSINESS; WORKING-CLASS; CANCER PREVENTION; MULTIETHNIC
POPULATIONS; FORMATIVE RESEARCH; SCHOOL-PERSONNEL; ORAL-CANCER; 2
REGIONS; WORKERS; PSYCHOLOGY
AB This article provides a theory-based, step-by-step approach to intervention development and illustrates its application in India to design an intervention to promote tobacco-use cessation among school personnel in Bihar. We employed a five-step approach to develop the intervention using the Social Contextual Model of Health Behavior Change (SCM) in Bihar, which involved conducting formative research, classifying factors in the social environment as mediating mechanisms and modifying conditions, developing a creative brief, designing an intervention and refining the intervention based on pilot test results. The intervention engages users and non-users of tobacco, involves teachers in implementing and monitoring school tobacco control policies and maximizes teachers' role as change agents in schools and communities. Intervention components include health educator visits, discussions led by lead teachers, cessation assistance, posters and other educational materials and is implemented over the entire academic year. The intervention is being tested in Bihar government schools as part of a randomized-controlled trial. SCM was a useful framework for developing a tobacco control intervention that responded to teachers' lives in Bihar.
C1 [Nagler, Eve M.; Viswanath, Kasisomayajula; Sorensen, Glorian C.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA.
[Pednekar, Mangesh S.; Gupta, Prakash C.] Healis Sekhsaria Inst Publ Hlth, Navi Mumbai 400614, India.
[Sinha, Dhirendra N.] Sch Prevent Oncol, Patna 800001, Bihar, India.
[Aghi, Mira B.] Healis Sekhsaria Inst Publ Hlth, New Delhi 110016, India.
[Pischke, Claudia R.] Inst Epidemiol & Prevent Res BIPS, D-28359 Bremen, Germany.
[Ebbeling, Cara B.] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.
[Lando, Harry A.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN 55454 USA.
[Sorensen, Glorian C.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA.
RP Nagler, EM (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA.
EM eve_nagler@dfci.harvard.edu
FU NCI NIH HHS [5 K05 CA108663-05, 5R01CA120958-02, K05 CA108663, 2 R25
CA057713-06]
NR 52
TC 6
Z9 6
U1 2
U2 15
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0268-1153
J9 HEALTH EDUC RES
JI Health Educ. Res.
PD FEB
PY 2013
VL 28
IS 1
BP 113
EP 129
DI 10.1093/her/cys060
PG 17
WC Education & Educational Research; Public, Environmental & Occupational
Health
SC Education & Educational Research; Public, Environmental & Occupational
Health
GA 079EF
UT WOS:000314152400011
PM 22669010
ER
PT J
AU Flynn, AW
Afilalo, J
Agnihotri, AK
Castrillo, C
Shahian, DM
Picard, MH
AF Flynn, Aidan W.
Afilalo, Jonathan
Agnihotri, Arvind K.
Castrillo, Cristina
Shahian, David M.
Picard, Michael H.
TI Aortic sclerosis is associated with mortality and major morbidity in
patients undergoing coronary artery bypass surgery
SO HEART
LA English
DT Article
ID VALVE SCLEROSIS; ECHOCARDIOGRAPHIC-ASSESSMENT; ANNULAR CALCIFICATION;
EUROPEAN-ASSOCIATION; AMERICAN-SOCIETY; STENOSIS; DISEASE;
RECOMMENDATIONS; HEART; GUIDELINES
AB Objective In this study, we aim to investigate the association between aortic sclerosis and mortality and major morbidity in patients with established coronary artery disease undergoing coronary artery bypass grafting (CABG).
Design Preoperative echocardiograms of consecutive patients undergoing isolated CABG between 2007 and 2009 (n=1150) were analysed, excluding patients without an echocardiogram in the 30 days prior to surgery (n=483). Using logistic regression, we evaluated the association between aortic sclerosis and inhospital mortality and major morbidity. Using Cox proportional hazards, the effect on long-term all-cause mortality was determined.
Setting Massachusetts General Hospital, Boston.
Patients Patients undergoing isolated CABG between 2007 and 2009.
Interventions Analysis of echocardiograms.
Main outcome measures Inhospital mortality and major morbidity, and long-term all-cause mortality.
Results 627 patients were suitable for enrolment; 207 (33%) had significant aortic sclerosis. These patients had higher rates of traditional cardiovascular risk factors. Significant aortic sclerosis was associated with an increased risk of inhospital mortality or major morbidity (OR 1.95; 95% CI 1.25 to 3.04). Following adjustment for baseline clinical and echocardiographic variables, the association remained significant (OR 1.90; 95% CI 1.15 to 3.11). The HR for adjusted all-cause mortality was 2.52 (mean follow-up 2.7 years).
Conclusions Aortic sclerosis is a common finding in patients undergoing CABG. In these patients, its presence is associated with a higher risk of inhospital mortality or major morbidity, and is associated with a higher risk of all-cause long-term mortality independent of other risk factors.
C1 [Flynn, Aidan W.; Castrillo, Cristina; Picard, Michael H.] Harvard Univ, Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Div Cardiol, Boston, MA 02114 USA.
[Afilalo, Jonathan] McGill Univ, Jewish Gen Hosp, Div Cardiol, Montreal, PQ H3T 1E2, Canada.
[Afilalo, Jonathan] McGill Univ, Jewish Gen Hosp, Div Clin Epidemiol, Montreal, PQ H3T 1E2, Canada.
[Agnihotri, Arvind K.; Shahian, David M.] Harvard Univ, Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02115 USA.
[Shahian, David M.] Harvard Univ, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Shahian, David M.] Harvard Univ, Ctr Qual & Safety, Massachusetts Gen Hosp, Boston, MA 02115 USA.
RP Picard, MH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Div Cardiol, 55 Fruit St, Boston, MA 02114 USA.
EM mhpicard@partners.org
OI Picard, Michael/0000-0002-9264-3243
NR 25
TC 1
Z9 1
U1 0
U2 0
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1355-6037
J9 HEART
JI Heart
PD FEB
PY 2013
VL 99
IS 4
BP 247
EP 252
DI 10.1136/heartjnl-2012-302957
PG 6
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 079HR
UT WOS:000314161700006
PM 23213174
ER
PT J
AU Romero-Perez, L
Castilla, MA
Lopez-Garcia, MA
Diaz-Martin, J
Biscuola, M
Ramiro-Fuentes, S
Oliva, E
Matias-Guiu, X
Prat, J
Cano, A
Moreno-Bueno, G
Palacios, J
AF Romero-Perez, Laura
Angeles Castilla, Maria
Angeles Lopez-Garcia, Maria
Diaz-Martin, Juan
Biscuola, Michele
Ramiro-Fuentes, Susana
Oliva, Esther
Matias-Guiu, Xavier
Prat, Jaime
Cano, Amparo
Moreno-Bueno, Gema
Palacios, Jose
TI Molecular events in endometrial carcinosarcomas and the role of high
mobility group AT-hook 2 in endometrial carcinogenesis
SO HUMAN PATHOLOGY
LA English
DT Article
DE Endometrial carcinosarcoma; HMGA2; let-7b; Lin28B
ID EPITHELIAL-MESENCHYMAL TRANSITION; MIXED MULLERIAN TUMORS; UTERINE
CARCINOSARCOMAS; CANCER PROGRESSION; BREAST-CANCER; FACTOR BORIS; GENE
HMGA2; EXPRESSION; TRANSFORMATION; CARCINOMAS
AB The molecular events implicated in the development of endometrial carcinosarcoma remain poorly understood. Using complementary DNA microarrays, we analyzed a group of 15 endometrial carcinosarcomas and compared their gene expression profiles with those obtained from a group of 23 endometrioid endometrial carcinomas. We demonstrated changes in the expression of genes modulating processes such as the epithelial to mesenchymal transition, muscle differentiation, the expression of cancer/testis antigens, and immune response in endometrial carcinosarcomas. The high mobility group AT-hook 2 gene is an embryonic nuclear factor that mediates epithelial to mesenchymal transition in various tumor models, and it was among the genes overexpressed in endometrial carcinosarcomas. High mobility group AT-hook 2 overexpression was confirmed in 54% of endometrial carcinosarcomas by quantitative real time-polymerase chain reaction and immunohistochemistry. Moreover, we found, a significant inverse correlation between the expression of high mobility group AT-hook 2 and let-7b, a member of the let-7 family of microRNAs that represses high mobility group AT-hook 2 expression. These changes were also associated with overexpression of Lin28B, a suppressor of microRNA biogenesis that is implicated in cancer progression and metastasis. Finally, high mobility group AT-hook 2 overexpression, which was detected in less than 3% of endometrioid endometrial carcinomas, was observed in many nonendometrioid carcinomas (46% of 28 samples). This pattern of expression, restricted to nonendometrioid carcinomas and endometrial carcinosarcomas, reflects a role for high mobility group AT-hook 2 in endometrial carcinogenesis that is associated with aggressive phenotypes and points to its potential use as a marker to distinguish between endometrioid and nonendometrioid tumors. (c) 2013 Elsevier Inc. All rights reserved.
C1 [Romero-Perez, Laura; Angeles Castilla, Maria; Angeles Lopez-Garcia, Maria; Diaz-Martin, Juan; Biscuola, Michele; Ramiro-Fuentes, Susana; Palacios, Jose] Univ Seville, CSIC, Hosp Univ Virgen del Rocio, Inst Biomed Sevilla IBiS,Dept Pathol, Seville 41013, Spain.
[Oliva, Esther] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Matias-Guiu, Xavier] Univ Lleida, IRBLLEIDA, Hosp Univ Arnau de Vilanova, Dept Pathol & Mol Genet, Lleida 25198, Spain.
[Prat, Jaime] Hosp Santa Creu & Sant Pau, Dept Pathol, Barcelona 08025, Spain.
[Cano, Amparo; Moreno-Bueno, Gema] Inst Invest Sanitaria La Paz, Inst Invest Biomed Alberto Sols, Dept Bioquim, CSIC UAM,UAM,IdiPAZ, Madrid 28046, Spain.
[Moreno-Bueno, Gema] Fdn MD Anderson Canc Ctr Madrid, Madrid 28033, Spain.
[Palacios, Jose] Hosp Univ Ramon y Cajal, Dept Pathol, Madrid 28031, Spain.
RP Palacios, J (reprint author), Hosp Univ Ramon y Cajal, Dept Pathol, Calle Colmenar Viejo 9, Madrid 28031, Spain.
EM jose.palacios@salud.madrid.org
RI Romero-Perez, Laura/C-8314-2015; Castilla, M Angeles/C-9454-2015;
Diaz-Martin, Juan/F-4765-2015; IBIS, SARCOMAS/O-1893-2015; matias-guiu,
xavier/C-3039-2009; IBIS, NEUROPEPTIDOS/H-7482-2016; Moreno-Bueno,
Gema/K-9354-2016
OI Romero-Perez, Laura/0000-0003-3196-4382; matias-guiu,
xavier/0000-0002-7201-6605; Moreno-Bueno, Gema/0000-0002-5030-6687
FU Instituto de Salud Carlos III (ISCIII) [PI07/90324, PI080971];
Ministerio de Ciencia e Innovacion (MCINN); European Development
Regional Fund "A way to achieve Europe" EDRF [RD06/0020/0013]; Junta de
Andalucia (Consejeria de Salud) [PI-0384/2007, PI0581/2009]; Consejeria
de Innovacion (Proyecto de Excelencia) [P07-CVI-03100]; Asociacion
Espanola Contra el Cancer, Red de Grupos estables en Oncologia (AECC);
PFIS fellowship [F109/00193]; ISCIII [PI080971, RD06/0020/0013];
ISCIII-Red de Biobancos [RD09/0076/00085]; [FISPI10/00922];
[2009SGR794]; [RD06/0020/134]; [RD/0020/15]
FX This work was supported by grants from the Instituto de Salud Carlos III
(ISCIII; grant nos. PI07/90324 and PI080971) and the Ministerio de
Ciencia e Innovacion (MCINN), cofinanced by the European Development
Regional Fund "A way to achieve Europe" EDRF (grant no. RD06/0020/0013);
the Junta de Andalucia (Consejeria de Salud, grant nos. PI-0384/2007 and
PI0581/2009) and the Consejeria de Innovacion (Proyecto de Excelencia,
grant no. P07-CVI-03100) to J. Pa.; grants FISPI10/00922, 2009SGR794,
and RD06/0020/134 to X. M-G. and RD/0020/15 to J. Pr.; and by a grant
from the Asociacion Espanola Contra el Cancer, Red de Grupos estables en
Oncologia (AECC-2011) to X. M-G., J. Pr., and G. M-B. L. R-P. is a PhD
student and a recipient of a PFIS fellowship (grant no. F109/00193). M.
A. C. and J. D. are PhD researchers funded by the ISCIII (grant no.
RD06/0020/0013) and the Consejeria de Salud de la Junta de Andalucia
(PI0581/2009), respectively. M. B. is a researcher funded by the
ISCIII-Red de Biobancos RD09/0076/00085. S. R-F. works as a laboratory
technician supported by the ISCIII (PI080971). Tumor samples were
obtained with the support of Xarxa Catalana de Bancs de Tumors, the
Tumor Bank Platform of RTICC RD09/0076/00085 and RD09/0076/00059.
NR 35
TC 14
Z9 14
U1 0
U2 21
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0046-8177
J9 HUM PATHOL
JI Hum. Pathol.
PD FEB
PY 2013
VL 44
IS 2
BP 244
EP 254
DI 10.1016/j.humpath.2012.05.013
PG 11
WC Pathology
SC Pathology
GA 082HM
UT WOS:000314382900011
PM 22974476
ER
PT J
AU Rosado, FGN
Tang, YW
Hasserjian, RP
McClain, CM
Wang, B
Mosse, CA
AF Rosado, Flavia Guimaraes Nunes
Tang, Yi-Wei
Hasserjian, Robert Paul
McClain, Colt M.
Wang, Beverly
Mosse, Claudio A.
TI Kikuchi-Fujimoto lymphadenitis: role of parvovirus B-19, Epstein-Barr
virus, human herpesvirus 6, and human herpesvirus 8
SO HUMAN PATHOLOGY
LA English
DT Article
DE Kikuchi-Fugimoto; Viral; Lymphadenitis; Etiology; PCR; Parvovirus B-19;
EBV; HHV-6; HHV-8
ID HISTIOCYTIC NECROTIZING LYMPHADENITIS; SYSTEMIC-LUPUS-ERYTHEMATOSUS;
REAL-TIME PCR; DISEASE; B19; DNA; INFECTION; CHILDREN
AB Kikuchi-Fujimoto lymphadenitis is a self-limited disorder that typically presents in young females as painless cervical lymphadenopathy with fever, anemia, and leukopenia. The clinical manifestations and pathologic findings suggest a viral etiology, yet specific etiologic agents remain unknown. Although there are studies reporting positive associations between Kikuchi-Fujimoto lymphadenitis and parvovirus B19 and herpesviruses, other studies have failed to find an association with these viruses. To our knowledge, this current study is the largest study of Kikuchi-Fujimoto lymphadenitis in Western patients that used polymerase chain reaction testing for 4 different common viral pathogens often implicated as etiologic agents in Kikuchi-Fujimoto lymphadenitis. Archival material from 3 institutions was included, following confirmation of the diagnosis of Kikuchi-Fujimoto lymphadenitis by 2 independent pathologists. Polymerase chain reaction from the paraffin-embedded tissue sections for parvovirus B19, Epstein-Barr virus, human herpesvirus 6, and human herpesvirus 8 was performed. Eighteen cases of Kikuchi-Fujimoto lymphadenitis were analyzed, 12 of which (60%) were cervical lymph nodes. All the cases showed typical geographic necrosis with abundant apoptotic debris, although the degree of necrosis was variable. Polymerase chain reaction revealed a high prevalence of parvovirus B19 in the controls (44%); there were fewer positive cases seen in the Kikuchi-Fujimoto lymphadenitis cases (11%), but this did not reach statistical significance (P = .25).There were no significant differences between cases and controls in the prevalence of Epstein-Barr virus, human herpesvirus 6, and human herpesvirus 8 (P = .50 for all 3). Polymerase chain reaction failed to reveal a positive association between Kikuchi-Fujimoto lymphadenitis and 4 common suspected viral agents. These findings do not support a role for Epstein-Barr virus, human herpesvirus 6, human herpesvirus 8, or parvovirus B19 in the pathogenesis of Kikuchi-Fujimoto lymphadenitis. (c) 2013 Elsevier Inc. All rights reserved.
C1 [Rosado, Flavia Guimaraes Nunes; McClain, Colt M.; Mosse, Claudio A.] Vanderbilt Univ, Med Ctr, Dept Pathol, Nashville, TN 37232 USA.
[Tang, Yi-Wei] Mem Sloan Kettering Canc Ctr, Dept Lab Med, New York, NY 10065 USA.
[Hasserjian, Robert Paul] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Wang, Beverly] NYU, Dept Pathol, New York, NY 10016 USA.
[Mosse, Claudio A.] VA Tennessee Valley Healthcare Syst, Pathol & Lab Med, Nashville, TN 37212 USA.
RP Rosado, FGN (reprint author), Vanderbilt Univ, Med Ctr, Dept Pathol, Nashville, TN 37232 USA.
EM flaviarosado21@gmail.com
OI Tang, Yi-Wei/0000-0003-4888-6771
NR 30
TC 12
Z9 15
U1 0
U2 3
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0046-8177
J9 HUM PATHOL
JI Hum. Pathol.
PD FEB
PY 2013
VL 44
IS 2
BP 255
EP 259
DI 10.1016/j.humpath.2012.05.016
PG 5
WC Pathology
SC Pathology
GA 082HM
UT WOS:000314382900012
PM 22939574
ER
PT J
AU Babadi, B
Tarokh, V
AF Babadi, Behtash
Tarokh, Vahid
TI Spectral Distribution of Product of Pseudorandom Matrices Formed From
Binary Block Codes
SO IEEE TRANSACTIONS ON INFORMATION THEORY
LA English
DT Article
DE Binary block codes; free probability theory; Levy distance;
Marchenko-Pastur law; pseudorandom matrices; random matrix theory
ID EIGENVALUES
AB Let A is an element of {-1, 1}(Naxn) and B is an element of {-1, 1}(Nbxn) be two matrices whose rows are drawn i.i.d. from the codewords of the binary codes C-a and C-b of length n and dual distances d'a and d'b, respectively, under the mapping 0 bar right arrow 1 and 1 bar right arrow -1. It is proven that as n -> infinity with y(a) := n/N-a is an element of (0, infinity) and y(b) ; = n/Nb is an element of (0, infinity) fixed, the empirical spectral distribution of the matrix AB*/root NaNb resembles a universal distribution (closely related to the distribution function of the free multiplicative convolution of two members of the Marchenko-Pastur family of densities) in the sense of the Levy distance, if the asymptotic dual distances of the underlying binary codes are large enough. Moreover, an explicit upper bound on the Levy distance of the two distributions in terms of y(a), y(b), d'(a) and d'(b) is given. Under mild conditions, the upper bound is strengthened to the Kolmogorov distance of the underlying distributions. Numerical studies on the empirical spectral distribution of the product of random matrices from BCH and Gold codes are provided, which verify the validity of this result.
C1 [Babadi, Behtash] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
[Babadi, Behtash] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA.
[Babadi, Behtash; Tarokh, Vahid] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
RP Babadi, B (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
EM behtash@nmr.mgh.harvard.edu; vahid@seas.harvard.edu
FU John Simon Guggenheim Memorial Foundation
FX This work was supported in part by a fellowship from the John Simon
Guggenheim Memorial Foundation. The material in this paper was presented
in part at the 2011 Allerton Conference on Communication, Control, and
Computing, Monticello, IL [3].
NR 20
TC 1
Z9 1
U1 1
U2 7
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 0018-9448
EI 1557-9654
J9 IEEE T INFORM THEORY
JI IEEE Trans. Inf. Theory
PD FEB
PY 2013
VL 59
IS 2
BP 970
EP 978
DI 10.1109/TIT.2012.2223812
PG 9
WC Computer Science, Information Systems; Engineering, Electrical &
Electronic
SC Computer Science; Engineering
GA 073FL
UT WOS:000313728800017
ER
PT J
AU Richter, LL
Miller, RM
Hillman, JD
Chiu, MW
AF Richter, Laura L.
Miller, Robert M.
Hillman, Joseph D.
Chiu, Melvin W.
TI Bilateral thick crusts on the legs
SO INTERNATIONAL JOURNAL OF DERMATOLOGY
LA English
DT Editorial Material
ID DERMATITIS NEGLECTA
AB What is your diagnosis?
C1 [Chiu, Melvin W.] Univ Calif Los Angeles, David Geffen Sch Med, Div Dermatol, Dept Med,Ctr Hlth Sci 52 121, Los Angeles, CA 90095 USA.
[Hillman, Joseph D.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA.
[Miller, Robert M.; Chiu, Melvin W.] W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA USA.
RP Chiu, MW (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Dermatol, Dept Med,Ctr Hlth Sci 52 121, 10833 Le Conte Ave, Los Angeles, CA 90095 USA.
EM mchiu@mednet.ucla.edu
NR 10
TC 1
Z9 1
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0011-9059
J9 INT J DERMATOL
JI Int. J. Dermatol.
PD FEB
PY 2013
VL 52
IS 2
BP 133
EP 135
DI 10.1111/j.1365-4632.2012.05678.x
PG 3
WC Dermatology
SC Dermatology
GA 077ZW
UT WOS:000314068900002
PM 23347299
ER
PT J
AU Worley, MJ
Nitschmann, CC
Shoni, M
Rauh-Hain, JA
Williams, KA
Feltmate, CM
AF Worley, Michael J., Jr.
Nitschmann, Caroline C.
Shoni, Melina
Rauh-Hain, Jose Alejandro
Williams, Kristina A.
Feltmate, Colleen M.
TI Preoperative Leukocytosis Imposes an Increased Risk of Recurrence and
Death Among Patients With Nonendometrioid Endometrial Carcinoma
SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER
LA English
DT Article
DE Nonendometrioid; Endometrial carcinoma; Preoperative leukocytosis
ID COLONY-STIMULATING FACTOR; PAPILLARY SEROUS CARCINOMA; POOR-PROGNOSIS;
CELL CARCINOMA; CANCER; CERVIX; CORPUS
AB Objective: To evaluate the impact of preoperative leukocytosis among patients with nonendometrioid endometrial carcinoma.
Methods: The medical records of all patients with nonendometrioid endometrial carcinoma who underwent surgical treatment between January 2005 and December 2010 were retrospectively reviewed. The patients were separated into 2 groups based on the presence or absence of preoperative leukocytosis (white blood cell count >= 10,000/mu L). The groups were then compared with respect to pathologic findings, progression-free survival, and overall survival.
Results: A total of 222 patients were identified, and preoperative leukocytosis was observed in 33 patients (14.9%). The leukocytosis group was associated with a larger mean size of the primary tumor (6.8 vs 4.6 cm, P = 0.016) and a greater percentage of patients with cervical stromal involvement (36.4% vs 20.1%, P = 0.039), adnexal involvement (42.4% vs. 22.8%, P = 0.017), and pelvic/para-aortic lymph node involvement (50% vs 27.4%, P = 0.025). On multivariate analysis, preoperative leukocytosis was independently associated with an increased risk of recurrence (hazard ratio, 2.07; 95% confidence interval, 1.12-3.84) and an increased risk of death (hazard ratio, 3.33; 95% confidence interval, 2.01-5.53).
Conclusions: Among patients with nonendometrioid endometrial carcinoma, preoperative leukocytosis is independently associated with an increased risk of recurrence and death.
C1 [Worley, Michael J., Jr.; Shoni, Melina; Feltmate, Colleen M.] Brigham & Womens Hosp, Div Gynecol Oncol, Boston, MA 02115 USA.
[Nitschmann, Caroline C.] Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA.
[Rauh-Hain, Jose Alejandro] Massachusetts Gen Hosp, Div Gynecol Oncol Vincent Obstet & Gynecol, Boston, MA 02114 USA.
[Williams, Kristina A.] Harvard Univ, Sch Med, Boston, MA USA.
RP Feltmate, CM (reprint author), Brigham & Womens Hosp, Div Gynecol Oncol, 75 Francis St, Boston, MA 02115 USA.
EM cfeltmate@partners.org
NR 21
TC 4
Z9 4
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1048-891X
J9 INT J GYNECOL CANCER
JI Int. J. Gynecol. Cancer
PD FEB
PY 2013
VL 23
IS 2
BP 312
EP 317
DI 10.1097/IGC.0b013e31827da21b
PG 6
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 080ZW
UT WOS:000314284900015
PM 23358179
ER
PT J
AU Wasse, H
Zhang, R
Johansen, KL
Kutner, N
AF Wasse, Haimanot
Zhang, Rebecca
Johansen, Kirsten L.
Kutner, Nancy
TI ESRD patients using permanent vascular access report greater physical
activity compared with catheter users
SO INTERNATIONAL UROLOGY AND NEPHROLOGY
LA English
DT Article
DE Dialysis vascular access; Physical function
ID STAGE RENAL-DISEASE; AMBULATORY PATIENTS; DIALYSIS PATIENTS;
HEMODIALYSIS; MORTALITY; SURVIVAL; EXERCISE; WAVE-2
AB Low levels of physical activity among end-stage renal disease (ESRD) patients are associated with increased risk of hospitalization and mortality, and contributors to low activity levels are important to identify. Among hemodialysis (HD) patients, use of a central venous catheter (CVC) might impede physical activity due to factors such as infection or patient fear of catheter dislodgement.
This Comprehensive Dialysis Study surveyed patients who had recently started regular dialysis. Physical activity level was ascertained using responses to the Human Activity Profile (HAP) provided by 1,458 HD participants. We examined the association of vascular access type with patients' scores on HAP subscales measuring self-care and leg effort, two dimensions that are especially important for daily living.
32.6% of patients used an arteriovenous fistula (AVF), 11.5% used an arteriovenous graft, 51.8% used a CVC, and 4.1% used a CVC with another maturing access. Patients' self-care and leg effort scores differed by vascular access type and receipt of early nephrology care, and the mean self-care score of AVF users who received early care was similar to the mean score reported for healthy adults.
Reported levels of self-care and leg effort activity were higher among incident HD patients using an AVF compared to those using a CVC. Future research should examine whether reinforcing the importance of regular physical activity in the pre-dialysis period, as well as wider early use of AVF in the HD population, may improve physical activity levels among ESRD patients.
C1 [Wasse, Haimanot] Emory Univ, Sch Med, Div Nephrol, WMB, Atlanta, GA 30322 USA.
[Wasse, Haimanot; Zhang, Rebecca; Johansen, Kirsten L.; Kutner, Nancy] Emory Univ, Rehabil Qual Life Special Studies Ctr, US Renal Data Syst, Atlanta, GA 30322 USA.
[Johansen, Kirsten L.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Johansen, Kirsten L.] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA.
[Johansen, Kirsten L.] Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94143 USA.
[Johansen, Kirsten L.] San Francisco VA Med Ctr, Nephrol Sect, San Francisco, CA USA.
RP Wasse, H (reprint author), Emory Univ, Sch Med, Div Nephrol, WMB, Room 338,1639 Pierce Dr, Atlanta, GA 30322 USA.
EM hwasse@emory.edu
FU National Institutes of Health [K23 DK65634, HHSN267200715004C,
N01-DK-7-5004]
FX The human activity profile was reproduced for use in the CDS with
permission of the author, David Daughton. This work was supported in
part by a National Institutes of Health Career Development Award K23
DK65634 (Haimanot Wasse) and by National Institutes of Health contract
HHSN267200715004C, ADB No. N01-DK-7-5004.
NR 15
TC 1
Z9 1
U1 0
U2 2
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0301-1623
J9 INT UROL NEPHROL
JI Int. Urol. Nephrol.
PD FEB
PY 2013
VL 45
IS 1
BP 199
EP 205
DI 10.1007/s11255-012-0137-9
PG 7
WC Urology & Nephrology
SC Urology & Nephrology
GA 081CD
UT WOS:000314292500030
PM 22350837
ER
PT J
AU Aston-Mourney, K
Zraika, S
Udayasankar, J
Subramanian, SL
Green, PS
Kahn, SE
Hull, RL
AF Aston-Mourney, Kathryn
Zraika, Sakeneh
Udayasankar, Jayalakshmi
Subramanian, Shoba L.
Green, Pattie S.
Kahn, Steven E.
Hull, Rebecca L.
TI Matrix Metalloproteinase-9 Reduces Islet Amyloid Formation by Degrading
Islet Amyloid Polypeptide
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID BETA-CELL APOPTOSIS; DIABETES-MELLITUS; TRANSGENIC MOUSE;
PANCREATIC-ISLETS; FIBRIL FORMATION; HUMAN AMYLIN; PEPTIDE; MICE;
INSULIN; HYPERGLYCEMIA
AB Deposition of islet amyloid polypeptide ( IAPP) as amyloid is a pathological hallmark of the islet in type 2 diabetes, which is toxic to beta-cells. We previously showed that the enzyme neprilysin reduces islet amyloid deposition and thereby reduces beta-cell apoptosis, by inhibiting fibril formation. Two other enzymes, matrix metalloproteinase ( MMP)-2 and MMP-9, are extracellular gelatinases capable of degrading another amyloidogenic peptide, A beta, the constituent of amyloid deposits in Alzheimer disease. We therefore investigated whether MMP-2 and MMP-9 play a role in reducing islet amyloid deposition. MMP-2 and MMP-9 mRNA were present in mouse islets but only MMP-9 activity was detectable. In an islet culture model where human IAPP ( hIAPP) transgenic mouse islets develop amyloid but nontransgenic islets do not, a broad spectrum MMP inhibitor ( GM6001) and an MMP-2/9 inhibitor increased amyloid formation and the resultant beta-cell apoptosis. In contrast, a specific MMP-2 inhibitor had no effect on either amyloid deposition or beta-cell apoptosis. Mass spectrometry demonstrated that MMP-9 degraded amyloidogenic hIAPP but not nonamyloidogenic mouse IAPP. Thus, MMP-9 constitutes an endogenous islet protease that limits islet amyloid deposition and its toxic effects via degradation of hIAPP. Because islet MMP-9 mRNA levels are decreased in type 2 diabetic subjects, islet MMP-9 activity may also be decreased in human type 2 diabetes, thereby contributing to increased islet amyloid deposition and beta-cell loss. Approaches to increase islet MMP-9 activity could reduce or prevent amyloid deposition and its toxic effects in type 2 diabetes.
C1 [Aston-Mourney, Kathryn; Zraika, Sakeneh; Udayasankar, Jayalakshmi; Subramanian, Shoba L.; Green, Pattie S.; Kahn, Steven E.; Hull, Rebecca L.] Vet Affairs Puget Sound Hlth Care Syst, Washington, WA 98108 USA.
[Aston-Mourney, Kathryn; Zraika, Sakeneh; Udayasankar, Jayalakshmi; Subramanian, Shoba L.; Green, Pattie S.; Kahn, Steven E.; Hull, Rebecca L.] Univ Washington, Dept Med, Seattle, WA 98195 USA.
[Aston-Mourney, Kathryn] Deakin Univ, Sch Med, Metab Res Unit, Waurn Ponds, Vic 3216, Australia.
RP Hull, RL (reprint author), VA Puget Sound Hlth Care Syst, 1660 S Columbian Way 151, Seattle, WA 98108 USA.
EM rhull@u.washington.edu
OI Aston-Mourney, Kathryn/0000-0003-1412-6715; Kahn,
Steven/0000-0001-7307-9002; Hull, Rebecca/0000-0001-9690-4087
FU Department of Veterans Affairs, Veterans Affairs Puget Sound Health Care
System (Seattle, WA); National Institutes of Health [DK-075998,
DK-074404, DK-080945, DK-017047, DK-007247]; American Diabetes
Association Mentor-Based fellowship; University of Washington McAbee
fellowship; Deakin University Alfred Deakin Postdoctoral research
fellowship; Juvenile Diabetes Research Foundation
FX This work was supported, in whole or in part, by the Department of
Veterans Affairs, Veterans Affairs Puget Sound Health Care System
(Seattle, WA) and National Institutes of Health Grants DK-075998 (to S.
E. K.), DK-074404 (to R. L. H.), DK-080945 (to S. Z.), DK-017047 (to the
Cellular and Molecular Imaging Core of the University of Washington
Diabetes Research Center), and DK-007247.; Supported by an American
Diabetes Association Mentor-Based fellowship, the University of
Washington McAbee fellowship, and a Deakin University Alfred Deakin
Postdoctoral research fellowship.; Supported by a Juvenile Diabetes
Research Foundation postdoctoral fellowship.
NR 36
TC 12
Z9 13
U1 0
U2 22
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 FEB 1
PY 2013
VL 288
IS 5
BP 3553
EP 3559
DI 10.1074/jbc.M112.438457
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 082NE
UT WOS:000314397900060
PM 23229548
ER
PT J
AU Bloch, MJ
Basile, JN
AF Bloch, Michael J.
Basile, Jan N.
TI Analysis of Recent Papers in Hypertension Treatment of Obstructive Sleep
Apnea With Continuous Positive Airway Pressure Appears to Decrease the
Incidence of Incident Hypertension
SO JOURNAL OF CLINICAL HYPERTENSION
LA English
DT Article
ID ASSOCIATION
C1 [Bloch, Michael J.] Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Seinsheimer Cardiovasc Hlth Program, Div Gen Internal Med Geriatr, Charleston, SC 29425 USA.
[Bloch, Michael J.] Univ Nevada, Sch Med, MedSch Associates N, Dept Internal Med, Reno, NV 89520 USA.
RP Bloch, MJ (reprint author), Univ Nevada, Sch Med, MedSch Associates N, Dept Internal Med, 1500 E 2nd St,Suite 302, Reno, NV 89520 USA.
EM mbloch@aol.com
NR 4
TC 1
Z9 1
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1524-6175
J9 J CLIN HYPERTENS
JI J. Clin. Hypertens.
PD FEB
PY 2013
VL 15
IS 2
BP 85
EP 87
DI 10.1111/jch.12041
PG 3
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 075PX
UT WOS:000313900100001
PM 23339724
ER
PT J
AU Wiederhold, NP
Najvar, LK
Bocanegra, R
Kirkpatrick, WR
Patterson, TF
Thornton, CR
AF Wiederhold, Nathan P.
Najvar, Laura K.
Bocanegra, Rosie
Kirkpatrick, William R.
Patterson, Thomas F.
Thornton, Christopher R.
TI Interlaboratory and Interstudy Reproducibility of a Novel Lateral-Flow
Device and Influence of Antifungal Therapy on Detection of Invasive
Pulmonary Aspergillosis
SO JOURNAL OF CLINICAL MICROBIOLOGY
LA English
DT Article
ID GALACTOMANNAN ENZYME-IMMUNOASSAY; NEUTROPENIC PATIENTS; RAPID
SERODIAGNOSIS; MURINE MODEL; DIAGNOSIS; ASSAY; HIV; ANTIBODIES;
FUMIGATUS
AB Interest in lateral-flow devices (LFDs) as potential point-of-care assays for the diagnosis of infectious diseases has increased. Our objective was to evaluate the interlaboratory and interstudy reproducibility and the effects of antifungal therapy on an LFD developed for invasive pulmonary aspergillosis (IPA) detection. An established neutropenic guinea pig model of IPA caused by Aspergillus fumigatus was used. At predetermined time points (1 h and 3, 5, and 7 days postinoculation), blood and bronchoalveolar lavage (BAL) fluid were collected from infected and uninfected animals. In a separate experiment, guinea pigs were treated with posaconazole (10 mg/kg of body weight orally [p.o.] twice a day [BID]), voriconazole (10 mg/kg p.o. BID), liposomal amphotericin B (10 mg/kg intraperitoneally [i.p.] once a day [QD]), or caspofungin (2 mg/kg i.p. QD), and samples were collected on days 7 and 11. Each laboratory independently evaluated the IgG monoclonal antibody-based LFD. Galactomannan and (1 -> 3)-beta-D-glucan were also measured using commercially available kits. Good interlaboratory agreement was observed with the LFD, as the results for 97% (32/33) of the serum and 78.8% (26/33) of the BAL fluid samples from infected animals were in agreement. Good interstudy agreement was also observed. The serum sensitivity of each surrogate-marker assay was reduced in animals treated with antifungals. In contrast, these markers remained elevated within the BAL fluids of treated animals, which was consistent with the fungal burden and histopathology results. These results demonstrate that the LFD assay is reproducible between different laboratories and studies. However, the sensitivity of this assay and other markers of IPA may be reduced with serum in the presence of antifungal therapy.
C1 [Wiederhold, Nathan P.; Najvar, Laura K.; Bocanegra, Rosie; Kirkpatrick, William R.; Patterson, Thomas F.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Wiederhold, Nathan P.] Univ Texas Austin, Coll Pharm, Austin, TX 78712 USA.
[Najvar, Laura K.; Bocanegra, Rosie; Kirkpatrick, William R.; Patterson, Thomas F.] S Texas Vet Hlth Care Syst, San Antonio, TX USA.
[Thornton, Christopher R.] Univ Exeter, Exeter, Devon, England.
RP Wiederhold, NP (reprint author), Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
EM wiederholdn@uthscsa.edu
OI Wiederhold, Nathan/0000-0002-2225-5122
FU National Institutes of Health/National Institute of Allergy and
Infectious Diseases (NIH/NIAID) [N01-AI-30041,
HHSN272201000038I/HHSN27200002-task order A05, R21AI085393]; Pfizer;
Schering-Plough; Merck; Basilea; Astellas
FX This work was supported by contracts from the National Institutes of
Health/National Institute of Allergy and Infectious Diseases (NIH/NIAID;
contract numbers N01-AI-30041 and HHSN272201000038I/HHSN27200002-task
order A05) to T. F. Patterson and NIH/NIAID grant R21AI085393 to N. P.
Wiederhold and C. R. Thornton.; N.P.W. has received research support
from Pfizer, Schering-Plough, Merck, Basilea, and Astellas and has
served on advisory boards for Merck, Astellas, Toyama, and Viamet.
T.F.P. has received research grants to the UT Health Science Center at
San Antonio from Astellas, Basilea, Merck, and Pfizer and has served as
a consultant for Astellas, Basilea, Merck, Pfizer, and Toyama. C.R.T.
has received support from Pfizer. None of the other authors has a
conflict of interest.
NR 26
TC 28
Z9 30
U1 0
U2 14
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0095-1137
J9 J CLIN MICROBIOL
JI J. Clin. Microbiol.
PD FEB
PY 2013
VL 51
IS 2
BP 459
EP 465
DI 10.1128/JCM.02142-12
PG 7
WC Microbiology
SC Microbiology
GA 078OH
UT WOS:000314108000012
PM 23175252
ER
PT J
AU Kulke, MH
AF Kulke, Matthew H.
TI Are Neuroendocrine Tumors Going Mainstream?
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Editorial Material
ID ENDOCRINE TUMORS; GRADING SYSTEM; CLASSIFICATION
C1 Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Kulke, MH (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA.
FU NCI NIH HHS [R01 CA151532]
NR 17
TC 5
Z9 6
U1 0
U2 3
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 FEB 1
PY 2013
VL 31
IS 4
BP 404
EP 405
DI 10.1200/JCO.2012.47.3884
PG 2
WC Oncology
SC Oncology
GA 078LG
UT WOS:000314099800004
PM 23248246
ER
PT J
AU Zhu, AX
Salem, R
AF Zhu, Andrew X.
Salem, Riad
TI Combining Transarterial Chemoembolization With Radiofrequency Ablation
for Hepatocellular Carcinoma: One Step Forward?
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Editorial Material
ID RANDOMIZED CONTROLLED-TRIAL; TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION;
ETHANOL INJECTION; PHASE-II; THERAPY; SORAFENIB; SURVIVAL; COMBINATION;
RADIOEMBOLIZATION; LIVER
C1 [Zhu, Andrew X.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA.
Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA.
RP Zhu, AX (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA.
NR 28
TC 6
Z9 8
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 FEB 1
PY 2013
VL 31
IS 4
BP 406
EP 408
DI 10.1200/JCO.2012.46.1897
PG 3
WC Oncology
SC Oncology
GA 078LG
UT WOS:000314099800005
PM 23269989
ER
PT J
AU Smith, DC
Smith, MR
Sweeney, C
Elfiky, AA
Logothetis, C
Corn, PG
Vogelzang, NJ
Small, EJ
Harzstark, AL
Gordon, MS
Vaishampayan, UN
Haas, NB
Spira, AI
Lara, PN
Lin, CC
Srinivas, S
Sella, A
Schoffski, P
Scheffold, C
Weitzman, AL
Hussain, M
AF Smith, David C.
Smith, Matthew R.
Sweeney, Christopher
Elfiky, Aymen A.
Logothetis, Christopher
Corn, Paul G.
Vogelzang, Nicholas J.
Small, Eric J.
Harzstark, Andrea L.
Gordon, Michael S.
Vaishampayan, Ulka N.
Haas, Naomi B.
Spira, Alexander I.
Lara, Primo N., Jr.
Lin, Chia-Chi
Srinivas, Sandy
Sella, Avishay
Schoeffski, Patrick
Scheffold, Christian
Weitzman, Aaron L.
Hussain, Maha
TI Cabozantinib in Patients With Advanced Prostate Cancer: Results of a
Phase II Randomized Discontinuation Trial
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; LEUKEMIA GROUP-B; C-MET;
PROGNOSTIC-SIGNIFICANCE; EXPRESSION; METASTASIS; INHIBITOR; RECEPTOR;
VEGF; ANGIOGENESIS
AB Purpose Cabozantinib (XL184) is an orally bioavailable tyrosine kinase inhibitor with activity against MET and vascular endothelial growth factor receptor 2. We evaluated the activity of cabozantinib in patients with castration-resistant prostate cancer (CRPC) in a phase II randomized discontinuation trial with an expansion cohort.
Patients and Methods Patients received 100 mg of cabozantinib daily. Those with stable disease per RECIST at 12 weeks were randomly assigned to cabozantinib or placebo. Primary end points were objective response rate at 12 weeks and progression-free survival (PFS) after random assignment.
Results One hundred seventy-one men with CRPC were enrolled. Random assignment was halted early based on the observed activity of cabozantinib. Seventy-two percent of patients had regression in soft tissue lesions, whereas 68% of evaluable patients had improvement on bone scan, including complete resolution in 12%. The objective response rate at 12 weeks was 5%, with stable disease in 75% of patients. Thirty-one patients with stable disease at week 12 were randomly assigned. Median PFS was 23.9 weeks (95% CI, 10.7 to 62.4 weeks) with cabozantinib and 5.9 weeks (95% CI, 5.4 to 6.6 weeks) with placebo (hazard ratio, 0.12; P < .001). Serum total alkaline phosphatase and plasma cross-linked C-terminal telopeptide of type I collagen were reduced by >= 50% in 57% of evaluable patients. On retrospective review, bone pain improved in 67% of evaluable patients, with a decrease in narcotic use in 56%. The most common grade 3 adverse events were fatigue (16%), hypertension (12%), and hand-foot syndrome (8%).
Conclusion Cabozantinib has clinical activity in men with CRPC, including reduction of soft tissue lesions, improvement in PFS, resolution of bone scans, and reductions in bone turnover markers, pain, and narcotic use. J Clin Oncol 31:412-419. (C) 2012 by American Society of Clinical Oncology
C1 [Smith, David C.; Hussain, Maha] Univ Michigan, Ann Arbor, MI 48109 USA.
[Vaishampayan, Ulka N.] Wayne State Univ, Detroit, MI USA.
[Smith, Matthew R.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Sweeney, Christopher; Elfiky, Aymen A.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Logothetis, Christopher; Corn, Paul G.] Univ Texas MD Anderson Canc Ctr, Houston, TX USA.
[Spira, Alexander I.] US Oncol Res, Houston, TX USA.
[Vogelzang, Nicholas J.] US Oncol Comprehens Canc Ctr Nevada, Las Vegas, NV USA.
[Small, Eric J.; Harzstark, Andrea L.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Scheffold, Christian; Weitzman, Aaron L.] Exelixis, San Francisco, CA USA.
[Lara, Primo N., Jr.] Univ Calif Davis, Ctr Comprehens Canc, Sacramento, CA 95817 USA.
[Srinivas, Sandy] Stanford Univ, Med Ctr, Stanford, CA 94305 USA.
[Gordon, Michael S.] Pinnacle Oncol Hematol, Scottsdale, AZ USA.
[Haas, Naomi B.] Abramson Canc Ctr, Philadelphia, PA USA.
[Spira, Alexander I.] Virginia Canc Specialists, Fairfax, VA USA.
[Lin, Chia-Chi] Natl Taiwan Univ Hosp, Taipei, Taiwan.
[Sella, Avishay] Assaf Harofeh Med Ctr, IL-70300 Zerifin, Israel.
[Schoeffski, Patrick] Katholieke Univ Leuven, Univ Hosp Leuven, Louvain, Belgium.
RP Smith, DC (reprint author), 7302 CC SPC 5946,1500 Med Ctr Dr, Ann Arbor, MI 48109 USA.
EM dcsmith@umich.edu
FU Exelixis, South San Francisco, CA; Exelixis; Bayer
Pharmaceuticals/Algeta; Progenics Pharmaceuticals; Tokai
Pharmaceuticals; Johnson Johnson; Veridex; Astellas Pharma; Dendreon;
sanofi-aventis; Biotechnology/Janssen Pharmaceutica; Genentech;
GlaxoSmithKline; Pfizer; Polaris Group
FX Supported by Exelixis, South San Francisco, CA.; David C. Smith,
Exelixis; Matthew R. Smith, Exelixis; Christopher Sweeney, Exelixis;
Christopher Logothetis, Exelixis; Nicholas J. Vogelzang, Exelixis, Bayer
Pharmaceuticals/Algeta, Progenics Pharmaceuticals, Tokai
Pharmaceuticals, Johnson & Johnson, Veridex, Astellas Pharma, Dendreon,
sanofi-aventis; Michael S. Gordon, Exelixis; Primo N. Lara Jr, Cougar
Biotechnology/Janssen Pharmaceutica, Exelixis, Genentech,
GlaxoSmithKline, Pfizer, Polaris Group
NR 28
TC 205
Z9 212
U1 0
U2 32
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 FEB 1
PY 2013
VL 31
IS 4
BP 412
EP 419
DI 10.1200/JCO.2012.45.0494
PG 8
WC Oncology
SC Oncology
GA 078LG
UT WOS:000314099800007
PM 23169517
ER
PT J
AU San Miguel, JF
Schlag, R
Khuageva, NK
Dimopoulos, MA
Shpilberg, O
Kropff, M
Spicka, I
Petrucci, MT
Palumbo, A
Samoilova, OS
Dmoszynska, A
Abdulkadyrov, KM
Delforge, M
Jiang, B
Mateos, MV
Anderson, KC
Esseltine, DL
Liu, K
Deraedt, W
Cakana, A
van de Velde, H
Richardson, PG
AF San Miguel, Jesus F.
Schlag, Rudolf
Khuageva, Nuriet K.
Dimopoulos, Meletios A.
Shpilberg, Ofer
Kropff, Martin
Spicka, Ivan
Petrucci, Maria Teresa
Palumbo, Antonio
Samoilova, Olga S.
Dmoszynska, Anna
Abdulkadyrov, Kudrat M.
Delforge, Michel
Jiang, Bin
Mateos, Maria-Victoria
Anderson, Kenneth C.
Esseltine, Dixie-Lee
Liu, Kevin
Deraedt, William
Cakana, Andrew
van de Velde, Helgi
Richardson, Paul G.
TI Persistent Overall Survival Benefit and No Increased Risk of Second
Malignancies With Bortezomib-Melphalan-Prednisone Versus
Melphalan-Prednisone in Patients With Previously Untreated Multiple
Myeloma
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID STEM-CELL TRANSPLANTATION; INTERNATIONAL STAGING SYSTEM; LONG-TERM
SURVIVAL; ELDERLY-PATIENTS; PLUS THALIDOMIDE; RANDOMIZED-TRIAL;
CYTOGENETIC ABNORMALITIES; INDUCTION THERAPY; ACUTE-LEUKEMIA; PHASE-III
AB Purpose
This final analysis of the phase III VISTA trial (Velcade As Initial Standard Therapy in Multiple Myeloma: Assessment With Melphalan and Prednisone) was conducted to determine whether the overall survival (OS) benefit with bortezomib-melphalan-prednisone (VMP) versus melphalan-prednisone (MP) in patients with myeloma who were ineligible for transplantation was maintained after 5 years of follow-up and to explore the risk of second primary malignancies.
Patients and Methods
In all, 682 patients received up to nine 6-week cycles of VMP or MP and were then observed every 12 weeks or less. Data on second primary malignancies were collected by individual patient inquiries at all sites from 655 patients.
Results
After median follow-up of 60.1 months (range, 0 to 74 months), there was a 31% reduced risk of death with VMP versus MP (hazard ratio [HR], 0.695; P < .001; median OS 56.4 v 43.1 months). OS benefit with VMP was seen across prespecified patient subgroups (age >= 75 years, stage III myeloma, creatinine clearance < 60 mL/min). Sixty-three percent of VMP patients and 73% of MP patients had received subsequent therapy. Time to next therapy (median, 30.7 v 20.5 months; HR, 0.557; P < .001) was longer with VMP than with MP. Among patients who received subsequent therapies, survival from start of subsequent therapy was similar following VMP (median, 28.1 months) or MP (median, 26.8 months; HR, 0.914). Following VMP/MP, incidence proportions of hematologic malignancies (1%/1%) and solid tumors (5%/3%) and exposure-adjusted incidence rates (0.017/0.013 per patient-year) were similar and were consistent with background rates.
Conclusion
VMP resulted in a significant reduction in risk of death versus MP that was maintained after 5 years' follow-up and despite substantial use of novel-agent-based salvage therapies. There is no emerging safety signal for second primary malignancies following VMP. J Clin Oncol 31:448-455. (C) 2012 by American Society of Clinical Oncology
C1 [San Miguel, Jesus F.; Mateos, Maria-Victoria] Hosp Univ Salamanca, Inst Invest Biomed Salamanca, Salamanca 37007, Spain.
[San Miguel, Jesus F.; Mateos, Maria-Victoria] Univ Salamanca, Inst Biol Mol & Celular Canc, Consejo Super Invest Cient, E-37008 Salamanca, Spain.
[Schlag, Rudolf] Praxisklin Dr Schlag, Wurzburg, Germany.
[Kropff, Martin] Univ Munster, D-48149 Munster, Germany.
[Khuageva, Nuriet K.] SP Botkin Moscow City Clin Hosp, Moscow, Russia.
[Samoilova, Olga S.] Nizhnii Novgorod Reg Clin Hosp, Nizhnii Novgorod, Russia.
[Abdulkadyrov, Kudrat M.] St Petersburg Clin Res Inst Hematol & Transfusiol, St Petersburg, Russia.
[Dimopoulos, Meletios A.] Univ Athens, Sch Med, GR-11527 Athens, Greece.
[Shpilberg, Ofer] Rabin Med Ctr, Petah Tiqwa, Israel.
[Spicka, Ivan] Charles Univ Prague, Prague, Czech Republic.
[Petrucci, Maria Teresa] Univ Roma La Sapienza, Rome, Italy.
[Palumbo, Antonio] Univ Turin, Turin, Italy.
[Dmoszynska, Anna] Med Univ Lublin, Lublin, Poland.
[Delforge, Michel] Belgian Hematol Soc, Myeloma Study Grp, Brussels, Belgium.
[Deraedt, William; van de Velde, Helgi] Janssen Res & Dev, Beerse, Belgium.
[Jiang, Bin] Peking Univ, Peoples Hosp, Beijing 100871, Peoples R China.
[Anderson, Kenneth C.; Richardson, Paul G.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Esseltine, Dixie-Lee] Millennium Pharmaceut Inc, Cambridge, MA USA.
[Liu, Kevin] Janssen Res & Dev, Raritan, NJ USA.
[Cakana, Andrew] Janssen Res & Dev, High Wycombe, Bucks, England.
RP San Miguel, JF (reprint author), Hosp Univ Salamanca, Inst Invest Biomed Salamanca, Paseo San Vicente 58-182, Salamanca 37007, Spain.
EM sanmigiz@usal.es
OI SAN MIGUEL, JESUS/0000-0002-9183-4857; abdulkadyrov,
kudrat/0000-0002-3771-909X
FU Millennium Pharmaceuticals; Janssen Research Development; Janssen Global
Services
FX Supported by Millennium Pharmaceuticals, Janssen Research & Development,
and Janssen Global Services.
NR 48
TC 98
Z9 99
U1 0
U2 14
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 FEB 1
PY 2013
VL 31
IS 4
BP 448
EP 455
DI 10.1200/JCO.2012.41.6180
PG 8
WC Oncology
SC Oncology
GA 078LG
UT WOS:000314099800012
PM 23233713
ER
PT J
AU Balboni, MJ
Sullivan, A
Amobi, A
Phelps, AC
Gorman, DP
Zollfrank, A
Peteet, JR
Prigerson, HG
VanderWeele, TJ
Balboni, TA
AF Balboni, Michael J.
Sullivan, Adam
Amobi, Adaugo
Phelps, Andrea C.
Gorman, Daniel P.
Zollfrank, Angelika
Peteet, John R.
Prigerson, Holly G.
VanderWeele, Tyler J.
Balboni, Tracy A.
TI Why Is Spiritual Care Infrequent at the End of Life? Spiritual Care
Perceptions Among Patients, Nurses, and Physicians and the Role of
Training
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID QUALITY-OF-LIFE; CANCER-PATIENTS; TREATMENT PREFERENCES; US PHYSICIANS;
MEDICAL-CARE; NEAR-DEATH; ASSOCIATIONS; SATISFACTION; ONCOLOGY; RELIGION
AB Purpose
To determine factors contributing to the infrequent provision of spiritual care (SC) by nurses and physicians caring for patients at the end of life (EOL).
Patients and Methods
This is a survey-based, multisite study conducted from March 2006 through January 2009. All eligible patients with advanced cancer receiving palliative radiation therapy and oncology physician and nurses at four Boston academic centers were approached for study participation; 75 patients (response rate = 73%) and 339 nurses and physicians (response rate = 63%) participated. The survey assessed practical and operational dimensions of SC, including eight SC examples. Outcomes assessed five factors hypothesized to contribute to SC infrequency.
Results
Most patients with advanced cancer had never received any form of spiritual care from their oncology nurses or physicians (87% and 94%, respectively; P for difference = .043). Majorities of patients indicated that SC is an important component of cancer care from nurses and physicians (86% and 87%, respectively; P = .1). Most nurses and physicians thought that SC should at least occasionally be provided (87% and 80%, respectively; P = .16). Majorities of patients, nurses, and physicians endorsed the appropriateness of eight examples of SC (averages, 78%, 93%, and 87%, respectively; P = .01). In adjusted analyses, the strongest predictor of SC provision by nurses and physicians was reception of SC training (odds ratio [OR] = 11.20, 95% CI, 1.24 to 101; and OR = 7.22, 95% CI, 1.91 to 27.30, respectively). Most nurses and physicians had not received SC training (88% and 86%, respectively; P = .83).
Conclusion
Patients, nurses, and physicians view SC as an important, appropriate, and beneficial component of EOL care. SC infrequency may be primarily due to lack of training, suggesting that SC training is critical to meeting national EOL care guidelines. J Clin Oncol 31:461-467. (C) 2012 by American Society of Clinical Oncology
C1 [Balboni, Michael J.; Peteet, John R.; Prigerson, Holly G.; Balboni, Tracy A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Balboni, Michael J.; Peteet, John R.; Prigerson, Holly G.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Sullivan, Adam; VanderWeele, Tyler J.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Zollfrank, Angelika] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Balboni, TA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dana 1101,450 Brookline Ave, Boston, MA 02115 USA.
EM tbalboni@lroc.harvard.edu
FU American Society of Clinical Oncology; Templeton Foundation; University
of Chicago Program in Religion and Medicine Faculty Scholars Award
FX Supported in part by an American Society of Clinical Oncology Young
Investigator Award and Career Development Award (T. A. B.), a Templeton
Foundation Award (T.J.V.), and a University of Chicago Program in
Religion and Medicine Faculty Scholars Award (M.J.B.).
NR 34
TC 63
Z9 64
U1 1
U2 23
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 FEB 1
PY 2013
VL 31
IS 4
BP 461
EP 467
DI 10.1200/JCO.2012.44.6443
PG 7
WC Oncology
SC Oncology
GA 078LG
UT WOS:000314099800014
PM 23248245
ER
PT J
AU Sanoff, HK
Carpenter, WR
Sturmer, T
Schrag, D
AF Sanoff, Hanna K.
Carpenter, William R.
Stuermer, Til
Schrag, Deborah
TI Does Adjuvant Chemotherapy in Elderly Patients With Stage III Colon
Cancer Really Save Lives? Reply
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Letter
C1 [Sanoff, Hanna K.; Carpenter, William R.; Stuermer, Til] Univ N Carolina, Chapel Hill, NC 27515 USA.
[Schrag, Deborah] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Sanoff, HK (reprint author), Univ N Carolina, Chapel Hill, NC 27515 USA.
RI Carpenter, William/E-5125-2013
NR 6
TC 0
Z9 0
U1 0
U2 3
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 FEB 1
PY 2013
VL 31
IS 4
BP 512
EP 513
DI 10.1200/JCO.2012.46.4859
PG 2
WC Oncology
SC Oncology
GA 078LG
UT WOS:000314099800026
PM 23472263
ER
PT J
AU Garrett, LA
Harmon, DC
Schorge, JO
AF Garrett, Leslie A.
Harmon, David C.
Schorge, John O.
TI Embryonal Rhabdomyosarcoma of the Uterine Corpus
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID INTERGROUP RHABDOMYOSARCOMA; SARCOMA BOTRYOIDES; CERVIX; THERAPY
C1 [Garrett, Leslie A.; Harmon, David C.; Schorge, John O.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA.
RP Garrett, LA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA.
NR 9
TC 2
Z9 2
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 FEB 1
PY 2013
VL 31
IS 4
BP E48
EP E50
DI 10.1200/JCO.2012.43.1841
PG 3
WC Oncology
SC Oncology
GA 078LG
UT WOS:000314099800001
PM 23248250
ER
PT J
AU Niederdeppe, J
Bigman, CA
Gonzales, AL
Gollust, SE
AF Niederdeppe, Jeff
Bigman, Cabral A.
Gonzales, Amy L.
Gollust, Sarah E.
TI Communication About Health Disparities in the Mass Media
SO JOURNAL OF COMMUNICATION
LA English
DT Article
ID SOCIAL DETERMINANTS; ENTERTAINMENT-EDUCATION; CANCER COMMUNICATION;
POPULATION HEALTH; UNITED-STATES; NEWS MEDIA; GROUP CUES; POLICY;
INEQUALITIES; AWARENESS
AB A variety of scholars have explored the role of communication in reducing, maintaining, and even widening health disparities, but comparatively less attention has focused on the content and effects of communication about health disparities in the mass media. This article aims to summarize the current state of knowledge about these issues by identifying key outcomes and audiences for mass-mediated communication about health disparities, describing what is known about public opinion about health disparities, reviewing selected research on the content and effects of mass-mediated communication about health disparities, and identifying priorities for future research to better understand the role of communication in shaping public support and collective action to reduce health disparities.
C1 [Niederdeppe, Jeff; Bigman, Cabral A.; Gonzales, Amy L.; Gollust, Sarah E.] Cornell Univ, Dept Commun, Ithaca, NY 14850 USA.
Dana Farber Canc Inst, Harvard Sch Publ Hlth, Cambridge, MA 02138 USA.
Indiana Univ, Dept Telecommunicat, Bloomington, IN 47405 USA.
Univ Minnesota Sch Publ Hlth, Minneapolis, MN 55455 USA.
RP Niederdeppe, J (reprint author), Cornell Univ, Dept Commun, Ithaca, NY 14850 USA.
EM jdn56@cornell.edu
NR 80
TC 6
Z9 6
U1 4
U2 49
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0021-9916
J9 J COMMUN
JI J. Commun.
PD FEB
PY 2013
VL 63
IS 1
BP 8
EP 30
DI 10.1111/jcom.12003
PG 23
WC Communication
SC Communication
GA 079QC
UT WOS:000314185400005
ER
PT J
AU Nagler, RH
Ramanadhan, S
Minsky, S
Viswanath, K
AF Nagler, Rebekah H.
Ramanadhan, Shoba
Minsky, Sara
Viswanath, K.
TI Recruitment and Retention for Community-Based eHealth Interventions with
Populations of Low Socioeconomic Position: Strategies and Challenges
SO JOURNAL OF COMMUNICATION
LA English
DT Article
ID RESEARCH PARTICIPANTS; RESIDENTIAL-MOBILITY; HEALTH INFORMATION;
PHYSICAL-ACTIVITY; DIGITAL-DIVIDE; CANCER; MINORITY; KNOWLEDGE; LESSONS;
SEEKING
AB Given persistent communication inequalities, it is important to develop interventions to improve Internet and health literacy among underserved populations. These goals drove the Click to Connect project, a community-based eHealth intervention that provided novice computer users of low socioeconomic position with broadband Internet access, training classes, a Web portal, and technical support. In this article, we describe the strategies used to recruit and retain this population, the budgetary implications of such strategies, and the challenges and successes we encountered. Results suggest that personal contact between study staff and participants and provision of in-depth technical support were central to successful recruitment and retention. Such investments are essential to realize the promise of eHealth with underserved populations.
C1 [Nagler, Rebekah H.; Viswanath, K.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02215 USA.
[Nagler, Rebekah H.; Ramanadhan, Shoba; Minsky, Sara; Viswanath, K.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02215 USA.
RP Nagler, RH (reprint author), Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02215 USA.
EM rebekah_nagler@dfci.harvard.edu
FU NCI NIH HHS [K05 CA108663, R01 CA122894, R25 CA057711]
NR 42
TC 11
Z9 12
U1 4
U2 44
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0021-9916
J9 J COMMUN
JI J. Commun.
PD FEB
PY 2013
VL 63
IS 1
BP 201
EP 220
DI 10.1111/jcom.12008
PG 20
WC Communication
SC Communication
GA 079QC
UT WOS:000314185400016
PM 23439871
ER
PT J
AU Kitch, BT
DesRoches, C
Lesser, C
Cunningham, A
Campbell, EG
AF Kitch, Barrett T.
DesRoches, Catherine
Lesser, Cara
Cunningham, Amy
Campbell, Eric G.
TI Systems model of physician professionalism in practice
SO JOURNAL OF EVALUATION IN CLINICAL PRACTICE
LA English
DT Article
DE costs; disclosure; errors; professionalism; systems
ID MEDICAL PROFESSIONALISM; PERFORMANCE; MILLENNIUM; CHARTER; DOCTORS
AB Rationale This article proposes a systems level conceptualization of physician professionalism that is embedded in and results from the characteristics of the organizations in which doctors work such as hospitals, group practices and physician organizations. Aims and objectives The goal of this study was to develop and test the systems model of professionalism. Methods In total, 25 interviews were conducted in Minneapolis and Miami. Job titles of the subjects included hospital presidents, medical directors, chairs of hospital departments, quality and safety directors, chief of quality improvement and practising physicians. The data from the interviews were coded and then sorted by members of the study team into major and minor themes. Results Virtually, all of the subjects were readily able to confirm aspects of the model by providing real-life examples of factors at the practice, hospital and market levels that they believed strongly influenced the extent to which physicians adhere, or fail to adhere, to the professional norms. Conclusions The systems model of professionalism was consistent with the views and experiences of physicians and administrators in two different geographic regions of the USA. If born out by further research, this model has implications for interventions aimed at improving professionalism as well as for professionalism as a field of study.
C1 [DesRoches, Catherine; Campbell, Eric G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mongan Inst Hlth Policy, Boston, MA USA.
[Lesser, Cara] ABIM Fdn, Fdn Programs, Philadelphia, PA USA.
RP Kitch, BT (reprint author), NSMC, 81 Highland Ave, Salem, MA 01970 USA.
EM bkitch@partners.org
FU American Board of Internal Medicine Foundation
FX The study was supported through a grant from the American Board of
Internal Medicine Foundation. The foundation played a major role in all
aspects of the study, including the study design, data collection,
analyses and reporting.
NR 20
TC 1
Z9 1
U1 0
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1356-1294
J9 J EVAL CLIN PRACT
JI J. Eval. Clin. Pract.
PD FEB
PY 2013
VL 19
IS 1
BP 1
EP 10
DI 10.1111/j.1365-2753.2011.01680.x
PG 10
WC Health Care Sciences & Services; Medical Informatics; Medicine, General
& Internal
SC Health Care Sciences & Services; Medical Informatics; General & Internal
Medicine
GA 078QN
UT WOS:000314114400001
PM 22435531
ER
PT J
AU Egede, LE
Lynch, CP
Gebregziabher, M
Hunt, KJ
Echols, C
Gilbert, GE
Mauldin, PD
AF Egede, Leonard E.
Lynch, Cheryl P.
Gebregziabher, Mulugeta
Hunt, Kelly J.
Echols, Carrae
Gilbert, Gregory E.
Mauldin, Patrick D.
TI Differential Impact of Longitudinal Medication Non-Adherence on
Mortality by Race/Ethnicity among Veterans with Diabetes
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Article
DE medication non-adherence; veterans; diabetes; mortality; race/ethnicity
ID RACIAL-DIFFERENCES; ADHERENCE; ADULTS; HEALTH; POPULATION; COHORT;
HOSPITALIZATION; PREVALENCE; MELLITUS; US
AB To examine the differential effect of medication non-adherence over time on all-cause mortality by race/ethnicity.
Data on a longitudinal cohort of veterans with type 2 diabetes was examined. The main outcome was time to death. Primary independent variables were race/ethnicity and mean medication possession ratio (MPR) categorized into quintiles over the study period. Cox regression was used to model the association between time to death and MPR quintiles and race/ethnicity, adjusting for relevant covariates.
The cohort of 629,563 veterans was followed for 5 years. After adjusting for all covariates, the hazard ratios (HR) for subjects in the lowest versus highest MPR quintile was 12.21 (95 % CI 11.89, 12.55) for non-Hispanic white (NHW), 10.01 (95 % CI 9.18, 10.91) for non-Hispanic black (NHB), 12.65 (95 % CI 11.10, 14.43) for Hispanic and 10.41 (95 % CI 9.06, 11.96) for Other race veterans. Furthermore, type of diabetes therapy (oral versus insulin) maintained a significant relationship with mortality that varied by racial/ethnic group.
This study demonstrates the differential impact of medication non-adherence on mortality by race. It also demonstrates that type of diabetes therapy (insulin with or without oral agents) is associated with mortality and varies by racial/ethnic group.
C1 [Egede, Leonard E.; Lynch, Cheryl P.; Gebregziabher, Mulugeta; Hunt, Kelly J.; Echols, Carrae; Gilbert, Gregory E.] Ralph H Johnson Vet Affairs Med Ctr, Ctr Dis Prevent & Hlth Intervent Diverse Populat, Charleston, SC 29425 USA.
[Egede, Leonard E.; Lynch, Cheryl P.; Mauldin, Patrick D.] Med Univ S Carolina, Ctr Hlth Dispar Res, Charleston, SC 29425 USA.
[Gebregziabher, Mulugeta; Hunt, Kelly J.] Med Univ S Carolina, Div Biostat & Epidemiol, Charleston, SC 29425 USA.
[Mauldin, Patrick D.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA.
[Mauldin, Patrick D.] Div Gen Internal Med & Geriatr, Charleston, SC USA.
RP Egede, LE (reprint author), Ralph H Johnson Vet Affairs Med Ctr, Ctr Dis Prevent & Hlth Intervent Diverse Populat, POB 250593, Charleston, SC 29425 USA.
EM Egedel@musc.edu
RI Gilbert, Gregory/C-7735-2016;
OI Gilbert, Gregory/0000-0003-0879-5496; Gebregziabher,
Mulugeta/0000-0002-4826-481X
FU VHA Health Services Research and Development (HSRD) program [IIR-06-219]
FX This study was supported by grant #IIR-06-219 funded by the VHA Health
Services Research and Development (HSR&D) program. The funding agency
did not participate in the design and conduct of the study; collection,
management, analysis, and interpretation of the data; and preparation,
review, or approval of the manuscript. The manuscript represents the
views of the authors and not those of the VA or HSR&D. All authors had
access to the data and contributed to the manuscript
NR 22
TC 13
Z9 13
U1 2
U2 7
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD FEB
PY 2013
VL 28
IS 2
BP 208
EP 215
DI 10.1007/s11606-012-2200-8
PG 8
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA 077ZM
UT WOS:000314067900011
PM 22948932
ER
PT J
AU Jena, AB
Sun, E
Goldman, DP
AF Jena, Anupam B.
Sun, Eric
Goldman, Dana P.
TI Confounding in the Association of Proton Pump Inhibitor Use With Risk of
Community-Acquired Pneumonia
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Article
DE proton pump inhibitors; pneumonia; falsification testing
ID GASTRIC-ACID; CHRONICALLY ILL; DRUG-USE; BACTERIAL; GASTROENTERITIS;
POPULATION; INFECTION; THERAPY
AB Use of proton pump inhibitors (PPIs) is associated with community-acquired pneumonia (CAP), an association which may be confounded by unobserved patient and prescriber characteristics.
We assessed for confounding in the association between PPI use and CAP by using a 'falsification approach,' which estimated whether PPI use is also implausibly associated with other common medical conditions for which no known pathophysiologic link exists.
Retrospective claims-based cohort study.
Six private U.S. health plans.
Individuals who filled at least one prescription for a PPI (N = 26,436) and those who never did (N = 28,054) over 11 years.
Multivariate linear regression of the association between a filled prescription for a PPI and a diagnosis of CAP in each 3-month quarter. In falsification analyses, we tested for implausible associations between PPI use in each quarter and rates of osteoarthritis, chest pain, urinary tract infection (UTI), deep venous thrombosis (DVT), skin infection, and rheumatoid arthritis. Independent variables included an indicator for whether a prescription for a PPI was filled in a given quarter, and quarterly indicators for various co-morbidities, age, income, geographic location, and marital status.
Compared to nonusers, those ever using a PPI had higher adjusted rates of CAP in quarters in which no prescription was filled (68 vs. 61 cases per 10,000 persons, p < 0.001). Similar associations were noted for all conditions (e.g. chest pain, 336 vs. 282 cases, p < 0.001; UTI, 151 vs. 139 cases, p < 0.001). Among those ever using a PPI, quarters in which a prescription was filled were associated with higher adjusted rates of CAP (111 vs. 68 cases per 10,000, p < 0.001) and all other conditions (e.g. chest pain, 597 vs. 336 cases, p < 0.001; UTI, 186 vs. 151 cases, p < 0.001), compared to quarters in which no prescription was filled.
PPI use is associated with CAP, but also implausibly associated with common medical conditions. Observed associations between PPI use and CAP may be confounded.
C1 [Jena, Anupam B.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
[Jena, Anupam B.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Jena, Anupam B.] Natl Bur Econ Res, Dept Med, Cambridge, MA 02138 USA.
[Sun, Eric] Stanford Univ Hosp, Dept Anesthesia, Stanford, CA 94305 USA.
[Goldman, Dana P.] Univ So Calif, Leonard Schaeffer Ctr Hlth Policy & Econ 7, Los Angeles, CA USA.
RP Jena, AB (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA.
EM jena@hcp.med.harvard.edu
FU National Institute on Aging
FX National Institute on Aging. The design, conduct, analysis,
interpretation, and presentation of the data are the responsibility of
the investigators, with no involvement from the funding sources.
NR 30
TC 21
Z9 21
U1 0
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD FEB
PY 2013
VL 28
IS 2
BP 223
EP 230
DI 10.1007/s11606-012-2211-5
PG 8
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA 077ZM
UT WOS:000314067900013
PM 22956446
ER
PT J
AU Wee, CC
Davis, RB
Huskey, KW
Jones, DB
Hamel, MB
AF Wee, Christina C.
Davis, Roger B.
Huskey, Karen W.
Jones, Daniel B.
Hamel, Mary B.
TI Quality of Life Among Obese Patients Seeking Weight Loss Surgery: The
Importance of Obesity-Related Social Stigma and Functional Status
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Article
ID BODY-MASS INDEX; BARIATRIC SURGERY; US ADULTS; HEALTH; CANCER; IMPACT;
BMI; COMMUNITY; MORTALITY; TRENDS
AB Obesity is a stigmatizing condition associated with adverse psychosocial consequences. The relative importance of weight stigma in reducing health utility or the value a person places on their current health state is unknown.
We conducted a telephone survey of patients with obesity. All were seeking weight loss surgery at two bariatric centers (70 % response rate). We assessed patients' health utility (preference-based quality life measure) via a series of standard gamble scenarios assessing patients' willingness to risk death to lose various amounts of weight or achieve perfect health (range 0 to 1; 0 = death and 1 = most valued health/weight state). Multivariable models assessed associations among quality of life domains from the Short-form 36 (SF-36) and Impact of Weight on Quality of Life-lite (IWQOL-lite) and patients' health utility.
Our study sample (n = 574) had a mean body mass index of 46.5 kg/m(2) and a mean health utility of 0.87, reflecting the group's average willingness to accept a 13 % risk of death to achieve their most desired health/weight state; utilities were highly variable, however, with 10 % reporting a utility of 1.00 and 27 % reporting a utility lower than 0.90. Among the IWQOL-lite subscales, Public Distress and Work Life were the only two subscales significantly associated with patients' utility after adjustment for sociodemographic factors. Among the SF-36 subscales, Role Physical, Physical Functioning, and Role Emotional were significantly associated with patients' utility. When the leading subscales on both IWQOL-lite and SF-36 were considered together, Role Physical, Public Distress, and to a lesser degree Role Emotional remained independently associated with patients' health utility.
Patients seeking weight loss surgery report health utilities similar to those reported for people living with diabetes or with laryngeal cancer; however, utility values varied widely with more than a quarter of patients willing to accept more than a 10 % risk of death to achieve their most valued health/weight state. Interference with role functioning due to physical limitations and obesity-related social stigma were strong determinants of reduced health utility.
C1 [Wee, Christina C.; Davis, Roger B.; Huskey, Karen W.; Hamel, Mary B.] Beth Israel Deaconess Med Ctr, Dept Med, Div Gen Med & Primary Care, Boston, MA 02215 USA.
[Wee, Christina C.; Davis, Roger B.; Huskey, Karen W.; Jones, Daniel B.; Hamel, Mary B.] Harvard Univ, Sch Med, Boston, MA USA.
[Jones, Daniel B.] Beth Israel Deaconess Med Ctr, Dept Surg, Div Gen Surg, Sect Minimally Invas Surg, Boston, MA 02215 USA.
RP Wee, CC (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Div Gen Med & Primary Care, Boston, MA 02215 USA.
EM cwee@bidmc.harvard.edu
FU National Institute of Diabetes, Digestive and Kidney Diseases [R01
DK073302]; National Institute of Health [K24DK087932]
FX This study was funded by the National Institute of Diabetes, Digestive
and Kidney Diseases (R01 DK073302). Dr. Wee is also supported by a
midcareer mentorship award from the National Institute of Health
(K24DK087932). The sponsor had no role in the design or conduct of the
study; the collection, management, analysis, and interpretation of the
data; and the preparation, review, or approval of the manuscript. Dr.
Wee conceived the research question, designed the study, obtained
funding, supervised the conduct of the study, and drafted the
manuscript. Drs. Jones and Wee facilitated the collection of the data.
Ms. Huskey had full access to all the data, conducted all the analyses,
and takes responsibility for the integrity of the data and accuracy of
the data analysis. Dr. Davis provided statistical expertise and along
with Drs. Hamel and Wee interpreted the data. All authors provided
critical revision of the manuscript for intellectual content and
approved the final manuscript. We thank the patients for participating
in our study and thank the ABS study team for their efforts.
NR 30
TC 18
Z9 18
U1 2
U2 21
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD FEB
PY 2013
VL 28
IS 2
BP 231
EP 238
DI 10.1007/s11606-012-2188-0
PG 8
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA 077ZM
UT WOS:000314067900014
PM 22956443
ER
PT J
AU Barnes, DE
Mehta, KM
Boscardin, WJ
Fortinsky, RH
Palmer, RM
Kirby, KA
Landefeld, CS
AF Barnes, Deborah E.
Mehta, Kala M.
Boscardin, W. John
Fortinsky, Richard H.
Palmer, Robert M.
Kirby, Katharine A.
Landefeld, C. Seth
TI Prediction of Recovery, Dependence or Death in Elders Who Become
Disabled During Hospitalization
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Article
DE functional status; disability; mortality; hospitalization; prognosis
ID ACUTE MEDICAL ILLNESS; FUNCTIONAL DECLINE; OLDER-ADULTS; PROGNOSTIC
INDEX; 1-YEAR MORTALITY; SCREENING TOOLS; ACUTE-CARE; RISK; VALIDATION;
OUTCOMES
AB Many older adults become dependent in one or more activities of daily living (ADLs: dressing, bathing, transferring, eating, toileting) when hospitalized, and their prognosis after discharge is unclear.
To develop a prognostic index to estimate one-year probabilities of recovery, dependence or death in older hospitalized patients who are discharged with incident ADL dependence.
Retrospective cohort study.
449 adults aged a parts per thousand yen 70 years hospitalized for acute illness and discharged with incident ADL dependence.
Potential predictors included demographics (age, sex, race, education, marital status), functional measures (ADL dependencies, instrumental activities of daily living [IADL] dependencies, walking ability), chronic conditions (e.g., congestive heart failure, dementia, cancer), reason for admission (e.g., neurologic, cardiovascular), and laboratory values (creatinine, albumin, hematocrit). Multinomial logistic regression was used to develop a prognostic index for estimating the probabilities of recovery, disability or death over 1 year. Discrimination of the index was assessed for each outcome based on the c statistic.
During the year following hospitalization, 36 % of patients recovered, 27 % remained dependent and 37 % died. Key predictors of recovery, dependence or death were age, sex, number of IADL dependencies 2 weeks prior to admission, number of ADL dependencies at discharge, dementia, cancer, number of other chronic conditions, reason for admission, and creatinine levels. The final prognostic index had good to excellent discrimination for all three outcomes based on the c statistic (recovery: 0.81, dependence: 0.72, death: 0.78).
This index accurately estimated the probabilities of recovery, dependence or death in adults aged 70 years or older who were discharged with incident disability following hospitalization. This tool may be useful in clinical settings to guide care discussions and inform decision-making related to post-hospitalization care.
C1 [Barnes, Deborah E.; Boscardin, W. John; Kirby, Katharine A.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Barnes, Deborah E.; Boscardin, W. John; Kirby, Katharine A.] San Francisco VA Med Ctr, San Francisco, CA USA.
[Mehta, Kala M.] Stanford Univ, Stanford, CA 94305 USA.
[Fortinsky, Richard H.] Univ Connecticut, Sch Med, Farmington, CT USA.
[Palmer, Robert M.] Eastern Virginia Med Sch, Norfolk, VA 23501 USA.
[Landefeld, C. Seth] Univ Alabama Birmingham, Birmingham, AL USA.
RP Barnes, DE (reprint author), Univ Calif San Francisco, San Francisco, CA 94143 USA.
EM Deborah.barnes@ucsf.edu
FU National Institutes of Health (Landefeld) [R01 AG029233, AG10418]; S. D.
Bechtel, Jr. Foundation
FX Support for this study was provided by the National Institutes of Health
(Landefeld: R01 AG029233, AG10418) and the S. D. Bechtel, Jr.
Foundation.
NR 44
TC 18
Z9 18
U1 3
U2 9
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD FEB
PY 2013
VL 28
IS 2
BP 261
EP 268
DI 10.1007/s11606-012-2226-y
PG 8
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA 077ZM
UT WOS:000314067900018
PM 23054919
ER
PT J
AU Eckstrom, E
Feeny, DH
Walter, LC
Perdue, LA
Whitlock, EP
AF Eckstrom, Elizabeth
Feeny, David H.
Walter, Louise C.
Perdue, Leslie A.
Whitlock, Evelyn P.
TI Individualizing Cancer Screening in Older Adults: A Narrative Review and
Framework for Future Research
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Review
DE older adults; cancer screening; patient preferences
ID SERVICES TASK-FORCE; QUALITY-OF-LIFE; CLINICAL DECISION-MAKING;
COLORECTAL-CANCER; BREAST-CANCER; MAMMOGRAPHY; WOMEN; PREVENTION;
GUIDELINES; SURVIVAL
AB Older adults often have multiple chronic conditions that may decrease additional life expectancy. Research evaluating the benefits and harms of screening must include consideration of competing morbidities and patient heterogeneity (beyond age), potentially increased harms of screening, and patient preferences. Other areas in need of additional research include the lack of evidence for older adults on the harms of screening tests; the overdiagnosis of disease; the burden of disease labeling; the effects of inaccurate test results; the harms of disease treatment; and harms related to prioritization of healthcare (e.g., for a particular patient, lifestyle counseling may be more important than screening). Nontraditional outcomes, such as the effects on family caregivers, are also relevant. Studies comparing trajectories of quality-adjusted survival with and without screening to assess net benefit are typically lacking. There is little evidence on the preferences of older adults for deciding whether to be screened, the process of being screened, and the health states associated with being or not being screened. To enhance the quality and quantity of evidence, older adults need to be enrolled in screening trials and clinical studies. Measures of functional status and health-related quality of life (HRQL) need to be included in trials, registries, and cohort studies. This article addresses these challenges, and presents a framework for what research is needed to better inform screening decisions in older adults.
C1 [Eckstrom, Elizabeth] Oregon Hlth & Sci Univ, Dept Med, Div Gen Internal Med & Geriatr, Portland, OR 97201 USA.
[Feeny, David H.; Perdue, Leslie A.; Whitlock, Evelyn P.] Kaiser Permanente NW, Ctr Hlth Res, Portland, OR USA.
[Walter, Louise C.] Univ Calif San Francisco, Dept Med, Div Geriatr, San Francisco, CA USA.
[Walter, Louise C.] San Francisco VA Med Ctr, San Francisco, CA USA.
RP Eckstrom, E (reprint author), Oregon Hlth & Sci Univ, Dept Med, Div Gen Internal Med Geriatr, 3181 SW Sam Jackson Pk Rd,L475, Portland, OR 97239 USA.
EM eckstrom@ohsu.edu
FU Agency for Health Care Research; National Cancer Institute; National
Cancer Institute [R01 CA134425]; National Institute on Aging
[K24AG041180]
FX Agency for Health Care Research; National Cancer Institute (Dr.
Eckstrom, Dr. Feeny, and Ms. Perdue). Dr. Walter's effort was supported
by the National Cancer Institute (grant number R01 CA134425) and the
National Institute on Aging (grant number K24AG041180).
NR 44
TC 7
Z9 7
U1 0
U2 19
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
EI 1525-1497
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD FEB
PY 2013
VL 28
IS 2
BP 292
EP 298
DI 10.1007/s11606-012-2227-x
PG 7
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA 077ZM
UT WOS:000314067900021
PM 23054920
ER
PT J
AU Chiovaro, J
AF Chiovaro, Joe
TI Haunted by the Unread
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Editorial Material
C1 Portland VA Med Ctr, Div Hosp Med, Dept Med, Portland, OR 97239 USA.
RP Chiovaro, J (reprint author), Portland VA Med Ctr, Div Hosp Med, Dept Med, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA.
EM jchiovaro@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 0884-8734
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD FEB
PY 2013
VL 28
IS 2
BP 326
EP 327
DI 10.1007/s11606-012-2143-0
PG 2
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA 077ZM
UT WOS:000314067900029
PM 22752590
ER
PT J
AU Bromley, SK
Yan, S
Tomura, M
Kanagawa, O
Luster, AD
AF Bromley, Shannon K.
Yan, Sha
Tomura, Michio
Kanagawa, Osami
Luster, Andrew D.
TI Recirculating Memory T Cells Are a Unique Subset of CD4(+) T Cells with
a Distinct Phenotype and Migratory Pattern
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID LYMPHOID ORGANS; PERIPHERAL-TISSUES; IMMUNE-RESPONSE; IN-VIVO;
LYMPHOCYTES; RECEPTOR; EGRESS; MICE; INFECTION; INTEGRIN
AB Several populations of memory T cells have been described that differ in their migration and function. In this study, we have identified a unique subset of memory T cells, which we have named recirculating memory T cells (T-RCM). By exposing Kaede transgenic mouse skin to violet light, we tracked the fate of cutaneous T cells. One population of memory CD4(+) T cells remained in the skin. A second population migrated from the skin into draining lymph nodes (LNs) in a CCR7-dependent manner. These migrating CD4(+) T cells expressed a novel cell surface phenotype (CCR7(int/+)CD62L(int)CD69(-)CD103(+/-) E-selectin ligands(+)) that is distinct from memory T cell subsets described to date. Unlike memory T cell subsets that remain resident within tissues long-term, or that migrate either exclusively between lymphoid tissues or into peripheral nonlymphoid sites, CD4(+) T-RCM migrate from the skin into draining LNs. From the draining LNs, CD4(+) T-RCM reenter into the circulation, distal LNs, and sites of non-specific cutaneous inflammation. In addition, CD4(+) T-RCM upregulated CD40L and secreted IL-2 following polyclonal stimulation. Our results identify a novel subset of recirculating memory CD4(+) T cells equipped to deliver help to both distal lymphoid and cutaneous tissues. The Journal of Immunology, 2013, 190: 970-976.
C1 [Bromley, Shannon K.; Yan, Sha; Luster, Andrew D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol,Ctr Immunol & Inf, Boston, MA 02114 USA.
[Tomura, Michio] Kyoto Univ, Ctr Innovat Immunoregulat Technol & Therapeut, Grad Sch Med, Kyoto 6068501, Japan.
[Kanagawa, Osami] Akashi City Hosp, Akashi, Hyogo 6738501, Japan.
RP Bromley, SK (reprint author), Massachusetts Gen Hosp, 149 13th St, Charlestown, MA 02129 USA.
EM sbromley@helix.mgh.harvard.edu; aluster@mgh.harvard.edu
FU National Institutes of Health [R01-CA069212, K01-AR053715]; Claflin
Distinguished Scholar Award
FX This work was supported by National Institutes of Health Grants
R01-CA069212 (to A.D.L.) and K01-AR053715 (to S.K.B.) and by a Claflin
Distinguished Scholar Award (to S.K.B.).
NR 27
TC 52
Z9 52
U1 2
U2 14
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD FEB 1
PY 2013
VL 190
IS 3
BP 970
EP 976
DI 10.4049/jimmunol.1202805
PG 7
WC Immunology
SC Immunology
GA 074AM
UT WOS:000313784200015
PM 23255361
ER
PT J
AU Bae, J
Munshi, A
Li, C
Samur, M
Prabhala, R
Mitsiades, C
Anderson, KC
Munshi, NC
AF Bae, Jooeun
Munshi, Aditya
Li, Cheng
Samur, Mehmet
Prabhala, Rao
Mitsiades, Constantine
Anderson, Kenneth C.
Munshi, Nikhil C.
TI Heat Shock Protein 90 Is Critical for Regulation of Phenotype and
Functional Activity of Human T Lymphocytes and NK Cells
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID NATURAL-KILLER-CELLS; HSP90 INHIBITORS; HSP90-SPECIFIC INHIBITOR; CANCER
THERAPEUTICS; SIGNAL-TRANSDUCTION; MULTIPLE-MYELOMA; TYROSINE KINASES;
MOLECULAR TARGET; ANTITUMOR AGENT; PLASMA-MEMBRANE
AB The 90-kDa heat shock protein (Hsp90) has become an important therapeutic target with ongoing evaluation in a number of malignancies. Although Hsp90 inhibitors have a high therapeutic index with limited effects on normal cells, they have been described to inhibit dendritic cell function. However, its effect on human immune effector cells may have significant clinical implications, but remains unexplored. In this study, we have evaluated the effects of Hsp90 inhibition on human T lymphocyte and NK cells, including their Ag expression, activation, proliferation, and functional activities. These studies demonstrate that Hsp90 inhibition irreversibly downregulates cell surface expression of critical Ags (CD3, CD4, CD8), the costimulatory molecule (CD28, CD40L), and ab receptors on T lymphocytes, as well as activating receptors (CD2, CD11a, CD94, NKp30, NKp44, NKp46, KARp50.3) on NK cells. Hsp90 inhibition significantly reduced CD4 protein expression on T lymphocytes at both the cell surface and intracellular level, which was shown to be associated with aberrant regulation of Src-kinase p56(Lck). Downregulation of the Ags triggered by Hsp90 inhibition on CD3(+) T lymphocytes, both in CD4(+) and CD8(+) T cell subsets, was associated with a disruption in their cellular activation, proliferation, and/or IFN-gamma production, when the inhibition occurred either in activated or inactivated cells. In addition, downregulation of key activating receptors on NK cells following Hsp90 inhibition resulted in decreased cytotoxicity against tumor cells. Therefore, these observations demonstrate the need to closely monitor immune function in patients being treated with a Hsp90 inhibitor and may provide a potential therapeutic application in autoimmune diseases. The Journal of Immunology, 2013, 190: 1360-1371.
C1 [Bae, Jooeun; Munshi, Aditya; Li, Cheng; Samur, Mehmet; Prabhala, Rao; Mitsiades, Constantine; Anderson, Kenneth C.; Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA.
[Munshi, Aditya; Li, Cheng; Samur, Mehmet] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA.
[Prabhala, Rao; Munshi, Nikhil C.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02115 USA.
RP Munshi, NC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, 44 Binney St, Boston, MA 02115 USA.
EM nikhil_munshi@dfci.harvard.edu
OI Munshi, Aditya/0000-0002-9111-7495
FU National Institutes of Health [RO1-124929, P50-100007, PO1-78378,
PO1-155258, RO1-50947]; VA merit review grant
FX This work was supported by National Institutes of Health Grant
RO1-124929 and a VA merit review grant (to N.C.M.); National Institutes
of Health Grants P50-100007, PO1-78378, and PO1-155258 (to N.C.M. and
K.C.A.); and National Institutes of Health Grant RO1-50947 (to K.C.A.).
NR 67
TC 20
Z9 20
U1 0
U2 4
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD FEB 1
PY 2013
VL 190
IS 3
BP 1360
EP 1371
DI 10.4049/jimmunol.1200593
PG 12
WC Immunology
SC Immunology
GA 074AM
UT WOS:000313784200054
PM 23293352
ER
PT J
AU Hirachan, P
Polnaszek, NM
Martinez, M
Wagner, B
AF Hirachan, P.
Polnaszek, N. M.
Martinez, M.
Wagner, B.
TI ACUTE KIDNEY INJURY FOLLOWING RETROGRADE PYELOGRAM
SO JOURNAL OF INVESTIGATIVE MEDICINE
LA English
DT Meeting Abstract
CT Southern Regional Meeting of the
American-Federation-for-Medical-Research
CY FEB 21-23, 2013
CL New Orleans, LA
SP Amer Federat Med Res, So Reg
C1 [Hirachan, P.; Polnaszek, N. M.; Martinez, M.; Wagner, B.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Wagner, B.] S Texas Vet Hlth Care Syst, San Antonio, TX 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 1081-5589
J9 J INVEST MED
JI J. Invest. Med.
PD FEB
PY 2013
VL 61
IS 2
MA 258
BP 445
EP 446
PG 2
WC Medicine, General & Internal; Medicine, Research & Experimental
SC General & Internal Medicine; Research & Experimental Medicine
GA 079FO
UT WOS:000314156100273
ER
PT J
AU Sewell, J
Wagner, B
AF Sewell, J.
Wagner, B.
TI NEPHROGENIC SYSTEMIC FIBROSIS: REDOX SENSITIVITY, DERMAL CCR7-EXPRESSING
FIBROCYTES, AND EVIDENCE OF PULMONARY INVOLVEMENT IN A RAT MODEL
SO JOURNAL OF INVESTIGATIVE MEDICINE
LA English
DT Meeting Abstract
CT Southern Regional Meeting of the
American-Federation-for-Medical-Research
CY FEB 21-23, 2013
CL New Orleans, LA
SP Amer Federat Med Res, So Reg
C1 [Sewell, J.; Wagner, B.] Univ Texas Hlth Care Syst San Antonio, San Antonio, TX USA.
[Wagner, B.] S Texas Vet Hlth Care Syst, San Antonio, TX 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 1081-5589
J9 J INVEST MED
JI J. Invest. Med.
PD FEB
PY 2013
VL 61
IS 2
MA 271
BP 449
EP 449
PG 1
WC Medicine, General & Internal; Medicine, Research & Experimental
SC General & Internal Medicine; Research & Experimental Medicine
GA 079FO
UT WOS:000314156100286
ER
PT J
AU Jessee, R
Weaver, F
Chin, A
Burns, S
Svircev, J
Hoenig, H
Heggeness, M
Carbone, L
AF Jessee, R.
Weaver, F.
Chin, A.
Burns, S.
Svircev, J.
Hoenig, H.
Heggeness, M.
Carbone, L.
TI MANAGEMENT OF LOWER EXTREMITY FRACTURES IN MEN WITH SPINAL CORD INJURIES
SO JOURNAL OF INVESTIGATIVE MEDICINE
LA English
DT Meeting Abstract
CT Southern Regional Meeting of the
American-Federation-for-Medical-Research
CY FEB 21-23, 2013
CL New Orleans, LA
SP Amer Federat Med Res, So Reg
C1 [Jessee, R.; Carbone, L.] Univ Tennessee, Hlth Sci Ctr, Memphis, TN USA.
[Weaver, F.; Chin, A.] Jr VA Hosp, Hines, IL USA.
[Weaver, F.] Loyola Univ, Stritch Sch Med, Maywood, IL 60153 USA.
[Burns, S.; Svircev, J.] VA Puget Sound Hlth Care Syst, Seattle, WA USA.
[Burns, S.; Svircev, J.] Univ Washington, Seattle, WA 98195 USA.
[Hoenig, H.] Durham VAMC, Durham, NC USA.
[Heggeness, M.] VA Med Ctr, Houston, TX USA.
[Heggeness, M.] Baylor Coll Med, Houston, TX 77030 USA.
[Carbone, L.] Memphis VA Med Ctr, Memphis, TN 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 1081-5589
J9 J INVEST MED
JI J. Invest. Med.
PD FEB
PY 2013
VL 61
IS 2
MA 297
BP 456
EP 456
PG 1
WC Medicine, General & Internal; Medicine, Research & Experimental
SC General & Internal Medicine; Research & Experimental Medicine
GA 079FO
UT WOS:000314156100312
ER
PT J
AU Sewell, J
Wagner, B
AF Sewell, J.
Wagner, B.
TI NEPHROGENIC SYSTEMIC FIBROSIS: REDOX SENSITIVITY, DERMAL CCR7-EXPRESSING
FIBROCYTES, AND EVIDENCE OF PULMONARY INVOLVEMENT IN A RAT MODEL
SO JOURNAL OF INVESTIGATIVE MEDICINE
LA English
DT Meeting Abstract
CT Southern Regional Meeting of the
American-Federation-for-Medical-Research
CY FEB 21-23, 2013
CL New Orleans, LA
SP Amer Federat Med Res
C1 [Sewell, J.; Wagner, B.] Univ Texas Hlth Care Syst San Antonio, San Antonio, TX USA.
[Wagner, B.] S Texas Vet Hlth Care Syst, San Antonio, TX 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 1081-5589
J9 J INVEST MED
JI J. Invest. Med.
PD FEB
PY 2013
VL 61
IS 2
MA 393
BP 484
EP 484
PG 1
WC Medicine, General & Internal; Medicine, Research & Experimental
SC General & Internal Medicine; Research & Experimental Medicine
GA 079FO
UT WOS:000314156100408
ER
PT J
AU Alge, J
Karakala, N
Neely, B
Janech, M
Arthur, J
AF Alge, J.
Karakala, N.
Neely, B.
Janech, M.
Arthur, J.
TI URINARY ANGIOTENSINOGEN: A PROGNOSTIC BIOMARKER OF ACUTE KIDNEY INJURY
SO JOURNAL OF INVESTIGATIVE MEDICINE
LA English
DT Meeting Abstract
CT Southern Regional Meeting of the
American-Federation-for-Medical-Research
CY FEB 21-23, 2013
CL New Orleans, LA
SP Amer Federat Med Res, So Reg
C1 [Alge, J.; Karakala, N.; Neely, B.; Janech, M.; Arthur, J.] Med Univ S Carolina, Charleston, SC 29425 USA.
[Janech, M.; Arthur, J.] Ralph H Johnson VAMC, Charleston, SC 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 1081-5589
J9 J INVEST MED
JI J. Invest. Med.
PD FEB
PY 2013
VL 61
IS 2
MA 504
BP 516
EP 516
PG 1
WC Medicine, General & Internal; Medicine, Research & Experimental
SC General & Internal Medicine; Research & Experimental Medicine
GA 079FO
UT WOS:000314156100519
ER
PT J
AU Bhensdadia, N
Hunt, K
Lopes-Virella, M
Tucker, M
Neely, B
Janech, M
Arthur, J
AF Bhensdadia, N.
Hunt, K.
Lopes-Virella, M.
Tucker, M.
Neely, B.
Janech, M.
Arthur, J.
TI URINE HAPTOGLOBIN TO CREATININE RATIO PREDICTS WORSENING RENAL FUNCTIONS
IN PATIENTS WITH TYPE 2 DIABETES
SO JOURNAL OF INVESTIGATIVE MEDICINE
LA English
DT Meeting Abstract
CT Southern Regional Meeting of the
American-Federation-for-Medical-Research
CY FEB 21-23, 2013
CL New Orleans, LA
SP Amer Federat Med Res, So Reg
C1 [Bhensdadia, N.; Hunt, K.; Lopes-Virella, M.; Tucker, M.; Neely, B.; Janech, M.; Arthur, J.] Med Univ S Carolina, Charleston, SC 29425 USA.
[Lopes-Virella, M.; Janech, M.; Arthur, J.] Ralph H Johnson VA Med Ctr, Charleston, SC USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1081-5589
J9 J INVEST MED
JI J. Invest. Med.
PD FEB
PY 2013
VL 61
IS 2
MA 506
BP 517
EP 517
PG 1
WC Medicine, General & Internal; Medicine, Research & Experimental
SC General & Internal Medicine; Research & Experimental Medicine
GA 079FO
UT WOS:000314156100521
ER
PT J
AU Davis, B
Stewart, EH
Clemans-Taylor, BL
Centor, R
Estrada, C
AF Davis, B.
Stewart, E. H.
Clemans-Taylor, B. L.
Centor, R.
Estrada, C.
TI A META-ANALYSIS OF THE RAPID ANTIGEN STREPTOCOCCUS TEST
SO JOURNAL OF INVESTIGATIVE MEDICINE
LA English
DT Meeting Abstract
CT Southern Regional Meeting of the
American-Federation-for-Medical-Research
CY FEB 21-23, 2013
CL New Orleans, LA
SP Amer Federat Med Res, So Reg
C1 [Davis, B.; Stewart, E. H.; Clemans-Taylor, B. L.; Centor, R.; Estrada, C.] Univ Alabama Birmingham, Birmingham, AL USA.
[Estrada, C.] Birmingham VAMC, Birmingham, AL USA.
NR 0
TC 0
Z9 0
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1081-5589
J9 J INVEST MED
JI J. Invest. Med.
PD FEB
PY 2013
VL 61
IS 2
MA 527
BP 523
EP 523
PG 1
WC Medicine, General & Internal; Medicine, Research & Experimental
SC General & Internal Medicine; Research & Experimental Medicine
GA 079FO
UT WOS:000314156100542
ER
PT J
AU Bryan, T
Snyder, E
Estrada, C
Castiglioni, A
AF Bryan, T.
Snyder, E.
Estrada, C.
Castiglioni, A.
TI EDUCATION IN DELIVERING PATIENT-CENTERED CARE: PROVIDER COMFORT LEVEL IN
COUNSELING WOMEN AGES 40-49 REGARDING BREAST CANCER SCREENING OPTIONS
SO JOURNAL OF INVESTIGATIVE MEDICINE
LA English
DT Meeting Abstract
CT Southern Regional Meeting of the
American-Federation-for-Medical-Research
CY FEB 21-23, 2013
CL New Orleans, LA
SP Amer Federat Med Res, So Reg
C1 [Bryan, T.; Snyder, E.; Estrada, C.] Univ Alabama Birmingham, Birmingham, AL USA.
[Castiglioni, A.] Univ Cent Florida, Coll Med, Tampa, FL USA.
[Bryan, T.; Snyder, E.; Estrada, C.] Birmingham VA Med Ctr, Birmingham, AL USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1081-5589
J9 J INVEST MED
JI J. Invest. Med.
PD FEB
PY 2013
VL 61
IS 2
MA 528
BP 524
EP 524
PG 1
WC Medicine, General & Internal; Medicine, Research & Experimental
SC General & Internal Medicine; Research & Experimental Medicine
GA 079FO
UT WOS:000314156100543
ER
PT J
AU Sullivan, G
Vasterling, JJ
Han, XT
Tharp, AT
Davis, T
Deitch, EA
Constans, JI
AF Sullivan, Greer
Vasterling, Jennifer J.
Han, Xiaotong
Tharp, Andra Teten
Davis, Teri
Deitch, Elizabeth A.
Constans, Joseph I.
TI Preexisting Mental Illness and Risk for Developing a New Disorder After
Hurricane Katrina
SO JOURNAL OF NERVOUS AND MENTAL DISEASE
LA English
DT Article
DE Hurricane Katrina; PTSD; disasters; preexisting mental illness
ID POSTTRAUMATIC-STRESS-DISORDER; DISASTER VICTIMS SPEAK; NATURAL DISASTER;
PSYCHIATRIC-DISORDERS; TRAUMA; DEPRESSION; MORTALITY
AB To investigate predisaster mental illness as a risk factor of poor postdisaster mental health outcomes, veterans with (n = 249) and without (n = 250) preexisting mental illness residing in the Gulf Coast during Hurricane Katrina were surveyed after Katrina and screened for posttraumatic stress disorder (PTSD), depression, generalized anxiety disorder, and panic. Logistic regression examined the association between preexisting mental disorders and positive screens after the hurricane, adjusting for demographics and exposure to hurricane-related stressors. The odds of screening positive for any new mental disorder were 6.8 times greater for those with preexisting mental illness compared with those without preexisting mental illness. Among those with preexisting PTSD, the odds of screening positive for any new mental illness were 11.9 times greater; among those with schizophrenia, 9.1 times greater; and among those with affective disorders, 4.4 times greater. Persons with preexisting mental illnesses, particularly PTSD, should be considered a high-risk group for poor outcomes after a disaster.
C1 [Sullivan, Greer; Han, Xiaotong; Davis, Teri; Constans, Joseph I.] Cent Arkansas Vet Healthcare Syst, VA S Cent Mental Illness Res Educ & Clin Ctr MIRE, N Little Rock, AR 72114 USA.
[Sullivan, Greer; Han, Xiaotong] Univ Arkansas Med Sci, Dept Psychiat, Little Rock, AR 72205 USA.
[Vasterling, Jennifer J.] VA Boston Healthcare Syst, Psychol Serv, Boston, MA USA.
[Vasterling, Jennifer J.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA.
[Vasterling, Jennifer J.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA.
[Tharp, Andra Teten] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA.
[Deitch, Elizabeth A.] Univ New Orleans, Dept Management, New Orleans, LA 70148 USA.
[Constans, Joseph I.] VA SE Louisiana Vet Hlth Care Syst, New Orleans, LA USA.
[Constans, Joseph I.] Tulane Univ, Dept Psychiat & Behav Sci, New Orleans, LA 70118 USA.
RP Sullivan, G (reprint author), Cent Arkansas Vet Healthcare Syst, VA S Cent Mental Illness Res Educ & Clin Ctr MIRE, 2200 Ft Roots Dr,Bldg 58, N Little Rock, AR 72114 USA.
EM gsullivan@uams.edu
FU VA South Central (VISN 16) Mental Illness Research, Education, and
Clinical Center (MIRECC), North Little Rock, AR
FX This work was funded by the VA South Central (VISN 16) Mental Illness
Research, Education, and Clinical Center (MIRECC), North Little Rock,
AR. The authors declare no conflict of interest.
NR 29
TC 8
Z9 8
U1 0
U2 15
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0022-3018
J9 J NERV MENT DIS
JI J. Nerv. Ment. Dis.
PD FEB
PY 2013
VL 201
IS 2
BP 161
EP 166
DI 10.1097/NMD.0b013e31827f636d
PG 6
WC Clinical Neurology; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 082CO
UT WOS:000314369500015
PM 23364127
ER
PT J
AU Barker, FG
AF Barker, Fred G., II
TI Stroke, geography, and provider density
SO JOURNAL OF NEUROSURGERY
LA English
DT Editorial Material
ID ASSOCIATION; MORTALITY; ADULTS; VOLUME; STATES
C1 Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA.
RP Barker, FG (reprint author), Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA.
NR 14
TC 0
Z9 0
U1 0
U2 1
PU AMER ASSOC NEUROLOGICAL SURGEONS
PI ROLLING MEADOWS
PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA
SN 0022-3085
J9 J NEUROSURG
JI J. Neurosurg.
PD FEB
PY 2013
VL 118
IS 2
BP 428
EP 429
DI 10.3171/2012.7.JNS121120
PG 2
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA 076DY
UT WOS:000313937900032
PM 23198832
ER
PT J
AU Adams, JM
Fulmer, T
AF Adams, Jeffrey M.
Fulmer, Terry
TI Influencing Collaborative Leadership An Interview With Dean Terry Fulmer
SO JOURNAL OF NURSING ADMINISTRATION
LA English
DT Editorial Material
C1 [Adams, Jeffrey M.] Massachusetts Gen Hosp, Ctr Innovat Care Delivery & Connell Res Scholar, Boston, MA 02114 USA.
RP Adams, JM (reprint author), Massachusetts Gen Hosp, Ctr Innovat Care Delivery & Connell Res Scholar, 275 Cambridge St,POB 4, Boston, MA 02114 USA.
EM Jadams9@partners.org
NR 2
TC 0
Z9 0
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0002-0443
J9 J NURS ADMIN
JI J. Nurs. Adm.
PD FEB
PY 2013
VL 43
IS 2
BP 66
EP 68
DI 10.1097/NNA.0b013e31827f2090
PG 3
WC Nursing
SC Nursing
GA 079HM
UT WOS:000314161200004
ER
PT J
AU Miller, AN
Barei, DP
Iaquinto, JM
Ledoux, WR
Beingessner, DM
AF Miller, Anna N.
Barei, David P.
Iaquinto, Joseph M.
Ledoux, William R.
Beingessner, Daphne M.
TI Iatrogenic Syndesmosis Malreduction via Clamp and Screw Placement
SO JOURNAL OF ORTHOPAEDIC TRAUMA
LA English
DT Article
DE Ankle; syndesmosis; iatrogenic; malreduction
ID ANKLE FRACTURES; OPERATIVE TREATMENT; FIXATION; STABILIZATION; INJURIES;
REMOVAL
AB Objectives: The purpose of this study was to assess the impact of variations in angulation of clamp placement to hold syndesmotic reduction and how subsequent syndesmotic screw placement affects malreduction of the syndesmosis. We hypothesized that an anatomic syndesmosis reduction cannot be reliably achieved with a clamp alone; and, inaccurate placement of intraoperative clamps and trans-syndesmotic screws after reduction can malreduce the ankle syndesmosis.
Methods: After computed tomography scanning of the intact limbs, 14 cadaver legs were dissected; the syndesmosis was completely disrupted in all. Using planned drill holes, clamps were first placed at 0 degrees, 15 degrees, and 30 degrees angles from the fibula, then separate posterolateral, followed by lateral, screws were placed. After each intervention, the limb had a computed tomography scan so the fibular reduction could be evaluated precisely.
Results: Clamps placed at 15 degrees and 30 degrees significantly displaced the fibula in external rotation and caused significant overcompression of the syndesmosis. Thirty-degree lateral screws caused significant anteromedial displacement, external rotation, and overcompression of the syndesmosis. The 15 degrees posterolateral screws also caused significant external rotation and overcompression of the syndesmosis.
Conclusions: Our study demonstrates that intraoperative clamping and fixation can cause statistically significant malreduction of the syndesmosis. This article should alert clinicians that clamp and screw placement can cause iatrogenic malreduction of the syndesmosis and make them aware that these dangers occur with specific clamp and screw angles in particular.
C1 [Miller, Anna N.] Wake Forest Univ, Bowman Gray Sch Med, Dept Orthopaed Surg, Winston Salem, NC 27157 USA.
[Barei, David P.; Beingessner, Daphne M.] Univ Washington, Harborview Med Ctr, Seattle, WA 98104 USA.
[Barei, David P.; Ledoux, William R.; Beingessner, Daphne M.] Univ Washington, Dept Orthopaed & Sports Med, Seattle, WA 98195 USA.
[Iaquinto, Joseph M.; Ledoux, William R.] VA Puget Sound Hlth Care Syst, Dept Vet Affairs, RR&D Ctr Excellence Limb Loss Prevent & Prosthet, Seattle, WA USA.
[Ledoux, William R.] Univ Washington, Dept Mech Engn, Seattle, WA 98195 USA.
RP Miller, AN (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Dept Orthopaed Surg, Med Ctr Blvd, Winston Salem, NC 27157 USA.
EM anmiller@wakehealth.edu
RI Ledoux, William/K-6815-2015;
OI Ledoux, William/0000-0003-4982-7714; Miller, Anna/0000-0002-7056-8502
FU University of Washington Department of Orthopaedic Surgery; Department
of Veterans Affairs Rehabilitation Research and Development Center of
Excellence
FX Supported by the University of Washington Department of Orthopaedic
Surgery and the Department of Veterans Affairs Rehabilitation Research
and Development Center of Excellence.
NR 22
TC 22
Z9 24
U1 0
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0890-5339
J9 J ORTHOP TRAUMA
JI J. Orthop. Trauma
PD FEB
PY 2013
VL 27
IS 2
BP 100
EP 106
DI 10.1097/BOT.0b013e31825197cb
PG 7
WC Orthopedics; Sport Sciences
SC Orthopedics; Sport Sciences
GA 077VV
UT WOS:000314058300013
PM 22549032
ER
PT J
AU Holgerson, PL
Vestman, NR
Claesson, R
Ohman, C
Domellof, M
Tanner, ACR
Hernell, O
Johansson, I
AF Holgerson, Pernilla L.
Vestman, Nelly R.
Claesson, Rolf
Ohman, Carina
Domellof, Magnus
Tanner, Anne C. R.
Hernell, Olle
Johansson, Ingegerd
TI Oral Microbial Profile Discriminates Breast-fed From Formula-fed Infants
SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION
LA English
DT Article
DE breast-feeding; lactobacilli. Lactobacillus gasseri; microbiota; oral
ID HYDROXYAPATITE IN-VITRO; UPPER RESPIRATORY-TRACT; MUTANS STREPTOCOCCI;
HUMAN-MILK; LACTOBACILLUS-REUTERI; GUT MICROBIOME; BODY HABITATS;
DENTAL-CARIES; CHILDREN; ADHESION
AB Objectives: Little is known about the effect of diet on the oral microbiota of infants, although diet is known to affect the gut microbiota. The aims of the present study were to compare the oral microbiota in breast-fed and formula-fed infants, and investigate growth inhibition of streptococci by infant-isolated lactobacilli.
Methods: A total of 207 mothers consented to participation of their 3-month-old infants. A total of 146 (70.5%) infants were exclusively and 38 (18.4%) partially breast-fed, and 23 (11.1%) were exclusively formula-fed. Saliva from all of their infants was cultured for Lactobacillus species, with isolate identifications from 21 infants. Lactobacillus isolates were tested for their ability to suppress Streptococcus mutans and S sanguinis. Oral swabs from 73 infants were analysed by the Human Oral Microbe Identification Microarray (HOMIM) and by quantitative polymerase chain reaction for Lactobacillus gasseri.
Results: Lactobacilli were cultured from 27.8% of exclusively and partially breast-fed infants, but not from formula-fed infants. The prevalence of 14 HOMIM-detected taxa, and total salivary lactobacilli counts differed by feeding method. Multivariate modelling of HOMIM-detected bacteria and possible confounders clustered samples from breast-fed infants separately from formula-fed infants. The microbiota of breast-fed infants differed based on vaginal or C-section delivery. Isolates of L plantarum, L gasseri, and L vaginalis inhibited growth of the cariogenic S mutans and the commensal S sanguinis: L plantarum >L gasseri >L vaginalis.
Conclusions: The microbiota of the mouth differs between 3-month-old breast-fed and formula-fed infants. Possible mechanisms for microbial differences observed include species suppression by lactobacilli indigenous to breast milk.
C1 [Holgerson, Pernilla L.; Vestman, Nelly R.; Claesson, Rolf; Ohman, Carina; Johansson, Ingegerd] Umea Univ, Dept Odontol, SE-90187 Umea, Sweden.
[Domellof, Magnus; Hernell, Olle] Umea Univ, Dept Clin Sci, SE-90187 Umea, Sweden.
[Tanner, Anne C. R.] Harvard Univ, Sch Publ Hlth, Dept Mol Genet, Forsyth Inst, Boston, MA 02115 USA.
RP Holgerson, PL (reprint author), Umea Univ, Dept Odontol, SE-90187 Umea, Sweden.
EM pernilla.lif@odont.umu.se
RI Domellof, Magnus/E-5307-2011
OI Domellof, Magnus/0000-0002-0726-7029
FU Vasterbotten County Council; Swedish Patent Revenue Foundation; Public
Health Service Grant, National Institute of Dental and Craniofacial
Research [DE-015847]; Henning and Johan Throne-Holst's Foundation
FX The study was supported by grants from Vasterbotten County Council, the
Swedish Patent Revenue Foundation, and by Public Health Service Grant
DE-015847 (A.T.) from the National Institute of Dental and Craniofacial
Research, and Henning and Johan Throne-Holst's Foundation (P.L.H.).
NR 51
TC 34
Z9 35
U1 4
U2 48
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0277-2116
J9 J PEDIATR GASTR NUTR
JI J. Pediatr. Gastroenterol. Nutr.
PD FEB
PY 2013
VL 56
IS 2
BP 127
EP 136
DI 10.1097/MPG.0b013e31826f2bc6
PG 10
WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics
SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics
GA 078LE
UT WOS:000314099600011
PM 22955450
ER
PT J
AU Moran, CJ
Kelsey, PB
Lauwers, GY
Biller, JA
AF Moran, Christopher J.
Kelsey, Peter B.
Lauwers, Gregory Y.
Biller, Jeffrey A.
TI Resection of Acquired Mucosal Web in Crohn Disease
SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION
LA English
DT Article
ID COLONIC DIAPHRAGM DISEASE; ENDOSCOPIC MEMBRANECTOMY; DUODENAL DIAPHRAGM;
ADULT
C1 [Moran, Christopher J.; Biller, Jeffrey A.] MassGen Hosp Children, Div Pediat Gastroenterol Hepatol & Nutr, Dept Pediat, Boston, MA 02114 USA.
[Kelsey, Peter B.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
[Lauwers, Gregory Y.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
RP Moran, CJ (reprint author), MassGen Hosp Children, Div Pediat Gastroenterol Hepatol & Nutr, Dept Pediat, 55 Fruit St, Boston, MA 02114 USA.
EM cjmoran@partners.org
NR 8
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0277-2116
J9 J PEDIATR GASTR NUTR
JI J. Pediatr. Gastroenterol. Nutr.
PD FEB
PY 2013
VL 56
IS 2
BP E8
EP E9
DI 10.1097/MPG.0b013e3182495b70
PG 2
WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics
SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics
GA 078LE
UT WOS:000314099600002
PM 22450147
ER
PT J
AU Bober, SL
Giobbie-Hurder, A
Emmons, KM
Winer, E
Partridge, A
AF Bober, Sharon L.
Giobbie-Hurder, Anita
Emmons, Karen M.
Winer, Eric
Partridge, Ann
TI Psychosexual Functioning and Body Image Following a Diagnosis of Ductal
Carcinoma In Situ
SO JOURNAL OF SEXUAL MEDICINE
LA English
DT Article
DE DCIS; Psychosexual; Body Image; Breast Cancer
ID QUALITY-OF-LIFE; BREAST-CANCER SURVIVORS; HEALTH; WOMEN; SURGERY;
ADJUSTMENT; SEXUALITY; OUTCOMES; END
AB Introduction. There has been exponential growth in diagnoses of ductal carcinoma in situ (DCIS) in the past decade, yet little is known about sexual functioning and body image in women after diagnosis of DCIS. This is of particular importance because many of the parallel treatment modalities also used to treat invasive breast cancer, e.g., surgery and hormonal therapy, have been shown to have a detrimental effect on psychosexual function. Aim. The aim was to explore changes in sexual function and body image after diagnosis and treatment of in situ cancer. Main Outcome Measures. Evidence-based self-report measures assessing psychosexual functioning and body image. Methods. Women diagnosed with DCIS within the past 3 months and who reported being sexually active completed measures assessing various aspects of psychosocial and sexual functioning and body image. Outcomes were evaluated at baseline, 9-, and 18-month time points. All statistical tests were two sided. Results. Three hundred four women completed this prospective survey. Overall, sexual function in women with DCIS appears to be very similar to women in the general population and does not seem to be significantly disrupted by a diagnosis of DCIS. Sexual function and body image were notably stable across the 18-month length of follow-up. Of those patients who underwent mastectomy, there were no differences in sexual satisfaction for patients who had reconstruction compared with patients who did not. Conclusion. Although it has been shown that women with DCIS have a number of psychosocial challenges, results from this large-scale prospective study of women suggest that sexual function and body image may not be significantly negatively affected by this diagnosis. Of note, these results were also the case for women who underwent mastectomy and hormonal therapy. These findings are reassuring for both patients and physicians in the context of decision making about treatment options. Bober SL, A Giobbie-Hurder, Emmons KM, Winer E, and Partridge A. Psychosexual functioning and body image following a diagnosis of ductal carcinoma in situ. J Sex Med **;**:****.
C1 [Bober, Sharon L.; Emmons, Karen M.; Winer, Eric; Partridge, Ann] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Bober, Sharon L.; Emmons, Karen M.; Winer, Eric; Partridge, Ann] Harvard Univ, Sch Med, Boston, MA USA.
[Giobbie-Hurder, Anita] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Emmons, Karen M.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
RP Bober, SL (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA.
EM Sharon_Bober@dfci.harvard.edu
NR 31
TC 7
Z9 7
U1 1
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1743-6095
J9 J SEX MED
JI J. Sex. Med.
PD FEB
PY 2013
VL 10
IS 2
BP 370
EP 377
DI 10.1111/j.1743-6109.2012.02852.x
PG 8
WC Urology & Nephrology
SC Urology & Nephrology
GA 078OC
UT WOS:000314107400008
PM 22812628
ER
PT J
AU Hosain, GMM
Latini, DM
Kauth, M
Goltz, HH
Helmer, DA
AF Hosain, G. M. Monawar
Latini, David M.
Kauth, Michael
Goltz, Heather Honore
Helmer, Drew A.
TI Sexual Dysfunction among Male Veterans Returning from Iraq and
Afghanistan: Prevalence and Correlates
SO JOURNAL OF SEXUAL MEDICINE
LA English
DT Article
DE Sexual Dysfunction; Veterans; Post-Traumatic Stress Disorder;
Prevalence; Male; Young
ID POSTTRAUMATIC-STRESS-DISORDER; MALE ERECTILE DYSFUNCTION; DEPRESSIVE
SYMPTOMS; UNITED-STATES; INTIMATE-RELATIONSHIPS; WAR VETERANS; MEN;
HYPERTENSION; SATISFACTION; PREDICTORS
AB Introduction. Sexual dysfunction (SD) is not well described in the Iraq/Afghanistan veteran population despite high prevalence of multiple risk factors for this issue. Aim. To estimate the prevalence and examine the association of various sociodemographic, mental health, comorbid conditions and life style factors with sexual dysfunction in Iraq/Afghanistan veterans. Methods. This exploratory cross-sectional study was conducted using data from the VA administrative database. A total of 4,755 Iraq/Afghanistan veterans were identified who sought treatment from the Michael E. DeBakey Veterans Affairs Medical Center inpatient and outpatient clinic between September 2007 and August 2009. Main Outcome Measures. Sexual dysfunction was determined by ICD9-CM codes related to sexual health issues and/or by specific medications, primarily phosphodiesterase-5 inhibitors (PDE5i), prescribed for erectile dysfunction. Results. The overall prevalence of sexual dysfunction was 5.5% (N = 265). By age category, it was 3.6% (N = 145) for Iraq/Afghanistan veterans aged 1840 years and 15.7% (N = 120) for Iraq/Afghanistan veterans aged > 40 years, respectively. A multivariate logistic-regression model revealed that annual income, marital status, post-traumatic stress disorder, and hypertension were significant risk factors of SD (all P < 0.05) among younger Iraq/Afghanistan veterans, whereas among the older Iraq/Afghanistan veterans, being African American and having PTSD and hypertension were significant risk factors of SD (all P < 0.05). There was marked discrepancy between documented erectile dysfunction and prescription of a PDE5i. Conclusions. These data demonstrate that a significant proportion of Iraq/Afghanistan veterans have SD and that the risk factors differ between younger and older veterans. Our findings also suggest that SD is likely under-coded. To better identify the scope of the problem, systematic screening for sexual dysfunction may be appropriate perhaps as part of an initial post-deployment health evaluation. Hosain GMM, Latini DM, Kauth M, Goltz HH, and Helmer DA. Sexual dysfunction among male veterans returning from Iraq and Afghanistan: Prevalence and correlates. J Sex Med 2013;10:516-523.
C1 [Hosain, G. M. Monawar; Latini, David M.; Kauth, Michael; Goltz, Heather Honore] Michael E DeBakey Vet Affairs Med Ctr 152, Houston VA HSR&D Ctr Excellence, Houston, TX 77030 USA.
[Hosain, G. M. Monawar; Latini, David M.] Baylor Coll Med, Scott Dept Urol, Houston, TX 77030 USA.
[Kauth, Michael] S Cent Mental Illness Res Educ & Clin Ctr, Houston, TX USA.
[Kauth, Michael] Baylor Coll Med, Dept Psychiat & Behav Sci, Houston, TX 77030 USA.
[Goltz, Heather Honore] Univ Houston Downtown, Houston, TX USA.
[Helmer, Drew A.] VA RRD Ctr Excellence & PrimeCare, Houston, TX USA.
[Helmer, Drew A.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA.
RP Hosain, GMM (reprint author), Michael E DeBakey Vet Affairs Med Ctr 152, Houston VA HSR&D Ctr Excellence, 2002 Holcombe Blvd, Houston, TX 77030 USA.
EM monawarhosain@gmail.com
OI Latini, David/0000-0002-6161-4861; Goltz, Heather/0000-0002-2875-7764
FU NIH [K12 DK0083014]
FX G. M. Monawar Hosain is working as an NIDDK K-12 scholar (NIH Grant K12
DK0083014). This work was also supported in part by the facilities and
resources of the Houston VA HSR&D Center of Excellence (HFP90-020). The
views expressed reflect those of the authors and not necessarily those
of the Department of Veterans Affairs/Baylor College of Medicine. The
NIH had no role in the design and conduct of the study; the collection,
management, analysis, and interpretation of the data; or the
preparation, review, or approval of the manuscript.
NR 37
TC 21
Z9 21
U1 1
U2 14
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1743-6095
J9 J SEX MED
JI J. Sex. Med.
PD FEB
PY 2013
VL 10
IS 2
BP 516
EP 523
DI 10.1111/j.1743-6109.2012.02978.x
PG 8
WC Urology & Nephrology
SC Urology & Nephrology
GA 078OC
UT WOS:000314107400024
PM 23088675
ER
PT J
AU Passias, PG
Wang, SL
Kozanek, M
Wang, SB
Wang, C
AF Passias, Peter G.
Wang, Shenglin
Kozanek, Michal
Wang, Shaobai
Wang, Chao
TI Relationship Between the Alignment of the Occipitoaxial and Subaxial
Cervical Spine in Patients With Congenital Atlantoxial Dislocations
SO JOURNAL OF SPINAL DISORDERS & TECHNIQUES
LA English
DT Article
DE atlantoaxial dislocation; alignment; occipitoaxial; subaxial; cervical;
DDD
ID RHEUMATOID-ARTHRITIS; OCCIPITOCERVICAL FUSION; FOLLOW-UP; INSTABILITY;
ARTHRODESIS
AB Study Design: Prospective radiographic analysis.
Objective: This study aimed to characterize the relationship between the alignment of the occipitoaxial (OA) and the subaxial spine, establish normal parameters, and to determine the influence of upper cervical spine alignment on subaxial degenerative disc disease (DDD) and clinical outcomes in this population.
Summary of Background Data: Previous studies reported that the alignments of the upper and lower cervical spine are closely interrelated in patients with atlantoaxial dislocations of a rheumatoid etiology. None have focused on congenital etiologies or included patients with OA kyphosis. The influence of the upper cervical alignment on subaxial (DDD) and outcomes is also unclear.
Methods: Fifty-eight patients with congenital AAD undergoing surgical reduction and fusion were included. C0-C2 and C2-C7 angles were measured and DDD was assessed using plain radiographs. The relationship between the alignment of the OA joint and the subaxial cervical spine was evaluated, as well as the relationships between the cervical alignment, outcomes, and cervical DDD.
Results: C0-2 improved from a mean of 1.59 +/- 17.3 degrees preoperatively to a mean of 15 +/- 9.8 degrees postoperatively (P < 0.001). C2-7 changed from a mean of 25.55 +/- 19.6 degrees to a mean of 14.2 +/- 14.4 degrees postoperatively (P < 0.001). The OA and subaxial alignment were negatively correlated in this population both before (r = -0.84; P < 0.001) and after (r = -0.64; P < 0.001) surgical treatment. There was an increased incidence of DDD postoperatively (P < 0.01), which was positively correlated with the postoperative C0-2 angle (r = 0.54; P < 0.001), but negatively correlated with the postoperative C2-7 angle (r = -0.79; P < 0.001).
Conclusions: Changes in OA alignment before and after surgery are associated with changes in the subaxial spine. There is a high incidence of postoperative DDD in the subaxial spine that seems to be related to sagittal alignment after surgery.
C1 [Passias, Peter G.] NYU, Hosp Joint Dis, New York Spine Inst, Langone Med Ctr, New York, NY USA.
[Wang, Shenglin; Wang, Chao] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Harvard Combined Orthopaed Residency Program, Boston, MA USA.
[Kozanek, Michal] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bioengn Lab, Boston, MA USA.
[Kozanek, Michal; Wang, Shaobai; Wang, Chao] Peking Univ, Hosp 3, Dept Orthopaed, Beijing 100191, Peoples R China.
RP Wang, C (reprint author), Peking Univ, Hosp 3, Dept Orthopaed, 49 N Garden St, Beijing 100191, Peoples R China.
EM wangchaoo@ynet.com
NR 19
TC 5
Z9 7
U1 0
U2 5
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 FEB
PY 2013
VL 26
IS 1
BP 15
EP 21
DI 10.1097/BSD.0b013e31823097f9
PG 7
WC Clinical Neurology; Orthopedics
SC Neurosciences & Neurology; Orthopedics
GA 079HW
UT WOS:000314162200009
PM 21959834
ER
PT J
AU Yao, Q
Wang, SB
Shin, JH
Li, GA
Wood, KB
AF Yao, Qi
Wang, Shaobai
Shin, Jae-Hyuk
Li, Guoan
Wood, Kirkham Burwick
TI Lumbar Facet Joint Motion in Patients With Degenerative
Spondylolisthesis
SO JOURNAL OF SPINAL DISORDERS & TECHNIQUES
LA English
DT Article
DE degenerative lumbar spondylolisthesis; facet joint kinematics; facet
orientation; facet joint osteoarthritis; disk degeneration
ID SPINAL STENOSIS; DISC DISEASE; IN-VIVO; ORIENTATION; OSTEOARTHRITIS;
DECOMPRESSION; ASSOCIATION; OUTCOMES; SYSTEM; GRADE
AB Study Design: Controlled laboratory study.
Objective: To investigate the in vivo biomechanical effect of degenerative lumbar spondylolisthesis (DLS) on the motion of the facet joint during various functional weight-bearing activities.
Summary of Background Data: Although the morphologic changes of the facet joints in patients with DLS have been reported in a few studies, no data have been reported on the kinematics of these facet joints.
Methods: Ten patients with DLS at L4-L5 were studied. Each patient underwent a magnetic resonance imaging scan to obtain 3-dimensional models of the lumbar vertebrae from L2-L5 and a dual fluoroscopic imaging scan in different postures: flexion-extension, left-right bending, and left-right torsion. The positions of the vertebrae were reproduced by matching the magnetic resonance imaging-based vertebral models to the fluoroscopic images. The kinematics of the facet joint and the ranges of motion were compared with those of healthy subjects and those of patients with degenerative disk diseases (DDD) previously published.
Results: In DLS patients, the range of rotation of the facet joints was significantly less at the DLS level (L4-L5) than that at the adjacent levels (L2-L3 and L3-L4), whereas the range of translation was similar at all levels. The range of rotation at the facet joints of the DLS level decreased compared with those of both the DDD patients and healthy subjects at the corresponding vertebral level (L4-L5), whereas no significant difference was found in the range of translation. The range of motion of facet joints in DLS and in DDD patients was similar at the adjacent levels (L2-L3 and L3-L4).
Conclusions: The range of rotation decreased at the facet joints at the DLS level (L4-L5) in patients compared with those in healthy subjects and DDD patients. This decrease in range of rotation implies that the DLS disease may cause restabilization of the joint. The data may help the selection of conservative treatment or different surgical techniques for the DLS patients.
C1 [Li, Guoan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bioengn Lab,Dept Orthopaed Surg, Boston, MA 02114 USA.
[Yao, Qi; Wang, Shaobai; Shin, Jae-Hyuk; Li, Guoan; Wood, Kirkham Burwick] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Yao, Qi] Capital Med Univ, Beijing Shijitan Hosp, Dept Orthopaed Surg, Beijing, Peoples R China.
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 NIH [R21AR057989]; National Natural, Science Foundation of China
[81000796]; Beijing Nova Program [2011085]; China Scholarship Council
[2011911025]
FX Supported by partially the NIH (R21AR057989), National Natural, Science
Foundation of China (81000796) and Beijing Nova Program (2011085), and
China Scholarship Council (2011911025).
NR 38
TC 2
Z9 4
U1 0
U2 5
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 FEB
PY 2013
VL 26
IS 1
BP E19
EP E27
DI 10.1097/BSD.0b013e31827a254f
PG 9
WC Clinical Neurology; Orthopedics
SC Neurosciences & Neurology; Orthopedics
GA 079HW
UT WOS:000314162200004
PM 23168388
ER
PT J
AU Sweeney, C
AF Sweeney, Christopher
TI Prostate cancer therapy: going forwards by going backwards
SO LANCET ONCOLOGY
LA English
DT Editorial Material
ID INCREASED SURVIVAL; TRIAL; CHEMOTHERAPY; MITOXANTRONE; PREDNISONE
C1 Dana Farber Canc Inst, Boston, MA 02215 USA.
RP Sweeney, C (reprint author), Dana Farber Canc Inst, Boston, MA 02215 USA.
EM christopher_sweeney@dfci.harvard.edu
NR 10
TC 3
Z9 3
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1470-2045
J9 LANCET ONCOL
JI Lancet Oncol.
PD FEB
PY 2013
VL 14
IS 2
BP 104
EP 105
DI 10.1016/S1470-2045(12)70591-0
PG 2
WC Oncology
SC Oncology
GA 079JP
UT WOS:000314166700016
PM 23306099
ER
PT J
AU Choueiri, TK
Pomerantz, MM
Signoretti, S
AF Choueiri, Toni K.
Pomerantz, Mark M.
Signoretti, Sabina
TI Renal-cell carcinoma: a step closer to a new classification
SO LANCET ONCOLOGY
LA English
DT Editorial Material
ID THERAPY
C1 [Choueiri, Toni K.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Choueiri, TK (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA.
EM toni_choueiri@dfci.harvard.edu
NR 9
TC 3
Z9 3
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1470-2045
J9 LANCET ONCOL
JI Lancet Oncol.
PD FEB
PY 2013
VL 14
IS 2
BP 105
EP 107
DI 10.1016/S1470-2045(12)70599-5
PG 4
WC Oncology
SC Oncology
GA 079JP
UT WOS:000314166700017
PM 23333115
ER
PT J
AU Farley, J
Brady, WE
Vathipadiekal, V
Lankes, HA
Coleman, R
Morgan, MA
Mannel, R
Yamada, SD
Mutch, D
Rodgers, WH
Birrer, M
Gershenson, DM
AF Farley, John
Brady, William E.
Vathipadiekal, Vinod
Lankes, Heather A.
Coleman, Robert
Morgan, Mark A.
Mannel, Robert
Yamada, S. Diane
Mutch, David
Rodgers, William H.
Birrer, Michael
Gershenson, David M.
TI Selumetinib in women with recurrent low-grade serous carcinoma of the
ovary or peritoneum: an open-label, single-arm, phase 2 study
SO LANCET ONCOLOGY
LA English
DT Article
ID PEGYLATED LIPOSOMAL DOXORUBICIN; PLATINUM-RESISTANT; CLINICAL BEHAVIOR;
CANCER; TUMORS; CHEMOTHERAPY; MUTATIONS; CISPLATIN; PATTERNS; THERAPY
AB Background Low-grade serous carcinoma of the ovary is chemoresistant but mutations in the MAPK pathway could be targeted to control tumour growth. We therefore assessed the safety and activity of selumetinib, an inhibitor of MEK1/2, for patients with this cancer.
Methods In this open-label, single-arm phase 2 study, women (aged >= 18 years) with recurrent low-grade serous ovarian or peritoneal carcinoma were given selumetinib (50 mg twice daily, orally) until progression. The primary endpoint was the proportion of patients who had an objective tumour response according to RECIST version 1.1, assessed for all the treated patients. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00551070.
Findings 52 patients were enrolled between Dec 17, 2007, and Nov 23, 2009. All were eligible for analyses. Eight (15%) patients had an objective response to treatment-one patient had a complete response and seven had partial responses. 34 (65%) patients had stable disease. There were no treatment-related deaths. Grade 4 toxicities were cardiac (one), pain (one), and pulmonary events (one). Grade 3 toxicities that occurred in more than one patient were gastrointestinal (13), dermatological (nine), metabolic (seven), fatigue (six), anaemia (four), pain (four), constitutional (three), and cardiac events (two).
Interpretation Selumetinib is well tolerated, and is active in the treatment of recurrent low-grade serous carcinoma of the ovary or peritoneum. The findings suggest that inhibitors of the MAPK pathway warrant further investigation in these patients.
C1 [Farley, John] Creighton Univ, Sch Med, St Josephs Hosp, Div Gynecol Oncol,Dept Obstet & Gynecol,Med Ctr, Phoenix, AZ 85013 USA.
[Brady, William E.; Lankes, Heather A.] Roswell Pk Canc Inst, Gynecol Oncol Grp, Stat & Data Ctr, Buffalo, NY 14263 USA.
[Vathipadiekal, Vinod; Birrer, Michael] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Coleman, Robert; Gershenson, David M.] Univ Texas MD Anderson Canc Ctr, Dept Gynecol & Oncol, Houston, TX 77030 USA.
[Morgan, Mark A.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
[Mannel, Robert] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA.
[Yamada, S. Diane] Univ Chicago, Gynecol Oncol Sect, Chicago, IL 60637 USA.
[Mutch, David] Washington Univ, Sch Med, Dept Obstet & Gynecol, Div Gynecol Oncol, St Louis, MO 63110 USA.
[Rodgers, William H.] Lenox Hill Hosp, Dept Pathol, New York, NY 10021 USA.
RP Farley, J (reprint author), Creighton Univ, Sch Med, St Josephs Hosp, Div Gynecol Oncol,Dept Obstet & Gynecol,Med Ctr, 500 W Thomas Rd,Suite 600, Phoenix, AZ 85013 USA.
EM John.farley@chw.edu
OI Vathipadiekal, Vinod/0000-0002-8181-6890
FU National Cancer Institute [CA 27469]; GOG; GOG Statistical Office [CA
37517]; Cancer Therapy Evaluation Program of the National Cancer
Institute
FX DMG received funding from the National Cancer Institute (Cancer Therapy
Evaluation Program) and the GOG. The other authors declare that they
have no conflicts of interest.; This study was supported by National
Cancer Institute grants to the GOG Administrative Office (CA 27469) and
the GOG Statistical Office (CA 37517). The trial was sponsored by the
Cancer Therapy Evaluation Program of the National Cancer Institute. The
following GOG member institutions participated in the primary treatment
studies: University of Mississippi Medical Center, University of
California Medical Center at Irvine, Cleveland Clinic Foundation,
Washington University School of Medicine, Memorial Sloan-Kettering
Cancer Center, Columbus Cancer Council, MD Anderson Cancer Center, Fox
Chase Cancer Center, University of Oklahoma, University of Chicago, Case
Western Reserve University, Women and Infants Hospital, and Community
Clinical Oncology Program.
NR 24
TC 113
Z9 118
U1 0
U2 14
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 FEB
PY 2013
VL 14
IS 2
BP 134
EP 140
DI 10.1016/S1470-2045(12)70572-7
PG 7
WC Oncology
SC Oncology
GA 079JP
UT WOS:000314166700026
PM 23261356
ER
PT J
AU Heng, DYC
Xie, WL
Regan, MM
Harshman, LC
Bjarnason, GA
Vaishampayan, UN
Mackenzie, M
Wood, L
Donskov, F
Tan, MH
Rha, SY
Agarwal, N
Kollmannsberger, C
Rini, BI
Choueiri, TK
AF Heng, Daniel Y. C.
Xie, Wanling
Regan, Meredith M.
Harshman, Lauren C.
Bjarnason, Georg A.
Vaishampayan, Ulka N.
Mackenzie, Mary
Wood, Lori
Donskov, Frede
Tan, Min-Han
Rha, Sun-Young
Agarwal, Neeraj
Kollmannsberger, Christian
Rini, Brian I.
Choueiri, Toni K.
TI External validation and comparison with other models of the
International Metastatic Renal-Cell Carcinoma Database Consortium
prognostic model: a population-based study
SO LANCET ONCOLOGY
LA English
DT Article
ID INTERFERON-ALPHA; SURVIVAL; RECLASSIFICATION; SORAFENIB; INTERVAL;
CANCER; TRIAL
AB Background The International Metastatic Renal-Cell Carcinoma Database Consortium model offers prognostic information for patients with metastatic renal-cell carcinoma. We tested the accuracy of the model in an external population and compared it with other prognostic models.
Methods We included patients with metastatic renal-cell carcinoma who were treated with first-line VEGF-targeted treatment at 13 international cancer centres and who were registered in the Consortium's database but had not contributed to the initial development of the Consortium Database model. The primary endpoint was overall survival. We compared the Database Consortium model with the Cleveland Clinic Foundation (CCF) model, the International Kidney Cancer Working Group (IKCWG) model, the French model, and the Memorial Sloan-Kettering Cancer Center (MSKCC) model by concordance indices and other measures of model fit.
Findings Overall, 1028 patients were included in this study, of whom 849 had complete data to assess the Database Consortium model. Median overall survival was 18.8 months (95% 17.6-21.4). The predefined Database Consortium risk factors (anaemia, thrombocytosis, neutrophilia, hypercalcaemia, Karnofsky performance status <80%, and <1 year from diagnosis to treatment) were independent predictors of poor overall survival in the external validation set (hazard ratios ranged between 1.27 and 2.08, concordance index 0.71, 95% CI 0.68-0.73). When patients were segregated into three risk categories, median overall survival was 43.2 months (95% CI 31.4-50.1) in the favourable risk group (no risk factors; 157 patients), 22.5 months (18.7-25.1) in the intermediate risk group (one to two risk factors; 440 patients), and 7.8 months (6.5-9.7) in the poor risk group (three or more risk factors; 252 patients; p<0.0001; concordance index 0.664, 95% CI 0.639-0.689). 672 patients had complete data to test all five models. The concordance index of the CCF model was 0.662 (95% CI 0.636-0.687), of the French model 0.640 (0.614-0.665), of the IKCWG model 0.668 (0.645-0.692), and of the MSKCC model 0.657 (0.632-0.682). The reported versus predicted number of deaths at 2 years was most similar in the Database Consortium model compared with the other models.
Interpretation The Database Consortium model is now externally validated and can be applied to stratify patients by risk in clinical trials and to counsel patients about prognosis.
C1 [Heng, Daniel Y. C.] Univ Calgary, Tom Baker Canc Ctr, Calgary, AB T2N 4N2, Canada.
[Xie, Wanling; Regan, Meredith M.; Choueiri, Toni K.] Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Harshman, Lauren C.] Stanford Univ, Stanford Canc Inst, Stanford, CA 94305 USA.
[Bjarnason, Georg A.] Sunnybrook Odette Canc Inst, Toronto, ON, Canada.
[Vaishampayan, Ulka N.] Wayne State Univ, Detroit, MI USA.
[Mackenzie, Mary] London Hlth Sci Ctr, London, ON, Canada.
[Wood, Lori] Queen Elizabeth 2 Hlth Sci Ctr, Halifax, NS, Canada.
[Donskov, Frede] Aarhus Univ Hosp, DK-8000 Aarhus, Denmark.
[Tan, Min-Han] Natl Canc Ctr, Inst Bioengn & Nanotechnol, Singapore, Singapore.
[Rha, Sun-Young] Yonsei Univ Hosp, Seoul, South Korea.
[Agarwal, Neeraj] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA.
[Kollmannsberger, Christian] BC Canc Agcy, Vancouver, BC, Canada.
[Rini, Brian I.] Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA.
RP Heng, DYC (reprint author), Univ Calgary, Tom Baker Canc Ctr, Calgary, AB T2N 4N2, Canada.
EM daniel.heng@albertahealthservices.ca
OI Bjarnason, Georg Arnold/0000-0001-6903-5357; Donskov,
Frede/0000-0002-8449-863X
FU Bristol-Myers Squibb; Novartis; Genentech; Pfizer; GlaxoSmithKline;
Bayer Korea
FX DYCH has an advisory role at Aveo, Pfizer, Novartis, and Bayer. LCH has
an advisory role at Novartis and Pfizer and has received research
funding from Bristol-Myers Squibb, Novartis, and Genentech. GAB has a
consultant and advisory role at Pfizer and has received honoraria and
research funding from Pfizer. MM has an advisory role at Novartis and
Pfizer and has received research funding from both. LW has an advisory
role at Pfizer and Novartis and has received research funding from
Pfizer, Novartis, and GlaxoSmithKline. UNV has received honoraria and
research funding from Pfizer, Novartis, and GlaxoSmithKline. S-YR has an
advisory role at Novartis, Pfizer, and GlaxoSmithKline, and has received
research funding from Novartis and Bayer Korea. FD has received research
funding from Novartis. CK has an advisory role at Pfizer, Novartis, and
GlaxoSmithKline and has received honoraria and research funding from
Pfizer, Novartis, and GlaxoSmithKline. BIR has an advisory role at
Pfizer, GlaxoSmithKline, Aveo, Bayer, Onyx, and has received research
funding from GlaxoSmithKline and Pfizer. TKC has received research
funding from Pfizer and has an advisory role at Aveo, Pfizer, Novartis,
GlaxoSmithKline, Genentech, Bayer, and Onyx. WX, MMR, M-HT, and NA
declare that they have no conflicts of interest.
NR 24
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U1 0
U2 7
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 FEB
PY 2013
VL 14
IS 2
BP 141
EP 148
DI 10.1016/S1470-2045(12)70559-4
PG 8
WC Oncology
SC Oncology
GA 079JP
UT WOS:000314166700027
PM 23312463
ER
PT J
AU Joffe, H
AF Joffe, Hadine
TI Antidepressant use after discontinuation of hormone therapy: what can
one infer about post-hormone therapy depression?
SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY
LA English
DT Editorial Material
ID REPLACEMENT THERAPY; VASOMOTOR SYMPTOMS; MENOPAUSAL TRANSITION;
PERIMENOPAUSAL WOMEN; ESTROGEN REPLACEMENT; PUBLICATION; TRIAL;
PREDICTORS; CESSATION; DURATION
C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Womens Mental Hlth,Dept Psychiat, Boston, MA 02115 USA.
RP Joffe, H (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Womens Mental Hlth,Dept Psychiat, Boston, MA 02115 USA.
NR 24
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U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1072-3714
J9 MENOPAUSE
JI Menopause-J. N. Am. Menopause Soc.
PD FEB
PY 2013
VL 20
IS 2
BP 123
EP 125
DI 10.1097/gme.0b013e31828059d4
PG 3
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 081SM
UT WOS:000314342600003
PM 23340264
ER
PT J
AU Scott, NS
AF Scott, Nandita S.
TI Coronary artery calcium and exercise: does a relationship exist and does
it matter?
SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY
LA English
DT Editorial Material
ID PHYSICAL-ACTIVITY; FUNCTIONAL-CAPACITY; SYNDROME-X; WOMEN;
CALCIFICATION; METAANALYSIS; MORTALITY; DISEASE; GENDER; RISK
C1 Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA.
RP Scott, NS (reprint author), Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA.
NR 20
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U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1072-3714
J9 MENOPAUSE
JI Menopause-J. N. Am. Menopause Soc.
PD FEB
PY 2013
VL 20
IS 2
BP 126
EP 127
DI 10.1097/gme.0b013e31827c44d2
PG 2
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 081SM
UT WOS:000314342600004
PM 23299705
ER
PT J
AU Trynka, G
Sandor, C
Han, B
Xu, H
Stranger, BE
Liu, XS
Raychaudhuri, S
AF Trynka, Gosia
Sandor, Cynthia
Han, Buhm
Xu, Han
Stranger, Barbara E.
Liu, X. Shirley
Raychaudhuri, Soumya
TI Chromatin marks identify critical cell types for fine mapping complex
trait variants
SO NATURE GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; DIABETES SUSCEPTIBILITY LOCI;
RHEUMATOID-ARTHRITIS; T-CELLS; EXPRESSION; ENHANCERS; DISEASE;
SCHIZOPHRENIA; METHYLATIONS; METAANALYSIS
AB If trait-associated variants alter regulatory regions, then they should fall within chromatin marks in relevant cell types. However, it is unclear which of the many marks are most useful in defining cell types associated with disease and fine mapping variants. We hypothesized that informative marks are phenotypically cell type specific; that is, SNPs associated with the same trait likely overlap marks in the same cell type. We examined 15 chromatin marks and found that those highlighting active gene regulation were phenotypically cell type specific. Trimethylation of histone H3 at lysine 4 (H3K4me3) was the most phenotypically cell type specific (P < 1 x 10(-6)), driven by colocalization of variants and marks rather than gene proximity (P < 0.001). H3K4me3 peaks overlapped with 37 SNPs for plasma low-density lipoprotein concentration in the liver (P < 7 x 10(-5)), 31 SNPs for rheumatoid arthritis within CD4(+) regulatory T cells (P = 1 x 10(-4)), 67 SNPs for type 2 diabetes in pancreatic islet cells (P = 0.003) and the liver (P = 0.003), and 14 SNPs for neuropsychiatric disease in neuronal tissues (P = 0.007). We show how cell type-specific H3K4me3 peaks can inform the fine mapping of associated SNPs to identify causal variation.
C1 [Trynka, Gosia; Sandor, Cynthia; Han, Buhm; Stranger, Barbara E.; Raychaudhuri, Soumya] Harvard Univ, Brigham & Womens Hosp, Div Genet, Sch Med, Boston, MA 02115 USA.
[Trynka, Gosia; Sandor, Cynthia; Han, Buhm; Raychaudhuri, Soumya] Harvard Univ, Brigham & Womens Hosp, Div Rheumatol, Sch Med, Boston, MA 02115 USA.
[Trynka, Gosia; Sandor, Cynthia; Han, Buhm; Raychaudhuri, Soumya] Partners Ctr Personalized Genet Med, Boston, MA USA.
[Trynka, Gosia; Sandor, Cynthia; Han, Buhm; Stranger, Barbara E.; Raychaudhuri, Soumya] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA.
[Xu, Han; Liu, X. Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Xu, Han; Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Raychaudhuri, Soumya] Univ Manchester, Fac Med & Human Sci, Manchester, Lancs, England.
RP Raychaudhuri, S (reprint author), Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA.
EM soumya@broadinstitute.org
OI Trynka, Gosia/0000-0002-6955-9529; Stranger, Barbara/0000-0001-9021-7331
FU Rubicon grant from The Netherlands Organization for Scientific Research
(NWO); Harvard University Milton Fund; Brigham and Women's Hospital; US
NIH [K08AR055688, U01HG0070033, R01 HG004069]; Arthritis Foundation;
NHGRI; NIH Roadmap Epigenomics Mapping Consortium
FX We thank M. Daly, M. Kellis, D. Diogo, X. Hu, Y. Okada, R. Plenge, S.
Ripke, G. Srivastava, E. Stahl and S. Sunyaev for critical feedback and
discussion. G.T. is supported by the Rubicon grant from The Netherlands
Organization for Scientific Research (NWO). B.E.S. and S.R. are
supported by the Harvard University Milton Fund, and Brigham and Women's
Hospital. S.R. is also supported by funds from the US NIH (K08AR055688
and U01HG0070033) and the Arthritis Foundation. X.S.L. is also supported
by funds from the US NIH (R01 HG004069). We thank the ENCODE Project,
supported by the NHGRI, and the NIH Roadmap Epigenomics Mapping
Consortium for making data available.
NR 55
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U1 3
U2 33
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 FEB
PY 2013
VL 45
IS 2
BP 124
EP 130
DI 10.1038/ng.2504
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA 081PB
UT WOS:000314333000005
PM 23263488
ER
PT J
AU Chmielecki, J
Crago, AM
Rosenberg, M
O'Connor, R
Walker, SR
Ambrogio, L
Auclair, D
McKenna, A
Heinrich, MC
Frank, DA
Meyerson, M
AF Chmielecki, Juliann
Crago, Aimee M.
Rosenberg, Mara
O'Connor, Rachael
Walker, Sarah R.
Ambrogio, Lauren
Auclair, Daniel
McKenna, Aaron
Heinrich, Michael C.
Frank, David A.
Meyerson, Matthew
TI Whole-exome sequencing identifies a recurrent NAB2-STAT6 fusion in
solitary fibrous tumors
SO NATURE GENETICS
LA English
DT Article
ID EXPRESSION; CANCER; MUTATIONS; NAB2; COREPRESSOR; ACTIVATION; GROWTH;
STAT6
AB Solitary fibrous tumors (SFTs) are rare mesenchymal tumors. Here, we describe the identification of a NAB2-STAT6 fusion from whole-exome sequencing of 17 SFTs. Analysis in 53 tumors confirmed the presence of 7 variants of this fusion transcript in 29 tumors (55%), representing a lower bound for fusion frequency at this locus and suggesting that the NAB2-STAT6 fusion is a distinct molecular feature of SFTs.
C1 [Chmielecki, Juliann; Walker, Sarah R.; Frank, David A.; Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Chmielecki, Juliann; Rosenberg, Mara; Ambrogio, Lauren; Auclair, Daniel; McKenna, Aaron; Meyerson, Matthew] Broad Inst Harvard & MIT, Canc Program, Cambridge, MA USA.
[Crago, Aimee M.; O'Connor, Rachael] Mem Sloan Kettering Canc Ctr, Dept Surg, Sarcoma Biol Lab, New York, NY 10021 USA.
[Walker, Sarah R.; Frank, David A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Walker, Sarah R.; Frank, David A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Heinrich, Michael C.] Portland Vet Affairs VA Med Ctr, Div Hematol & Med Oncol, Portland, OR USA.
[Heinrich, Michael C.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA.
[Meyerson, Matthew] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RP Meyerson, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
EM matthew_meyerson@dfci.harvard.edu
OI Crago, Aimee/0000-0002-2965-752X; O'Connor, Rachael/0000-0002-6869-7954
FU Carlos Slim Health Institute in Mexico; Specialized Program of Research
Excellence (SPORE) grant in Soft Tissue Sarcoma [P50 CA140146]; MSKCC
[P01CA47179]; American Cancer Society AstraZeneca; Kristen Ann Carr
Foundation
FX We are grateful to the individuals with SFT who contributed material for
this study. We thank members of the Genomics Platform at the Broad
Institute for their technical expertise and M. Abazeed and A. Dulak for
critically reviewing the manuscript. This work was conducted as part of
the Slim Initiative for Genomic Medicine in the Americas (SIGMA), a
project funded by the Carlos Slim Health Institute in Mexico. This work
was supported by a Specialized Program of Research Excellence (SPORE)
grant in Soft Tissue Sarcoma (P50 CA140146) and a P01 grant (P01CA47179)
to S. Singer (MSKCC). J.C. is supported by an American Cancer Society
AstraZeneca Postdoctoral Fellowship. A.M.C. is supported by a grant from
the Kristen Ann Carr Foundation. M.M. is supported by generous donations
from M.B. Zuckerman and Team Dragonfly of the Pan-Mass Challenge.
Material was collected under institutional review board (IRB)-approved
protocols at the Memorial Sloan-Kettering Cancer Center and the Oregon
Health & Science University Biolibrary. All patients provided informed
consent.
NR 15
TC 122
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U1 0
U2 10
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 FEB
PY 2013
VL 45
IS 2
BP 131
EP 132
DI 10.1038/ng.2522
PG 2
WC Genetics & Heredity
SC Genetics & Heredity
GA 081PB
UT WOS:000314333000006
PM 23313954
ER
PT J
AU Kottgen, A
Albrecht, E
Teumer, A
Vitart, V
Krumsiek, J
Hundertmark, C
Pistis, G
Ruggiero, D
O'Seaghdha, CM
Haller, T
Yang, Q
Tanaka, T
Johnson, AD
Kutalik, Z
Smith, AV
Shi, JL
Struchalin, M
Middelberg, RPS
Brown, MJ
Gaffo, AL
Pirastu, N
Li, G
Hayward, C
Zemunik, T
Huffman, J
Yengo, L
Zhao, JH
Demirkan, A
Feitosa, MF
Liu, X
Malerba, G
Lopez, LM
van der Harst, P
Li, XZ
Kleber, ME
Hicks, AA
Nolte, IM
Johansson, A
Murgia, F
Wild, SH
Bakker, SJL
Peden, JF
Dehghan, A
Steri, M
Tenesa, A
Lagou, V
Salo, P
Mangino, M
Rose, LM
Lehtimaki, T
Woodward, OM
Okada, Y
Tin, A
Muller, C
Oldmeadow, C
Putku, M
Czamara, D
Kraft, P
Frogheri, L
Thun, GA
Grotevendt, A
Gislason, GK
Harris, TB
Launer, LJ
McArdle, P
Shuldiner, AR
Boerwinkle, E
Coresh, J
Schmidt, H
Schallert, M
Martin, NG
Montgomery, GW
Kubo, M
Nakamura, Y
Tanaka, T
Munroe, PB
Samani, NJ
Jacobs, DR
Liu, K
D'Adamo, P
Ulivi, S
Rotter, JI
Psaty, BM
Vollenweider, P
Waeber, G
Campbell, S
Devuyst, O
Navarro, P
Kolcic, I
Hastie, N
Balkau, B
Froguel, P
Esko, T
Salumets, A
Khaw, KT
Langenberg, C
Wareham, NJ
Isaacs, A
Kraja, A
Zhang, QY
Wild, PS
Scott, RJ
Holliday, EG
Org, E
Viigimaa, M
Bandinelli, S
Metter, JE
Lupo, A
Trabetti, E
Sorice, R
Doring, A
Lattka, E
Strauch, K
Theis, F
Waldenberger, M
Wichmann, HE
Davies, G
Gow, AJ
Bruinenberg, M
Stolk, RP
Kooner, JS
Zhang, WH
Winkelmann, BR
Boehm, BO
Lucae, S
Penninx, BW
Smit, JH
Curhan, G
Mudgal, P
Plenge, RM
Portas, L
Persico, I
Kirin, M
Wilson, JF
Leach, IM
van Gilst, WH
Goel, A
Ongen, H
Hofman, A
Rivadeneira, F
Uitterlinden, AG
Imboden, M
von Eckardstein, A
Cucca, F
Nagaraja, R
Piras, MG
Nauck, M
Schurmann, C
Budde, K
Ernst, F
Farrington, SM
Theodoratou, E
Prokopenko, I
Stumvoll, M
Jula, A
Perola, M
Salomaa, V
Shin, SY
Spector, TD
Sala, C
Ridker, PM
Kahonen, M
Viikari, J
Hengstenberg, C
Nelson, CP
Meschia, JF
Nalls, MA
Sharma, P
Singleton, AB
Kamatani, N
Zeller, T
Burnier, M
Attia, J
Laan, M
Klopp, N
Hillege, HL
Kloiber, S
Choi, H
Pirastu, M
Tore, S
Probst-Hensch, NM
Volzke, H
Gudnason, V
Parsa, A
Schmidt, R
Whitfield, JB
Fornage, M
Gasparini, P
Siscovick, DS
Polasek, O
Campbell, H
Rudan, I
Bouatia-Naji, N
Metspalu, A
Loos, RJF
van Duijn, CM
Borecki, IB
Ferrucci, L
Gambaro, G
Deary, IJ
Wolffenbuttel, BHR
Chambers, JC
Marz, W
Pramstaller, PP
Snieder, H
Gyllensten, U
Wright, AF
Navis, G
Watkins, H
Witteman, JCM
Sanna, S
Schipf, S
Dunlop, MG
Tonjes, A
Ripatti, S
Soranzo, N
Toniolo, D
Chasman, DI
Raitakari, O
Kao, WHL
Ciullo, M
Fox, CS
Caulfield, M
Bochud, M
Gieger, C
AF Koettgen, Anna
Albrecht, Eva
Teumer, Alexander
Vitart, Veronique
Krumsiek, Jan
Hundertmark, Claudia
Pistis, Giorgio
Ruggiero, Daniela
O'Seaghdha, Conall M.
Haller, Toomas
Yang, Qiong
Tanaka, Toshiko
Johnson, Andrew D.
Kutalik, Zoltan
Smith, Albert V.
Shi, Julia
Struchalin, Maksim
Middelberg, Rita P. S.
Brown, Morris J.
Gaffo, Angelo L.
Pirastu, Nicola
Li, Guo
Hayward, Caroline
Zemunik, Tatijana
Huffman, Jennifer
Yengo, Loic
Zhao, Jing Hua
Demirkan, Ayse
Feitosa, Mary F.
Liu, Xuan
Malerba, Giovanni
Lopez, Lorna M.
van der Harst, Pim
Li, Xinzhong
Kleber, Marcus E.
Hicks, Andrew A.
Nolte, Ilja M.
Johansson, Asa
Murgia, Federico
Wild, Sarah H.
Bakker, Stephan J. L.
Peden, John F.
Dehghan, Abbas
Steri, Maristella
Tenesa, Albert
Lagou, Vasiliki
Salo, Perttu
Mangino, Massimo
Rose, Lynda M.
Lehtimaki, Terho
Woodward, Owen M.
Okada, Yukinori
Tin, Adrienne
Mueller, Christian
Oldmeadow, Christopher
Putku, Margus
Czamara, Darina
Kraft, Peter
Frogheri, Laura
Thun, Gian Andri
Grotevendt, Anne
Gislason, Gauti Kjartan
Harris, Tamara B.
Launer, Lenore J.
McArdle, Patrick
Shuldiner, Alan R.
Boerwinkle, Eric
Coresh, Josef
Schmidt, Helena
Schallert, Michael
Martin, Nicholas G.
Montgomery, Grant W.
Kubo, Michiaki
Nakamura, Yusuke
Tanaka, Toshihiro
Munroe, Patricia B.
Samani, Nilesh J.
Jacobs, David R., Jr.
Liu, Kiang
D'Adamo, Pio
Ulivi, Sheila
Rotter, Jerome I.
Psaty, Bruce M.
Vollenweider, Peter
Waeber, Gerard
Campbell, Susan
Devuyst, Olivier
Navarro, Pau
Kolcic, Ivana
Hastie, Nicholas
Balkau, Beverley
Froguel, Philippe
Esko, Tonu
Salumets, Andres
Khaw, Kay Tee
Langenberg, Claudia
Wareham, Nicholas J.
Isaacs, Aaron
Kraja, Aldi
Zhang, Qunyuan
Wild, Philipp S.
Scott, Rodney J.
Holliday, Elizabeth G.
Org, Elin
Viigimaa, Margus
Bandinelli, Stefania
Metter, Jeffrey E.
Lupo, Antonio
Trabetti, Elisabetta
Sorice, Rossella
Doering, Angela
Lattka, Eva
Strauch, Konstantin
Theis, Fabian
Waldenberger, Melanie
Wichmann, H-Erich
Davies, Gail
Gow, Alan J.
Bruinenberg, Marcel
Stolk, Ronald P.
Kooner, Jaspal S.
Zhang, Weihua
Winkelmann, Bernhard R.
Boehm, Bernhard O.
Lucae, Susanne
Penninx, Brenda W.
Smit, Johannes H.
Curhan, Gary
Mudgal, Poorva
Plenge, Robert M.
Portas, Laura
Persico, Ivana
Kirin, Mirna
Wilson, James F.
Leach, Irene Mateo
van Gilst, Wiek H.
Goel, Anuj
Ongen, Halit
Hofman, Albert
Rivadeneira, Fernando
Uitterlinden, Andre G.
Imboden, Medea
von Eckardstein, Arnold
Cucca, Francesco
Nagaraja, Ramaiah
Piras, Maria Grazia
Nauck, Matthias
Schurmann, Claudia
Budde, Kathrin
Ernst, Florian
Farrington, Susan M.
Theodoratou, Evropi
Prokopenko, Inga
Stumvoll, Michael
Jula, Antti
Perola, Markus
Salomaa, Veikko
Shin, So-Youn
Spector, Tim D.
Sala, Cinzia
Ridker, Paul M.
Kaehoenen, Mika
Viikari, Jorma
Hengstenberg, Christian
Nelson, Christopher P.
Meschia, James F.
Nalls, Michael A.
Sharma, Pankaj
Singleton, Andrew B.
Kamatani, Naoyuki
Zeller, Tanja
Burnier, Michel
Attia, John
Laan, Maris
Klopp, Norman
Hillege, Hans L.
Kloiber, Stefan
Choi, Hyon
Pirastu, Mario
Tore, Silvia
Probst-Hensch, Nicole M.
Voelzke, Henry
Gudnason, Vilmundur
Parsa, Afshin
Schmidt, Reinhold
Whitfield, John B.
Fornage, Myriam
Gasparini, Paolo
Siscovick, David S.
Polasek, Ozren
Campbell, Harry
Rudan, Igor
Bouatia-Naji, Nabila
Metspalu, Andres
Loos, Ruth J. F.
van Duijn, Cornelia M.
Borecki, Ingrid B.
Ferrucci, Luigi
Gambaro, Giovanni
Deary, Ian J.
Wolffenbuttel, Bruce H. R.
Chambers, John C.
Maerz, Winfried
Pramstaller, Peter P.
Snieder, Harold
Gyllensten, Ulf
Wright, Alan F.
Navis, Gerjan
Watkins, Hugh
Witteman, Jacqueline C. M.
Sanna, Serena
Schipf, Sabine
Dunlop, Malcolm G.
Toenjes, Anke
Ripatti, Samuli
Soranzo, Nicole
Toniolo, Daniela
Chasman, Daniel I.
Raitakari, Olli
Kao, W. H. Linda
Ciullo, Marina
Fox, Caroline S.
Caulfield, Mark
Bochud, Murielle
Gieger, Christian
CA LifeLines Cohort Study
CARDIoGRAM Consortium
DIAGRAM Consortium
ICBP Consortium
MAGIC Consortium
TI Genome-wide association analyses identify 18 new loci associated with
serum urate concentrations
SO NATURE GENETICS
LA English
DT Article
ID URIC-ACID LEVELS; CARDIOVASCULAR-DISEASE RISK; MOLECULAR PHYSIOLOGY;
METABOLIC SYNDROME; GENETIC-LOCI; GOUT; HYPERURICEMIA; POPULATION;
IDENTIFICATION; TRANSPORTER
AB Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from >140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with serum urate concentrations (18 new regions in or near TRIM46, INHBB, SEMBT1, TMEM171, VEGFA, BAZ1B, PRKAG2, STC1, HNF4G, A1CF, ATXN2, UBE2Q2, IGF1R, NFAT5, MAF, HLF, ACVR1B-ACVRL1 and B3GNT4). Associations for many of the loci were of similar magnitude in individuals of non-European ancestry. We further characterized these loci for associations with gout, transcript expression and the fractional excretion of urate. Network analyses implicate the inhibins-activins signaling pathways and glucose metabolism in systemic urate control. New candidate genes for serum urate concentration highlight the importance of metabolic control of urate production and excretion, which may have implications for the treatment and prevention of gout.
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RP Kottgen, A (reprint author), Freiburg Univ Hosp, Renal Div, Freiburg, Germany.
EM anna.koettgen@uniklinik-freiburg.de; veronique.vitart@igmm.ed.ac.uk;
murielle.bochud@chuv.ch; christian.gieger@helmholtz-muenchen.de
RI Colaus, PsyColaus/K-6607-2013; Farrington, Susan/C-7319-2013; Deary,
Ian/C-6297-2009; Krumsiek, Jan/B-3961-2013; Pirastu, Nicola/G-4358-2011;
Johnson, Andrew/G-6520-2013; Ulivi, Sheila/H-3700-2013; Gow,
Alan/A-6070-2009; Rudan, Igor/I-1467-2012; Attia, John/F-5376-2013;
Laan, Maris/A-4100-2011; Lagou, Vasiliki/N-8451-2013; mangino,
massimo/F-5134-2011; Hayward, Caroline/M-8818-2016; BOUATIA-NAJI,
NABILA/D-5863-2013; Dunlop, Malcolm/F-1973-2011; Yengo,
Loic/D-2692-2017; Kolcic, Ivana/E-2713-2017; Feitosa, Mary/K-8044-2012;
Hicks, Andrew/E-9518-2017; Gudnason, Vilmundur/K-6885-2015; Ripatti,
Samuli/H-9446-2014; Wilson, James F/A-5704-2009; Polasek,
Ozren/B-6002-2011; Montgomery, Grant/B-7148-2008; Rivadeneira,
Fernando/O-5385-2015; Prokopenko, Inga/H-3241-2014; Tanaka,
Toshihiro/J-9310-2014; Smith, Albert/K-5150-2015; Kubo,
Michiaki/N-7947-2015; ruggiero, daniela/K-5638-2016; Schurmann,
Claudia/L-1204-2016; Bochud, Murielle/A-3981-2010; Reischl,
Eva/B-9311-2013; Waldenberger, Melanie/B-5355-2014; Gasparini,
Paolo/B-6173-2014; d'Adamo, Adamo Pio/G-4064-2011; Theodoratou,
Evropi/C-3430-2014; Singleton, Andrew/C-3010-2009; Yang,
Qiong/G-5438-2014; Pramstaller, Peter/C-2357-2008; Johansson,
Asa/G-5270-2011; Boehm, Bernhard/F-8750-2015; Salumets,
Andres/J-2278-2015; Bakker, Stephan/J-4023-2015
OI Ulivi, Sheila/0000-0003-3606-835X; Gow, Alan/0000-0002-3320-4531; Rudan,
Igor/0000-0001-6993-6884; Attia, John/0000-0001-9800-1308; Laan,
Maris/0000-0002-8519-243X; Kleber, Marcus/0000-0003-0663-7275; Martin,
Nicholas/0000-0003-4069-8020; Dehghan, Abbas/0000-0001-6403-016X;
Watkins, Hugh/0000-0002-5287-9016; Theis, Fabian/0000-0002-2419-1943;
Steri, Anna Maristella/0000-0001-5869-3872; Soranzo,
Nicole/0000-0003-1095-3852; Gieger, Christian/0000-0001-6986-9554;
Wolffenbuttel, Bruce H.R./0000-0001-9262-6921; Org,
Elin/0000-0003-1451-9375; Esko, Tonu/0000-0003-1982-6569; Malerba,
Giovanni/0000-0001-8705-8560; piras, maria grazia/0000-0001-9004-0900;
sanna, serena/0000-0002-3768-1749; Kloiber, Stefan/0000-0002-6838-4114;
mangino, massimo/0000-0002-2167-7470; Hayward,
Caroline/0000-0002-9405-9550; Dunlop, Malcolm/0000-0002-3033-5851;
Yengo, Loic/0000-0002-4272-9305; Kolcic, Ivana/0000-0001-7918-6052;
Feitosa, Mary/0000-0002-0933-2410; Hicks, Andrew/0000-0001-6320-0411;
Thun, Gian Andri/0000-0003-4436-3455; Pirastu,
Nicola/0000-0002-5363-3886; Bouatia-Naji, Nabila/0000-0001-5424-2134;
Navarro, Pau/0000-0001-5576-8584; Gudnason,
Vilmundur/0000-0001-5696-0084; Ripatti, Samuli/0000-0002-0504-1202;
Wilson, James F/0000-0001-5751-9178; Polasek, Ozren/0000-0002-5765-1862;
Montgomery, Grant/0000-0002-4140-8139; Rivadeneira,
Fernando/0000-0001-9435-9441; Prokopenko, Inga/0000-0003-1624-7457;
Tanaka, Toshihiro/0000-0001-6201-9784; Smith,
Albert/0000-0003-1942-5845; ruggiero, daniela/0000-0003-3898-7827;
Schurmann, Claudia/0000-0003-4158-9192; Bochud,
Murielle/0000-0002-5727-0218; Reischl, Eva/0000-0003-4055-8060;
Waldenberger, Melanie/0000-0003-0583-5093; d'Adamo, Adamo
Pio/0000-0001-9367-4909; Theodoratou, Evropi/0000-0001-5887-9132;
Johansson, Asa/0000-0002-2915-4498; Salumets,
Andres/0000-0002-1251-8160; Bakker, Stephan/0000-0003-3356-6791
FU Biotechnology and Biological Sciences Research Council [BB/F019394/1];
Cancer Research UK [12076, 14136]; Chief Scientist Office [CZB/4/710];
Intramural NIH HHS [Z01 AG000954-06]; Medical Research Council
[G0401527, G0600237, G0700704, G1000143, G1002084, G9521010,
MC_PC_U127592696, MC_U106179471, MC_U106188470, MC_U127527198,
MC_U127592696, MR/K006584/1, MR/K026992/1]; NCATS NIH HHS [UL1
TR000124]; NCI NIH HHS [P01 CA087969, R01 CA047988]; NCRR NIH HHS [K12
RR023250, M01 RR016500, UL1 RR025005]; NHGRI NIH HHS [U01 HG004402, U01
HG004424, U01 HG004446, U01 HG004729]; NHLBI NIH HHS [HHSN268201100008C,
HHSN268201100005C, HHSN268201100006C, HHSN268201100007C,
HHSN268201100009C, HHSN268201100010C, HHSN268201100011C,
HHSN268201100012C, HHSN268201200036C, N01 HC025195, N01 HC045134, N01
HC095170, N01 HC095171, N01 HC095172, N01HC05187, N01HC45204,
N01HC45205, N01HC48047, N01HC48048, N01HC48049, N01HC48050, N01HC55222,
N01HC75150, N01HC85079, N01HC85086, N01HC95095, N02HL64278, R01
HL043851, R01 HL059367, R01 HL080295, R01 HL084099, R01 HL086694, R01
HL087641, R01 HL087652, R01 HL088119, R01 HL105756, U01 HL069757, U01
HL072515, U01 HL084756]; NIA NIH HHS [N01AG12100, N01AG12109, R01
AG015928, R01 AG018728, R01 AG020098, R01 AG023629, R01 AG027058]; NIAAA
NIH HHS [K05 AA017688, P50 AA011998, R01 AA007535, R01 AA013320, R01
AA013321, R01 AA013326, R01 AA014041]; NIAMS NIH HHS [P60 AR047785, R01
AR056291, R21 AR056042]; NIDA NIH HHS [R01 DA012854]; NIDDK NIH HHS [P30
DK063491, P30 DK072488, P30 DK079637, P60 DK079637]; NIGMS NIH HHS [U01
GM074518]; NIMH NIH HHS [R01 MH066206]; Wellcome Trust [090532]
NR 41
TC 163
Z9 174
U1 6
U2 83
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
EI 1546-1718
J9 NAT GENET
JI Nature Genet.
PD FEB
PY 2013
VL 45
IS 2
BP 145
EP 154
DI 10.1038/ng.2500
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA 081PB
UT WOS:000314333000009
PM 23263486
ER
PT J
AU Lu, Y
Vitart, V
Burdon, KP
Khor, CC
Bykhovskaya, Y
Mirshahi, A
Hewitt, AW
Koehn, D
Hysi, PG
Ramdas, WD
Zeller, T
Vithana, EN
Cornes, BK
Tay, WT
Tai, ES
Cheng, CY
Liu, JJ
Foo, JN
Saw, SM
Thorleifsson, G
Stefansson, K
Dimasi, DP
Mills, RA
Mountain, J
Ang, W
Hoehn, R
Verhoeven, VJM
Grus, F
Wolfs, R
Castagne, R
Lackner, KJ
Springelkamp, H
Yang, J
Jonasson, F
Leung, DYL
Chen, LJ
Tham, CCY
Rudan, I
Vatavuk, Z
Hayward, C
Gibson, J
Cree, AJ
MacLeod, A
Ennis, S
Polasek, O
Campbell, H
Wilson, JF
Viswanathan, AC
Fleck, B
Li, XH
Siscovick, D
Taylor, KD
Rotter, JI
Yazar, S
Ulmer, M
Li, J
Yaspan, BL
Ozel, AB
Richards, JE
Moroi, SE
Haines, JL
Kang, JH
Pasquale, LR
Allingham, RR
Ashley-Koch, A
Mitchell, P
Wang, JJ
Wright, AF
Pennell, C
Spector, TD
Young, TL
Klaver, CCW
Martin, NG
Montgomery, GW
Anderson, MG
Aung, T
Willoughby, CE
Wiggs, JL
Pang, CP
Thorsteinsdottir, U
Lotery, AJ
Hammond, CJ
van Duijn, CM
Hauser, MA
Rabinowitz, YS
Pfeiffer, N
Mackey, DA
Craig, JE
Macgregor, S
Wong, TY
AF Lu, Yi
Vitart, Veronique
Burdon, Kathryn P.
Khor, Chiea Chuen
Bykhovskaya, Yelena
Mirshahi, Alireza
Hewitt, Alex W.
Koehn, Demelza
Hysi, Pirro G.
Ramdas, Wishal D.
Zeller, Tanja
Vithana, Eranga N.
Cornes, Belinda K.
Tay, Wan-Ting
Tai, E. Shyong
Cheng, Ching-Yu
Liu, Jianjun
Foo, Jia-Nee
Saw, Seang Mei
Thorleifsson, Gudmar
Stefansson, Kari
Dimasi, David P.
Mills, Richard A.
Mountain, Jenny
Ang, Wei
Hoehn, Rene
Verhoeven, Virginie J. M.
Grus, Franz
Wolfs, Roger
Castagne, Raphaele
Lackner, Karl J.
Springelkamp, Henriet
Yang, Jian
Jonasson, Fridbert
Leung, Dexter Y. L.
Chen, Li J.
Tham, Clement C. Y.
Rudan, Igor
Vatavuk, Zoran
Hayward, Caroline
Gibson, Jane
Cree, Angela J.
MacLeod, Alex
Ennis, Sarah
Polasek, Ozren
Campbell, Harry
Wilson, James F.
Viswanathan, Ananth C.
Fleck, Brian
Li, Xiaohui
Siscovick, David
Taylor, Kent D.
Rotter, Jerome I.
Yazar, Seyhan
Ulmer, Megan
Li, Jun
Yaspan, Brian L.
Ozel, Ayse B.
Richards, Julia E.
Moroi, Sayoko E.
Haines, Jonathan L.
Kang, Jae H.
Pasquale, Louis R.
Allingham, R. Rand
Ashley-Koch, Allison
Mitchell, Paul
Wang, Jie Jin
Wright, Alan F.
Pennell, Craig
Spector, Timothy D.
Young, Terri L.
Klaver, Caroline C. W.
Martin, Nicholas G.
Montgomery, Grant W.
Anderson, Michael G.
Aung, Tin
Willoughby, Colin E.
Wiggs, Janey L.
Pang, Chi P.
Thorsteinsdottir, Unnur
Lotery, Andrew J.
Hammond, Christopher J.
van Duijn, Cornelia M.
Hauser, Michael A.
Rabinowitz, Yaron S.
Pfeiffer, Norbert
Mackey, David A.
Craig, Jamie E.
Macgregor, Stuart
Wong, Tien Y.
CA NEIGHBOR Consortium
TI Genome-wide association analyses identify multiple loci associated with
central corneal thickness and keratoconus
SO NATURE GENETICS
LA English
DT Article
ID OPEN-ANGLE GLAUCOMA; OSTEOGENESIS IMPERFECTA; OCULAR HYPERTENSION; ASIAN
POPULATIONS; COMMON VARIANTS; BLUE SCLERA; GENE; MUTATIONS; COLLAGEN;
IDENTIFICATION
AB Central corneal thickness (CCT) is associated with eye conditions including keratoconus and glaucoma. We performed a meta-analysis on >20,000 individuals in European and Asian populations that identified 16 new loci associated with CCT at genome-wide significance (P < 5 x 10(-8)). We further showed that 2 CCT-associated loci, FOXO1 and FNDC3B, conferred relatively large risks for keratoconus in 2 cohorts with 874 cases and 6,085 controls (rs2721051 near FOXO1 had odds ratio (OR) = 1.62, 95% confidence interval (Cl) = 1.4-1.88, P = 2.7 x 10(-10), and rs4894535 in FNDC3B had OR = 1.47,95% Cl = 1.29-1.68, P = 4.9 x 10(-9)). FNDC3B was also associated with primary open-angle glaucoma (P = 5.6 x 10(-4); tested in 3 cohorts with 2,979 cases and 7,399 controls). Further analyses implicate the collagen and extracellular matrix pathways in the regulation of CCT.
C1 [Lu, Yi; Martin, Nicholas G.; Montgomery, Grant W.; Macgregor, Stuart] Queensland Inst Med Res, Brisbane, Qld 4006, Australia.
[Vitart, Veronique; Hayward, Caroline; Wright, Alan F.] Univ Edinburgh, Med Res Council MRC Human Genet Unit, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland.
[Burdon, Kathryn P.; Dimasi, David P.; Mills, Richard A.; Craig, Jamie E.] Flinders Univ S Australia, Dept Ophthalmol, Flinders Med Ctr, Adelaide, SA 5001, Australia.
[Khor, Chiea Chuen; Vithana, Eranga N.; Cornes, Belinda K.; Tay, Wan-Ting; Cheng, Ching-Yu; Aung, Tin] Singapore Eye Res Inst, Singapore, Singapore.
[Khor, Chiea Chuen; Vithana, Eranga N.; Cheng, Ching-Yu; Aung, Tin] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore 117595, Singapore.
[Khor, Chiea Chuen; Tai, E. Shyong; Cheng, Ching-Yu; Liu, Jianjun; Saw, Seang Mei; Wong, Tien Y.] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 117548, Singapore.
[Khor, Chiea Chuen; Liu, Jianjun; Foo, Jia-Nee] ASTAR, Genome Inst Singapore, Human Genet, Singapore, Singapore.
[Bykhovskaya, Yelena; Rabinowitz, Yaron S.] Cedars Sinai Med Ctr, Dept Surg, Regenerat Med Inst, Div Surg Res, Los Angeles, CA 90048 USA.
[Mirshahi, Alireza; Hoehn, Rene; Grus, Franz; Pfeiffer, Norbert] Univ Med Ctr Mainz, Dept Ophthalmol, Mainz, Germany.
[Hewitt, Alex W.; Mackey, David A.] Univ Melbourne, Ctr Eye Res Australia, Royal Victorian Eye & Ear Hosp, Melbourne, Vic, Australia.
[Hewitt, Alex W.; Yazar, Seyhan; Mackey, David A.] Univ Western Australia, Lions Eye Inst, Ctr Ophthalmol & Visual Sci, Perth, WA 6009, Australia.
[Koehn, Demelza; Anderson, Michael G.] Univ Iowa, Dept Mol Physiol & Biophys, Iowa City, IA USA.
[Hysi, Pirro G.; Spector, Timothy D.; Hammond, Christopher J.] Kings Coll London, Dept Twin Res & Genet Epidemiol, Sch Med, St Thomas Hosp, London WC2R 2LS, England.
[Ramdas, Wishal D.; Verhoeven, Virginie J. M.; Wolfs, Roger; Springelkamp, Henriet; Klaver, Caroline C. W.] Erasmus MC, Dept Ophthalmol, Rotterdam, Netherlands.
[Ramdas, Wishal D.; Verhoeven, Virginie J. M.; Wolfs, Roger; Springelkamp, Henriet; Klaver, Caroline C. W.; van Duijn, Cornelia M.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
[Zeller, Tanja] Univ Heart Ctr Hamburg, Clin Gen & Intervent Cardiol, Hamburg, Germany.
[Tai, E. Shyong] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Med, Singapore 117595, Singapore.
[Cheng, Ching-Yu] Duke Natl Univ Singapore, Grad Sch Med, Ctr Quantitat Med, Off Clin Sci, Singapore, Singapore.
[Thorleifsson, Gudmar; Stefansson, Kari; Thorsteinsdottir, Unnur] deCODE Genet, Reykjavik, Iceland.
[Stefansson, Kari; Jonasson, Fridbert; Thorsteinsdottir, Unnur] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Mountain, Jenny] Univ Western Australia, Telethon Inst Child Hlth Res, Ctr Child Hlth Res, Perth, WA 6009, Australia.
[Ang, Wei; Pennell, Craig] Univ Western Australia, Sch Womens & Infants Hlth, Perth, WA 6009, Australia.
[Castagne, Raphaele] Univ Paris 06, INSERM, UMRS 937, Paris, France.
[Castagne, Raphaele] Sch Med, Paris, France.
[Lackner, Karl J.] Univ Med Ctr Mainz, Mainz, Germany.
[Yang, Jian] Univ Queensland, Diamantina Inst, Princess Alexandra Hosp, Brisbane, Qld, Australia.
[Jonasson, Fridbert] Landspitali Natl Univ Hosp, Dept Ophthalmol, Reykjavik, Iceland.
[Leung, Dexter Y. L.; Chen, Li J.; Tham, Clement C. Y.; Pang, Chi P.] Chinese Univ Hong Kong, Hong Kong Eye Hosp, Dept Ophthalmol & Visual Sci, Hong Kong, Hong Kong, Peoples R China.
[Rudan, Igor; Campbell, Harry; Wilson, James F.] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland.
[Rudan, Igor; Polasek, Ozren] Univ Split, Sch Med, Croatian Ctr Global Hlth, Split, Croatia.
[Vatavuk, Zoran] Hosp Sestre Milosrdnice, Dept Ophthalmol, Zagreb, Croatia.
[Gibson, Jane; Ennis, Sarah] Univ Southampton, Fac Med, Genet Epidemiol & Genom Informat Grp, Southampton Gen Hosp, Southampton SO9 5NH, Hants, England.
[Cree, Angela J.; Lotery, Andrew J.] Univ Southampton, Fac Med, Clin Neurosci Res Grp, Southampton Gen Hosp, Southampton SO9 5NH, Hants, England.
[MacLeod, Alex; Lotery, Andrew J.] Southampton Gen Hosp, Southampton Eye Unit, Southampton SO9 4XY, Hants, England.
[Polasek, Ozren] Univ Split, Dept Publ Hlth, Split, Croatia.
[Viswanathan, Ananth C.] Moorfields Eye Hosp Natl Hlth Serv NHS Fdn Trust, Natl Inst Hlth Res NIHR Biomed Res Ctr, London, England.
[Viswanathan, Ananth C.] Univ Coll London UCL Inst Ophthalmol, London, England.
[Fleck, Brian] Princess Alexandra Eye Pavil, Edinburgh, Midlothian, Scotland.
[Li, Xiaohui; Taylor, Kent D.; Rotter, Jerome I.] Cedars Sinai Med Ctr, Med Genet Inst, Los Angeles, CA 90048 USA.
[Siscovick, David] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
[Ulmer, Megan; Ashley-Koch, Allison; Hauser, Michael A.] Duke Univ, Dept Med, Durham, NC USA.
[Li, Jun; Ozel, Ayse B.] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA.
[Yaspan, Brian L.; Haines, Jonathan L.] Vanderbilt Univ, Sch Med, Ctr Human Genet Res, Nashville, TN 37212 USA.
[Richards, Julia E.; Moroi, Sayoko E.] Univ Michigan, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48109 USA.
[Kang, Jae H.; Pasquale, Louis R.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA.
[Pasquale, Louis R.; Wiggs, Janey L.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA.
[Allingham, R. Rand; Wong, Tien Y.] Duke Univ, Sch Med, Dept Ophthalmol, Durham, NC USA.
[Mitchell, Paul; Wang, Jie Jin] Univ Sydney, Ctr Vis Res, Dept Ophthalmol, Westmead, NSW 2145, Australia.
[Mitchell, Paul; Wang, Jie Jin] Univ Sydney, Westmead Millennium Inst, Westmead, NSW 2145, Australia.
[Young, Terri L.] Duke Univ, Med Ctr, Ctr Human Genet, Durham, NC USA.
[Young, Terri L.] Duke Natl Univ Singapore, Singapore, Singapore.
[Anderson, Michael G.] Univ Iowa, Dept Ophthalmol & Visual Sci, Iowa City, IA USA.
[Aung, Tin] Singapore Natl Eye Ctr, Singapore, Singapore.
[Willoughby, Colin E.] Queens Univ Belfast, Ctr Vis & Vasc Sci, Belfast, Antrim, North Ireland.
[Rabinowitz, Yaron S.] Cedars Sinai Med Ctr, Cornea Genet Eye Inst, Los Angeles, CA 90048 USA.
RP Macgregor, S (reprint author), Queensland Inst Med Res, Brisbane, Qld 4006, Australia.
EM stuart.macgregor@qimr.edu.au; tien_yin_wong@nuhs.edu.sg
RI Klaver, Caroline/A-2013-2016; Foo, Jia Nee/D-6069-2014; Rudan,
Igor/I-1467-2012; Yang, Jian/A-5852-2010; Mackey, David/H-5340-2014;
Hayward, Caroline/M-8818-2016; Pang, Chi/I-5388-2014; Wang, Jie
Jin/P-1499-2014; Mitchell, Paul/P-1498-2014; Wilson, James
F/A-5704-2009; Polasek, Ozren/B-6002-2011; Montgomery,
Grant/B-7148-2008; Haines, Jonathan/C-3374-2012; Macgregor,
Stuart/C-6442-2009; Hewitt, Alex/D-1936-2013; Cheng,
Ching-Yu/K-7017-2013; Burdon, Kathryn/A-5026-2009; Anderson,
Michael/B-4580-2009; Chen, Li Jia/I-5078-2014
OI Hohn, Rene /0000-0003-2870-1469; Ashley-Koch,
Allison/0000-0001-5409-9155; Khor, Chiea Chuen/0000-0002-1128-4729;
Hammond, Christopher/0000-0002-3227-2620; Tai, E
Shyong/0000-0003-2929-8966; Martin, Nicholas/0000-0003-4069-8020; Foo,
Jia Nee/0000-0001-9899-2308; Rudan, Igor/0000-0001-6993-6884; Yang,
Jian/0000-0003-2001-2474; Mackey, David/0000-0001-7914-4709; Hayward,
Caroline/0000-0002-9405-9550; Yazar, Seyhan/0000-0003-0994-6196; Carnes,
Megan/0000-0002-7270-132X; Leung, Dexter/0000-0002-9830-3143; Wang, Jie
Jin/0000-0001-9491-4898; Wilson, James F/0000-0001-5751-9178; Polasek,
Ozren/0000-0002-5765-1862; Montgomery, Grant/0000-0002-4140-8139;
Macgregor, Stuart/0000-0001-6731-8142; Hewitt, Alex/0000-0002-5123-5999;
Cheng, Ching-Yu/0000-0003-0655-885X; Burdon,
Kathryn/0000-0001-8217-1249; Anderson, Michael/0000-0001-5730-6105;
Chen, Li Jia/0000-0003-3500-5840
FU Chief Scientist Office [CZB/4/438, CZB/4/710]; Department of Health
[SRF/01/010]; Medical Research Council [MC_PC_U127561128]; NCATS NIH HHS
[UL1 TR000124]; NEI NIH HHS [F32 EY021436, R01 EY018246, R01 EY018825,
R01 EY022305]
NR 49
TC 84
Z9 87
U1 4
U2 51
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 FEB
PY 2013
VL 45
IS 2
BP 155
EP 163
DI 10.1038/ng.2506
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA 081PB
UT WOS:000314333000010
PM 23291589
ER
PT J
AU Huyghe, JR
Jackson, AU
Fogarty, MP
Buchkovich, ML
Stancakova, A
Stringham, HM
Sim, XL
Yang, LY
Fuchsberger, C
Cederberg, H
Chines, PS
Teslovich, TM
Romm, JM
Ling, H
McMullen, I
Ingersoll, R
Pugh, EW
Doheny, KF
Neale, BM
Daly, MJ
Kuusisto, J
Scott, LJ
Kang, HM
Collins, FS
Abecasis, GR
Watanabe, RM
Boehnke, M
Laakso, M
Mohlke, KL
AF Huyghe, Jeroen R.
Jackson, Anne U.
Fogarty, Marie P.
Buchkovich, Martin L.
Stancakova, Alena
Stringham, Heather M.
Sim, Xueling
Yang, Lingyao
Fuchsberger, Christian
Cederberg, Henna
Chines, Peter S.
Teslovich, Tanya M.
Romm, Jane M.
Ling, Hua
McMullen, Ivy
Ingersoll, Roxann
Pugh, Elizabeth W.
Doheny, Kimberly F.
Neale, Benjamin M.
Daly, Mark J.
Kuusisto, Johanna
Scott, Laura J.
Kang, Hyun Min
Collins, Francis S.
Abecasis, Goncalo R.
Watanabe, Richard M.
Boehnke, Michael
Laakso, Markku
Mohlke, Karen L.
TI Exome array analysis identifies new loci and low-frequency variants
influencing insulin processing and secretion
SO NATURE GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; COMMON VARIANTS; GLYCEMIC
TRAITS; GLUCOSE; PROTEIN; POPULATION; EXPRESSION; RELEASE; GTPASES
AB Insulin secretion has a crucial role in glucose homeostasis, and failure to secrete sufficient insulin is a hallmark of type 2 diabetes. Genome-wide association studies (GWAS) have identified loci contributing to insulin processing and secretion(1,2); however, a substantial fraction of the genetic contribution remains undefined. To examine low-frequency (minor allele frequency (MAF) 0.5-5%) and rare (MAF < 0.5%) nonsynonymous variants, we analyzed exome array data in 8,229 nondiabetic Finnish males using the Illumina HumanExome Beadchip. We identified low-frequency coding variants associated with fasting proinsulin concentrations at the SGSM2 and MADD GWAS loci and three new genes with low-frequency variants associated with fasting proinsulin or insulinogenic index: TBC1D30, KANK1 and PAM. We also show that the interpretation of single-variant and gene-based tests needs to consider the effects of noncoding SNPs both nearby and megabases away. This study demonstrates that exome array genotyping is a valuable approach to identify low-frequency variants that contribute to complex traits.
C1 [Huyghe, Jeroen R.; Jackson, Anne U.; Stringham, Heather M.; Sim, Xueling; Yang, Lingyao; Fuchsberger, Christian; Teslovich, Tanya M.; Scott, Laura J.; Kang, Hyun Min; Abecasis, Goncalo R.; Boehnke, Michael] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
[Fogarty, Marie P.; Buchkovich, Martin L.; Mohlke, Karen L.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
[Stancakova, Alena; Cederberg, Henna; Kuusisto, Johanna; Laakso, Markku] Univ Eastern Finland, Dept Med, Kuopio, Finland.
[Stancakova, Alena; Cederberg, Henna; Kuusisto, Johanna; Laakso, Markku] Kuopio Univ Hosp, SF-70210 Kuopio, Finland.
[Chines, Peter S.; Collins, Francis S.] NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA.
[Romm, Jane M.; Ling, Hua; McMullen, Ivy; Ingersoll, Roxann; Pugh, Elizabeth W.; Doheny, Kimberly F.] Johns Hopkins Univ, Ctr Inherited Dis Res, Baltimore, MD USA.
[Neale, Benjamin M.; Daly, Mark J.] Broad Inst MIT & Harvard, Cambridge, MA USA.
[Neale, Benjamin M.; Daly, Mark J.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Neale, Benjamin M.; Daly, Mark J.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA.
[Watanabe, Richard M.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Watanabe, Richard M.] Univ So Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA 90033 USA.
RP Mohlke, KL (reprint author), Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
EM mohlke@med.unc.edu
RI Abecasis, Goncalo/B-7840-2010;
OI Fuchsberger, Christian/0000-0002-5918-8947; Abecasis,
Goncalo/0000-0003-1509-1825
FU Academy of Finland [124243]; Finnish Heart Foundation; Finnish Diabetes
Foundation; Tekes [1510/31/06]; Commission of the European Community
[HEALTH-F2-2007-201681]; US National Institutes of Health [DK093757,
DK072193, DK062370, 1Z01 HG000024]
FX This study was supported by the Academy of Finland (contract 124243) (to
M.L.), the Finnish Heart Foundation (to M.L.), the Finnish Diabetes
Foundation (to M.L.), Tekes (contract 1510/31/06) (to M.L.), the
Commission of the European Community (HEALTH-F2-2007-201681) (to M.L.)
and US National Institutes of Health grants DK093757 (to K.L.M.),
DK072193 (to K.L.M.), DK062370 (to M.B.) and 1Z01 HG000024 (to F.S.C.).
Genotyping was conducted at the Genetic Resources Core Facility (GRCF)
at the Johns Hopkins Institute of Genetic Medicine.
NR 31
TC 120
Z9 122
U1 1
U2 25
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 FEB
PY 2013
VL 45
IS 2
BP 197
EP 201
DI 10.1038/ng.2507
PG 5
WC Genetics & Heredity
SC Genetics & Heredity
GA 081PB
UT WOS:000314333000016
PM 23263489
ER
PT J
AU Kornblum, C
Nicholls, TJ
Haack, TB
Scholer, S
Peeva, V
Danhauser, K
Hallmann, K
Zsurka, G
Rorbach, J
Iuso, A
Wieland, T
Sciacco, M
Ronchi, D
Comi, GP
Moggio, M
Quinzii, CM
DiMauro, S
Calvo, SE
Mootha, VK
Klopstock, T
Strom, TM
Meitinger, T
Minczuk, M
Kunz, WS
Prokisch, H
AF Kornblum, Cornelia
Nicholls, Thomas J.
Haack, Tobias B.
Schoeler, Susanne
Peeva, Viktoriya
Danhauser, Katharina
Hallmann, Kerstin
Zsurka, Gabor
Rorbach, Joanna
Iuso, Arcangela
Wieland, Thomas
Sciacco, Monica
Ronchi, Dario
Comi, Giacomo P.
Moggio, Maurizio
Quinzii, Catarina M.
DiMauro, Salvatore
Calvo, Sarah E.
Mootha, Vamsi K.
Klopstock, Thomas
Strom, Tim M.
Meitinger, Thomas
Minczuk, Michal
Kunz, Wolfram S.
Prokisch, Holger
TI Loss-of-function mutations in MGME1 impair mtDNA replication and cause
multisystemic mitochondrial disease
SO NATURE GENETICS
LA English
DT Article
ID PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA; BASE EXCISION-REPAIR; DNA
DEPLETION; PROTEIN; DEFICIENCY; GENE; POLG; MAINTENANCE; DELETIONS;
TWINKLE
AB Known disease mechanisms in mitochondria! DNA (mtDNA) maintenance disorders alter either the mitochondrial replication machinery (POLG, POLG2 and C10orf2)(1-3) or the biosynthesis pathways of deoxyribonucleoside 5'-triphosphates for mtDNA synthesis(4-11). However, in many of these disorders, the underlying genetic defect has yet to be discovered. Here, we identify homozygous nonsense and missense mutations in the orphan gene C20orf72 in three families with a mitochondrial syndrome characterized by external ophthalmoplegia, emaciation and respiratory failure. Muscle biopsies showed mtDNA depletion and multiple mtDNA deletions. C20orf72, hereafter MGME1 (mitochondrial genome maintenance exonuclease 1), encodes a mitochondria! RecB-type exonuclease belonging to the PD-(D/E)XK nuclease superfamily. We show that MGME1 cleaves single-stranded DNA and processes DNA flap substrates. Fibroblasts from affected individuals do not repopulate after chemically induced mtDNA depletion. They also accumulate intermediates of stalled replication and show increased levels of 7S DNA, as do MGME1-depleted cells. Thus, we show that MGME1-mediated mtDNA processing is essential for mitochondrial genome maintenance.
C1 [Kornblum, Cornelia] Univ Bonn, Dept Neurol, Med Ctr, Bonn, Germany.
[Nicholls, Thomas J.; Rorbach, Joanna; Minczuk, Michal] MRC, Mitochondrial Biol Unit, Cambridge, England.
[Haack, Tobias B.; Danhauser, Katharina; Iuso, Arcangela; Wieland, Thomas; Strom, Tim M.; Meitinger, Thomas; Prokisch, Holger] Tech Univ Munich, Inst Human Genet, D-80290 Munich, Germany.
[Haack, Tobias B.; Danhauser, Katharina; Iuso, Arcangela; Wieland, Thomas; Strom, Tim M.; Meitinger, Thomas; Prokisch, Holger] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Munich, Germany.
[Schoeler, Susanne; Peeva, Viktoriya; Hallmann, Kerstin; Zsurka, Gabor; Kunz, Wolfram S.] Univ Bonn, Med Ctr, Dept Epileptol, Bonn, Germany.
[Schoeler, Susanne; Peeva, Viktoriya; Hallmann, Kerstin; Zsurka, Gabor; Kunz, Wolfram S.] Univ Bonn, Med Ctr, Life & Brain Ctr, Bonn, Germany.
[Sciacco, Monica; Moggio, Maurizio] Univ Milan, Fdn Ist Ricovero & Cura Carattere Sci IRCCS Ca Gr, Neuromuscular Unit, Osped Maggiore Policlin,Ctr Dino Ferrari, Milan, Italy.
[Ronchi, Dario; Comi, Giacomo P.] Univ Milan, Fdn IRCCS Ca Granda, Neurol Unit, Osped Maggiore Policlin,Ctr Dino Ferrari, Milan, Italy.
[Quinzii, Catarina M.; DiMauro, Salvatore] Columbia Univ, Dept Neurol, Med Ctr, New York, NY USA.
[Calvo, Sarah E.; Mootha, Vamsi K.] Massachusetts Gen Hosp, Dept Mol Biol & Med, Boston, MA 02114 USA.
[Calvo, Sarah E.; Mootha, Vamsi K.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA.
[Calvo, Sarah E.; Mootha, Vamsi K.] Broad Inst, Cambridge, MA USA.
[Klopstock, Thomas] Univ Munich, Dept Neurol, Friedrich Baur Inst, D-80539 Munich, Germany.
RP Minczuk, M (reprint author), MRC, Mitochondrial Biol Unit, Cambridge, England.
EM michal.minczuk@mrc-mbu.cam.ac.uk; wolfram.kunz@ukb.uni-bonn.de
RI Prokisch, Holger/N-8964-2013; Meitinger, Thomas/O-1318-2015; Comi,
Giacomo /K-5702-2016; Ronchi, Dario/K-8011-2016
OI Comi, Giacomo /0000-0002-1383-5248; Ronchi, Dario/0000-0002-6093-9816
FU Medical Research Council UK; German Bundesministerium fur Bildung und
Forschung (BMBF) [SysMBo 0315494A]; E-Rare project GENOMIT [01GM1207];
German Network for mitochondrial disorders (mitoNET) [mitoNET 01GM0862,
01GM1113A, mitoNET 01GM0867, 01GM1113C, mitoNET 01GM0868]; Deutsche
Forschungsgemeinschaft [SFB TR3 All, D12]; US National Institutes of
Health [GM077465, GM097136]; Associazione Amici del Centro Dino Ferrari;
University of Milan; Telethon project [GTB07001ER]; Eurobiobank project
[QLTR-2001-02769]; Criobanca Automatizzata di Materiale Biologico
[R.F.02.187]
FX T.J.N. and M. Minczuk are grateful to S. Wood and I. Holt for
stimulating discussions during the course of this work We are grateful
to S. Beyer, K. Kappes-Horn, M. Stepien-Mering, E. Botz and R. Hellinger
for technical assistance. We thank R. Wiesner (University of Cologne)
for providing the TFAM antibody. This work was supported by the Medical
Research Council UK (T.J.N., J.R. and M. Minczuk) and the German
Bundesministerium fur Bildung und Forschung (BMBF) through funding of
the Systems Biology of Metabotypes grant (SysMBo 0315494A), the E-Rare
project GENOMIT (01GM1207) and the German Network for mitochondrial
disorders (mitoNET), including C.K., T.K. (mitoNET 01GM0862 and
01GM1113A), T.M., H.P. (mitoNET 01GM0867 and 01GM1113C) and W.S.K.
(mitoNET 01GM0868). W.S.K. was funded by the Deutsche
Forschungsgemeinschaft (SFB TR3 All and D12). V.K.M. was supported by
grants from the US National Institutes of Health (GM077465 and
GM097136). The financial support of Associazione Amici del Centro Dino
Ferrari, University of Milan, the Telethon project GTB07001ER, the
Eurobiobank project QLTR-2001-02769 and R.F.02.187 Criobanca
Automatizzata di Materiale Biologico to M.M. and M.S. are gratefully
acknowledged.
NR 28
TC 58
Z9 60
U1 3
U2 19
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 FEB
PY 2013
VL 45
IS 2
BP 214
EP 219
DI 10.1038/ng.2501
PG 6
WC Genetics & Heredity
SC Genetics & Heredity
GA 081PB
UT WOS:000314333000019
PM 23313956
ER
PT J
AU Liu, S
Ren, JA
Hong, ZW
Yan, DS
Gu, GS
Han, G
Wang, GF
Ren, HJ
Chen, J
Li, JS
AF Liu, Song
Ren, Jianan
Hong, Zhiwu
Yan, Dongsheng
Gu, Guosheng
Han, Gang
Wang, Gefei
Ren, Huajian
Chen, Jun
Li, Jieshou
TI Efficacy of Erythropoietin Combined With Enteral Nutrition for the
Treatment of Anemia in Crohn's Disease: A Prospective Cohort Study
SO NUTRITION IN CLINICAL PRACTICE
LA English
DT Article
DE Crohn disease; anemia; erythropoietin; enteral nutrition; biological
markers
ID INFLAMMATORY-BOWEL-DISEASE; INTRAVENOUS IRON SUCROSE; DEFICIENCY ANEMIA;
OXIDATIVE STRESS; FERROUS FUMARATE; MANAGEMENT; DIAGNOSIS; TRIPTOLIDE;
COLITIS; IBD
AB Background: Anemia is a common and serious complication in patients with inflammatory bowel disease. The present study was dedicated to evaluate the therapeutic efficacy of erythropoietin (EPO) combined with enteral nutrition (EN) in anemic Crohn's disease (CD) patients, in terms of hemoglobin level, treatment success rate, adverse events, and predictor of this therapy. Materials and Methods: We performed a prospective study in CD patients. On the basis of hemoglobin level, all enrolled patients were divided into anemic and nonanemic groups. The anemic group was further divided into EPO and non-EPO subgroups, depending on whether EPO was prescribed. Hematological and other parameters were measured initially and in the first 4 weeks after starting treatment. Results: In total, 109 patients (49 nonanemic and 60 anemic, including 38 EPO and 22 non-EPO) were included. The prevalence of anemia in CD was 55.05%. Age, disease behavior, Crohn's Disease Activity Index scores, C-reactive protein, and erythrocyte sedimentation rate were significantly different between anemic and nonanemic groups. An increase in hemoglobin level and a significant decrease in C-reactive protein level were observed in the EPO treatment group. Treatment success rate was 63.16% in the EPO group, whereas none of patients achieved treatment success in the non-EPO group. Conclusion: EPO combined with EN can improve the hemoglobin level in anemic CD patients. (Nutr Clin Pract. 2013;28:120-127)
C1 [Liu, Song; Ren, Jianan; Hong, Zhiwu; Yan, Dongsheng; Gu, Guosheng; Wang, Gefei; Ren, Huajian; Chen, Jun; Li, Jieshou] Nanjing Univ, Sch Med, Jinling Hosp, Dept Gen Surg, Nanjing 210002, Jiangsu, Peoples R China.
[Han, Gang] Jilin Univ, Gen Surg Ctr, Dept Gen Surg, Affiliated Hosp 2, Changchun, Jilin, Peoples R China.
[Liu, Song] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA.
[Liu, Song] Harvard Univ, Sch Med, Boston, MA USA.
RP Ren, JA (reprint author), Nanjing Univ, Sch Med, Jinling Hosp, Dept Gen Surg, 305 E Zhongshan Rd, Nanjing 210002, Jiangsu, Peoples R China.
EM jiananr@gmail.com
OI LIU, SONG/0000-0002-4780-9697; Ren, Jianan/0000-0002-7978-8093
FU Climb Program in Natural Science Foundation of Jiangsu Province for
Distinguished Scholars [BK2010017]
FX This work was supported by grants from the Climb Program in Natural
Science Foundation of Jiangsu Province for Distinguished Scholars (No.
BK2010017).
NR 30
TC 8
Z9 8
U1 1
U2 17
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0884-5336
J9 NUTR CLIN PRACT
JI Nutr. Clin. Pract.
PD FEB
PY 2013
VL 28
IS 1
BP 120
EP 127
DI 10.1177/0884533612462744
PG 8
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 074PH
UT WOS:000313824200013
PM 23064018
ER
PT J
AU Lee, MS
Hang, JQ
Zhang, FY
Zheng, BY
Su, L
Zhao, Y
Dai, HL
Zhang, HX
Christiani, DC
AF Lee, Mi-Sun
Hang, Jing-qing
Zhang, Feng-ying
Zheng, Bu-yong
Su, Li
Zhao, Yang
Dai, He-lian
Zhang, Hong-xi
Christiani, David C.
TI Household solid fuel use and pulmonary function in an urban population
in Shanghai, China
SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE
LA English
DT Article
ID INDOOR AIR-POLLUTION; LUNG-CANCER; OXIDATIVE STRESS; METABOLIC SYNDROME;
RISK; INFLAMMATION; EXPOSURE; PARTICLES; CHILDREN; SMOKING
AB Objectives We examined the association between household solid fuel exposure and lung function in a densely populated district in urban Shanghai, China.
Methods Spirometry was performed in 12 506 subjects, aged 18 and over, residing in the Putuo District in Shanghai, China, in a cross-sectional survey. Exposure to solid fuel use at home was assessed by an administered questionnaire, estimating duration and total amount of solid fuel use at home during the lifetime.
Results After adjusting for confounders, the subjects with exposure to household solid fuel had a 1.3% (95% CI 0.57 to 2.02) decrease in forced expiratory volume in 1 s (FEV1) percent predicted and 3.5% (95% CI 2.74 to 4.18) decrease in forced vital capacity (FVC) percent predicted, respectively. Trends towards decreased pulmonary function measures were seen for longer duration and greater amount of household fuel use at home, in the highest compared with lowest tertile (p values for trend <0.001). We observed decrease in FEV1 and FVC percent predicted across increase in tertile of body mass index in association with in-home solid fuel exposure.
Conclusions This study suggests that in-home solid fuel exposure is associated with reduced lung function in an urban population.
C1 [Lee, Mi-Sun; Su, Li; Zhao, Yang; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Environm & Occupat Med & Epidemiol Program, Dept Environm Hlth, Boston, MA 02115 USA.
[Hang, Jing-qing; Zhang, Feng-ying; Zheng, Bu-yong; Dai, He-lian; Zhang, Hong-xi] Shanghai Putuo Dist Peoples Hosp, Shanghai, Peoples R China.
[Christiani, David C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA.
RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Environm & Occupat Med & Epidemiol Program, Dept Environm Hlth, 665 Huntington Ave,Bldg 1,Room 1401, Boston, MA 02115 USA.
EM dchris@hsph.harvard.edu
FU National Institute of Environmental Health Science [ES000002]; National
Institute for Occupational Safety and Health [R010421]; Shanghai Putuo
District People's Hospital
FX This study was supported by grants from the National Institute of
Environmental Health Science (Grant ES000002); and the National
Institute for Occupational Safety and Health (Grant R010421); and
Shanghai Putuo District People's Hospital.
NR 29
TC 3
Z9 3
U1 1
U2 8
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1351-0711
J9 OCCUP ENVIRON MED
JI Occup. Environ. Med.
PD FEB
PY 2013
VL 70
IS 2
BP 120
EP 125
DI 10.1136/oemed-2011-100569
PG 6
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 074FC
UT WOS:000313797300008
PM 23155189
ER
PT J
AU Batey, LA
Welt, CK
Rohr, F
Wessel, A
Anastasoaie, V
Feldman, HA
Guo, CY
Rubio-Gozalbo, E
Berry, G
Gordon, CM
AF Batey, L. A.
Welt, C. K.
Rohr, F.
Wessel, A.
Anastasoaie, V.
Feldman, H. A.
Guo, C. -Y.
Rubio-Gozalbo, E.
Berry, G.
Gordon, C. M.
TI Skeletal health in adult patients with classic galactosemia
SO OSTEOPOROSIS INTERNATIONAL
LA English
DT Article
DE Bone density; Calcium; Galactosemia; Premature ovarian insufficiency;
Vitamin D
ID BONE TURNOVER; CHILDREN; ADOLESCENTS; DEFICIENCY; CALCIUM; WOMEN
AB This study evaluated bone health in adults with galactosemia. Associations between bone mineral density (BMD) and nutritional and biochemical variables were explored. Calcium level predicted hip and spine BMD, and gonadotropin levels were inversely associated with spinal BMD in women. These results afford insights into management strategies for these patients.
Bone loss is a complication of galactosemia. Dietary restriction, primary ovarian insufficiency in women, and disease-related alterations of bone metabolism may contribute. This study examined relationships between clinical factors and BMD in patients with galactosemia.
This cross-sectional sample included 33 adults (16 women) with classic galactosemia, mean age 32.0 +/- 11.8 years. BMD was measured by dual-energy X-ray absorptiometry, and was correlated with age, height, weight, fractures, nutritional factors, hormonal status, and bone biomarkers.
There was a significant difference in hip BMD between women and men (0.799 vs. 0.896 g/cm(2), p = 0.014). The percentage of subjects with BMD-Z <-2.0 was also greater for women than men [33 vs. 18 % (spine), 27 vs. 6 % (hip)], and more women reported sustaining fractures. Bivariate analyses yielded correlations between BMI and BMD-Z [at the hip in women (r = 0.58, p < 0.05) and spine in men (r = 0.53, p < 0.05)]. In women, weight was also correlated with BMD-Z (r = 0.57, p < 0.05 at hip), and C-telopeptides (r = -0.59 at spine and -0.63 hip, p < 0.05) and osteocalcin (r = -0.71 at spine and -0.72 hip, p < 0.05) were inversely correlated with BMD-Z. In final regression models, higher gonadotropin levels were associated with lower spinal BMD in women (p = 0.017); serum calcium was a significant predictor of hip (p = 0.014) and spine (p = 0.013) BMD in both sexes.
Bone density in adults with galactosemia is low, indicating the potential for increased fracture risk, the etiology of which appears to be multifactorial.
C1 [Batey, L. A.; Rohr, F.; Wessel, A.; Anastasoaie, V.; Feldman, H. A.; Berry, G.; Gordon, C. M.] Childrens Hosp Boston, Boston, MA USA.
[Welt, C. K.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Rubio-Gozalbo, E.] Maastricht Univ, Med Ctr, Dept Pediat, Maastricht, Netherlands.
[Rubio-Gozalbo, E.] Maastricht Univ, Med Ctr, Lab Inherited Metab Dis, Maastricht, Netherlands.
[Berry, G.] Manton Ctr Orphan Dis Res, Boston, MA USA.
[Guo, C. -Y.] Natl Yang Ming Univ, Inst Publ Hlth, Taipei 112, Taiwan.
[Gordon, C. M.] Childrens Hosp Boston, Div Adolescent Med & Endocrinol, Boston, MA 02115 USA.
RP Gordon, CM (reprint author), Childrens Hosp Boston, Div Adolescent Med & Endocrinol, 300 Longwood Ave, Boston, MA 02115 USA.
EM catherine.gordon@childrens.harvard.edu
RI rubio, estela/H-1833-2011;
OI Berry, Gerard/0000-0001-5299-3313; Welt, Corrine/0000-0002-8219-5504
FU Galactosemia Foundation
FX The authors gratefully acknowledge all of the study participants and
their families who made this study possible. We also thank Jamie
Nydegger, CDT and Yailka Cardenas, CDT for the excellent technical
assistance (Bone Health Program, Children's Hospital Boston) and Nicolle
Quinn, MS RD (research dietitian, Clinical and Translational Study Unit,
Children's Hospital Boston) for performing the food record analyses.
This project was funded by the Galactosemia Foundation.
NR 25
TC 3
Z9 4
U1 0
U2 7
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 FEB
PY 2013
VL 24
IS 2
BP 501
EP 509
DI 10.1007/s00198-012-1983-0
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 080WI
UT WOS:000314274400012
PM 22525982
ER
PT J
AU Fernandes, JR
Samayoa, JC
Broelsch, GF
McCormack, MC
Nicholls, AM
Randolph, MA
Mihm, MC
Austen, WG
AF Fernandes, Justin R.
Samayoa, Juan C.
Broelsch, G. Felix
McCormack, Michael C.
Nicholls, Alexa M.
Randolph, Mark A.
Mihm, Martin C.
Austen, William G., Jr.
TI Micro-Mechanical Fractional Skin Rejuvenation
SO PLASTIC AND RECONSTRUCTIVE SURGERY
LA English
DT Article
ID CARBON-DIOXIDE LASER; INTENSE PULSED-LIGHT; PHOTOAGED SKIN; STRAND
BREAKS; SHORT-TERM; YAG LASER; BURN SCAR; COLLAGEN; PHOTOTHERMOLYSIS;
DERMABRASION
AB Background: The most commonly performed skin rejuvenation procedure, laser resurfacing, is associated with adverse events and significant expense. The authors have developed a novel device that uses micro-coring needles to remove tissue in a fractional pattern and avoid the side effects of laser therapy. The authors compare the efficacy of these needles to standard needles in a pig model.
Methods: One swine was treated with three needle types: standard hypodermic, solid hypodermic, and the authors' novel coring needles. Thirty-two 1 x 1-inch sites per flank received either 20 or 40 percent treatment coverage. Photographs were taken and punch biopsies were performed at days 0, 7, 28, 56, and 84. Biopsy specimens were evaluated for histology and collagen content.
Results: All treatment sites healed quickly, with no evidence of scarring or infection. Coring sites were easily identified and contained increased fibroblast activity and newly synthesized collagen. At 1 month, the papillary dermis and epidermis of the coring sites were up to 196 percent thicker compared with controls (p < 0.001). The coring sites had enhanced undulating rete ridges-consistent with regeneration. At 3 months, a pronounced increase in collagen fibers and newly organized and augmented elastic fibers was seen. Enzyme-linked immunosorbent assay confirmed an 89 percent increase in collagen content in these coring sites (p < 0.001).
Conclusions: This novel approach to skin rejuvenation was found to effectively induce the microscopic and biological endpoints of skin rejuvenation. This may provide a new modality for the safe and cost-effective treatment of age-related rhytides, skin laxity, photodamage, scarring, and striae. (Plast. Reconstr. Surg. 131: 216, 2013.)
C1 [Austen, William G., Jr.] Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, Boston, MA 02114 USA.
Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA.
RP Austen, WG (reprint author), Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, 15 Parkman St,WAC 435, Boston, MA 02114 USA.
EM wausten@partners.org
NR 41
TC 2
Z9 2
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0032-1052
J9 PLAST RECONSTR SURG
JI Plast. Reconstr. Surg.
PD FEB
PY 2013
VL 131
IS 2
BP 216
EP 223
DI 10.1097/PRS.0b013e3182789afa
PG 8
WC Surgery
SC Surgery
GA 081XL
UT WOS:000314355700051
PM 23357983
ER
PT J
AU Okechukwu, CA
Dutra, LM
Bacic, J
El Ayadi, A
Emmons, KM
AF Okechukwu, C. A.
Dutra, L. M.
Bacic, J.
El Ayadi, A.
Emmons, K. M.
TI Home matters: Work and household predictors of smoking and cessation
among blue-collar workers
SO PREVENTIVE MEDICINE
LA English
DT Article
DE Smoking; Occupational class; Blue-collar; Partner smoking
ID WORKPLACE POLICIES; TOBACCO USE; ENVIRONMENT; RESTRICTIONS; DISPARITIES;
POPULATION; BEHAVIORS; RELAPSE; GENDER; IMPACT
AB Objective: This study examined the joint influence of work- and household-related variables on smoking behavior among a population representative sample of blue-collar workers with live-in partners.
Methods: The study used data on 1389 blue-collar workers from the Tobacco Use Supplement to the United States Current Population Survey 2002 to 2003 longitudinal overlap sample. Unadjusted and adjusted logistical regression analyses, which employed sampling and replicate weights to account for sampling design, were run to estimate independent and joint effects of the predictors.
Results: In adjusted analyses, partner smoking (OR = 4.97, 95%CI = 3.02-8.18) and complete and partial home smoking policy (OR = 0.16, 95%CI = 0.09-0.29 and OR = 0.39, 95%CI = 0.23-0.68, respectively) were significant predictors of smoking status, but worksite smoking policies and presence of a young child under 5 in the household were not (p > 0.05). Baseline complete home smoking ban was a significant predictor of subsequent cessation (OR = 3.49, 95%CI = 1.19-10.23), while partner smoking status, workplace smoking policy, and the presence of a young child in the home did not predict cessation (p > 0.05).
Conclusion: Household-related variables were significant predictors of smoking status and cessation among blue-collar workers. Current efforts to decrease smoking in this group, which are mostly focused on work-related risk factors, should consider how to incorporate household risk factors. (c) 2012 Elsevier Inc. All rights reserved.
C1 [Okechukwu, C. A.; Dutra, L. M.; Bacic, J.; El Ayadi, A.; Emmons, K. M.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA.
[Bacic, J.] Boston Univ, Dept Hlth Policy & Management, Sch Publ Hlth, Boston, MA 02118 USA.
[Emmons, K. M.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA.
RP Okechukwu, CA (reprint author), Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Kresge Bldg,7th Floor,677 Huntington Ave, Boston, MA 02115 USA.
EM cokechuk@hsph.hatvard.edu
FU NIMHD NIH HHS [L60 MD003645]
NR 33
TC 4
Z9 5
U1 2
U2 13
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0091-7435
J9 PREV MED
JI Prev. Med.
PD FEB
PY 2013
VL 56
IS 2
BP 130
EP 134
DI 10.1016/j.ypmed.2012.12.005
PG 5
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 082HJ
UT WOS:000314382600008
PM 23262360
ER
PT J
AU Almony, A
Nudleman, E
Shah, GK
Blinder, KJ
Eliott, D
Mittra, RA
Tewari, A
AF Almony, Arghavan
Nudleman, Eric
Shah, Gaurav K.
Blinder, Kevin J.
Eliott, Dean
Mittra, Robert A.
Tewari, Asheesh
TI Untitled Reply
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Letter
ID LARGE MACULAR HOLES
C1 [Almony, Arghavan] Carolina Eye Associates, Southern Pines, NC USA.
[Nudleman, Eric] William Beaumont Hosp, Royal Oak, MI 48072 USA.
[Shah, Gaurav K.; Blinder, Kevin J.] Retina Inst, St Louis, MO USA.
[Eliott, Dean] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
[Mittra, Robert A.] VitreoRetinal Surg, Minneapolis, MN USA.
[Tewari, Asheesh] Wayne State Univ, Kresge Eye Inst, Detroit, MI USA.
RP Almony, A (reprint author), Carolina Eye Associates, Southern Pines, NC USA.
NR 4
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0275-004X
J9 RETINA-J RET VIT DIS
JI Retin.-J. Retin. Vitr. Dis.
PD FEB
PY 2013
VL 33
IS 2
BP 457
EP 458
DI 10.1097/IAE.0b013e31828451c9
PG 2
WC Ophthalmology
SC Ophthalmology
GA 081TI
UT WOS:000314344800038
PM 23343824
ER
PT J
AU Marusyk, A
Polyak, K
AF Marusyk, Andriy
Polyak, Kornelia
TI Cancer Cell Phenotypes, in Fifty Shades of Grey
SO SCIENCE
LA English
DT Editorial Material
ID TUMOR HETEROGENEITY; STEM-CELLS
C1 [Marusyk, Andriy] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Boston, MA 02215 USA.
Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA.
RP Marusyk, A (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
EM kornelia_polyak@dfci.harvard.edu
NR 8
TC 24
Z9 24
U1 2
U2 33
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD FEB 1
PY 2013
VL 339
IS 6119
BP 528
EP 529
DI 10.1126/science.1234415
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 080UR
UT WOS:000314270000043
PM 23372002
ER
PT J
AU Yu, M
Bardia, A
Wittner, B
Stott, SL
Smas, ME
Ting, DT
Isakoff, SJ
Ciciliano, JC
Wells, MN
Shah, AM
Concannon, KF
Donaldson, MC
Sequist, LV
Brachtel, E
Sgroi, D
Baselga, J
Ramaswamy, S
Toner, M
Haber, DA
Maheswaran, S
AF Yu, Min
Bardia, Aditya
Wittner, Ben S.
Stott, Shannon L.
Smas, Malgorzata E.
Ting, David T.
Isakoff, Steven J.
Ciciliano, Jordan C.
Wells, Marissa N.
Shah, Ajay M.
Concannon, Kyle F.
Donaldson, Maria C.
Sequist, Lecia V.
Brachtel, Elena
Sgroi, Dennis
Baselga, Jose
Ramaswamy, Sridhar
Toner, Mehmet
Haber, Daniel A.
Maheswaran, Shyamala
TI Circulating Breast Tumor Cells Exhibit Dynamic Changes in Epithelial and
Mesenchymal Composition
SO SCIENCE
LA English
DT Article
ID LUNG-CANCER; METASTASIS; TRANSITION; PROGRESSION; EMT; DISSEMINATION;
PHENOTYPE
AB Epithelial-mesenchymal transition (EMT) of adherent epithelial cells to a migratory mesenchymal state has been implicated in tumor metastasis in preclinical models. To investigate its role in human cancer, we characterized EMT in circulating tumor cells (CTCs) from breast cancer patients. Rare primary tumor cells simultaneously expressed mesenchymal and epithelial markers, but mesenchymal cells were highly enriched in CTCs. Serial CTC monitoring in 11 patients suggested an association of mesenchymal CTCs with disease progression. In an index patient, reversible shifts between these cell fates accompanied each cycle of response to therapy and disease progression. Mesenchymal CTCs occurred as both single cells and multicellular clusters, expressing known EMT regulators, including transforming growth factor (TGF)-beta pathway components and the FOXC1 transcription factor. These data support a role for EMT in the blood-borne dissemination of human breast cancer.
C1 [Yu, Min; Bardia, Aditya; Wittner, Ben S.; Stott, Shannon L.; Smas, Malgorzata E.; Ting, David T.; Isakoff, Steven J.; Ciciliano, Jordan C.; Wells, Marissa N.; Concannon, Kyle F.; Donaldson, Maria C.; Sequist, Lecia V.; Brachtel, Elena; Sgroi, Dennis; Baselga, Jose; Ramaswamy, Sridhar; Haber, Daniel A.; Maheswaran, Shyamala] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA.
[Stott, Shannon L.; Shah, Ajay M.; Toner, Mehmet] Harvard Univ, Sch Med, Ctr Bioengn Med, Charlestown, MA 02129 USA.
[Bardia, Aditya; Isakoff, Steven J.; Sequist, Lecia V.; Baselga, Jose; Ramaswamy, Sridhar; Haber, Daniel A.] Harvard Univ, Sch Med, Dept Med, Charlestown, MA 02129 USA.
[Brachtel, Elena; Sgroi, Dennis] Harvard Univ, Sch Med, Dept Pathol, Charlestown, MA 02129 USA.
[Toner, Mehmet; Maheswaran, Shyamala] Harvard Univ, Sch Med, Dept Surg, Charlestown, MA 02129 USA.
[Haber, Daniel A.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
RP Haber, DA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA.
EM haber@helix.mgh.harvard.edu; maheswaran@helix.mgh.harvard.edu
OI Ting, David/0000-0002-3261-2322
FU Breast Cancer Research Foundation; Stand Up To Cancer; Susan G. Komen
for the Cure [KG090412]; NIBIB [EB008047]; NCI [CA129933]; National
Cancer Institute-MGH Federal Share Program; Howard Hughes Medical
Institute
FX We are grateful to all the patients who participated in this study; we
thank D. Juric, C. Koris, and the Massachusetts General Hospital (MGH)
clinical research coordinators for help with clinical studies; A.
Gilman, B. Brannigan, and M. Zeinali for technical support; F. Ozsolak
and P. Milos (Helicos) for RNA sequencing; A. Forrest-Hay and Q. Nguyen
(Affymetrix) for RNA-ISH reagents; L. Libby for mouse studies; and J.
Walsh for expertise with microscopy. This work was supported by grants
from the Breast Cancer Research Foundation (D. A. H.), Stand Up To
Cancer (D. A. H., M. T., and S. M.), Susan G. Komen for the Cure
KG090412 (S. M.), NIBIB EB008047 (M. T., D. A. H.), NCI CA129933 (D. A.
H.), the National Cancer Institute-MGH Federal Share Program (S. M.),
and the Howard Hughes Medical Institute (M.Y. and D. A. H.). The MGH and
M. T. have filed a patent for the HB (Herringbone) microchip (U.S.
patent 09816815.4). Sequencing data have been deposited in the Gene
Expression Omnibus database (accession no. GSE41245).
NR 29
TC 603
Z9 634
U1 45
U2 365
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD FEB 1
PY 2013
VL 339
IS 6119
BP 580
EP 584
DI 10.1126/science.1228522
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 080UR
UT WOS:000314270000059
PM 23372014
ER
PT J
AU Gradus, JL
Shipherd, JC
Suvak, MK
Giasson, HL
Miller, M
AF Gradus, Jaimie L.
Shipherd, Jillian C.
Suvak, Michael K.
Giasson, Hannah L.
Miller, Matthew
TI Suicide Attempts and Suicide among Marines: A Decade of Follow-up
SO SUICIDE AND LIFE-THREATENING BEHAVIOR
LA English
DT Article
ID SEXUAL EXPERIENCES QUESTIONNAIRE; RISK-FACTORS; PSYCHOMETRIC PROPERTIES;
PREVALENCE; MILITARY; HARASSMENT; VICTIMIZATION; AGGRESSION; PERSONNEL;
ANXIETY
AB Suicidal behavior among military personnel is of paramount public health importance because of the increased risk of death from suicide in this population. Pre- and post-Marine recruit training risk factors for suicide attempts among current and former Marines were examined in 10 years following recruit training. The characteristics of the subsample of current and former Marines who died by suicide during this time are also described. Stressful and traumatic life events (e.g., childhood physical, sexual, and emotional abuse, sexual harassment during recruit training) and pre-recruit training suicide attempts emerged as having strong associations with post-recruit training attempts. Half of those who died by suicide in the 10 years following recruit training endorsed at least one significant life stressor prior to joining the Marines. This study highlights the importance of screening for stressful and potentially traumatic experiences occurring both before and during military service as part of a comprehensive suicide risk assessment in military samples.
C1 [Gradus, Jaimie L.; Shipherd, Jillian C.; Suvak, Michael K.; Giasson, Hannah L.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA.
[Gradus, Jaimie L.; Shipherd, Jillian C.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA.
[Gradus, Jaimie L.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Suvak, Michael K.] Suffolk Univ, Dept Psychol, Boston, MA 02114 USA.
[Miller, Matthew] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA.
RP Gradus, JL (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, 150 S Huntington Ave,116B-3, Boston, MA 02130 USA.
EM jaimie.gradus@va.gov
OI Gradus, Jaimie/0000-0003-1459-5327
NR 28
TC 8
Z9 8
U1 4
U2 23
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0363-0234
J9 SUICIDE LIFE-THREAT
JI Suicide Life-Threat. Behav.
PD FEB
PY 2013
VL 43
IS 1
BP 39
EP 49
DI 10.1111/j.1943-278X.2012.00126.x
PG 11
WC Psychiatry; Psychology, Multidisciplinary
SC Psychiatry; Psychology
GA 079OR
UT WOS:000314180600003
PM 23082753
ER
PT J
AU Velmahos, GC
AF Velmahos, George C.
TI Direct and Recurrent Inguinal Hernias Are Associated with Ventral Hernia
Repair: A Database Study
SO WORLD JOURNAL OF SURGERY
LA English
DT Editorial Material
C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA.
RP Velmahos, GC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 165 Cambridge St,Suite 810, Boston, MA 02114 USA.
EM gvelmahos@partners.org
NR 1
TC 0
Z9 0
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0364-2313
J9 WORLD J SURG
JI World J.Surg.
PD FEB
PY 2013
VL 37
IS 2
BP 312
EP 312
DI 10.1007/s00268-012-1883-7
PG 1
WC Surgery
SC Surgery
GA 077KJ
UT WOS:000314026300006
PM 23238798
ER
PT J
AU Ambrosy, AP
Vaduganathan, M
Mentz, RJ
Greene, SJ
Subacius, H
Konstam, MA
Maggioni, AP
Swedberg, K
Gheorghiade, M
AF Ambrosy, Andrew P.
Vaduganathan, Muthiah
Mentz, Robert J.
Greene, Stephen J.
Subacius, Haris
Konstam, Marvin A.
Maggioni, Aldo P.
Swedberg, Karl
Gheorghiade, Mihai
CA EVEREST Trial Investgators
TI Clinical profile and prognostic value of low systolic blood pressure in
patients hospitalized for heart failure with reduced ejection fraction:
Insights from the Efficacy of Vasopressin Antagonism in Heart Failure:
Outcome Study with Tolvaptan (EVEREST) trial
SO AMERICAN HEART JOURNAL
LA English
DT Article
ID MORTALITY; ASSOCIATION; UPDATE
AB Background Systolic blood pressure (SBP) is related to the pathophysiologic development and progression of heart failure (HF) and is inversely associated with adverse outcomes during hospitalization for HF (HHF). The prognostic value of SBP after initiating inhospital therapy and the mode of death and etiology of cardiovascular readmissions based on SBP have not been well characterized in HHF.
Methods A post hoc analysis was performed of the placebo group (n = 2061) of the EVEREST trial, which enrolled patients within 48 hours of admission for worsening HF with an ejection fraction (EF) <= 40% and an SBP >= 90 mm Hg, for a median followup of 9.9 months. Systolic blood pressure was measured at baseline, daily during hospitalization, and at discharge/day 7. Patients were divided into the following quartiles by SBP at baseline: <= 105, 106 to 119, 120 to 130, and >= 131 mm Hg. Outcomes were all-cause mortality (ACM) and the composite of cardiovascular mortality or HHF (CVM + HHF). The associations between baseline, discharge, and inhospital change in SBP and ACM and CVM + HHF were assessed using multivariable Cox proportional hazards regression models adjusted for known covariates.
Results Median (25th, 75th) SBP at baseline was 120 (105, 130) mm Hg and ranged from 82 to 202 mm Hg. Patients with a lower SBP were younger and more likely to be male; had a higher prevalence of prior revascularization and ventricular arrhythmias; had a lower EF, worse renal function, higher natriuretic peptide concentrations, and wider QRS durations; and were more likely to require intravenous inotropes during hospitalization. Lower SBP was associated with increased mortality, driven by HF and sudden cardiac death, and cardiovascular hospitalization, primarily caused by HHF. After adjusting for potential confounders, SBP was inversely associated with risk of the coprimary end points both at baseline (ACM: hazard ratio [HR]/10-mm Hg decrease 1.15, 95% CI1.08-1.22; CVM + HHF: HR 1.09/10-mm Hg decrease, 95% CI 1.04-1.14) and at the time of discharge/ day 7 (ACM: HR 1.15/10-mm Hg decrease, 95% CI 1.08-1.22; CVM + HHF: HR 1.07/10-mm Hg decrease, 95% CI 1.02-1.13), but the association with inhospital SBP change was not significant.
Conclusion Systolic blood pressure is an independent clinical predictor of morbidity and mortality after initial therapy during HHF with reduced EF. (Am Heart J 2013;165:216-25.)
C1 [Ambrosy, Andrew P.] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA.
[Vaduganathan, Muthiah] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Mentz, Robert J.] Duke Univ, Med Ctr, Div Cardiol, Durham, NC 27710 USA.
[Greene, Stephen J.; Gheorghiade, Mihai] Northwestern Univ, Feinberg Sch Med, Ctr Cardiovasc Innovat, Chicago, IL 60611 USA.
[Subacius, Haris] Northwestern Univ, Feinberg Sch Med, Dept Med, Div Cardiol, Chicago, IL 60611 USA.
[Konstam, Marvin A.] Tufts Med Ctr, Dept Med, Div Cardiol, Boston, MA USA.
[Maggioni, Aldo P.] ANMCO Res Ctr, Florence, Italy.
[Swedberg, Karl] Univ Gothenburg, Sahlgrenska Acad, Dept Mol & Clin Med, Gothenburg, Sweden.
RP Gheorghiade, M (reprint author), Northwestern Univ, Feinberg Sch Med, Ctr Cardiovasc Innovat, 645 N Michigan Ave,Suite 1006, Chicago, IL 60611 USA.
EM m-gheorghiade@northwestern.edu
FU Abbott Labs; Astellas; AstraZeneca; Bayer Schering PharmaAG; CorThera
Inc; Cytokinetics Inc; DebioPharm SA; ErrekappaTerapeutici (Milan,
Italy); Glaxo Smith Kline; JNJ; Medtronic; Novartis Pharma AG; Otsuka;
Sigma Tau; Solvay Pharmaceuticals; Pericor Therapeutics
FX Mihai Gheorghiade is a consultant for and/or has received research
support from Abbott Labs, Astellas, AstraZeneca, Bayer Schering
PharmaAG, CorThera Inc, Cytokinetics Inc, DebioPharm SA,
ErrekappaTerapeutici (Milan, Italy), Glaxo Smith Kline, JNJ, Medtronic,
Novartis Pharma AG, Otsuka, Sigma Tau, Solvay Pharmaceuticals, and
Pericor Therapeutics. The other authors declare no conflicts of
interest.
NR 20
TC 22
Z9 22
U1 1
U2 9
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-8703
J9 AM HEART J
JI Am. Heart J.
PD FEB
PY 2013
VL 165
IS 2
BP 216
EP 225
DI 10.1016/j.ahj.2012.11.004
PG 10
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 078PS
UT WOS:000314112300016
PM 23351825
ER
PT J
AU Tse, JY
Nguyen, AT
Le, LP
Hoang, MP
AF Tse, Julie Y.
Nguyen, Anh T.
Le, Long P.
Hoang, Mai P.
TI Microcystic Adnexal Carcinoma Versus Desmoplastic Trichoepithelioma: A
Comparative Study
SO AMERICAN JOURNAL OF DERMATOPATHOLOGY
LA English
DT Article
DE microcystic adnexal carcinoma; desmoplastic trichoepithelioma; CK19;
CK17; epidermal growth factor receptor; immunohistochemistry
ID BASAL-CELL CARCINOMA; FACTOR RECEPTOR GENE; OF-THE-LITERATURE; SEBACEOUS
DIFFERENTIATION; CYTOKERATIN 15; MERKEL CELLS; STEM-CELLS; SKIN;
EXPRESSION; MARKERS
AB The histologic distinction between microcystic adnexal carcinoma (MAC) and desmoplastic trichoepithelioma (dTE) can be challenging in the setting of a superficial biopsy. However, accurate diagnosis has treatment implication because the standard of care for MAC is wide local excision but more conservative care for dTE. We reviewed the histologic features of 30 MAC and 39 dTE cases and performed cytokeratin (CK) 17, CK19, and epidermal growth factor receptor (EGFR) immunostains on 20 MACs and 18 dTEs. MAC cases occurred in older patients in comparison with dTE (median, 67 years vs. 34 years). The head and neck was the most commonly involved site, 88% and 89% for MAC and dTE, respectively. In addition to features previously reported as specific for MAC, such as skeletal muscle and subcutaneous tissue invasion, perineural invasion, and ductal differentiation, we found the presence of mitotic figures to be significantly more frequent in MAC cases (P < 0.0001). In contrast, the presence of keratocyst, keratin granuloma, and calcification was significantly more frequent in dTE cases (P < 0.0001). CK19 seems to be a helpful adjunct because its expression was seen in 70% (14/20) of MAC versus 22% (4/18) of dTE cases (P = 0.0044); however, the clinical usefulness in individual cases may be limited because of the overlapping immunoprofile. CK17 and EGFR expression was seen in all the MAC and dTE cases. Low polysomy of EGFR gene was observed in only one MAC case, suggesting that molecular mechanisms other than gene amplification play a role in EGFR overexpression.
C1 [Tse, Julie Y.; Nguyen, Anh T.; Le, Long P.; Hoang, Mai P.] Harvard Univ, Dept Pathol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA.
RP Hoang, MP (reprint author), Harvard Univ, Dept Pathol, Massachusetts Gen Hosp, Sch Med, 55 Fruit St,Warren 820, Boston, MA 02114 USA.
EM mhoang@partners.org
NR 34
TC 3
Z9 3
U1 1
U2 2
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 FEB
PY 2013
VL 35
IS 1
BP 50
EP 55
DI 10.1097/DAD.0b013e31825988df
PG 6
WC Dermatology
SC Dermatology
GA 078MR
UT WOS:000314103600012
PM 22722464
ER
PT J
AU Zhang, GY
Bai, HX
Yang, L
Ma, MH
Su, YW
Luo, YY
Wen, HQ
Lu, QJ
Xiao, R
AF Zhang, Guiying
Bai, Harrison X.
Yang, Li
Ma, Michael H.
Su, Yuwen
Luo, Yangyang
Wen, Haiquan
Lu, Qianjin
Xiao, Rong
TI NK-/T-Cell Lymphoma Resembling Hydroa Vacciniforme With Positive CD4
Marker Expression: A Diagnostic Difficulty
SO AMERICAN JOURNAL OF DERMATOPATHOLOGY
LA English
DT Article
DE CD4(+) lymphoma; hydroa vacciniforme; cutaneous NK-/T-cell lymphoma
ID NATURAL-KILLER-CELL; NASAL-TYPE; CUTANEOUS LYMPHOMA; HEMATOLOGICAL
NEOPLASMS; RECOGNIZED ENTITY; SKIN; INVOLVEMENT; WORKSHOP; CD56+; GENE
AB A 35-year-old Chinese woman presented with a 2.5-year history of facial swelling in the left lower quadrant and a 10-month history of relapsing red papules and vesicles in the perioral area resembling hydroa vacciniforme. Histologically, a tissue biopsy showed a dense infiltration of medium-sized atypical lymphocytic cells expressing CD4 and CD56. A diagnosis of cutaneous NK-/T-cell lymphoma was made. The patient was treated with alpha-interferon, valaciclovir hydrochloride, and low-dose prednisone for 2 months. Her skin lesions and lymphoadenopathy resolved initially, but she succumbed to the disease shortly after starting chemotherapy treatment 11 months later. To our knowledge, this is the first case of CD4(+)CD56(+) NK-/T-cell lymphoma with clinical features resembling hydroa vacciniforme.
C1 [Zhang, Guiying; Yang, Li; Su, Yuwen; Luo, Yangyang; Wen, Haiquan; Lu, Qianjin; Xiao, Rong] Cent S Univ, Dept Dermatol, Xiang Ya Hosp 2, Changsha 410011, Hunan, Peoples R China.
[Bai, Harrison X.; Ma, Michael H.] Yale Univ, Sch Med, Dept Dermatol, New Haven, CT 06510 USA.
[Ma, Michael H.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA.
RP Xiao, R (reprint author), Cent S Univ, Dept Dermatol, Xiang Ya Hosp 2, 139 Ren Min Middle Rd, Changsha 410011, Hunan, Peoples R China.
EM xiaorong65@yahoo.com.cn
NR 24
TC 2
Z9 2
U1 1
U2 3
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 FEB
PY 2013
VL 35
IS 1
BP 94
EP 97
DI 10.1097/DAD.0b013e3182674895
PG 4
WC Dermatology
SC Dermatology
GA 078MR
UT WOS:000314103600019
PM 22885552
ER
PT J
AU Fett, NM
Teng, J
Longley, BJ
AF Fett, Nicole M.
Teng, Joyce
Longley, B. Jack
TI Familial Urticaria Pigmentosa: Report of a Family and Review of the Role
of KIT Mutations
SO AMERICAN JOURNAL OF DERMATOPATHOLOGY
LA English
DT Review
DE mastocytosis; urticarial pigmentosa; c-kit protooncogene; KIT tyrosine
kinase
ID GASTROINTESTINAL STROMAL TUMORS; C-KIT; GERMLINE MUTATION; PEDIATRIC
MASTOCYTOSIS; CUTANEOUS MASTOCYTOSIS; DOMAIN MUTATIONS; DISEASE
AB Cutaneous mastocytosis is a rare clinically heterogeneous disorder characterized by mast cell infiltration. Mastocytosis affects both children and adults and has been reported to occur in families. Recent data suggest that mutations in the c-kit protooncogene are causative of mastocytosis not only in adults but in children and familial cases as well; however, mutation analysis other than D816V is not widely available, making detection of causative mutations problematic. We present the case of a 33-year-old man with a 30-year history of persistent urticaria pigmentosa and his 2 affected children. Sequencing of KIT exons 8, 10, 11, and 17 was carried out on a skin biopsy specimen and mucosal swabs of the incident case and was negative for known KIT mutations. Additional work-up was deferred by the family. Presentation of this familial case of urticaria pigmentosa demonstrates the complexity of genetic evaluation in clinical settings. It suggests that mutations other than those reported in exons 8, 10, 11, and 17 may also result in familial mastocytosis. Presentation of this case also allows for review of the mechanism of action of causative KIT mutations and the recent literature supporting KIT mutations in childhood and familial mastocytosis.
C1 [Fett, Nicole M.] Philadelphia VA Med Ctr, Dept Dermatol, Philadelphia, PA USA.
[Fett, Nicole M.] Univ Penn, Dept Dermatol, Perelman Ctr Adv Med, Sch Med, Philadelphia, PA 19104 USA.
[Teng, Joyce; Longley, B. Jack] Univ Wisconsin, Hosp & Clin, Dept Dermatol, Madison, WI 53792 USA.
RP Fett, NM (reprint author), Univ Penn, Dept Dermatol, Perelman Ctr Adv Med, Sch Med, Suite 1-330A,3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA.
EM nicole.fett@uphs.upenn.edu
NR 22
TC 9
Z9 9
U1 1
U2 4
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 FEB
PY 2013
VL 35
IS 1
BP 113
EP 116
DI 10.1097/DAD.0b013e31826330bf
PG 4
WC Dermatology
SC Dermatology
GA 078MR
UT WOS:000314103600024
PM 22892471
ER
PT J
AU Chlebicki, MP
Safdar, N
O'Horo, JC
Maki, DG
AF Chlebicki, Maciej Piotr
Safdar, Nasia
O'Horo, John Charles
Maki, Dennis G.
TI Preoperative chlorhexidine shower or bath for prevention of surgical
site infection: A meta-analysis
SO AMERICAN JOURNAL OF INFECTION CONTROL
LA English
DT Review
DE Antiseptic; Systematic review; Clean; Clean-contaminated
ID WHOLE-BODY DISINFECTION; WOUND-INFECTION; CONTROLLED-TRIAL; PRISMA
STATEMENT; POVIDONE-IODINE; CLINICAL-TRIALS; SURGERY; GLUCONATE;
DETERGENT; PROPHYLAXIS
AB Background: Chlorhexidine showering is frequently recommended as an important preoperative measure to prevent surgical site infection (SSI). However, the efficacy of this approach is uncertain.
Methods: A search of electronic databases was undertaken to identify prospective controlled trials evaluating whole-body preoperative bathing with chlorhexidine versus placebo or no bath for prevention of SSI. Summary risk ratios were calculated using a DerSimonian-Laird random effects model and a Mantel-Haenzel dichotomous effects model.
Results: Sixteen trials met inclusion criteria with a total of 17,932 patients: 7,952 patients received a chlorhexidine bath, and 9,980 patients were allocated to various comparator groups. Overall, 6.8% of patients developed SSI in the chlorhexidine group compared with 7.2% of patients in the comparator groups. Chlorhexidine bathing did not significantly reduce overall incidence of SSI when compared with soap, placebo, or no shower or bath (relative risk, 0.90; 95% confidence interval: 0.77-1.05, P = .19).
Conclusions: Meta-analysis of available clinical trials suggests no appreciable benefit of preoperative whole-body chlorhexidine bathing for prevention of SSI. However, most studies omitted details of chlorhexidine application. Better designed trials with a specified duration and frequency of exposure to chlorhexidine are needed to determine whether preoperative whole-body chlorhexidine bathing reduces SSI. Copyright (C) 2013 by the Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.
C1 [Chlebicki, Maciej Piotr] Singapore Gen Hosp, Dept Infect Dis, Singapore, Singapore.
[Safdar, Nasia] Univ Wisconsin, MFCB, Infect Dis Sect, Dept Med,Med Sch, Madison, WI 53705 USA.
[Safdar, Nasia; Maki, Dennis G.] Univ Wisconsin Hosp & Clin, Infect Control Dept, Madison, WI 53792 USA.
[Safdar, Nasia] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA.
[O'Horo, John Charles] Aurora Healthcare, Dept Grad Med Educ, Milwaukee, WI USA.
RP Safdar, N (reprint author), Univ Wisconsin, MFCB, Infect Dis Sect, Dept Med,Med Sch, 1685 Highland Ave, Madison, WI 53705 USA.
EM ns2@medicine.wisc.edu
RI O'Horo, John/A-8787-2013; O'Horo, John/N-8681-2013
OI O'Horo, John/0000-0002-0880-4498; O'Horo, John/0000-0002-0880-4498
NR 42
TC 33
Z9 33
U1 1
U2 30
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0196-6553
J9 AM J INFECT CONTROL
JI Am. J. Infect. Control
PD FEB
PY 2013
VL 41
IS 2
BP 167
EP 173
DI 10.1016/j.ajic.2012.02.014
PG 7
WC Public, Environmental & Occupational Health; Infectious Diseases
SC Public, Environmental & Occupational Health; Infectious Diseases
GA 078NJ
UT WOS:000314105500018
PM 22722008
ER
PT J
AU Ahmed, A
Rich, MW
Zile, M
Sanders, PW
Patel, K
Zhang, Y
Aban, IB
Love, TE
Fonarow, GC
Aronow, WS
Allman, RM
AF Ahmed, Ali
Rich, Michael W.
Zile, Michael
Sanders, Paul W.
Patel, Kanan
Zhang, Yan
Aban, Inmaculada B.
Love, Thomas E.
Fonarow, Gregg C.
Aronow, Wilbert S.
Allman, Richard M.
TI Renin-Angiotensin Inhibition in Diastolic Heart Failure and Chronic
Kidney Disease
SO AMERICAN JOURNAL OF MEDICINE
LA English
DT Article
DE Angiotensin-converting enzyme inhibitors; Angiotensin receptor blockers;
Chronic kidney disease; Diastolic heart failure
ID FUNCTIONAL RENAL-INSUFFICIENCY; CONVERTING-ENZYME-INHIBITION; PRESERVED
EJECTION FRACTION; OLDER-ADULTS; SYSTOLIC FUNCTION; PROPENSITY SCORE;
ATRIAL-FIBRILLATION; PRACTICE GUIDELINES; OUTCOMES; ASSOCIATION
AB BACKGROUND: The role of renin-angiotensin inhibition in older patients with diastolic heart failure and chronic kidney disease remains unclear.
METHODS: Of the 1340 patients (age >= 65 years) with diastolic heart failure (ejection fraction >= 45%) and chronic kidney disease (estimated glomerular filtration rate < 60 mL/min/1.73 m(2)), 717 received angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Propensity scores for the use of these drugs, estimated for each of the 1340 patients, were used to assemble a cohort of 421 pairs of patients, receiving and not receiving these drugs, who were balanced on 56 baseline characteristics.
RESULTS: During more than 8 years of follow-up, all-cause mortality occurred in 63% and 69% of matched patients with chronic kidney disease receiving and not receiving angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, respectively (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.70-0.97; P = .021). There was no association with heart failure hospitalization (HR, 0.98; 95% CI, 0.82-1.18; P = .816). Similar mortality reduction (HR, 0.81; 95% CI, 0.66-0.995; P = .045) occurred in a subgroup of matched patients with an estimated glomerular filtration rate less than 45 mL/min/1.73 m2. Among 207 pairs of propensity-matched patients without chronic kidney disease, the use of these drugs was not associated with mortality (HR, 1.03; 95% CI, 0.80-1.33; P = .826) or heart failure hospitalization (HR, 0.99; 95% CI, 0.76-1.30; P = .946).
CONCLUSIONS: A discharge prescription for angiotensin-converting enzyme inhibitors or angiotensin receptor blockers was associated with a significant reduction in all-cause mortality in older patients with diastolic heart failure and chronic kidney disease, including those with more advanced chronic kidney disease. Published by Elsevier Inc. The American Journal of Medicine (2013) 126, 150-161
C1 [Ahmed, Ali; Sanders, Paul W.; Patel, Kanan; Zhang, Yan; Aban, Inmaculada B.; Allman, Richard M.] Univ Alabama Birmingham, Birmingham, AL USA.
[Ahmed, Ali; Sanders, Paul W.; Allman, Richard M.] Vet Affairs Med Ctr, Birmingham, AL USA.
[Rich, Michael W.] Washington Univ, St Louis, MO USA.
[Zile, Michael] Med Univ S Carolina, Charleston, SC 29425 USA.
[Zile, Michael] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA.
[Love, Thomas E.] Case Western Reserve Univ, Cleveland, OH 44106 USA.
[Fonarow, Gregg C.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Aronow, Wilbert S.] New York Med Coll, Valhalla, NY 10595 USA.
RP Ahmed, A (reprint author), UAB Ctr Aging, CH19,Ste 219,1720 2nd Ave S, Birmingham, AL 35294 USA.
EM aahmed@uab.edu
OI Sanders, Paul/0000-0002-2915-5714
FU National Heart, Lung, and Blood Institute (NHLBI)/National Institutes of
Health (NIH) [R01-HL085561, R01-HL085561-S]; NIH/NHLBI [R01-HL097047];
NIH/National Center for Research Resources [5UL1 RR025777]; NIH/National
Institute of Diabetes and Digestive and Kidney Diseases [R01-DK46199];
Department of Veterans Affairs
FX The project was supported by Grant Numbers R01-HL085561 and
R01-HL085561-S from the National Heart, Lung, and Blood Institute
(NHLBI)/National Institutes of Health (NIH). Its contents are solely the
responsibility of the authors and do not necessarily represent the
official views of the NHLBI or NIH. Dr Ahmed also is supported by
NIH/NHLBI Grant R01-HL097047 and a generous gift from Jean B. Morris of
Birmingham, Alabama. Dr Allman is supported by NIH/National Center for
Research Resources Grant 5UL1 RR025777. Dr Sanders is supported by
NIH/National Institute of Diabetes and Digestive and Kidney Diseases
Grant R01-DK46199 and funding from the Department of Veterans Affairs.
NR 41
TC 13
Z9 13
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9343
J9 AM J MED
JI Am. J. Med.
PD FEB
PY 2013
VL 126
IS 2
BP 150
EP 161
DI 10.1016/j.amjmed.2012.06.031
PG 12
WC Medicine, General & Internal
SC General & Internal Medicine
GA 072WP
UT WOS:000313704500022
PM 23331442
ER
PT J
AU Pasquale, LR
Loomis, SJ
Kang, JH
Yaspan, BL
Abdrabou, W
Budenz, DL
Chen, TC
Delbono, E
Friedman, DS
Gaasterland, D
Gaasterland, T
Grosskreutz, CL
Lee, RK
Lichter, PR
Liu, YT
McCarty, CA
Moroi, SE
Olson, LM
Realini, T
Rhee, DJ
Schuman, JS
Singh, K
Vollrath, D
Wollstein, G
Zack, DJ
Allingham, RR
Pericak-Vance, MA
Weinreb, RN
Zhang, K
Hauser, MA
Richards, JE
Haines, JL
Wiggs, JL
AF Pasquale, Louis R.
Loomis, Stephanie J.
Kang, Jae H.
Yaspan, Brian L.
Abdrabou, Wael
Budenz, Donald L.
Chen, Teresa C.
Delbono, Elizabeth
Friedman, David S.
Gaasterland, Douglas
Gaasterland, Terry
Grosskreutz, Cynthia L.
Lee, Richard K.
Lichter, Paul R.
Liu, Yutao
McCarty, Catherine A.
Moroi, Sayoko E.
Olson, Lana M.
Realini, Tony
Rhee, Douglas J.
Schuman, Joel S.
Singh, Kuldev
Vollrath, Douglas
Wollstein, Gadi
Zack, Donald J.
Allingham, R. Rand
Pericak-Vance, Margaret A.
Weinreb, Robert N.
Zhang, Kang
Hauser, Michael A.
Richards, Julia E.
Haines, Jonathan L.
Wiggs, Janey L.
TI CDKN2B-AS1 Genotype-Glaucoma Feature Correlations in Primary Open-Angle
Glaucoma Patients From the United States
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; BASE-LINE CHARACTERISTICS; REPLICATIVE
SENESCENCE; SUSCEPTIBILITY LOCI; OPTIC DISC; POPULATION; VARIANTS;
INHIBITORS; P15(INK4B); PRESSURE
AB PURPOSE: To assess the association between single nucleotide polymorphisms (SNPs) of the gene region containing cyclin-dependent kinase inhibitor 2B antisense noncoding RNA (CDKN2B-AS1) and glaucoma features among primary open-angle glaucoma (POAG) patients.
DESIGN: Retrospective observational case series.
METHODS: We studied associations between 10 CDKN2B-AS1 SNPs and glaucoma features among 976 POAG cases from the Glaucoma Genes and Environment (GLAUGEN) study and 1971 cases from the National Eye Institute Glaucoma Human Genetics Collaboration (NEIGHBOR) consortium. For each patient, we chose the feature from the eye with the higher value. We created cohort-specific multivariable models for glaucoma features and then meta-analyzed the results.
RESULTS: For 9 of the 10 protective CDKN2B-AS1 SNPs with minor alleles associated with reduced disease risk (eg, the G allele at rs2157719), POAG patients carrying these minor alleles had smaller cup-to-disc ratio (0.05 units smaller per G allele at diagnosis; 95% CI: -0.08, -0.03; P = 6.23E-05) despite having higher intraocular pressure (IOP) (0.70 mm Hg higher per G allele at DNA collection; 95% CI: 0.40, 1.00; P = 5.45E-06). For the 1 adverse rs3217992 SNP with minor allele A associated with increased disease risk, POAG patients with A alleles had larger cup-to-disc ratio (0.05 units larger per A allele at diagnosis; 95% CI: 0.02, 0.07; P = 4.74E-04) despite having lower IOP (-0.57 mm Hg per A allele at DNA collection; 95% CI: -0.84, -0.29; P = 6.55E-05).
CONCLUSION: Alleles of CDKN2B-AS1 SNPs, which influence risk of developing POAG, also modulate optic nerve degeneration among POAG patients, underscoring the role of CDKN2B-AS1 in POAG. (Am J Ophthalmol 2013;155:342-353. (c) 2013 by Elsevier Inc. All rights reserved.)
C1 [Pasquale, Louis R.; Loomis, Stephanie J.; Abdrabou, Wael; Chen, Teresa C.; Delbono, Elizabeth; Grosskreutz, Cynthia L.; Rhee, Douglas J.; Wiggs, Janey L.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA.
[Pasquale, Louis R.; Kang, Jae H.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Div Network Med, Boston, MA 02114 USA.
[Yaspan, Brian L.; Olson, Lana M.; Haines, Jonathan L.] Vanderbilt Univ, Ctr Human Genet Res, Nashville, TN USA.
[Budenz, Donald L.] Univ N Carolina, Dept Ophthalmol, Chapel Hill, NC USA.
[Friedman, David S.; Zack, Donald J.] Johns Hopkins Univ Hosp, Wilmer Eye Inst, Baltimore, MD 21205 USA.
[Gaasterland, Douglas] Eye Doctors Washington, Chevy Chase, MD USA.
[Gaasterland, Terry] Univ Calif San Diego, Scripps Genome Ctr, San Diego, CA 92103 USA.
[Lee, Richard K.; Pericak-Vance, Margaret A.] Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, Miami, FL 33136 USA.
[Lichter, Paul R.; Moroi, Sayoko E.; Richards, Julia E.] Univ Michigan, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48109 USA.
[Liu, Yutao; Allingham, R. Rand; Hauser, Michael A.] Duke Univ, Med Ctr, Dept Ophthalmol, Durham, NC 27710 USA.
[McCarty, Catherine A.] Marshfield Clin Res Fdn, Ctr Human Genet, Marshfield, WI USA.
[Realini, Tony] W Virginia Univ, Dept Ophthalmol, Inst Eye, Morgantown, WV 26506 USA.
[Schuman, Joel S.; Wollstein, Gadi] Univ Pittsburgh, Dept Ophthalmol, UPMC Eye Ctr, Pittsburgh, PA 15260 USA.
[Singh, Kuldev] Stanford Univ, Dept Ophthalmol, Palo Alto, CA 94304 USA.
[Vollrath, Douglas] Stanford Univ, Dept Genet, Palo Alto, CA 94304 USA.
[Weinreb, Robert N.; Zhang, Kang] Univ Calif San Diego, Dept Ophthalmol, La Jolla, CA 92093 USA.
[Weinreb, Robert N.; Zhang, Kang] Univ Calif San Diego, Hamilton Glaucoma Ctr, La Jolla, CA 92093 USA.
[Liu, Yutao; Hauser, Michael A.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.
[Richards, Julia E.] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA.
RP Pasquale, LR (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA.
EM Louis_Pasquale@meei.harvard.edu
RI Haines, Jonathan/C-3374-2012; Schuman, Joel/K-7304-2012;
OI Schuman, Joel/0000-0002-8885-3766; Zack, Don/0000-0002-7966-1973
FU Merck; Carl Zeiss Meditec; New World Medical; Harvard Catalyst group;
National Institutes of Health (NIH); Agency for Healthcare Research;
National Eye Institute (NEI); American Glaucoma Society; NEI; Alcon;
NIH; Novartis; Nidek; Topcon; Aeries; Research to Prevent Blindness;
Sramek Foundation; Allergan (Irvine, California); The Harvard Glaucoma
Center of Excellence; Margolis fund (Boston, Massachusetts); Research to
Prevent Blindness, Inc (New York, New York); The Glaucoma Research
Foundation (San Francisco, California); American Health Assistance
Foundation (Clarksburg, Maryland); Glaucoma Foundation (New York, New
York); National Institutes of Health [CA87969, CA49449, CA55075,
HL35464, NEI R01 EY015473, HHSN268200782096C]; National Human Genome
Research Institute (Bethesda, Maryland) [HG004728, HG004424, HG004446];
National Eye Institute [HG005259-01]; The National Eye Institute
(Bethesda, Maryland) through ARRA [3R01EY015872-05S1,
3R01EY019126-02S1]; National Institutes of Health (Bethesda, Maryland)
[EY015543, EY006827, HL073389, EY13315, EY09611, EY009149, HG004608,
EY008208, EY015473, EY012118, EY015682, EY011671, EY09580, EY013178,
EY015872, EY010886, EY009847, EY011008, EY144428, EY144448, EY18660]
FX ALL AUTHORS HAVE COMPLETED AND SUBMITTED THE ICMJE FORM FOR DISCLOSURE
OF POTENTIAL CONFLICTS OF INTEREST. Dr Pasquale has received funding
from Merck for unrelated investigator-initiated research. He was also
reimbursed for travel to an ARVO-Pfizer meeting on biomarkers in
glaucoma research in May 2011. Dr T. Gaasterland has received an
honorarium for a lecture given on glaucoma genomics by Sequenom. Dr
Yaspan contributed to this research while he was at Vanderbilt
University and is currently an employee of Genentech. He has no other
financial conflicts to declare. Dr Grosskreutz is an employee of
Novartis and retains stock options from her employer. She has no other
financial conflicts to declare. The following coauthors declare the
following financial activities for work outside the scope of the current
publication. Dr Budenz is a consultant to Alcon Labs, Allergan, Santen,
Ivantis, and Alimera. His institution receives grant support from Carl
Zeiss Meditec and New World Medical. Dr Budenz is on the speakers bureau
for Merck, Alcon, and Allergan. Dr Chen receives grant support from the
Harvard Catalyst group, the National Institutes of Health (NIH), and the
Agency for Healthcare Research. She also receives royalties from
Elsevier for her role as a book editor. Dr Friedman is a consultant for
Alcon, Bausch & Lomb, Merck, Pfizer, and QLT. Dr D. Gaasterland has been
paid royalties as inventor of the G probe for Index. He also owns a
small amount of IRIDEX stock. Dr Lee receives research support from
National Eye Institute (NEI) and the American Glaucoma Society. He is
also on the speakers bureaus of Merck and Pfizer. Dr Lee receives
royalties from Pharmigen and has been reimbursed for meeting travel by
Alcon. Dr Realini is a consultant for Alcon and received payment for
manuscript preparation from this company. He is also on the speakers
bureau for Lumenis. Dr Mono receives grant support from Merck and NEI as
well as royalties from Lippicott. Dr Rhee is a consultant for Alcon,
Allergan, Merck, Novagali, and Santen. He also receives grant support
from Alcon and Merck. Dr Schuman receives grant support from the NIH and
is an inventor on a patent (paid to University of Pittsburgh). He
receives royalties from Carl Zeiss Meditec. Dr Singh is consultant to
Alcon, Allergan, Santen, and Bausch & Lomb. Dr Wollstein receives grant
support from NIH. Drs Allingham and Pericak-Vance receive grant support
from NIH. Dr Zack retains Board membership with Alcon and has received
grant support form Merck. Dr Weinreb is a consultant to Alcon, Allergan,
Merck, Bausch & Lomb, Zeis Meditec and Optovue. He also receives grant
support from Novartis, Nidek, Topcon, and Aeries. Dr Richards receives
grant support from NIH, Research to Prevent Blindness, and the Sramek
Foundation. She also receives royalties for authoring a textbook from
Elsevier and has been reimbursed for travel to a Think Tank meeting by
the Glaucoma Foundation, NYC.; Publication of this article was supported
by the following: a Horizon Grant to MEEI from Allergan (Irvine,
California) supported the collection of some glaucoma feature data. The
Harvard Glaucoma Center of Excellence and Margolis fund (Boston,
Massachusetts) support W.A., L.R.P., and J.L.W.. L.R.P., J.E.R., and
J.L.W. are also supported by Research to Prevent Blindness, Inc (New
York, New York). The Glaucoma Research Foundation (San Francisco,
California), American Health Assistance Foundation (Clarksburg,
Maryland), and the Glaucoma Foundation (New York, New York) support Y.L.
The following National Institutes of Health grants support the
maintenance of the Nurses Health Study and Health Professionals
Follow-up, allowing these health professionals to contribute to this
analysis: CA87969, CA49449, CA55075, HL35464, and NEI R01 EY015473
(L.R.P.). The following grants from the National Human Genome Research
Institute (Bethesda, Maryland) supported GLAUGEN: HG004728 (L.R.P.),
HG004424 (Broad Institute to support genotyping), HG004446 (C. Laurie,
U. Washington, to support genotype data cleaning and analysis).
Genotyping services for the NEIGHBOR study were provided by the Center
for Inherited Disease Research (CIDR) and were supported by the National
Eye Institute through grant HG005259-01 (J.L.W.). Additionally, CIDR is
funded through a federal contract from the National Institutes of Health
to The Johns Hopkins University, contract number HHSN268200782096C. The
National Eye Institute (Bethesda, Maryland), through ARRA grants
3R01EY015872-05S1 (J.L.W.) and 3R01EY019126-02S1 (M.A.H.), supported the
collection and processing of samples for the NEIGHBOR dataset. Funding
for the collection of cases and controls was provided by National
Institutes of Health (Bethesda, Maryland) grants: EY015543 (R.R.A.),
EY006827 (D.G.), HL073389 (Hauser, E); EY13315 (M.A.H.); EY09611
(Hankinson, S), EY009149 (P.R.L.), HG004608 (C.A.M.), EY008208
(Medeiros, P), EY015473 (L.R.P.), EY012118 (M.A.P.V.), EY015682 (T.R.),
EY011671 (J.E.R.) EY09580 (J.E.R.), EY013178 (J.S.S.), EY015872
(J.L.W.), EY010886 (J.L.W.), EY009847 (J.L.W.), EY011008 (Zangwill, L),
EY144428 (K.Z.), EY144448 (K.Z.), EY18660 (K.Z.).
NR 36
TC 18
Z9 18
U1 0
U2 14
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 FEB
PY 2013
VL 155
IS 2
BP 342
EP 353
DI 10.1016/j.ajo.2012.07.023
PG 12
WC Ophthalmology
SC Ophthalmology
GA 078YQ
UT WOS:000314137400019
PM 23111177
ER
PT J
AU Jakobiec, FA
Zakka, FR
Perry, LP
AF Jakobiec, Frederick A.
Zakka, Fouad R.
Perry, Lynn P.
TI The Cytologic Composition of Dacryops: An Immunohistochemical
Investigation of 15 Lesions Compared to the Normal Lacrimal Gland
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID DUCTAL CYSTS; BILATERAL DACRYOPS; WOLFRING DACRYOPS; CONJUNCTIVAL CYST;
LIESEGANG RINGS; PALPEBRAL LOBE; CASE SERIES; TISSUE; ORBIT;
MARSUPIALIZATION
AB PURPOSE: To define the cytologic composition of the double-layered epithelial lining of dacryops (lacrimal duct cyst), improve histopathologic diagnosis, and better understand pathogenesis.
DESIGN: Clinicopathologic retrospective study with immunohistochemical studies of 15 lesions compared with normal lacrimal gland.
METHODS: Clinical data from 14 patients were reviewed and microscopy was performed with routine stains and immunohistochemical probes for epithelial membrane antigen (EMA), gross cystic disease fluid protein-15 (GCDFP-15), cytokeratin 7 (CK7), and smooth muscle actin (SMA).
RESULTS: The major lacrimal gland was involved in 13 lesions; 2 lesions arose in an accessory gland of Krause. One case was bilateral; the average age of the patients was 50.7 years. Neither visual acuity nor motility was disturbed. No lesion was discovered to have recurred after excision. Microscopically, in all dacryops specimens goblet cells and luminal pseudoapocrine apical cytoplasmic projections were identified. Lacrimal acinar cells immunoreacted with GCDFP-15 and CK7, whereas the normal ducts and the epithelium of the dacryops lesions reacted diffusely only with CK7. SMA-positive myoepithelial cells were found in the acini but not in the normal ducts or dacryops epithelium.
CONCLUSIONS: Negative GCDFP-15 staining ruled out apocrine metaplasia in dacryops. Normal ducts and dacryops showed no immunohistochemical evidence for the presence of myoepithelial cells. Pathogenetic theories of dacryops that implicate a failure of ductular "neuromuscular" contractility must therefore be revised. A dysfunction of the rich neural plexus around the ductules may play a role in the development of dacryops in conjunction with periductular inflammation and induced scarring. (Am J Ophthalmol 2013;155:380-396. (c) 2013 by Elsevier Inc. All rights reserved.)
C1 [Jakobiec, Frederick A.; Zakka, Fouad R.; Perry, Lynn P.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Lab Ophthalm Pathol,Dept Ophthalmol, Boston, MA 02114 USA.
RP Jakobiec, FA (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Lab Ophthalm Pathol,Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA.
EM Fred_Jakobiec@meei.harvard.edu
FU Heed Foundation, Cleveland, Ohio
FX ALL AUTHORS HAVE COMPLETED AND SUBMITTED THE ICMJE FORM FOR DISCLOSURE
OF POTENTIAL CONFLICTS OF INTEREST. The authors have no financial
disclosures. L.P.P. is supported in part by the Heed Foundation,
Cleveland, Ohio. Involved in design and conduct of the study (F.A.J.);
collection, management, analysis, and interpretation of the data
(F.A.J., F.R.Z., L.P.P.); and preparation, review, and approval of the
manuscript (F.A.J., F.R.Z., L.P.P.). This retrospective study received
prior Institutional Review Board approval to retrospectively review
patient data and was conducted in compliance with the rules and
regulations of the Health Insurance Portability and Accountability Act
and in adherence to the Declaration of Helsinki and all federal and
state laws.
NR 72
TC 9
Z9 9
U1 1
U2 9
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 FEB
PY 2013
VL 155
IS 2
BP 380
EP 396
DI 10.1016/j.ajo.2012.07.028
PG 17
WC Ophthalmology
SC Ophthalmology
GA 078YQ
UT WOS:000314137400023
PM 23114708
ER
PT J
AU Sahani, DV
Kambadakone, A
Macari, M
Takahashi, N
Chari, S
Fernandez-del Castillo, C
AF Sahani, Dushyant V.
Kambadakone, Avinash
Macari, Michael
Takahashi, Noaki
Chari, Suresh
Fernandez-del Castillo, Carlos
TI Diagnosis and Management of Cystic Pancreatic Lesions
SO AMERICAN JOURNAL OF ROENTGENOLOGY
LA English
DT Review
DE cystic pancreatic lesion; MDCT; MRI
ID PAPILLARY-MUCINOUS NEOPLASM; POSITRON-EMISSION-TOMOGRAPHY;
COMPUTED-TOMOGRAPHY; SEROUS-CYSTADENOMA; FOLLOW-UP; CLINICOPATHOLOGICAL
FEATURES; MR CHOLANGIOPANCREATOGRAPHY; PATHOLOGICAL CORRELATION;
DIFFERENTIAL-DIAGNOSIS; ENDOSCOPIC ULTRASOUND
AB OBJECTIVE. The purpose of this review is to outline the management guidelines for the care of patients with cystic pancreatic lesions.
CONCLUSION. The guidelines are as follows: Annual imaging surveillance is generally sufficient for benign serous cystadenomas smaller than 4 cm and for asymptomatic lesions. Asymptomatic thin-walled unilocular cystic lesions smaller than 3 cm or side-branch intraductal papillary mucinous neoplasms should be followed up with CT or MRI at 6 and 12 months interval after detection. Cystic lesions with more complex features or with growth rates greater than 1 cm/year should be followed more closely or recommended for resection if the patient's condition allows surgery. Symptomatic cystic lesions, neoplasms with high malignant potential, and lesions larger than 3 cm should be referred for surgical evaluation. Endoscopic ultrasound with fine-needle aspiration (FNA) biopsy can be used preoperatively to assess the risk of malignancy.
C1 [Sahani, Dushyant V.; Kambadakone, Avinash] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Abdominal Imaging & Intervent, Boston, MA 02114 USA.
[Macari, Michael] NYU, Dept Radiol, Div Abdominal Imaging, Langone Med Ctr, New York, NY 10016 USA.
[Takahashi, Noaki] Mayo Clin, Dept Radiol, Div Abdominal Imaging, Rochester, MN USA.
[Chari, Suresh] Mayo Clin, Dept Med, Div Gastroenterol, Rochester, MN USA.
[Fernandez-del Castillo, Carlos] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Pancreat Surg, Boston, MA 02114 USA.
RP Sahani, DV (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Abdominal Imaging & Intervent, 55 Fruit St,White 270, Boston, MA 02114 USA.
EM dsahani@partners.org
NR 93
TC 34
Z9 37
U1 0
U2 8
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 FEB
PY 2013
VL 200
IS 2
BP 343
EP 354
DI 10.2214/AJR.12.8862
PG 12
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 076LG
UT WOS:000313957400034
PM 23345356
ER
PT J
AU Gallotti, A
Johnston, RP
Bonaffini, PA
Ingkakul, T
Deshpande, V
Fernandez-del Castillo, C
Sahani, DV
AF Gallotti, Anna
Johnston, Rocio Perez
Bonaffini, Pietro A.
Ingkakul, Thun
Deshpande, Vikram
Fernandez-del Castillo, Carlos
Sahani, Dushyant V.
TI Incidental Neuroendocrine Tumors of the Pancreas: MDCT Findings and
Features of Malignancy
SO AMERICAN JOURNAL OF ROENTGENOLOGY
LA English
DT Article
DE incidental lesions; MDCT; neuroendocrine tumors; pancreas; pancreatic
malignancy
ID ISLET-CELL TUMORS; ENDOCRINE TUMORS; SURGICAL-TREATMENT; HELICAL CT;
NEOPLASMS; CLASSIFICATION; SURVIVAL; ANGIOGENESIS; PREDICTORS; DENSITY
AB OBJECTIVE. The objective of our study was to evaluate the MDCT features of incidentally detected neuroendocrine tumors (NETs) of the pancreas, identify features that can predict tumor biology or aggressiveness and long-term outcome, and determine the incidence of "nonbenign" behavior.
MATERIALS AND METHODS. In this retrospective study, 60 histologically verified pancreatic NETs incidentally detected with contrast-enhanced MDCT were included. Various MDCT features such as size, morphology, enhancement, and presence of calcifications were evaluated and were correlated with tumor biology on histopathology. The sensitivity, specificity, predictive values, and accuracy were calculated for MDCT features in predicting nonbenign biology and risk of recurrence.
RESULTS. A total of 32 of 60 (53%) NETs were nonbenign: most were large (mean, 29.1 mm) with a solid or complex pattern. NET size of 3 cm or larger yielded a positive predictive value of 61% for nonbenign tumors and 100% when calcification was present. In 12 patients with recurrence, 92% of NETs were nonbenign. The presence of calcification, local invasion, main pancreatic duct dilatation, vascular invasion, and lymph node enlargement along with angioinvasion and a Ki-67 index greater than 2% on histology were associated with a nonbenign diagnosis and a higher risk of recurrence.
CONCLUSION. Approximately 50% of incidental NETs show uncertain or malignant behavior. Solid tumors 3 cm or larger are commonly nonbenign; however, about 30% of tumors smaller than that size cutoff can be malignant. Nonbenign tumors and those with invasive features on MDCT have a higher incidence of recurrence.
C1 [Gallotti, Anna] Univ Verona, Dept Radiol, Univ Hosp GB Rossi, I-37100 Verona, Italy.
[Gallotti, Anna; Johnston, Rocio Perez; Bonaffini, Pietro A.; Sahani, Dushyant V.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Abdominal Imaging & Intervent, Boston, MA 02114 USA.
[Bonaffini, Pietro A.] Univ Milano Bicocca, San Gerardo Hosp, Dept Diagnost Radiol, Monza, Italy.
[Ingkakul, Thun; Fernandez-del Castillo, Carlos] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Deshpande, Vikram] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
RP Sahani, DV (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Abdominal Imaging & Intervent, 55 Fruit St,White 270, Boston, MA 02114 USA.
EM dsahani@partners.org
RI Bonaffini, Pietro/M-8067-2016
OI Bonaffini, Pietro/0000-0001-5335-9429
NR 47
TC 13
Z9 15
U1 0
U2 4
PU AMER ROENTGEN RAY SOC
PI RESTON
PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA
SN 0361-803X
J9 AM J ROENTGENOL
JI Am. J. Roentgenol.
PD FEB
PY 2013
VL 200
IS 2
BP 355
EP 362
DI 10.2214/AJR.11.8037
PG 8
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 076LG
UT WOS:000313957400035
PM 23345357
ER
PT J
AU Drubach, LA
Zurakowski, D
Palmer, EL
Tracy, DA
Lee, EY
AF Drubach, Laura A.
Zurakowski, David
Palmer, Edwin L., III
Tracy, Donald A.
Lee, Edward Y.
TI Utility of Salivagram in Pulmonary Aspiration in Pediatric Patients:
Comparison of Salivagram and Chest Radiography
SO AMERICAN JOURNAL OF ROENTGENOLOGY
LA English
DT Article
DE chest radiography; pediatric patients; pulmonary aspiration; salivagram
ID RADIONUCLIDE SALIVAGRAM; CHILDREN; AGREEMENT; SIALORRHEA; PNEUMONIA
AB OBJECTIVE. The purpose of our study was to correlate the results of the radionuclide salivagram with the corresponding chest radiography findings on patients being evaluated for salivary aspiration to determine the utility of the salivagram.
MATERIALS AND METHODS. We identified 222 patients younger than 21 years who underwent salivagram and chest radiography within 3 months of each other. Salivagrams were blindly interpreted by two readers and chest radiographs were blindly interpreted by two other readers. The kappa coefficient with 95% CI was used to measure the level of interobserver agreement. Multivariate logistic regression was applied to determine whether age, sex, and neurologic diagnosis were predictors of a positive salivagram, with the odds ratio used to estimate association.
RESULTS. Interobserver agreement on salivagram interpretation was excellent (kappa = 0.988; p < 0.0001; 95% CI, 0.968-1.000). Interobserver agreement on chest radiography interpretation was excellent (kappa = 0.905; p < 0.0001; 95% CI, 0.845-0.965). The salivagram was positive for aspiration in 55 patients (25%). Chest radiography was positive in 54 patients (24%). When the interpretations of the salivagram (normal or abnormal) were compared with interpretations of the chest radiograph (normal or abnormal), there were 213 agreements and nine disagreements (intermethod agreement kappa = 0.891; p < 0.0001; 95% CI, 0.831-0.952). Independent of age (p = 0.80) and sex (p = 0.31), patients with a neurologic diagnosis had odds of a positive salivagram 5.6 times higher than other diagnoses (odds ratio = 5.6; 95% CI, 2.5-13.1; p < 0.0001).
CONCLUSION. Infants with abnormal findings on salivagrams also had a high rate of abnormal findings on chest radiographs, which may indicate that some of the lung disease may be due to aspirated saliva. Salivagrams may be useful in children at risk of aspiration to identify those in whom intervention may help minimize the consequences of aspiration.
C1 [Drubach, Laura A.] Childrens Hosp, Dept Radiol, Div Nucl Med, Boston, MA 02115 USA.
[Drubach, Laura A.; Zurakowski, David; Palmer, Edwin L., III; Tracy, Donald A.; Lee, Edward Y.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Zurakowski, David] Childrens Hosp, Dept Anesthesia, Div Biostat, Boston, MA 02115 USA.
[Palmer, Edwin L., III] Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med, Boston, MA 02114 USA.
[Tracy, Donald A.; Lee, Edward Y.] Childrens Hosp, Dept Radiol, Div Thorac Imaging, Boston, MA 02115 USA.
RP Lee, EY (reprint author), Childrens Hosp, Dept Radiol, Div Thorac Imaging, 300 Longwood Ave, Boston, MA 02115 USA.
EM edward.lee@childrens.harvard.edu
NR 26
TC 4
Z9 4
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 FEB
PY 2013
VL 200
IS 2
BP 437
EP 441
DI 10.2214/AJR.12.8792
PG 5
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 076LG
UT WOS:000313957400046
PM 23345368
ER
PT J
AU Hunt, KJ
Gebregziabher, M
Lynch, CP
Echols, C
Mauldin, PD
Egede, LE
AF Hunt, Kelly J.
Gebregziabher, Mulugeta
Lynch, Cheryl P.
Echols, Carrae
Mauldin, Patrick D.
Egede, Leonard E.
TI Impact of diabetes control on mortality by race in a national cohort of
veterans
SO ANNALS OF EPIDEMIOLOGY
LA English
DT Article
DE Type 2 diabetes; Race; Hemoglobin A1c; Retrospective cohort; Medication
adherence; Mortality
ID ALL-CAUSE MORTALITY; MEDICATION ADHERENCE; HEMOGLOBIN A(1C);
CARDIOVASCULAR-DISEASE; LONGITUDINAL COHORT; RACIAL-DIFFERENCES; GLUCOSE
CONTROL; DRUG-THERAPY; TYPE-2; MELLITUS
AB Purpose: The association between glycated hemoglobin (HbA1c), medication use/adherence, and mortality stratified by race/ethnicity was examined in a national cohort of veterans with type 2 diabetes.
Methods: A total of 892,223 veterans with diabetes in 2002 were followed through 2006. HbA1c category was the main exposure (i.e., HbA1c <7%, HbA1c 7%-8% [reference], HbA1c 8%-9%, and HbA1c >9%). Covariates included age, sex, marital status, rural/urban residence, geographic region, number of comorbidities, and diabetes medication use/adherence (i.e., adherent, medication possession ratio >= 80%; nonadherent; and nonusers). HbA1c and medication use/adherence varied over time, and Cox regression models accounting for time-varying variables were used.
Results: In nonmedication users, HbA1c greater than 9% predicted higher mortality risk relative to HbA1c of 7%-8% in non-Hispanic whites (hazard ratio [HR], 1.55; 95% confidence interval [95% CI], 1.43-1.69), non-Hispanic blacks (NHB) (HR, 1.58; 95% CI, 1.34-1.87), and Hispanics (HR, 2.22; 95% CI, 1.75-2.82). In contrast, in nonadherent medication users, HbA1c less than 7% predicted higher mortality risk in NHB (HR, 1.12; 95% CI, 1.05-1.20), whereas HbA1c greater than 9% only predicted mortality in non-Hispanic whites (HR, 1.11; 95% CI, 1.06-1.16). In adherent medication users, HbA1c less than 7% predicted higher mortality in NHB (HR, 1.18; 95% CI, 1.07-1.31), whereas HbA1c greater than 9.0% predicted higher mortality risk across all race/ethnic groups.
Conclusion: We found evidence for racial/ethnic differences in the association between glycemic control and mortality, which varied by medication use/adherence. (c) 2013 Elsevier Inc. All rights reserved.
C1 [Hunt, Kelly J.; Gebregziabher, Mulugeta; Lynch, Cheryl P.; Echols, Carrae; Mauldin, Patrick D.; Egede, Leonard E.] Vet Affairs Med Ctr, Ctr Dis Prevent & Hlth Intervent Diverse Populat, Ralph H Johnson Dept, Charleston, SC 29403 USA.
[Hunt, Kelly J.; Gebregziabher, Mulugeta] Med Univ S Carolina, Dept Med, Div Biostat & Epidemiol, Charleston, SC 29425 USA.
[Hunt, Kelly J.; Lynch, Cheryl P.; Echols, Carrae; Mauldin, Patrick D.; Egede, Leonard E.] Med Univ S Carolina, Dept Med, Div Gen Internal Med, Ctr Hlth Dispar Res, Charleston, SC 29425 USA.
RP Egede, LE (reprint author), Med Univ S Carolina, Dept Med, Div Gen Internal Med, Ctr Hlth Dispar Res, 135 Rutledge Ave,MSC 593, Charleston, SC 29425 USA.
EM egedel@musc.edu
OI Gebregziabher, Mulugeta/0000-0002-4826-481X
FU VHA Health Services Research and Development program; [IIR-06-219]
FX This study was supported by grant IIR-06-219 funded by the VHA Health
Services Research and Development program. The funding agency did not
participate in the design and conduct of the study; collection,
management, analysis, and interpretation of the data; and preparation,
review, or approval of the manuscript.
NR 39
TC 6
Z9 6
U1 2
U2 11
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1047-2797
J9 ANN EPIDEMIOL
JI Ann. Epidemiol.
PD FEB
PY 2013
VL 23
IS 2
BP 74
EP 79
DI 10.1016/j.annepidem.2012.11.002
PG 6
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 074WO
UT WOS:000313846000007
PM 23238350
ER
PT J
AU Vaduganathan, M
AF Vaduganathan, Muthiah
TI The Perils of Long Surgical Experiences: Changes in Case Mix Over Time
SO ANNALS OF THORACIC SURGERY
LA English
DT Letter
ID AORTIC-VALVE-REPLACEMENT; OUTCOMES
C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
RP Vaduganathan, M (reprint author), Massachusetts Gen Hosp, Dept Med, 55 Fruit St,GRB 740, Boston, MA 02114 USA.
EM mvaduganathan@partners.org
NR 3
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 0003-4975
J9 ANN THORAC SURG
JI Ann. Thorac. Surg.
PD FEB
PY 2013
VL 95
IS 2
BP 771
EP 772
PG 3
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA 074DF
UT WOS:000313792000083
PM 23336903
ER
PT J
AU Wiederhold, NP
Najvar, LK
Bocanegra, R
Kirkpatrick, WR
Sorrell, TC
Patterson, TF
AF Wiederhold, Nathan P.
Najvar, Laura K.
Bocanegra, Rosie
Kirkpatrick, William R.
Sorrell, Tania C.
Patterson, Thomas F.
TI Limited Activity of Miltefosine in Murine Models of Cryptococcal
Meningoencephalitis and Disseminated Cryptococcosis
SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
LA English
DT Article
ID INDIAN VISCERAL LEISHMANIASIS; WORLD CUTANEOUS LEISHMANIASIS;
AMPHOTERICIN-B; FUNGICIDAL ACTIVITY; ORAL MILTEFOSINE; IN-VITRO;
MENINGITIS; FLUCONAZOLE; HEXADECYLPHOSPHOCHOLINE; FLUCYTOSINE
AB Miltefosine is an alkyl phosphocholine with good oral bioavailability and in vitro activity against Cryptococcus species that has gained interest as an additional agent for cryptococcal infections. Our objective was to further evaluate the in vivo efficacy of miltefosine in experimental in vivo models of cryptococcal meningoencephalitis and disseminated cryptococcosis. Mice were infected intracranially or intravenously with either C. neoformans USC1597 or H99. Miltefosine treatment (1.8 to 45 mg/kg of body weight orally once daily) began at either 1 h or 1 day postinoculation. Fluconazole (10 mg/kg orally twice daily) or amphotericin B deoxycholate (3 mg/kg intraperitoneally once daily) served as positive controls. In our standard models, miltefosine did not result in significant improvements in survival or reductions in fungal burden against either C. neoformans isolate. There was a trend toward improved survival with miltefosine at 7.2 mg/kg against disseminated cryptococcosis with the H99 strain but only at a low infecting inoculum. In contrast, both fluconazole and amphotericin B significantly improved survival in mice with cryptococcal meningoencephalitis and disseminated cryptococcosis due to USC1597. Amphotericin B also improved survival against both cryptococcal infections caused by H99. Combination therapy with miltefosine demonstrated neither synergy nor antagonism in both models. These results demonstrate limited efficacy of miltefosine and suggest caution with the potential use of this agent for the treatment of C. neoformans infections.
C1 [Wiederhold, Nathan P.; Najvar, Laura K.; Bocanegra, Rosie; Kirkpatrick, William R.; Patterson, Thomas F.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Wiederhold, Nathan P.] Univ Texas Austin, Coll Pharm, Austin, TX 78712 USA.
[Najvar, Laura K.; Bocanegra, Rosie; Kirkpatrick, William R.; Patterson, Thomas F.] S Texas Vet Hlth Care Adm, San Antonio, TX USA.
[Sorrell, Tania C.] Sydney Emerging Infect & Biosecur Inst, Sydney, NSW, Australia.
[Sorrell, Tania C.] Univ Sydney, Sydney, NSW 2006, Australia.
[Sorrell, Tania C.] Westmead Millennium Inst, Sydney, NSW, Australia.
RP Wiederhold, NP (reprint author), Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
EM wiederholdn@uthscsa.edu
OI Wiederhold, Nathan/0000-0002-2225-5122
FU National Institutes of Health/National Institute of Allergy and
Infectious Diseases [N01-AI-25475]; Pfizer; Schering-Plough; Merck;
Basilea; Astellas
FX This work was supported by a contract from the National Institutes of
Health/National Institute of Allergy and Infectious Diseases
(N01-AI-25475) to T.F.P. T.C.S. is a Sydney Medical School Foundation
Fellow.; N.P.W. has received research support from Pfizer,
Schering-Plough, Merck, Basilea, and Astellas and has served on advisory
boards for Merck, Astellas, Toyama, and Viamet. T.F.P. has received
research grants to UT Health Science Center San Antonio from Astellas,
Basilea, Merck, and Pfizer and has been a consultant for Astellas,
Basilea, Merck, Pfizer, and Toyama. We have no other conflicts of
interest.
NR 30
TC 10
Z9 10
U1 0
U2 4
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0066-4804
J9 ANTIMICROB AGENTS CH
JI Antimicrob. Agents Chemother.
PD FEB
PY 2013
VL 57
IS 2
BP 745
EP 750
DI 10.1128/AAC.01624-12
PG 6
WC Microbiology; Pharmacology & Pharmacy
SC Microbiology; Pharmacology & Pharmacy
GA 075ON
UT WOS:000313896500008
PM 23165465
ER
PT J
AU Halford, C
Gonzalez, R
Campuzano, S
Hu, B
Babbitt, JT
Liu, J
Wang, J
Churchill, BM
Haake, DA
AF Halford, Colin
Gonzalez, Rodrigo
Campuzano, Susana
Hu, Bo
Babbitt, Jane T.
Liu, Jun
Wang, Joseph
Churchill, Bernard M.
Haake, David A.
TI Rapid Antimicrobial Susceptibility Testing by Sensitive Detection of
Precursor rRNA Using a Novel Electrochemical Biosensing Platform
SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
LA English
DT Article
ID CLINICAL URINE SPECIMENS; AMBIENT-TEMPERATURE; UROPATHOGENS;
HYBRIDIZATION
AB Precursor rRNA (pre-rRNA) is an intermediate stage in the formation of mature rRNA and is a useful marker for cellular metabolism and growth rate. We developed an electrochemical sensor assay for Escherichia coli pre-rRNA involving hybridization of capture and detector probes with tail sections that are spliced away during rRNA maturation. A ternary self-assembled monolayer (SAM) prepared on gold electrode surfaces by coassembly of thiolated capture probes with hexanedithiol and posttreatment with 6-mercapto-1-hexanol minimized the background signal and maximized the signal-to-noise ratio. Inclusion of internal calibration controls allowed accurate estimation of the pre-rRNA copy number per cell. As expected, the ratio of pre-rRNA to mature rRNA was low during stationary phase and high during log phase. Pre-rRNA levels were highly dynamic, ranging from 2 copies per cell during stationary phase to similar to 1,200 copies per cell within 60 min of inoculation into fresh growth medium. Specificity of the assay for pre-rRNA was validated using rifampin and chloramphenicol, which are known inhibitors of pre-rRNA synthesis and processing, respectively. The DNA gyrase inhibitor, ciprofloxacin, was found to act similarly to rifampin; a decline in pre-rRNA was detectable within 15 min in ciprofloxacin-susceptible bacteria. Assays for pre-rRNA provide insight into cellular metabolism and are promising predictors of antibiotic susceptibility.
C1 [Halford, Colin; Gonzalez, Rodrigo; Babbitt, Jane T.; Haake, David A.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
[Halford, Colin; Churchill, Bernard M.; Haake, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA 90095 USA.
[Babbitt, Jane T.; Haake, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA.
[Haake, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA.
[Campuzano, Susana; Wang, Joseph] Univ Calif San Diego, Dept Nanoengn, La Jolla, CA 92093 USA.
[Hu, Bo; Liu, Jun] Univ Texas Med Sch Houston, Dept Pathol & Lab Med, Houston, TX USA.
RP Haake, DA (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
EM dhaake@ucla.edu
RI Campuzano Ruiz, Susana/C-6448-2011; Wang, Joseph/C-6175-2011
FU National Institute of Allergy and Infectious Diseases [AI075565]; Wendy
and Ken Ruby Fund for Excellence in Pediatric Urology Research; Welch
Foundation [AU-1714]
FX This study was supported by Cooperative Agreement Award AI075565 (to
D.A.H.) from the National Institute of Allergy and Infectious Diseases
and by the Wendy and Ken Ruby Fund for Excellence in Pediatric Urology
Research. B.M.C. is the Judith and Robert Winston Chair in Pediatric
Urology. B.H. and J.L. were supported by a grant from Welch Foundation
(AU-1714).
NR 18
TC 4
Z9 4
U1 1
U2 19
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0066-4804
J9 ANTIMICROB AGENTS CH
JI Antimicrob. Agents Chemother.
PD FEB
PY 2013
VL 57
IS 2
BP 936
EP 943
DI 10.1128/AAC.00615-12
PG 8
WC Microbiology; Pharmacology & Pharmacy
SC Microbiology; Pharmacology & Pharmacy
GA 075ON
UT WOS:000313896500033
PM 23229486
ER
PT J
AU Saremi, A
Schwenke, DC
Buchanan, TA
Hodis, HN
Mack, WJ
Banerji, M
Bray, GA
Clement, SC
Henry, RR
Kitabchi, AE
Mudaliar, S
Ratner, RE
Stentz, FB
Musi, N
Tripathy, D
DeFronzo, RA
Reaven, PD
AF Saremi, Aramesh
Schwenke, Dawn C.
Buchanan, Thomas A.
Hodis, Howard N.
Mack, Wendy J.
Banerji, MaryAnn
Bray, George A.
Clement, Stephen C.
Henry, Robert R.
Kitabchi, Abbas E.
Mudaliar, Sunder
Ratner, Robert E.
Stentz, Frankie B.
Musi, Nicolas
Tripathy, Devjit
DeFronzo, Ralph A.
Reaven, Peter D.
TI Pioglitazone Slows Progression of Atherosclerosis in Prediabetes
Independent of Changes in Cardiovascular Risk Factors
SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
LA English
DT Article
DE carotid atherosclerosis progression; impaired glucose tolerance; insulin
resistance; inflammation; pioglitazone
ID IMPAIRED GLUCOSE-TOLERANCE; TYPE-2 DIABETES-MELLITUS;
ACTIVATED-RECEPTOR-GAMMA; INTIMA-MEDIA THICKNESS; RANDOMIZED
CONTROLLED-TRIAL; SMOOTH-MUSCLE-CELLS; PPAR-GAMMA; INSULIN SENSITIVITY;
SUBCLINICAL ATHEROSCLEROSIS; CORONARY ATHEROSCLEROSIS
AB Objective-To determine whether changes in standard and novel risk factors during the Actos Now for Prevention of Diabetes trial explained the slower rate of carotid intima media thickness (CIMT) progression with pioglitazone treatment in persons with prediabetes.
Methods and Results-CIMT was measured in 382 participants at the beginning and up to 3 additional times during follow-up of the Actos Now for Prevention of Diabetes trial. During an average follow-up of 2.3 years, the mean unadjusted annual rate of CIMT progression was significantly (P=0.01) lower with pioglitazone treatment (4.76x10(-3) mm/year; 95% CI: 2.39x10(-3)-7.14x10(-3) mm/year) compared with placebo (9.69x10(-3) mm/year; 95% CI: 7.24x10(-3)-12.15x10(-3) mm/year). High-density lipoprotein cholesterol, fasting and 2-hour glucose, HbA(1c), fasting insulin, Matsuda insulin sensitivity index, adiponectin, and plasminogen activator inhibitor-1 levels improved significantly with pioglitazone treatment compared with placebo (P<0.001). However, the effect of pioglitazone on CIMT progression was not attenuated by multiple methods of adjustment for traditional, metabolic, and inflammatory risk factors and concomitant medications, and was independent of changes in risk factors during pioglitazone treatment.
Conclusion-Pioglitazone slowed progression of CIMT, independent of improvement in hyperglycemia, insulin resistance, dyslipidemia, and systemic inflammation in prediabetes. These results suggest a possible direct vascular benefit of pioglitazone. (Arterioscler Thromb Vasc Biol. 2013;33:393-399.)
C1 [Saremi, Aramesh; Schwenke, Dawn C.; Reaven, Peter D.] Phoenix Vet Affair VA Hlth Care Syst, Phoenix, AZ USA.
[Buchanan, Thomas A.; Hodis, Howard N.; Mack, Wendy J.] Univ So Calif, Sch Med, Los Angeles, CA USA.
[Banerji, MaryAnn] SUNY Hlth Sci Ctr, Brooklyn, NY USA.
[Bray, George A.] Louisiana State Univ, Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA.
[Clement, Stephen C.] Georgetown Univ, Washington, DC USA.
[Henry, Robert R.; Mudaliar, Sunder] San Diego VA Hlth Care Syst, San Diego, CA USA.
[Henry, Robert R.; Mudaliar, Sunder] Univ San Diego, San Diego, CA 92110 USA.
[Kitabchi, Abbas E.; Stentz, Frankie B.] Univ Tennessee, Memphis, TN USA.
[Ratner, Robert E.] Medstar Res Inst, Hyattsville, MD USA.
[Musi, Nicolas; Tripathy, Devjit; DeFronzo, Ralph A.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Musi, Nicolas] S Texas Vet Healthcare Syst, San Antonio, TX USA.
RP Reaven, PD (reprint author), Carl T Hayden VAMC 111E, Diabet Program, 650 E Indian Sch Rd, Phoenix, AZ 85012 USA.
EM Peter.Reaven@va.gov
FU Takeda Pharmaceuticals [NCT00220961]; office of Research and
Development, Medical Research Service, Department of Veterans Affairs;
BMS; Novartis; Boehringer Ingelheim; Sanofi-Aventis; Merck; Roche;
Takeda; Amylin; Eli Lilly; Daiichi-Sankyo; NovoNordisk; Genentech-Roche;
GlaxoSmithKline; Bayhill; Halozyme; Integrium; Takeda Pharmaceuticals
FX This investigator-initiated study was supported by a grant from Takeda
Pharmaceuticals. (ClinicalTrial.gov number, NCT00220961). This work was
supported in part by the office of Research and Development, Medical
Research Service, Department of Veterans Affairs. We are grateful to ACT
NOW study participants, study staff, and investigators. The contents of
this article do not repre-sent the views of the Department of Veterans
Affairs or the U.S. Government.; Dr Banerji reports receiving consulting
fees from BMS, Novartis, Boehringer Ingelheim, Sanofi-Aventis, Merck,
and Roche, and lecture fees from Merck and Sanofi-Aventis; Dr Buchanan
reports receiving consulting fees and lecture fees from Takeda and
reports that the University of Southern California Keck School of
Medicine has received grant support from Takeda; Dr DeFronzo reports
receiving payments for board membership from Amylin, Takeda, ISIS, and
Boehringer Ingelheim and reports that the University of Texas Health
Science Center at San Antonio has received grant support from Takeda,
Amylin, and Eli Lilly; Dr Henry reports receiving consulting fees,
lecture fees, and payment for expert testimony from Takeda; Dr Musi
reports receiving consulting fees from Merck, Daiichi-Sankyo, Takeda,
and Novartis; Dr Ratner reports that the Medstar Research Institute has
received consulting fees from Amylin, NovoNordisk, Sanofi-Aventis, and
Genentech-Roche and grant support from Amylin, NovoNordisk,
GlaxoSmithKline, Bayhill, Halozyme, and Integrium; Dr Reaven reports
receiving consulting fees from BMS and Gilead, lecture fees from Merck
and Amylin, and payment for the development of educational presentations
from Amylin, and that the Carl T. Hayden Veterans Affairs Medical Center
has received grant support from Amylin; and Dr Tripathy reports
receiving grant support from Takeda Pharmaceuticals. No other potential
conflict of interest relevant to this article was reported.
NR 40
TC 33
Z9 33
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1079-5642
J9 ARTERIOSCL THROM VAS
JI Arterioscler. Thromb. Vasc. Biol.
PD FEB
PY 2013
VL 33
IS 2
BP 393
EP +
DI 10.1161/ATVBAHA.112.300346
PG 16
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 073MS
UT WOS:000313747700035
PM 23175674
ER
PT J
AU Dhonnchadha, BAN
Lin, A
Leite-Morris, KA
Kaplan, GB
Man, HY
Kantak, KM
AF Dhonnchadha, B. A. Nic
Lin, A.
Leite-Morris, K. A.
Kaplan, G. B.
Man, H. Y.
Kantak, K. M.
TI Alterations in expression and phosphorylation of GluA1 receptors
following cocaine-cue extinction learning
SO BEHAVIOURAL BRAIN RESEARCH
LA English
DT Article
DE Basolateral amygdala; Cocaine; Cocaine-cue extinction learning; GluA1
receptor; Self-administration; Ventromedial prefrontal cortex
ID MEDIAL PREFRONTAL CORTEX; AMPA RECEPTORS; SYNAPTIC PLASTICITY; PKA
PHOSPHORYLATION; FEAR; TRAFFICKING; SUBUNIT; MEMORY; FOS
AB Brain regional analyses of total GluA1 and GluA1-pSer(845) were used to delineate plasticity of the AMPA receptor in conjunction with cocaine-cue extinction learning. Rats were trained to self-administer cocaine paired with a 2-s light cue and later underwent a single 2 h extinction session for which cocaine was withheld but response-contingent cues were presented. Control groups received yoked-saline sessions or received cocaine self-administration training without undergoing extinction training. Extinction-related increases and decreases, respectively, in total GluA1 were observed in the ventromedial prefrontal cortex (vmPFC) and basolateral amygdala (BLA). Phosphorylation of GluA1 at Ser(845) was increased in the vmPFC and nucleus accumbens (NAc). Though total GluA1 did not change in NAc, there was a positive association between the number of responses during extinction training and the magnitude of total GluA1 in NAc. No significant changes were evident in the dorsal hippocampus. We conclude that the BLA and vmPFC, in particular, appear to be loci for the inhibition of learned behavior induced via extinction training, but each site may have different signaling functions for cocaine-cue extinction learning. (c) 2012 Elsevier B.V. All rights reserved.
C1 [Dhonnchadha, B. A. Nic; Kantak, K. M.] Boston Univ, Dept Psychol, Boston, MA 02215 USA.
[Lin, A.; Man, H. Y.] Boston Univ, Dept Biol, Boston, MA 02215 USA.
[Leite-Morris, K. A.; Kaplan, G. B.] VA Boston Healthcare, Res Serv, Boston, MA USA.
[Leite-Morris, K. A.; Kaplan, G. B.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA.
[Leite-Morris, K. A.; Kaplan, G. B.] Boston Univ, Sch Med, Dept Pharmacol & Expt Therapeut, Boston, MA 02215 USA.
RP Kantak, KM (reprint author), Boston Univ, Dept Psychol, 64 Cummington Mall, Boston, MA 02215 USA.
EM kkantak@bu.edu
OI Leite-Morris, Kimberly/0000-0003-3407-7375
FU Boston University Center for Neuroscience; [DA011716]
FX This study was supported by seed funding from the Boston University
Center for Neuroscience and DA011716. We thank Ms. Jamie Gauthier for
assistance with data collection.
NR 25
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U1 0
U2 5
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0166-4328
EI 1872-7549
J9 BEHAV BRAIN RES
JI Behav. Brain Res.
PD FEB 1
PY 2013
VL 238
BP 119
EP 123
DI 10.1016/j.bbr.2012.10.012
PG 5
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA 078ZE
UT WOS:000314138800016
ER
PT J
AU Courtwright, A
AF Courtwright, Andrew
TI STIGMATIZATION AND PUBLIC HEALTH ETHICS
SO BIOETHICS
LA English
DT Article
DE contractualism; denormalization; Martha Nussbaum; public health ethics;
social identity; stigma
ID STIGMA; TUBERCULOSIS; PREJUDICE; OBESITY
AB Encouraged by the success of smoking denormalization strategies as a tobacco-control measure, public health institutions are adopting a similar approach to other health behaviors. For example, a recent controversial ad campaign in New York explicitly aimed to denormalize HIV/AIDS amongst gay men. Authors such as Scott Burris have argued that efforts like this are tantamount to stigmatization and that such stigmatization is unethical because it is dehumanizing. Others have offered a limited endorsement of denormalization/stigmatization campaigns as being justified on consequentialist grounds; namely, that the potential public health benefits outweigh any stigmatizing side effects. In this paper, I examine and reject the blanket condemnation of stigmatization efforts in public health. I argue that the moral status of such efforts are best evaluated within a contractualist, as opposed to a consequentialist, framework. Contractualism in public health ethics asks whether a particular stigmatizing policy could be justified to reasonable individuals who do not know whether they will be affected by that policy. Using this approach, I argue that it is sometimes permissible for public health institutions to engage in health-related stigmatization.
RP Courtwright, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Internal Med,Womens Hlth Associates, Yawkey 4B,55 Fruit St, Boston, MA 02114 USA.
EM acourtwright@partners.org
NR 25
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Z9 7
U1 2
U2 32
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0269-9702
J9 BIOETHICS
JI Bioethics
PD FEB
PY 2013
VL 27
IS 2
BP 74
EP 80
DI 10.1111/j.1467-8519.2011.01904.x
PG 7
WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical
SC Social Sciences - Other Topics; Medical Ethics; Social Issues;
Biomedical Social Sciences
GA 070MO
UT WOS:000313511300004
PM 21797912
ER
PT J
AU Liu, R
Gilmore, DM
Zubris, KAV
Xu, XY
Catalano, PJ
Padera, RF
Grinstaff, MW
Colson, YL
AF Liu, Rong
Gilmore, Denis M.
Zubris, Kimberly Ann V.
Xu, Xiaoyin
Catalano, Paul J.
Padera, Robert F.
Grinstaff, Mark W.
Colson, Yolonda L.
TI Prevention of nodal metastases in breast cancer following the lymphatic
migration of paclitaxel-loaded expansile nanoparticles
SO BIOMATERIALS
LA English
DT Article
DE Nanoparticle; Drug delivery; Polymer; Metastases; Breast cancer;
Lymphatic
ID EPITHELIAL OVARIAN-CANCER; DRUG-DELIVERY; CHEMOTHERAPY; TUMORS; MODEL;
RECURRENCE; MORBIDITY; EFFICACY; CARRIERS; THERAPY
AB Although breast cancer patients with localized disease exhibit an excellent long-term prognosis, up to 40% of patients treated with local resection alone may harbor occult nodal metastatic disease leading to increased locoregional recurrence and decreased survival. Given the potential for targeted drug delivery to result in more efficacious locoregional control with less morbidity, the current study assessed the ability of drug-loaded polymeric expansile nanoparticles (eNP) to migrate from the site of tumor to regional lymph nodes, locally deliver a chemotherapeutic payload, and prevent primary tumor growth as well as lymph node metastases. Expansile nanoparticles entered tumor cells and paclitaxel-loaded eNP (Pax-eNP) exhibited dose-dependent cytotoxicity in vitro and significantly decreased tumor doubling time in vivo against human triple negative breast cancer in both microscopic and established murine breast cancer models. Furthermore, migration of Pax-eNP to axillary lymph nodes resulted in higher intranodal paclitaxel concentrations and a significantly lower incidence of lymph node metastases. These findings demonstrate that lymphatic migration of drug-loaded eNP provides regionally targeted delivery of chemotherapy to both decrease local tumor growth and strategically prevent the development of nodal metastases within the regional tumor-draining lymph node basin. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Liu, Rong; Gilmore, Denis M.; Colson, Yolonda L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Thorac Surg,Dept Surg, Boston, MA 02115 USA.
[Zubris, Kimberly Ann V.; Grinstaff, Mark W.] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA.
[Zubris, Kimberly Ann V.; Grinstaff, Mark W.] Boston Univ, Dept Chem, Boston, MA 02215 USA.
[Xu, Xiaoyin] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA.
[Catalano, Paul J.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Padera, Robert F.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RP Colson, YL (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Thorac Surg,Dept Surg, 75 Francis St,PBB 544, Boston, MA 02115 USA.
EM mgrin@bu.edu; ycolson@partners.org
FU Center for Integration of Medicine and Innovative Technologies (CIMIT)
[07-004]; National Science Foundation [DMR-1006601, CNS-0958345]; Boston
University's Nanomedicine Program and Cross-Disciplinary Training in
Nanotechnology for Cancer [NIH R25 CA153955]; Brigham and Women's
Hospital; Boston University
FX This work was supported in part by the Center for Integration of
Medicine and Innovative Technologies (CIMIT #07-004), National Science
Foundation (DMR-1006601 and CNS-0958345), the Boston University's
Nanomedicine Program and Cross-Disciplinary Training in Nanotechnology
for Cancer (NIH R25 CA153955), Brigham and Women's Hospital, and Boston
University. The authors wish to express appreciation for the excellent
care provided by the staff at the Animal Resources Facility at
Dana-Farber Cancer Institute, and to acknowledge the contributions of
the Confocal Core Facility at Beth Israel Deaconess Medical Center under
the direction of Lay-Hong Ang.
NR 41
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U1 1
U2 50
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0142-9612
EI 1878-5905
J9 BIOMATERIALS
JI Biomaterials
PD FEB
PY 2013
VL 34
IS 7
BP 1810
EP 1819
DI 10.1016/j.biomaterials.2012.11.038
PG 10
WC Engineering, Biomedical; Materials Science, Biomaterials
SC Engineering; Materials Science
GA 078GV
UT WOS:000314087600007
PM 23228419
ER
PT J
AU Slopen, N
McLaughlin, KA
Dunn, EC
Koenen, KC
AF Slopen, Natalie
McLaughlin, Katie A.
Dunn, Erin C.
Koenen, Karestan C.
TI Childhood adversity and cell-mediated immunity in young adulthood: Does
type and timing matter?
SO BRAIN BEHAVIOR AND IMMUNITY
LA English
DT Article
DE Cell-mediated immune response; Epstein-Barr Virus (EBV) antibody titers;
Childhood adversity; Child abuse; Socioeconomic status; National
Longitudinal Study of Adolescent Health (Add Health)
ID EPSTEIN-BARR-VIRUS; EARLY-LIFE; PSYCHOLOGICAL STRESS;
SOCIOECONOMIC-STATUS; HEALTH OUTCOMES; INFECTIOUS-DISEASE;
ANTIBODY-LEVELS; MENTAL-HEALTH; MALTREATMENT; INFLAMMATION
AB Childhood adversity can have powerful effects on health over the life course. Persistent changes in cell-mediated immune function may be one pathway linking adverse childhood experiences with later disease risk. However, limited research has examined childhood adversity in relation to cell-mediated immune function, and in particular, immune response to latent viruses in adulthood. The present study investigated the association of two types of childhood adversity, socioeconomic disadvantage during adolescence and abuse prior to age 18, with Epstein-Barr Virus (EBV) antibody titers in a large nationally representative sample of young adults aged 24-32 years. Data were drawn from the National Longitudinal Study on Adolescent Health, Wave 4 (n = 13,162). We examined the associations of three indicators of adolescent SES (parental education, household income, and occupational status) and frequency and timing of physical and sexual abuse with EBV antibodies, controlling for age, sex, race/ethnicity, and presence of a smoker in the household during adolescence. Lower parental occupational status and some categories of lower education were associated with elevated EBV antibodies (p < .05), and individuals who reported sexual abuse that occurred more than 10 times had elevated EBV antibodies relative to individuals who were not sexually abused (p = 0.03). Among individuals exposed to physical abuse, those who were first abused at age 3-5 years had heightened EBV antibodies relative to those first abused during adolescence (p = 0.004). This study extends prior research linking early adversity and immune function, and provides initial evidence that childhood adversity has a persistent influence on immune responses to latent infection in adulthood. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Slopen, Natalie] Harvard Univ, Ctr Developing Child, Cambridge, MA 02138 USA.
[McLaughlin, Katie A.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Dunn, Erin C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA.
[Koenen, Karestan C.] Columbia Univ, Mailman Sch Publ Hlth, New York, NY 10032 USA.
RP Slopen, N (reprint author), Harvard Univ, Ctr Developing Child, 50 Church St,4th Floor, Cambridge, MA 02138 USA.
EM nslopen@hsph.harvard.edu
RI Koenen, Karestan/K-5402-2014;
OI Koenen, Karestan/0000-0003-3293-4281; McLaughlin,
Katie/0000-0002-1362-2410
FU Robert Wood Johnson Foundation; Eunice Kennedy Shriver National
Institute of Child Health and Human Development [P01-HD31921]
FX This research was funded by a postdoctoral fellowship to the first
author from the Robert Wood Johnson Foundation to support the Early
Childhood Innovation Project. This research uses data from Add Health, a
program project directed by Kathleen Mullan Harris and designed by J.
Richard Udry, Peter S. Bearman, and Kathleen Mullan Harris at the
University of North Carolina at Chapel Hill, and funded by Grant
P01-HD31921 from the Eunice Kennedy Shriver National Institute of Child
Health and Human Development, with cooperative funding from 23 other
federal agencies and foundations. Special acknowledgment is due Ronald
R. Rindfuss and Barbara Entwisle for assistance in the original design.
Information on how to obtain the Add Health data files is available on
the Add Health website (http://www.cpc.unc.edu/addhealth). No direct
support was received from Grant P01-HD31921 for this analysis.
NR 77
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U1 8
U2 38
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0889-1591
J9 BRAIN BEHAV IMMUN
JI Brain Behav. Immun.
PD FEB
PY 2013
VL 28
BP 63
EP 71
DI 10.1016/j.bbi.2012.10.018
PG 9
WC Immunology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA 076YV
UT WOS:000313996000008
PM 23108062
ER
PT J
AU Irwin, KE
Greer, JA
Khatib, J
Temel, JS
Pirl, WF
AF Irwin, Kelly E.
Greer, Joseph A.
Khatib, Jude
Temel, Jennifer S.
Pirl, William F.
TI Early palliative care and metastatic non-small cell lung cancer:
Potential mechanisms of prolonged survival
SO CHRONIC RESPIRATORY DISEASE
LA English
DT Article
DE Early palliative care; survival; lung cancer; advanced cancer
ID QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIAL; CLINICAL-TRIALS; MEDICINE
CONSULTATION; ELDERLY-PATIENTS; REPORTED HEALTH; MARITAL-STATUS;
DEPRESSION; INTERVENTION; OUTCOMES
AB Patients with advanced cancer experience a significant burden of physical symptoms and psychological distress at the end of life, and many elect to receive aggressive cancer-directed therapy. The goal of palliative care is to relieve suffering and promote quality of life (QOL) for patients and families. Traditionally, both the public and medical community have conceptualized the need for patients to make a choice between pursuing curative therapy or receiving palliative care. However, practice guidelines from the World Health Organization and leadership from the oncology and palliative care communities advocate a different model of palliative care that is introduced from the point of diagnosis of life-threatening illness. Early palliative care has been shown to provide benefits in QOL, mood, and health care utilization. Additionally, preliminary research has suggested that in contrast to fears about palliative care hastening death, referral to palliative care earlier in the course of illness may have the potential to lengthen survival, particularly in patients with advanced nonsmall-cell lung cancer. This review summarizes the literature on potential survival benefits of palliative care and presents a model of how early integrated palliative care could potentially influence survival in patients with advanced cancer.
C1 [Irwin, Kelly E.; Greer, Joseph A.; Temel, Jennifer S.; Pirl, William F.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
[Khatib, Jude] Royal Coll Surgeons Ireland, Dublin 2, Ireland.
RP Pirl, WF (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
EM wpirl@partners.org
NR 58
TC 24
Z9 25
U1 2
U2 23
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1479-9723
J9 CHRON RESP DIS
JI Chronic Respir. Dis.
PD FEB
PY 2013
VL 10
IS 1
BP 35
EP 47
DI 10.1177/1479972312471549
PG 13
WC Respiratory System
SC Respiratory System
GA 078UW
UT WOS:000314126200006
PM 23355404
ER
PT J
AU Bragdon, CR
Doerner, M
Martell, J
Jarrett, B
Palm, H
Malchau, H
AF Bragdon, Charles R.
Doerner, Michael
Martell, John
Jarrett, Bryan
Palm, Henrik
Malchau, Henrik
CA Multicenter Study Grp
TI The 2012 John Charnley Award: Clinical Multicenter Studies of the Wear
Performance of Highly Crosslinked Remelted Polyethylene in THA
SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH
LA English
DT Article
ID MOLECULAR-WEIGHT POLYETHYLENE; TOTAL HIP-ARTHROPLASTY; FEMORAL-HEAD
PENETRATION; TOTAL JOINT ARTHROPLASTY; RADIOSTEREOMETRIC ANALYSIS;
UNCEMENTED SOCKETS; ACETABULAR LINER; 3RD-BODY WEAR; FOLLOW-UP; IN-VITRO
AB Highly crosslinked polyethylene (HXLPE) in THA was developed to reduce particle-induced periprosthetic osteolysis. A series of clinical studies were initiated to determine the clinical efficacy as judged by patient-reported scores, radiographic osteolysis, and wear analysis of one form of HXLPE.
The purposes of this series of studies were to (1) determine the wear rates of one form of HXLPE; (2) report long-term (7-10 years) patient-reported outcome measures; (3) assess the effect of femoral head size on wear; and (4) determine the incidence of periprosthetic osteolysis.
A single-center and two multicenter studies were conducted on 768 primary patients (head size 26-36 mm) undergoing THA at eight medical centers. Patient-reported outcome scores, radiographic grading for osteolysis, and radiographic wear evaluation were performed.
Serial plain radiographs showed no periprosthetic osteolysis in the three studies. The average femoral head penetration rates did not correlate with time in vivo for patients with standard femoral head sizes. Although there was an indication of higher wear in patients with 36-mm diameter femoral heads, it was below the threshold for producing osteolysis.
The introduction of this HXLPE substantially improved the prognosis of patients after THA up to 13 years as judged by clinical scores, incidence of osteolysis, and polyethylene wear measurements.
Level III, therapeutic study. See the Guideline for Authors for a complete description of levels of evidence.
C1 [Bragdon, Charles R.; Doerner, Michael; Jarrett, Bryan; Malchau, Henrik] Massachusetts Gen Hosp, Harris Orthopaed Lab, Boston, MA 02114 USA.
[Martell, John] Univ Chicago, Med Ctr, Chicago, IL 60637 USA.
[Palm, Henrik] Hvidovre Univ Hosp, Copenhagen, Denmark.
RP Bragdon, CR (reprint author), Massachusetts Gen Hosp, Harris Orthopaed Lab, 55 Fruit St,GRJ 1126, Boston, MA 02114 USA.
EM cbragdon@partners.org
OI Malchau, Henrik/0000-0002-4291-2441
FU Zimmer Inc; Curing Hip Disease Fund; DePuy; William H. Harris Foundation
FX Sahlgrenska University Hospital, Gothenburg, Sweden One of the authors
(CDV) certifies he has or may receive payments or benefits, in any one
year, an amount in excess of $10,000 from a commercial entity (Biomet,
Warsaw, IN, USA, and Smith & Nephew, Memphis TN, USA). One of the
authors (KB) certifies that he has or may receive payments or benefits,
during the study period, an amount of more than $1,000,001 from Zimmer
Inc (Warsaw, IN, USA) and DePuy Ortho Inc (Warsaw, IN, USA). One of the
authors (DB) certifies that he has or may receive payments or benefits,
during the study period, an amount of more than $1,000,001 from DePuy
Ortho Inc. The institution of two contributors (PL, DB) receives
research funds From (DePuy Ortho Inc or Zimmer Inc). The institution of
one or more of the authors (CRB, MD, BJ, YMK, HM, PEJ, DB, JC) received
funding from Zimmer Inc, Curing Hip Disease Fund, DePuy, and/or the
William H. Harris Foundation. Seven contributors (JC, MD, YMK, BJ, PEJ,
HP, HM) certifies that he or she, or a member of their immediate family,
has no commercial associations (eg, consultancies, stock ownership,
equity interest, patent/licensing arrangements, etc) that might pose a
conflict of interest in connection with the submitted article.
NR 55
TC 36
Z9 36
U1 0
U2 6
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0009-921X
J9 CLIN ORTHOP RELAT R
JI Clin. Orthop. Rel. Res.
PD FEB
PY 2013
VL 471
IS 2
BP 393
EP 402
DI 10.1007/s11999-012-2604-0
PG 10
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA 074FO
UT WOS:000313798500010
PM 23070661
ER
PT J
AU Bozic, KJ
Ong, K
Lau, E
Berry, DJ
Vail, TP
Kurtz, SM
Rubash, HE
AF Bozic, Kevin J.
Ong, Kevin
Lau, Edmund
Berry, Daniel J.
Vail, Thomas P.
Kurtz, Steven M.
Rubash, Harry E.
TI Estimating Risk in Medicare Patients With THA: An Electronic Risk
Calculator for Periprosthetic Joint Infection and Mortality
SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH
LA English
DT Article
ID TOTAL HIP-ARTHROPLASTY; QUALITY-OF-LIFE; POSTOPERATIVE MORTALITY; KNEE;
REPLACEMENT; OSTEOARTHRITIS
AB Although risk factors for periprosthetic joint infection (PJI) and mortality after total hip arthroplasty (THA) have been identified, interactions between specific patient risk factors are poorly understood. Therefore, it is difficult for surgeons to counsel patients on their individual risk of PJI or mortality after THA.
We evaluated the interaction between patient clinical and demographic factors on the risk of PJI and mortality after THA and developed an electronic risk calculator for estimating the patient-specific risk of PJI and mortality in Medicare patients with THA.
We used the Medicare 5% sample claims database to calculate the risk of PJI within 2 years and mortality within 90 days after THA in 53,252 Medicare patients with primary THAs between 1998 and 2009. Logistic regression using 29 comorbid conditions, age, sex, race, and socioeconomic status were used as inputs to develop an electronic risk calculator to estimate patient-specific risk of PJI and mortality after THA.
The overall 2-year risk of PJI and 90-day risk of mortality after primary THA were 2.07% and 1.30%, respectively. White women aged 70 to 74 years with alcohol abuse, depression, electrolyte disorder, peptic ulcer disease, urinary tract infection, rheumatologic disease, preoperative anemia, cardiopulmonary (cardiac arrhythmia, congestive heart failure, ischemic heart disease, chronic pulmonary disease) comorbidities, and peripheral vascular disease were at highest risk for PJI. White women aged 65 to 69 years with electrolyte disorder, hemiplegia/paraplegia, hypertension, hypothyroidism, metastatic tumor, preoperative anemia, coagulopathy, cardiopulmonary (congestive heart failure, chronic pulmonary disease) and psychiatric (psychoses, depression) comorbidities, malignancies, and peripheral vascular disease were at highest risk for mortality. An electronic risk calculator was developed to estimate the risk of PJI and mortality in Medicare patients with THA.
This electronic risk calculator can be used to counsel Medicare patients regarding their patient-specific risks of PJI and mortality after THA.
Level II, prognostic study. See the Instructions for Authors for a complete description of levels of evidence.
C1 [Bozic, Kevin J.; Vail, Thomas P.] Univ Calif San Francisco, Dept Orthopaed Surg, San Francisco, CA 94143 USA.
[Bozic, Kevin J.] Univ Calif San Francisco, Philip R Lee Inst Hlth Policy Studies, San Francisco, CA 94143 USA.
[Ong, Kevin; Kurtz, Steven M.] Exponent Inc, Philadelphia, PA USA.
[Lau, Edmund] Exponent Inc, Menlo Pk, CA USA.
[Berry, Daniel J.] Mayo Clin, Dept Orthopaed Surg, Rochester, MN USA.
[Rubash, Harry E.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA.
RP Bozic, KJ (reprint author), Univ Calif San Francisco, Dept Orthopaed Surg, 500 Parnassus,MU 320W, San Francisco, CA 94143 USA.
EM kevin.bozic@ucsf.edu
FU Orthopaedic Research and Education Foundation (Rosemont, IL, USA);
Exponent, Inc (Philadelphia, PA, USA); Exponent, Inc.; DePuy
Orthopaedics, Inc (Warsaw, IN, USA); DePuy Orthopaedics, Inc.; Zimmer,
Inc (Warsaw, IN, USA)
FX The institution of one or more of the authors (KJB) has received, during
the study period, funding from the Orthopaedic Research and Education
Foundation (Rosemont, IL, USA). One of the authors (SMK) certifies that
he has received or may receive payments or benefits, during the study
period, an amount in excess of $100,000, from Exponent, Inc
(Philadelphia, PA, USA). One of the authors (KO) certifies that he has
received or may receive payments or benefits, during the study period,
an amount in excess of $100,000, from Exponent, Inc. One of the authors
(EL) certifies that he has received or may receive payments or benefits,
during the study period, an amount in excess of $100,000, from Exponent,
Inc. One of the authors (DJB) certifies that he has received or may
receive payments or benefits, during the study period, an amount in
excess of $100,000, from DePuy Orthopaedics, Inc (Warsaw, IN, USA). One
of the authors (TPV) certifies that he has received or may receive
payments or benefits, during the study period, an amount in excess of
$10,000, from DePuy Orthopaedics, Inc. One of the authors (HER)
certifies that he has received or may receive payments or benefits,
during the study period, an amount in excess of $100,000, from Zimmer,
Inc (Warsaw, IN, USA).
NR 16
TC 39
Z9 39
U1 0
U2 13
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0009-921X
J9 CLIN ORTHOP RELAT R
JI Clin. Orthop. Rel. Res.
PD FEB
PY 2013
VL 471
IS 2
BP 574
EP 583
DI 10.1007/s11999-012-2605-z
PG 10
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA 074FO
UT WOS:000313798500033
PM 23179112
ER
PT J
AU Jain, NB
Kuye, I
Higgins, LD
Warner, JJP
AF Jain, Nitin B.
Kuye, Ifedayo
Higgins, Laurence D.
Warner, Jon J. P.
TI Surgeon Volume is Associated With Cost and Variation in Surgical
Treatment of Proximal Humeral Fractures
SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH
LA English
DT Article
ID TOTAL HIP-REPLACEMENT; SHOULDER ARTHROPLASTY; HOSPITAL VOLUME; TERM
OUTCOMES; UNITED-STATES; CARE; CLASSIFICATION; HEMIARTHROPLASTY;
REPRODUCIBILITY; MORBIDITY
AB The issue of rising costs will likely dominate the healthcare debate in the forthcoming years.
We assessed factors including surgeon volume that were associated with lower hospital costs and variations in surgical treatment for proximal humeral fractures.
We used national databases for 2001 to 2008 to extract information on 25,731 patients undergoing surgery for proximal humeral fractures. We calculated hospital cost by converting hospital charges based on the hospital accounting reports collected by the Centers for Medicare & Medicaid Services.
In a multivariate linear regression analysis, higher surgeon volume, open reduction and internal fixation (versus hemiarthroplasty), and lower burden of comorbidities were associated with lower hospital cost. Higher surgeon volume was linearly associated with lower hospital costs such that, on average, adjusting for all other factors, a surgeon performing 20 shoulder arthroplasties per year saves a hospital approximately US $1800 per surgery. Factors associated with higher utilization of hemiarthroplasty included high surgeon volume (odds ratio [OR] = 1.46; 95% CI = 1.43, 1.97; as compared with low surgeon volume) and earlier years of our study period (OR = 0.61; 95% CI = 0.56, 0.66; for hemiarthroplasty in 2007-2008 versus 2001-2002).
Higher surgeon volume was associated with lower hospital costs for proximal humeral fractures. Therefore, policies on minimum volume requirements by hospitals may result in substantial cost savings. There is provider-based practice variation in the surgical treatment of proximal humeral fractures and evidence-based guidelines in this area are needed.
Level III, economic analysis. See Instructions for Authors for a complete description of levels of evidence.
C1 [Jain, Nitin B.] Brigham & Womens Hosp, Orthoped & Arthrit Ctr Outcomes Res, Boston, MA 02115 USA.
[Jain, Nitin B.; Kuye, Ifedayo; Higgins, Laurence D.; Warner, Jon J. P.] Harvard Univ, Sch Med, Harvard Shoulder Serv, Boston, MA USA.
[Jain, Nitin B.] Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA USA.
[Jain, Nitin B.; Kuye, Ifedayo; Higgins, Laurence D.] Brigham & Womens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA.
[Warner, Jon J. P.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA.
RP Jain, NB (reprint author), Brigham & Womens Hosp, Orthoped & Arthrit Ctr Outcomes Res, 75 Francis St,BC-4-016, Boston, MA 02115 USA.
EM njain1@partners.org
FU National Institute of Arthritis and Musculoskeletal and Skin Diseases
[1K23AR059199]; Foundation for Physical Medicine and Rehabilitation
(Rosemont, IL, USA); Biomedical Research Institute (Boston, MA, USA)
FX One of the authors (NBJ) certifies that he, or a member of his immediate
family, has received or may receive payments or benefits, during the
study period, from National Institute of Arthritis and Musculoskeletal
and Skin Diseases Project Number 1K23AR059199, Foundation for Physical
Medicine and Rehabilitation (Rosemont, IL, USA), and Biomedical Research
Institute (Boston, MA, USA).
NR 46
TC 14
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U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0009-921X
J9 CLIN ORTHOP RELAT R
JI Clin. Orthop. Rel. Res.
PD FEB
PY 2013
VL 471
IS 2
BP 655
EP 664
DI 10.1007/s11999-012-2481-6
PG 10
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA 074FO
UT WOS:000313798500044
PM 22826013
ER
PT J
AU Larkin, ME
Beauharnais, CC
Magyar, K
Macey, L
Grennan, KB
Boykin, EE
Russell, SJ
AF Larkin, Mary E.
Beauharnais, Catherine C.
Magyar, Kendra
Macey, Laurel
Grennan, Kerry B.
Boykin, Emily E.
Russell, Steven J.
TI Obtaining surrogate consent for a minimal-risk research study in the
intensive care unit setting
SO CLINICAL TRIALS
LA English
DT Article
AB Background Obtaining surrogate consent for clinical research studies conducted in the intensive care unit (ICU) setting is logistically challenging.
Purpose To determine whether differences in proportions consenting to trial enrollment existed among patients eligible to consent directly versus those requiring surrogate decision makers in a minimal-risk study to evaluate the accuracy of continuous glucose monitoring in the ICU setting.
Methods Low initial enrollment rates prompted a detailed tracking of the screening and consent process. We analyzed the subset of eligible patients identified during a single year to document whether they were approached about trial enrollment, whether they consented or declined, the reasons for declining, and the method of consent (self or surrogate). The proportion of participants who consented and the reasons for declining were compared for self-consenting and surrogate-consenting participants.
Results Of the 3041 patients screened, one-third (n = 982) were eligible; 119 of the 982 were approached regarding enrollment. Absence of a surrogate accounted for the majority of eligible patients (726; 84%) not approached. The most common reasons for refusal in the self versus surrogate groups included feeling overwhelmed (13% vs 24%), fear of discomfort (22% vs 12%), and fear of risk (7% vs 4%). Of the 57 eligible patients capable of consenting directly, 11 (19%) enrolled versus 12 (19%) of the 62 who required surrogate consent. When recruitment hours were expanded to include evening time, more eligible patients or their surrogates could be approached than during the day-shift hours alone. Consent was obtained for a larger proportion of potential participants with a history of diabetes (40%) than for those without a history of diabetes (14%).
Limitations The findings are from a subset of the entire study sample; data were available only for participants who could be approached, who may have differed from those who could not be approached.
Conclusions Surrogate and self-consent rates were similar. Surrogate unavailability was a major barrier to enrollment; overlap of staffing with usual visiting hours should be considered when planning trials in the ICU. Clinical Trials 2012; 10: 93-96. http://ctj.sagepub.com
C1 [Larkin, Mary E.; Beauharnais, Catherine C.; Magyar, Kendra; Macey, Laurel; Grennan, Kerry B.; Boykin, Emily E.; Russell, Steven J.] Massachusetts Gen Hosp, Diabet Res Ctr, Boston, MA 02114 USA.
RP Larkin, ME (reprint author), Massachusetts Gen Hosp, Diabet Res Ctr, 50 Staniford St,Ste 301, Boston, MA 02114 USA.
EM mlarkin1@partners.org
FU Abbott Diabetes Care; R01 [5R01DK085633-03]
FX This work was funded by a grant from Abbott Diabetes Care for an
investigator-initiated study of continuous glucose monitoring (to SJ
Russell, MGH Principal Investigator) and from R01 (#5R01DK085633-03) to
Edward Damiano (with SJR as MGH Principal Investigator).
NR 7
TC 2
Z9 2
U1 0
U2 4
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1740-7745
J9 CLIN TRIALS
JI Clin. Trials
PD FEB
PY 2013
VL 10
IS 1
BP 93
EP 96
DI 10.1177/1740774512464727
PG 4
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 075RT
UT WOS:000313904900012
PM 23169873
ER
PT J
AU Hinton, DE
Pich, V
Hofmann, SG
Otto, MW
AF Hinton, Devon E.
Pich, Vuth
Hofmann, Stefan G.
Otto, Michael W.
TI Acceptance and Mindfulness Techniques as Applied to Refugee and Ethnic
Minority Populations With PTSD: Examples From "Culturally Adapted CBT"
SO COGNITIVE AND BEHAVIORAL PRACTICE
LA English
DT Article
DE acceptance; mindfulness; PTSD; cross-cultural
ID TREATMENT-RESISTANT PTSD; CAMBODIAN REFUGEES; EMOTION REGULATION;
INITIAL VALIDATION; PANIC-ATTACKS; SCALE; PERSPECTIVE; COMPASSION;
MEDITATION; MECHANISMS
AB In this article we illustrate how we utilize acceptance and mindfulness techniques in our treatment (Culturally Adapted CBT, or CA-CBT) for traumatized refugees and ethnic minority populations. We present a Nodal Network Model (NNM) of Affect to explain the treatment's emphasis on body-centered mindfulness techniques and its focus on psychological flexibility. We explain the definition of mindfulness that guides our treatment, and we outline a typology of mindfulness states and show how many of the techniques in our treatment can be analyzed by these categories. We argue that acceptance and mindfulness are therapeutic for refugees and minority populations for several reasons. These include their increasing psychological flexibility, decreasing somatic distress, decreasing rumination, serving as emotion regulation techniques, decreasing the attentional bias to threat, and forming part of a new adaptive processing mode (which in CA-CBT centers on psychological flexibility). We describe the specific ways we teach acceptance and mindfulness with Latino and Southeast Asian refugee populations and present case examples of the treatment of a traumatized Latino and Cambodian patient.
C1 [Hinton, Devon E.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Hinton, Devon E.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[Hinton, Devon E.; Pich, Vuth] Arbour Counseling Serv, Lowell, MA USA.
[Hofmann, Stefan G.; Otto, Michael W.] Boston Univ, Boston, MA 02215 USA.
RP Hinton, DE (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 15 Parkman St,WACC 812, Boston, MA 02114 USA.
EM devon_hinton@hms.harvard.edu
RI Hofmann, Stefan/B-8769-2014
OI Hofmann, Stefan/0000-0002-3548-9681
NR 44
TC 13
Z9 13
U1 4
U2 47
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1077-7229
J9 COGN BEHAV PRACT
JI Cogn. Behav. Pract.
PD FEB
PY 2013
VL 20
IS 1
BP 33
EP 46
PG 14
WC Psychology, Clinical
SC Psychology
GA 073UY
UT WOS:000313769800004
ER
PT J
AU Otis, JD
AF Otis, John D.
TI Chronic Pain: An Integrated Biobehavioral Approach
SO COGNITIVE AND BEHAVIORAL PRACTICE
LA English
DT Book Review
AB Chronic pain is a significant health-care problem that impacts millions of Americans and costs our economy billions of dollars each year. Research indicates that cognitive behavioral therapy (CBT) can be an effective approach for teaching individuals with chronic pain ways of managing their pain more effectively. In Chronic Pain: An Integrated Biobehavioral Approach, Drs. Dennis Turk and Herta Nor (2011) provide a well-written and clear product that skillfully integrates pain-relevant science and research with information that is directly relevant for clinical practice. This book is highly recommended for any clinician interested in working with patients who have chronic pain.
C1 [Otis, John D.] VA Boston Healthcare Syst, Boston, MA 02130 USA.
RP Otis, JD (reprint author), VA Boston Healthcare Syst, 150 S Huntington Ave, Boston, MA 02130 USA.
EM John.Otis@va.gov
NR 3
TC 0
Z9 0
U1 1
U2 9
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1077-7229
J9 COGN BEHAV PRACT
JI Cogn. Behav. Pract.
PD FEB
PY 2013
VL 20
IS 1
BP 117
EP 118
PG 2
WC Psychology, Clinical
SC Psychology
GA 073UY
UT WOS:000313769800013
ER
PT J
AU Anzueto, A
Restrepo, MI
Pugh, MJV
Wilson, BZ
Mortensen, EM
AF Anzueto, Antonio
Restrepo, Marcos I.
Pugh, Mary Jo V.
Wilson, Bryan Z.
Mortensen, Eric M.
TI Severe Community-Acquired Pneumonia: Don't Get Rid of Fluoroquinolone
reply
SO CRITICAL CARE MEDICINE
LA English
DT Letter
C1 [Anzueto, Antonio; Restrepo, Marcos I.; Pugh, Mary Jo V.] Univ Texas Hlth Sci Ctr San Antonio, VERDICT S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA.
[Pugh, Mary Jo V.] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol, San Antonio, TX 78229 USA.
[Pugh, Mary Jo V.] Univ Texas Hlth Sci Ctr San Antonio, Dept Biostat, San Antonio, TX 78229 USA.
[Wilson, Bryan Z.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA.
[Mortensen, Eric M.] VA N Texas Hlth Care Syst, Dallas, TX USA.
[Mortensen, Eric M.] Univ Texas SW, Dallas, TX USA.
RP Anzueto, A (reprint author), Univ Texas Hlth Sci Ctr San Antonio, VERDICT S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA.
RI Restrepo, Marcos/H-4442-2014
FU NHLBI NIH HHS [K23 HL096054]
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 0090-3493
J9 CRIT CARE MED
JI Crit. Care Med.
PD FEB
PY 2013
VL 41
IS 2
BP E16
EP E17
DI 10.1097/CCM.0b013e318277103a
PG 2
WC Critical Care Medicine
SC General & Internal Medicine
GA 078NO
UT WOS:000314106000006
PM 23353969
ER
PT J
AU Wedel, SK
Orr, RA
Frakes, MA
Conn, AKT
AF Wedel, Suzanne K.
Orr, Richard A.
Frakes, Michael A.
Conn, Alasdair K. T.
TI Improving the Incomplete Infrastructure for Interhospital Patient
Transfer
SO CRITICAL CARE MEDICINE
LA English
DT Letter
ID MEDICARE BENEFICIARIES; TRANSPORT; CARE; CERTIFICATION; HOSPITALS;
EVENTS
C1 [Wedel, Suzanne K.; Frakes, Michael A.] Boston MedFlight, Boston, MA USA.
[Wedel, Suzanne K.] Boston Univ, Sch Med, Dept Surg, Boston, MA 02118 USA.
[Orr, Richard A.] Univ Pittsburgh, Sch Med, Dept Crit Care Med & Pediat, Pittsburgh, PA USA.
[Conn, Alasdair K. T.] Massachusetts Gen Hosp, Dept Emergency Serv, Boston, MA 02114 USA.
[Conn, Alasdair K. T.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA.
RP Wedel, SK (reprint author), Boston MedFlight, Boston, MA USA.
NR 10
TC 1
Z9 1
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0090-3493
J9 CRIT CARE MED
JI Crit. Care Med.
PD FEB
PY 2013
VL 41
IS 2
BP E21
EP E22
DI 10.1097/CCM.0b013e318275861e
PG 2
WC Critical Care Medicine
SC General & Internal Medicine
GA 078NO
UT WOS:000314106000014
PM 23353977
ER
PT J
AU Wei, NJ
Wexler, DJ
Nathan, DM
Grant, RW
AF Wei, N. J.
Wexler, D. J.
Nathan, D. M.
Grant, R. W.
TI Intensification of diabetes medication and risk for 30-day readmission
SO DIABETIC MEDICINE
LA English
DT Article
ID ACUTE MYOCARDIAL-INFARCTION; HOSPITAL ADMISSION; HEMOGLOBIN A1C;
PRIMARY-CARE; DIAGNOSIS; SERVICE; DISCONTINUATION; HYPERGLYCEMIA;
PREVALENCE; MORTALITY
AB Aim To examine the association of in-hospital diabetes regimen intensification with subsequent 30-day risk for unplanned readmission/emergency department admission. Methods We retrospectively studied 1949 adults with Type 2 diabetes receiving primary care within an academic health network admitted to the hospital between January 2007 and December 2009. Glucose therapy intensification was defined as new start of insulin or oral hypoglycaemic agents, or addition of prandial insulin or insulin mixtures. The association of glucose therapy intensification with subsequent 30-day risk for unplanned readmission/emergency department admission was examined, with focus on medicine service patients with poorly controlled glycaemia (baseline HbA1c = 64 mmol/mol). Results One in six patients (324/1949, 17%) had early readmission/emergency department admission. Compared with patients without early readmission, readmitted patients were more often male (58 vs. 52%, P = 0.03), had higher Charlson co-morbidity score [mean (sd) 3.0 (2.0) vs. 2.8 (1.8), P = 0.02], longer length of stay [5 (4.4) vs. 3.9 (3.3) days, P < 0.01] and were more often discharged home with nursing services (38 vs. 32%, P = 0.03). Overall, glucose therapy intensification was not associated with early hospital readmission/emergency department admission (odds ratio 0.94, 95% CI 0.641.37, P = 0.74). However, among medicine service patients with baseline HbA1c = 64 mmol/mol (8%), glucose therapy intensification was associated with a significantly decreased early readmission risk (adjusted odds ratio 0.33, 95% CI 0.120.88, P = 0.03) and lower post-discharge HbA1c {mean decrease (sd): 20 (26) mmol/mol [1.8 (2.4)%] vs. 7 (15) mmol/mol [0.6 (1.4)%], P < 0.01}. Conclusions Diabetes medical regimen intensification during hospitalization was not associated with early readmission. Among patients with elevated HbA1c, glucose therapy intensification was associated with a decreased 30-day readmission/emergency department admission risk and lower outpatient HbA1c levels. Our findings support the safety and durable impact of diabetes regimen optimization during hospital admission.
C1 [Wei, N. J.; Wexler, D. J.; Nathan, D. M.] Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA.
[Wei, N. J.; Wexler, D. J.; Nathan, D. M.] Harvard Univ, Sch Med, Boston, MA USA.
[Grant, R. W.] Kaiser Permanente, Div Res, Oakland, CA USA.
RP Wei, NJ (reprint author), Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA.
EM ncwei@partners.org
OI Grant, Richard/0000-0002-6164-8025
FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
[T32 DK007-028]; NIDDK [K23-DK 080-28]; Charlton Fund for Innovative
Research in Diabetes
FX NJW is supported by a National Institute of Diabetes and Digestive and
Kidney Diseases (NIDDK) training grant (T32 DK007-028). DJW is supported
by a NIDDK Patient-Oriented Research Career Development Award (K23-DK
080-28). DMN is supported in part by the Charlton Fund for Innovative
Research in Diabetes.
NR 26
TC 6
Z9 6
U1 2
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0742-3071
J9 DIABETIC MED
JI Diabetic Med.
PD FEB
PY 2013
VL 30
IS 2
BP E56
EP E62
DI 10.1111/dme.12061
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 075HV
UT WOS:000313876500004
PM 23126686
ER
PT J
AU Tirado, A
Wu, T
Noble, VE
Huang, C
Lewiss, RE
Martin, JA
Murphy, MC
Sivitz, A
AF Tirado, Alfredo
Wu, Teresa
Noble, Vicki E.
Huang, Calvin
Lewiss, Resa E.
Martin, Jennifer A.
Murphy, Michael C.
Sivitz, Adam
TI Ultrasound-Guided Procedures in the Emergency Department-Diagnostic and
Therapeutic Asset
SO EMERGENCY MEDICINE CLINICS OF NORTH AMERICA
LA English
DT Article
DE Ultrasound; Procedures; Pericardiocentesis; Abscess; Lumbar puncture;
Paracentesis; Arthrocentesis; Thoracentesis
ID SOFT-TISSUE INFECTIONS; FOREIGN-BODIES; LUMBAR PUNCTURE;
EPIDURAL-ANESTHESIA; SONOGRAPHIC DETECTION; BEDSIDE SONOGRAPHY; JOINT
EFFUSIONS; LOCALIZATION; PERICARDIOCENTESIS; ULTRASONOGRAPHY
AB Bedside ultrasound is an extremely valuable and rapidly accessible diagnostic and therapeutic modality in potentially life- and limb-threatening situations in the emergency department. In this report, the authors discuss the role of ultrasound in quick assessment of pathologic conditions and its use to aid in diagnostic and therapeutic interventions.
C1 [Tirado, Alfredo] Florida Hosp E Orlando, Dept Emergency Med, Orlando, FL 32822 USA.
[Wu, Teresa] Univ Arizona, Coll Med, Maricopa Med Ctr, Dept Emergency Med,EM Residency Program, Phoenix, AZ 85008 USA.
[Noble, Vicki E.; Huang, Calvin] Harvard Univ, Massachusetts Gen Hosp, Dept Emergency Med, Emergency Ultrasound Div, Boston, MA 02114 USA.
[Lewiss, Resa E.; Martin, Jennifer A.] St Lukes Roosevelt Hosp, Dept Emergency Med, Emergency Ultrasound Div, New York, NY 10025 USA.
[Murphy, Michael C.] Harvard Univ, Sch Med, Mt Auburn Hosp, Dept Emergency Med, Cambridge, MA 02138 USA.
[Sivitz, Adam] Univ Med & Dent New Jersey, Newark Beth Israel Med Ctr, Newark, NJ 07112 USA.
[Sivitz, Adam] Univ Med & Dent New Jersey, Childrens Hosp New Jersey, Newark, NJ 07112 USA.
RP Tirado, A (reprint author), Florida Hosp E Orlando, Dept Emergency Med, 7727 Lake Underhill Rd, Orlando, FL 32822 USA.
EM tirado_alfredo@yahoo.com
NR 68
TC 10
Z9 10
U1 1
U2 6
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0733-8627
J9 EMERG MED CLIN N AM
JI Emerg. Med. Clin. N. Am.
PD FEB
PY 2013
VL 31
IS 1
BP 117
EP +
DI 10.1016/j.emc.2012.09.009
PG 34
WC Emergency Medicine
SC Emergency Medicine
GA 067RL
UT WOS:000313312700007
PM 23200331
ER
PT J
AU Erqou, S
Lee, CTC
Suffoletto, M
Echouffo-Tcheugui, JB
de Boer, RA
van Melle, JP
Adler, AI
AF Erqou, Sebhat
Lee, Chee-Tin Christine
Suffoletto, Matthew
Echouffo-Tcheugui, Justin B.
de Boer, Rudolf A.
van Melle, Joost P.
Adler, Amanda I.
TI Association between glycated haemoglobin and the risk of congestive
heart failure in diabetes mellitus: systematic review and meta-analysis
SO EUROPEAN JOURNAL OF HEART FAILURE
LA English
DT Review
DE Heart failure; Diabetes; Epidemiology; HbA(1c); Hyperglycaemia;
Meta-analysis; Risk factor; Systematic review
ID GLYCEMIC CONTROL; ATHEROSCLEROSIS RISK; TASK-FORCE; TYPE-2; DISEASE;
GLUCOSE; HOSPITALIZATION; CARDIOMYOPATHY; COLLABORATION; COMPLICATIONS
AB Clinical trials to date have not provided definitive evidence regarding the effects of glucose lowering on the incidence of congestive heart failure (CHF). We synthesized available prospective epidemiological data on the association between glycaemia measured by haemoglobin A(1c) (HbA(1c)) and incident CHF in individuals with diabetes.
We searched electronic databases and reference lists of selected articles for relevant prospective epidemiological studies. We abstracted data from relevant studies using standardized forms and obtained additional data from investigators when required. We pooled study-specific relative risk estimates using random-effects model meta-analysis.
Of the 1044 citations identified, we included 10 studies comprising 178 929 participants with diabetes and 14 176 incident CHF cases. Five studies included only patients with type 2 diabetes, four studies had predominantly patients with type 2 diabetes, and one study included only patients with type 1 diabetes. All studies except one showed an increased risk of CHF with higher HbA(1c). The overall adjusted risk ratio (RR) for CHF was 1.15 [95 confidence interval (CI) 1.101.21] for each percentage point higher HbA(1c). There was substantial heterogeneity across the 10 studies (I-2: 83; 95 CI 6991; P 0.001) not explained by available study-level characteristics such as study design or average HbA(1c) level. In seven studies reporting RRs with more than one degree of adjustment, the association was minimally altered after adjustment for several cardiovascular risk factors.
In observational studies of individuals with diabetes, a higher HbA(1c) level was associated with a significantly increased incidence of CHF.
C1 [Erqou, Sebhat] Univ Pittsburgh, Med Ctr, Dept Internal Med, Pittsburgh, PA 15213 USA.
[Lee, Chee-Tin Christine] Univ Toronto, Dept Nutr Sci, Toronto, ON M5S 1A1, Canada.
[Suffoletto, Matthew] Vet Affairs Pittsburgh Hlth Care Syst, Dept Cardiol, Pittsburgh, PA USA.
[Echouffo-Tcheugui, Justin B.] Emory Univ, Rollins Sch Publ Hlth, Dept Global Hlth, Atlanta, GA 30322 USA.
[de Boer, Rudolf A.; van Melle, Joost P.] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, NL-9700 AB Groningen, Netherlands.
[Adler, Amanda I.] Addenbrookes Hosp, Inst Metab Sci, Cambridge, England.
RP Erqou, S (reprint author), Univ Pittsburgh, Med Ctr, Dept Internal Med, Pittsburgh, PA 15213 USA.
EM sebhaterqou@googlemail.com
NR 40
TC 17
Z9 17
U1 0
U2 12
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1388-9842
J9 EUR J HEART FAIL
JI Eur. J. Heart Fail.
PD FEB
PY 2013
VL 15
IS 2
BP 185
EP 193
DI 10.1093/eurjhf/hfs156
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 074RV
UT WOS:000313831900010
PM 23099356
ER
PT J
AU Lim, K
Merfeld, DM
AF Lim, Koeun
Merfeld, Daniel M.
TI Signal detection theory and vestibular perception: II. Fitting
perceptual thresholds as a function of frequency (vol 222, pg 303, 2012)
SO EXPERIMENTAL BRAIN RESEARCH
LA English
DT Correction
C1 [Lim, Koeun; Merfeld, Daniel M.] Massachusetts Eye & Ear Infirm, Jenks Vestibular Physiol Lab, Boston, MA 02114 USA.
[Merfeld, Daniel M.] Harvard Univ, Sch Med, Boston, MA USA.
RP Merfeld, DM (reprint author), Massachusetts Eye & Ear Infirm, Jenks Vestibular Physiol Lab, 243 Charles St,Suite 421, Boston, MA 02114 USA.
EM koeunlim@mit.edu; dan_merfeld@meei.harvard.edu
NR 1
TC 0
Z9 0
U1 1
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0014-4819
J9 EXP BRAIN RES
JI Exp. Brain Res.
PD FEB
PY 2013
VL 224
IS 3
BP 501
EP 501
DI 10.1007/s00221-012-3306-2
PG 1
WC Neurosciences
SC Neurosciences & Neurology
GA 077PO
UT WOS:000314040000018
ER
PT J
AU Young, RH
AF Young, Robert H.
TI Dr Robert E. Scully - Obituary
SO HISTOPATHOLOGY
LA English
DT Biographical-Item
C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA.
RP Young, RH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA.
NR 1
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0309-0167
J9 HISTOPATHOLOGY
JI Histopathology
PD FEB
PY 2013
VL 62
IS 3
BP 525
EP 527
DI 10.1111/his.12074
PG 3
WC Cell Biology; Pathology
SC Cell Biology; Pathology
GA 075US
UT WOS:000313913000020
PM 23339368
ER
PT J
AU Chirinos, JA
Segers, P
Rietzschel, ER
De Buyzere, ML
Raja, MW
Claessens, T
De Bacquer, D
Sutton, MSJ
Gillebert, TC
AF Chirinos, Julio A.
Segers, Patrick
Rietzschel, Ernst R.
De Buyzere, Marc L.
Raja, Muhammad W.
Claessens, Tom
De Bacquer, Dirk
Sutton, Martin St. John
Gillebert, Thierry C.
CA Asklepios Investigators
TI Early and Late Systolic Wall Stress Differentially Relate to Myocardial
Contraction and Relaxation in Middle-Aged Adults The Asklepios Study
SO HYPERTENSION
LA English
DT Article
DE afterload; diastolic function; loading sequence; myocardial function;
myocardial wall stress; systolic function; tissue Doppler imaging
ID LEFT-VENTRICULAR RELAXATION; WAVE REFLECTION MAGNITUDE; INTACT CANINE
HEART; LOADING SEQUENCE; DEPENDENT RELAXATION; CARDIAC-MUSCLE; ARTERIAL
LOAD; PRESSURE FALL; DETERMINANTS; VELOCITY
AB Experimental studies implicate late systolic load as a determinant of impaired left-ventricular relaxation. We aimed to assess the relationship between the myocardial loading sequence and left-ventricular contraction and relaxation. Time-resolved central pressure and time-resolved left-ventricular geometry were measured with carotid tonometry and speckle-tracking echocardiography, respectively, for computation of time-resolved ejection-phase myocardial wall stress (EP-MWS) among 1214 middle-aged adults without manifest cardiovascular disease from the general population. Early diastolic annular velocity and systolic annular velocities were measured with tissue Doppler imaging, and segment-averaged longitudinal strain was measured with speckle-tracking echocardiography. After adjustment for age, sex, and potential confounders, late EP-MWS was negatively associated with early diastolic mitral annular velocity (standardized beta=-0.25; P<0.0001) and mitral inflow propagation velocity (standardized beta=-0.13; P=0.02). In contrast, early EP-MWS was positively associated with early diastolic mitral annular velocity (standardized beta=0.18; P<0.0001) and mitral inflow propagation velocity (standardized beta=0.22; P<0.0001). A higher late EP-MWS predicted a lower systolic mitral annular velocity (standardized beta=-0.31; P<0.0001) and lesser myocardial longitudinal strain (standardized beta=0.32; P<0.0001), whereas a higher early EP-MWS was associated with a higher systolic mitral annular velocity (standardized beta=0.16; P=0.002) and greater longitudinal strain (standardized beta=-0.24; P=0.002). The loading sequence remained independently associated with early diastolic mitral annular velocity after adjustment for systolic mitral annular velocity or systolic longitudinal strain. In the context of available experimental data, our findings support the role of the myocardial loading sequence as a determinant of left-ventricular systolic and diastolic function. A loading sequence characterized by prominent late systolic wall stress was associated with lower longitudinal systolic function and diastolic relaxation. (Hypertension. 2013;61:296-303.). circle Online Data Supplement
C1 [Chirinos, Julio A.; Raja, Muhammad W.; Sutton, Martin St. John] Philadelphia VA Med Ctr, Philadelphia, PA USA.
[Chirinos, Julio A.; Raja, Muhammad W.; Sutton, Martin St. John] Univ Penn, Philadelphia, PA 19104 USA.
[Segers, Patrick; Claessens, Tom] Univ Ghent, Inst Biomed Technol, B-9000 Ghent, Belgium.
[Rietzschel, Ernst R.; De Bacquer, Dirk] Univ Ghent, Dept Publ Hlth, B-9000 Ghent, Belgium.
[Rietzschel, Ernst R.; De Buyzere, Marc L.; Gillebert, Thierry C.] Ghent Univ Hosp, Dept Cardiovasc Dis, Ghent, Belgium.
[Claessens, Tom] Univ Coll Ghent, Dept Mech, Ghent, Belgium.
RP Chirinos, JA (reprint author), 3800 Woodland Ave,Rm 8B111, Philadelphia, PA 19104 USA.
EM Julio.chirinos@uphs.upenn.edu
RI Claessens, Tom/B-2737-2009;
OI Claessens, Tom/0000-0002-3182-6820; Gillebert,
Thierry/0000-0002-3832-919X
FU Fonds voor Wetenschappelijk Onderzoek Vlaanderen [G.0.838.10]; Edna G.
Kynett Memorial Foundation; National Institutes of Health; American
Heart Association
FX This study was supported by Fonds voor Wetenschappelijk Onderzoek
Vlaanderen grant G.0.838.10 and Edna G. Kynett Memorial Foundation (Dr
Chirinos).; Dr Chirinos has received significant (>$ 10 000) grants from
the National Institutes of Health and the American Heart Association for
research studies related to arterial hemodynamics and has received minor
support (equipment loans) from Atcor Medical, Cardiodynamics, and APC
cardiovascular.
NR 38
TC 30
Z9 30
U1 2
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0194-911X
J9 HYPERTENSION
JI Hypertension
PD FEB
PY 2013
VL 61
IS 2
BP 296
EP 303
DI 10.1161/HYPERTENSIONAHA.111.00530
PG 8
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 073JU
UT WOS:000313740100026
PM 23283359
ER
PT J
AU Reeves, RM
Ong, FR
Matheny, ME
Denny, JC
Aronsky, D
Gobbel, GT
Montella, D
Speroff, T
Brown, SH
AF Reeves, Ruth M.
Ong, Ferdo R.
Matheny, Michael E.
Denny, Joshua C.
Aronsky, Dominik
Gobbel, Glenn T.
Montella, Diane
Speroff, Theodore
Brown, Steven H.
TI Detecting temporal expressions in medical narratives
SO INTERNATIONAL JOURNAL OF MEDICAL INFORMATICS
LA English
DT Article
DE Event sequence; TimeML; Temporal reasoning; Narration; Natural language
processing
ID DISCHARGE SUMMARIES; CLASSIFICATION; ARCHITECTURE; INFORMATION;
KNOWLEDGE; SYSTEM; TEXT
AB Background: Clinical practice and epidemiological information aggregation require knowing when, how long, and in what sequence medically relevant events occur. The Temporal Awareness and Reasoning Systems for Question Interpretation (TARSQI) Toolkit (TTK) is a complete, open source software package for the temporal ordering of events within narrative text documents. TTK was developed on newspaper articles. We extended TTK to support medical notes using veterans' affairs (VA) clinical notes and compared it to TTK.
Methods: We used a development set consisting of 200 VA clinical notes to modify and append rules to TTK's time tagger, creating Med-TTK. We then evaluated the performances of TTK and Med-TTK on an independent random selection of 100 clinical notes. Evaluation tasks were to identify and classify time-referring expressions as one of four temporal classes (DATE, TIME, DURATION, and SET). The reference standard for this test set was generated by dual human manual review with disagreements resolved by a third reviewer. Outcome measures included recall and precision for each class, and inter-rater agreement scores.
Results: There were 3146 temporal expressions in the reference standard. TTK identified 1595 temporal expressions. Recall was 0.15 (95% confidence interval [CI] 0.12-0.15) and precision was 0.27 (95% CI 0.25-0.29) for TTK. Med-TTK identified 3174 expressions. Recall was 0.86 (95% CI 0.84-0.87) and precision was 0.85 (95% CI 0.84-0.86) for Med-TTK.
Conclusion: The algorithms for identifying and classifying temporal expressions in medical narratives developed within Med-TTK significantly improved performance compared to TTK. Natural language processing applications such as Med-TTK provide a foundation for meaningful longitudinal mapping of patient history events among electronic health records. The tool can be accessed at the following site: http://code.google.com/p/med-ttk/. (c) 2012 Elsevier Ireland Ltd. All rights reserved.
C1 [Reeves, Ruth M.; Matheny, Michael E.; Gobbel, Glenn T.; Speroff, Theodore; Brown, Steven H.] Tennessee Valley Healthcare Syst, Dept Vet Affairs, Geriatr Res Educ & Clin Ctr, Nashville, TN USA.
[Reeves, Ruth M.; Ong, Ferdo R.; Matheny, Michael E.; Denny, Joshua C.; Aronsky, Dominik; Gobbel, Glenn T.; Montella, Diane; Brown, Steven H.] Vanderbilt Univ, Med Ctr, Dept Biomed Informat, Nashville, TN USA.
[Matheny, Michael E.; Speroff, Theodore] Vanderbilt Univ, Sch Med, Dept Med, Div Gen Internal Med, Nashville, TN 37212 USA.
[Matheny, Michael E.; Speroff, Theodore] Vanderbilt Univ, Med Ctr, Dept Biostat, Nashville, TN USA.
[Montella, Diane; Brown, Steven H.] Vet Hlth Adm, Dept Vet Affairs, Off Informat & Analyt, Nashville, TN USA.
RP Reeves, RM (reprint author), US Dept Vet Affairs, Tennessee Valley Healthcare Syst, 1310 24th Ave S, Nashville, TN 37212 USA.
EM ruth.reeves2@va.gov
OI Matheny, Michael/0000-0003-3217-4147
FU VA Medical Informatics Fellowship, Office of Academic Affiliations;
Veterans Health Administration HSR&D Career Development Award
[CDA-08-020]; Veterans Health Consortium for Health Informatics Research
(CHIR) [HIR 09-001, HIR 09-003]; Department of Veterans Affairs,
Veterans Health Administration, Office of Research and Development
FX The research reported here began with the 2009 Medical Informatics
Master's Thesis of Dr. Ferdo Ong who initiated his research with an
interest in adapting TTK for eventual clinical usage. This thesis
entitled "The Tarsqi Toolkit's Recognition of Temporal Expressions
within Medical Documents" is available at
http://etd.library.vanderbilt.edu/available/etd-05242010-101636/. Drs.
Reeves, Montella and Ong were supported by VA Medical Informatics
Fellowship, Office of Academic Affiliations. Dr. Matheny is supported by
the Veterans Health Administration HSR&D Career Development Award
CDA-08-020. Drs. Matheny and Speroff and Gobbel are supported by the
Veterans Health Consortium for Health Informatics Research (CHIR) awards
HIR 09-001 and HIR 09-003.; This material is based upon work supported
by the Department of Veterans Affairs, Veterans Health Administration,
Office of Research and Development with resources and the use of
facilities at the VA Tennessee Valley Healthcare System. The views
expressed in this article are those of the authors and do not
necessarily reflect the position or policy of the Department of Veterans
Affairs or the United States government.
NR 54
TC 12
Z9 12
U1 1
U2 15
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 1386-5056
J9 INT J MED INFORM
JI Int. J. Med. Inform.
PD FEB
PY 2013
VL 82
IS 2
BP 118
EP 127
DI 10.1016/j.ijmedinf.2012.04.006
PG 10
WC Computer Science, Information Systems; Health Care Sciences & Services;
Medical Informatics
SC Computer Science; Health Care Sciences & Services; Medical Informatics
GA 078RJ
UT WOS:000314116700006
PM 22595284
ER
PT J
AU Ohning, GV
AF Ohning, Gordon V.
TI Intestinal Mucins The First Line of Defense
SO JOURNAL OF CLINICAL GASTROENTEROLOGY
LA English
DT Editorial Material
ID INFLAMMATORY-BOWEL-DISEASE; MECHANISMS
C1 Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, W Los Angeles VA Healthcare Ctr, Los Angeles, CA 90073 USA.
RP Ohning, GV (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, W Los Angeles VA Healthcare Ctr, Bld 115,Rm 217,11301 Wilshire Blvd, Los Angeles, CA 90073 USA.
EM gordon.ohning@va.gov
NR 10
TC 0
Z9 0
U1 0
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0192-0790
J9 J CLIN GASTROENTEROL
JI J. Clin. Gastroenterol.
PD FEB
PY 2013
VL 47
IS 2
BP 104
EP 105
DI 10.1097/MCG.0b013e3182713185
PG 2
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 075UP
UT WOS:000313912700005
PM 23314666
ER
PT J
AU Onozato, ML
Hammond, S
Merren, M
Yagi, Y
AF Onozato, Maristela L.
Hammond, Stephen
Merren, Mark
Yagi, Yukako
TI Evaluation of a completely automated tissue-sectioning machine for
paraffin blocks
SO JOURNAL OF CLINICAL PATHOLOGY
LA English
DT Article
AB Tissue-sectioning automation can be a resourceful tool in processing anatomical pathology specimens. The advantages of an automated system compared with traditional manual sectioning are the invariable thickness, uniform orientation and fewer tissue-sectioning artefacts. This short report presents the design of an automated tissue-sectioning device and compares the sectioned specimens with normal manual tissue sectioning performed by an experienced histology technician. The automated system was easy to use, safe and the sectioned material showed acceptable quality with well-preserved morphology and tissue antigenicity. It is expected that the turnaround time will be improved in the near future.
C1 [Onozato, Maristela L.; Yagi, Yukako] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Pathol, Pathol Informat & Commun Technol PICT Lab, Boston, MA 02114 USA.
[Onozato, Maristela L.; Merren, Mark; Yagi, Yukako] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Hammond, Stephen] Boston Univ, Dept Pathol, Boston, MA 02215 USA.
RP Onozato, ML (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, PICT Lab,Dept Pathol, 101 Merrimac St,Suite 820, Boston, MA 02114 USA.
EM likaono@gmail.com
NR 4
TC 3
Z9 3
U1 1
U2 5
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0021-9746
J9 J CLIN PATHOL
JI J. Clin. Pathol.
PD FEB
PY 2013
VL 66
IS 2
BP 151
EP 154
DI 10.1136/jclinpath-2011-200205
PG 4
WC Pathology
SC Pathology
GA 078NM
UT WOS:000314105800011
PM 21900334
ER
PT J
AU Kar, HL
O'Leary, KD
AF Kar, Heidi L.
O'Leary, K. Daniel
TI Patterns of Psychological Aggression, Dominance, and Jealousy within
Marriage
SO JOURNAL OF FAMILY VIOLENCE
LA English
DT Article
DE Emotional abuse; Intimate-partner violence; Partner aggression; Control;
Bilateral aggression
ID RISK YOUNG COUPLES; PHYSICAL AGGRESSION; DOMESTIC VIOLENCE; PARTNER
VIOLENCE; GENDER; CONFLICT; DEPRESSION; FREQUENCY; EMOTIONS; SYMMETRY
AB Few empirical studies with representative samples have focused on the gendered aspect of psychological aggression and its sub-constructs of dominance and jealousy. Those that do report on gender differences, often fail to report on important dyadic factors such as whether the aggression is unilateral or bilateral in nature. Differences in psychological aggression, dominance, and jealousy constructs were assessed in a representative sample of 453 married parents. Overall, women had significantly higher dominance, jealousy, and psychological aggression scores. Both male and female respondents in relationships where there was bi-directional severe psychological aggression demonstrated higher mean levels of severe psychological aggression, dominance, and jealousy than did their counterparts who were unilaterally severely aggressive. This is the first study to demonstrate that bilateral psychological aggression is associated with higher mean levels of psychological aggression, dominance, and jealousy scores for both male and female partners than unilateral aggression. Contrary to our hypothesis, there was no differential impact of severe psychological aggression by gender.
C1 [Kar, Heidi L.] San Francisco VA Med Ctr, Psychol Serv 116B, San Francisco, CA 94121 USA.
[O'Leary, K. Daniel] SUNY Stony Brook, Dept Psychol, Stony Brook, NY 11794 USA.
RP Kar, HL (reprint author), San Francisco VA Med Ctr, Psychol Serv 116B, 4150 Clement St, San Francisco, CA 94121 USA.
EM Heidi.Kar@va.gov
NR 72
TC 2
Z9 2
U1 6
U2 55
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0885-7482
J9 J FAM VIOLENCE
JI J. Fam. Violence
PD FEB
PY 2013
VL 28
IS 2
BP 109
EP 119
DI 10.1007/s10896-012-9492-7
PG 11
WC Psychology, Clinical; Family Studies
SC Psychology; Family Studies
GA 077LL
UT WOS:000314029100001
ER
PT J
AU Jin, BJ
Thiagarajah, JR
Verkman, AS
AF Jin, Byung-Ju
Thiagarajah, Jay R.
Verkman, A. S.
TI Convective washout reduces the antidiarrheal efficacy of enterocyte
surface-targeted antisecretory drugs
SO JOURNAL OF GENERAL PHYSIOLOGY
LA English
DT Article
ID POLYCYSTIC KIDNEY-DISEASE; SMALL INTESTINAL MUCOSA; CFTR INHIBITORS;
FLUID SECRETION; CYSTIC-FIBROSIS; CHOLERA-TOXIN; ENTEROTOXIN;
ABSORPTION; TRANSPORT; DIARRHEA
AB Secretory diarrheas such as cholera are a major cause of morbidity and mortality in developing countries. We previously introduced the concept of antisecretory therapy for diarrhea using chloride channel inhibitors targeting the cystic fibrosis transmembrane conductance regulator channel pore on the extracellular surface of enterocytes. However, a concern with this strategy is that rapid fluid secretion could cause convective drug washout that would limit the efficacy of extracellularly targeted inhibitors. Here, we developed a convection-diffusion model of washout in an anatomically accurate three-dimensional model of human intestine comprising cylindrical crypts and villi secreting fluid into a central lumen. Input parameters included initial lumen flow and inhibitor concentration, inhibitor dissociation constant (K-d), crypt/villus secretion, and inhibitor diffusion. We modeled both membrane-impermeant and permeable inhibitors. The model predicted greatly reduced inhibitor efficacy for high crypt fluid secretion as occurs in cholera. We conclude that the antisecretory efficacy of an orally administered membrane-impermeant, surface-targeted inhibitor requires both (a) high inhibitor affinity (low nanomolar K-d) to obtain sufficiently high luminal inhibitor concentration (>100-fold K-d), and (b) sustained high luminal inhibitor concentration or slow inhibitor dissociation compared with oral administration frequency. Efficacy of a surface-targeted permeable inhibitor delivered from the blood requires high inhibitor permeability and blood concentration (relative to K-d).
C1 [Jin, Byung-Ju; Thiagarajah, Jay R.; Verkman, A. S.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
[Jin, Byung-Ju; Thiagarajah, Jay R.; Verkman, A. S.] Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94143 USA.
[Thiagarajah, Jay R.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA.
RP Verkman, AS (reprint author), Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
EM alan.verkman@ucsf.edu
FU National Institutes of Health [DK72517, EB00415, HL73856, DK35124,
EY13574]
FX This work was supported by National Institutes of Health grants DK72517,
EB00415, HL73856, DK35124, and EY13574.
NR 29
TC 11
Z9 11
U1 0
U2 5
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1295
J9 J GEN PHYSIOL
JI J. Gen. Physiol.
PD FEB
PY 2013
VL 141
IS 2
BP 261
EP 272
DI 10.1085/jgp.201210885
PG 12
WC Physiology
SC Physiology
GA 079HI
UT WOS:000314160800011
PM 23359285
ER
PT J
AU Raskin, KA
Schwab, JH
Mankin, HJ
Springfield, DS
Hornicek, FJ
AF Raskin, Kevin A.
Schwab, Joseph H.
Mankin, Henry J.
Springfield, Dempsey S.
Hornicek, Francis J.
TI Giant Cell Tumor of Bone
SO JOURNAL OF THE AMERICAN ACADEMY OF ORTHOPAEDIC SURGEONS
LA English
DT Review
ID GENE-EXPRESSION; CRYOSURGERY; MANAGEMENT; CURETTAGE; THERAPY; LESIONS
AB Giant cell tumor (GOT) of bone is one type of giant cell-rich lesion of bone. This benign mesenchymal tumor has characteristic multinuclear giant cells. Mononuclear stromal cells are the physiologically active and diagnostic cell type. Most GCTs are located in the epiphyseal regions of long bones. The axial skeleton primarily the sacrum is a secondary site of involvement. Most patients present with pain, swelling, joint effusion, and disability in the third and fourth decades of life. Imaging studies are important for tumor staging and radiographic grading. Typically, these clinically active but slow-growing tumors are confined to bone, with relatively well-defined radiographic borders. Monostotic disease is most common. Metastatic spread to the lungs is rare. Extended intralesional curettage with or without adjuvant therapy is the primary treatment choice. Local recurrence is seen in <= 20% of cases, and a second local intralesional procedure is typically sufficient in cases that are detected early. Medical therapies include diphosphonates and denosumab. Denosumab has been approved for use in osteoporosis as well as breast and prostate cancer metastatic to bone. Medical therapy and radiotherapy can alter the management of GOT of bone, especially in multifocal disease, local recurrences, and bulky central/axial disease.
C1 [Raskin, Kevin A.; Schwab, Joseph H.; Mankin, Henry J.; Springfield, Dempsey S.; Hornicek, Francis J.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Raskin, KA (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.
FU Globus Medical; Stryker
FX Dr. Raskin or an immediate family member serves as an unpaid consultant
to KCI. Dr. Schwab or an immediate family member is a member of a
speakers' bureau or has made paid presentations on behalf of Synthes and
Stryker Spine; serves as a paid consultant to or is an employee of
Biom'Up; has received nonincome support (such as equipment or services),
commercially derived honoraria, or other non-research-related funding
(such as paid travel) from Globus Medical and Stryker; and serves as a
board member, owner, officer, or committee member of Biom'Up. Dr.
Springfield or an immediate family member has stock or stock options
held in Johnson & Johnson and Merck. Dr. Hornicek or an immediate family
member serves as a paid consultant to or is an employee of Stryker,
Stryker Spine, and AO Spine; has received research or institutional
support from Stryker; and serves as a board member, owner, officer, or
committee member of the American Association of Tissue Banks. Neither
Dr. Mankin nor any immediate family member has received anything of
value from or has stock or stock options held in a commercial company or
institution related directly or indirectly to the subject of this
article.
NR 35
TC 43
Z9 46
U1 1
U2 15
PU AMER ACAD ORTHOPAEDIC SURGEONS
PI ROSEMENT
PA 6300 N RIVER ROAD, ROSEMENT, IL 60018-4262 USA
SN 1067-151X
J9 J AM ACAD ORTHOP SUR
JI J. Am. Acad. Orthop. Surg.
PD FEB
PY 2013
VL 21
IS 2
BP 118
EP 126
DI 10.5435/JAAOS-21-02-118
PG 9
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA 079TS
UT WOS:000314195700008
PM 23378375
ER
PT J
AU Sheth, RA
Hesketh, R
Deipolyi, AR
Oklu, R
AF Sheth, Rahul A.
Hesketh, Robin
Deipolyi, Amy R.
Oklu, Rahmi
TI Circulating Tumor Cells: Personalized Medicine in Interventional
Oncology?
SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY
LA English
DT Review
ID METASTATIC BREAST-CANCER; PROSTATE-CANCER; LUNG-CANCER;
COLORECTAL-CANCER; PERIPHERAL-BLOOD; SURVIVAL; EVOLUTION;
ADENOCARCINOMA; PERSPECTIVE; PROGRESSION
AB Innovative technologic advancements have expanded the ability of interventional radiologists to capture and visualize directly tumor cells that have intravasated into the circulation. The detection of these circulating tumor cells (CTCs) is revolutionizing the understanding of the pathogenesis of metastasis and is paving the way for exquisitely sensitive techniques to detect malignancy, monitor recurrence, and prognosticate outcomes. In this review, the prevailing theories on the pathobiology of metastasis and the tools that have been developed to investigate CTCs are summarized. The tremendous impact CTCs are likely to have in oncology is discussed, with particular emphasis on their relevance to interventional oncology.
C1 [Sheth, Rahul A.; Deipolyi, Amy R.; Oklu, Rahmi] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Imaging,Div Vasc Imaging & Intervent, Boston, MA 02114 USA.
[Hesketh, Robin] Univ Cambridge, Dept Biochem, Cambridge CB2 1QW, England.
RP Oklu, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Imaging,Div Vasc Imaging & Intervent, 55 Fruit St,290 Gray Bigelow, Boston, MA 02114 USA.
EM roklu@partners.org
OI Deipolyi, Amy/0000-0003-3144-386X
NR 45
TC 2
Z9 2
U1 0
U2 16
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1051-0443
J9 J VASC INTERV RADIOL
JI J. Vasc. Interv. Radiol.
PD FEB
PY 2013
VL 24
IS 2
BP 221
EP 228
DI 10.1016/j.jvir.2012.10.018
PG 8
WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular
Disease
SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System &
Cardiology
GA 078HC
UT WOS:000314088300011
PM 23265726
ER
PT J
AU Kalva, SP
Pectasides, M
Yeddula, K
Ganguli, S
Blaszkowsky, LS
Zhu, AX
AF Kalva, Sanjeeva P.
Pectasides, Melina
Yeddula, Kalpana
Ganguli, Suvranu
Blaszkowsky, Lawrence S.
Zhu, Andrew X.
TI Factors Affecting Survival following Chemoembolization with
Doxorubicin-eluting Microspheres for Inoperable Hepatocellular Carcinoma
SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY
LA English
DT Article
ID TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION; RANDOMIZED CONTROLLED TRIAL;
PROGNOSTIC-FACTORS; TRANSARTERIAL CHEMOEMBOLIZATION;
MULTIVARIATE-ANALYSIS; LIPIODOL CHEMOEMBOLIZATION; Y-90
RADIOEMBOLIZATION; RISK-FACTORS; PHASE-II; BEADS
AB Purpose: To assess factors associated with better overall survival (OS) and progression-free survival (PFS) following chemoembolization with doxorubicin-eluting microspheres for inoperable hepatocellular carcinoma (HCC)
Materials and Methods: Data of 130 patients (104 men;, median age, 62 y) with inoperable HCC who underwent successful DEB chemoembolization with 100-300 -mu m LC Bead particles loaded with 50 mg doxorubicin per vial were reviewed following human research committee approval. Effects of various clinical, imaging, and response factors on OS and PFS were assessed by univariate Kaplan-Meier survival. analysis. Multiple Cox regression with backward elimination was performed for terms found significant (P <= .05) on univariate analysis.
Results: The number of DEB chemoembolization procedures per patient ranged from one to four (mean, 2 +/- 1). The median PFS and OS were 5.7 months (95% confidence interval, 4.6-7.6 mo) and 14.7 months (95% confidence interval; 12.3-19.7 mo), respectively. On multivariate Cox regression, Canter of the Liver Italian Program (CLIP) store of 1 or lower, necrosis of More than 50%, and response or stable disease per Response Evaluation Criteria hi Solid Tumors after DEB chemoembolization were associated with better PFS. CLIP score of 1 or lower, Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 1 or lower, absence of portal vein (PV) thrombosis, and necrosis greater than 50% following DEB chemoembolization were associated with better OS.
Conclusions: CLIP score of 1 or lower and necrosis of more than 50% are independent variables affecting PPS. and OS after DEB chemoembolization, whereas absence of PV thrombosis,and ECOG PS of 1 or lower affected OS but riot PFS
C1 [Kalva, Sanjeeva P.] Massachusetts Gen Hosp, Ctr Image Guided Canc Therapy, Boston, MA 02114 USA.
Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
RP Kalva, SP (reprint author), Massachusetts Gen Hosp, Ctr Image Guided Canc Therapy, GRB-297,55 Fruit St, Boston, MA 02114 USA.
EM skalva@partners.org
NR 57
TC 5
Z9 5
U1 0
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1051-0443
J9 J VASC INTERV RADIOL
JI J. Vasc. Interv. Radiol.
PD FEB
PY 2013
VL 24
IS 2
BP 257
EP 265
DI 10.1016/j.jvir.2012.10.021
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular
Disease
SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System &
Cardiology
GA 078HC
UT WOS:000314088300016
PM 23369560
ER
PT J
AU Gupta, PK
Ramanan, B
MacTaggart, JN
Sundaram, A
Fang, X
Gupta, H
Johanning, JM
Pipinos, II
AF Gupta, Prateek K.
Ramanan, Bala
MacTaggart, Jason N.
Sundaram, Abhishek
Fang, Xiang
Gupta, Himani
Johanning, Jason M.
Pipinos, Iraklis I.
TI Risk index for predicting perioperative stroke, myocardial infarction,
or death risk in asymptomatic patients undergoing carotid endarterectomy
SO JOURNAL OF VASCULAR SURGERY
LA English
DT Article; Proceedings Paper
CT Annual Meeting of the American-College-of-Surgeons
CY OCT 03, 2012
CL Chicago, IL
SP Amer Coll Surg
ID CARDIAC RISK; ARTERIAL-DISEASE; LOWER-EXTREMITY; BYPASS-SURGERY;
SURGICAL CARE; YOUNG-ADULTS; MORTALITY; VALIDATION; ADJUSTMENT; QUALITY
AB Objective: The latest guidelines recommend performance of carotid endarterectomy (CEA) on asymptomatic patients with high-grade carotid stenosis, only if the combined perioperative stroke, myocardial infarction (MI), or death risk is <= 3%. Our objective was to develop and validate a risk index to estimate the combined risk of perioperative stroke, MI, or death in asymptomatic patients undergoing elective CEA.
Methods: Asymptomatic patients who underwent an elective CEA (n = 17,692) were identified from the 2005-2010 National Surgical Quality Improvement Program, a multicenter, prospective database. Multivariable logistic regression analysis was performed with primary outcome of interest being the composite of any stroke, MI, or death during the 30-day periprocedural period. Bootstrapping was used for internal validation. A risk index was created by assigning weighted points to each predictor using the beta-coefficients from the regression analysis.
Results: Fifty-eight percent of the patients were men with a median age of 72 years. Thirty-day incidences of stroke, MI, and death were 0.9% (n = 167), 0.6% (n = 108), and 0.4% (n = 72), respectively. The combined 30-day stroke, MI, or death incidence was 1.8%(n = 324). On multivariable analysis, six independent predictors were identified and a risk index created by assigning weighted points to each predictor using the b-coefficients from the regression analysis. The predictors included age in years (<60: 0 point; 60-69: -1 point; 70-79: -1 point; >= 80: 2 points), dyspnea (2 points), chronic obstructive pulmonary disease (3 points), previous peripheral revascularization or amputation (3 points), recent angina within 1 month (4 points), and dependent functional status (5 points). Patients were classified as low(<3%), intermediate (3%-6%), or high (>6%) risk for combined 30-day stroke, MI, or death, based on a total point score of <4, 4-7, and >7, respectively. There were 15,249 patients (86.2%) in the low-risk category, 2233 (12.6%) in the intermediate-risk category, and 210 (1.2%) in the high-risk category.
Conclusions: The validated risk index can help identify asymptomatic patients who are at greatest risk for 30-day stroke, MI, and death after CEA, thereby aiding patient selection. (J Vasc Surg 2013; 57: 318-26.)
C1 [Gupta, Prateek K.] Univ Wisconsin Hosp & Clin, Dept Surg, Madison, WI 53792 USA.
[Gupta, Himani] William S Middleton Mem Vet Adm Med Ctr, Dept Med, Madison, WI USA.
[Ramanan, Bala; Sundaram, Abhishek] Creighton Univ, Dept Surg, Omaha, NE 68178 USA.
[MacTaggart, Jason N.; Johanning, Jason M.; Pipinos, Iraklis I.] Univ Nebraska, Med Ctr, Dept Surg, Omaha, NE 68154 USA.
[MacTaggart, Jason N.; Johanning, Jason M.; Pipinos, Iraklis I.] VA Nebraska & Western Iowa Hlth Care Syst, Omaha, NE 68154 USA.
[Fang, Xiang] Creighton Univ, Biostat Core, Omaha, NE 68178 USA.
RP Pipinos, II (reprint author), Univ Nebraska, Med Ctr, Dept Surg, Omaha, NE 68154 USA.
EM ipipinos@unmc.edu
FU NIA NIH HHS [R01 AG034995]
NR 34
TC 19
Z9 20
U1 0
U2 5
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 FEB
PY 2013
VL 57
IS 2
BP 318
EP 326
DI 10.1016/j.jvs.2012.08.116
PG 9
WC Surgery; Peripheral Vascular Disease
SC Surgery; Cardiovascular System & Cardiology
GA 073NX
UT WOS:000313750800003
PM 23159474
ER
PT J
AU Doores, KJ
Huber, M
Le, KM
Wang, SK
Doyle-Cooper, C
Cooper, A
Pantophlet, R
Wong, CH
Nemazee, D
Burton, DR
AF Doores, Katie J.
Huber, Michael
Le, Khoa M.
Wang, Sheng-Kai
Doyle-Cooper, Colleen
Cooper, Anthony
Pantophlet, Ralph
Wong, Chi-Huey
Nemazee, David
Burton, Dennis R.
TI 2G12-Expressing B Cell Lines May Aid in HIV Carbohydrate Vaccine Design
Strategies
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; GERMLINE ANTIBODY RECOGNITION;
NEUTRALIZING ANTIBODIES; GLYCAN SHIELD; 2G12 RECOGNIZES; DOMAIN
EXCHANGE; EPITOPE; POTENT; BROAD; GP120
AB The highly conserved cluster of high-mannose glycans on the HIV-1 envelope glycoprotein, gp120, has been highlighted as a target for neutralizing antibodies. 2G12, the first HIV-1 antiglycan neutralizing antibody described, binds with an unusual domain-exchanged structure that creates a high-affinity multivalent binding surface. It is an interesting challenge for rational vaccine design to generate immunogens capable of eliciting domain-exchanged 2G12-like responses. We recently showed that di-mannose recognition by the variable domains of 2G12 is independent of domain exchange but that exchange is critical for virus neutralization. Carbohydrate-based immunogens aimed at inducing 2G12-like antibodies may need to drive both di-mannose recognition and domain exchange through interactions with B cell receptors. Here we assessed the ability of such immunogens to activate mouse B cell lines displaying domain-exchanged wild-type 2G12 (2G12 WT), a non-domain-exchanged Y-shaped variant (2G12 I19R), and germ line 2G12 (2G12 gl). We show that several immunogens, including heat-killed yeast and bacteria, can activate both 2G12 WT and 2G12 I19R B cells. However, only discrete clusters of high-mannose glycans, as on recombinant forms of the HIV-1 envelope trimer and oligodendrons, activate 2G12 WT B cells. Furthermore, no immunogen tested activated 2G12 gl cells. Our results support the hypothesis that in order to drive domain exchange of an antimannose antibody response, a boost with an immunogen displaying discrete clusters of high-mannose glycans not recognized by conventional Y-shaped antibodies will be required. Additionally, a molecule capable of activating 2G12 gl cells might also be required. The results highlight broadly neutralizing antibody-expressing mouse B cells as potentially useful tools for carbohydrate immunogen screening.
C1 [Doores, Katie J.; Huber, Michael; Le, Khoa M.; Doyle-Cooper, Colleen; Cooper, Anthony; Nemazee, David; Burton, Dennis R.] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.
[Wang, Sheng-Kai; Wong, Chi-Huey] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA.
[Wang, Sheng-Kai; Wong, Chi-Huey] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA.
[Burton, Dennis R.] Scripps Res Inst, IAVI Neutralizing Antibody Ctr, La Jolla, CA 92037 USA.
[Burton, Dennis R.] Scripps Res Inst, Ctr HIV AIDS Vaccine Immunol & Immunogen Design, La Jolla, CA 92037 USA.
[Doores, Katie J.; Huber, Michael; Burton, Dennis R.] MIT, Massachusetts Gen Hosp, Ragon Inst, Boston, MA USA.
[Pantophlet, Ralph] Simon Fraser Univ, Fac Hlth Sci, Burnaby, BC V5A 1S6, Canada.
[Pantophlet, Ralph] Simon Fraser Univ, Dept Mol Biol & Biochem, Burnaby, BC V5A 1S6, Canada.
RP Burton, DR (reprint author), Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.
EM burton@scripps.edu
RI Huber, Michael/B-8509-2015;
OI Doores, Katie/0000-0002-5507-1725
FU International AIDS Vaccine Initiative through the Neutralizing Antibody
Consortium; National Institute of Allergy and Infectious Diseases, NIH
[5R01 AI033292, 5U01 AI078224, AI073148, UM1AI100663]; Ragon Institute
of MGH, MIT, and Harvard
FX This work was funded by the International AIDS Vaccine Initiative
through the Neutralizing Antibody Consortium, the National Institute of
Allergy and Infectious Diseases, NIH (grants 5R01 AI033292, 5U01
AI078224, AI073148, and UM1AI100663), and the Ragon Institute of MGH,
MIT, and Harvard.
NR 40
TC 7
Z9 7
U1 0
U2 24
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 FEB
PY 2013
VL 87
IS 4
BP 2234
EP 2241
DI 10.1128/JVI.02820-12
PG 8
WC Virology
SC Virology
GA 078BB
UT WOS:000314072000029
PM 23221565
ER
PT J
AU Iezzoni, LI
AF Iezzoni, Lisa I.
TI Imperatives for HSR Addressing Individuals With Disabilities-The
Canaries in Health Care's Coal Mine
SO MEDICAL CARE
LA English
DT Editorial Material
C1 Harvard Univ, Sch Med, Dept Med, Mongan Inst Hlth Policy,Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Iezzoni, LI (reprint author), Harvard Univ, Sch Med, Dept Med, Mongan Inst Hlth Policy,Massachusetts Gen Hosp, 50 Staniford St,Room 901B, Boston, MA 02114 USA.
EM liezzoni@partners.org
NR 14
TC 4
Z9 4
U1 1
U2 7
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 FEB
PY 2013
VL 51
IS 2
BP 133
EP 136
DI 10.1097/MLR.0b013e31827da9b9
PG 4
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 078LW
UT WOS:000314101400004
PM 23254696
ER
PT J
AU Sullivan, JL
Shwartz, M
Burgess, JF
Pekoz, EA
Christiansen, CL
Gerena-Melia, M
Berlowitz, D
AF Sullivan, Jennifer L.
Shwartz, Michael
Burgess, James F., Jr.
Pekoez, Erol A.
Christiansen, Cindy L.
Gerena-Melia, Mariana
Berlowitz, Dan
TI Person-centered Care Practices and Quality in Department of Veterans
Affairs Nursing Homes Is There a Relationship?
SO MEDICAL CARE
LA English
DT Article
DE nursing home quality; nursing home culture change; person-centered care
ID CULTURE-CHANGE; OUTCOMES; STAFF
AB Objective: To examine variation in culture change to a person-centered care (PCC) model, and the association between culture change and a composite measure of quality in 107 Department of Veterans Affairs nursing homes.
Methods: We examined the relationship between a composite quality measure calculated from 24 quality indicators (QIs) from the Minimum Data Set (that measure unfavorable events), and PCC summary scores calculated from the 6 domains of the Artifact of Culture Change Tool, using 3 different methods of calculating the summary scores. We also use a Bayesian hierarchical model to analyze the relationship between a latent construct measuring extent of culture change and the composite quality measure.
Results: Using the original Artifacts scores, the highest performing facility has a 2.9 times higher score than the lowest. There is a statistically significant relationship between the composite quality measure and each of the 3 summary Artifacts scores. Depending on whether original scores, standardized scores, or optimal scores are used, a facility at the 10th percentile in terms of culture change compared with one at the 90th percentile has 8.0%, 8.9%, or 10.3% more QI events. When PCC implementation is considered as a latent construct, 18 low performance PCC facilities have, on an average, 16.3% more QI events than 13 high performance facilities.
Conclusions: Our results indicate that culture change to a PCC model is associated with higher Minimum Data Set-based quality. Longitudinal data are needed to better assess whether there is a causal relationship between the extent of culture change and quality.
C1 [Sullivan, Jennifer L.; Shwartz, Michael; Burgess, James F., Jr.; Pekoez, Erol A.] VA Boston Healthcare Syst, COLMR, Boston, MA 02130 USA.
[Sullivan, Jennifer L.; Burgess, James F., Jr.; Christiansen, Cindy L.; Berlowitz, Dan] Boston Univ, Sch Publ Hlth, Boston, MA USA.
[Shwartz, Michael; Pekoez, Erol A.] Boston Univ, Sch Management, Boston, MA 02215 USA.
[Gerena-Melia, Mariana] Univ Massachusetts, Amherst, MA 01003 USA.
[Berlowitz, Dan] CHQOER Edith Nourse Rogers Mem VAMC, Bedford, MA USA.
RP Sullivan, JL (reprint author), VA Boston Healthcare Syst, COLMR, 150 S Huntington Ave,152M, Boston, MA 02130 USA.
EM jennifer.sullivan@va.gov
OI Burgess, James/0000-0002-6646-7071; Christiansen,
Cindy/0000-0001-9951-480X; Sullivan, Jennifer/0000-0003-2906-2232
FU Veterans Health Administration HSRD [IIR-06-260]
FX Funded by Veterans Health Administration HSR&D grant IIR-06-260.
NR 35
TC 9
Z9 9
U1 3
U2 8
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 FEB
PY 2013
VL 51
IS 2
BP 165
EP 171
DI 10.1097/MLR.0b013e3182763230
PG 7
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 078LW
UT WOS:000314101400009
PM 23132200
ER
PT J
AU Epstein, AJ
Busch, SH
Busch, AB
Asch, DA
Barry, CL
AF Epstein, Andrew J.
Busch, Susan H.
Busch, Alisa B.
Asch, David A.
Barry, Colleen L.
TI Does Exposure to Conflict of Interest Policies in Psychiatry Residency
Affect Antidepressant Prescribing?
SO MEDICAL CARE
LA English
DT Article
DE drug utilization; pharmaceutical policy; physician practice patterns;
psychiatry
ID ACADEMIC MEDICAL-CENTERS; PHARMACEUTICAL REPRESENTATIVES;
NATIONAL-SURVEY; PRESCRIPTION DRUGS; PHYSICIANS; INDUSTRY; ATTITUDES;
BEHAVIOR; INFORMATION
AB Background: Academic medical institutions have instituted conflict of interest (COI) policies in response to concerns about pharmaceutical industry influence.
Objective: To determine whether exposure to COI policies during psychiatry residency training affects psychiatrists' antidepressant prescribing patterns after graduation.
Research Design: We used 2009 physician-level national administrative prescribing data from IMS Health for 1652 psychiatrists from 162 residency programs. We used difference-in-differences estimation to compare antidepressant prescribing based on graduation before (2001) or after (2008) COI policy adoption across residency program groups with maximally, moderately, and minimally restrictive COI policies. The primary outcomes were shares of psychiatrists' prescribing of heavily promoted, brand reformulated, and brand antidepressants.
Results: Rates of prescribing heavily promoted, brand reformulated, and brand antidepressants in 2009 were lower among post-COI graduates than pre-COI graduates at all levels of COI restrictiveness. However, differences between pre-COI and post-COI graduates' prescribing of heavily promoted medications were larger for maximally restrictive programs than both minimally restrictive programs [- 4.3 percentage points; 95% confidence interval (CI), - 7.0, - 1.6] and moderately restrictive programs (- 3.6 percentage points; 95% CI, - 6.2, - 1.1). The difference in prescribing reformulations was larger for maximally restrictive programs than minimally restrictive programs (- 3.0 percentage points; 95% CI, - 5.3, - 0.7). Results were consistent for prescribing of brand drugs.
Conclusions: This study provides the first empirical evidence of the effects of COI policies. Our results suggest that COI policies can help inoculate physicians against persuasive aspects of pharmaceutical promotion. Further research should assess whether these policies affect other drug classes and physician specialties similarly.
C1 [Epstein, Andrew J.; Asch, David A.] Univ Penn, Dept Vet Affairs, Ctr Hlth Equ Res & Promot, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA.
[Epstein, Andrew J.; Asch, David A.] Univ Penn, Dept Med, Div Gen Internal Med, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Epstein, Andrew J.; Asch, David A.; Barry, Colleen L.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA.
[Busch, Susan H.] Yale Univ, Sch Publ Hlth, Dept Hlth Policy & Adm, New Haven, CT USA.
[Busch, Alisa B.] McLean Hosp, Belmont, MA 02178 USA.
[Busch, Alisa B.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
[Barry, Colleen L.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD USA.
RP Epstein, AJ (reprint author), Univ Penn, Dept Med, Div Gen Internal Med, Perelman Sch Med, 423 Guardian Dr, Philadelphia, PA 19104 USA.
EM eandrew@mail.med.upenn.edu
OI Asch, David/0000-0002-7970-286X
NR 32
TC 23
Z9 23
U1 0
U2 6
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 FEB
PY 2013
VL 51
IS 2
BP 199
EP 203
DI 10.1097/MLR.0b013e318277eb19
PG 5
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 078LW
UT WOS:000314101400014
PM 23142772
ER
PT J
AU Catalano, PJ
Ayanian, JZ
Weeks, JC
Kahn, KL
Landrum, MB
Zaslavsky, AM
Lee, J
Pendergast, J
Harrington, DP
AF Catalano, Paul J.
Ayanian, John Z.
Weeks, Jane C.
Kahn, Katherine L.
Landrum, Mary Beth
Zaslavsky, Alan M.
Lee, Jeannette
Pendergast, Jane
Harrington, David P.
CA Canc Care Outcomes Res Surveillanc
TI Representativeness of Participants in the Cancer Care Outcomes Research
and Surveillance Consortium Relative to the Surveillance, Epidemiology,
and End Results Program
SO MEDICAL CARE
LA English
DT Article
DE lung cancer; colorectal cancer; cancer populations
ID POPULATION; GENERALIZABILITY
AB Background: The research goals of the Cancer Care Outcomes Research and Surveillance (CanCORS) Consortium are to determine how characteristics and beliefs of patients, providers, and health care organizations influence the treatments and outcomes of individuals with newly diagnosed lung and colorectal cancers. As CanCORS results will inform national policy, it is important to know how they generalize to the United States population with these cancers.
Research Design: This study assessed the representativeness of the CanCORS cohort of 10,547 patients with lung cancer (LC) or colorectal cancer (CRC) enrolled between 2003 and 2005. We compared characteristics (sex, race, age, and disease stage) with the Surveillance, Epidemiology, and End Results (SEER) population of 234,464 patients with new onset of these cancers during the CanCORS recruitment period.
Results: The CanCORS sample is well matched to the SEER Program for both cancers. In CanCORS, 41% LC/47% CRC were female versus 47% LC/49% CRC in SEER. African American, Hispanic, and Asian cases differed by no more than 5 percentage points between CanCORS and SEER. The SEER population is slightly older, with the percentage of patients older than 75 years 33.1% LC/37.3% CRC in SEER versus 26.9% LC/29.4% in CanCORS, and also has a slightly higher proportion of early stage patients. We also found that the CanCORS cohort was representative within specific SEER regions that map closely to CanCORS sites.
Conclusions: This study demonstrates that the CanCORS Consortium was successful in enrolling a demographically representative sample within the CanCORS regions.
C1 [Catalano, Paul J.; Harrington, David P.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA.
[Catalano, Paul J.; Harrington, David P.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Ayanian, John Z.; Landrum, Mary Beth; Zaslavsky, Alan M.] Harvard Univ, Sch Publ Hlth, Dept Hlth Care Policy, Boston, MA 02115 USA.
[Ayanian, John Z.] Womens Hosp Med Ctr, Div Gen Med, Boston, MA USA.
[Weeks, Jane C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Kahn, Katherine L.] RAND Corp, Santa Monica, CA USA.
[Kahn, Katherine L.] Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90095 USA.
[Lee, Jeannette] Univ Arkansas Med Sci, Dept Biostat, Little Rock, AR 72205 USA.
[Pendergast, Jane] Univ Iowa, Coll Publ Hlth, Dept Biostat, Iowa City, IA USA.
RP Catalano, PJ (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, 450 Brookline Ave, Boston, MA 02215 USA.
EM pcata@jimmy.harvard.edu
FU National Cancer Institute (NCI) [U01 CA093344]; Primary Data Collection
and Research Centers at the Harvard Medical School and Northern
California Cancer Center [U01 CA093324]; Dana-Farber Cancer Institute
and Cancer Research Network [U01 CA093332]; RAND and University of
California, Los Angeles [U01 CA093348]; University of Alabama at
Birmingham [U01 CA093329]; University of Iowa [U01 CA093339]; University
of North Carolina [U01 CA093326]; Department of Veteran's Affairs [U01
CDA093344 (MOU), HARQ 03-438MO-03]
FX The Cancer Care Outcomes Research and Surveillance (CanCORS) Consortium
was supported by grants from the National Cancer Institute (NCI) to the
Statistical Coordinating Center at the Dana-Farber Cancer Institute (U01
CA093344) and the Primary Data Collection and Research Centers at the
Harvard Medical School and Northern California Cancer Center (U01
CA093324); Dana-Farber Cancer Institute and Cancer Research Network (U01
CA093332); RAND and University of California, Los Angeles (U01
CA093348); University of Alabama at Birmingham (U01 CA093329);
University of Iowa (U01 CA093339); University of North Carolina (U01
CA093326); and by a Department of Veteran's Affairs grant to the Durham
VA Medical Center (U01 CDA093344 (MOU) and HARQ 03-438MO-03).
NR 9
TC 45
Z9 45
U1 0
U2 7
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 FEB
PY 2013
VL 51
IS 2
BP E9
EP E15
DI 10.1097/MLR.0b013e318222a711
PG 7
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 078LW
UT WOS:000314101400001
PM 22406968
ER
PT J
AU Dusseault-Belanger, F
Cohen, AA
Hivert, MF
Courteau, J
Vanasse, A
AF Dusseault-Belanger, Francis
Cohen, Alan A.
Hivert, Marie-France
Courteau, Josiane
Vanasse, Alain
TI Validating Metabolic Syndrome Through Principal Component Analysis in a
Medically Diverse, Realistic Cohort
SO METABOLIC SYNDROME AND RELATED DISORDERS
LA English
DT Article
ID INSULIN-RESISTANCE SYNDROME; CARDIOVASCULAR-DISEASE;
MYOCARDIAL-INFARCTION; DIABETES-MELLITUS; SYNDROME-X; RISK; ADULTS;
WOMEN
AB Background: The concept of metabolic syndrome has been subject to etiological and clinical controversies in recent years. Associations among the five risk factors (obesity, hypertension, hyperglycemia, high triglyceride levels, and low high-density lipoprotein cholesterol) may help establish the validity of the concept, especially in a cohort representative of an actual population.
Methods: We used principal component analysis (PCA) to analyze the structure of the physiological components of metabolic syndrome in 7213 patients contained in an administrative database for the Centre Hospitalier Universitaire de Sherbrooke in Sherbrooke, Quebec, a realistic cohort with diverse medical histories. We validated the results by repeating the analysis on stratified and random subgroups of patients, and on different combinations of risk factors. The first axis of the PCA was used to predict coronary heart disease (CHD) and diabetes.
Results: The two first axes explained 53% of the variance. The first axis (33%) was associated in the expected direction with all five predictor variables, consistent with its interpretation as metabolic syndrome. The first axis was more predictive of subsequent CHD and diabetes than the formal definition of metabolic syndrome.
Conclusions: These results suggest that the concept of metabolic syndrome accurately captures an existing underlying physiological process. A continuous indicator could be constructed to identify metabolic syndrome more accurately, thus improving risk assessment for CHD and diabetes mellitus. Metabolic syndrome can be measured well even without all five predictors. However, discrepancies with other studies suggest that our results may not be generalizable, perhaps because our cohort tends to be sicker.
C1 [Dusseault-Belanger, Francis] Univ Sherbrooke, Dept Math, Sherbrooke, PQ J1K 2R1, Canada.
[Dusseault-Belanger, Francis; Cohen, Alan A.; Hivert, Marie-France; Courteau, Josiane; Vanasse, Alain] Univ Sherbrooke, Ctr Rech Clin Etienne Lebel Ctr Hosp, Sherbrooke, PQ J1K 2R1, Canada.
[Cohen, Alan A.; Vanasse, Alain] Univ Sherbrooke, Dept Med Famille, Sherbrooke, PQ J1K 2R1, Canada.
[Cohen, Alan A.] Inst Univ Geriatrie Sherbrooke, Ctr Rech Vieillissement, Ctr Sante & Serv Sociaux, Sherbrooke, PQ, Canada.
[Hivert, Marie-France] Univ Sherbrooke, Dept Med, Sherbrooke, PQ J1K 2R1, Canada.
[Hivert, Marie-France] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Cohen, AA (reprint author), Grp Rech PRIMUS, 3001,12E Ave Nord, Sherbrooke, PQ J1H 5N4, Canada.
EM alan.cohen@usherbrooke.ca
FU Fonds de Recherche en Sante du Quebec (FRSQ); Canadian Diabetes
Association
FX The Centre de Recherche Clinique Etienne-LeBel and the Centre de
Recherche sur le Vieillissement are two clinical research centers
supported by the Fonds de Recherche en Sante du Quebec (FRSQ).
Marie-France Hivert is supported by an FRSQ Scholar Award (junior 1
level) and a Canadian Diabetes Association Clinical Scientist award.
Alain Vanasse receives a career award form the FRSQ as a senior
clinician scholar.
NR 26
TC 3
Z9 3
U1 0
U2 6
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1540-4196
J9 METAB SYNDR RELAT D
JI Metab. Syndr. Relat. Disord.
PD FEB
PY 2013
VL 11
IS 1
BP 21
EP 28
DI 10.1089/met.2012.0094
PG 8
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 076OF
UT WOS:000313965200005
PM 22978288
ER
PT J
AU Stanley, T
Bredella, MA
Pierce, L
Misra, M
AF Stanley, Takara
Bredella, Miriam A.
Pierce, Lisa
Misra, Madhusmita
TI The Ratio of Parathyroid Hormone to Vitamin D Is a Determinant of
Cardiovascular Risk and Insulin Sensitivity in Adolescent Girls
SO METABOLIC SYNDROME AND RELATED DISORDERS
LA English
DT Article
ID 25-HYDROXYVITAMIN D CONCENTRATIONS; CYTOKINE-INDUCED APOPTOSIS; 1,25
DIHYDROXYVITAMIN D-3; METABOLIC SYNDROME; MORBIDLY OBESE;
GROWTH-HORMONE; D DEFICIENCY; RESISTANCE; WOMEN; ADIPOSITY
AB Background: Vitamin D insufficiency and higher testosterone are common in obese girls and may adversely affect glucose homeostasis and cardiovascular risk. Data are conflicting regarding the impact of parathyroid hormone (PTH) on these factors. Our objective was to determine associations of 25-hydroxyvitamin D (25-OHD), PTH, and testosterone with measures of glucose homeostasis and cardiovascular risk in adolescent girls after controlling for regional adiposity, with the hypothesis that lower 25-OHD, a higher PTH or PTH/25-OHD ratio, and higher testosterone would be associated with lower insulin sensitivity and greater cardiovascular risk.
Methods: A total of 15 obese girls and 15 matched normal weight controls (12-18 years) underwent fasting measurements of 25-OHD, PTH, testosterone, sex hormone-binding globulin (SHBG), high-sensitivity C-reactive protein (hsCRP), oral glucose tolerance testing, and quantification of visceral (VAT) and subcutaneous (SAT) fat by magnetic resonance imaging (MRI).
Results: There were no associations of 25-OHD with measures of glucose homeostasis or hsCRP. In contrast, PTH and PTH/25-OHD were associated negatively with homeostasis model assessment of insulin resistance (HOMA-IR) and positively with quantitative insulin sensitivity check index (QUICKI) in obese girls but not controls. These associations remained significant after controlling for body mass index standard deviation score (BMI-SDS), but not for VAT. On regression modeling, PTH/25-OHD was positively associated with hsCRP after controlling for BMI-SDS or VAT. Free testosterone positively predicted the corrected insulin response.
Conclusions: In obese girls, PTH/25-OHD is positively associated with measures of insulin sensitivity and hsCRP. Further studies are needed to investigate the relationship between PTH and glucose homeostasis in obesity.
C1 [Stanley, Takara; Pierce, Lisa; Misra, Madhusmita] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA.
[Stanley, Takara; Misra, Madhusmita] Massachusetts Gen Hosp, Pediat Endocrine Unit, Boston, MA 02114 USA.
[Bredella, Miriam A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Misra, M (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, BUL 457, Boston, MA 02114 USA.
EM mmisra@partners.org
FU National Institutes of Health [5P30DK4620-15, 1 UL1 RR025758]
FX This study was supported in part by grants National Institutes of Health
grants 5P30DK4620-15 and 1 UL1 RR025758.
NR 40
TC 8
Z9 8
U1 0
U2 8
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1540-4196
EI 1557-8518
J9 METAB SYNDR RELAT D
JI Metab. Syndr. Relat. Disord.
PD FEB
PY 2013
VL 11
IS 1
BP 56
EP 62
DI 10.1089/met.2012.0102
PG 7
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 076OF
UT WOS:000313965200010
PM 23130887
ER
PT J
AU Gesty-Palmer, D
Yuan, L
Martin, B
Wood, WH
Lee, MH
Janech, MG
Tsoi, LC
Zheng, WJ
Luttrell, LM
Maudsley, S
AF Gesty-Palmer, Diane
Yuan, Ling
Martin, Bronwen
Wood, William H., III
Lee, Mi-Hye
Janech, Michael G.
Tsoi, Lam C.
Zheng, W. Jim
Luttrell, Louis M.
Maudsley, Stuart
TI beta-Arrestin-Selective G Protein-Coupled Receptor Agonists Engender
Unique Biological Efficacy in Vivo
SO MOLECULAR ENDOCRINOLOGY
LA English
DT Article
ID PARATHYROID-HORMONE PTH; SIGNALING PATHWAYS; BONE-FORMATION; ACTIVATION;
BETA-ARRESTIN-2; MICE; KINASE; CELLS; BINDING; CANCER
AB Biased G protein-coupled receptor agonists are orthosteric ligands that possess pathway-selective efficacy, activating or inhibiting only a subset of the signaling repertoire of their cognate receptors. In vitro, D-Trp(12), Tyr(34)-bPTH(7-34) [bPTH(7-34)], a biased agonist for the type 1 PTH receptor, antagonizes receptor-G protein coupling but activates arrestin-dependent signaling. In vivo, both bPTH(7-34) and the conventional agonist hPTH(1-34) stimulate anabolic bone formation. To understand how two PTH receptor ligands with markedly different in vitro efficacy could elicit similar in vivo responses, we analyzed transcriptional profiles from calvarial bone of mice treated for 8 wk with vehicle, bPTH(7-34) or hPTH(1-34). Treatment of wild-type mice with bPTH(7-34) primarily affected pathways that promote expansion of the osteoblast pool, notably cell cycle regulation, cell survival, and migration. These responses were absent in beta-arrestin2-null mice, identifying them as downstream targets of beta-arrestin2-mediated signaling. In contrast, hPTH(1-34) primarily affected pathways classically associated with enhanced bone formation, including collagen synthesis and matrix mineralization. hPTH(1-34) actions were less dependent on beta-arrestin2, as might be expected of a ligand capable of G protein activation. In vitro, bPTH(7-34) slowed the rate of preosteoblast proliferation, enhanced osteoblast survival when exposed to an apoptotic stimulus, and stimulated cell migration in wild-type, but not beta-arrestin2-null, calvarial osteoblasts. These results suggest that bPTH(7-34) and hPTH(1-34) affect bone mass in vivo through predominantly separate genomic mechanisms created by largely distinct receptor-signaling networks and demonstrate that functional selectivity can be exploited to change the quality of G protein-coupled receptor efficacy. (Molecular Endocrinology 27: 296-314, 2013)
C1 [Gesty-Palmer, Diane; Yuan, Ling] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.
[Martin, Bronwen; Maudsley, Stuart] NIA, NIH, Receptor Pharmacol Unit, Baltimore, MD 21224 USA.
[Wood, William H., III] NIA, NIH, Gene Express & Genom Unit, Baltimore, MD 21224 USA.
[Luttrell, Louis M.] Med Univ S Carolina, Dept Med, Div Endocrinol Diabet & Med Genet, Charleston, SC 29425 USA.
[Tsoi, Lam C.; Zheng, W. Jim; Luttrell, Louis M.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA.
[Janech, Michael G.; Luttrell, Louis M.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA.
RP Luttrell, LM (reprint author), Med Univ S Carolina, Dept Med, Div Endocrinol Diabet & Med Genet, 96 Jonathan Lucas St,Suite 816 CSB,MSC 624, Charleston, SC 29425 USA.
EM luttrell@musc.edu
OI Janech, Michael/0000-0002-3202-4811
FU National Institutes of Health [DK64353, DK55524, HD043446]; Arthritis
Foundation; Research Services of the Charleston, South Carolina;
Research Services of the Charleston, Durham; North Carolina Veterans
Affairs Medical Centers; Neph-cure Young Investigator; Department of
Veterans Affairs Career Development Awards; National Institute on Aging
Intramural Research Program of the NIH
FX This work was supported by National Institutes of Health Grants DK64353
(to L.M.L./D.G.-P.), DK55524 (to L.M.L.), HD043446 (to D.G.-P.), the
Arthritis Foundation (to D.G.-P.), and the Research Services of the
Charleston, South Carolina and Durham, North Carolina Veterans Affairs
Medical Centers (to L.M.L., M.G.J., and D.G.-P.). M.G.J. was supported
by Neph-cure Young Investigator and Department of Veterans Affairs
Career Development Awards. This work was supported in part by the
National Institute on Aging Intramural Research Program of the NIH (to
S.M., B.M., and W.W.).
NR 68
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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 FEB
PY 2013
VL 27
IS 2
BP 296
EP 314
DI 10.1210/me.2012-1091
PG 19
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 078RK
UT WOS:000314116900010
PM 23315939
ER
PT J
AU Saha, D
Takahashi, K
de Prost, N
Winkler, T
Pinilla-Vera, M
Baron, RM
Melo, MFV
AF Saha, Dalia
Takahashi, Kazue
de Prost, Nicolas
Winkler, Tilo
Pinilla-Vera, Miguel
Baron, Rebecca M.
Melo, Marcos F. Vidal
TI Micro-Autoradiographic Assessment of Cell Types Contributing to
2-Deoxy-2-[F-18]Fluoro-d-Glucose Uptake During Ventilator-Induced and
Endotoxemic Lung Injury
SO MOLECULAR IMAGING AND BIOLOGY
LA English
DT Article
DE Micro-autoradiography; 2-Deoxy-2-[F-18]fluoro-D-glucose; Positron
emission tomography; Ventilator-induced lung injury; Acute lung injury;
Endotoxin lung injury; Neutrophil; Macrophage; Type 2 epithelial cell;
Lung
ID RESPIRATORY-DISTRESS-SYNDROME; POSITRON-EMISSION-TOMOGRAPHY; IN-VIVO
MEASUREMENT; MECHANICAL VENTILATION; METABOLIC-ACTIVITY; CYTOKINE
RELEASE; EPITHELIAL-CELLS; P-SELECTIN; FDG-PET; INFLAMMATION
AB The aim of the study was to use micro-autoradiography to investigate the lung cell types responsible for 2-deoxy-2-[F-18]fluoro-d-glucose (FDG) uptake in murine models of acute lung injury (ALI).
C57/BL6 mice were studied in three groups: controls, ventilator-induced lung injury (VILI), and endotoxin. VILI was produced by high tidal volumes and zero end-expiratory pressure and endotoxin ALI, by intranasal administration. Following FDG injection, the lungs were processed and exposed to autoradiographic emulsion. Grain density over cells was used to quantify FDG uptake.
Neutrophils, macrophages, and type 2 epithelial cells presented higher grain densities during VILI and endotoxin ALI than controls. Remarkably, cell grain density in specific cell types was dependent on the injury mechanism. Whereas macrophages showed high grain densities during endotoxin ALI, similar to those exhibited by neutrophils, type 2 epithelial cells demonstrated the second highest grain density (with neutrophils as the highest) during VILI.
In murine models of VILI and endotoxin ALI, FDG uptake occurs not only in neutrophils but also in macrophages and type 2 epithelial cells. FDG uptake by individual cell types depends on the mechanism underlying ALI.
C1 [Saha, Dalia; de Prost, Nicolas; Winkler, Tilo; Melo, Marcos F. Vidal] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
[Takahashi, Kazue] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Dev Immunol,Dept Pediat, Boston, MA 02114 USA.
[Pinilla-Vera, Miguel; Baron, Rebecca M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med Pulm & Crit Care, Boston, MA 02114 USA.
RP Melo, MFV (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA.
EM mvidalmelo@partners.org
RI Winkler, Tilo/B-5337-2009;
OI Winkler, Tilo/0000-0002-7276-5550; de Prost, Nicolas/0000-0002-4833-4320
FU National Heart, Lung, and Blood Institute/National Institutes of Health
[HL 5R01HL086827]
FX This work was partially supported by the National Heart, Lung, and Blood
Institute/National Institutes of Health grant HL 5R01HL086827. We would
like to express our profound gratitude to Dr. Rosemary Jones and Diane
E. Capen for the guidance and criticism on the experiments and
manuscript. We would also like to thank Dr. Mauro Tucci for performance
of pilot studies, Steve Weise for the technical aspects in manipulation
of FDG samples, and Teri Bowman for assistance with methodology for
immunohistochemistry.
NR 35
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U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1536-1632
J9 MOL IMAGING BIOL
JI Mol. Imaging. Biol.
PD FEB
PY 2013
VL 15
IS 1
BP 19
EP 27
DI 10.1007/s11307-012-0575-x
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 077MY
UT WOS:000314033000004
PM 22752654
ER
PT J
AU Fu, MY
Brewer, S
Olafsen, T
Wu, AM
Gordon, LK
Said, J
Braun, J
Wadehra, M
AF Fu, Maoyong
Brewer, Sarah
Olafsen, Tove
Wu, Anna M.
Gordon, Lynn K.
Said, Jonathan
Braun, Jonathan
Wadehra, Madhuri
TI Positron Emission Tomography Imaging of Endometrial Cancer Using
Engineered Anti-EMP2 Antibody Fragments
SO MOLECULAR IMAGING AND BIOLOGY
LA English
DT Article
DE Epithelial membrane protein-2; Endometrial cancer; PET imaging;
Minibody; Copper-64
ID EPITHELIAL MEMBRANE PROTEIN-2; IN-VIVO; SURFACE EXPRESSION; EMP2;
COMPLEXES; PET; ANTIGEN; TUMORIGENICITY; XENOGRAFTS; PROSTATE
AB As imaging of the cell surface tetraspan protein epithelial membrane protein-2 (EMP2) expression in malignant tumors may provide important prognostic and predictive diagnostic information, the goal of this study is to determine if antibody fragments to EMP2 may be useful for imaging EMP2 positive tumors.
The normal tissue distribution of EMP2 protein expression was evaluated by immunohistochemistry and found to be discretely expressed in both mouse and human tissues. To detect EMP2 in tumors, a recombinant human anti-EMP2 minibody (scFv-hinge-C(H)3 dimer; 80 kDa) was designed to recognize a common epitope in mice and humans and characterized. In human tumor cell lines, the antibody binding induced EMP2 internalization and degradation, prompting the need for a residualizing imaging strategy. Following conjugation to DOTA (1,4,7,10-tetraazacyclododecane-N,N',N',N'aEuro(3)-tetraacetic acid), the minibody was radiolabeled with Cu-64 (t (1/2) = 12.7 h) and evaluated in mice as a positron emission tomography (PET) imaging agent for human EMP2-expressing endometrial tumor xenografts.
The residualizing agent, Cu-64-DOTA anti-EMP2 minibody, achieved high uptake in endometrial cancer xenografts overexpressing EMP2 (10.2 +/- 2.6, percent injected dose per gram (%ID/g) +/- SD) with moderate uptake in wild-type HEC1A tumors (6.0 +/- 0.1). In both cases, precise tumor delineation was observed from the PET images. In contrast, low uptake was observed with anti-EMP2 minibodies in EMP2-negative tumors (1.9 +/- 0.5).
This new immune-PET agent may be useful for preclinical assessment of anti-EMP2 targeting in vivo. It may also have value for imaging of tumor localization and therapeutic response in patients with EMP2-positive malignancies.
C1 [Fu, Maoyong; Brewer, Sarah; Said, Jonathan; Braun, Jonathan; Wadehra, Madhuri] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA.
[Olafsen, Tove; Wu, Anna M.; Braun, Jonathan] Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA.
[Wu, Anna M.; Said, Jonathan; Braun, Jonathan; Wadehra, Madhuri] Univ Calif Los Angeles, David Geffen Sch Med, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA.
[Gordon, Lynn K.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Ophthalmol, Jules Stein Eye Inst, Los Angeles, CA 90095 USA.
[Gordon, Lynn K.] Greater Los Angeles Vet Affairs Healthcare Syst, Dept Surg, Los Angeles, CA 90099 USA.
RP Wadehra, M (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA.
EM mwadehra@mednet.ucla.edu
FU NIH [HD48540, R21 CA131756, CA016042, R24 CA86307]
FX This work was supported by NIH grants HD48540 (J. Braun), R21 CA131756
(M. Wadehra), CA016042 (University of California at Los Angeles Jonsson
Comprehensive Cancer Center flow cytometry core), and R24 CA86307
(Production of 64Cu at Washington University School of
Medicine). A.M.W., J.S., J.B., and M.W. are members of the Jonsson
Comprehensive Cancer Center. We are especially grateful to Dr. David Ho
and Arye Lipman in ImaginAb, Inc. for the assistance with minibody KS83
construction and Dr. David Stout and Waldemar Ladno at the Crump
Institute for Molecular Imaging at UCLA (U24 CA092865) for the
assistance with the small animal PET/CT scans.
NR 43
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U1 0
U2 10
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1536-1632
J9 MOL IMAGING BIOL
JI Mol. Imaging. Biol.
PD FEB
PY 2013
VL 15
IS 1
BP 68
EP 78
DI 10.1007/s11307-012-0558-y
PG 11
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 077MY
UT WOS:000314033000009
PM 22585360
ER
PT J
AU Lee, MN
Roy, M
Ong, SE
Mertins, P
Villani, AC
Li, WB
Dotiwala, F
Sen, J
Doench, JG
Orzalli, MH
Kramnik, I
Knipe, DM
Lieberman, J
Carr, SA
Hacohen, N
AF Lee, Mark N.
Roy, Matthew
Ong, Shao-En
Mertins, Philipp
Villani, Alexandra-Chloe
Li, Weibo
Dotiwala, Farokh
Sen, Jayita
Doench, John G.
Orzalli, Megan H.
Kramnik, Igor
Knipe, David M.
Lieberman, Judy
Carr, Steven A.
Hacohen, Nir
TI Identification of regulators of the innate immune response to cytosolic
DNA and retroviral infection by an integrative approach
SO NATURE IMMUNOLOGY
LA English
DT Article
ID AICARDI-GOUTIERES-SYNDROME; EXONUCLEASE TREX1; NUCLEIC-ACID; RIG-I;
AUTOIMMUNE-DISEASE; INTRACELLULAR DNA; CELL-DEATH; MUTATIONS; PROTEINS;
PATHWAY
AB The innate immune system senses viral DNA that enters mammalian cells, or in aberrant situations self-DNA, and triggers type I interferon production. Here we present an integrative approach that combines quantitative proteomics, genomics and small molecule perturbations to identify genes involved in this pathway. We silenced 809 candidate genes, measured the response to dsDNA and connected resulting hits with the known signaling network. We identified ABCF1 as a critical protein that associates with dsDNA and the DNA-sensing components HMGB2 and IFI204. We also found that CDC37 regulates the stability of the signaling molecule TBK1 and that chemical inhibition of the CDC37-HSP90 interaction and several other pathway regulators potently modulates the innate immune response to DNA and retroviral infection.
C1 [Lee, Mark N.; Roy, Matthew; Ong, Shao-En; Mertins, Philipp; Villani, Alexandra-Chloe; Li, Weibo; Doench, John G.; Carr, Steven A.; Hacohen, Nir] Broad Inst MIT & Harvard, Cambridge, MA USA.
[Lee, Mark N.; Roy, Matthew; Li, Weibo; Hacohen, Nir] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA USA.
[Lee, Mark N.; Roy, Matthew; Hacohen, Nir] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Dotiwala, Farokh; Lieberman, Judy] Childrens Hosp, Immune Dis Inst, Boston, MA 02115 USA.
[Dotiwala, Farokh; Lieberman, Judy] Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA.
[Dotiwala, Farokh; Lieberman, Judy] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
[Sen, Jayita; Orzalli, Megan H.; Knipe, David M.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA.
[Kramnik, Igor] Boston Univ, Sch Med, Dept Med, Natl Emerging Infect Dis Lab,Pulm Ctr, Boston, MA 02118 USA.
RP Hacohen, N (reprint author), Broad Inst MIT & Harvard, Cambridge, MA USA.
EM nhacohen@partners.org
RI Lieberman, Judy/A-2717-2015;
OI Kramnik, Igor/0000-0001-6511-9246; Doench, John/0000-0002-3707-9889
FU US National Human Genome Research Institute [HG005062]; US National
Institutes of Health [DP2OD002230]; National Institutes of Health;
GlaxoSmithKline Immune Disease Institute; National Institute of Allergy
and Infectious Diseases [AI102816]
FX We are grateful to Y.J. Crow for AGS patient fibroblasts and control
cells; T. Lindahl for Trex1-/- MEFs and wild-type control
MEFs; D. Sabatini and D. Kwiatkowski for p53-/- MEFs; N.A.
DeLuca for HSV-1 d109 virus; C. Shamu (Institute of Chemistry and Cell
Biology at Harvard Medical School) for the siRNA library and expert
advice; The RNAi Consortium at the Broad Institute for assistance with
siRNA screening; J. Qiao for assistance with mass spectrometry; M.
Rooney and C. Ye for advice about statistical analyses; D. Londono for
help with microscopy; J. Kagan, N. Haining, L. Glimcher and M. Brenner
for valuable discussions; and W.F. Pendergraft III and other members of
the Hacohen laboratory for critical review of the manuscript. This work
was supported by the US National Human Genome Research Institute grant
HG005062 and US National Institutes of Health Director's New Innovator
award DP2OD002230 (N.H.). M.N.L. is supported by a National Institutes
of Health Medical Scientist Training Program fellowship; F.D. by a
GlaxoSmithKline Immune Disease Institute fellowship; and J.L. by
National Institute of Allergy and Infectious Diseases grant AI102816.
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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 FEB
PY 2013
VL 14
IS 2
BP 179
EP 185
DI 10.1038/ni.2509
PG 7
WC Immunology
SC Immunology
GA 075WR
UT WOS:000313918400013
PM 23263557
ER
PT J
AU Bourne, SK
Sheth, SA
Neal, J
Strong, C
Mian, MK
Cosgrove, GR
Eskandar, EN
Dougherty, DD
AF Bourne, Sarah K.
Sheth, Sameer A.
Neal, Jonathan
Strong, Christian
Mian, Matthew K.
Cosgrove, G. Rees
Eskandar, Emad N.
Dougherty, Darin D.
TI Beneficial Effect of Subsequent Lesion Procedures After Nonresponse to
Initial Cingulotomy for Severe, Treatment-Refractory
Obsessive-Compulsive Disorder
SO NEUROSURGERY
LA English
DT Article
DE Cingulotomy; Obsessive-compulsive disorder; Psychosurgery; Subcaudate
tractotomy
ID TERM-FOLLOW-UP; STEREOTACTIC LIMBIC LEUCOTOMY; ANTERIOR CINGULOTOMY;
CEREBRAL GLUCOSE; LEUKOTOMY; PREVALENCE; METABOLISM; DEPRESSION
AB BACKGROUND: Anterior cingulotomy (AC) can be an effective therapy for patients with severe obsessive-compulsive disorder who are refractory to traditional medical therapy. For patients who do not respond to AC, the benefit of additional lesion procedures vs continued medical management remains unknown.
OBJECTIVE: To determine whether a second lesion procedure is beneficial after unsuccessful initial AC.
METHODS: In this retrospective cohort study, we reviewed the records of 31 patients who were nonresponders to initial AC. Full response was defined as at least a 35% decrease and partial response as a 25% to 34% decrease in Yale-Brown Obsessive-Compulsive Scale scores. Yale-Brown Obsessive-Compulsive Scale change was compared between patients who underwent additional surgery and those treated nonsurgically. In addition, for patients who underwent additional surgery, we compared the benefit of subcaudate tractotomy with repeat AC (extension of the initial lesion) as the second procedure.
RESULTS: Nineteen patients underwent a second surgery and 12 patients continued nonsurgical therapy. Fifty-three percent of patients who received additional surgery were full responders and 21% were partial responders at the most recent follow-up compared with 17% full responders and 25% partial responders among those who continued conventional therapy (P = .02). Of the patients who underwent an additional surgery, there were 64% full and 9% partial responders in the subcaudate tractotomy group compared with 38% full and 38% partial responders in the repeat AC group (P = .04).
CONCLUSION: Second lesion surgery can be a safe and effective therapy for patients who do not respond to initial AC. Subcaudate tractotomy may confer a higher response rate than repeat cingulotomy.
C1 [Bourne, Sarah K.; Sheth, Sameer A.; Neal, Jonathan; Strong, Christian; Mian, Matthew K.; Eskandar, Emad N.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA.
[Dougherty, Darin D.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Bourne, Sarah K.] Vanderbilt Univ Sch Med, Nashville, TN USA.
[Cosgrove, G. Rees] Brown Univ, Warren Alpert Med Sch, Dept Neurosurg, Providence, RI 02912 USA.
RP Dougherty, DD (reprint author), Massachusetts Gen Hosp E, Dept Psychiat, 149 13th St,Room 2612, Charlestown, MA 02129 USA.
EM ddougherty@partners.org
FU Howard Hughes Medical Institute Medical Fellows Program
FX S.K. Bourne received funding support from Howard Hughes Medical
Institute Medical Fellows Program. The authors have no personal
financial or institutional interest in any of the drugs, materials, or
devices described in this article.
NR 27
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U1 4
U2 9
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0148-396X
J9 NEUROSURGERY
JI Neurosurgery
PD FEB
PY 2013
VL 72
IS 2
BP 196
EP 202
DI 10.1227/NEU.0b013e31827b9c7c
PG 7
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA 073HP
UT WOS:000313734400032
PM 23147780
ER
PT J
AU Gowrishankar, TR
Smith, KC
Weaver, JC
AF Gowrishankar, Thiruvallur R.
Smith, Kyle C.
Weaver, James C.
TI Transport-Based Biophysical System Models of Cells for Quantitatively
Describing Responses to Electric Fields
SO PROCEEDINGS OF THE IEEE
LA English
DT Review
DE Distributed transport model; electroporation (EP); meshed transport
networks (MTNs); transport lattice
ID PLANAR BILAYER-MEMBRANES; SOLID TUMOR TREATMENT; SINGLE-CELL;
IRREVERSIBLE ELECTROPORATION; SUPRA-ELECTROPORATION; ASYMPTOTIC MODEL;
ORGANELLES; VOLTAGE; PULSES; MECHANISMS
AB In this paper, we review computational methods based on spatially distributed transport models that we have used to describe biological cell system responses to electric fields. Application to electroporation (EP) is emphasized, as it is increasingly used experimentally, but is not well understood quantitatively. We argue that Cartesian transport lattices (CTLs) and meshed transport networks (MTNs) are appropriate for describing transport in cellular systems generally. The approach is based on mathematical descriptions of transport in 1-D, which are then assigned to intranodal regions in 1-D, 2-D, and 3-D cell system geometries. Electrical behavior is based on nonspecific charge movement. Descriptions of heat transfer and both molecular and ionic transport have also been examined. This approach allows both traditional, idealized geometries [e. g., cylindrical, spherical plasma membrane (PM)] and also more realistic, irregular cell shapes and sizes to be used approximately, with little difference in computational difficulty. The more complex (active) local membrane models are similar to "agents" in agent-based modeling, in the sense that it is the individual responses of interactions within local regions that yield overall system behavior, which can be emergent and nonintuitive. Cell system models may be useful for screening of EP candidate combinations of pulse parameters, cell characteristics, and molecular transport properties with the goal of optimizing existing experimental protocols and possibly discovering new effects and applications.
C1 [Gowrishankar, Thiruvallur R.; Smith, Kyle C.; Weaver, James C.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
[Smith, Kyle C.] Massachusetts Gen Hosp, Ctr Engn & Med, Boston, MA 02114 USA.
RP Gowrishankar, TR (reprint author), MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
EM jcw@mit.edu
FU National Institutes of Health [GM063857]
FX Manuscript received September 23, 2011; revised February 27, 2012 and
April 24, 2012; accepted May 5, 2012. Date of publication July 16, 2012;
date of current version January 16, 2013. This work was supported by the
National Institutes of Health under Grant GM063857.
NR 47
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U1 2
U2 27
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 0018-9219
J9 P IEEE
JI Proc. IEEE
PD FEB
PY 2013
VL 101
IS 2
SI SI
BP 505
EP 517
DI 10.1109/JPROC.2012.2200289
PG 13
WC Engineering, Electrical & Electronic
SC Engineering
GA 073DT
UT WOS:000313724400023
ER
PT J
AU Tuzer, F
Madani, N
Kamanna, K
Zentner, I
LaLonde, J
Holmes, A
Upton, E
Rajagopal, S
McFadden, K
Contarino, M
Sodroski, J
Chaiken, I
AF Tuzer, Ferit
Madani, Navid
Kamanna, Kantharaju
Zentner, Isaac
LaLonde, Judith
Holmes, Andrew
Upton, Elizabeth
Rajagopal, Srivats
McFadden, Karyn
Contarino, Mark
Sodroski, Joseph
Chaiken, Irwin
TI HIV-1 ENV gp120 structural determinants for peptide triazole dual
receptor site antagonism
SO PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
LA English
DT Article
DE entry inhibitor; KR21; dual antagonism; binding site
ID IMMUNODEFICIENCY-VIRUS TYPE-1; SMALL-MOLECULE INHIBITORS; CD4
BINDING-SITE; ENVELOPE GLYCOPROTEIN; VIROLOGICAL FAILURE; ENTRY
INHIBITORS; ANTIBODY; AFFINITY; CONFORMATION; BIOSENSOR
AB Despite advances in HIV therapy, viral resistance and side-effects with current drug regimens require targeting new components of the virus. Dual antagonist peptide triazoles (PT) are a novel class of HIV-1 inhibitors that specifically target the gp120 component of the viral spike and inhibit its interaction with both of its cell surface protein ligands, namely the initial receptor CD4 and the co-receptor (CCR5/CXCR4), thus preventing viral entry. Following an initial survey of 19 gp120 alanine mutants by ELISA, we screened 11 mutants for their importance in binding to, and inhibition by the PT KR21 using surface plasmon resonance. Key mutants were purified and tested for their effects on the peptide's affinity and its ability to inhibit binding of CD4 and the co-receptor surrogate mAb 17b. Effects of the mutations on KR21 viral neutralization were measured by single-round cell infection assays. Two mutations, D474A and T257A, caused large-scale loss of KR21 binding, as well as losses in both CD4/17b and viral inhibition by KR21. A set of other Ala mutants revealed more moderate losses in direct binding affinity and inhibition sensitivity to KR21. The cluster of sensitive residues defines a PT functional epitope. This site is in a conserved region of gp120 that overlaps the CD4 binding site and is distant from the co-receptor/17b binding site, suggesting an allosteric mode of inhibition for the latter. The arrangement and sequence conservation of the residues in the functional epitope explain the breadth of antiviral activity, and improve the potential for rational inhibitor development. Proteins 2013. (C) 2012 Wiley Periodicals, Inc.
C1 [Tuzer, Ferit; Kamanna, Kantharaju; Zentner, Isaac; Holmes, Andrew; Upton, Elizabeth; Contarino, Mark; Chaiken, Irwin] Drexel Univ, Coll Med, Dept Biochem & Mol Biol, Philadelphia, PA 19102 USA.
[Madani, Navid; Sodroski, Joseph] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
[LaLonde, Judith] Bryn Mawr Coll, Dept Chem, Bryn Mawr, PA 19010 USA.
[Rajagopal, Srivats] Syngene Int, Div Biol, Bangalore, Karnataka, India.
[McFadden, Karyn] Duke Univ, Dept Mol Genet & Microbiol, Med Ctr, Durham, NC 27710 USA.
RP Chaiken, I (reprint author), New Coll Bldg,Room 11101,245 N 15th St, Philadelphia, PA 19102 USA.
EM ichaiken@drexelmed.edu
FU NIH [P01 GM 56550]; Ragon Institute of MGH, MIT and Harvard;
International AIDS Vaccine Initiative; Center for HIV/AIDS Vaccine
Immunology
FX Grant sponsor: NIH; Grant number: P01 GM 56550; Grant sponsor: Ragon
Institute of MGH, MIT and Harvard, the International AIDS Vaccine
Initiative, the Center for HIV/AIDS Vaccine Immunology, the late William
F. McCarty-Cooper (to J.S.).
NR 34
TC 8
Z9 8
U1 0
U2 16
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0887-3585
J9 PROTEINS
JI Proteins
PD FEB
PY 2013
VL 81
IS 2
BP 271
EP 290
DI 10.1002/prot.24184
PG 20
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 074KP
UT WOS:000313811700008
PM 23011758
ER
PT J
AU Asami, T
Saito, Y
Whitford, TJ
Makris, N
Niznikiewicz, M
McCarley, RW
Shenton, ME
Kubicki, M
AF Asami, Takeshi
Saito, Yukiko
Whitford, Thomas J.
Makris, Nikos
Niznikiewicz, Margaret
McCarley, Robert W.
Shenton, Martha E.
Kubicki, Marek
TI Abnormalities of middle longitudinal fascicle and disorganization in
patients with schizophrenia
SO SCHIZOPHRENIA RESEARCH
LA English
DT Article
DE Schizophrenia; DTI; FA; Middle longitudinal fascicle; Disorganization;
Attention deficit
ID POSITRON-EMISSION-TOMOGRAPHY; SYNDROME SCALE PANSS; AUDITORY
HALLUCINATIONS; SYNAPTIC PLASTICITY; CORPUS-CALLOSUM; TEMPORAL-LOBE;
HUMAN BRAIN; DIFFUSION; PSYCHOSIS; SYMPTOMS
AB Introduction: The middle longitudinal fascicle (MdLF) is a long association fiber connecting the superior temporal gyrus (STG) and temporal pole with the angular gyrus through the white matter of the STG, structures which are known to play a crucial role in the pathology of schizophrenia. Functions of MdLF are thought to be related to language and thought processing in the left hemisphere, and with attention in the right hemisphere. While deficits of these functions are core clinical features of schizophrenia, no study has investigated the structural abnormalities of MdLF in schizophrenia.
Method: 3 T diffusion tensor data was acquired from twenty-six patients with schizophrenia and twenty-five healthy control subjects. Streamline tractography technique was used to extract MdLF. Fractional anisotropy (FA) was compared between the two groups. In addition, relationships were investigated between FA in the left MdLF and the Disorganized Thoughts Factor derived from the Positive and Negative Symptom Scale five factor model, and between FA in the right MdLF and the Poor Attention.
Result: Relative to control subjects, the patients with chronic schizophrenia showed significant mean FA reductions in the bilateral MdLF. The FA of the left MdLF demonstrated a significant negative association with the Disorganized Thoughts Factor, and the FA of the right MdLF showed a significant negative relationship with the Poor Attention.
Conclusions: This study provides new evidence for structural deficits in the bilateral MdLF in patients with chronic schizophrenia. It further demonstrates the contribution of these abnormalities to the core clinical features - especially to disorganization and attention deficit. (C) 2012 Elsevier B. V. All rights reserved.
C1 [Asami, Takeshi; Niznikiewicz, Margaret; McCarley, Robert W.; Shenton, Martha E.; Kubicki, Marek] Harvard Univ, Sch Med, Boston Vet Affairs Healthcare Syst,Brockton Div, Lab Neurosci,Clin Neurosci Div,Dept Psychiat, Brockton, MA 02401 USA.
[Asami, Takeshi; Saito, Yukiko; Whitford, Thomas J.; Shenton, Martha E.; Kubicki, Marek] Harvard Univ, Sch Med, Brigham & Womens Hosp, Psychiat Neuroimaging Lab,Dept Psychiat, Boston, MA 02215 USA.
[Whitford, Thomas J.] Univ New S Wales, Sch Psychol, Sydney, NSW, Australia.
[Makris, Nikos] Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Psychiat, Ctr Morphometr Anal,Athinoula A Martinos Ctr Biom, Boston, MA 02215 USA.
[Makris, Nikos] Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Neurol, Ctr Morphometr Anal,Athinoula A Martinos Ctr Biom, Boston, MA 02215 USA.
[Makris, Nikos] Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Radiol Serv, Ctr Morphometr Anal,Athinoula A Martinos Ctr Biom, Boston, MA 02215 USA.
[Makris, Nikos] Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA.
[Shenton, Martha E.; Kubicki, Marek] Harvard Univ, Sch Med, Brigham & Womens Hosp, Surg Planning Lab,MRI Div,Dept Radiol, Boston, MA 02215 USA.
RP Kubicki, M (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Psychiat Neuroimaging Lab,Dept Psychiat, 1249 Boylston St, Boston, MA 02215 USA.
EM kubicki@bwh.harvard.edu
RI McCarley, Robert/N-5562-2014
OI McCarley, Robert/0000-0001-5705-7495
FU National Institute of Health [K05 MH070047, R01 MH 50740, R01 MH 40799,
R01MH 074794, P50MH 080272-CIDAR, R21MH084041, R01DA027804];
ARRA-NIH-NCCAM; Department of Veterans Affairs; VA Schizophrenia Center;
National Alliance for Medical Image Computing (NA-MIC); National
Institutes of Health Roadmap for Medical Research [U54 EB005149];
National Health and Medical Research Council of Australia [520627];
National Alliance for Research on Schizophrenia and Depression (NARSAD)
FX This study was supported, in part, by grants from the National Institute
of Health (K05 MH070047 and R01 MH 50740 to MES, R01 MH 40799 to RWM,
R01MH 074794 to MK, P50MH 080272-CIDAR award to RWM, MES, MK;
R21MH084041, R01DA027804 and ARRA-NIH-NCCAM to NM), the Department of
Veterans Affairs Merit Awards (MES, RWM), and the VA Schizophrenia
Center Grant (RWM/MES/MK). This work is also, in part, supported by the
National Alliance for Medical Image Computing (NA-MIC), the latter a
grant supported through the National Institutes of Health Roadmap for
Medical Research, Grant U54 EB005149 (MK). TJW is supported by an
Overseas-Based Biomedical Training Fellowship from the National Health
and Medical Research Council of Australia (#520627), and a Young
Investigator Award from the National Alliance for Research on
Schizophrenia and Depression (NARSAD).
NR 51
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Z9 9
U1 3
U2 13
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0920-9964
J9 SCHIZOPHR RES
JI Schizophr. Res.
PD FEB
PY 2013
VL 143
IS 2-3
BP 253
EP 259
DI 10.1016/j.schres.2012.11.030
PG 7
WC Psychiatry
SC Psychiatry
GA 072GX
UT WOS:000313659000004
PM 23290607
ER
PT J
AU Zhuo, KM
Lu, Y
Yang, ZL
Fan, XD
Song, ZH
Liao, LW
Ji, CF
Zhu, DM
Yu, SY
Yan, C
Chan, RCK
Goff, DC
Xu, YF
Liu, DT
AF Zhuo, Kaiming
Lu, Yun
Yang, Zhiliang
Fan, Xiaoduo
Song, Zhenhua
Liao, Liwei
Ji, Chenfeng
Zhu, Dianming
Yu, Shunying
Yan, Chao
Chan, Raymond C. K.
Goff, Donald C.
Xu, Yifeng
Liu, Dengtang
TI Prospective memory performance in patients with drug-naive,
first-episode psychosis
SO SCHIZOPHRENIA RESEARCH
LA English
DT Article
DE Prospective memory; Schizophrenia; First-episode
ID RETROSPECTIVE-MEMORY; COGNITIVE IMPAIRMENT; WORKING-MEMORY;
SCHIZOPHRENIA; NEUROCOGNITION; DEFICITS; METAANALYSIS; PREDICTORS;
SYMPTOMS; CORE
AB Schizophrenia is associated with an impairment of prospective memory (PM) which refers to the ability to remember to carry out an intended action in the future. However, most of these studies were limited to chronic samples. The current study examined the event-based PM and time-based PM using a dual-task paradigm in 22 drug-naive, first-episode psychosis (FEP) patients and 23 healthy controls. Results indicated that FEP patients performed significantly poorer than healthy controls in both event-based and time-based PM. However, the significant difference in time-based PM disappeared after controlling for working memory. Correlation analysis indicated that both types of PM did not correlate with positive symptoms or negative symptoms, duration of illness, or duration of untreated psychosis. However, time-based PM was correlated with the general psychopathology subscale of the PANSS. Taken together, these findings suggest that PM deficits are present in drug-naive FEP patients; impairment of event-based PM appears to occur independently, whereas time-based PM impairment may be, in part, a secondary consequence of a working memory deficit. (C) 2012 Elsevier B. V. All rights reserved.
C1 [Zhuo, Kaiming; Lu, Yun; Song, Zhenhua; Liao, Liwei; Ji, Chenfeng; Zhu, Dianming; Yu, Shunying; Xu, Yifeng; Liu, Dengtang] Shanghai Jiao Tong Univ, Sch Med, Shanghai Mental Hlth Ctr, Schizophrenia Program,Dept Psychiat, Shanghai 200030, Peoples R China.
[Yang, Zhiliang; Liu, Dengtang] E China Normal Univ, Dept Psychol, Shanghai 200062, Peoples R China.
[Fan, Xiaoduo] Harvard Univ, Sch Med, Dept Psychiat, Schizophrenia Program,Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Yan, Chao; Chan, Raymond C. K.] Chinese Acad Sci, Inst Psychol, Key Lab Mental Hlth, Neuropsychol & Appl Cognit Neurosci Lab, Beijing 100101, Peoples R China.
[Goff, Donald C.] NYU, Med Ctr, Nathan S Kline Inst Psychiat Res, New York, NY 10016 USA.
RP Xu, YF (reprint author), Shanghai Jiao Tong Univ, Sch Med, Shanghai Mental Hlth Ctr, Schizophrenia Program,Dept Psychiat, 600 Wan Ping Nan Rd, Shanghai 200030, Peoples R China.
EM hyyyyb@gmail.com; erliu110@126.com
FU Science and Technology Commission of Shanghai Municipality
[11ZR1431600]; China Postdoctoral Science Foundation [20080430634];
National Key Clinical Disciplines at Shanghai Mental Health Center
(OMA-MH) [2011-873]
FX This work was supported by a grant 11ZR1431600 from the Science and
Technology Commission of Shanghai Municipality to Dr Liu and a grant
20080430634 from China Postdoctoral Science Foundation to Dr Liu. It was
also supported by National Key Clinical Disciplines at Shanghai Mental
Health Center (OMA-MH, 2011-873).
NR 47
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Z9 9
U1 2
U2 19
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0920-9964
J9 SCHIZOPHR RES
JI Schizophr. Res.
PD FEB
PY 2013
VL 143
IS 2-3
BP 285
EP 290
DI 10.1016/j.schres.2012.12.002
PG 6
WC Psychiatry
SC Psychiatry
GA 072GX
UT WOS:000313659000008
PM 23267733
ER
PT J
AU Zhang, XY
Chen, DC
Xiu, MH
De Yang, F
Tan, YL
He, SC
Kosten, TA
Kosten, TR
AF Zhang, Xiang Yang
Chen, Da Chun
Xiu, Mei Hong
De Yang, Fu
Tan, Yun Long
He, Shuchang
Kosten, Therese A.
Kosten, Thomas R.
TI Thioredoxin, a novel oxidative stress marker and cognitive performance
in chronic and medicated schizophrenia versus healthy controls
SO SCHIZOPHRENIA RESEARCH
LA English
DT Article
DE Schizophrenia; Cognition; Oxidative stress; Psychopathology
ID FREE-RADICAL PATHOLOGY; SUPEROXIDE-DISMUTASE; 1ST-EPISODE SCHIZOPHRENIA;
NEUROPSYCHOLOGICAL STATUS; PLASMA THIOREDOXIN; REPEATABLE BATTERY;
TARDIVE-DYSKINESIA; LIPID-PEROXIDATION; DIFFERENT FORMS; PSYCHOSIS
AB Oxidative stress-induced damage to neurons may contribute to cognitive deficits during aging and in neuro-degenerative disorders. Schizophrenia has a range of cognitive deficits that may evolve from oxidative stress. Thioredoxin (TRX), a redox-regulating protein with antioxidant activity recognized as an oxidative-stress marker has recently been found to be involved in pathogenesis and psychopathology of schizophrenia. The aim of this study was to examine the association of TRX with cognitive deficits in schizophrenia. We recruited 45 chronic schizophrenic patients and 66 healthy control subjects and examined the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and serum TRX in both groups. Schizophrenic symptoms were assessed using the positive and negative syndrome scale (PANSS). We found no significant difference in TRX levels between patients and healthy controls. Cognitive scores on the RBANS and four of its five subscales (all p<0.001) except for the Visuospatial/Constructional index (p>0.05) were significantly lower in schizophrenic patients than normal controls. For the patients, TRX was inversely associated with the Attention domain of cognitive deficits in schizophrenia; however, TRX was positively associated with Attention in controls. The significantly lower TRX levels in attention impaired schizophrenia compared to controls suggest that oxidative stress may be involved in the cognitive impairment, especially attention in schizophrenia. The differential association of TRX and cognitive performance in schizophrenia and controls may be related to the impaired oxidative stress status of schizophrenia patients. (C) 2012 Elsevier B. V. All rights reserved.
C1 [Zhang, Xiang Yang; Kosten, Therese A.; Kosten, Thomas R.] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA.
[Zhang, Xiang Yang; Kosten, Therese A.; Kosten, Thomas R.] Michael E DeBakey VA Med Ctr, Houston, TX USA.
[Zhang, Xiang Yang; Chen, Da Chun; Xiu, Mei Hong; De Yang, Fu; Tan, Yun Long; Kosten, Thomas R.] Peking Univ, Beijing HuiLongGuan Hosp, Beijing 100871, Peoples R China.
[He, Shuchang] Peking Univ, Dept Psychol, 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
FU 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 Funding for this study was provided by grants from the Stanley Medical
Research Institute (03T-459 and 05T-726), the Department of Veterans
Affairs, VISN 16, Mental Illness Research, Education and Clinical Center
(MIRECC), and United States National Institute of Health (K05-DA0454,
P50-DA18827 and U01-MH79639). These sources had no further role in study
design; in the collection, analysis and interpretation of data; in the
writing of the report; and in the decision to submit the paper for
publication.
NR 62
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U1 1
U2 14
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0920-9964
J9 SCHIZOPHR RES
JI Schizophr. Res.
PD FEB
PY 2013
VL 143
IS 2-3
BP 301
EP 306
DI 10.1016/j.schres.2012.11.017
PG 6
WC Psychiatry
SC Psychiatry
GA 072GX
UT WOS:000313659000011
PM 23238053
ER
PT J
AU Jahshan, C
Wynn, JK
Green, MF
AF Jahshan, Carol
Wynn, Jonathan K.
Green, Michael F.
TI Relationship between auditory processing and affective prosody in
schizophrenia
SO SCHIZOPHRENIA RESEARCH
LA English
DT Article
DE Schizophrenia; Auditory processing; Affective prosody; Mismatch
negativity; P300
ID FACIAL AFFECT RECOGNITION; MISMATCH NEGATIVITY; SENSORY CONTRIBUTIONS;
VOCAL EXPRESSION; COGNITION; PERCEPTION; DEFICITS; DISCRIMINATION;
COMMUNICATION; METAANALYSIS
AB Patients with schizophrenia have well-established deficits in their ability to identify emotion from facial expression and tone of voice. In the visual modality, there is strong evidence that basic processing deficits contribute to impaired facial affect recognition in schizophrenia. However, few studies have examined the auditory modality for mechanisms underlying affective prosody identification. In this study, we explored links between different stages of auditory processing, using event-related potentials (ERPs), and affective prosody detection in schizophrenia. Thirty-six schizophrenia patients and 18 healthy control subjects received tasks of affective prosody, facial emotion identification, and tone matching, as well as two auditory oddball paradigms, one passive for mismatch negativity (MMN) and one active for P300. Patients had significantly reduced MMN and P300 amplitudes, impaired auditory and visual emotion recognition, and poorer tone matching performance, relative to healthy controls. Correlations between ERP and behavioral measures within the patient group revealed significant associations between affective prosody recognition and both MMN and P300 amplitudes. These relationships were modality specific, as MMN and P300 did not correlate with facial emotion recognition. The two ERP waves accounted for 49% of the variance in affective prosody in a regression analysis. Our results support previous suggestions of a relationship between basic auditory processing abnormalities and affective prosody dysfunction in schizophrenia, and indicate that both relatively automatic pre-attentive processes (MMN) and later attention-dependent processes (P300) are involved with accurate auditory emotion identification. These findings provide support for bottom-up (e. g., perceptually based) cognitive remediation approaches. Published by Elsevier B.V.
C1 VA Greater Los Angeles Healthcare Syst, Sierra Pacific Mental Illness Res Educ & Clin Ctr, Los Angeles, CA 90073 USA.
Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90095 USA.
RP Jahshan, C (reprint author), VA Greater Los Angeles Healthcare Syst, MIRECC, Bldg 210,Room 117,11301 Wilshire Blvd, Los Angeles, CA 90073 USA.
EM caroljahshan@hotmail.com
RI Wynn, Jonathan/H-3749-2014
OI Wynn, Jonathan/0000-0002-1763-8540
FU Department of Veterans Affairs Sierra Pacific Mental Illness Research,
Education and Clinical Center (MIRECC); National Institute of Mental
Health [MH065707]; Department of Veterans Affairs Office of Academic
Affiliations Advanced Fellowship Program in Mental Illness Research and
Treatment
FX Funding for this study was provided by grants from the Department of
Veterans Affairs Sierra Pacific Mental Illness Research, Education and
Clinical Center (MIRECC) and the National Institute of Mental Health
(MH065707 to MFG). The MIRECC and NIH had no further role in study
design; in the collection, analysis, and interpretation of data; in the
writing of the report; and in the decision to submit the paper for
publication.; Writing of this manuscript was supported by the Department
of Veterans Affairs Office of Academic Affiliations Advanced Fellowship
Program in Mental Illness Research and Treatment. The authors would like
to thank Crystal Gibson, Cory Tripp, Katie Weiner, Mark McGee, Christen
Waldon and Amanda Bender for their assistance with recruitment and
testing. The authors would also like to thank Petri Laukka, Ph.D. and
David I. Leitman, Ph.D. for providing the affective prosody task and
tone matching task, respectively.
NR 42
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U1 0
U2 15
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0920-9964
J9 SCHIZOPHR RES
JI Schizophr. Res.
PD FEB
PY 2013
VL 143
IS 2-3
BP 348
EP 353
DI 10.1016/j.schres.2012.11.025
PG 6
WC Psychiatry
SC Psychiatry
GA 072GX
UT WOS:000313659000018
PM 23276478
ER
PT J
AU Antonius, D
Kline, B
Sinclair, SJ
White-Ajmani, M
Gianfagna, S
Malaspina, D
Tremeau, F
AF Antonius, Daniel
Kline, Brian
Sinclair, Samuel Justin
White-Ajmani, Mandi
Gianfagna, Sara
Malaspina, Dolores
Tremeau, Fabien
TI Deficits in implicit facial recognition of fear in aggressive patients
with schizophrenia
SO SCHIZOPHRENIA RESEARCH
LA English
DT Letter
ID METAANALYSIS
C1 [Antonius, Daniel] SUNY Buffalo, Dept Psychiat, Erie Cty Med Ctr, Buffalo, NY 14125 USA.
[Antonius, Daniel] Erie Cty Forens Mental Hlth Serv, Buffalo, NY USA.
[Antonius, Daniel; White-Ajmani, Mandi; Malaspina, Dolores; Tremeau, Fabien] NYU, Sch Med, Inst Social & Psychiat Initiat InSPIRES, New York, NY USA.
[Sinclair, Samuel Justin] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Sinclair, Samuel Justin] Harvard Univ, Sch Med, Psychol Evaluat & Res Lab PEaRL, Boston, MA USA.
[Gianfagna, Sara] Georgetown Univ, Washington, DC USA.
[Malaspina, Dolores] Creedmoor Psychiat Ctr, Queens Village, NY USA.
[Tremeau, Fabien] Nathan S Kline Inst Psychiat Res, Orangeburg, NY USA.
RP Antonius, D (reprint author), SUNY Buffalo, Dept Psychiat, Erie Cty Med Ctr, 462 Grider St, Buffalo, NY 14125 USA.
EM danielan@buffalo.edu
FU NIMH NIH HHS [5K24MH001699-10, K24 MH001699, R01 MH066428, R01MH066428]
NR 10
TC 1
Z9 1
U1 0
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0920-9964
J9 SCHIZOPHR RES
JI Schizophr. Res.
PD FEB
PY 2013
VL 143
IS 2-3
BP 401
EP 402
DI 10.1016/j.schres.2012.11.038
PG 2
WC Psychiatry
SC Psychiatry
GA 072GX
UT WOS:000313659000030
PM 23276483
ER
PT J
AU Mavandadi, S
Rook, KS
Newsom, JT
Oslin, DW
AF Mavandadi, Shahrzad
Rook, Karen S.
Newsom, Jason T.
Oslin, David W.
TI Suicidal ideation and social exchanges among at-risk veterans referred
for a behavioral health assessment
SO SOCIAL PSYCHIATRY AND PSYCHIATRIC EPIDEMIOLOGY
LA English
DT Article
DE Suicide; Positive social exchanges; Negative social exchanges; Mental
health; Veterans
ID PSYCHOLOGICAL DISTRESS; RELATIVE IMPORTANCE; COMMUNITY SAMPLE;
DEPRESSION; POPULATION; AFFAIRS; SUPPORT; STRESS; ADULTS; LIFE
AB The current study examined the independent association between positive (e.g., emotional and instrumental support) and negative (e.g., insensitive behavior, unwanted advice from others) social exchanges and suicidal ideation among veterans referred for a behavioral health assessment.
The sample included 606 veterans [mean age = 54.96 (SD = 14.96)] referred by primary care for a clinical mental health/substance abuse (MH/SA) assessment following a positive MH/SA screen. Data on sociodemographics, MH/SA conditions (e.g., depression, PTSD, anxiety, and alcohol abuse), the self-reported frequency of positive and negative social exchanges, and suicidal ideation were extracted from clinical interviews and evaluated.
Veterans were primarily male, non-married, and had adequate financial resources, and approximately half were White. 74.4 and 20.3 % met criteria for a MH/SA condition and suicidal ideation, respectively. Multiple logistic regression analyses revealed that, adjusting for sociodemographics, physical functioning, and comorbid MH/SA conditions, veterans reporting more frequent negative exchanges with network members were significantly more likely to report suicidal ideation. Positive exchanges, in contrast, were not significantly related to the outcome. Inadequate finances and MH/SA conditions also were significantly related to suicidal ideation.
Findings highlight the value of exploring the quality of social exchanges among veterans in primary care who screen positive for behavioral health issues, as such information has the potential to inform screening and intervention efforts aimed at reducing suicidal ideation.
C1 [Mavandadi, Shahrzad; Oslin, David W.] Philadelphia VA Med Ctr, Mental Illness Res Educ & Clin Ctr, Philadelphia, PA 19104 USA.
[Mavandadi, Shahrzad; Oslin, David W.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA.
[Rook, Karen S.] Univ Calif Irvine, Sch Social Ecol, Dept Psychol & Social Behav, Irvine, CA 92697 USA.
[Newsom, Jason T.] Portland State Univ, Sch Community Hlth, Inst Aging, Portland, OR 97207 USA.
RP Mavandadi, S (reprint author), Philadelphia VA Med Ctr, Mental Illness Res Educ & Clin Ctr, 3900 Woodland Ave,B215, Philadelphia, PA 19104 USA.
EM Shahrzad.Mavandadi@va.gov
FU VISN 4 Mental Illness Research, Education, and Clinical Center (MIRECC)
at the Philadelphia Veterans Affairs Medical Center (PVAMC); VA Office
of Research and Development
FX This work was supported by the VISN 4 Mental Illness Research,
Education, and Clinical Center (MIRECC) at the Philadelphia Veterans
Affairs Medical Center (PVAMC) and VA Office of Research and
Development. The content of this article does not reflect the views of
the VHA or of the Government.
NR 58
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U2 26
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 0933-7954
EI 1433-9285
J9 SOC PSYCH PSYCH EPID
JI Soc. Psychiatry Psychiatr. Epidemiol.
PD FEB
PY 2013
VL 48
IS 2
BP 233
EP 243
DI 10.1007/s00127-012-0534-5
PG 11
WC Psychiatry
SC Psychiatry
GA 074LR
UT WOS:000313814500007
PM 22722536
ER
PT J
AU Falcone, GJ
Biffi, A
Devan, WJ
Brouwers, HB
Anderson, CD
Valant, V
Ayres, AM
Schwab, K
Rost, NS
Goldstein, JN
Viswanathan, A
Greenberg, SM
Selim, M
Meschia, JF
Brown, DL
Worrall, BB
Silliman, SL
Tirschwell, DL
Rosand, J
AF Falcone, Guido J.
Biffi, Alessandro
Devan, William J.
Brouwers, H. Bart
Anderson, Christopher D.
Valant, Valerie
Ayres, Alison M.
Schwab, Kristin
Rost, Natalia S.
Goldstein, Joshua N.
Viswanathan, Anand
Greenberg, Steven M.
Selim, Magdy
Meschia, James F.
Brown, Devin L.
Worrall, Bradford B.
Silliman, Scott L.
Tirschwell, David L.
Rosand, Jonathan
CA GOCHA Investigators
TI Burden of Blood Pressure-Related Alleles Is Associated With Larger
Hematoma Volume and Worse Outcome in Intracerebral Hemorrhage
SO STROKE
LA English
DT Article
DE common genetic variants; genetic risk score; hypertension; ICH volume;
intracerebral hemorrhage
ID GENOME-WIDE ASSOCIATION; CEREBRAL-HEMORRHAGE; RISK; HYPERTENSION;
REDUCTION; INTERACT; GENOTYPE; ADULTS; TRIAL
AB Background and Purpose-Intracerebral hemorrhage (ICH) is the acute manifestation of a progressive disease of the cerebral small vessels. The severity of this disease seems to influence not only risk of ICH but also the size of the hematoma. As the burden of high blood pressure-related alleles is associated with both hypertension-related end-organ damage and risk of ICH, we sought to determine whether this burden influences ICH baseline hematoma volume.
Methods-Prospective study in subjects of European descent with supratentorial ICH who underwent genome-wide genotyping. Forty-two single nucleotide polymorphisms associated with high blood pressure were identified from a publicly available database. A genetic risk score was constructed based on these single nucleotide polymorphisms. The score was used as the independent variable in univariate and multivariate regression models for admission ICH volume and poor clinical outcome (modified Rankin Scale, 3-6).
Results-A total of 323 ICH cases were enrolled in the study (135 deep and 188 lobar intracranial hematomas). The blood pressure-based genetic risk score was associated with both baseline hematoma volume and poor clinical outcome specifically in deep ICH. In multivariate regression analyses, each additional SD of the score increased mean deep ICH volume by 28% (or 2.7 mL increase; beta=0.28; SE=0.11; P=0.009) and risk of poor clinical outcome by 71% (odds ratio, 1.71; 95% confidence interval, 1.05-2.80; P=0.03).
Conclusions-Increasing numbers of high blood pressure-related alleles are associated with mean baseline hematoma volume and poor clinical outcome in ICH. These findings suggest that the small vessel vasculopathy responsible for the occurrence of the hemorrhage also influences its volume. (Stroke. 2013; 44: 321-326.)
C1 [Falcone, Guido J.; Biffi, Alessandro; Devan, William J.; Brouwers, H. Bart; Anderson, Christopher D.; Valant, Valerie; Rost, Natalia S.; Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Falcone, Guido J.; Biffi, Alessandro; Devan, William J.; Brouwers, H. Bart; Anderson, Christopher D.; Valant, Valerie; Ayres, Alison M.; Schwab, Kristin; Rost, Natalia S.; Viswanathan, Anand; Greenberg, Steven M.; Rosand, Jonathan] Massachusetts Gen Hosp, Hemorrhag Stroke Res Grp, Boston, MA 02114 USA.
[Falcone, Guido J.; Biffi, Alessandro; Devan, William J.; Brouwers, H. Bart; Anderson, Christopher D.; Rost, Natalia S.; Rosand, Jonathan] Massachusetts Gen Hosp, Dept Neurol, Div Neurocrit Care & Emergency Neurol, Boston, MA 02114 USA.
[Falcone, Guido J.; Biffi, Alessandro; Devan, William J.; Brouwers, H. Bart; Anderson, Christopher D.; Rost, Natalia S.; Rosand, Jonathan] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
[Falcone, Guido J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Goldstein, Joshua N.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.
[Selim, Magdy] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA.
[Meschia, James F.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA.
[Brown, Devin L.] Univ Michigan Hlth Syst, Dept Neurol, Stroke Program, Ann Arbor, MI USA.
[Worrall, Bradford B.] Univ Virginia Hlth Syst, Dept Neurol & Publ Hlth Sci, Charlottesville, VA USA.
[Silliman, Scott L.] Univ Florida, Coll Med, Dept Neurol, Jacksonville, FL USA.
[Tirschwell, David L.] Univ Washington, Harborview Med Ctr, Stroke Ctr, Seattle, WA 98104 USA.
RP Rosand, J (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, 185 Cambridge St,CPZN 6818, Boston, MA 02114 USA.
EM jrosand@partners.org
RI Goldstein, Joshua/H-8953-2016; Falcone, Guido/L-2287-2016;
OI Falcone, Guido/0000-0002-6407-0302; Brown, Devin/0000-0002-9815-3421;
Anderson, Christopher/0000-0002-0053-2002
FU National Institutes of Health (NIH)-National Institute of Neurological
Disorders and Stroke (NINDS) [R01NS059727]; Keane Stroke Genetics
Research Fund; Edward and Maybeth Sonn Research Fund; University of
Michigan General Clinical Research Center [M01 RR000042]; National
Center for Research Resources; NIH-NINDS [5U54NS057405 (DECIPHER)];
American Heart Association/Bugher Foundation Centers for Stroke
Prevention Research [0775010 N]; NIH-NINDS Specialized Programs of
Translational Research in Acute Stroke fellowship [P50NS051343]; NIH;
NINDS; National Institutes of Health; American Heart Association;
[NIH-K23NS059774]
FX Genetics of Cerebral Hemorrhage on Anticoagulation: This study was
funded by National Institutes of Health (NIH)-National Institute of
Neurological Disorders and Stroke (NINDS) Grants R01NS059727, the Keane
Stroke Genetics Research Fund, the Edward and Maybeth Sonn Research
Fund, by the University of Michigan General Clinical Research Center
(M01 RR000042) and by a grant from the National Center for Research
Resources.; DECIPHER Study: This study is funded by NIH-NINDS Grant
5U54NS057405 (DECIPHER). Dr Goldstein was supported by the
NIH-K23NS059774. Drs Biffi and Anderson were supported in part by the
American Heart Association/Bugher Foundation Centers for Stroke
Prevention Research (0775010 N). Dr Brouwers was supported by the
NIH-NINDS Specialized Programs of Translational Research in Acute Stroke
fellowship Grant P50NS051343.; Steven M. Greenberg received a research
grant from the NIH, received honoraria from Medtronic and Pfizer, and is
a consultant/on the advisory board of Hoffman-La Roche, Janssen
Alzheimer Immunotherapy, and Bristol-Myers Squibb Company; Joshua N.
Goldstein received a research grant from the NINDS and is a
consultant/on the advisory board of CSL Behring. Jonathan Rosand
received a research grant from the National Institutes of Health and the
American Heart Association. The other authors have no conflicts to
report.
NR 23
TC 11
Z9 12
U1 1
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
J9 STROKE
JI Stroke
PD FEB
PY 2013
VL 44
IS 2
BP 321
EP +
DI 10.1161/STROKEAHA.112.675181
PG 10
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 073PK
UT WOS:000313754800016
PM 23321443
ER
PT J
AU Sirimarco, G
Amarenco, P
Labreuche, J
Touboul, PJ
Alberts, M
Goto, S
Rother, J
Mas, JL
Bhatt, DL
Steg, PG
AF Sirimarco, Gaia
Amarenco, Pierre
Labreuche, Julien
Touboul, Pierre-Jean
Alberts, Mark
Goto, Shinya
Rother, Joachim
Mas, Jean-Louis
Bhatt, Deepak L.
Steg, Philippe Gabriel
CA REACH Registry Investigators
TI Carotid Atherosclerosis and Risk of Subsequent Coronary Event in
Outpatients With Atherothrombosis
SO STROKE
LA English
DT Article
DE atherosclerosis; carotid plaque; coronary disease
ID INTIMA-MEDIA THICKNESS; ARTERY-DISEASE; CARDIOVASCULAR-DISEASE;
PREDICTIVE-VALUE; ANGINA-PECTORIS; STROKE; PLAQUE; PREVALENCE; RATES;
DETERMINANTS
AB Background and Purpose-The presence of carotid plaque reflects overall atherosclerotic burden and may predict coronary artery disease events. We examined the association among carotid atherosclerosis, history of atherothrombotic events, and risk of coronary events.
Methods-Among 45 227 patients in the Reduction of Atherothrombosis for Continued Health (REACH) Registry with 4-year follow-up, 23 364 patients with information on carotid atherosclerosis at baseline were analyzed. The primary outcome was the composite of first occurrence of cardiovascular death, myocardial infarction, or coronary hospitalization.
Results-The carotid atherosclerosis was present in 46% of patients (n=10 725) and was associated with increasing conventional cardiovascular risk factors and extent of symptomatic vascular disease. During 4-year follow-up, 4304 patients experienced >= 1 coronary event. After adjustment for cardiovascular risk factors and geographic region, the risk of coronary events increased by 22% (95% confidence interval [CI], 14%-30%) in patients with versus without carotid atherosclerosis. The relative increase was 18% (95% CI, -7%-51%) in patients enrolled with multiple risk factors only, 25% (95% CI, 16%-35%) in patients with coronary artery disease, 46% (95% CI, 28%-65%) in patients with cerebrovascular disease, and 37% (95% CI, 17%-60%) in patients with peripheral artery disease. Carotid atherosclerosis was associated with increased risk, even among patients with previous myocardial infarction but no known stroke (P=0.001) or among patients with previous stroke but no known myocardial infarction (P<0.001).
Conclusions-Carotid atherosclerosis was an independent predictor of coronary events across all types of symptomatic vascular disease and had an incremental effect on risk regardless of risk factors or location of vessel disease. (Stroke. 2013;44:373-379.)
C1 [Sirimarco, Gaia; Amarenco, Pierre; Touboul, Pierre-Jean] Univ Paris Diderot, Hop Bichat Claude Bernard, AP HP, Dept Neurol, Paris, France.
[Sirimarco, Gaia; Amarenco, Pierre; Touboul, Pierre-Jean] Univ Paris Diderot, Hop Bichat Claude Bernard, AP HP, Stroke Ctr, Paris, France.
[Amarenco, Pierre; Labreuche, Julien; Touboul, Pierre-Jean; Steg, Philippe Gabriel] Univ Paris Diderot, Hop Bichat Claude Bernard, AP HP, INSERM U 698, Paris, France.
[Steg, Philippe Gabriel] Univ Paris Diderot, Hop Bichat Claude Bernard, AP HP, Dept Cardiol, Paris, France.
[Alberts, Mark] Northwestern Univ, Feinberg Sch Med, Dept Neurol, Chicago, IL 60611 USA.
[Goto, Shinya] Tokai Univ, Sch Med, Dept Med Cardiol, Isehara, Kanagawa 25911, Japan.
[Rother, Joachim] Klinikum Minden, Hannover Med Sch, Dept Neurol, Minden, Germany.
[Mas, Jean-Louis] Paris Descartes Univ, St Anne Hosp, Stroke Unit, Neurol Dept,INSERM UMR S 894, Paris, France.
[Bhatt, Deepak L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, VA Boston Healthcare Syst, Boston, MA 02115 USA.
RP Steg, PG (reprint author), Hop Bichat Claude Bernard, Dept Cardiol, 46 Rue Henri Huchard, F-75877 Paris 18, France.
EM gabriel.steg@bch.aphp.fr
FU SOS-ATTAQUE CEREBRALE Association; Sanofi-Aventis; Bristol-Myers Squibb;
Waksman Foundation (Tokyo, Japan); Boehringer Ingelheim; Otsuka;
Daiichi-Sankyo; Amarin; AstraZeneca; Eisai; Ethicon; Medtronic;
Medicines Company; FlowCo; PLx Pharma; Takeda
FX Drs Lloyd and Rushton-Smith provided editorial help in checking language
and formatting the final version of the manuscript. They were funded by
SOS-ATTAQUE CEREBRALE Association.; The Reduction of Atherothrombosis
for Continued Health Registry (REACH) is sponsored by Sanofi-Aventis,
Bristol-Myers Squibb, and the Waksman Foundation (Tokyo, Japan). The
REACH Registry is endorsed by the World Heart Federation.; P.-J. Touboul
is involved in medical research and development in the IMT company and
received royalties for intellectual property of IMT software. S. Goto
received significant amount of honoraria from Sanofi-Aventis and
AstraZenneca, and also received a significant amount of research grants
from Sanofi-Aventis, Boehringer Ingelheim, Otsuka, and Daiichi-Sankyo.
D.L. Bhatt is a member of the Advisory Board for Medscape Cardiology, is
on the Board of Directors for: Boston VA Research Institute and Society
of Chest Pain Centers, is Chair for American Heart Association Get With
The Guidelines Science Subcommittee, received Honoraria from American
College of Cardiology (Editor, Clinical Trials, and Cardiosource), Duke
Clinical Research Institute (clinical trial steering committees), Slack
Publications (Chief Medical Editor, Cardiology Today Intervention), and
WebMD (CME steering committees) is Senior Associate Editor for Journal
of Invasive Cardiology, received research grants from Amarin,
AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic,
Sanofi-Aventis, and The Medicines Company, and performed unfunded
research for FlowCo, PLx Pharma, and Takeda.
NR 34
TC 13
Z9 17
U1 5
U2 10
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
J9 STROKE
JI Stroke
PD FEB
PY 2013
VL 44
IS 2
BP 373
EP +
DI 10.1161/STROKEAHA.112.673129
PG 9
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 073PK
UT WOS:000313754800024
PM 23306325
ER
PT J
AU Chroinin, DN
Asplund, K
Asberg, S
Callaly, E
Cuadrado-Godia, E
Diez-Tejedor, E
Di Napoli, M
Engelter, ST
Furie, KL
Giannopoulos, S
Gotto, AM
Hannon, N
Jonsson, F
Kapral, MK
Marti-Fabregas, J
Martinez-Sanchez, P
Milionis, HJ
Montaner, J
Muscari, A
Pikija, S
Probstfield, J
Rost, NS
Thrift, AG
Vemmos, K
Kelly, PJ
AF Chroinin, Danielle Ni
Asplund, Kjell
Asberg, Signild
Callaly, Elizabeth
Cuadrado-Godia, Elisa
Diez-Tejedor, Exuperio
Di Napoli, Mario
Engelter, Stefan T.
Furie, Karen L.
Giannopoulos, Sotirios
Gotto, Antonio M., Jr.
Hannon, Niamh
Jonsson, Fredrik
Kapral, Moira K.
Marti-Fabregas, Joan
Martinez-Sanchez, Patricia
Milionis, Haralampos J.
Montaner, Joan
Muscari, Antonio
Pikija, Slaven
Probstfield, Jeffrey
Rost, Natalia S.
Thrift, Amanda G.
Vemmos, Konstantinos
Kelly, Peter J.
TI Statin Therapy and Outcome After Ischemic Stroke Systematic Review and
Meta-Analysis of Observational Studies and Randomized Trials
SO STROKE
LA English
DT Review
DE cerebral infarction; ischemia; neuroprotective agents; outcomes
assessment; stroke; therapy
ID COA REDUCTASE INHIBITOR; NITRIC-OXIDE SYNTHASE; TISSUE-PLASMINOGEN
ACTIVATOR; FOCAL CEREBRAL-ISCHEMIA; INFARCT VOLUME; ACUTE-PHASE;
INTRAVENOUS THROMBOLYSIS; LOWERING TREATMENT; LIPID PROFILE;
PRETREATMENT
AB Background and Purpose-Although experimental data suggest that statin therapy may improve neurological outcome after acute cerebral ischemia, the results from clinical studies are conflicting. We performed a systematic review and meta-analysis investigating the relationship between statin therapy and outcome after ischemic stroke.
Methods-The primary analysis investigated statin therapy at stroke onset (prestroke statin use) and good functional outcome (modified Rankin score 0 to 2) and death. Secondary analyses included the following: (1) acute poststroke statin therapy (<= 72 hours after stroke), and (2) thrombolysis-treated patients.
Results-The primary analysis included 113 148 subjects (27 studies). Among observational studies, statin treatment at stroke onset was associated with good functional outcome at 90 days (pooled odds ratio [OR], 1.41; 95% confidence interval [CI], 1.29-1.56; P<0.001), but not 1 year (OR, 1.12; 95% CI, 0.9-1.4; P=0.31), and with reduced fatality at 90 days (pooled OR, 0.71; 95% CI, 0.62-0.82; P<0.001) and 1 year (OR, 0.80;95% CI, 0.67-0.95; P=0.01). In the single randomized controlled trial reporting 90-day functional outcome, statin treatment was associated with good outcome (OR, 1.5; 95% CI, 1.0-2.24; P=0.05). No reduction in fatality was observed on meta-analysis of data from 3 randomized controlled trials (P=0.9). In studies restricted to of thrombolysis-treated patients, an association between statins and increased fatality at 90 days was observed (pooled OR, 1.25; 95% CI, 1.02-1.52; P=0.03, 3 studies, 4339 patients). However, this association was no longer present after adjusting for age and stroke severity in the largest study (adjusted OR, 1.14; 95% CI, 0.90-1.44; 4012 patients).
Conclusion-In the largest meta-analysis to date, statin therapy at stroke onset was associated with improved outcome, a finding not observed in studies restricted to thrombolysis-treated patients. Randomized trials of statin therapy in acute ischemic stroke are needed. (Stroke. 2013;44:448-456.)
C1 [Chroinin, Danielle Ni; Callaly, Elizabeth; Hannon, Niamh; Kelly, Peter J.] Natl Univ Ireland Univ Coll Dublin, Neurovasc Unit Appl Translat Res & Therapeut, Mater Univ Hosp, Dublin Acad Med Ctr, Dublin, Ireland.
[Asplund, Kjell; Jonsson, Fredrik] Umea Univ Hosp, Dept Med, S-90185 Umea, Sweden.
[Asberg, Signild] Uppsala Univ, Dept Med Sci, Uppsala, Sweden.
[Cuadrado-Godia, Elisa] Hosp del Mar IMIM, Dept Neurol, Barcelona, Spain.
[Diez-Tejedor, Exuperio; Martinez-Sanchez, Patricia] Univ Autonoma Madrid, Dept Neurol, La Paz Univ Hosp, Madrid, Spain.
[Diez-Tejedor, Exuperio; Martinez-Sanchez, Patricia] Univ Autonoma Madrid, Stroke Ctr, La Paz Univ Hosp, Madrid, Spain.
[Di Napoli, Mario] San Camillo deLellis Gen Hosp, Neurol Serv, Rieti, Italy.
[Di Napoli, Mario] Ctr Cardiovasc Med & Cerebrovasc Dis Prevent, SMDN, Laquila, Italy.
[Engelter, Stefan T.] Univ Basel Hosp, Dept Neurol, Basel, Switzerland.
[Furie, Karen L.; Rost, Natalia S.] Massachusetts Gen Hosp, J Philip Kistler Stroke Res Ctr, Ctr Human Genet Res, Boston, MA 02114 USA.
[Giannopoulos, Sotirios; Milionis, Haralampos J.] Univ Ioannina, Sch Med, GR-45110 Ioannina, Greece.
[Gotto, Antonio M., Jr.] Weill Cornell Med Coll, New York, NY USA.
[Kapral, Moira K.] Toronto Gen Hosp, Inst Clin Evaluat Sci, Toronto, ON, Canada.
[Marti-Fabregas, Joan] Hosp Santa Creu & Sant Pau, Barcelona, Spain.
[Montaner, Joan] Autonomous Univ Barcelona, Hosp Vall dHebron, Barcelona, Spain.
[Montaner, Joan] Autonomous Univ Barcelona, Vall dHebron Res Inst VHIR, Barcelona, Spain.
[Muscari, Antonio] Univ Bologna, S Orsola Malpighi Hosp, Bologna, Italy.
[Pikija, Slaven] Gen Hosp Varazdin, Varazhdin, Croatia.
[Probstfield, Jeffrey] Univ Washington, Dept Med, Seattle, WA USA.
[Probstfield, Jeffrey] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Thrift, Amanda G.] Monash Univ, Monash Med Ctr, Stroke & Ageing Res Ctr, Dept Med, Clayton, Vic, Australia.
[Thrift, Amanda G.] Natl Stroke Res Inst, Heidelberg, Vic, Australia.
[Vemmos, Konstantinos] Univ Athens, Dept Therapeut, Alexandra Hosp, GR-10679 Athens, Greece.
RP Chroinin, DN (reprint author), Natl Univ Ireland Univ Coll Dublin, Neurovasc Unit Appl Translat Res & Therapeut, Mater Univ Hosp, Dublin Acad Med Ctr, Dublin, Ireland.
EM dmmnic@umail.ucc.ie
RI Thrift, Amanda/I-6251-2012; Di Napoli, Mario/J-6418-2014; Montaner,
Joan/D-3063-2015; IBIS, NEUROVASCULAR/O-1855-2015; Martinez-Sanchez,
Patricia/O-5687-2016;
OI Thrift, Amanda/0000-0001-8533-4170; Di Napoli,
Mario/0000-0001-9609-4926; Martinez-Sanchez,
Patricia/0000-0003-1945-4435; Diez Tejedor,
Exuperio/0000-0003-2295-1707; Asberg, Signild/0000-0001-8693-1014
FU National Institutes of Health/NINDS [K23NS064052]; National Health and
Medical Research Council of Australia [438700]; Irish Health Services
Executive; National Lottery of Ireland; Servier; Boehringer Ingelheim;
Pfizer Inc; Sanofi-aventis; Shire plc; Kaethe-Zingg-Schwichtenberg-Fonds
of the Swiss Academy of Medical Sciences; Swiss Heart Foundation; Swiss
National Funds; Health Research Board of Ireland; Irish Heart
Foundation; Instituto de Salud Carlo III
FX Dr Rost is supported by the National Institutes of Health/NINDS
(K23NS064052). Dr Thrift is supported by a Senior Research Fellowship
from the National Health and Medical Research Council of Australia
(Grant 438700). Funding was also received by the Neurovascular Unit for
Applied Translational Research and Therapeutics, Dublin from the Irish
Health Services Executive, National Lottery of Ireland, and an
unrestricted educational grant for stroke research and education from
Servier. Funding sources were not involved in the design, conduct,
analysis, or reporting of the study findings.; Dr Diez-Tejedor has
collaborated as a clinical advisor, preclinical and clinical trial
researcher, or as a speaker with the following companies: Astra-Zeneca,
Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Cellerix, Ferrer
Grupo, Pfizer, Sanofi, Sygnis Pharma AG, Roche, and EVER Neuro Pharma.
Dr Engelter has received funding for travel or speaker honoraria from
Boehringer Ingelheim, Pfizer Inc, Sanofi-aventis, and Shire plc; serves
on scientific advisory boards for Bayer and Boehringer Ingelheim and on
the editorial board of Stroke. He has received research support from the
Kaethe-Zingg-Schwichtenberg-Fonds of the Swiss Academy of Medical
Sciences, the Swiss Heart Foundation, and Swiss National Funds. Dr Gotto
Jr is a consultant for Kowa and Merck, and he serves on the Board of
Directors for Aegerion Pharmaceuticals and Arisph Pharmaceuticals. He is
a member of advisory boards for DuPont and Vatera Capital. Dr Hannon is
funded by the Health Research Board of Ireland. Dr Kapral holds a Career
Investigator Award from the Heart and Stroke Foundation of Canada. Dr
Kelly is the recipient of a Clinician Scientist Award from the Health
Research Board of Ireland and research funding from the Irish Heart
Foundation. Dr has collaborated as clinical trial researcher with the
following companies: Astra-Zeneca, Bayer, Bristol-Myers Squibb, Ferrer
Grupo, Pfizer, Sanofi and Roche. Dr Montaner is the Principal
Investigator of the project: EC07/90195: Strategies to improve safety
and efficacy of the treatment with simvastatin in the acute phase of
ischemic stroke: STARS trial, funded by the Instituto de Salud Carlo
III, through a call for nonprofit drugs independent research. The other
authors report no conflicts.
NR 75
TC 25
Z9 26
U1 0
U2 29
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
J9 STROKE
JI Stroke
PD FEB
PY 2013
VL 44
IS 2
BP 448
EP 456
DI 10.1161/STROKEAHA.112.668277
PG 9
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 073PK
UT WOS:000313754800036
ER
PT J
AU Hanchate, AD
Schwamm, LH
Huang, W
Hylek, EM
AF Hanchate, Amresh D.
Schwamm, Lee H.
Huang, Wei
Hylek, Elaine M.
TI Comparison of Ischemic Stroke Outcomes and Patient and Hospital
Characteristics by Race/Ethnicity and Socioeconomic Status
SO STROKE
LA English
DT Article
DE ethnicity; ischemic stroke; inpatient mortality; length of stay; race;
risk factors; socioeconomic status
ID ATHEROSCLEROSIS RISK; NORTHERN MANHATTAN; ETHNIC DISPARITIES;
MEXICAN-AMERICANS; MEDICARE PATIENTS; HEALTH-CARE; FOLLOW-UP; MORTALITY;
POPULATION; QUALITY
AB Background and Purpose-Current literature provides mixed evidence on disparities by race/ethnicity and socioeconomic status in discharge outcomes after hospitalization for acute ischemic stroke. Using comprehensive data from 8 states, we sought to compare inpatient mortality and length of stay by race/ethnicity and socioeconomic status.
Methods-We examined all 2007 hospitalizations for acute ischemic stroke in all nonfederal acute care hospitals in Arizona, California, Florida, Maine, New Jersey, New York, Pennsylvania, and Texas. Population was stratified by race/ethnicity (non-Hispanic whites, non-Hispanic blacks, and Hispanics) and socioeconomic status, measured by median income of patient zip code. For each stratum, we estimated risk-adjusted rates of inpatient mortality and longer length of stay (greater than median length of stay). We also compared the hospitals where these subpopulations received care.
Results-Hispanic and black patients accounted for 14% and 12% of all ischemic stroke admissions (N=147 780), respectively, and had lower crude inpatient mortality rates (Hispanic=4.5%, blacks=4.4%; all P<0.001) compared with white patients (5.8%). Hispanic and black patients were younger and fewer had any form of atrial fibrillation. Adjusted for patient risk, inpatient mortality was similar by race/ethnicity, but was significantly higher for low-income area patients than that for high-income area patients (odds ratio, 1.08; 95% confidence interval, 1.02-1.15). Risk-adjusted rates of longer length of stay were higher among minority and low-income area populations.
Conclusions-Risk-adjusted inpatient mortality was similar among patients by race/ethnicity but higher among patients from lower income areas. However, this pattern was not evident in sensitivity analyses, including the use of mechanical ventilation as a partial surrogate for stroke severity. (Stroke. 2013;44:469-476.)
C1 [Hanchate, Amresh D.] VA Boston Healthcare Syst, Boston, MA USA.
[Hanchate, Amresh D.; Hylek, Elaine M.] Boston Univ, Sch Med, Gen Internal Med Sect, Boston, MA 02118 USA.
[Schwamm, Lee H.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA.
[Schwamm, Lee H.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Huang, Wei] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02118 USA.
[Hylek, Elaine M.] Boston Med Ctr, Boston, MA USA.
RP Hanchate, AD (reprint author), Boston Univ, Sch Med, Gen Internal Med Sect, 801 Massachusetts Ave,2092, Boston, MA 02118 USA.
EM hanchate@bu.edu
OI Hanchate, Amresh/0000-0002-7038-4463; Schwamm, Lee/0000-0003-0592-9145
FU National Institutes of Health [1R21NS062677, 1R01HL106029-01]
FX This research has been funded by National Institutes of Health grants
1R21NS062677 (PI=Dr Hanchate) and 1R01HL106029-01 (principal
investigator=Dr Hylek).
NR 41
TC 9
Z9 10
U1 0
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
J9 STROKE
JI Stroke
PD FEB
PY 2013
VL 44
IS 2
BP 469
EP +
DI 10.1161/STROKEAHA.112.669341
PG 21
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 073PK
UT WOS:000313754800039
PM 23306327
ER
PT J
AU Campos, F
Qin, T
Castillo, J
Seo, JH
Arai, K
Lo, EH
Waeber, C
AF Campos, Francisco
Qin, Tao
Castillo, Jose
Seo, Ji Hae
Arai, Ken
Lo, Eng H.
Waeber, Christian
TI Fingolimod Reduces Hemorrhagic Transformation Associated With Delayed
Tissue Plasminogen Activator Treatment in a Mouse Thromboembolic Model
SO STROKE
LA English
DT Article
DE fingolimod; hemorrhage; stroke; tPA; thromboembolic model
ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; SPHINGOSINE 1-PHOSPHATE
RECEPTOR; ACUTE ISCHEMIC-STROKE; BLOOD-BRAIN-BARRIER; CEREBRAL-ISCHEMIA;
MULTIPLE-SCLEROSIS; LASER SPECKLE; FTY720; RECANALIZATION; REPERFUSION
AB Background and Purpose-The sphingosine 1-phosphate receptor agonist fingolimod reduces infarct size in rodent models of stroke and enhances blood-brain barrier integrity. Based on these observations, we hypothesized that combination of fingolimod with tissue plasminogen activator (tPA) would reduce the risk of hemorrhagic transformation associated with delayed administration of tPA.
Methods-We evaluated the effects of fingolimod in a mouse model of thromboembolic stroke, in which both the beneficial effect of reperfusion associated with early tPA treatment and hemorrhagic transformation associated with delayed administration mimic clinical observations in humans.
Results-Our results demonstrate that fingolimod treatment attenuates the neurological deficit and reduces infarct volume after in situ thromboembolic occlusion of the middle cerebral artery. Combination of fingolimod and tPA improves the neurological outcome of the thrombolytic therapy and reduces the risk of hemorrhagic transformation associated with delayed administration of tPA.
Conclusion-This study confirms the protective efficacy of fingolimod as a treatment against ischemic stroke in another rodent model of stroke (thromboembolic occlusion), and suggests that fingolimod could potentially be used in combination with tPA to reduce the risk of brain hemorrhage. (Stroke. 2013;44:505-511.)
C1 [Campos, Francisco; Qin, Tao; Waeber, Christian] Massachusetts Gen Hosp, Stroke Res Lab, Dept Radiol, Charlestown, MA USA.
[Campos, Francisco; Castillo, Jose] Univ Santiago de Compostela, Clin Neurosci Res Lab, Univ Clin Hosp, Dept Neurol,IDIS, Santiago De Compostela, Spain.
[Seo, Ji Hae; Arai, Ken; Lo, Eng H.] Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Radiol, Charlestown, MA USA.
[Seo, Ji Hae; Arai, Ken; Lo, Eng H.] Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Neurol, Charlestown, MA USA.
RP Waeber, C (reprint author), Natl Univ Ireland Univ Coll Cork, Room 1-26,Cavanagh Pharm Bldg,Coll Rd, Cork, Ireland.
EM c.waeber@ucc.ie
RI Waeber, Christian/A-8333-2009;
OI Waeber, Christian/0000-0001-6078-0027; Castillo,
Jose/0000-0002-6685-3001
FU NIH [NS049263, NS055104]; Interdepartmental Neuroscience Center
[P30NS045776]; Spanish Ministry of Science and Innovation
[SAF2011-30517]; RENEVAS [RD06/0026/000]; Conselleria de Industria,
Xunta de Galicia (Programa Angeles Alvarino)
FX This work was supported by NIH grants (NS049263 and NS055104) to CW and
grant P30NS045776 (Interdepartmental Neuroscience Center). Spanish
Ministry of Science and Innovation SAF2011-30517 AND RENEVAS
(RD06/0026/000). Furthermore, FC is the recipient of a fellowship from
the Conselleria de Industria, Xunta de Galicia (Programa Angeles
Alvarino).
NR 32
TC 28
Z9 31
U1 0
U2 11
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
J9 STROKE
JI Stroke
PD FEB
PY 2013
VL 44
IS 2
BP 505
EP +
DI 10.1161/STROKEAHA.112.679043
PG 16
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 073PK
UT WOS:000313754800044
PM 23287783
ER
PT J
AU Richards, A
Cheng, EM
AF Richards, Adam
Cheng, Eric M.
TI Stroke Risk Calculators in the Era of Electronic Health Records Linked
to Administrative Databases
SO STROKE
LA English
DT Review
DE cardiovascular disease; database management systems; electronic health
records; epidemiology; risk assessment; stroke
ID CORONARY-HEART-DISEASE; GLOBAL CARDIOVASCULAR RISK; TRANSIENT ISCHEMIC
ATTACK; ATRIAL-FIBRILLATION; PRIMARY-CARE; SOCIOECONOMIC-STATUS;
NATIONWIDE COHORT; VALIDATION; PREDICTION; SCORES
C1 [Richards, Adam; Cheng, Eric M.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Cheng, Eric M.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
RP Cheng, EM (reprint author), VA Greater Los Angeles, Dept Neurol, 11301 Wilshire Blvd,ML 127, Los Angeles, CA 90073 USA.
EM eric.cheng@va.gov
FU National Institutes of Health/National Institute of Neurological
Disorders and Stroke [K23NS058571]; UCLA Outcomes Research Center;
American Heart Association Pharmaceutical Roundtable
FX Dr Cheng is supported by a Career Development Award from National
Institutes of Health/National Institute of Neurological Disorders and
Stroke (K23NS058571). Drs Cheng and Richards are supported by the UCLA
Outcomes Research Center, funded through the American Heart Association
Pharmaceutical Roundtable and David and Stevie Spina. The views
expressed in this article are those of the authors and do not
necessarily reflect the position or policy of the Department of Veterans
Affairs or the United States government.
NR 40
TC 2
Z9 3
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 FEB
PY 2013
VL 44
IS 2
BP 564
EP 569
DI 10.1161/STROKEAHA.111.649798
PG 6
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 073PK
UT WOS:000313754800059
PM 23204057
ER
PT J
AU Wahlster, L
Arimon, M
Nasser-Ghodsi, N
Post, KL
Serrano-Pozo, A
Uemura, K
Berezovska, O
AF Wahlster, Lara
Arimon, Muriel
Nasser-Ghodsi, Navine
Post, Kathryn Leigh
Serrano-Pozo, Alberto
Uemura, Kengo
Berezovska, Oksana
TI Presenilin-1 adopts pathogenic conformation in normal aging and in
sporadic Alzheimer's disease
SO ACTA NEUROPATHOLOGICA
LA English
DT Article
DE Alzheimer's disease; Aging; Presenilin-1; Amyloid beta; Oxidative stress
ID AMYLOID-BETA-PROTEIN; MILD COGNITIVE IMPAIRMENT; GAMMA-SECRETASE
ACTIVITY; IN-VIVO; OXIDATIVE STRESS; FRONTOTEMPORAL DEMENTIA;
LIPID-PEROXIDATION; PRECURSOR PROTEIN; SYNAPSE LOSS; MOUSE MODEL
AB Accumulation of amyloid-beta (A beta) and neurofibrillary tangles in the brain, inflammation and synaptic and neuronal loss are some of the major neuropathological hallmarks of Alzheimer's disease (AD). While genetic mutations in amyloid precursor protein and presenilin-1 and -2 (PS1 and PS2) genes cause early-onset familial AD, the etiology of sporadic AD is not fully understood. Our current study shows that changes in conformation of endogenous wild-type PS1, similar to those found with mutant PS1, occur in sporadic AD brain and during normal aging. Using a mouse model of Alzheimer's disease (Tg2576) that overexpresses the Swedish mutation of amyloid precursor protein but has normal levels of endogenous wild-type presenilin, we report that the percentage of PS1 in a pathogenic conformation increases with age. Importantly, we found that this PS1 conformational shift is associated with amyloid pathology and precedes amyloid-beta deposition in the brain. Furthermore, we found that oxidative stress, a common stress characteristic of aging and AD, causes pathogenic PS1 conformational change in neurons in vitro, which is accompanied by increased A beta 42/40 ratio. The results of this study provide important information about the timeline of pathogenic changes in PS1 conformation during aging and suggest that structural changes in PS1/gamma-secretase may represent a molecular mechanism by which oxidative stress triggers amyloid-beta accumulation in aging and in sporadic AD brain.
C1 [Wahlster, Lara; Arimon, Muriel; Nasser-Ghodsi, Navine; Post, Kathryn Leigh; Serrano-Pozo, Alberto; Uemura, Kengo; Berezovska, Oksana] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,MassGen Inst Neurodegenerat Dis MIND, Charlestown, MA 02129 USA.
RP Berezovska, O (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,MassGen Inst Neurodegenerat Dis MIND, CNY 114,16th St, Charlestown, MA 02129 USA.
EM wahlster@stud.uni-heidelberg.de; Arimon.Muriel@mgh.harvard.edu;
NNasserghodsi@gmail.com; klpost@partners.org; ASerrano1@partners.org;
ueken@kuhp.kyoto-u.ac.jp; OBerezovska@partners.org
RI SERRANO-POZO, ALBERTO/F-5119-2013; Arimon, Muriel/I-4054-2015;
OI Arimon, Muriel/0000-0002-0894-3324; SERRANO-POZO,
ALBERTO/0000-0003-0899-7530
FU National Institutes of Health [AG15379]; German National Academic
Foundation ("Studienstiftung des deutschen Volkes"); Fundacion Ibercaja
(Zaragoza, Spain); Fundacion Alfonso Martin Escudero (Madrid, Spain)
FX We thank Dr. Bradley T. Hyman, Dr. Matthew Frosch, Karlotta Fitch, and
the Alzheimer's Disease Research Center for providing the human brain
tissue that was used in this study. This work was supported by National
Institutes of Health Grant [AG15379 to O.B.]; the German National
Academic Foundation ("Studienstiftung des deutschen Volkes")
[scholarship to L. W.]; the Fundacion Ibercaja (Zaragoza, Spain)
[fellowship to M. A.]; the Fundacion Alfonso Martin Escudero (Madrid,
Spain) [fellowship to A.S.P.].
NR 73
TC 20
Z9 20
U1 1
U2 24
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0001-6322
J9 ACTA NEUROPATHOL
JI Acta Neuropathol.
PD FEB
PY 2013
VL 125
IS 2
BP 187
EP 199
DI 10.1007/s00401-012-1065-6
PG 13
WC Clinical Neurology; Neurosciences; Pathology
SC Neurosciences & Neurology; Pathology
GA 074DS
UT WOS:000313793400002
PM 23138650
ER
PT J
AU Byatt, N
Deligiannidis, KM
Freeman, MP
AF Byatt, N.
Deligiannidis, K. M.
Freeman, M. P.
TI Antidepressant use in pregnancy: a critical review focused on risks and
controversies
SO ACTA PSYCHIATRICA SCANDINAVICA
LA English
DT Review
DE antidepressant; in utero; teratogenicity; postnatal adaptation syndrome;
persistent pulmonary hypertension
ID SEROTONIN-REUPTAKE INHIBITORS; PERSISTENT PULMONARY-HYPERTENSION;
IN-UTERO EXPOSURE; MAJOR CONGENITAL-MALFORMATIONS; REPEAT CESAREAN
DELIVERY; MATERNAL USE; PRENATAL EXPOSURE; BIRTH OUTCOMES; NEONATAL
OUTCOMES; WITHDRAWAL SYNDROME
AB Objective Conflicting data have led to controversy regarding antidepressant use during pregnancy. The objectives of this study are to i) review the risks of untreated depression and anxiety, ii) review the literature on risks of exposure to antidepressants during pregnancy, iii) discuss the strengths and weaknesses of the different study designs used to evaluate those risks, and iv) provide clinical recommendations. Method MEDLINE/PubMed was searched for reports and studies on the risk of first-trimester teratogenicity, postnatal adaptation syndrome (PNAS), and persistent pulmonary hypertension (PPHN) with in utero antidepressant exposure. Results While some individual studies suggest associations between some specific major malformations, the findings are inconsistent. Therefore, the absolute risks appear small. PNAS occurs in up to 30% of neonates exposed to antidepressants. In some studies, PPHN has been weakly associated with in utero antidepressant exposure, while in other studies, there has been no association. Conclusion Exposures of concern include that of untreated maternal illness as well as medication exposure. It is vital to have a careful discussion, tailored to each patient, which incorporates the evidence to date and considers methodological and statistical limitations. Past medication trials, previous success with symptom remission, and women's preference should guide treatment decisions.
C1 [Byatt, N.; Deligiannidis, K. M.] Univ Massachusetts, Sch Med, UMass Mem Med Ctr,Ctr Psychopharmacol Res & Treat, Depress Specialty Clin,Womens Mental Hlth Special, Worcester, MA 01655 USA.
[Freeman, M. P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Psychiat Perinatal & Reprod Psychiat Program, Boston, MA USA.
RP Byatt, N (reprint author), Univ Massachusetts, Sch Med, UMass Mem Med Ctr,Ctr Psychopharmacol Res & Treat, Depress Specialty Clin,Womens Mental Hlth Special, 55 Lake Ave N, Worcester, MA 01655 USA.
EM nancy.byatt@umassmemorial.org
RI Deligiannidis, Kristina/C-3654-2014;
OI Deligiannidis, Kristina/0000-0001-7439-2236; Byatt,
Nancy/0000-0002-4010-8919
FU NCATS NIH HHS [KL2 TR000160, UL1 TR000161]
NR 160
TC 52
Z9 53
U1 5
U2 52
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0001-690X
J9 ACTA PSYCHIAT SCAND
JI Acta Psychiatr. Scand.
PD FEB
PY 2013
VL 127
IS 2
BP 94
EP 114
DI 10.1111/acps.12042
PG 21
WC Psychiatry
SC Psychiatry
GA 070FT
UT WOS:000313492300002
PM 23240634
ER
PT J
AU Yaffe, K
Ackerson, L
Hoang, TD
Go, AS
Maguire, MG
Ying, GS
Daniel, E
Bazzano, LA
Coleman, M
Cohen, DL
Kusek, JW
Ojo, A
Seliger, S
Xie, DW
Grunwald, JE
AF Yaffe, Kristine
Ackerson, Lynn
Hoang, Tina D.
Go, Alan S.
Maguire, Maureen G.
Ying, Gui-Shuang
Daniel, Ebenezer
Bazzano, Lydia A.
Coleman, Martha
Cohen, Debbie L.
Kusek, John W.
Ojo, Akinlolu
Seliger, Stephen
Xie, Dawei
Grunwald, Juan E.
CA CRIC Study Investigators
TI Retinopathy and Cognitive Impairment in Adults With CKD
SO AMERICAN JOURNAL OF KIDNEY DISEASES
LA English
DT Article
DE Chronic kidney disease; cognitive impairment; retinopathy
ID RETINAL MICROVASCULAR ABNORMALITIES; CHRONIC KIDNEY-DISEASE;
SMALL-VESSEL DISEASE; GLOMERULAR-FILTRATION-RATE; CARDIOVASCULAR HEALTH;
ATHEROSCLEROSIS RISK; ELDERLY POPULATION; RENAL-DISEASE; OLDER-ADULTS;
FOLLOW-UP
AB Background: Retinal microvascular abnormalities have been associated with cognitive impairment, possibly serving as a marker of cerebral small-vessel disease. This relationship has not been evaluated in persons with chronic kidney disease (CKD), a condition associated with increased risk of both retinal pathology and cognitive impairment.
Study Design: Cross-sectional study.
Setting & Participants: 588 participants 52 years or older with CKD in the Chronic Renal Insufficiency Cohort (CRIC) Study.
Predictor: Retinopathy graded using the Early Treatment Diabetic Retinopathy Study severity scale and diameters of retinal vessels.
Outcomes: Neuropsychological battery of 6 cognitive tests.
Measurements: Logistic regression models were used to evaluate the association of retinopathy, individual retinopathy features, and retinal vessel diameters with cognitive impairment (<= 1 SD from the mean), and linear regression models were used to compare cognitive test scores across levels of retinopathy, adjusting for age, race, sex, education, and medical comorbid conditions.
Results: The mean age of the cohort was 65.3 +/- 5.6 (SD) years, 51.9% were nonwhite, and 52.6% were men. The prevalence of retinopathy was 30.1%, and the prevalence of cognitive impairment was 14.3%. Compared with those without retinopathy, participants with retinopathy had an increased likelihood of cognitive impairment on executive function (35.1% vs 11.5%; OR, 3.4 [ 95% CI, 2.0-6.0]), attention (26.7% vs 7.3%; OR, 3.0 [ 95% CI, 1.8-4.9]), and naming (26.0% vs 10.0%; OR, 2.1 [ 95% CI, 1.2-3.4]) after multivariable adjustment. Increased level of retinopathy also was associated with lower cognitive performance on executive function and attention. Microaneurysms were associated with cognitive impairment on some domains, but there were no significant associations with other retinal measures after multivariable adjustment.
Limitations: Unknown temporal relationship between retinopathy and impairment.
Conclusions: In adults with CKD, retinopathy is associated with poor performance on several cognitive domains, including executive function and attention. Evaluation of retinal microvascular abnormalities may be a promising tool for identifying patients with CKD who are at increased risk of cognitive impairment. Am J Kidney Dis. 61(2): 219-227. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. This is a US Government Work. There are no restrictions on its use.
C1 [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94121 USA.
[Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA.
[Ackerson, Lynn; Go, Alan S.] Kaiser Permanente, Div Res, Oakland, CA USA.
[Hoang, Tina D.] No Calif Inst Res & Educ, San Francisco, CA USA.
[Maguire, Maureen G.; Ying, Gui-Shuang; Daniel, Ebenezer; Grunwald, Juan E.] Univ Penn, Dept Ophthalmol, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Bazzano, Lydia A.] Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA USA.
[Coleman, Martha] Univ Hosp Cleveland, Cleveland Clin Fdn, Cleveland, OH 44106 USA.
[Cohen, Debbie L.] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Kusek, John W.] NIDDKD, Div Kidney Urol & Hematol Dis, Bethesda, MD USA.
[Ojo, Akinlolu] Univ Michigan Hlth Syst, Dept Internal Med, Ann Arbor, MI USA.
[Ojo, Akinlolu] Univ Michigan Hlth Syst, Dept Nephrol, Ann Arbor, MI USA.
[Seliger, Stephen] Univ Maryland, Sch Med, Div Nephrol, Baltimore, MD 21201 USA.
[Xie, Dawei] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
RP Yaffe, K (reprint author), Univ Calif San Francisco, Dept Psychiat, Box 181,4150 Clement St, San Francisco, CA 94121 USA.
EM kristine.yaffe@ucsf.edu
OI Daniel, Ebenezer/0000-0002-2027-2316
FU National Institutes of Health (NIH) [U01 DK060980, U01 DK060902, U01
DK060963, U01 DK060984, U01 DK060990, U01 DK061021, U01 DK061022];
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
[UL1 RR-024134, UL1 RR-025005, MO1 RR-16500, UL1 RR-024989, MO1
RR-000042, UL1 RR-024986, UL1 RR-029879, UL1 RR-024131]; NIDDK grant
[R01 DK069406]; NIH [R01 DK74151]; Vivian S. Lasko Research Fund; Nina
C. Mackall Trust, and Research to Prevent Blindness
FX The CRIC Study is funded by National Institutes of Health (NIH) grants
U01 DK060980, U01 DK060902, U01 DK060963, U01 DK060984, U01 DK060990,
U01 DK061021, and U01 DK061022 and National Institute of Diabetes and
Digestive and Kidney Diseases (NIDDK) grants UL1 RR-024134, UL1
RR-025005, MO1 RR-16500, UL1 RR-024989, MO1 RR-000042, UL1 RR-024986,
UL1 RR-029879, and UL1 RR-024131. The ancillary studies also were
supported by NIDDK grant R01 DK069406, which was administered by the
Northern California Institute for Research and Education and with
resources of the Veterans Affairs Medical Center, San Francisco, CA, and
by NIH R01 DK74151, Vivian S. Lasko Research Fund, Nina C. Mackall
Trust, and Research to Prevent Blindness.
NR 47
TC 9
Z9 10
U1 0
U2 7
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0272-6386
J9 AM J KIDNEY DIS
JI Am. J. Kidney Dis.
PD FEB
PY 2013
VL 61
IS 2
BP 219
EP 227
DI 10.1053/j.ajkd.2012.10.006
PG 9
WC Urology & Nephrology
SC Urology & Nephrology
GA 071KP
UT WOS:000313591800008
PM 23206534
ER
PT J
AU La Fountaine, MF
Rivera, DR
Radulovic, M
Bauman, WA
AF La Fountaine, Michael F.
Rivera, Dwindally Rosado
Radulovic, Miroslav
Bauman, William A.
TI The Hemodynamic Actions of Insulin Are Blunted in the Sublesional
Microvasculature of Healthy Persons with Spinal Cord Injury
SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION
LA English
DT Article
DE Iontophoresis; Insulin; Autonomic; Laser Doppler Flowmetry; Skin Blood
Flow
ID SKELETAL-MUSCLE VASODILATION; NITRIC-OXIDE RELEASE;
CARDIOVASCULAR-DISEASE; ENDOTHELIAL FUNCTION; GLUCOSE-INTOLERANCE;
BLOOD-FLOW; SKIN; RESISTANCE; HUMANS; RISK
AB La Fountaine MF, Rivera DR, Radulovic M, Bauman WA: The hemodynamic actions of insulin are blunted in the sublesional microvasculature of healthy persons with spinal cord injury. Am J Phys Med Rehabil 2013;92:127-135.
Objective: The aim of this study was to gain a better understanding of the hemodynamic actions of insulin on cutaneous microcirculation in persons with spinal cord injury (SCI).
Design: A prospective, open-label, nonrandomized, placebo-controlled investigation was performed in an otherwise healthy cohort of persons with SCI (n = 10) and in an age- and sex-matched cohort of control subjects whose neurologic function is intact (n = 10). Laser Doppler flowmetry characterized the peak blood perfusion unit (BPU) response (percent change from baseline) to insulin or placebo iontophoresis above and below the neurologic level of injury.
Results: Placebo iontophoresis did not result in any statistically significant changes in BPU. In the arm, insulin iontophoresis resulted in a 20% mean increase in BPU (P < 0.05) in the control group and a 9% mean increase in the SCI group (P = 0.14). In the leg, insulin iontophoresis resulted in an 81% (P < 0.01) mean increase in BPU in the control group and a 29% (P < 0.001) mean increase in BPU in the SCI group. The relative effect of insulin on the lower extremity BPU response was significantly greater (P < 0.05) in the control group compared with the SCI group (77% vs. 35%, respectively).
Conclusions: The hemodynamic actions of insulin are markedly blunted in the sublesional microvasculature of persons with SCI, most likely as a result of impaired sublesional sympathetic nervous system control.
C1 [La Fountaine, Michael F.; Rivera, Dwindally Rosado; Radulovic, Miroslav; Bauman, William A.] James J Peters VA Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, Bronx, NY 10468 USA.
[La Fountaine, Michael F.; Radulovic, Miroslav; Bauman, William A.] James J Peters VA Med Ctr, Med Serv, Bronx, NY 10468 USA.
[La Fountaine, Michael F.; Bauman, William A.] Mt Sinai Sch Med, Dept Med, New York, NY USA.
[Radulovic, Miroslav] Mt Sinai Sch Med, Dept Rehabil Med, New York, NY USA.
[La Fountaine, Michael F.] Seton Hall Univ, Dept Phys Therapy, Sch Hlth & Med Sci, S Orange, NJ 07079 USA.
RP La Fountaine, MF (reprint author), James J Peters VA Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, 130 W Kingsbridge Rd, Bronx, NY 10468 USA.
FU Veterans Affairs Rehabilitation Research & Development National Center
of Excellence for the Medical Consequences of Spinal Cord Injury
[B9212-C]; James J. Peters VA Medical Center; James J. Peters VA Medical
Center, Bronx, NY; Department of Veterans Affairs Rehabilitation
Research & Development Service
FX Funded by the Veterans Affairs Rehabilitation Research & Development
National Center of Excellence for the Medical Consequences of Spinal
Cord Injury (#B9212-C) and James J. Peters VA Medical Center.; The
authors thank James J. Peters VA Medical Center, Bronx, NY, and the
Department of Veterans Affairs Rehabilitation Research & Development
Service for their support.
NR 31
TC 0
Z9 0
U1 1
U2 2
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 FEB
PY 2013
VL 92
IS 2
BP 127
EP 135
DI 10.1097/PHM.0b013e31827d63ee
PG 9
WC Rehabilitation; Sport Sciences
SC Rehabilitation; Sport Sciences
GA 072KA
UT WOS:000313668600004
PM 23328885
ER
PT J
AU Wang, QM
Wei, Y
Zheng, Y
Waeber, C
AF Wang, Qing Mei
Wei, Ying
Zheng, Yi
Waeber, Christian
TI Efficacy of Combined Atorvastatin and Sildenafil in Promoting Recovery
After Ischemic Stroke in Mice
SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION
LA English
DT Article
DE Stroke; Atorvastatin; Sildenafil; Recovery; Angiogenesis
ID FUNCTIONAL RECOVERY; CEREBRAL-ISCHEMIA; NEUROGENESIS; STATIN;
ANGIOGENESIS; INJURY; RATS; INFLAMMATION; SIMVASTATIN; PROTECTION
AB Wang QM, Wei Y, Zheng Y, Waeber C: Efficacy of combined atorvastatin and sildenafil in promoting recovery after ischemic stroke in mice. Am J Phys Med Rehabil 2013;92:143-150.
Objective: The aim of this study was to test the hypothesis that a combination of atorvastatin and sildenafil promotes recovery in an additive manner after ischemic stroke in mice.
Design: Adult C57BL/6 mice (n = 67) were subjected to transient middle cerebral artery occlusion. Vehicle-control (H2O), atorvastatin (0.3 mg/kg), sildenafil (0.3 mg/kg), or combined atorvastatin (0.3 mg/kg) and sildenafil (0.3 mg/kg) were administrated via oral gavage daily for 6 days starting 24 hrs after ischemia. Behavioral studies including neurologic score and adhesive removal test were performed before surgery and on postoperative days 1 and 7; cylinder test was performed before surgery and on postoperative day 7. Mice were killed after 7 days and brain slices were stained with hematoxylin and eosin to measure the infarct volume.
Results: The combination group performed significantly better in the adhesive removal test (mean +/- SD) (50 +/- 54 secs) as compared with the control group (147 +/- 109 secs) (P < 0.05) and to atorvastatin (144 +/- 102 secs) (P < 0.05) but did not show statistically significant improvement as compared with sildenafil (107 +/- 115 secs) (P = 0.148). There were no significant differences among the groups in neurologic score and cylinder test. There was no significant difference in the infarct volume.
Conclusions: The data suggest that combined atorvastatin and sildenafil generates a better functional outcome as compared with atorvastatin-only treatment, but not sildenafil-only treatment, in one of multiple variables tested.
C1 [Wang, Qing Mei] Harvard Univ, Dept Phys Med & Rehabil, Spaulding Rehabil Hosp, Sch Med, Boston, MA 02114 USA.
[Wei, Ying; Zheng, Yi; Waeber, Christian] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Wang, QM (reprint author), Harvard Univ, Dept Phys Med & Rehabil, Spaulding Rehabil Hosp, Sch Med, 125 Nashua St, Boston, MA 02114 USA.
RI Waeber, Christian/A-8333-2009
OI Waeber, Christian/0000-0001-6078-0027
FU Rehabilitation Medicine Scientist Training Program
FX The authors disclosure unlabeled use of pharmaceutical products on the
animals in this study. No human subjects were involved. Dr Qing Mei Wang
is funded by the Rehabilitation Medicine Scientist Training Program.
There is no financial disclosure from any of the authors.
NR 30
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U1 0
U2 10
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 FEB
PY 2013
VL 92
IS 2
BP 143
EP 150
DI 10.1097/PHM.0b013e3182643f1a
PG 8
WC Rehabilitation; Sport Sciences
SC Rehabilitation; Sport Sciences
GA 072KA
UT WOS:000313668600006
PM 22854903
ER
PT J
AU Elias, JA
Morgenroth, DC
AF Elias, Joseph Abraham
Morgenroth, David Crespi
TI Amputee Care Education in Physical Medicine and Rehabilitation Residency
Programs
SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION
LA English
DT Article
DE Residency; Amputee; Education; Physical Medicine and Rehabilitation
ID LOWER-LIMB AMPUTATIONS; MUSCULOSKELETAL EDUCATION; INPATIENT
REHABILITATION; UNITED-STATES; BACK-PAIN; PREVALENCE; OSTEOARTHRITIS;
SERVICES; KNEE
AB Elias JA, Morgenroth DC: Amputee care education in physical medicine and rehabilitation residency programs. Am J Phys Med Rehabil 2013;92:157-162.
Objective: The aim of this study was to assess amputee care-related educational offerings and barriers to further educational opportunities in United States physical medicine and rehabilitation residency programs.
Design: A two-part survey was distributed to all United States physical medicine and rehabilitation residency program directors. Part 1 assessed the use of educational tools in amputee education. Part 2 assessed the potential barriers to amputee care-related education.
Results: Sixty-nine percent of the program directors responded. Seventy-five percent or more of the programs that responded have didactic lectures; grand rounds; reading lists; self-assessment exam review; gait analysis training; training with prosthetists; faculty with amputee expertise; and amputee care during inpatient, outpatient, and consult rotations. Less than 25% of the programs use intranet resources. No more than 14% of the programs said any one factor was a major barrier. However, some of the most prominent major barriers were limited faculty number, finances, and patient volume. The factors many of the programs considered somewhat of a barrier included lack of national standardized resources for curriculum, resident time, and faculty time.
Conclusions: This study identified the most commonly used amputee educational opportunities and methods in physical medicine and rehabilitation residencies as well as the barriers to furthering resident amputee education. Developing Web-based resources on amputee care and increasing awareness of physiatrists as perioperative consultants could improve resident amputee education and have important implications toward optimizing care of individuals with amputation.
C1 [Elias, Joseph Abraham; Morgenroth, David Crespi] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA.
[Morgenroth, David Crespi] Dept Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA.
RP Morgenroth, DC (reprint author), Vet Affairs Puget Sound Hlth Care Syst, 1660 S Columbian Way,RCS-117, Seattle, WA 98108 USA.
OI Morgenroth, David/0000-0002-0226-7775
NR 24
TC 1
Z9 1
U1 0
U2 6
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 FEB
PY 2013
VL 92
IS 2
BP 157
EP 162
DI 10.1097/PHM.0b013e318269d7c8
PG 6
WC Rehabilitation; Sport Sciences
SC Rehabilitation; Sport Sciences
GA 072KA
UT WOS:000313668600008
PM 23334616
ER
PT J
AU Ip, PPC
Irving, JA
McCluggage, WG
Clement, PB
Young, RH
AF Ip, Philip P. C.
Irving, Julie A.
McCluggage, W. Glenn
Clement, Philip B.
Young, Robert H.
TI Papillary Proliferation of the Endometrium A Clinicopathologic Study of
59 Cases of Simple and Complex Papillae Without Cytologic Atypia
SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY
LA English
DT Article
DE papillary proliferation; papillary endometrial hyperplasia; papillary
carcinoma; endometrial carcinoma; endometrial polyp; mucinous
hyperplasia; Lehman and Hart
ID WELL-DIFFERENTIATED CARCINOMA; K-RAS MUTATIONS; MICROSATELLITE
INSTABILITY; MUCINOUS ADENOCARCINOMA; DIAGNOSTIC PITFALLS; SEROUS
CARCINOMA; SYNCYTIAL CHANGE; HYPERPLASIA; PATHOLOGY; CRITERIA
AB Papillary proliferation of the endometrium (PPE) without cytologic atypia is uncommon and has only been studied in detail by Lehman and Hart in 2001. On histologic examination, PPE ranges from simple papillae with fibrovascular cores, often involving the surface of endometrial polyps, to complex intracystic proliferations; some consider the latter to be analogous to nonatypical complex hyperplasia. To further characterize PPE, with emphasis on the risk of and features associated with concurrent or subsequent neoplasia, the clinicopathologic features of 59 cases without cytologic atypia were studied. The cases were classified into 2 groups according to the degree of architectural complexity and extent of proliferation. Group 1 consisted of those with localized simple papillae. Simple papillae were defined as those with short, predominantly nonbranching stalks; those with occasional secondary branches and/or detached papillae were also included in this group. Localized proliferations were those with 1 or 2 foci involving the surface or the subjacent glands of polyps or nonpolypoid endometrium. Group 2 consisted of those with complex papillae and/or those with diffuse and crowded intracystic papillae. Complex papillae were those with either short or long stalks, with frequent secondary and complex branches. Diffuse proliferation was defined as presence of 3 or more foci within a specimen or involvement of > 50% of the endometrial polyp by simple or complex PPE. Any coexistent or subsequent hyperplasia of conventional type (World Health Organization classification) or adenocarcinoma was recorded. The age of patients ranged from 23 to 82 years (median, 53 y); 36 (61%) were postmenopausal. The majority presented with abnormal vaginal bleeding. Sixteen patients (27%) were receiving hormonal preparations including 5 who were treated with a progestogen for preexisting endometrial hyperplasia or low-grade endometrioid adenocarcinoma. The histologic diagnosis of PPE was made in 49 biopsies and in 10 hysterectomy specimens. Thirty-six cases (61%) were classified as group 1 and 23 (39%) as group 2. In 47 cases (80%), there was a coexisting endometrial polyp, 39 (66%) of which were involved by the PPE. Fifty-three cases (90%) had coexisting epithelial metaplastic changes, 41 (77%) of which were involved by the PPE. The most common type of metaplasia was mucinous (41 of 59 cases, or 69%). Follow-up information was known for 46 patients (78%). Coexistent or subsequent nonatypical and atypical hyperplasia was found in 8 (17%) and 6 cases (13%), respectively. In 6 of the 46 cases (13%), a low-grade endometrioid adenocarcinoma was present either in the original specimen or during follow-up. In contrast to group 1 PPE, those with group 2 features were significantly associated with concurrent or subsequent premalignant lesions (non-atypical and atypical hyperplasia) or carcinoma (P < 0.0001). This study indicates that localized and architecturally simple PPEs confined to a completely removed polyp are usually associated with a benign outcome and may be appropriately labeled as "benign papillary proliferation of the endometrium." Lesions with architecturally complex papillae, especially when extensive, have an increased risk of concurrent or subsequent endometrial hyperplasia and carcinoma and should probably be regarded as analogous to atypical complex hyperplasia, and the term "complex papillary hyperplasia" is appropriate.
As the distinction between simple and complex PPE may be difficult in small endometrial aspirational samples, consideration for curettage should be given to ascertain whether the lesion has been completely removed.
C1 [Ip, Philip P. C.] Univ Hong Kong, Queen Mary Hosp, Dept Pathol, Hong Kong, Hong Kong, Peoples R China.
[Irving, Julie A.] Royal Jubilee Hosp, Dept Pathol, Victoria, BC, Canada.
[Clement, Philip B.] Vancouver Gen Hosp, Dept Pathol, Vancouver, BC V5Z 1M9, Canada.
[McCluggage, W. Glenn] Belfast Hlth & Social Care Trust, Dept Pathol, Belfast, Antrim, North Ireland.
[Young, Robert H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Lab, Boston, MA USA.
RP Ip, PPC (reprint author), Univ Hong Kong, Queen Mary Hosp, Dept Pathol, Hong Kong, Hong Kong, Peoples R China.
EM philipip@pathology.hku.hk
NR 52
TC 9
Z9 9
U1 2
U2 10
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 FEB
PY 2013
VL 37
IS 2
BP 167
EP 177
DI 10.1097/PAS.0b013e318272d428
PG 11
WC Pathology; Surgery
SC Pathology; Surgery
GA 071FY
UT WOS:000313576200002
PM 23211295
ER
PT J
AU Onozato, ML
Kovach, AE
Yeap, BY
Morales-Oyarvide, V
Klepeis, VE
Tammireddy, S
Heist, RS
Mark, EJ
Dias-Santagata, D
Iafrate, AJ
Yagi, Y
Mino-Kenudson, M
AF Onozato, Maristela L.
Kovach, Alexandra E.
Yeap, Beow Y.
Morales-Oyarvide, Vicente
Klepeis, Veronica E.
Tammireddy, Swathi
Heist, Rebecca S.
Mark, Eugene J.
Dias-Santagata, Dora
Iafrate, A. John
Yagi, Yukako
Mino-Kenudson, Mari
TI Tumor Islands in Resected Early-stage Lung Adenocarcinomas are
Associated With Unique Clinicopathologic and Molecular Characteristics
and Worse Prognosis
SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY
LA English
DT Article
DE lung adenocarcinoma; 3D; intra-alveolar; tumor islands; prognosis
ID SIGNIFICANTLY POOR-PROGNOSIS; DISTINCT PATHOLOGICAL MARKER;
MICROPAPILLARY PATTERN; INTERNATIONAL-ASSOCIATION; HISTOLOGIC SUBTYPE;
CANCER; CLASSIFICATION; COMPONENT; BRONCHIOLOALVEOLAR; EXPRESSION
AB Tumor islands-large collections of tumor cells isolated within alveolar spaces-can be seen in lung adenocarcinomas. Recently we observed by 3-dimensional reconstruction that these structures were connected with each other and with the main tumor in different tissue planes, raising the possibility of tumor islands being a means of extension. However, the clinical and prognostic significance of tumor islands remains unknown. In this study, we compared clinicopathologic and molecular characteristics and prognosis of stages I to II lung adenocarcinomas with tumor islands (n = 58) and those without (n = 203). Lung adenocarcinomas with tumor islands were more likely to occur in smokers, exhibit higher nuclear grade and a solid or micropapillary pattern of growth, and harbor KRAS mutations. In contrast, lung adenocarcinomas without tumor islands were more likely to present as minimally invasive adenocarcinoma, show a lepidic pattern of growth, and harbor EGFR mutations. Although there was no difference in stage, the prognosis of lung adenocarcinomas with tumor islands was significantly worse than those without. The 5-year recurrence-free survival for patients with tumor islands and those without was 44.6% and 74.4%, respectively (log rank P = 0.010). The survival difference remained significant (P < 0.020) by multivariate analysis, and the presence of tumor islands was associated with almost 2-fold increase in the risk of recurrence. Even in the stage IA cohort, more than half of the patients with tumor islands experienced recurrence within 5 years. Thus, aggressive surveillance and/or further intervention may be indicated for patients whose tumors exhibit tumor islands.
C1 [Onozato, Maristela L.; Kovach, Alexandra E.; Morales-Oyarvide, Vicente; Klepeis, Veronica E.; Mark, Eugene J.; Dias-Santagata, Dora; Iafrate, A. John; Yagi, Yukako; Mino-Kenudson, Mari] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Yeap, Beow Y.; Tammireddy, Swathi; Heist, Rebecca S.; Dias-Santagata, Dora; Iafrate, A. John; Mino-Kenudson, Mari] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
[Yeap, Beow Y.; Heist, Rebecca S.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Mark, Eugene J.; Dias-Santagata, Dora; Iafrate, A. John; Yagi, Yukako; Mino-Kenudson, Mari] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RP Mino-Kenudson, M (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Warren 122, Boston, MA 02114 USA.
EM mminokenudson@partners.org
FU National Cancer Institute Lung SPORE [P50-CA090578]
FX B.Y. was supported by grants from the National Cancer Institute Lung
SPORE P50-CA090578. The authors have disclosed that they have no
significant relationships with, or financial interest in, any commercial
companies pertaining to this article.
NR 27
TC 21
Z9 22
U1 1
U2 4
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 FEB
PY 2013
VL 37
IS 2
BP 287
EP 294
DI 10.1097/PAS.0b013e31826885fb
PG 8
WC Pathology; Surgery
SC Pathology; Surgery
GA 071FY
UT WOS:000313576200017
PM 23095504
ER
PT J
AU Montecucco, F
Bauer, I
Braunersreuther, V
Bruzzone, S
Akhmedov, A
Luscher, TF
Speer, T
Poggi, A
Mannino, E
Pelli, G
Galan, K
Bertolotto, M
Lenglet, S
Garuti, A
Montessuit, C
Lerch, R
Pellieux, C
Vuilleumier, N
Dallegri, F
Mage, J
Sebastian, C
Mostoslavsky, R
Gayet-Ageron, A
Patrone, F
Mach, F
Nencioni, A
AF Montecucco, Fabrizio
Bauer, Inga
Braunersreuther, Vincent
Bruzzone, Santina
Akhmedov, Alexander
Luescher, Thomas F.
Speer, Timo
Poggi, Alessandro
Mannino, Elena
Pelli, Graziano
Galan, Katia
Bertolotto, Maria
Lenglet, Sebastien
Garuti, Anna
Montessuit, Christophe
Lerch, Rene
Pellieux, Corinne
Vuilleumier, Nicolas
Dallegri, Franco
Mage, Jacqueline
Sebastian, Carlos
Mostoslavsky, Raul
Gayet-Ageron, Angele
Patrone, Franco
Mach, Francois
Nencioni, Alessio
TI Inhibition of Nicotinamide Phosphoribosyltransferase Reduces
Neutrophil-Mediated Injury in Myocardial Infarction
SO ANTIOXIDANTS & REDOX SIGNALING
LA English
DT Article
ID COLONY-ENHANCING FACTOR; CARDIAC MYOCYTES; OXIDATIVE STRESS; NAD;
ISCHEMIA/REPERFUSION; VISFATIN; HEART; MICE; ATHEROSCLEROSIS;
LYMPHOCYTES
AB Aims: Nicotinamide phosphoribosyltransferase (Nampt) is a key enzyme for nicotinamide adenine dinucleotide (NAD(+)) biosynthesis, and recent evidence indicates its role in inflammatory processes. Here, we investigated the potential effects of pharmacological Nampt inhibition with FK866 in a mouse myocardial ischemia/reperfusion model. In vivo and ex vivo mouse myocardial ischemia/reperfusion procedures were performed. Results: Treatment with FK866 reduced myocardial infarct size, neutrophil infiltration, and reactive oxygen species (ROS) generation within infarcted hearts in vivo in a mouse model of ischemia and reperfusion. The benefit of FK866 was not shown in the Langendorff model (ex vivo model of working heart without circulating leukocytes), suggesting a direct involvement of these cells in cardiac injury. Sera from FK866-treated mice showed reduced circulating levels of the neutrophil chemoattractant CXCL2 and impaired capacity to prime migration of these cells in vitro. The release of CXCL8 (human homolog of murine chemokine CXCL2) by human peripheral blood mononuclear cells (PBMCs) and Jurkat cells was also reduced by FK866, as well as by sirtuin (SIRT) inhibitors and SIRT6 silencing, implying a pivotal role for this NAD(+)-dependent deacetylase in the production of this chemokine. Innovation: The pharmacological inhibition of Nampt might represent an effective approach to reduce neutrophilic inflammation-and oxidative stress-mediated tissue damage in early phases of reperfusion after a myocardial infarction. Conclusions: Nampt inhibition appears as a new strategy to dampen CXCL2-induced neutrophil recruitment and thereby reduce neutrophil-mediated tissue injury in mice. Antioxid. Redox Signal. 18, 630-641.
C1 [Montecucco, Fabrizio; Braunersreuther, Vincent; Pelli, Graziano; Galan, Katia; Lenglet, Sebastien; Montessuit, Christophe; Lerch, Rene; Pellieux, Corinne; Mage, Jacqueline; Mach, Francois] Univ Hosp Geneva, Div Cardiol, Fdn Med Res, Fac Med,Dept Internal Med, CH-1211 Geneva, Switzerland.
[Vuilleumier, Nicolas] Univ Hosp Geneva, Dept Genet & Lab Med, Div Lab Med, CH-1211 Geneva, Switzerland.
[Gayet-Ageron, Angele] Univ Hosp Geneva, Div Clin Epidemiol, CH-1211 Geneva, Switzerland.
[Bauer, Inga; Bertolotto, Maria; Garuti, Anna; Dallegri, Franco; Patrone, Franco; Nencioni, Alessio] Univ Genoa, Dept Internal Med, I-16126 Genoa, Italy.
[Bruzzone, Santina; Mannino, Elena] Univ Genoa, Biochem Sect, Dept Expt Med, Genoa, Italy.
[Akhmedov, Alexander; Luescher, Thomas F.; Speer, Timo] Univ Zurich Hosp, Ctr Cardiovasc, CH-8091 Zurich, Switzerland.
[Poggi, Alessandro] Natl Inst Canc Res, Unit Mol Oncol & Angiogenesis, Genoa, Italy.
[Sebastian, Carlos; Mostoslavsky, Raul] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA.
RP Montecucco, F (reprint author), Univ Hosp Geneva, Div Cardiol, Dept Med, Fdn Med Res, 64 Ave Roseraie, CH-1211 Geneva, Switzerland.
EM fabrizio.montecucco@unige.ch
RI Montessuit, Christophe/B-5650-2011; LENGLET, Sebastien/N-8923-2013;
Bruzzone, Santina/A-4264-2015; Poggi, Alessandro/K-6664-2016;
Montecucco, Fabrizio/K-8543-2016;
OI Montessuit, Christophe/0000-0002-2580-7711; LENGLET,
Sebastien/0000-0002-4853-8163; Bruzzone, Santina/0000-0003-2034-3716;
Poggi, Alessandro/0000-0002-1860-430X; Montecucco,
Fabrizio/0000-0003-0823-8729; Gayet-Ageron, Angele/0000-0002-6164-9693;
DALLEGRI, FRANCO/0000-0001-9537-4547; Speer,
Thimoteus/0000-0002-2491-6393; Bertolotto, Maria
Bianca/0000-0002-4889-8046
FU EU [201668]; AtheroRemo; Novartis Foundation; Swiss National Science
Foundation [310030B-133127]; Montecucco [32003B-134963/1]; Associazione
Italiana per la Ricerca sul Cancro; Associazione Italiana per la Lotta
alle Leucemie/Linfomi e al Mieloma; University of Genoa
FX This research was funded by EU FP7, Grant number 201668, AtheroRemo and
by Novartis Foundation to Mach, by grants from the Swiss National
Science Foundation (to Mach [# 310030B-133127] and Montecucco [#
32003B-134963/1]), by the Associazione Italiana per la Ricerca sul
Cancro (to Nencioni and Bauer), by the Associazione Italiana per la
Lotta alle Leucemie/Linfomi e al Mieloma, and by the University of
Genoa.
NR 36
TC 38
Z9 43
U1 0
U2 16
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1523-0864
EI 1557-7716
J9 ANTIOXID REDOX SIGN
JI Antioxid. Redox Signal.
PD FEB
PY 2013
VL 18
IS 6
BP 630
EP 641
DI 10.1089/ars.2011.4487
PG 12
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 072LV
UT WOS:000313673400004
PM 22452634
ER
PT J
AU Huang, YY
Vecchio, D
Avci, P
Yin, R
Garcia-Diaz, M
Hamblin, MR
AF Huang, Ying-Ying
Vecchio, Daniela
Avci, Pinar
Yin, Rui
Garcia-Diaz, Maria
Hamblin, Michael R.
TI Melanoma resistance to photodynamic therapy: new insights
SO BIOLOGICAL CHEMISTRY
LA English
DT Review
DE antitumor immune response; depigmentation; drug efflux systems;
melanoma; melanosomes; photodynamic therapy; photosensitizers;
resistance mechanisms
ID IN-SITU PHOTOIMMUNOTHERAPY; B16 PIGMENTED MELANOMA; MALIGNANT-MELANOMA;
METASTATIC MELANOMA; DRUG-RESISTANCE; CHLORIN E(6); CELL LINES; SKIN;
HYPERICIN; REPAIR
AB Melanoma is the most dangerous form of skin cancer, with a steeply rising incidence and a poor prognosis in its advanced stages. Melanoma is highly resistant to traditional chemotherapy and radiotherapy, although modern targeted therapies such as BRAF inhibitors are showing some promise. Photodynamic therapy (PDT, the combination of photosensitizing dyes and visible light) has been tested in the treatment of melanoma with some promising results, but melanoma is generally considered to be resistant to it. Optical interference by the highly-pigmented melanin, the antioxidant effect of melanin, the sequestration of photosensitizers inside melanosomes, defects in apoptotic pathways, and the efflux of photosensitizers by ATP-binding cassette transporters have all been implicated in melanoma resistance to PDT. Approaches to overcoming melanoma resistance to PDT include: the discovery of highly active photosensitizers absorbing in the 700-800-nm near infrared spectral region; interventions that can temporarily reduce the amount or pigmentation of the melanin; compounds that can reverse apoptotic defects or inhibit drug-efflux of photosensitizers; and immunotherapy approaches that can take advantage of the ability of PDT to activate the host immune system against the tumor being treated.
C1 [Huang, Ying-Ying; Vecchio, Daniela; Avci, Pinar; Yin, Rui; Garcia-Diaz, Maria; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.
[Huang, Ying-Ying; Vecchio, Daniela; Yin, Rui; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA.
[Huang, Ying-Ying] Guangxi Med Univ, Dept Pathol, Nanning, Guangxi, Peoples R China.
[Yin, Rui] Third Mil Med Univ, Southwest Hosp, Dept Dermatol, Chongqing, Peoples R China.
[Garcia-Diaz, Maria] Ramon Llull Univ, IQS Sch Engn, Mol Engn Grp, Barcelona, Spain.
[Garcia-Diaz, Maria] Univ Barcelona, Dept Biochem & Mol Biol, Barcelona, Spain.
[Hamblin, Michael R.] Harvard MIT, Div Hlth Sci & Technol, Cambridge, MA USA.
RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.
EM hamblin@helix.mgh.harvard.edu
RI Huang, Ying-ying/G-3153-2011; Garcia-Diaz, Maria/J-9202-2014;
OI Huang, Ying-ying/0000-0003-3066-6981; Garcia-Diaz,
Maria/0000-0002-4794-5437; Hamblin, Michael/0000-0001-6431-4605
FU US National Institutes of Health [R01AI050875]; Fondazione MPS, Italy;
National Natural Science Foundation of China [81172495]; Comissionat per
a Universitats i Recerca del Departament d'Innovacio, Universitats i
Empresa de la Generalitat de Catalunya i del Fons Social Europeu
FX This work was supported by the US National Institutes of Health
(R01AI050875). D. V. was supported by Fondazione MPS, Italy. R. Y. was
supported by National Natural Science Foundation of China (Grant No:
81172495), M. G.-D. was supported by a predoctoral fellowship from the
Comissionat per a Universitats i Recerca del Departament d'Innovacio,
Universitats i Empresa de la Generalitat de Catalunya i del Fons Social
Europeu.
NR 56
TC 20
Z9 21
U1 4
U2 70
PU WALTER DE GRUYTER & CO
PI BERLIN
PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY
SN 1431-6730
J9 BIOL CHEM
JI Biol. Chem.
PD FEB
PY 2013
VL 394
IS 2
BP 239
EP 250
DI 10.1515/hsz-2012-0228
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 070PR
UT WOS:000313522800008
PM 23152406
ER
PT J
AU Seton, M
Jupner, H
AF Seton, Margaret
Juepner, Harald
TI Autosomal dominant hypophosphatemic rickets in an 85 year old woman:
Characterization of her disease from infancy through adulthood
SO BONE
LA English
DT Article
DE Autosomal dominant hypophosphatemic rickets; Osteomalacia; Fibroblast
growth factor 23 (FGF23); Renal phosphate wasting; Metabolic bone
disease
ID PROTEOLYTIC CLEAVAGE; GENE-EXPRESSION; IRON-DEFICIENCY; NPT2A GENE;
IN-VIVO; PHOSPHATE; FGF23; FIBROBLAST-GROWTH-FACTOR-23; MUTATIONS;
RESISTANT
AB Background: Autosomal dominant hypophosphatemic rickets (ADHR) is a rare genetic disorder of phosphate homeostasis characterized, when severely expressed, by osteomalacia, suppressed levels of calcitriol, and renal phosphate wasting due to elevated levels of fibroblast growth factor 23 (FGF23). The disease is caused by heterozygous FGF23 mutations at the RXXR site that prevent cleavage of the intact hormone.
Objectives: An FGF23 mutation was identified in the proband an 85-year-old woman with elevated FGF23 levels, and her clinical course was characterized. Medical records revealed she was treated for rickets as an infant. She was then asymptomatic until soon after her 4th pregnancy, when she suffered incapacitating bone pain and weakness, age 37. Symptoms remitted with brief treatment.
Results: The proband and one son, but not other family members, were found to be heterozygous for the R176Q mutation in FGF23. Expression of this germ line mutation was strikingly different in both individuals in terms of skeletal health, FGF23 levels and disease activity.
Conclusions: The identified FGF23 mutation in two members of this family raises questions about molecular mechanisms that have led to intermittent increases in FGF23 synthesis and secretion, and disease expression. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Seton, Margaret] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Juepner, Harald] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA.
RP Seton, M (reprint author), Massachusetts Gen Hosp, Bulfinch 165,55 Fruit St, Boston, MA 02114 USA.
EM mseton@partners.org; jueppner@helix.mgh.harvard.edu
FU NIDDK NIH HHS [R01 DK046718]
NR 26
TC 3
Z9 3
U1 1
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 8756-3282
J9 BONE
JI Bone
PD FEB
PY 2013
VL 52
IS 2
BP 640
EP 643
DI 10.1016/j.bone.2012.11.012
PG 4
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 071PW
UT WOS:000313607700014
PM 23174215
ER
PT J
AU Ciaranello, AL
Perez, F
Engelsmann, B
Walensky, RP
Mushavi, A
Rusibamayila, A
Keatinge, J
Park, JE
Maruva, M
Cerda, R
Wood, R
Dabis, F
Freedberg, KA
AF Ciaranello, Andrea L.
Perez, Freddy
Engelsmann, Barbara
Walensky, Rochelle P.
Mushavi, Angela
Rusibamayila, Asinath
Keatinge, Jo
Park, Ji-Eun
Maruva, Matthews
Cerda, Rodrigo
Wood, Robin
Dabis, Francois
Freedberg, Kenneth A.
TI Cost-effectiveness of World Health Organization 2010 Guidelines for
Prevention of Mother-to-Child HIV Transmission in Zimbabwe
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
DE HIV; mother-to-child transmission; PMTCT; pediatric HIV;
cost-effectiveness
ID SINGLE-DOSE NEVIRAPINE; ANTIRETROVIRAL THERAPY PROGRAMS; SUB-SAHARAN
AFRICA; SOUTH-AFRICA; RANDOMIZED-TRIAL; INFECTED CHILDREN; POOLED
ANALYSIS; PREGNANT-WOMEN; FOLLOW-UP; POSTPARTUM WOMEN
AB Background. In 2010, the World Health Organization (WHO) released revised guidelines for prevention of mother-to-child human immunodeficiency virus (HIV) transmission (PMTCT). We projected clinical impacts, costs, and cost-effectiveness of WHO-recommended PMTCT strategies in Zimbabwe.
Methods. We used Zimbabwean data in a validated computer model to simulate a cohort of pregnant, HIV-infected women (mean age, 24 years; mean CD4 count, 451 cells/mu L; subsequent 18 months of breastfeeding). We simulated guideline-concordant care for 4 PMTCT regimens: single-dose nevirapine (sdNVP); WHO-recommended Option A, WHO-recommended Option B, and Option B+ (lifelong maternal 3-drug antiretroviral therapy regardless of CD4). Outcomes included maternal and infant life expectancy (LE) and lifetime healthcare costs (2008 US dollars [USD]). Incremental cost-effectiveness ratios (ICERs, in USD per year of life saved [YLS]) were calculated from combined (maternal + infant) discounted costs and LE.
Results. Replacing sdNVP with Option A increased combined maternal and infant LE from 36.97 to 37.89 years and would reduce lifetime costs from $5760 to $5710 per mother-infant pair. Compared with Option A, Option B further improved LE (38.32 years), and saved money within 4 years after delivery ($ 5630 per mother-infant pair). Option B+ (LE, 39.04 years; lifetime cost, $ 6620 per mother-infant pair) improved maternal and infant health, with an ICER of $ 1370 per YLS compared with Option B.
Conclusions. Replacing sdNVP with Option A or Option B will improve maternal and infant outcomes and save money; Option B increases health benefits and decreases costs compared with Option A. Option B+ further improves maternal outcomes, with an ICER (compared with Option B) similar to many current HIV-related healthcare interventions.
C1 [Ciaranello, Andrea L.; Walensky, Rochelle P.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Infect Dis, Med Practice Evaluat Ctr, Boston, MA 02114 USA.
[Walensky, Rochelle P.; Rusibamayila, Asinath; Park, Ji-Eun; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA.
[Cerda, Rodrigo] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Walensky, Rochelle P.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Infect Dis, Boston, MA 02115 USA.
[Walensky, Rochelle P.; Freedberg, Kenneth A.] Harvard Univ, Sch Med, Ctr AIDS Res, Boston, MA USA.
[Perez, Freddy; Dabis, Francois] Univ Bordeaux, Inst Sante Publ Epidemiol & Dev, Bordeaux, France.
[Perez, Freddy; Dabis, Francois] Ctr INSERM, Epidemiol Biostat U897, Bordeaux, France.
[Perez, Freddy] Pan Amer Hlth Org, HIV AIDS Unit, Washington, DC USA.
[Engelsmann, Barbara] Org Publ Hlth Intervent & Dev, Harare, Zimbabwe.
[Mushavi, Angela] Minist Hlth & Child Welf, Harare, Zimbabwe.
[Keatinge, Jo; Maruva, Matthews] US Agcy Int Dev, Harare, Zimbabwe.
[Wood, Robin] Univ Cape Town, Inst Infect Dis & Mol Med, Desmond Tutu HIV Ctr, ZA-7700 Rondebosch, South Africa.
RP Ciaranello, AL (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Med Practice Evaluat Ctr, 50 Staniford St,9th Fl, Boston, MA 02114 USA.
EM aciaranello@partners.org
RI 杜, 美晨/S-4063-2016;
OI 杜, 美晨/0000-0002-1562-1155; Walensky, Rochelle P./0000-0002-8795-379X
FU Elizabeth Glaser Pediatric AIDS Foundation; National Institute of
Allergy and Infectious Diseases; National Institute of Child Health and
Human Development, National Institutes of Health [K01 AI078754, K24
AI062476, R01 AI058736]; Harvard University Center for AIDS Research
FX This work was supported by the Elizabeth Glaser Pediatric AIDS
Foundation; the National Institute of Allergy and Infectious Diseases
and the National Institute of Child Health and Human Development,
National Institutes of Health (K01 AI078754 to A. L. C.; K24 AI062476 to
K. A. F.; R01 AI058736 to R. P. W., A. R., J.-E. P., K. A. F; IMPAACT
network to R. P. W., J.-E. P., K. A. F.); and Harvard University Center
for AIDS Research (to K. A. F., R. P. W.). The funders had no role in
study design, interpretation of results, or decision to publish.
NR 99
TC 29
Z9 29
U1 3
U2 26
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD FEB 1
PY 2013
VL 56
IS 3
BP 430
EP 446
DI 10.1093/cid/cis858
PG 17
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 071TM
UT WOS:000313617400025
PM 23204035
ER
PT J
AU Thoonen, R
Sips, PY
Bloch, KD
Buys, ES
AF Thoonen, Robrecht
Sips, Patrick Y.
Bloch, Kenneth D.
Buys, Emmanuel S.
TI Pathophysiology of Hypertension in the Absence of Nitric Oxide/Cyclic
GMP Signaling
SO CURRENT HYPERTENSION REPORTS
LA English
DT Article
DE Cyclic guanosine monophosphate; Blood pressure; Hypertension;
Cardiovascular function; Soluble guanylate cyclase; Nitric oxide; Mutant
mice; Genetic variants; Renin-angiotensin-aldosterone signaling; Gender;
S-nitrosylation; Therapeutics
ID SOLUBLE GUANYLATE-CYCLASE; DEPENDENT PROTEIN-KINASE; VASCULAR
SMOOTH-MUSCLE; ENDOTHELIAL NO SYNTHASE; CARDIOMYOCYTE-SPECIFIC
OVEREXPRESSION; SYSTEMIC VASODILATOR RESPONSES; S-NITROSOGLUTATHIONE
REDUCTASE; GENOME-WIDE ASSOCIATION; CINACIGUAT BAY 58-2667;
DOUBLE-KNOCKOUT MICE
AB The nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) signaling system is a well-characterized modulator of cardiovascular function, in general, and blood pressure, in particular. The availability of mice mutant for key enzymes in the NO-cGMP signaling system facilitated the identification of interactions with other blood pressure modifying pathways (e.g. the renin-angiotensin-aldosterone system) and of gender-specific effects of impaired NO-cGMP signaling. In addition, recent genome-wide association studies identified blood pressure-modifying genetic variants in genes that modulate NO and cGMP levels. Together, these findings have advanced our understanding of how NO-cGMP signaling regulates blood pressure. In this review, we will summarize the results obtained in mice with disrupted NO-cGMP signaling and highlight the relevance of this pathway as a potential therapeutic target for the treatment of hypertension.
C1 [Thoonen, Robrecht] Tufts Med Ctr, Mol Cardiol Res Inst, Mol Cardiol Res Ctr, Boston, MA 02111 USA.
[Sips, Patrick Y.] Harvard Univ, Anesthesia Ctr Crit Care Res, Dept Anesthesia Crit Care & Pain Med, Massachusetts Gen Hosp,Med Sch, Charlestown, MA 02129 USA.
[Bloch, Kenneth D.; Buys, Emmanuel S.] Harvard Univ, Anesthesia Ctr Crit Care Res, Dept Anesthesia Crit Care & Pain Med, Massachusetts Gen Hosp,Med Sch, Boston, MA 02114 USA.
RP Buys, ES (reprint author), Harvard Univ, Anesthesia Ctr Crit Care Res, Dept Anesthesia Crit Care & Pain Med, Massachusetts Gen Hosp,Med Sch, 55 Fruit St,Thier 511B, Boston, MA 02114 USA.
EM rthoonen@tuftsmedicalcenter.org; psips@partners.org;
kdbloch@partners.org; ebuys@partners.org
OI Sips, Patrick/0000-0001-9241-5980
FU NEI NIH HHS [R01 EY022746, R21 EY020987]
NR 145
TC 14
Z9 15
U1 1
U2 14
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1522-6417
J9 CURR HYPERTENS REP
JI Curr. Hypertens. Rep.
PD FEB
PY 2013
VL 15
IS 1
BP 47
EP 58
DI 10.1007/s11906-012-0320-5
PG 12
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 070OE
UT WOS:000313518100008
PM 23233080
ER
PT J
AU Bowden, MG
Woodbury, ML
Duncan, PW
AF Bowden, Mark G.
Woodbury, Michelle L.
Duncan, Pamela W.
TI Promoting neuroplasticity and recovery after stroke: future directions
for rehabilitation clinical trials
SO CURRENT OPINION IN NEUROLOGY
LA English
DT Review
DE neuroplasticity; recovery; rehabilitation; stroke
ID DIRECT-CURRENT STIMULATION; CONSTRAINT-INDUCED MOVEMENT; RANDOMIZED
CONTROLLED-TRIAL; NONINVASIVE CORTICAL STIMULATION; ADULT
SQUIRREL-MONKEYS; MOTOR CORTEX; NEURAL PLASTICITY; AMBULATORY FUNCTION;
DC-STIMULATION; BRAIN-INJURY
AB Purpose of review
The purpose is to establish a theoretical framework by which new interventions for poststroke rehabilitation may be developed incorporating knowledge of neuroplasticity and the critical ingredients of rehabilitation.
Recent findings
Large phase III randomized controlled trials (RCTs) are rare in neurorehabilitation, and the results of those that have been completed are perplexing because the experimental and control treatments were not different when matched for activity level. In addition, the outcome measures used to define treatment effects reflected behavioral endpoints, but did not reveal how neuroplastic mechanisms or other mechanistic factors may have contributed to the treatment response. Knowledge of both the neurophysiologic basis of recovery and key elements of interventions that drive motor learning, such as intensity and task progression, are critical for optimizing future poststroke motor rehabilitation clinical trials.
Summary
Future neurorehabilitation RCTs require a better understanding of the interaction of interventions and neurophysiological recovery in order to target interventions at specific neurophysiologic substrates, develop a more clear understanding of the impact of intervention parameters (e.g. dose, intensity), and advance discussions regarding optimal ways to partner medical and rehabilitation interventions in order to improve outcomes.
C1 [Bowden, Mark G.; Woodbury, Michelle L.] Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Charleston, SC 29425 USA.
[Bowden, Mark G.; Woodbury, Michelle L.] Med Univ S Carolina, Dept Hlth Sci & Res, Charleston, SC 29425 USA.
[Bowden, Mark G.] Med Univ S Carolina, Div Phys Therapy, Charleston, SC 29425 USA.
[Woodbury, Michelle L.] Med Univ S Carolina, Div Occupat Therapy, Charleston, SC 29425 USA.
[Duncan, Pamela W.] Wake Forest Baptist Med Ctr, Dept Neurol, Winston Salem, NC USA.
RP Bowden, MG (reprint author), Med Univ S Carolina, Ralph H Johnson VA Med Ctr, 77 President St,MSC 700, Charleston, SC 29425 USA.
EM bowdenm@musc.edu
FU Ralph H. Johnson Veterans Affairs Medical Center; Department of Veterans
Affairs Office of Research and Development [B-7177M, B-6332W]; South
Carolina Clinical and Translational Research Institute Discovery Grant;
American Heart Association Innovative Research Grant
FX This work was supported in part by the Ralph H. Johnson Veterans Affairs
Medical Center and the Department of Veterans Affairs Office of Research
and Development, Rehabilitation Research and Development; Career
Development-1 Award (B-7177M), PI: M. G. Bowden; Career Development-2
Award (B-6332W), PI: M.L. Woodbury.; None of the authors has a conflict
of interest with this manuscript. Dr Duncan has been involved with
private industry, notably she has received honorarium for consulting
with Allergan to develop a post stroke disability measures and with
Glaxo to design phase 2 trials to enhance stroke recovery. The authors
are supported by the following grants: South Carolina Clinical and
Translational Research Institute Discovery Grant; American Heart
Association Innovative Research Grant.
NR 57
TC 20
Z9 22
U1 1
U2 51
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1350-7540
J9 CURR OPIN NEUROL
JI Curr. Opin. Neurol.
PD FEB
PY 2013
VL 26
IS 1
BP 37
EP 42
DI 10.1097/WCO.0b013e32835c5ba0
PG 6
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 070XI
UT WOS:000313547000005
PM 23254556
ER
PT J
AU Rodriguez-Galindo, C
Friedrich, P
Morrissey, L
Frazier, L
AF Rodriguez-Galindo, Carlos
Friedrich, Paola
Morrissey, Lisa
Frazier, Lindsay
TI Global challenges in pediatric oncology
SO CURRENT OPINION IN PEDIATRICS
LA English
DT Review
DE global health; low-income and middle-income countries; pediatric cancer
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; LOW-INCOME COUNTRIES; TREATMENT-RELATED
MORTALITY; PALLIATIVE-CARE SERVICES; CHILDHOOD-CANCER; CENTRAL-AMERICA;
BURKITT-LYMPHOMA; NURSING-EDUCATION; WILMS-TUMOR; EL SALVADOR
AB Purpose of review
Reduction of child mortality is one of the Millennium Development Goals; as low-income and middle-income countries (LMICs) advance toward the achievement of this goal, initiatives aimed at reducing the burden of noncommunicable diseases, including childhood cancer, need to be developed.
Recent findings
Approximately 200 000 children and adolescents are diagnosed with cancer every year worldwide; of those, 80% live in LMICs, which account for 90% of the deaths. Lack of quality population-based cancer registries in LMICs limits our knowledge of the epidemiology of pediatric cancer; however, available information showing variations in incidence may indicate unique interactions between environmental and genetic factors that could provide clues to cause. Outcome of children with cancer in LMICs is dictated by late presentation and underdiagnosis, high abandonment rates, high prevalence of malnutrition and other comorbidities, suboptimal supportive and palliative care, and limited access to curative therapies. Initiatives integrating program building with education of healthcare providers and research have proven to be successful in the development of regional capacity. Intensity-graduated treatments adjusted to the local capacity have been developed.
Summary
Childhood cancer burden is shifted toward LMICs; global initiatives directed at pediatric cancer care and control are urgently needed. International partnerships facilitating stepwise processes that build capacity while incorporating epidemiology and health services research and implementing intensity-graduated treatments have been shown to be effective.
C1 [Rodriguez-Galindo, Carlos; Friedrich, Paola; Morrissey, Lisa; Frazier, Lindsay] Harvard Univ, Sch Med, Div Hematol Oncol, Dana Farber Childrens Hosp Canc Ctr, Boston, MA USA.
[Rodriguez-Galindo, Carlos; Friedrich, Paola; Frazier, Lindsay] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
RP Rodriguez-Galindo, C (reprint author), Dana Farber Canc Inst, 450 Brookline Ave SW350, Boston, MA 02215 USA.
EM carlos_rodriguez-galindo@dfci.harvard.edu
OI Friedrich, Paola/0000-0002-5265-3113
NR 82
TC 29
Z9 34
U1 2
U2 36
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1040-8703
EI 1531-698X
J9 CURR OPIN PEDIATR
JI CURR. OPIN. PEDIATR.
PD FEB
PY 2013
VL 25
IS 1
BP 3
EP 15
DI 10.1097/MOP.0b013e32835c1cbe
PG 13
WC Pediatrics
SC Pediatrics
GA 069DC
UT WOS:000313414400002
PM 23295716
ER
PT J
AU Van Eeghen, AM
Pulsifer, MB
Merker, VL
Neumeyer, AM
Van Eeghen, EE
Thibert, RL
Cole, AJ
Leigh, FA
Plotkin, SR
Thiele, EA
AF Van Eeghen, Agnies M.
Pulsifer, Margaret B.
Merker, Vanessa L.
Neumeyer, Ann M.
Van Eeghen, Elmer E.
Thibert, Ronald L.
Cole, Andrew J.
Leigh, Fawn A.
Plotkin, Scott R.
Thiele, Elizabeth A.
TI Understanding relationships between autism, intelligence, and epilepsy:
a cross-disorder approach
SO DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY
LA English
DT Article
ID TUBEROUS SCLEROSIS COMPLEX; PERVASIVE DEVELOPMENTAL DISORDERS; INFANTILE
SPASMS; DOWN-SYNDROME; FRAGILE-X; CHILDREN; SPECTRUM; INDIVIDUALS;
DEFINITION; MUTATIONS
AB Aim As relationships between autistic traits, epilepsy, and cognitive functioning remain poorly understood, these associations were explored in the biologically related disorders tuberous sclerosis complex (TSC), neurofibromatosis type 1 (NF1), and epilepsy. Method The Social Responsiveness Scale (SRS), a quantitative measure of autistic traits, was distributed to caregivers or companions of patients with TSC, NF1, and childhood-onset epilepsy of unknown cause (EUC), and these results were compared with SRS data from individuals with idiopathic autism spectrum disorders (ASDs) and their unaffected siblings. Scores and trait profiles of autistic features were compared with cognitive outcomes, epilepsy variables, and genotype. Results A total of 180 SRS questionnaires were completed in the TSC, NF1, and EUC outpatient clinics at the Massachusetts General Hospital (90 females, 90 males; mean age 21y, range 463y), and SRS data from 210 patients with ASD recruited from an autism research collaboration (167 males, 43 females; mean age 9y, range 422y) and 130 unaffected siblings were available. Regression models showed a significant association between SRS scores and intelligence outcomes (p<0.001) and various seizure variables (p<0.02), but not with a specific underlying disorder or genotype. The level of autistic features was strongly associated with intelligence outcomes in patients with TSC and epilepsy (p<0.01); in patients with NF1 these relationships were weaker (p=0.25). For all study groups, autistic trait subdomains covaried with neurocognitive comorbidity, with endophenotypes similar to that of idiopathic autism. Interpretation Our data show that in TSC and childhood-onset epilepsy, the severity and phenotype of autistic features are inextricably linked with intelligence and epilepsy outcomes. Such relationships were weaker for individuals with NF1. Findings suggest that ASDs are not specific in these conditions.
C1 [Van Eeghen, Agnies M.; Van Eeghen, Elmer E.; Thiele, Elizabeth A.] Massachusetts Gen Hosp, Dept Neurol, Carol & James Herscot Ctr Tuberous Sclerosis Comp, Boston, MA 02114 USA.
[Van Eeghen, Agnies M.] Erasmus MC, Expertise Ctr Neurodev Disorders, ENCORE, Dept Neurosci, Rotterdam, Netherlands.
[Pulsifer, Margaret B.] Massachusetts Gen Hosp, Dept Psychiat, Psychol Assessment Ctr, Boston, MA 02114 USA.
[Merker, Vanessa L.; Leigh, Fawn A.; Plotkin, Scott R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
[Neumeyer, Ann M.] Massachusetts Gen Hosp, Dept Neurol, Lurie Ctr Autism, Boston, MA 02114 USA.
[Thibert, Ronald L.] Massachusetts Gen Hosp, Dept Neurol, Pediat Epilepsy Serv, Boston, MA 02114 USA.
[Cole, Andrew J.] Massachusetts Gen Hosp, Dept Neurol, Epilepsy Serv, Boston, MA 02114 USA.
RP Thiele, EA (reprint author), Carol & James Herscot Ctr Tuberous Sclerosis, 175 Cambridge St,Suite 340, Boston, MA 02114 USA.
EM ethiele@partners.org
OI Merker, Vanessa/0000-0002-4542-5227
FU Herscot Center for Tuberous Sclerosis Complex; NIH/NINDS [P01 NS024279]
FX We are grateful to the families and individuals who agreed to
participate in this study and the Autism Consortium for their valuable
time and effort. We are grateful to the Autism Consortium for access to
the data analyzed here, and for the support from Christine Ferrone and
Roksana Sasanfar for assisting with the Autism Consortium data
collection. We thank Zaida Ortega, Christina Anagnos, Jill Beamon, and
Joseph Nimon for assisting with distribution and scoring of the
questionnaires. Lastly, we are grateful to the MGH Department of
Biostatistics for assistance with statistical analysis. This study was
sponsored by the Herscot Center for Tuberous Sclerosis Complex, and
NIH/NINDS P01 NS024279.
NR 46
TC 31
Z9 31
U1 1
U2 37
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0012-1622
J9 DEV MED CHILD NEUROL
JI Dev. Med. Child Neurol.
PD FEB
PY 2013
VL 55
IS 2
BP 146
EP 153
DI 10.1111/dmcn.12044
PG 8
WC Clinical Neurology; Pediatrics
SC Neurosciences & Neurology; Pediatrics
GA 073FT
UT WOS:000313729600013
PM 23205844
ER
PT J
AU Saylor, PJ
Armstrong, AJ
Fizazi, K
Freedland, S
Saad, F
Smith, MR
Tombal, B
Pienta, K
AF Saylor, Philip J.
Armstrong, Andrew J.
Fizazi, Karim
Freedland, Stephen
Saad, Fred
Smith, Matthew R.
Tombal, Bertrand
Pienta, Kenneth
TI New and Emerging Therapies for Bone Metastases in Genitourinary Cancers
SO EUROPEAN UROLOGY
LA English
DT Review
DE Prostate cancer; Bladder cancer; Urothelial cancer; Bone metastases;
Zoledronic acid; Denosumab; Radium-223
ID RESISTANT PROSTATE-CANCER; RENAL-CELL CARCINOMA; PLACEBO-CONTROLLED
TRIAL; ORAL SODIUM CLODRONATE; PHASE-II TRIAL; ZOLEDRONIC ACID;
DOUBLE-BLIND; SKELETAL COMPLICATIONS; OSTEOCLAST DIFFERENTIATION;
BREAST-CANCER
AB Context: Bone metastases are a common feature of advanced genitourinary malignancies and a prominent cause of morbidity and mortality.
Objective: The objective of this review is to discuss the incidence, pathophysiology, and management of bone metastases in the most prevalent genitourinary malignancies.
Evidence acquisition: We reviewed the relevant medical literature, with a particular emphasis on prospective randomized controlled trials. Much of the relevant clinical trial data focus on prostate cancer (PCa). We provide a nonsystematic review and our perspective on the available data.
Evidence synthesis: Clinical manifestations can include pain, hypercalcemia, pathologic fractures, and spinal cord compression. Optimal systemic therapy for skeletal metastases often features a combination of disease-specific therapy and bone-targeted therapy. Some agents, such as the radiopharmaceutical radium-223, blur the line between those categories. Osteoclast inhibition is a validated strategy in the management of selected patients with bone metastases. Zoledronic acid, a bisphosphonate, is approved for the prevention of skeletal events caused by solid tumors metastatic to bone. Denosumab is a fully human monoclonal antibody that inactivates receptor activator of nuclear factor-kappa B ligand and is approved for the same indication. Beta-emitting radiopharmaceuticals can be effective for the palliation of pain caused by bone metastases, but their use is often limited by marrow suppression. The alpha-emitting radiopharmaceutical radium-223 has recently been shown to improve overall survival and prevent skeletal events in select men with castration-resistant PCa metastatic to bone. Multiple ongoing clinical trials are designed to examine the potential for therapeutic inhibition of additional targets such as Src and hepatocyte growth factor (MET).
Conclusions: Bone metastases cause considerable morbidity and mortality among patients with genitourinary malignancies. Optimal management requires consideration of bone-targeted therapy as well as disease-specific therapy. Further research is needed to optimize the use of existing agents and to define the therapeutic potential of novel targets. (C) 2012 European Association of Urology. Published by Elsevier B. V. All rights reserved.
C1 [Saylor, Philip J.] Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, Boston, MA 02114 USA.
[Armstrong, Andrew J.] Duke Univ, Med Ctr, Duke Canc Inst, Durham, NC USA.
[Armstrong, Andrew J.] Duke Univ, Med Ctr, Duke Prostate Ctr, Durham, NC USA.
[Fizazi, Karim] Inst Gustave Roussy, Dept Canc Med, Villejuif, France.
[Freedland, Stephen] VA Med Ctr, Dept Surg, Durham, NC USA.
[Freedland, Stephen] Duke Univ, Dept Surg & Pathol, Div Urol Surg, Durham, NC USA.
[Saad, Fred] Ctr Hosp Univ Montreal, Montreal, PQ, Canada.
[Tombal, Bertrand] Catholic Univ Louvain, Clin Univ St Luc, Serv Urol, B-1200 Brussels, Belgium.
[Pienta, Kenneth] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA.
RP Saylor, PJ (reprint author), Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, 55 Fruit St,Yawkey 7E, Boston, MA 02114 USA.
EM psaylor@partners.org
RI Pienta, Kenneth/E-7679-2015
OI TOMBAL, Bertrand/0000-0002-0093-8408; Pienta,
Kenneth/0000-0002-4138-2186
FU Novartis; Prostate Cancer Foundation; US National Institutes of Health
[5K24CA121990-02]
FX Philip J. Saylor certifies that all conflicts of interest, including
specific financial interests and relationships and affiliations relevant
to the subject matter or materials discussed in the manuscript (eg,
employment/affiliation, grants or funding, consultancies, honoraria,
stock ownership or options, expert testimony, royalties, or patents
filed, received, or pending), are the following: Dr Armstrong is a
speaker for and on the advisory board of Amgen and has received research
support from Novartis. Dr Fizazi participates on the advisory boards of
or is a speaker for Amgen, Novartis, Exelixis, and Bayer. Dr Freedland
is a speaker and consultant for Amgen and Janssen. Dr Saad is a
consultant and researcher for Amgen and Novartis. Dr Saylor is supported
by a Young Investigator Award from the Prostate Cancer Foundation. Dr
Smith is supported by a US National Institutes of Health K24 Midcareer
Investigator Award (5K24CA121990-02) and awards from the Prostate Cancer
Foundation and is a consultant for Amgen and Bayer. Dr Tombal is an
advisor and consultant to Amgen.
NR 81
TC 24
Z9 25
U1 1
U2 15
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0302-2838
J9 EUR UROL
JI Eur. Urol.
PD FEB
PY 2013
VL 63
IS 2
BP 309
EP 320
DI 10.1016/j.eururo.2012.10.007
PG 12
WC Urology & Nephrology
SC Urology & Nephrology
GA 071FE
UT WOS:000313572100026
PM 23201471
ER
PT J
AU Saini, N
Mahindra, A
AF Saini, Neeraj
Mahindra, Anuj
TI Novel immunomodulatory compounds in multiple myeloma
SO EXPERT OPINION ON INVESTIGATIONAL DRUGS
LA English
DT Review
DE IMiDs; lenalidomide; multiple myeloma; pomalidomide
ID STEM-CELL TRANSPLANTATION; LENALIDOMIDE PLUS DEXAMETHASONE; PHASE-II
TRIALS; NF-KAPPA-B; COMBINATION THERAPY; MULTICENTER PHASE-2; INDUCTION
THERAPY; DRUG-RESISTANCE; THALIDOMIDE; MOBILIZATION
AB Introduction: The treatment options for patients with multiple myeloma (MM) remain limited. Immunomodulatory agents (IMiDs), such as thalidomide and lenalidomide, have changed the landscape in the treatment of patients with MM while newer IMiDs such as pomalidomide are showing promise in early clinical trials.
Areas covered: This review focuses on the biologic rationales of IMiDs and the clinical results supporting their use in MM. It includes data on the new IMiD, pomalidomide and also explores the possible utility of combining IMiDs with other agents. A PubMed search and abstracts from oncology scientific meetings (ASCO and ASH) of articles related to IMiDs and MM was conducted.
Expert opinion: IMiDs have shown clinical activity as single agents and in combination. Thalidomide was the first in class drug. Lenalidomide has a better toxicity profile than thalidomide. Pomalidomide may overcome resistance to lenalidomide indicating differences in their mechanisms of action and resistance. Molecular biomarkers may allow us to identify patients who will respond to IMiDs.
C1 [Saini, Neeraj] N Shore Med Ctr, Boston, MA USA.
[Mahindra, Anuj] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Mahindra, A (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA.
EM amahindra@partners.org
OI saini, Neeraj/0000-0001-7435-0933
NR 56
TC 5
Z9 5
U1 0
U2 8
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1354-3784
J9 EXPERT OPIN INV DRUG
JI Expert Opin. Investig. Drugs
PD FEB
PY 2013
VL 22
IS 2
BP 207
EP 215
DI 10.1517/13543784.2013.749235
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 071KR
UT WOS:000313592000004
PM 23265189
ER
PT J
AU Thakurathi, N
Vincenzi, B
Henderson, DC
AF Thakurathi, Neelam
Vincenzi, Brenda
Henderson, David C.
TI Assessing the prospect of donepezil in improving cognitive impairment in
patients with schizophrenia
SO EXPERT OPINION ON INVESTIGATIONAL DRUGS
LA English
DT Editorial Material
DE acetylcholinesterase inhibitor; atypical antipsychotics; cognitive
impairments; donepezil; schizophrenia
ID PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; ADJUNCTIVE TREATMENT; FUNCTIONAL
CONSEQUENCES; NEUROCOGNITIVE DEFICITS; STABLE SCHIZOPHRENIA;
WORKING-MEMORY; GALANTAMINE; RISPERIDONE; NICOTINE
AB Introduction: Even though cognitive impairment is manifested in almost all patients with schizophrenia, the Clinical Antipsychotic Trials for Intervention Effectiveness (CATIE) study showed no significant difference between first- and second-generation psychotropic drugs in improving cognitive abilities. Discovering new drugs that can improve impaired cognition, thus, is an attractive treatment target for patients with schizophrenia.
Areas covered: This article briefly reviews about donepezil, a highly selective (IC50 = 6.7 nM) centrally acting reversible acetylcholinesterase inhibitor that has been approved by FDA for treating cognitive deficit states such as in Alzheimer's disease and its uses in clinical trials for the treatment of schizophrenia. The literature search included PubMed and Cochrane library with the following words: donepezil, schizophrenia and cognitive impairments.
Expert opinion: The results of several clinical trials utilizing donepezil as an adjunct to second-generation antipsychotic drugs targeting cognitive deficits in schizophrenia subjects have been disappointing and would not lead clinicians to consider this as a potential treatment option. While longer randomized controlled trials, increase dosage and selected groups of patients at different stage of cognitive impairment may provide a better understanding of the potential for this drug in addressing cognitive deficits, results to date have not been encouraging.
C1 [Thakurathi, Neelam; Vincenzi, Brenda; Henderson, David C.] Massachusetts Gen Hosp, Schizophrenia Clin & Res Program, Boston, MA 02114 USA.
[Henderson, David C.] Harvard Univ, Sch Med, Freedom Trail Clin, Boston, MA 02114 USA.
RP Henderson, DC (reprint author), Massachusetts Gen Hosp, Schizophrenia Clin & Res Program, Boston, MA 02114 USA.
EM dchenderson@partners.org
NR 47
TC 6
Z9 6
U1 0
U2 6
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1354-3784
J9 EXPERT OPIN INV DRUG
JI Expert Opin. Investig. Drugs
PD FEB
PY 2013
VL 22
IS 2
BP 259
EP 265
DI 10.1517/13543784.2013.750650
PG 7
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 071KR
UT WOS:000313592000008
PM 23215841
ER
PT J
AU Chen, H
Meigs, JB
Dupuis, J
AF Chen, Han
Meigs, James B.
Dupuis, Josee
TI Sequence Kernel Association Test for Quantitative Traits in Family
Samples
SO GENETIC EPIDEMIOLOGY
LA English
DT Article
DE rare variant analysis; quantitative traits; family samples;
heritability; linear mixed effects model
ID HAPLOTYPE RELATIVE RISK; COMMON DISEASES; RARE VARIANTS; MODELS
AB A large number of rare genetic variants have been discovered with the development in sequencing technology and the lowering of sequencing costs. Rare variant analysis may help identify novel genes associated with diseases and quantitative traits, adding to our knowledge of explaining heritability of these phenotypes. Many statistical methods for rare variant analysis have been developed in recent years, but some of them require the strong assumption that all rare variants in the analysis share the same direction of effect, and others requiring permutation to calculate the P-values are computer intensive. Among these methods, the sequence kernel association test (SKAT) is a powerful method under many different scenarios. It does not require any assumption on the directionality of effects, and statistical significance is computed analytically. In this paper, we extend SKAT to be applicable to family data. The family-based SKAT (famSKAT) has a different test statistic and null distribution compared to SKAT, but is equivalent to SKAT when there is no familial correlation. Our simulation studies show that SKAT has inflated type I error if familial correlation is inappropriately ignored, but has appropriate type I error if applied to a single individual per family to obtain an unrelated subset. In contrast, famSKAT has the correct type I error when analyzing correlated observations, and it has higher power than competing methods in many different scenarios. We illustrate our approach to analyze the association of rare genetic variants using glycemic traits from the Framingham Heart Study.
C1 [Chen, Han; Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA.
[Meigs, James B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Dupuis, Josee] NHLBI, Framingham Heart Study, Framingham, MA USA.
RP Chen, H (reprint author), 801 Massachusetts Ave,3rd Floor, Boston, MA 02118 USA.
EM hanchen@bu.edu
OI Dupuis, Josee/0000-0003-2871-3603; Chen, Han/0000-0002-9510-4923
FU NIH [R01 DK078616, U01 DK85526, K24 DK080140]; National Heart, Lung, and
Blood Institute (NHLBI) [N01-HC-25195]; Affymetrix, Inc.
[N02-HL-6-4278]; Boston University [N01-HC-25195]
FX Contract grant sponsor: NIH; Contract grant numbers: R01 DK078616; U01
DK85526; K24 DK080140; Contract grant sponsor: National Heart, Lung, and
Blood Institute (NHLBI); Contract grant number: N01-HC-25195; Contract
grant sponsor: Affymetrix, Inc.; Contract grant number: N02-HL-6-4278.;
The authors thank Dr. Thomas Lumley for his insights into Kuonen's
saddlepoint method. This research was partially supported by NIH awards
R01 DK078616, U01 DK85526, and K24 DK080140. A portion of this research
was conducted using the Linux Clusters for Genetic Analysis (LinGA)
computing resources at Boston University Medicine Campus. The Framingham
Heart Study is conducted and supported by the National Heart, Lung, and
Blood Institute (NHLBI) in collaboration with Boston University
(Contract No. N01-HC-25195). This work was partially supported by a
contract with Affymetrix, Inc. for genotyping services (Contract No.
N02-HL-6-4278).
NR 22
TC 72
Z9 74
U1 0
U2 12
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD FEB
PY 2013
VL 37
IS 2
BP 196
EP 204
DI 10.1002/gepi.21703
PG 9
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 074AK
UT WOS:000313784000008
PM 23280576
ER
PT J
AU Minelli, C
De Grandi, A
Weichenberger, CX
Gogele, M
Modenese, M
Attia, J
Barrett, JH
Boehnke, M
Borsani, G
Casari, G
Fox, CS
Freina, T
Hicks, AA
Marroni, F
Parmigiani, G
Pastore, A
Pattaro, C
Pfeufer, A
Ruggeri, F
Schwienbacher, C
Taliun, D
Pramstaller, PP
Domingues, FS
Thompson, JR
AF Minelli, Cosetta
De Grandi, Alessandro
Weichenberger, Christian X.
Goegele, Martin
Modenese, Mirko
Attia, John
Barrett, Jennifer H.
Boehnke, Michael
Borsani, Giuseppe
Casari, Giorgio
Fox, Caroline S.
Freina, Thomas
Hicks, Andrew A.
Marroni, Fabio
Parmigiani, Giovanni
Pastore, Andrea
Pattaro, Cristian
Pfeufer, Arne
Ruggeri, Fabrizio
Schwienbacher, Christine
Taliun, Daniel
Pramstaller, Peter P.
Domingues, Francisco S.
Thompson, John R.
TI Importance of Different Types of Prior Knowledge in Selecting
Genome-Wide Findings for Follow-Up
SO GENETIC EPIDEMIOLOGY
LA English
DT Article
DE gene prioritization; genome-wide association studies; bioinformatics
databases
ID SCALE ASSOCIATION ANALYSIS; SUSCEPTIBILITY LOCI; GENE PRIORITIZATION;
HUMAN-DISEASE; DATABASE; MOUSE; REPLICATION; PATHWAY; INCONSISTENCY;
METAANALYSES
AB Biological plausibility and other prior information could help select genome-wide association (GWA) findings for further follow-up, but there is no consensus on which types of knowledge should be considered or how to weight them. We used experts opinions and empirical evidence to estimate the relative importance of 15 types of information at the single-nucleotide polymorphism (SNP) and gene levels. Opinions were elicited from 10 experts using a two-round Delphi survey. Empirical evidence was obtained by comparing the frequency of each type of characteristic in SNPs established as being associated with seven disease traits through GWA meta-analysis and independent replication, with the corresponding frequency in a randomly selected set of SNPs. SNP and gene characteristics were retrieved using a specially developed bioinformatics tool. Both the expert and the empirical evidence rated previous association in a meta-analysis or more than one study as conferring the highest relative probability of true association, whereas previous association in a single study ranked much lower. High relative probabilities were also observed for location in a functional protein domain, although location in a region evolutionarily conserved in vertebrates was ranked high by the data but not by the experts. Our empirical evidence did not support the importance attributed by the experts to whether the gene encodes a protein in a pathway or shows interactions relevant to the trait. Our findings provide insight into the selection and weighting of different types of knowledge in SNP or gene prioritization, and point to areas requiring further research.
C1 [Minelli, Cosetta; De Grandi, Alessandro; Weichenberger, Christian X.; Goegele, Martin; Modenese, Mirko; Freina, Thomas; Hicks, Andrew A.; Pattaro, Cristian; Schwienbacher, Christine; Taliun, Daniel; Pramstaller, Peter P.; Domingues, Francisco S.] European Acad Bozen Bolzano EURAC, Ctr Biomed, Bolzano, Italy.
[Attia, John] Univ Newcastle, Hunter Med Res Inst, Ctr Clin Epidemiol & Biostatist, Newcastle, NSW 2300, Australia.
[Attia, John] John Hunter Hosp, Dept Gen Med, Newcastle, NSW, Australia.
[Barrett, Jennifer H.] Univ Leeds, Sect Epidemiol & Biostat, Leeds Inst Mol Med, Leeds, W Yorkshire, England.
[Boehnke, Michael] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.
[Boehnke, Michael] Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
[Borsani, Giuseppe] Univ Brescia, Dept Biomed Sci & Biotechnol, Brescia, Italy.
[Casari, Giorgio] Univ Vita Salute San Raffaele, Milan, Italy.
[Casari, Giorgio] Ctr Translat Genom & Bioinformat, Milan, Italy.
[Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Fox, Caroline S.] Ctr Populat Studies, Framingham, MA USA.
[Marroni, Fabio] Inst Appl Genom, Udine, Italy.
[Parmigiani, Giovanni] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Parmigiani, Giovanni] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Pastore, Andrea] Ca Foscari Venezia Univ, Dept Econ, Venice, Italy.
[Pfeufer, Arne] German Res Ctr Environm Hlth GmbH, Helmholtz Zentrum Munich, Dept Bioinformat & Syst Biol IBIS, Neuherberg, Germany.
[Ruggeri, Fabrizio] Inst Appl Math & Informat Technol, Natl Res Council, Milan, Italy.
[Pramstaller, Peter P.] Cent Hosp, Dept Neurol, Bolzano, Italy.
[Pramstaller, Peter P.] Med Univ Lubeck, Dept Neurol, D-23538 Lubeck, Germany.
[Thompson, John R.] Univ Leicester, Dept Hlth Sci, Leicester, Leics, England.
RP Minelli, C (reprint author), EURAC Res, Ctr Biomed, Viale Druso 1, I-39100 Bolzano, Italy.
EM cosetta.minelli@eurac.edu
RI Pfeufer, Arne/B-6634-2013; Attia, John/F-5376-2013; Pramstaller,
Peter/C-2357-2008; Ruggeri, Fabrizio/A-9383-2012; Hicks,
Andrew/E-9518-2017;
OI Barrett, Jenny/0000-0002-1720-7724; Borsani,
Giuseppe/0000-0003-0110-1148; Attia, John/0000-0001-9800-1308; Ruggeri,
Fabrizio/0000-0002-7655-6254; Hicks, Andrew/0000-0001-6320-0411; CASARI,
Giorgio/0000-0002-0115-8980; Marroni, Fabio/0000-0002-1556-5907
FU Department for Promotion of Educational Policies, Universities and
Research of the Autonomous Province of Bolzano, South Tyrol, Italy; NIH
[HG000376]
FX All researchers from the Center for Biomedicine at EURAC were supported
by the Department for Promotion of Educational Policies, Universities
and Research of the Autonomous Province of Bolzano, South Tyrol, Italy;
M. B. was supported by NIH grant HG000376. None of the authors declare
any conflict of interest.
NR 47
TC 4
Z9 6
U1 0
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD FEB
PY 2013
VL 37
IS 2
BP 205
EP 213
DI 10.1002/gepi.21705
PG 9
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 074AK
UT WOS:000313784000009
PM 23307621
ER
PT J
AU Thompson, JR
Gogele, M
Weichenberger, CX
Modenese, M
Attia, J
Barrett, JH
Boehnke, M
De Grandi, A
Domingues, FS
Hicks, AA
Marroni, F
Pattaro, C
Ruggeri, F
Borsani, G
Casari, G
Parmigiani, G
Pastore, A
Pfeufer, A
Schwienbacher, C
Taliun, D
Fox, CS
Pramstaller, PP
Minelli, C
AF Thompson, John R.
Goegele, Martin
Weichenberger, Christian X.
Modenese, Mirko
Attia, John
Barrett, Jennifer H.
Boehnke, Michael
De Grandi, Alessandro
Domingues, Francisco S.
Hicks, Andrew A.
Marroni, Fabio
Pattaro, Cristian
Ruggeri, Fabrizio
Borsani, Giuseppe
Casari, Giorgio
Parmigiani, Giovanni
Pastore, Andrea
Pfeufer, Arne
Schwienbacher, Christine
Taliun, Daniel
Fox, Caroline S.
Pramstaller, Peter P.
Minelli, Cosetta
CA CKDGen Consortium
TI SNP Prioritization Using a Bayesian Probability of Association
SO GENETIC EPIDEMIOLOGY
LA English
DT Article
DE replication; prior knowledge; genome-wide studies
ID GENOME-WIDE ASSOCIATION; CHRONIC KIDNEY-DISEASE; STATISTICAL-METHODS;
POSITIVE REPORT; FALSE; EPIDEMIOLOGY; DISCOVERY
AB Prioritization is the process whereby a set of possible candidate genes or SNPs is ranked so that the most promising can be taken forward into further studies. In a genome-wide association study, prioritization is usually based on the P-values alone, but researchers sometimes take account of external annotation information about the SNPs such as whether the SNP lies close to a good candidate gene. Using external information in this way is inherently subjective and is often not formalized, making the analysis difficult to reproduce. Building on previous work that has identified 14 important types of external information, we present an approximate Bayesian analysis that produces an estimate of the probability of association. The calculation combines four sources of information: the genome-wide data, SNP information derived from bioinformatics databases, empirical SNP weights, and the researchers subjective prior opinions. The calculation is fast enough that it can be applied to millions of SNPS and although it does rely on subjective judgments, those judgments are made explicit so that the final SNP selection can be reproduced. We show that the resulting probability of association is intuitively more appealing than the P-value because it is easier to interpret and it makes allowance for the power of the study. We illustrate the use of the probability of association for SNP prioritization by applying it to a meta-analysis of kidney function genome-wide association studies and demonstrate that SNP selection performs better using the probability of association compared with P-values alone.
C1 [Thompson, John R.; CKDGen Consortium] Univ Leicester, Dept Hlth Sci, Leicester LE1 7RH, Leics, England.
[Goegele, Martin; Weichenberger, Christian X.; Modenese, Mirko; De Grandi, Alessandro; Domingues, Francisco S.; Hicks, Andrew A.; Pattaro, Cristian; Schwienbacher, Christine; Taliun, Daniel; Pramstaller, Peter P.; Minelli, Cosetta] European Acad Bozen Bolzano EURAC, Ctr Biomed, Bolzano, Italy.
[Attia, John] Univ Newcastle, Hunter Med Res Inst, Ctr Clin Epidemiol & Biostat, Newcastle, NSW 2300, Australia.
[Attia, John] John Hunter Hosp, Dept Gen Med, Newcastle, NSW, Australia.
[Barrett, Jennifer H.] Univ Leeds, Leeds Inst Mol Med, Sect Epidemiol & Biostat, Leeds, W Yorkshire, England.
[Boehnke, Michael] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.
[Boehnke, Michael] Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
[Marroni, Fabio] Inst Appl Genom, Udine, Italy.
[Ruggeri, Fabrizio] Inst Appl Math & Informat Technol, Natl Res Council, Milan, Italy.
[Borsani, Giuseppe] Univ Brescia, Dept Biomed Sci & Biotechnol, Brescia, Italy.
[Casari, Giorgio] Univ Vita Salute San Raffaele, Milan, Italy.
[Casari, Giorgio] Ctr Translat Genom & Bioinformat, Milan, Italy.
[Parmigiani, Giovanni] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Parmigiani, Giovanni] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Pastore, Andrea] Ca Foscari Venezia Univ, Dept Econ, Venice, Italy.
[Pfeufer, Arne] German Res Ctr Environm Hlth GmbH, Helmholtz Zentrum Munich, Dept Bioinformat & Syst Biol IBIS, Neuherberg, Germany.
[Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Fox, Caroline S.] Ctr Populat Studies, Framingham, MA USA.
[Pramstaller, Peter P.] Cent Hosp, Dept Neurol, Bolzano, Italy.
[Pramstaller, Peter P.] Med Univ Lubeck, Dept Neurol, D-23538 Lubeck, Germany.
RP Thompson, JR (reprint author), Univ Leicester, Dept Hlth Sci, Room 214F,Adrian Bldg, Leicester LE1 7RH, Leics, England.
EM john.thompson@le.ac.uk
RI Pfeufer, Arne/B-6634-2013; Attia, John/F-5376-2013; Pramstaller,
Peter/C-2357-2008; Ruggeri, Fabrizio/A-9383-2012; Hicks,
Andrew/E-9518-2017;
OI Borsani, Giuseppe/0000-0003-0110-1148; Attia, John/0000-0001-9800-1308;
Ruggeri, Fabrizio/0000-0002-7655-6254; Hicks,
Andrew/0000-0001-6320-0411; CASARI, Giorgio/0000-0002-0115-8980;
Marroni, Fabio/0000-0002-1556-5907; Barrett, Jenny/0000-0002-1720-7724
FU Department for Promotion of Educational Policies, Universities and
Research of the Autonomous Province of Bolzano, South Tyrol, Italy; NIH
[HG000376]
FX All researchers from the Center for Biomedicine at EURAC were supported
by the Department for Promotion of Educational Policies, Universities
and Research of the Autonomous Province of Bolzano, South Tyrol, Italy;
Michael Boehnke was supported by NIH grant HG000376. None of the authors
declares any conflict of interest.
NR 22
TC 1
Z9 3
U1 0
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD FEB
PY 2013
VL 37
IS 2
BP 214
EP 221
DI 10.1002/gepi.21704
PG 8
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 074AK
UT WOS:000313784000010
PM 23280596
ER
PT J
AU Van Houtven, CH
Thorpe, JM
Chestnutt, D
Molloy, M
Boling, JC
Davis, LL
AF Van Houtven, Courtney Harold
Thorpe, Joshua M.
Chestnutt, Deborah
Molloy, Margory
Boling, John C.
Davis, Linda Lindsey
TI Do Nurse-Led Skill Training Interventions Affect Informal Caregivers'
Out-of-Pocket Expenditures?
SO GERONTOLOGIST
LA English
DT Article
DE Cost analysis; Intervention study; Nurses/midwives/nursing; Alzheimer's
disease; Parkinson's disease; Average treatment effect
ID RANDOMIZED CONTROLLED-TRIAL; ALZHEIMERS-DISEASE; HOME PLACEMENT; CARE;
DEMENTIA; COST; BURDEN; CANCER; METAANALYSIS
AB Purpose of the Study: This paper is a report of a study of the Assistance, Support, and Self-health Initiated through Skill Training (ASSIST) randomized control trial. The aim of this paper is to understand whether participating in ASSIST significantly changed the out-of-pocket (OOP) costs for family caregivers of Alzheimer's disease (AD) or Parkinson's disease (PD) patients. Design and Methods: Secondary analysis of randomized control trial data, calculating average treatment effects of the intervention on OOP costs. Enrollment in the ASSIST trial occurred between 2002 and 2007 at 2 sites: Durham, North Carolina, and Birmingham, Alabama. We profile OOP costs for caregivers who participated in the ASSIST study and use 2-part expenditure models to examine the average treatment effect of the intervention on caregiver OOP expenditures. Results: ASSIST-trained AD and PD caregivers reported monthly OOP expenditures that averaged $500-$600. The intervention increased the likelihood of caregivers spending any money OOP by 26 percentage points over usual care, but the intervention did not significantly increase overall OOP costs. Implications: The ASSIST intervention was effective and inexpensive to the caregiver in direct monetary outlays; thus, there are minimal unintended consequences of the trial on caregiver financial well-being.
C1 [Van Houtven, Courtney Harold] Durham VA, Ctr Excellence Hlth Serv Res Primary Care, Durham, NC 27705 USA.
[Van Houtven, Courtney Harold] Duke Univ, Dept Med, Durham, NC USA.
[Thorpe, Joshua M.] Univ Pittsburgh, Sch Pharm, Pittsburgh, PA 15260 USA.
[Thorpe, Joshua M.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA.
[Chestnutt, Deborah] Ralph H Johnson Charleston Vet Adm Hosp, VA Nurse Acad, Charleston, SC USA.
[Molloy, Margory] Duke Univ, Sch Nursing, Ctr Nursing Discovery, Durham, NC USA.
RP Van Houtven, CH (reprint author), Durham VA, Ctr Excellence Hlth Serv Res Primary Care, 508 Fulton St, Durham, NC 27705 USA.
EM courtney.vanhoutven@duke.edu
RI Thorpe, Joshua/C-1188-2013
FU NINR NIH HHS [R01 NR 008285, R01 NR008285]
NR 36
TC 3
Z9 3
U1 2
U2 10
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
J9 GERONTOLOGIST
JI Gerontologist
PD FEB
PY 2013
VL 53
IS 1
BP 60
EP 70
DI 10.1093/geront/gns045
PG 11
WC Gerontology
SC Geriatrics & Gerontology
GA 071RV
UT WOS:000313612800007
PM 22459694
ER
PT J
AU Goodman, KA
Khalid, N
Kachnic, LA
Minsky, BD
Crozier, C
Owen, JB
Devlin, PM
Thomas, CR
AF Goodman, Karyn A.
Khalid, Najma
Kachnic, Lisa A.
Minsky, Bruce D.
Crozier, Cheryl
Owen, Jean B.
Devlin, Phillip M.
Thomas, Charles R., Jr.
TI Quality Research in Radiation Oncology Analysis of Clinical Performance
Measures in the Management of Gastric Cancer
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Article
ID POSTOPERATIVE CHEMORADIOTHERAPY; LOCAL-CONTROL; RADIOTHERAPY;
CHEMOTHERAPY; CARCINOMA; ADENOCARCINOMA; PROLONGATION; PATTERNS;
SURGERY; CARE
AB Background: The specific aim was to determine national patterns of radiation therapy (RT) practice in patients treated for stage IB-IV (nonmetastatic) gastric cancer (GC).
Methods and Materials: A national process survey of randomly selected US RT facilities was conducted which retrospectively assessed demographics, staging, geographic region, practice setting, and treatment by using on-site record review of eligible GC cases treated from 2005 to 2007. Three clinical performance measures (CPMs), (1) use of computed tomography (CT)-based treatment planning; (2) use of dose volume histograms (DVHs) to evaluate RT dose to the kidneys and liver; and (3) completion of RT within the prescribed time frame; and emerging quality indicators, (i) use of intensity modulated RT (IMRT); (ii) use of image-guided tools (IGRT) other than CT for RT target delineation; and (iii) use of preoperative RT, were assessed.
Results: CPMs were computed for 250 eligible patients at 45 institutions (median age, 62 years; 66% male; 60% Caucasian). Using 2000 American Joint Committee on Cancer criteria, 13% of patients were stage I, 29% were stage II, 32% were stage IIIA, 10% were stage IIIB, and 12% were stage IV. Most patients (43%) were treated at academic centers, 32% were treated at large nonacademic centers, and 25% were treated at small to medium sized facilities. Almost all patients (99.5%) underwent CT-based planning, and 75% had DVHs to evaluate normal tissue doses to the kidneys and liver. Seventy percent of patients completed RT within the prescribed time frame. IMRT and IGRT were used in 22% and 17% of patients, respectively. IGRT techniques included positron emission tomography (n=20), magnetic resonance imaging (n=1), respiratory gating and 4-dimensional CT (n=22), and on-board imaging (n=10). Nineteen percent of patients received preoperative RT.
Conclusions: This analysis of radiation practice patterns for treating nonmetastatic GC indicates widespread adoption of CT-based planning with use of DVH to evaluate normal tissue doses. Most patients completed adjuvant RT in the prescribed time frame. IMRT and IGRT were not routinely incorporated into clinical practice during the 2005-2007 period. These data will be a benchmark for future Quality Research in Radiation Oncology GC surveys. (C) 2013 Elsevier Inc.
C1 [Goodman, Karyn A.] Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10065 USA.
[Khalid, Najma; Crozier, Cheryl; Owen, Jean B.] Amer Coll Radiol, Clin Res Ctr, Philadelphia, PA USA.
[Kachnic, Lisa A.] Boston Univ, Med Ctr, Dept Radiat Oncol, Boston, MA USA.
[Minsky, Bruce D.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA.
[Devlin, Phillip M.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA.
[Thomas, Charles R., Jr.] Oregon Hlth & Sci Univ, Knight Canc Inst, Dept Radiat Med, Portland, OR 97201 USA.
RP Goodman, KA (reprint author), Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, 1275 York Ave, New York, NY 10065 USA.
EM goodmank@mskcc.org
FU National Institutes of Health National Cancer Institute [CA065435]
FX Quality Research in Radiation Oncology is supported by National
Institutes of Health National Cancer Institute grant CA065435.
NR 20
TC 1
Z9 2
U1 0