FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Poole, EM
Shu, XO
Caan, BJ
Flatt, SW
Holmes, MD
Lu, W
Kwan, ML
Nechuta, SJ
Pierce, JP
Chen, WY
AF Poole, Elizabeth M.
Shu, XiaoOu
Caan, Bette J.
Flatt, Shirley W.
Holmes, Michelle D.
Lu, Wei
Kwan, Marilyn L.
Nechuta, Sarah J.
Pierce, John P.
Chen, Wendy Y.
TI Postdiagnosis supplement use and breast cancer prognosis in the After
Breast Cancer Pooling Project
SO BREAST CANCER RESEARCH AND TREATMENT
LA English
DT Article
DE Breast cancer; Vitamins; Survival; Mortality
ID VITAMIN-D; COLORECTAL-CANCER; POSTMENOPAUSAL WOMEN; 25-HYDROXYVITAMIN D;
PROSPECTIVE COHORT; RADIATION-THERAPY; RANDOMIZED-TRIAL; NURSES HEALTH;
BETA-CAROTENE; LUNG-CANCER
AB Vitamin supplement use after breast cancer diagnosis is common, but little is known about long-term effects on recurrence and survival. We examined postdiagnosis supplement use and risk of death or recurrence in the After Breast Cancer Pooling Project, a consortium of four cohorts of 12,019 breast cancer survivors from the United States and China. Post-treatment supplement use (vitamins A, B, C, D, E, and multivitamins) was assessed 1-5 years postdiagnosis. Associations with risk of recurrence, breast cancer-specific mortality, or total mortality were analyzed in Cox proportional hazards models separately by cohort. Individual cohort results were combined using random effects meta-analysis. Interactions with smoking, treatment, and hormonal status were examined. In multivariate models, vitamin E was associated with a decreased risk of recurrence (RR: 0.88; 95 % CI 0.79-0.99), and vitamin C with decreased risk of death (RR: 0.81; 95 % CI 0.72-0.92). However, when supplements were mutually adjusted, all associations were attenuated. There were no statistically significant associations with breast cancer mortality. The use of antioxidant supplements (multivitamins, vitamin C, or E) was not associated with recurrence, but was associated with a 16 % decreased risk of death (95 % CI 0.72-0.99). In addition, vitamin D was associated with decreased risk of recurrence among ER positive, but not ER negative tumors (p-interaction = 0.01). In this large consortium of breast cancer survivors, post-treatment use of vitamin supplements was not associated with increased risk of recurrence or death. Post-treatment use of antioxidant supplements was associated with improved survival, but the associations with individual supplement were difficult to determine. Stratification by ER status and considering antioxidants as a group may be more clinically relevant when evaluating associations with cancer risk and mortality.
C1 [Poole, Elizabeth M.; Holmes, Michelle D.; Chen, Wendy Y.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Div Network Med,Dept Med, Boston, MA 02115 USA.
[Poole, Elizabeth M.; Holmes, Michelle D.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Shu, XiaoOu; Nechuta, Sarah J.] Vanderbilt Univ, Sch Med, Dept Med, Div Epidemiol, Nashville, TN 37212 USA.
[Shu, XiaoOu] Shanghai Inst Prevent Med, Shanghai, Peoples R China.
[Caan, Bette J.; Kwan, Marilyn L.] Kaiser Permanente, Div Res, Oakland, CA USA.
[Flatt, Shirley W.; Pierce, John P.] Univ Calif San Diego, Canc Prevent & Control Program, Moores UCSD Canc Ctr, San Diego, CA 92103 USA.
[Lu, Wei] Shanghai Municipal Ctr Dis Control & Prevent, Shanghai, Peoples R China.
[Chen, Wendy Y.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
RP Poole, EM (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Div Network Med,Dept Med, Boston, MA 02115 USA.
EM nhlip@channing.harvard.edu
OI Poole, Elizabeth/0000-0002-4680-4587
FU National Institutes of Health [R01 CA118229-03S1, R01 CA118229, R01
CA129059, P01 CA87969, T32 CA009001]; U.S. Army Medical Research and
Materiel Command [DAMD 17-02-1-0607]; Susan G. Komen for the Cure
[KG100988]
FX The NHS thanks the following state cancer registries for their help: AL,
AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI,
NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, and WY.
This study was supported by the National Institutes of Health (R01
CA118229-03S1, R01 CA118229, R01 CA129059, P01 CA87969, and T32
CA009001); the U.S. Army Medical Research and Materiel Command (DAMD
17-02-1-0607); and Susan G. Komen for the Cure (KG100988).
NR 34
TC 10
Z9 10
U1 2
U2 11
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-6806
J9 BREAST CANCER RES TR
JI Breast Cancer Res. Treat.
PD JUN
PY 2013
VL 139
IS 2
BP 529
EP 537
DI 10.1007/s10549-013-2548-4
PG 9
WC Oncology
SC Oncology
GA 173HM
UT WOS:000321069600023
PM 23660948
ER
PT J
AU Biswas, S
Atienza, P
Chipman, J
Hughes, K
Barrera, AMG
Amos, CI
Arun, B
Parmigiani, G
AF Biswas, Swati
Atienza, Philamer
Chipman, Jonathan
Hughes, Kevin
Barrera, Angelica M. Gutierrez
Amos, Christopher I.
Arun, Banu
Parmigiani, Giovanni
TI Simplifying clinical use of the genetic risk prediction model BRCAPRO
SO BREAST CANCER RESEARCH AND TREATMENT
LA English
DT Article
DE BRCA1; BRCA2; Genetic counseling; FHAT; CancerGene; BRCAPRO;
HughesRiskApps; Genetic risk
ID CARRIER PROBABILITY ESTIMATION; OVARIAN-CANCER; FAMILY-HISTORY; BREAST;
MUTATIONS; MANAGEMENT; MARKERS; WOMEN
AB Health care providers need simple tools to identify patients at genetic risk of breast and ovarian cancers. Genetic risk prediction models such as BRCAPRO could fill this gap if incorporated into Electronic Medical Records or other Health Information Technology solutions. However, BRCAPRO requires potentially extensive information on the counselee and her family history. Thus, it may be useful to provide simplified version(s) of BRCAPRO for use in settings that do not require exhaustive genetic counseling. We explore four simplified versions of BRCAPRO, each using less complete information than the original model. BRCAPROLYTE uses information on affected relatives only up to second degree. It is in clinical use but has not been evaluated. BRCAPROLYTE-Plus extends BRCAPROLYTE by imputing the ages of unaffected relatives. BRCAPRO-LYTE-Simple reduces the data collection burden associated with BRCAPROLYTE and BRCAPROLYTE-Plus by not collecting the family structure. BRCAPRO-1Degree only uses first-degree affected relatives. We use data on 2,713 individuals from seven sites of the Cancer Genetics Network and MD Anderson Cancer Center to compare these simplified tools with the Family History Assessment Tool (FHAT) and BRCAPRO, with the latter serving as the benchmark. BRCAPROLYTE retains high discrimination; however, because it ignores information on unaffected relatives, it overestimates carrier probabilities. BRCAPROLYTE-Plus and BRCAPROLYTE-Simple provide better calibration than BRCAPROLYTE, so they have higher specificity for similar values of sensitivity. BRCAPROLYTE-Plus performs slightly better than BRCAPROLYTE-Simple. The Areas Under the ROC curve are 0.783 (BRCAPRO), 0.763 (BRCAPROLYTE), 0.772 (BRCAPROLYTE-Plus), 0.773 (BRCAPROLYTE-Simple), 0.728 (BRCAPRO-1Degree), and 0.745 (FHAT). The simpler versions, especially BRCAPROLYTE-Plus and BRCAPROLYTE-Simple, lead to only modest loss in overall discrimination compared to BRCAPRO in this dataset. Thus, we conclude that simplified implementations of BRCAPRO can be used for genetic risk prediction in settings where collection of complete pedigree information is impractical.
C1 [Biswas, Swati] Univ Texas Dallas, Dept Math Sci, Richardson, TX 75080 USA.
[Atienza, Philamer] Univ N Texas, Dept Biostat, Sch Publ Hlth, Hlth Sci Ctr, Ft Worth, TX USA.
[Atienza, Philamer] Alcon Res Ltd, Ft Worth, TX USA.
[Chipman, Jonathan; Parmigiani, Giovanni] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Hughes, Kevin] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Barrera, Angelica M. Gutierrez; Arun, Banu] Univ Texas MD Anderson Canc Ctr, Dept Breast Med Oncol & Clin Canc Genet, Houston, TX 77030 USA.
[Amos, Christopher I.] Dartmouth Coll, Geisel Coll Med, Dept Community & Family Med, Hanover, NH 03755 USA.
[Parmigiani, Giovanni] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
RP Biswas, S (reprint author), Univ Texas Dallas, Dept Math Sci, FO 35,800 West Campbell Rd, Richardson, TX 75080 USA.
EM swati.biswas@utdallas.edu
OI Hughes, Kevin/0000-0003-4084-6484
FU Susan G Komen [KG081303]; National Cancer Institute [1R03CA173834-01,
2P30CA006516-47]; Dana Farber Cancer Institute
FX This work was supported in part by Susan G Komen Grant KG081303,
National Cancer Institute Grants 1R03CA173834-01 and 2P30CA006516-47 and
the Dana Farber Cancer Institute.
NR 19
TC 8
Z9 8
U1 0
U2 10
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 JUN
PY 2013
VL 139
IS 2
BP 571
EP 579
DI 10.1007/s10549-013-2564-4
PG 9
WC Oncology
SC Oncology
GA 173HM
UT WOS:000321069600027
PM 23690142
ER
PT J
AU Freedman, RA
Pitcher, B
Keating, NL
Ballman, KV
Mandelblatt, J
Kornblith, AB
Kimmick, GG
Hurria, A
Winer, EP
Hudis, CA
Cohen, HJ
Muss, HB
AF Freedman, Rachel A.
Pitcher, Brandelyn
Keating, Nancy L.
Ballman, Karla V.
Mandelblatt, Jeanne
Kornblith, Alice B.
Kimmick, Gretchen G.
Hurria, Arti
Winer, Eric P.
Hudis, Clifford A.
Cohen, Harvey Jay
Muss, Hyman B.
CA Alliance Clinical Trials Oncology
TI Cognitive function in older women with breast cancer treated with
standard chemotherapy and capecitabine on Cancer and Leukemia Group B
49907
SO BREAST CANCER RESEARCH AND TREATMENT
LA English
DT Article
DE Cognitive function; Older women; Breast cancer; Age
ID RECEIVING ADJUVANT CHEMOTHERAPY; MENOPAUSAL SYMPTOMS; DOSE CHEMOTHERAPY;
FOLLOW-UP; SURVIVORS; IMPAIRMENT; FATIGUE; ADULTS; QUESTIONNAIRE;
METAANALYSIS
AB Cognitive changes in older women receiving chemotherapy are poorly understood. We examined self-reported cognitive function for older women who received adjuvant chemotherapy on Cancer and Leukemia Group B (CALGB) 49907. CALGB 49907 randomized 633 women aged >= 65 with stage I-III breast cancer to standard adjuvant chemotherapy (cyclophosphamide-methotrexate-5-fluorouracil or doxorubicin-cyclophosphamide) versus capecitabine. We examined self-reported cognitive function in 297 women (CALGB 361002) who enrolled on the quality of life substudy and had no gross impairment on cognitive screening. Women were evaluated using an 18-item instrument at six time points (baseline through 24 months). At each time point for each patient, we calculated a cognitive function score (CFS) defined as themean response of items 1-18 and defined impairment as a score >1.5 standard deviations above the overall average baseline score. Differences in scores by patient characteristics were evaluated using a Kruskal-Wallis test. A linear mixed-effects model was used to assess CFSs by treatment over time. Among 297 women, the median age was 71.5 (range 65-85) and 73 % had performance status of 0. Baseline depression and fatigue were reported in 6 and 14 % of patients, respectively. The average CFS at baseline was 2.08 (corresponding to "normal ability"), and baseline cognitive function did not differ by treatment regimen (p = 0.350). Over 24 months, women reported minimal changes at each time point and insignificant differences by treatment arm were observed. In a healthy group of older women, chemotherapy was not associated with longitudinal changes in self-reported cognitive function.
C1 [Freedman, Rachel A.; Kornblith, Alice B.; Winer, Eric P.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
[Pitcher, Brandelyn] Duke Univ, Alliance Stat & Data Ctr, Durham, NC USA.
[Keating, Nancy L.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
[Keating, Nancy L.] Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA.
[Ballman, Karla V.] Mayo Clin, Alliance Stat & Data Ctr, Rochester, MN USA.
[Mandelblatt, Jeanne] Georgetown Univ, Dept Oncol, Lombardi Comprehens Canc Ctr, Washington, DC USA.
[Kimmick, Gretchen G.] Duke Med Oncol, Durham, NC USA.
[Hurria, Arti] City Hope Natl Med Ctr, Dept Med Oncol & Therapeut Res, Duarte, CA USA.
[Hurria, Arti] City Hope Natl Med Ctr, Dept Populat Sci, Duarte, CA USA.
[Hudis, Clifford A.] Mem Sloan Kettering, Dept Med Oncol, New York, NY USA.
[Cohen, Harvey Jay] Duke Med Oncol, Ctr Study Aging, Durham, NC USA.
[Muss, Hyman B.] Univ N Carolina, Dept Med, Chapel Hill, NC USA.
[Muss, Hyman B.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
RP Freedman, RA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA.
EM rafreedman@partners.org
OI Ballman, Karla/0000-0002-4492-0357
FU Celgene through Cancer and Leukemia Group B Foundation; National Cancer
Institute at the National Institutes of Health [U10 CA 84131, CA 127617,
CA096940, CA129769, CA31946, CA33601]; National Institute on Aging at
the National Institutes of Health [CA85850]
FX We thank all of the breast cancer patients who shared their experiences
while participating in this study. We also thank Dr. Andrew Saykin for
his guidance in using his cognitive function measure and Jacqueline
Lafky for her administrative and logistical support. We acknowledge
support from Celgene provided through the Cancer and Leukemia Group B
Foundation Young Investigator Award [RF]. This research was also
supported in part by the National Cancer Institute at the National
Institutes of Health [Grant # U10 CA 84131, CA 127617, CA096940, and
CA129769 to JSM] and by the National Institute on Aging at the National
Institutes of Health [Grant #CA85850 to HM]. The research for CALGB
49907 was also supported, in part, by the National Cancer Institute at
the National Institutes of Health [Grant # CA31946 to the Cancer and
Leukemia Group B (Monica Bernagnoli, MD, Chairman) and Grant # CA33601
to the CALGB Statistical Center (Stephen George, PhD)].
NR 42
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U1 1
U2 5
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 JUN
PY 2013
VL 139
IS 2
BP 607
EP 616
DI 10.1007/s10549-013-2562-6
PG 10
WC Oncology
SC Oncology
GA 173HM
UT WOS:000321069600031
PM 23681403
ER
PT J
AU Gainor, JF
Shaw, AT
AF Gainor, Justin F.
Shaw, Alice T.
TI The New Kid on the Block: RET in Lung Cancer
SO CANCER DISCOVERY
LA English
DT Editorial Material
ID FUSIONS; IDENTIFICATION; GENE; ADENOCARCINOMA; MUTATIONS; GEFITINIB;
KIF5B-RET; ALK
AB RET has recently been identified as a potential new oncogenic driver in a subset of patients with non-small cell lung cancer (NSCLC). In this issue of Cancer Discovery, Drilon and colleagues report preliminary trial data with a RET inhibitor in RET fusion-positive NSCLC, validating RET as a therapeutic target in lung cancer.
C1 [Gainor, Justin F.; Shaw, Alice T.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
RP Shaw, AT (reprint author), Massachusetts Gen Hosp, Dept Med, 55 Fruit St, Boston, MA 02114 USA.
EM ashaw1@partners.org
NR 15
TC 6
Z9 6
U1 0
U2 15
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 2159-8274
J9 CANCER DISCOV
JI Cancer Discov.
PD JUN
PY 2013
VL 3
IS 6
BP 604
EP 606
DI 10.1158/2159-8290.CD-13-0174
PG 3
WC Oncology
SC Oncology
GA 180RV
UT WOS:000321614100015
PM 23749525
ER
PT J
AU Killian, JK
Kim, SY
Miettinen, M
Smith, C
Merino, M
Tsokos, M
Quezado, M
Smith, WI
Jahromi, MS
Xekouki, P
Szarek, E
Walker, RL
Lasota, J
Raffeld, M
Klotzle, B
Wang, ZF
Jones, L
Zhu, YL
Wang, YH
Waterfall, JJ
O'Sullivan, MJ
Bibikova, M
Pacak, K
Stratakis, C
Janeway, KA
Schiffman, JD
Fan, JB
Helman, L
Meltzer, PS
AF Killian, J. Keith
Kim, Su Young
Miettinen, Markku
Smith, Carly
Merino, Maria
Tsokos, Maria
Quezado, Martha
Smith, William I., Jr.
Jahromi, Mona S.
Xekouki, Paraskevi
Szarek, Eva
Walker, Robert L.
Lasota, Jerzy
Raffeld, Mark
Klotzle, Brandy
Wang, Zengfeng
Jones, Laura
Zhu, Yuelin
Wang, Yonghong
Waterfall, Joshua J.
O'Sullivan, Maureen J.
Bibikova, Marina
Pacak, Karel
Stratakis, Constantine
Janeway, Katherine A.
Schiffman, Joshua D.
Fan, Jian-Bing
Helman, Lee
Meltzer, Paul S.
TI Succinate Dehydrogenase Mutation Underlies Global Epigenomic Divergence
in Gastrointestinal Stromal Tumor
SO CANCER DISCOVERY
LA English
DT Article
ID OF-FUNCTION MUTATIONS; IDH2 MUTATIONS; COPY-NUMBER; KIT; SUPPRESSORS;
INHIBITION; HISTONE; UPDATE; ASSAY; SDHA
AB Gastrointestinal stromal tumors (GIST) harbor driver mutations of signal transduction kinases such as KIT, or, alternatively, manifest loss-of-function defects in the mitochondrial succinate dehydrogenase (SDH) complex, a component of the Krebs cycle and electron transport chain. We have uncovered a striking divergence between the DNA methylation profiles of SDH-deficient GIST (n = 24) versus KIT tyrosine kinase pathway-mutated GIST (n = 39). Infinium 450K methylation array analysis of formalin-fixed paraffin-embedded tissues disclosed an order of magnitude greater genomic hypermethylation relative to SDH-deficient GIST versus the KIT-mutant group (84.9 K vs. 8.4 K targets). Epigenomic divergence was further found among SDH-mutant paraganglioma/pheochromocytoma (n = 29), a developmentally distinct SDH-deficient tumor system. Comparison of SDH-mutant GIST with isocitrate dehydrogenase-mutant glioma, another Krebs cycle-defective tumor type, revealed comparable measures of global hypo- and hypermethylation. These data expose a vital connection between succinate metabolism and genomic DNA methylation during tumorigenesis, and generally implicate the mitochondrial Krebs cycle in nuclear epigenomic maintenance.
SIGNIFICANCE: This study shows that SDH deficiency underlies pervasive DNA hypermethylation in multiple tumor lineages, generally defining the Krebs cycle as mitochondrial custodian of the methylome. We propose that this phenomenon may result from a failure of maintenance CpG demethylation, secondary to inhibition of the TET 5-methylcytosine dioxgenase demethylation pathway, by inhibitory metabolites that accumulate in tumors with Krebs cycle dysfunction. (c) 2013 AACR.
C1 [Killian, J. Keith; Kim, Su Young; Miettinen, Markku; Smith, Carly; Merino, Maria; Tsokos, Maria; Quezado, Martha; Walker, Robert L.; Lasota, Jerzy; Raffeld, Mark; Wang, Zengfeng; Jones, Laura; Zhu, Yuelin; Wang, Yonghong; Waterfall, Joshua J.; Helman, Lee; Meltzer, Paul S.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
[Smith, William I., Jr.] Suburban Hosp, Bethesda, MD USA.
[Xekouki, Paraskevi; Szarek, Eva; Pacak, Karel; Stratakis, Constantine] Eunice Kennedy Shriver NICHD, Bethesda, MD USA.
[Jahromi, Mona S.; Schiffman, Joshua D.] Univ Utah, Salt Lake City, UT USA.
[Klotzle, Brandy; Bibikova, Marina; Fan, Jian-Bing] Illumina Inc, San Diego, CA USA.
[Janeway, Katherine A.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[O'Sullivan, Maureen J.] Our Ladys Childrens Hosp, Dublin, Ireland.
RP Meltzer, PS (reprint author), NCI, Genet Branch, 37 Convent Dr MSC 4265, Bethesda, MD 20892 USA.
EM pmeltzer@mail.nih.gov
FU Intramural Research Program of NIH; National Cancer Institute; Center
for Cancer Research
FX This work was supported by grants from the Intramural Research Program
of NIH, the National Cancer Institute, and the Center for Cancer
Research.
NR 26
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U1 1
U2 24
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 2159-8274
J9 CANCER DISCOV
JI Cancer Discov.
PD JUN
PY 2013
VL 3
IS 6
BP 648
EP 657
DI 10.1158/2159-8290.CD-13-0092
PG 10
WC Oncology
SC Oncology
GA 180RV
UT WOS:000321614100022
PM 23550148
ER
PT J
AU Lum, G
AF Lum, Gifford
TI Severe Hyponatremia in a Schizophrenic Patient
SO CLINICAL CHEMISTRY
LA English
DT Editorial Material
ID BEER-DRINKERS; POTOMANIA
C1 VA Boston Healthcare Syst, Boston, MA 02132 USA.
RP Lum, G (reprint author), VA Boston Healthcare Syst, 1400 VFW Pkwy, Boston, MA 02132 USA.
EM gifford.lum@va.gov
NR 10
TC 1
Z9 1
U1 0
U2 1
PU AMER ASSOC CLINICAL CHEMISTRY
PI WASHINGTON
PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA
SN 0009-9147
J9 CLIN CHEM
JI Clin. Chem.
PD JUN
PY 2013
VL 59
IS 6
BP 887
EP 889
DI 10.1373/clinchem.2012.194969
PG 3
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA 179VC
UT WOS:000321548500005
PM 23719823
ER
PT J
AU Udell, JA
Morrow, DA
Braunwald, E
Swedberg, K
Bode, C
Rifai, N
Brunel, PC
Prescott, MF
Ren, F
Hoffman, EB
Scirica, BM
AF Udell, Jacob A.
Morrow, David A.
Braunwald, Eugene
Swedberg, Karl
Bode, Christoph
Rifai, Nader
Brunel, Patrick C.
Prescott, Margaret F.
Ren, Fang
Hoffman, Elaine B.
Scirica, Benjamin M.
TI Inhibition of the Renin-Angiotensin System Reduces the Rise in Serum
Aldosterone in Acute Coronary Syndrome Patients with Preserved Left
Ventricular Function: Observations from the AVANT GARDE-TIMI 43 Trial
SO CLINICAL CHEMISTRY
LA English
DT Article
ID ACUTE MYOCARDIAL-INFARCTION; NATRIURETIC-PEPTIDE; HEART-FAILURE; ORAL
CAPTOPRIL; DYSFUNCTION; MORTALITY; MORBIDITY; SURVIVAL; ACTIVATION;
EXTRACTION
AB BACKGROUND: Acute coronary syndrome (ACS) activates neurohormonal pathways, including elevations in circulating aldosterone, with deleterious cardiovascular effects. We aimed to determine if early, more complete renin-angiotensin-aldosterone system inhibition (RAASI) in post-ACS patients without ventricular dysfunction or heart failure would result in a graded reduction in aldosterone concentrations.
METHODS: We performed serial measurement of serum aldosterone within the Aliskiren and Valsartan to Reduce NT-proBNP via Renin-Angiotensin-Aldosterone-System Blockade (AVANT GARDE)-Thrombolysis in Myocardial Infarction (TIMI) 43 trial, a randomized double-blind, placebo controlled trial of RAASI by valsartan, aliskiren, or both in post-ACS patients with preserved ventricular function but increased natriuretic peptides. Aldosterone was measured at randomization and week 8.
RESULTS: Median aldosterone concentrations were comparable across treatment arms at baseline (9.26 ng/dL; interquartile range 7.12-12.76; n = 1073). In the placebo group, there was a significant increase in aldosterone over 8 weeks (19.7% rise, 2.20 (0.36) ng/dL, P < 0.0001) that was significantly reduced across active RAASI therapies (1.36 (0.39) ng/dL with aliskiren; 1.02 (0.37) ng/dL with valsartan; and 0.85 (0.37) ng/dL with combination therapy, P trend = 0.008). Compared to placebo, RAASI monotherapy resulted in a pooled relative absolute aldosterone change of -1.01 (0.45) ng/dL (P < 0.026 vs placebo), and combination therapy resulted in a relative absolute aldosterone change of -1.35 (0.52) ng/dL (P = 0.01 vs placebo). No significant difference in aldosterone concentrations was achieved between dual vs single RAASI (P = 0.47).
CONCLUSIONS: In ACS patients with preserved ventricular function but increased natriuretic peptides, serum aldosterone rises over time and is blunted by more complete RAASI. The clinical implications and role for RAASI in this population warrant further investigation. (C) 2013 American Association for Clinical Chemistry
C1 [Udell, Jacob A.; Morrow, David A.; Braunwald, Eugene; Ren, Fang; Hoffman, Elaine B.; Scirica, Benjamin M.] Brigham & Womens Hosp, Dept Med, Cardiovasc Div, TIMI Study Grp, Boston, MA 02115 USA.
[Udell, Jacob A.; Morrow, David A.; Braunwald, Eugene; Hoffman, Elaine B.; Scirica, Benjamin M.] Harvard Univ, Sch Med, Boston, MA USA.
[Udell, Jacob A.] Womens Coll Hosp, Dept Med, Cardiovasc Div, Toronto, ON, Canada.
[Udell, Jacob A.] Univ Toronto, Toronto, ON, Canada.
[Swedberg, Karl] Univ Gothenburg, Sahlgrenska Acad, Dept Emergency & Cardiovasc Med, Gothenburg, Sweden.
[Bode, Christoph] Med Univ Klin, Dept Internal Med Cardiol, Freiburg, Germany.
[Rifai, Nader] Childrens Hosp Boston, Dept Lab Med, Boston, MA USA.
[Brunel, Patrick C.] Novartis Pharma AG, Clin Dev & Med Affairs, Basel, Switzerland.
[Prescott, Margaret F.] Novartis Pharmaceut, Clin Dev & Med Affairs, E Hanover, NJ USA.
RP Scirica, BM (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.
EM bscirica@partners.org
FU Novartis Pharmaceuticals; Roche Diagnostics; Novartis; Bayer; Medtronic;
Sanofi-Aventis
FX AVANT GARDE-TIMI 43 was supported by a research grant to the TIMI Study
Group from Novartis Pharmaceuticals. Reagents for NT-proBNP were
provided via an unrestricted grant from Roche Diagnostics. D.A. Morrow,
Novartis; K. Swedberg, Novartis; C. Bode, Bayer, Medtronic, and
Sanofi-Aventis.
NR 39
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Z9 5
U1 0
U2 3
PU AMER ASSOC CLINICAL CHEMISTRY
PI WASHINGTON
PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA
SN 0009-9147
J9 CLIN CHEM
JI Clin. Chem.
PD JUN
PY 2013
VL 59
IS 6
BP 959
EP 967
DI 10.1373/clinchem.2012.199729
PG 9
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA 179VC
UT WOS:000321548500015
PM 23509108
ER
PT J
AU Kang, JX
Gleason, ED
AF Kang, Jing X.
Gleason, Erin D.
TI Omega-3 Fatty Acids and Hippocampal Neurogenesis in Depression
SO CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS
LA English
DT Article
DE Depression; docosahexaenoic acid (DHA); fat-1 mouse; hippocampus;
neurogenesis; omega-3 fatty acids
ID POLYUNSATURATED FATTY-ACID; PLACEBO-CONTROLLED TRIAL; BLOOD-CELL
MEMBRANES; DOCOSAHEXAENOIC ACID; MAJOR DEPRESSION; DOUBLE-BLIND; FISH
CONSUMPTION; FAT-1 MICE; EICOSAPENTAENOIC ACID; TRANSGENIC MICE
AB The mammalian brain and central nervous system are especially dependent on the omega-3 (n-3) fatty acid docosahexaenoic acid (DHA) for normative signaling and function, and research suggests that n-3 fatty acid deficiencies are one contributing factor in the increasing prevalence of depressive disorders. However, the reasons for which n-3 fatty acids and mood are connected remain unknown. Atrophy in the hippocampus is one of the most significant neuroanatomical findings in depressed patients, and current therapies for depression tend to increase hippocampal neurogenesis. We recently discovered that the fat-1 transgenic mouse, which has enriched levels of DHA in the brain because it can convert n-6 to n-3 fatty acids, exhibits increased hippocampal neurogenesis. This finding suggests a mechanism by which omega-3 could influence depression and mood; here we expand on the argument that n-3 fatty acids, and DHA in particular, may help prevent and treat depression by virtue of their effects on neurogenesis in the hippocampus. Because DHA can be obtained through the diet, increasing DHA intake in depressed patients or those at risk for depression may be one way of managing the disease and perhaps providing aid to those who have not been able to achieve remission via pharmacological means.
C1 Massachusetts Gen Hosp, Lab Lipid Med & Technol, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Kang, JX (reprint author), Massachusetts Gen Hosp, 149-13th St,Room 4433, Charlestown, MA 02129 USA.
EM jxkang@partners.org
NR 60
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U1 2
U2 15
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1871-5273
J9 CNS NEUROL DISORD-DR
JI CNS Neurol. Disord.-Drug Targets
PD JUN
PY 2013
VL 12
IS 4
BP 460
EP 465
PG 6
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 173UY
UT WOS:000321108000004
PM 23574158
ER
PT J
AU Race, E
Keane, MM
Verfaellie, M
AF Race, Elizabeth
Keane, Margaret M.
Verfaellie, Mieke
TI Living in the moment: Patients with MTL amnesia can richly describe the
present despite deficits in past and future thought
SO CORTEX
LA English
DT Letter
ID THINKING; MEMORY
C1 [Race, Elizabeth; Keane, Margaret M.; Verfaellie, Mieke] VA Boston Healthcare Syst, Boston, MA 02130 USA.
[Race, Elizabeth; Keane, Margaret M.; Verfaellie, Mieke] Boston Univ, Sch Med, Boston, MA 02130 USA.
[Keane, Margaret M.] Wellesley Coll, Dept Psychol, Wellesley, MA 02481 USA.
RP Race, E (reprint author), Boston VA Healthcare Syst, Memory Disorders Res Ctr, 150 S Huntington Ave 151-A, Boston, MA 02130 USA.
EM race@bu.edu
OI Verfaellie, Mieke/0000-0001-5535-4584
FU NIMH NIH HHS [R01 MH093431]; NINDS NIH HHS [F32 NS073212]
NR 5
TC 5
Z9 6
U1 0
U2 5
PU ELSEVIER MASSON
PI MILANO
PA VIA PALEOCAPA 7, 20121 MILANO, ITALY
SN 0010-9452
J9 CORTEX
JI Cortex
PD JUN
PY 2013
VL 49
IS 6
BP 1764
EP 1766
DI 10.1016/j.cortex.2013.02.010
PG 3
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA 174PZ
UT WOS:000321169200025
PM 23535365
ER
PT J
AU Shen, L
Zhang, Y
AF Shen, Li
Zhang, Yi
TI 5-Hydroxymethylcytosine: generation, fate, and genomic distribution
SO CURRENT OPINION IN CELL BIOLOGY
LA English
DT Article
ID EMBRYONIC STEM-CELLS; ACTIVE DNA DEMETHYLATION; HOST-INDUCED
MODIFICATION; DEOXYRIBONUCLEIC ACID; BASE-RESOLUTION; MAMMALIAN DNA; TET
PROTEINS; 5-METHYLCYTOSINE; METHYLATION; 5-CARBOXYLCYTOSINE
AB 5-Methylcytosine (5mC) can be converted to 5-hydroxymethylcytosine (5hmC) in mammalian cells by the ten-eleven translocation (Tet) family of dioxygenases. While 5mC has been extensively studied, we have just started to understand the distribution and function of 5hmC in mammalian genomes. Despite the fact that this new epigenetic mark has only been discovered three years ago, exciting progress has been made in understanding its generation, fate, and genomic distribution. In this review we discuss these progresses as well as the recent advance in the single-base resolution mapping of 5hmC.
C1 [Shen, Li; Zhang, Yi] Howard Hughes Med Inst, Boston, MA 02115 USA.
[Shen, Li; Zhang, Yi] Program Cellular & Mol Med, Boston, MA 02115 USA.
[Shen, Li; Zhang, Yi] Boston Childrens Hosp, Dept Pediat, Div Hematol Oncol, Boston, MA 02115 USA.
[Zhang, Yi] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Zhang, Yi] Harvard Stem Cell Inst, Boston, MA 02115 USA.
RP Zhang, Y (reprint author), Howard Hughes Med Inst, WAB 149G,200 Longwood Av, Boston, MA 02115 USA.
EM yzhang@genetics.med.harvard.edu
FU HHMI; NIH [U01DK089565]
FX We thank Diana Cai and Dr Hao Wu for critical reading of the manuscript.
This work was supported by HHMI and NIH (U01DK089565). Y.Z. is an
Investigator of the Howard Hughes Medical Institute.
NR 59
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U1 2
U2 31
PU CURRENT BIOLOGY LTD
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0955-0674
J9 CURR OPIN CELL BIOL
JI Curr. Opin. Cell Biol.
PD JUN
PY 2013
VL 25
IS 3
BP 289
EP 296
DI 10.1016/j.ceb.2013.02.017
PG 8
WC Cell Biology
SC Cell Biology
GA 177ZF
UT WOS:000321413200003
PM 23498661
ER
PT J
AU Beverly, EA
Fitzgerald, S
Sitnikov, L
Ganda, OP
Caballero, AE
Weinger, K
AF Beverly, Elizabeth A.
Fitzgerald, Shane
Sitnikov, Lilya
Ganda, Om P.
Caballero, A. Enrique
Weinger, Katie
TI Do Older Adults Aged 60-75 Years Benefit From Diabetes Behavioral
Interventions?
SO DIABETES CARE
LA English
DT Article
ID QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIALS; SELF-CARE; GLYCEMIC
CONTROL; EDUCATIONAL INTERVENTIONS; META-ANALYSIS; MANAGEMENT; MELLITUS;
METAANALYSIS; COMPLICATIONS
AB OBJECTIVE-In this secondary analysis, we examined whether older adults with diabetes (aged 60-75 years) could benefit from self-management interventions compared with younger adults. Seventy-one community-dwelling older adults and 151 younger adults were randomized to attend a structured behavioral group, an attention control group, or one-to-one education.
RESEARCH DESIGN AND METHODS-We measured AlC, self-care (3-day pedometer readings, blood glucose checks, and frequency of self-care), and psychosocial factors (quality of life, diabetes distress, frustration with self-care, depression, self-efficacy, and coping styles) at baseline and 3, 6, and 12 months postintervention.
RESULTS-Both older (age 67 +/- 5 years, AlC 8.7 +/- 0.8%, duration 20 +/- 12 years, 30% type 1 diabetes, 83% white, 41% female) and younger (age 47 +/- 9 years, AlC 9.2 +/- 1.2%, 18 +/- 12 years with diabetes, 59% type 1 diabetes, 82% white, 55% female) adults had improved AlC equally overtime. Importantly, older and younger adults in the group conditions improved more and maintained improvements at 12 months (older structured behavioral group change in AlC -0.72 +/- 1.4%, older control group -0.65 +/- 0.9%, younger behavioral group -0.55 +/- 1.2%, younger control group -0.43 +/- 1.7%). Furthermore, frequency of self-care, glucose checks, depressive symptoms, quality of life, distress, frustration with self-care, self-efficacy, and emotional coping improved in older and younger participants at follow-up.
CONCLUSIONS-The findings suggest that, compared with younger adults, older adults receive equal glycemic benefit from participating in self-management interventions. Moreover, older adults showed the greatest glycemic improvement in the two group conditions. Clinicians can safely recommend group diabetes interventions to community-dwelling older adults with poor glycemic control.
C1 [Beverly, Elizabeth A.; Fitzgerald, Shane; Sitnikov, Lilya; Ganda, Om P.; Caballero, A. Enrique; Weinger, Katie] Joslin Diabet Ctr, Boston, MA 02215 USA.
[Beverly, Elizabeth A.; Ganda, Om P.; Caballero, A. Enrique; Weinger, Katie] Harvard Univ, Sch Med, Boston, MA USA.
[Sitnikov, Lilya] Univ Vermont, Burlington, VT USA.
RP Weinger, K (reprint author), Joslin Diabet Ctr, Boston, MA 02215 USA.
EM katie.weinger@joslin.harvard.edu
FU National Institutes of Health (NIH) [R01-DK-060115]; Diabetes and
Endocrinology Research Core NIH [P30-DK-36836]; NIH [T32-DK-007260];
Merck; Abbott; GlaxoSmithKline; Bristol-Myers Squibb; AstraZeneca;
Daiichi-Sankyo
FX This work was supported by National Institutes of Health (NIH) Grant
R01-DK-060115 (to K.W.), Diabetes and Endocrinology Research Core NIH
Grant P30-DK-36836, and NIH Training Grant T32-DK-007260. The following
companies contributed glucose meters and test strips: Abbott
Laboratories (Abbott Park, IL), Life Scan (Milpitas, CA), and Roche
Diagnostics (Indianapolis, IN). O.P.G. has provided consulting services
to Abbott; received payment for lectures from Merck, Abbott,
GlaxoSmithKline, Bristol-Myers Squibb, AstraZeneca, and Daiichi-Sankyo;
and has stock options with Bristol-Myers Squibb. A.E.C. serves on the
advisory panels of the following companies: Eli Lilly and Company;
Amylin Pharmaceuticals, Inc.; Takeda Pharmaceuticals America, Inc;
sanofi-aventis; and Daiichi-Sankyo. No other potential conflicts of
interest relevant to this article were reported.
NR 40
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U1 1
U2 13
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
J9 DIABETES CARE
JI Diabetes Care
PD JUN
PY 2013
VL 36
IS 6
BP 1501
EP 1506
DI 10.2337/dc12-2110
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 178UJ
UT WOS:000321472600012
PM 23315603
ER
PT J
AU Lacroix, M
Battista, MC
Doyon, M
Menard, J
Ardilouze, JL
Perron, P
Hivert, MF
AF Lacroix, Marilyn
Battista, Marie-Claude
Doyon, Myriam
Menard, Julie
Ardilouze, Jean-Luc
Perron, Patrice
Hivert, Marie-France
TI Lower Adiponectin Levels at First Trimester of Pregnancy Are Associated
With Increased Insulin Resistance and Higher Risk of Developing
Gestational Diabetes Mellitus
SO DIABETES CARE
LA English
DT Article
ID GLUCOSE-TOLERANCE; LIPID-METABOLISM; SENSITIVITY; WOMEN;
RECOMMENDATIONS; HYPERGLYCEMIA; SECRETION; ALPHA
AB OBJECTIVE-To evaluate the associations between adiponectin levels and 1) the risk of developing gestational diabetes mellitus (GDM), and 2) insulin resistance/sensitivity, beta-cell function, and compensation indices in a prospective cohort representative of the general population of pregnant women.
RESEARCH DESIGN AND METHODS-We performed anthropometric measurements and collected blood samples at 1st (6-13 weeks) and 2nd (24-28 weeks) trimesters. Diagnosis of GDM was made at 2nd trimester based on a 75-g oral glucose tolerance test (International Association of the Diabetes and Pregnancy Study Groups criteria). Insulin was measured (ELISA; Luminex) to estimate homeostasis model assessment of insulin resistance (HOMA-IR), beta-cell function (HOMA-B), insulin sensitivity (Matsuda index), insulin secretion (AUC(insulin/glucose)), and beta-cell compensation (insulin secretion sensitivity index-2). Adiponectin was measured by radioimmunoassay.
RESULTS-Among the 445 participants included in this study, 38 women developed GDM. Women who developed GDM had lower 1st-trimester adiponectin levels (9.67 +/- 3.84 vs. 11.92 +/- 4.59 mu g/mL in women with normal glucose tolerance). Lower adiponectin levels were associated with higher risk of developing GDM (OR, 1.12 per 1 mu g/mL decrease of adiponectin levels; P = 0.02, adjusted for BMI and HbA(1c) at 1st trimester). Adiponectin levels at 1st and 2nd trimesters were associated with HOMA-IR (both: r = -0.22, P < 0.0001) and Matsuda index (r = 0.28, P < 0.0001, and r = 0.29, P < 0.0001). After adjustment for confounding factors, we found no significant association with HOMA-B and AUC(insulin/glucose).
CONCLUSIONS-Pregnant women with lower adiponectin levels at 1st trimester have higher levels of insulin resistance and are more likely to develop GDM independently of adiposity or glycemic measurements.
C1 [Lacroix, Marilyn; Battista, Marie-Claude; Ardilouze, Jean-Luc; Perron, Patrice; Hivert, Marie-France] Univ Sherbrooke, Fac Med, Sherbrooke, PQ, Canada.
[Doyon, Myriam; Menard, Julie; Ardilouze, Jean-Luc; Perron, Patrice; Hivert, Marie-France] CHU Sherbrooke, Ctr Rech Clin Etienne Le Bel, Sherbrooke, PQ J1H 5N4, Canada.
[Hivert, Marie-France] Massachusetts Gen Hosp, Gen Med Div, Boston, MA 02114 USA.
RP Hivert, MF (reprint author), Univ Sherbrooke, Fac Med, Sherbrooke, PQ, Canada.
EM marie-france.hivert@usherbrooke.ca
FU Fonds de la Recherche en Sante du Quebec (FRSQ); Diabete Quebec;
Canadian Diabetes Association; Institute of Genetics-Canadian Institute
of Health Research (CIHR)
FX The study was supported by a Fonds de la Recherche en Sante du Quebec
(FRSQ) operating grant (to M.-F.H.) and by Diabete Quebec (to P.P.).
M.-F.H. is an FRSQ research scholar and was awarded a Clinical Scientist
Award by the Canadian Diabetes Association and the Maud Menten Award
from the Institute of Genetics-Canadian Institute of Health Research
(CIHR). J.-L.A. is a CIHR scholar (New Investigator award). M.L. was
supported by Diabete Quebec. Clinical assessments were performed at the
Clinical Research Center Etienne-Le Bel (CRCEL) affiliated with the
CHUS; the CRCEL is an FRSQ-supported research center.
NR 30
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U1 1
U2 6
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
EI 1935-5548
J9 DIABETES CARE
JI Diabetes Care
PD JUN
PY 2013
VL 36
IS 6
BP 1577
EP 1583
DI 10.2337/dc12-1731
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 178UJ
UT WOS:000321472600022
PM 23300287
ER
PT J
AU Katon, JG
Reiber, GE
Nelson, KM
AF Katon, Jodie G.
Reiber, Gayle E.
Nelson, Karin M.
TI Peripheral Neuropathy Defined by Monofilament Insensitivity and Diabetes
Status NHANES 1999-2004
SO DIABETES CARE
LA English
DT Article
ID IMPAIRED GLUCOSE-TOLERANCE; SENSORY NEUROPATHY; PREVALENCE;
POLYNEUROPATHY; POPULATION; MELLITUS; FOOT
AB OBJECTIVE-To determine whether diabetes status, including prediabetes, is associated with increased risk of peripheral neuropathy as defined by monofilament insensitivity.
RESEARCH DESIGN AND METHODS-This study used data from the 1999-2004 National Health and Nutrition Examination Survey (n = 7,818). Peripheral neuropathy was defined as one or more insensate sites detected by a Semmes-Weinstein 10-g monofilament. Generalized linear models were used to directly estimate relative risks (RRs) for the association of diabetes status and peripheral neuropathy.
RESULTS-After adjustment compared with no diabetes, prediabetes [RR 1.11(95% CI 0.92-1.34)] and undiagnosed diabetes [1.08 (0.73-1.61)] were associated with modest increases in risk of peripheral neuropathy, and diabetes was associated with a 74% higher risk of peripheral neuropathy [1.74 (1.50-2.01)].
CONCLUSIONS-Diabetes is associated with increased risk of peripheral neuropathy defined by monofilament insensitivity, but prediabetes and undiagnosed diabetes may be associated with only a modest increase in risk.
C1 [Katon, Jodie G.; Reiber, Gayle E.; Nelson, Karin M.] Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA.
[Katon, Jodie G.; Reiber, Gayle E.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
[Reiber, Gayle E.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Nelson, Karin M.] Univ Washington, Dept Med, Seattle, WA USA.
[Nelson, Karin M.] Vet Affairs Puget Sound Hlth Care Syst, Gen Med Serv, Seattle, WA USA.
RP Katon, JG (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA.
EM jkaton@uw.edu
FU Office of Research and Development; Health Services Research and
Development; U.S. Department of Veterans Affairs [TPP 61-026, RCS
98-353]
FX This material is based on work supported by the Office of Research and
Development, Health Services Research and Development, U.S. Department
of Veterans Affairs, including a postdoctoral fellowship to J.G.K. (TPP
61-026) and a Senior Career Scientist Award to G.E.R. (grant RCS
98-353).
NR 18
TC 6
Z9 6
U1 0
U2 2
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
J9 DIABETES CARE
JI Diabetes Care
PD JUN
PY 2013
VL 36
IS 6
BP 1604
EP 1606
DI 10.2337/dc12-1102
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 178UJ
UT WOS:000321472600026
PM 23275365
ER
PT J
AU Copeland, KC
Higgins, J
El Ghormli, L
Delahanty, L
Grey, M
Kriska, AM
Lipman, TH
Pyle, L
Shepherd, J
Hirst, K
AF Copeland, Kenneth C.
Higgins, Janine
El Ghormli, Laure
Delahanty, Linda
Grey, Margaret
Kriska, Andrea M.
Lipman, Terri H.
Pyle, Laura
Shepherd, John
Hirst, Kathryn
CA TODAY Study Grp
TI Treatment Effects on Measures of Body Composition in the TODAY Clinical
Trial
SO DIABETES CARE
LA English
DT Article
ID SAGITTAL ABDOMINAL DIAMETER; CARDIOVASCULAR RISK-FACTORS; TYPE-2
DIABETES-MELLITUS; WAIST CIRCUMFERENCE; GLYCEMIC CONTROL;
ANTIHYPERGLYCEMIC AGENTS; GLUCOSE-METABOLISM; INSULIN-RESISTANCE;
ADIPOSE-TISSUE; YOUNG-ADULTS
AB OBJECTIVE-The Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) trial showed superiority of metformin plus rosiglitazone (M+R) over metformin alone (M), with metformin plus lifestyle (M+L) intermediate in maintaining glycemic control. We report here treatment effects on measures of body composition and their relationships to demographic and metabolic variables including glycemia.
RESEARCH DESIGN AND METHODS-Measures of adiposity (BMI, waist circumference, abdominal height, percent and absolute fat, and bone mineral content [BMC] and density [BMD]) were analyzed as change from baseline at 6 and 24 months.
RESULTS-Measures of fat accumulation were greatest in subjects treated with M+R and least in M+L. Although fat measures in M+L were less than those of M+R and M at 6 months, differences from M were no longer apparent at 24 months, whereas differences from M+R persisted at 24 months. The only body composition measure differing by race and/or ethnicity was waist circumference, greater in M+R than either M or M+L at both 6 and 24 months in whites. BMD and BMC increased in all groups, but increased less in M+R compared with the other two groups by 24 months. Measures of adiposity (increases in BMI, waist circumference, abdominal height, and fat) were associated with reduced insulin sensitivity and increased hemoglobin A(1c) (HbA(1c)), although effects of adiposity on HbA(1c) were less evident in those treated with M+R.
CONCLUSIONS-Despite differential effects on measures of adiposity (with M+R resulting in the most and M+L in the least fat accumulation), group differences generally were small and unrelated to treatment effects in sustaining glycemic control.
C1 [Copeland, Kenneth C.] Univ Oklahoma, Hlth Sci Ctr, Norman, OK 73019 USA.
[Higgins, Janine] Univ Colorado, Hlth Sci Ctr, Boulder, CO 80309 USA.
[El Ghormli, Laure; Pyle, Laura; Hirst, Kathryn] George Washington Univ, Ctr Biostat, Washington, DC 20052 USA.
[Delahanty, Linda] Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA.
[Grey, Margaret] Yale Univ, Sch Nursing, New Haven, CT 06520 USA.
[Kriska, Andrea M.] Childrens Hosp Pittsburgh, Pittsburgh, PA USA.
[Lipman, Terri H.] Childrens Hosp Philadelphia, Philadelphia, PA USA.
[Shepherd, John] Univ Calif San Francisco, San Francisco, CA 94143 USA.
RP El Ghormli, L (reprint author), George Washington Univ, Ctr Biostat, Washington, DC 20052 USA.
EM elghorml@bsc.gwu.edu
OI Kriska, Andrea/0000-0002-3522-0869
FU NIDDK of the National Institutes of Health [U01-DK61212, U01-DK-61230,
U01-DK-61239, U01-DK-61242, U01-DK-61254]; National Center for Research
Resources (NCRR) General Clinical Research Centers Program [Washington
University School of Medicine] [M01RR-00036]; National Center for
Research Resources (NCRR) General Clinical Research Centers Program
[Children's Hospital Los Angeles] [M01-RR-00043-45]; National Center for
Research Resources (NCRR) General Clinical Research Centers Program
[University of Colorado Denver] [M01-RR-00069]; National Center for
Research Resources (NCRR) General Clinical Research Centers Program
[Children's Hospital of Pittsburgh] [M01-RR-00084]; National Center for
Research Resources (NCRR) General Clinical Research Centers Program
[Massachusetts General Hospital] [M01-RR-01066]; National Center for
Research Resources (NCRR) General Clinical Research Centers Program
[Yale University] [M01-RR00125]; National Center for Research Resources
(NCRR) General Clinical Research Centers Program [University of Oklahoma
Health Sciences Center] [M01-RR-14467]; NCRR Clinical and Translational
Science Award [Children's Hospital of Philadelphia] [UL1-RR-024134];
NCRR Clinical and Translational Science Award [Yale University] [UL1
-RR024139]; NCRR Clinical and Translational Science Award [Children's
Hospital of Pittsburgh] [UL1-RR-024153]; NCRR Clinical and Translational
Science Award [Case Western Reserve University] [UL1-RR024989]; NCRR
Clinical and Translational Science Award [Washington University in St.
Louis] [UL1-RR-024992]; NCRR Clinical and Translational Science Award
[Massachusetts General Hospital] [UL1-RR-025758]; NCRR Clinical and
Translational Science Award [University of Colorado Denver]
[UL1-RR-025780]
FX This work was completed with funding from the NIDDK of the National
Institutes of Health (grants U01-DK61212, U01-DK-61230, U01-DK-61239,
U01-DK-61242, and U01-DK-61254), the National Center for Research
Resources (NCRR) General Clinical Research Centers Program (grants
M01-RR-00036 [Washington University School of Medicine], M01-RR-00043-45
[Children's Hospital Los Angeles], M01-RR-00069 [University of Colorado
Denver], M01-RR-00084 [Children's Hospital of Pittsburgh], M01-RR-01066
[Massachusetts General Hospital], M01-RR00125 [Yale University], and
M01-RR-14467 [University of Oklahoma Health Sciences Center]), and the
NCRR Clinical and Translational Science Awards (grants UL1-RR-024134
[Children's Hospital of Philadelphia], UL1 -RR024139 [Yale University],
UL1-RR-024153 [Children's Hospital of Pittsburgh], UL1-RR024989 [Case
Western Reserve University], UL1-RR-024992 [Washington University in St.
Louis], UL1-RR-025758 [Massachusetts General Hospital], and
UL1-RR-025780 [University of Colorado Denver]).
NR 31
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U1 0
U2 1
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
EI 1935-5548
J9 DIABETES CARE
JI Diabetes Care
PD JUN
PY 2013
VL 36
IS 6
BP 1742
EP 1748
DI 10.2337/dc12-2534
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 178UJ
UT WOS:000321472600048
ER
PT J
AU Weinstock, RS
Caprio, S
Copeland, KC
Gidding, SS
Hirst, K
Katz, LL
Marcovina, S
Nadeau, KJ
Nathan, DM
AF Weinstock, Ruth S.
Caprio, Sonia
Copeland, Kenneth C.
Gidding, Samuel S.
Hirst, Kathryn
Katz, Lorraine L.
Marcovina, Santica
Nadeau, Kristen J.
Nathan, David M.
CA TODAY Study Grp
TI Lipid and Inflammatory Cardiovascular Risk Worsens Over 3 Years in Youth
With Type 2 Diabetes The TODAY clinical trial
SO DIABETES CARE
LA English
DT Article
ID BLOOD-GLUCOSE CONTROL; LIPOPROTEIN CHOLESTEROL; LIFE-STYLE; FOLLOW-UP;
COMPLICATIONS; ADOLESCENTS; ATHEROSCLEROSIS; PREVENTION; OVERWEIGHT;
METFORMIN
AB OBJECTIVE-Type 2 diabetes increases cardiovascular risk. We examined lipid profiles and inflammatory markers in 699 youth with recent-onset type 2 diabetes in the TODAY clinical trial and compared changes across treatment groups: metformin alone (M), metformin plus rosiglitazone (M+R), and metformin plus intensive lifestyle program (M+L).
RESEARCH DESIGN AND METHODS-Multiethnic youth with type 2 diabetes received M, M+R, or M+L. Statin drugs were begun for LDL cholesterol (LDL) >= 130 mg/dL or triglycerides >= 300 mg/dL. Lipids, apolipoprotein B (apoB), LDL particle size, high-sensitivity c-reactive protein (hsCRP), homocysteine, plasminogen activator inhibitor-1 (PAT-1), and HbA(1c) were measured over 36 months or until loss of glycemic control.
RESULTS-LDL, apoB, triglycerides, and non-HDL cholesterol (HDL) rose over 12 months and then stabilized over the next 24 months. Participants with LDL >= 130 mg/dL or using LDL-lowering therapy increased from 4.5 to 10.7% over 36 months, while 55.9% remained at LDL goal (<100 mg/dL) over that time. Treatment group did not impact LDL, apoB, or non-HDL. Small dense LDL (particle size, <= 0.263 relative flotation rate) was most common in M. Triglycerides were lower in M+L than M, and M+L attenuated the negative effect of hyperglycemia on triglycerides and HDL in females. hsCRP, PAI-1, and homocysteine increased over time. However, hsCRP was lower in M+R compared with M or M+L.
CONCLUSIONS-Dyslipidemia and chronic inflammation were common in youth with type 2 diabetes and worsened over time. Diabetes treatment, despite some treatment group differences in lipid and inflammatory marker change over time, is generally inadequate to control this worsening risk.
C1 [Weinstock, Ruth S.] SUNY Upstate Med Univ, Syracuse, NY 13210 USA.
[Caprio, Sonia] Yale Univ, Sch Med, New Haven, CT 06520 USA.
[Copeland, Kenneth C.] Univ Oklahoma, Hlth Sci Ctr, Norman, OK 73019 USA.
[Hirst, Kathryn] George Washington Univ, Washington, DC 20052 USA.
[Katz, Lorraine L.] Childrens Hosp Philadelphia, Philadelphia, PA USA.
[Nadeau, Kristen J.] Univ Colorado Denver, Denver, CO USA.
[Nathan, David M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Hirst, K (reprint author), George Washington Univ, Washington, DC 20052 USA.
EM khirst@bsc.gwu.edu
FU National Institute of Diabetes and Digestive and Kidney
Diseases/National Institutes of Health [U01DK-61212, U01-DK-61230,
U01-DK-61239, U01-DK-61242, U01-DK-61254]; National Center for Research
Resources General Clinical Research Centers Program (Washington
University School of Medicine) [M01-RR00036]; National Center for
Research Resources General Clinical Research Centers Program (Children's
Hospital Los Angeles) [M01-RR00043-45]; National Center for Research
Resources General Clinical Research Centers Program (University of
Colorado Denver) [M01-RR00069]; National Center for Research Resources
General Clinical Research Centers Program (Children's Hospital of
Pittsburgh) [M01-RR00084, ULI-RR024153]; National Center for Research
Resources General Clinical Research Centers Program (Massachusetts
General Hospital) [M01-RR01066, UL1-8R025758]; National Center for
Research Resources General Clinical Research Centers Program (Yale
University) [M01-RR00125, UL1-RR024139]; National Center for Research
Resources General Clinical Research Centers Program (University of
Oklahoma Health Sciences Center) [M01-RR14467]; National Center for
Research Resources Clinical and Translational Science Award (Children's
Hospital of Philadelphia) [UL1-RR024134]; National Center for Research
Resources General Clinical Research Centers Program (Case Western
Reserve University) [UL1RR024989]; National Center for Research
Resources General Clinical Research Centers Program (Washington
University in St. Louis) [ULI-RR024992]; National Center for Research
Resources General Clinical Research Centers Program (University of
Colorado Denver [UL1-RR025780]; Eli Lilly and Company; GlaxoSmithKline;
Medtronic; AstraZeneca; Daiichi Sankyo
FX This work was completed with funding from National Institute of Diabetes
and Digestive and Kidney Diseases/National Institutes of Health grants
U01DK-61212, U01-DK-61230, U01-DK-61239, U01-DK-61242, and U01-DK-61254;
National Center for Research Resources General Clinical Research Centers
Program grants M01-RR00036 (Washington University School of Medicine),
M01-RR00043-45 (Children's Hospital Los Angeles), M01-RR00069
(University of Colorado Denver), M01-RR00084 (Children's Hospital of
Pittsburgh), M01-RR01066 (Massachusetts General Hospital), M01-RR00125
(Yale University), and M01-RR14467 (University of Oklahoma Health
Sciences Center); and National Center for Research Resources Clinical
and Translational Science Awards grants UL1-RR024134 (Children's
Hospital of Philadelphia), UL1-RR024139 (Yale University), ULI-RR024153
(Children's Hospital of Pittsburgh), UL1RR024989 (Case Western Reserve
University), ULI-RR024992 (Washington University in St. Louis),
UL1-8R025758 (Massachusetts General Hospital), and UL1-RR025780
(University of Colorado Denver).; R.S.W. is site principal investigator
with no salary support for industry-sponsored multicenter clinical
trials funded by grants administered through the State University of New
York Upstate Medical University from Eli Lilly and Company,
GlaxoSmithKline, Medtronic, and AstraZeneca. K.C.C. receives a
consulting fee and honorarium as a member of the Steering Committee for
a research study conducted by Daiichi Sankyo. S.S.G. has a clinical
trial of fish oil for high triglycerides in adolescents funded by
GlaxoSmithKline. No other potential conflicts of interest relevant to
this article were reported.
NR 21
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U1 1
U2 2
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
J9 DIABETES CARE
JI Diabetes Care
PD JUN
PY 2013
VL 36
IS 6
BP 1758
EP 1764
DI 10.2337/dc12-2388
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 178UJ
UT WOS:000321472600050
ER
PT J
AU Levitsky, LL
Danis, RP
Drews, KL
Tamborlane, WV
Haymond, MW
Laffel, L
Lipman, TH
AF Levitsky, Lynne L.
Danis, Ronald P.
Drews, Kimberly L.
Tamborlane, William V.
Haymond, Morey W.
Laffel, Lori
Lipman, Terri H.
CA TODAY Study Grp
TI Retinopathy in Youth With Type 2 Diabetes Participating in the TODAY
Clinical Trial
SO DIABETES CARE
LA English
DT Article
ID PREVALENCE; COHORT; COMPLICATIONS; ADOLESCENTS; PROGRAM
AB OBJECTIVE-To determine the prevalence of retinopathy in 517 youth with type 2 diabetes of 2-8 years duration enrolled in the TODAY study.
RESEARCH DESIGN AND METHODS-Retinal photographs were graded centrally for retinopathy using established standards.
RESULTS-Retinopathy was identified in 13.7% of subjects. Prevalence increased with age, diabetes duration, and mean HbA(1c). Subjects in the highest BMI tertile had the lowest prevalence of retinopathy.
CONCLUSIONS-Prevalence of retinopathy and its association with HbA(1c) and diabetes duration is similar to that previously reported in youth with type 1 diabetes and in adults with type 2 diabetes of known duration. The mechanism underlying the reduced risk of retinopathy in the most obese individuals is unknown. Follow-up of this cohort will help define the natural history of retinopathy in youth with type 2 diabetes.
C1 [Levitsky, Lynne L.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Danis, Ronald P.] Univ Wisconsin, Madison, WI 53706 USA.
[Drews, Kimberly L.] George Washington Univ, Washington, DC 20052 USA.
[Tamborlane, William V.] Yale Univ, Sch Med, New Haven, CT 06520 USA.
[Haymond, Morey W.] Baylor Coll Med, Houston, TX 77030 USA.
[Lipman, Terri H.] Childrens Hosp Philadelphia, Philadelphia, PA USA.
RP Drews, KL (reprint author), George Washington Univ, Washington, DC 20052 USA.
EM kdrews@bsc.gwu.edu
FU National Institute of Diabetes and Digestive and Kidney
Diseases/National Institutes of Health [U01-DK61212, U01-DK61230,
U01-DK61239, U01-DK61242, U01-DK61254]; National Center for Research
Resources General Clinical Research Centers Program [M01-RR00036,
M01-RR00043-45, M01-RR00069, M01-RR00084, M01-RR01066, M01-RR00125,
M01-RR14467]; National Center for Research Resources Clinical and
Translational Science Awards [UL1-RR024134, UL1-RR024139, UL1-RR024153,
UL1-RR024989, UL1-RR024992, UL1-RR025758, UL1-RR025780]
FX This work was completed with funding from National Institute of Diabetes
and Digestive and Kidney Diseases/National Institutes of Health (grant
numbers U01-DK61212, U01-DK61230, U01-DK61239, U01-DK61242, and
U01-DK61254); the National Center for Research Resources General
Clinical Research Centers Program (grant numbers M01-RR00036 [Washington
University School of Medicine], M01-RR00043-45 [Children's Hospital Los
Angeles], M01-RR00069 [University of Colorado Denver], M01-RR00084
[Children's Hospital of Pittsburgh], M01-RR01066 [Massachusetts General
Hospital], M01-RR00125 [Yale University], and M01-RR14467 [University of
Oklahoma Health Sciences Center]); and the National Center for Research
Resources Clinical and Translational Science Awards (grant numbers
UL1-RR024134 [Children's Hospital of Philadelphia], UL1-RR024139 [Yale
University], UL1-RR024153 [Children's Hospital of Pittsburgh],
UL1-RR024989 [Case Western Reserve University], UL1-RR024992 [Washington
University in St. Louis], UL1-RR025758 [Massachusetts General Hospital],
and UL1-RR025780 [University of Colorado Denver]).
NR 13
TC 26
Z9 26
U1 0
U2 1
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
J9 DIABETES CARE
JI Diabetes Care
PD JUN
PY 2013
VL 36
IS 6
BP 1772
EP 1774
DI 10.2337/dc12-2387
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 178UJ
UT WOS:000321472600052
ER
PT J
AU Griffith, JW
Luster, AD
AF Griffith, Jason W.
Luster, Andrew D.
TI Targeting cells in motion: Migrating toward improved therapies
SO EUROPEAN JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID RELAPSING MULTIPLE-SCLEROSIS; PROGRESSIVE MULTIFOCAL
LEUKOENCEPHALOPATHY; ALPHA-4 INTEGRIN EXPRESSION; NOVO
RENAL-TRANSPLANTATION; CXC CHEMOKINE RECEPTOR-5; PLACEBO-CONTROLLED
TRIAL; T-CELLS; SPHINGOSINE 1-PHOSPHATE; LYMPHOCYTE RECIRCULATION;
DIFFERENTIALLY AFFECTS
AB The development of clinical therapeutics that interfere with the migration of leukocytes has revolutionized the treatment of multiple sclerosis and holds great promise for the treatment of a wide range of inflammatory diseases. As the molecules essential for the multi-step adhesion cascade that mediates cellular migration have been elucidated, the number of potential targets available to modulate leukocyte trafficking has increased exponentially. In this Viewpoint, we briefly review our current understanding of these molecular targets and how these targets vary by tissue and leukocyte subset with emphasis on T cells. We then describe the two currently approved therapeutics that target cell migration, natalizumab and fingolimod, and discuss how an improved understanding of their function could pave the way for the development of safer and more efficacious therapies for inflammatory and autoimmune diseases.
C1 [Griffith, Jason W.; Luster, Andrew D.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA.
[Griffith, Jason W.; Luster, Andrew D.] Harvard Univ, Sch Med, Boston, MA USA.
[Griffith, Jason W.] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA.
[Luster, Andrew D.] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA.
RP Luster, AD (reprint author), Massachusetts Gen Hosp, Bldg 149,13th St, Charlestown, MA 02129 USA.
EM aluster@mgh.harvard.edu
FU NHLBI/NIH T32 training grant; NIAID; NCI at the NIH
FX J.W.G. was supported by an NHLBI/NIH T32 training grant and A. D. L. was
supported by grants from the NIAID and the NCI at the NIH.
NR 75
TC 16
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U1 1
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0014-2980
J9 EUR J IMMUNOL
JI Eur. J. Immunol.
PD JUN
PY 2013
VL 43
IS 6
BP 1430
EP 1435
DI 10.1002/eji.201243183
PG 6
WC Immunology
SC Immunology
GA 169MZ
UT WOS:000320785700009
PM 23580465
ER
PT J
AU Ruiz-Riol, M
Mothe, B
Gandhi, RT
Bhardwaj, N
Scadden, DT
Sanchez-Merino, V
Brander, C
AF Ruiz-Riol, Marta
Mothe, Beatriz
Gandhi, Rajesh T.
Bhardwaj, Nina
Scadden, David T.
Sanchez-Merino, Victor
Brander, Christian
TI Influenza, but not HIV-specific CTL epitopes, elicits delayed-type
hypersensitivity (DTH) reactions in HIV-infected patients
SO EUROPEAN JOURNAL OF IMMUNOLOGY
LA English
DT Article
DE Delayed-type hypersensitivity; Epitope-specific CTL; HIV infection;
Homing markers
ID CD8(+) T-CELLS; LYMPHOCYTE-ASSOCIATED ANTIGEN; SKIN-ASSOCIATED
LYMPHOCYTES; ATOPIC-DERMATITIS; HOMING RECEPTOR; MEMORY CD4(+);
EXPRESSION; VIRUS; RESPONSES; DISEASE
AB The induction of cytotoxic T lymphocytes (CTLs) is believed to be an important defense mechanism against viral infections. The availability of simple, sensitive, specific and physiologically informative in vivo tests, applicable to humans, would greatly elucidate the nature of protective immune responses and facilitate immune monitoring in large vaccine trials. Here we studied the possibility of using defined HLA-A*02:01-restricted CTL epitopes from influenza matrix protein (GL9, GILGFVFTL) and HIV Gag p17 (SL9, SLYNTVATL) to elicit a cutaneous delayed-type hypersensitivity (DTH) reaction. Our results show that the GL9 but not the SL9 epitope was able to induce a DTH reaction. HIV infection status, HIV RNA level and CD4(+) T-cell counts were not predictive of the extent of DTH reactions. However, a markedly reduced expression of skin homing markers CD103 and cutaneous lymphocyte associated Ag (CLA) on epitope-specific CTL populations was associated with a lack of SL9 DTH reactivity. These data demonstrate that DTH reactions can be elicited by optimally defined CTL epitopes per se and point towards specific homing markers that are required for such reactions. These data may offer new insights into the immune pathogenesis of HIV infection and provide the basis of novel immune monitoring approaches for large-scale HIV vaccine trials.
C1 [Ruiz-Riol, Marta; Mothe, Beatriz; Brander, Christian] HIVACAT, IrsiCaixa AIDS Res Inst, Barcelona, Spain.
[Mothe, Beatriz] Univ Autonoma Barcelona, Hosp Germans Trias & Pujol, Lluita Sida Fdn, E-08193 Barcelona, Spain.
[Gandhi, Rajesh T.] Massachusetts Gen Hosp, Div Infect Dis, Hematol Malignancies MGH Canc Ctr, Boston, MA 02114 USA.
[Bhardwaj, Nina] NYU, Sch Med, Dept Med Pathol & Dermatol, New York, NY USA.
[Scadden, David T.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA.
[Sanchez-Merino, Victor] Hosp Clin Barcelona, Serv Immunol, Barcelona, Spain.
[Sanchez-Merino, Victor] Hosp Clin Barcelona, IDIBAPS, AIDS Res Grp, HIVACAT, Barcelona, Spain.
[Brander, Christian] ICREA, Barcelona, Spain.
RP Brander, C (reprint author), Hosp Badalona Germans Trias & Pujol, Lab Retrovirol, Irsicaixa AIDS Res Inst, Ctra Canyet S-N, Barcelona 08916, Spain.
EM cbrander@irsicaixa.es
OI Brander, Christian/0000-0002-0548-5778
FU amfAR (American Foundation for AIDS Research) [02741-30-RGT]
FX This work was funded by a grant from amfAR (American Foundation for AIDS
Research, Grant 02741-30-RGT). We thank Lea Henry for excellent
technical support and Alysse Wurzel, Walter Howard and Paula O'Connor
for help with patient recruitment and follow-up.
NR 41
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U1 0
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0014-2980
J9 EUR J IMMUNOL
JI Eur. J. Immunol.
PD JUN
PY 2013
VL 43
IS 6
BP 1545
EP 1554
DI 10.1002/eji.201242732
PG 10
WC Immunology
SC Immunology
GA 169MZ
UT WOS:000320785700022
PM 23504637
ER
PT J
AU Choi, NC
Chun, TT
Niemierko, A
Ancukiewicz, M
Fidias, PM
Kradin, RL
Mathisen, DJ
Lynch, TJ
Fischman, AJ
AF Choi, Noah C.
Chun, Tristen T.
Niemierko, Andrzej
Ancukiewicz, Marek
Fidias, Panos M.
Kradin, Richard L.
Mathisen, Douglas J.
Lynch, Thomas J.
Fischman, Alan J.
TI Potential of F-18-FDG PET toward personalized radiotherapy or
chemoradiotherapy in lung cancer
SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
LA English
DT Article
DE F-FDG PET; Personalized radiotherapy; Individualized therapy; Lung
cancer; Chemoradiotherapy
ID RADIATION-DOSE ESCALATION; FDG-PET; TUMOR-CONTROL; SOLID TUMORS;
CHEMOTHERAPY; THERAPY; PROBABILITY; CISPLATIN; SURVIVAL; CRITERIA
AB Purpose We investigated the metabolic response of lung cancer to radiotherapy or chemoradiotherapy by F-18-FDG PET and its utility in guiding timely supplementary therapy.
Methods Glucose metabolic rate (MRglc) was measured in primary lung cancers during the 3 weeks before, and 10-12 days (S2), 3 months (S3), 6 months (S4), and 12 months (S5) after radiotherapy or chemoradiotherapy. The association between the lowest residual MRglc representing the maximum metabolic response (MRglc-MMR) and tumor control probability (TCP) at 12 months was modeled using logistic regression.
Results We accrued 106 patients, of whom 61 completed the serial F-18-FDG PET scans. The median values of MRglc at S2, S3 and S4 determined using a simplified kinetic method (SKM) were, respectively, 0.05, 0.06 and 0.07 mu mol/min/g for tumors with local control and 0.12, 0.16 and 0.19 mu mol/min/g for tumors with local failure, and the maximum standard uptake values (SUVmax) were 1.16, 1.33 and 1.45 for tumors with local control and 2.74, 2.74 and 4.07 for tumors with local failure (p<0.0001). MRglc-MMR was realized at S2 (MRglc-S2) and the values corresponding to TCP 95 %, 90 % and 50 % were 0.036, 0.050 and 0.134 mu mol/min/g using the SKM and 0.70, 0.91 and 1.95 using SUVmax, respectively. Probability cut-off values were generated for a given level of MRglc-S2 based on its predicted TCP, sensitivity and specificity, and MRglc <= 0.071 mu mol/min/g and SUVmax <= 1.45 were determined as the optimum cut-off values for predicted TCP 80 %, sensitivity 100 % and specificity 63 %.
Conclusion The cut-off values (MRglc <= 0.071 mu mol/min/g using the SKM and SUVmax <= 1.45) need to be tested for their utility in identifying patients with a high risk of residual cancer after standard dose radiotherapy or chemoradiotherapy and in guiding a timely supplementary dose of radiation or other means of salvage therapy.
C1 [Choi, Noah C.; Chun, Tristen T.; Niemierko, Andrzej; Ancukiewicz, Marek] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA.
[Fidias, Panos M.; Lynch, Thomas J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA.
[Kradin, Richard L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA.
[Mathisen, Douglas J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA.
[Fischman, Alan J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA.
RP Choi, NC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, 55 Fruit St, Boston, MA 02114 USA.
EM nchoi@partners.org
FU National Institute of Biomedical Imaging and Bioengineering at the
National Institutes of Health [R01 EB002907]
FX This work was supported in part by the National Institute of Biomedical
Imaging and Bioengineering at the National Institutes of Health (grant
number R01 EB002907).
NR 28
TC 4
Z9 4
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1619-7070
J9 EUR J NUCL MED MOL I
JI Eur. J. Nucl. Med. Mol. Imaging
PD JUN
PY 2013
VL 40
IS 6
BP 832
EP 841
DI 10.1007/s00259-013-2348-4
PG 10
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 179KO
UT WOS:000321519400003
PM 23400506
ER
PT J
AU Treon, SP
AF Treon, Steven P.
TI Waldenstrom's macroglobulinaemia: an indolent B-cell lymphoma with
distinct molecular and clinical features
SO HEMATOLOGICAL ONCOLOGY
LA English
DT Article
DE Waldenstrom's macroglobulinemia; MYD88; hyperviscosity; neuropathy;
cryoglobulins; hepcidin
ID COLD-REACTING AUTOANTIBODIES; IGM MONOCLONAL GAMMOPATHY; PERIPHERAL
NEUROPATHY; SOMATIC MUTATION; ANTIBODY-ACTIVITY; BIOLOGIC ACTIVITY; 6Q
DELETION; GENE; IMMUNOGLOBULINS; PARAPROTEINEMIA
C1 [Treon, Steven P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, Boston, MA 02115 USA.
RP Treon, SP (reprint author), Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, Mayer 548,44 Binney St, Boston, MA 02215 USA.
EM Steven_Treon@dfci.harvard.edu
NR 59
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Z9 3
U1 1
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0278-0232
J9 HEMATOL ONCOL
JI Hematol. Oncol.
PD JUN
PY 2013
VL 31
SU 1
SI SI
BP 76
EP 80
DI 10.1002/hon.2071
PG 5
WC Oncology; Hematology
SC Oncology; Hematology
GA 165GX
UT WOS:000320472600013
PM 23775655
ER
PT J
AU Fukuta, Y
Doi, Y
Muder, RR
Agha, ME
Hensler, AM
Wagener, MM
Clarke, LG
AF Fukuta, Y.
Doi, Y.
Muder, R. R.
Agha, M. E.
Hensler, A. M.
Wagener, M. M.
Clarke, L. G.
TI Risk factors for acquisition of multi-drug resistant Acinetobacter
baumannii among cancer patients
SO INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
LA English
DT Meeting Abstract
CT 28th International Congress of Chemotherapy and Infection Incorporating
/ 14th Asia-Pacific Congress of Clinical Microbiology and Infection
CY JUN 05-08, 2013
CL Yokohama, JAPAN
SP Int Soc Chemotherapy
C1 [Fukuta, Y.; Doi, Y.; Clarke, L. G.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA.
[Muder, R. R.] VA Pittsburgh Healthcare Syst, Infect Control, Pittsburgh, PA USA.
[Agha, M. E.] Univ Pittsburgh, Med Ctr, Hilman Canc Ctr, Pittsburgh, PA USA.
[Hensler, A. M.] Univ Pittsburgh, Med Ctr Shadyside, Pittsburgh, PA USA.
[Wagener, M. M.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15213 USA.
EM nana-yuri@hotmail.co.jp
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0924-8579
J9 INT J ANTIMICROB AG
JI Int. J. Antimicrob. Agents
PD JUN
PY 2013
VL 42
SU 2
BP S140
EP S141
PG 2
WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy
SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy
GA 178KS
UT WOS:000321447400436
ER
PT J
AU Neilan, TG
Coelho, OR
Shah, RV
Abbasi, SA
Heydari, B
Watanabe, E
Chen, YC
Mandry, D
Pierre-Mongeon, F
Blankstein, R
Kwong, RY
Jerosch-Herold, M
AF Neilan, Tomas G.
Coelho-Filho, Otavio R.
Shah, Ravi V.
Abbasi, Siddique A.
Heydari, Bobak
Watanabe, Eri
Chen, Yucheng
Mandry, Damien
Pierre-Mongeon, Francois
Blankstein, Ron
Kwong, Raymond Y.
Jerosch-Herold, Michael
TI Myocardial Extracellular Volume Fraction From T1 Measurements in Healthy
Volunteers and Mice Relationship to Aging and Cardiac Dimensions
SO JACC-CARDIOVASCULAR IMAGING
LA English
DT Article
DE cardiac magnetic resonance; extracellular matrix; myocardial fibrosis;
T1 measurements
ID CARDIOVASCULAR MAGNETIC-RESONANCE; DIASTOLIC HEART-FAILURE; HYPERTROPHIC
CARDIOMYOPATHY; DILATED CARDIOMYOPATHY; PARTITION-COEFFICIENT; GD-DTPA;
GADOPENTETATE DIMEGLUMINE; BLOOD-FLOW; FIBROSIS; INFARCTION
AB OBJECTIVES This study aimed to test the characteristics of the myocardial extracellular volume fraction (ECV) derived from pre- and post-contrast T1 measurements among healthy volunteers.
BACKGROUND Cardiac magnetic resonance (CMR) T1 measurements of myocardium and blood before and after contrast allow quantification of the ECV, a tissue parameter that has been shown to change in proportion to the connective tissue fraction.
METHODS Healthy volunteers underwent standard CMR imaging with administration of gadolinium. T1 measurements were performed with a Look-Locker sequence followed by gradient-echo acquisition. We tested the segmental, interslice, inter-, intra-, and test-retest characteristics of the ECV, as well as the association of the ECV with other variables. Juvenile and aged mice underwent a similar protocol, and cardiac sections were harvested for measurement of fibrosis.
RESULTS In healthy volunteers (N = 32, 56% female; age 21 to 72 years), the ECV averaged 0.28 +/- 0.03 (range 0.23 to 0.33). The intraclass coefficients for the intraobserver, interobserver, and test-retest absolute agreements of the ECV were 0.94 (95% confidence interval: 0.84 to 0.98), 0.93 (95% confidence interval: 0.80 to 0.98), and 0.95 (95% confidence interval: 0.52 to 0.99), respectively. In volunteers, the ECV was associated with age (r = 0.74, p < 0.001), maximal left atrial volume index.(r = 0.67, p < 0.001), and indexed left ventricular mass. There were no differences in the ECV between segments in a slice or between slices. In mice (N = 12), the myocardial ECV ranged from 0.20 to 0.32 and increased with age (0.22 +/- 0.02 vs. 0.30 +/- 0.02, juvenile vs. aged mice, p < 0.001). In mice, the ECV correlated with the extent of myocardial fibrosis (r = 0.94, p < 0.001).
CONCLUSIONS In healthy volunteers, the myocardial ECV ranges from 0.23 to 0.33, has acceptable test characteristics, and is associated with age, left atrial volume, and left ventricular mass. In mice, the ECV also increases with age and strongly correlates with the extent of myocardial fibrosis. (c) 2013 by the American College of Cardiology Foundation
C1 [Neilan, Tomas G.; Coelho-Filho, Otavio R.; Shah, Ravi V.; Abbasi, Siddique A.; Heydari, Bobak; Chen, Yucheng; Mandry, Damien; Pierre-Mongeon, Francois; Blankstein, Ron; Kwong, Raymond Y.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA.
[Neilan, Tomas G.; Shah, Ravi V.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA.
[Coelho-Filho, Otavio R.] Univ Estadual Campinas, UNICAMP, Sch Med Sci, Div Cardiol, Sao Paulo, Brazil.
[Watanabe, Eri; Jerosch-Herold, Michael] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Radiol, Boston, MA 02115 USA.
[Pierre-Mongeon, Francois] Univ Montreal, Montreal Heart Inst, Dept Med, Div Noninvas Cardiol, Montreal, PQ, Canada.
RP Jerosch-Herold, M (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.
EM mjerosch-herold@bics.bwh.harvard.edu
OI Abbasi, Siddique/0000-0002-9601-7565
FU American Heart Association Fellow [12FTF12060588]; NIH T32 Training
Grant [T32HL09430101A1]; Montreal Heart Institute Foundation, Montreal,
Canada; National Institutes of Health [R01HL091157, R01HL090634-01A1]
FX From *Noninvasive Cardiovascular Imaging, Cardiovascular Division,
Department of Medicine, Brigham and Women's Hospital, Boston,
Massachusetts; dagger Division of Cardiology, Department of Medicine,
Massachusetts General Hospital, Boston, Massachusetts; double dagger
Cardiology Division, School of Medical Science, State University of
Campinas (UNICAMP), Campinas, Sao Paulo, Brazil; Division of Radiology,
Brigham and Women's Hospital, Harvard Medical School, Boston,
Massachusetts; and the parallel to Division of Noninvasive Cardiology,
Department of Medicine, Montreal Heart Institute, Universite de
Montreal, Montreal, Quebec, Canada. Dr. Neilan is supported by an
American Heart Association Fellow to Faculty grant (12FTF12060588) and
previously by an NIH T32 Training Grant (T32HL09430101A1). Dr. Mongeon
receives financial support for research from the Montreal Heart
Institute Foundation, Montreal, Canada. Dr. Kwong receives salary
support from a research grant from the National Institutes of Health
(R01HL091157). Dr. Jerosch-Herold is supported in part by a research
grant from the National Institutes of Health (R01HL090634-01A1); and is
listed as co-inventor on a pending patent application related to
detection of diffuse fibrosis by MRI. All other authors have reported
that they have no relationships relevant to the contents of this paper
to disclose. Drs. Neilan and Coelho-Filho contributed equally to this
work.
NR 41
TC 23
Z9 24
U1 2
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1936-878X
J9 JACC-CARDIOVASC IMAG
JI JACC-Cardiovasc. Imag.
PD JUN
PY 2013
VL 6
IS 6
BP 672
EP 683
DI 10.1016/j.jcmg.2012.09.020
PG 12
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA 172CI
UT WOS:000320977200006
PM 23643283
ER
PT J
AU Pearson, DA
Santos, CW
Aman, MG
Arnold, LE
Casat, CD
Mansour, R
Lane, DM
Loveland, KA
Bukstein, OG
Jerger, SW
Factor, P
Vanwoerden, S
Perez, E
Cleveland, LA
AF Pearson, Deborah A.
Santos, Cynthia W.
Aman, Michael G.
Arnold, L. Eugene
Casat, Charles D.
Mansour, Rosleen
Lane, David M.
Loveland, Katherine A.
Bukstein, Oscar G.
Jerger, Susan W.
Factor, Perry
Vanwoerden, Salome
Perez, Evelyn
Cleveland, Lynne A.
TI Effects of Extended Release Methylphenidate Treatment on Ratings of
Attention-Deficit/Hyperactivity Disorder (ADHD) and Associated Behavior
in Children with Autism Spectrum Disorders and ADHD Symptoms
SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY
LA English
DT Article
ID PERVASIVE DEVELOPMENTAL DISORDERS; DEFICIT HYPERACTIVITY DISORDER; EARLY
INFANTILE-AUTISM; STIMULANT MEDICATION; MENTAL-RETARDATION;
PSYCHIATRIC-DISORDERS; FOLLOW-UP; TRIAL; PHARMACOTHERAPY; PREVALENCE
AB Objective: The purpose of this study was to examine the behavioral effects of four doses of psychostimulant medication, combining extended-release methylphenidate (MPH) in the morning with immediate-release MPH in the afternoon.
Method: The sample comprised 24 children (19 boys; 5 girls) who met American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV-TR) criteria for an autism spectrum disorder (ASD) on the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS), and had significant symptoms of attention-deficit/hyperactivity disorder (ADHD). This sample consisted of elementary school-age, community-based children (mean chronological age = 8.8 years, SD = 1.7; mean intelligence quotient [IQ] = 85; SD = 16.8). Effects of four dose levels of MPH on parent and teacher behavioral ratings were investigated using a within-subject, crossover, placebo-controlled design.
Results: MPH treatment was associated with significant declines in hyperactive and impulsive behavior at both home and school. Parents noted significant declines in inattentive and oppositional behavior, and improvements in social skills. No exacerbation of stereotypies was noted, and side effects were similar to those seen in typically developing children with ADHD. Dose response was primarily linear in the dose range studied.
Conclusions: The results of this study suggest that MPH formulations are efficacious and well-tolerated for children with ASD and significant ADHD symptoms.
C1 [Pearson, Deborah A.; Santos, Cynthia W.; Mansour, Rosleen; Loveland, Katherine A.; Bukstein, Oscar G.; Factor, Perry; Vanwoerden, Salome; Perez, Evelyn; Cleveland, Lynne A.] Univ Texas Houston, Sch Med, Houston, TX 77054 USA.
[Aman, Michael G.; Arnold, L. Eugene] Ohio State Univ, Nisonger Ctr, Columbus, OH 43210 USA.
[Casat, Charles D.] Ralph H Johnson VA Med Ctr, Charleston, SC USA.
[Lane, David M.] Rice Univ, Dept Psychol, Houston, TX 77251 USA.
[Jerger, Susan W.] Univ Texas Dallas, Sch Behav & Brain Sci, Dallas, TX 75230 USA.
RP Pearson, DA (reprint author), Univ Texas Houston, Sch Med, Dept Psychiat & Behav Sci, 1941 East Rd, Houston, TX 77054 USA.
EM Deborah.A.Pearson@uth.tmc.edu
FU National Institute of Mental Health (NIMH) [MH072263]
FX This study was funded by grant number MH072263 from the National
Institute of Mental Health (NIMH).
NR 73
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Z9 11
U1 1
U2 32
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1044-5463
J9 J CHILD ADOL PSYCHOP
JI J. Child Adolesc. Psychopharmacol.
PD JUN
PY 2013
VL 23
IS 5
BP 337
EP 351
DI 10.1089/cap.2012.0096
PG 15
WC Pediatrics; Pharmacology & Pharmacy; Psychiatry
SC Pediatrics; Pharmacology & Pharmacy; Psychiatry
GA 168LJ
UT WOS:000320707000006
PM 23782128
ER
PT J
AU Joshi, G
Biederman, J
Petty, C
Goldin, RL
Furtak, SL
Wozniak, J
AF Joshi, Gagan
Biederman, Joseph
Petty, Carter
Goldin, Rachel L.
Furtak, Stephannie L.
Wozniak, Janet
TI Examining the Comorbidity of Bipolar Disorder and Autism Spectrum
Disorders: A Large Controlled Analysis of Phenotypic and Familial
Correlates in a Referred Population of Youth With Bipolar I Disorder
With and Without Autism Spectrum Disorders
SO JOURNAL OF CLINICAL PSYCHIATRY
LA English
DT Article
ID PSYCHIATRIC CO-MORBIDITY; CONDUCT DISORDER; ONSET MANIA; CHILDREN;
ADOLESCENTS; INTERVIEW; CHILDHOOD; DIAGNOSIS; TRAITS; SCALE
AB Objective: Although mood dysregulation is frequently associated with autism spectrum disorders (ASD) and autistic traits are common in youth with bipolar disorder, uncertainties remain regarding the comorbid occurrence of bipolar disorder and ASD. This study examines the clinical and familial correlates of bipolar disorder when it occurs with and without ASD comorbidity in a well-characterized, research-referred population of youth with bipolar disorder. We hypothesized that in youth with bipolar disorder, the clinical and familial correlates of bipolar disorder will be comparable irrespective of the comorbidity with ASD.
Method: Clinical correlates and familial risk were assessed by secondary analysis of the data from a large family study of youth with bipolar I disorder (diagnosis based on DSM-IV criteria; probands n=157, relatives n=487; study period: November 1997-September 2002). Findings in bipolar I youth were compared with those in youth with attention-deficit/hyperactivity disorder (diagnosis based on DSM-III-R criteria) without bipolar I disorder (probands n=162, relatives n=511) and age- and sex-matched controls without bipolar I disorder or attention-deficit/hyperactivity disorder (probands n=136, relatives n=411). All subjects were comprehensively assessed using structured diagnostic interviews and a wide range of nonoverlapping measures assessing multiple dimensions of functioning.
Results: Thirty percent (47/155) of the bipolar I probands met criteria for ASD (diagnosis based on DSM-III-R criteria). The mean +/- SD age at onset of bipolar I disorder was significantly earlier in the presence of ASD comorbidity (4.7 +/- 2.9 vs 6.3 +/- 3.7 years; P=.01).The phenotypic and familial correlates of bipolar disorder were similar in youth with and without ASD comorbidity.
Conclusions: A clinically significant minority of youth with bipolar I disorder suffers from comorbid ASD. Phenotypic and familial correlates of bipolar disorder were typical of the disorder in the presence of ASD comorbidity. Bipolar I disorder comorbidity with ASD represents a very severe psychopathologic state in youth.
C1 [Joshi, Gagan; Biederman, Joseph; Petty, Carter; Goldin, Rachel L.; Furtak, Stephannie L.; Wozniak, Janet] Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA.
[Joshi, Gagan; Biederman, Joseph; Wozniak, Janet] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
RP Joshi, G (reprint author), Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, 55 Fruit St,YAW 6900, Boston, MA 02114 USA.
EM joshi.gagan@mgh.harvard.edu
FU Forest and Duke University; Schering-Plough; Shire; ElMindA; US
Department of Defense; Johnson Johnson; Eli Lilly; Forest; National
Institute of Mental Health (NIMH); Ethel DuPont Warren Fellowship Award;
Pilot Research Award from the American Academy of Child and Adolescent
Psychiatry; NIMH; McNeil Pediatrics (SynerMed Communications);
Bristol-Myers Squibb; GlaxoSmithKline; Pfizer; Merck; Cephalon; McNeil;
Abbott; Novartis; Organon; Otsuka; Takeda; New River; Janssen; Next
Wave; Fundacion Areces; Medice; Spanish Child Psychiatry Association;
Alza; AstraZeneca; Celltech; Esai; Glaxo; Gliatech; National Alliance
for Research on Schizophrenia and Depression; National Institute on Drug
Abuse, New River; National Institute of Child Health and Human
Development; Noven; Neurosearch; Pharmacia; Prechter Foundation; Stanley
Foundation; UCB; Wyeth; Merck/Schering-Plough; Zeo; Axon;
Boehringer-Ingelheim; Covance; Jazz; King; Luitpold; Neurogen; Novadel;
Sanofi-Aventis; Sepracor; Sunovion; UCB (Schwarz); National Institutes
of Health [K08MH001503, R01MH066237, R01MH050657, R01HD036317]; Norma
Fine Pediatric Psychopharmacology Fellowship Fund; Pediatric
Psychopharmacology Council Fund; Heinz C. Prechter Bipolar Research Fund
FX Dr Joshi currently receives research support from Forest and Duke
University and is a coinvestigator for clinical trials sponsored by
Schering-Plough, Shire, ElMindA, and US Department of Defense. In 2011,
Dr Joshi received research support from Shire, Johnson & Johnson, Eli
Lilly, Forest, Schering-Plough, ElMindA, and National Institute of
Mental Health (NIMH). In previous years, Dr Joshi received research
support from the following sources: Ethel DuPont Warren Fellowship Award
(2005-2006), Pilot Research Award from the American Academy of Child and
Adolescent Psychiatry (2005), NIMH (reviewer and member of the NIMH
Editorial Board), McNeil Pediatrics (CME sponsored by SynerMed
Communications), Bristol-Myers Squibb (site principal investigator [PI]
for multicenter trial); and GlaxoSmithKline (site PI for multicenter
trial); Shire (member of national advisory board) and was a
subinvestigator for clinical trials sponsored by Shire, Johnson &
Johnson, Pfizer, Merck, Cephalon, McNeil, Eli Lilly, Abbott, Novartis,
Bristol-Myers Squibb, Organon, Otsuka, Takeda, and New River. Dr
Biederman currently receives research support from ElMindA, Janssen,
McNeil, Next Wave, and Shire. In 2011, Dr Biederman gave a single unpaid
talk for Juste Pharmaceutical Spain and received honoraria from MGH
Psychiatry Academy for a tuition-funded CME course. He also received an
honorarium from Cambridge University Press for a chapter publication. In
2010, Dr Biederman received a speaker's fee from Fundacion Dr. Manuel
Camelo AC, provided single consultations for Shionogi and Cipher, and
received honoraria from the MGH Psychiatry Academy for a tuition-funded
CME course. In 2009, Dr Biederman received speaker's fees from Fundacion
Areces, Medice, and the Spanish Child Psychiatry Association. In
previous years, Dr Biederman received research support, consultation
fees, or speaker's fees from Abbott, Alza, AstraZeneca, Bristol-Myers
Squibb, Celltech, Cephalon, Eli Lilly, Esai, Forest, Glaxo, Gliatech,
Janssen, McNeil, Merck, National Alliance for Research on Schizophrenia
and Depression, National Institute on Drug Abuse, New River, National
Institute of Child Health and Human Development, NIMH, Novartis, Noven,
Neurosearch, Organon, Otsuka, Pfizer, Pharmacia, Prechter Foundation,
Shire, Stanley Foundation, UCB, and Wyeth. In 2011-2012, Dr Wozniak
received research support from Merck/Schering-Plough, McNeil, and Shire.
In the past, she has received research support, consultation fees, or
speaker's fees from Eli Lilly, Janssen, Johnson & Johnson, McNeil,
Pfizer, and Shire. She is the author of the book Is Your Child Bipolar?
published May 2008, Bantam Books. In 2011-2012, her spouse, John
Winkelman, MD, PhD, received consultation fees from Pfizer, UCB, Zeo,
and Sunovion for his role as consultant. He received research support
from GlaxoSmithKline for his role as research study staff In the past,
he has received research support, consultation fees, or speaker's fees
from Axon, Boehringer-Ingelheim, Covance, Cephalon, Eli Lilly,
GlaxoSmithKline, Impax, Jazz, King, Luitpold, Novartis, Neurogen,
Novadel, Pfizer, Sanofi-Aventis, Sepracor, Sunovion, Takeda, UCB
(Schwarz), Wyeth, and Zeo. Mr Petty and Mss Goldin and Furtak have no
conflicts of interest to report.; This work was supported by National
Institutes of Health grants K08MH001503 and R01MH066237 to Dr Wozniak
and R01MH050657 and R01HD036317 to Dr Biederman. This work was also
funded in part by the Norma Fine Pediatric Psychopharmacology Fellowship
Fund, the Pediatric Psychopharmacology Council Fund, and the Heinz C.
Prechter Bipolar Research Fund.
NR 41
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U1 4
U2 27
PU PHYSICIANS POSTGRADUATE PRESS
PI MEMPHIS
PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA
SN 0160-6689
J9 J CLIN PSYCHIAT
JI J. Clin. Psychiatry
PD JUN
PY 2013
VL 74
IS 6
BP 578
EP 586
DI 10.4088/JCP.12m07392
PG 9
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA 176QJ
UT WOS:000321318900002
PM 23842009
ER
PT J
AU McHugh, RK
Whitton, SW
Peckham, AD
Welge, JA
Otto, MW
AF McHugh, R. Kathryn
Whitton, Sarah W.
Peckham, Andrew D.
Welge, Jeffrey A.
Otto, Michael W.
TI Patient Preference for Psychological vs Pharmacologic Treatment of
Psychiatric Disorders: A Meta-Analytic Review
SO JOURNAL OF CLINICAL PSYCHIATRY
LA English
DT Review
ID COGNITIVE-BEHAVIORAL THERAPY; DEPRESSION TREATMENT PREFERENCES;
PRIMARY-CARE PATIENTS; RANDOMIZED-CONTROLLED-TRIAL;
POSTTRAUMATIC-STRESS-DISORDER; OBSESSIVE-COMPULSIVE DISORDER;
GENERALIZED ANXIETY DISORDER; MAJOR DEPRESSION; PANIC DISORDER;
COST-EFFECTIVENESS
AB Objective: Evidence-based practice involves the consideration of efficacy and effectiveness, clinical expertise, and patient preference in treatment selection. However, patient preference for psychiatric treatment has been understudied, The aim of this meta-analytic review was to provide an estimate of the proportion of patients preferring psychological treatment relative to medication for psychiatric disorders.
Data Sources: A literature search was conducted using PubMed, PsycINFO, and the Cochrane Collaboration library through August 2011 for studies written in English that assessed adult patient preferences for the treatment of psychiatric disorders. The following search terms and subject headings were used in combination: patient preference, consumer preference, therapeutics, psychotherapy, drug therapy, mental disorders, depression, anxiety, insomnia, bipolar disorder, schizophrenia, substance-related disorder, eating disorder, and personality disorder. In addition, the reference sections of identified articles were examined to locate any additional articles not captured by this search.
Study Selection: Studies that assessed preferred type of treatment and included at least 1 psychological treatment and 1 pharmacologic treatment were included. Of the 644 articles identified, 34 met criteria for inclusion.
Data Extraction: Authors extracted relevant data including the proportion of participants reporting preference for psychological or pharmacologic treatment.
Results:The proportion of adult patients preferring psychological treatment was 0.75 (95% Cl, 0.69-0.80), which was significantly higher than equivalent preference (ie, higher than 0.50; P<.001). Sensitivity analyses suggested that younger patients (P=.05) and women (P<.01) were significantly more likely to choose psychological treatment. A preference for psychological treatment was consistently evident in both treatment-seeking and unselected (ie, non-treatment-seeking) samples (P<.001 for both) but was somewhat stronger for unselected samples.
Conclusions: Aggregation of patient preferences across diverse settings yielded a significant 3-fold preference for psychological treatment. Given evidence for enhanced outcomes among those receiving their preferred psychiatric treatment and the trends for decreasing utilization of psychotherapy, strategies to maximize the linkage of patients to preferred care are needed.
C1 [McHugh, R. Kathryn] McLean Hosp, Div Alcohol & Drug Abuse, Belmont, MA 02478 USA.
[McHugh, R. Kathryn] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
[Whitton, Sarah W.] Univ Cincinnati, Dept Psychol, Cincinnati, OH 45221 USA.
[Peckham, Andrew D.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Welge, Jeffrey A.] Univ Cincinnati, Coll Med, Dept Psychiat & Behav Neurosci, Cincinnati, OH USA.
[Otto, Michael W.] Boston Univ, Dept Psychol, Boston, MA 02215 USA.
RP McHugh, RK (reprint author), McLean Hosp, Proctor House 3 MS 222,115 Mill St, Belmont, MA 02478 USA.
EM kmchugh@mclean.harvard.edu
OI McHugh, R. Kathryn/0000-0002-3011-8697
FU National Institutes of Health Institutional Clinical and Translational
Science Award [5ULIRR026314-02]; National Institute of Mental Health
Excellence in Training Award [R25 MH08478]; Oxford University Press;
Routledge; Springer; National Institute of Mental Health
FX Dr Otto has been a consultant for MicroTransponder and has received book
royalties from Oxford University Press, Routledge, and Springer. Drs
McHugh, Whitton, and Welge and Mr Peckham have no conflicts of interest
to report.; Supported in part by National Institutes of Health
Institutional Clinical and Translational Science Award 5ULIRR026314-02
(Drs Whitton and Welge) and by National Institute of Mental Health
Excellence in Training Award R25 MH08478 (Dr Otto).; The National
Institutes of Health had no role in the study design; in the collection,
analysis, and interpretation of data; in the writing of the report; or
in the decision to submit the manuscript for publication. The National
Institute of Mental Health had no role other than financial support.
NR 68
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U1 5
U2 65
PU PHYSICIANS POSTGRADUATE PRESS
PI MEMPHIS
PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA
SN 0160-6689
J9 J CLIN PSYCHIAT
JI J. Clin. Psychiatry
PD JUN
PY 2013
VL 74
IS 6
BP 595
EP 602
DI 10.4088/JCP.12r07757
PG 8
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA 176QJ
UT WOS:000321318900004
PM 23842011
ER
PT J
AU Herr, MW
Gray, ST
Erman, AB
Curry, WT
Deschler, DG
Lin, DT
AF Herr, Marc W.
Gray, Stacey T.
Erman, Audrey B.
Curry, William T.
Deschler, Daniel G.
Lin, Derrick T.
TI Orbital Preservation in Patients with Esthesioneuroblastoma
SO JOURNAL OF NEUROLOGICAL SURGERY PART B-SKULL BASE
LA English
DT Article
DE esthesioneuro-blastoma; anterior craniofacial resection; orbital
preservation; skull base
ID OLFACTORY NEUROBLASTOMA; SURGICAL-MANAGEMENT; PARANASAL SINUSES;
EXPERIENCE; EYE; CHEMOTHERAPY; RADIATION; NEOPLASMS; RESECTION; SURGERY
AB Objectives Surgical resection in addition to adjuvant radiation with or without chemotherapy is the mainstay of treatment for esthesioneuroblastoma (ENB). However, management of patients with orbital involvement remains controversial. Historically, orbital exenteration has been advocated when there is evidence of periorbital invasion. Recently, the indications for orbital exenteration have become more selective and orbital preservation has been advocated. We report our experience with anterior craniofacial resection and orbital preservation in patients with ENB.
Design Retrospective review of all patients diagnosed with esthesioneuroblastoma who underwent traditional open anterior craniofacial resection at the Massachusetts General Hospital/Massachusetts Eye and Ear Infirmary Cranial Base Center from 1997 to 2008.
Results Sixteen patients were identified with a mean follow-up of 76 months. All patients underwent anterior craniofacial resection via an open approach and adjuvant proton beam radiation. Six of the 16 patients had evidence of either periorbital or lacrimal sac involvement at the time of surgery. All of these patients underwent periorbital resection to negative histologic margins with preservation of the orbit.
Conclusion In our study, patients with ENB and periorbital invasion-who were treated with anterior craniofacial resection and periorbital resection with orbital preservation-had no evidence of decreased survival. In all patients, negative histologic margins of the periorbital resection were achieved.
C1 [Herr, Marc W.; Gray, Stacey T.; Deschler, Daniel G.; Lin, Derrick T.] Massachusetts Gen Hosp, Dept Otol & Laryngol, Massachusetts Eye & Ear Infirm, Cranial Base Ctr, Boston, MA 02114 USA.
[Erman, Audrey B.] Univ Arizona, Dept Otolaryngol Head & Neck Surg, Ctr Canc, Tucson, AZ USA.
[Curry, William T.] Massachusetts Gen Hosp, Dept Neurosurg, Pappas Ctr Neurooncol, Boston, MA 02114 USA.
RP Herr, MW (reprint author), Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02114 USA.
EM marc_herr@meei.harvard.edu
NR 17
TC 2
Z9 2
U1 0
U2 1
PU THIEME MEDICAL PUBL INC
PI NEW YORK
PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA
SN 2193-6331
J9 J NEUROL SURG PART B
JI Journal of Neurol. Surg. Part B
PD JUN
PY 2013
VL 74
IS 3
BP 142
EP 145
DI 10.1055/s-0033-1338259
PG 4
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA 175ZQ
UT WOS:000321272900007
PM 24436904
ER
PT J
AU Rosenberg, SM
Partridge, AH
AF Rosenberg, Shoshana M.
Partridge, Ann H.
TI Premature menopause in young breast cancer: effects on quality of life
and treatment interventions
SO JOURNAL OF THORACIC DISEASE
LA English
DT Review
DE Premature menopause; young women; breast cancer; quality of life (QOL)
ID RANDOMIZED CONTROLLED-TRIAL; BONE-MINERAL DENSITY; HOT FLASHES; ADJUVANT
CHEMOTHERAPY; OVARIAN FAILURE; PHYSICAL-ACTIVITY; VASOMOTOR SYMPTOMS;
BODY-COMPOSITION; SEXUAL PROBLEMS; BLACK COHOSH
AB Many young women are at increased risk for premature menopause following adjuvant treatment for breast cancer. These women must deal with consequences of menopause, including loss of fertility and physiologic symptoms such as night sweats, hot flashes, vaginal dryness, and weight gain. These symptoms can be particularly distressing for young women and can adversely affect both health-related and psychosocial quality of life (QOL). While there are a wide range of pharmacologic and non-pharmacologic interventions available to help with these symptoms and in turn, improve QOL, there is little data available about the use and efficacy of these interventions in younger women who become menopausal as a result of their breast cancer treatment. Future studies should focus on this vulnerable population, with the goal of identifying effective strategies to relieve symptoms and improve quality of life in young breast cancer survivors.
C1 [Rosenberg, Shoshana M.; Partridge, Ann H.] Dana Farber Canc Inst, Boston, MA 02215 USA.
[Rosenberg, Shoshana M.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Partridge, Ann H.] Harvard Univ, Sch Med, Boston, MA USA.
RP Rosenberg, SM (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,LW601, Boston, MA 02215 USA.
EM shoshana_rosenberg@dfci.harvard.edu
FU NIH [5 R25 CA057711]
FX Dr. Rosenberg is funded by NIH 5 R25 CA057711.
NR 72
TC 14
Z9 14
U1 1
U2 7
PU PIONEER BIOSCIENCE PUBL CO
PI HONG KONG
PA 9A GOLD SHINE TOWER, 346-348 QUEEN'S RD CENTRAL, SHEUNG WAN, HONG KONG,
00000, PEOPLES R CHINA
SN 2072-1439
J9 J THORAC DIS
JI J. Thorac. Dis.
PD JUN
PY 2013
VL 5
SU 1
BP S55
EP S61
DI 10.3978/j.issn.2072-1439.2013.06.20
PG 7
WC Respiratory System
SC Respiratory System
GA 182ME
UT WOS:000321746200008
PM 23819028
ER
PT J
AU Ryan, J
Letai, A
AF Ryan, Jeremy
Letai, Anthony
TI BH3 profiling in whole cells by fluorimeter or FACS
SO METHODS
LA English
DT Article
DE Mitochondria; Apoptosis; BCL-2; Flow Cytometry; Cancer; Chemotherapy
ID REVERSIBLE MEMBRANE PERMEABILIZATION; STREPTOLYSIN-O; CYTOCHROME-C;
MITOCHONDRIA; APOPTOSIS; PROTEINS; DEATH; SIGNALS
AB Rapid analysis of a cell's propensity to undergo apoptosis through the mitochondrial pathway is hindered by the complex network of interactions between more than fifteen known members of the BCL2 family that govern the decision to undergo mitochondrial apoptosis, and measurement of protein levels alone fails to account for critical interactions between the proteins. To address this issue, we have developed two functional assays for same-day analysis of cell lines or primary tissue samples. Using defined inputs in the form of peptides derived primarily from the BH3 domains of pro-apoptotic members of the BCL2 family, we invoke a response in the mitochondria in the form of mitochondrial outer membrane permeabilization measured indirectly using potential sensitive dyes. BH3 profiling can be applied to any viable single cell suspension and provides a response from the sum total of all known and unknown interactions within the BCL2 family for each stimulus, and the pattern of response can provide both a cell's propensity towards mitochondrial apoptosis, or 'priming', as well as indicate dependencies on specific anti-apoptotic proteins. Described here are optimized conditions for both plate-based and FACS-based BH3 profiling for homogeneous and heterogeneous samples. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Ryan, Jeremy; Letai, Anthony] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
[Letai, Anthony] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
RP Letai, A (reprint author), 450 Brookline Ave,Mayer 429, Boston, MA 02215 USA.
EM Anthony_Letai@dfci.harvard.edu
FU NIH [F31 CA150562, P01 CA139980, R01 CA129974]
FX The authors gratefully acknowledge support from the following sources:
NIH grants F31 CA150562, P01 CA139980, and R01 CA129974. A.L. is a
Leukemia and Lymphoma Society Scholar. A.L. was a cofounder and formerly
served on the scientific advisory board of Eutropics Pharmaceuticals,
which has a license for BH3 profiling.
NR 28
TC 32
Z9 32
U1 1
U2 5
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1046-2023
J9 METHODS
JI Methods
PD JUN 1
PY 2013
VL 61
IS 2
BP 156
EP 164
DI 10.1016/j.ymeth.2013.04.006
PG 9
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 175ML
UT WOS:000321234700010
PM 23607990
ER
PT J
AU Peters, MAK
Thompson, B
Merabet, LB
Wu, AD
Shams, L
AF Peters, Megan A. K.
Thompson, Benjamin
Merabet, Lotfi B.
Wu, Allan D.
Shams, Ladan
TI Anodal tDCS to V1 blocks visual perceptual learning consolidation
SO NEUROPSYCHOLOGIA
LA English
DT Article
DE Transcranial direct current stimulation; Visual perception; Perceptual
learning; External modulation of visual cortex; Contrast enhancement;
Consolidation; Visual learning; Anodal tDCS
ID DIRECT-CURRENT STIMULATION; HUMAN MOTOR CORTEX; EXCITABILITY CHANGES;
ELECTROPHYSIOLOGICAL EVIDENCE; PHOSPHENE THRESHOLDS; MODULATION; HUMANS;
IMPLICIT; NOISE
AB This study examined the effects of visual cortex transcranial direct current stimulation (tDCS) on visual processing and learning. Participants performed a contrast detection task on two consecutive days. Each session consisted of a baseline measurement followed by measurements made during active or sham stimulation. On the first day, one group received anodal stimulation to primary visual cortex (V1), while another received cathodal stimulation. Stimulation polarity was reversed for these groups on the second day. The third (control) group of subjects received sham stimulation on both days. No improvements or decrements in contrast sensitivity relative to the same-day baseline were observed during real tDCS, nor was any within-session learning trend observed. However, task performance improved significantly from Day 1 to Day 2 for the participants who received cathodal tDCS on Day 1 and for the sham group. No such improvement was found for the participants who received anodal stimulation on Day 1, indicating that anodal tDCS blocked overnight consolidation of visual learning, perhaps through engagement of inhibitory homeostatic plasticity mechanisms or alteration of the signal-to-noise ratio within stimulated cortex. These results show that applying tDCS to the visual cortex can modify consolidation of visual learning. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Peters, Megan A. K.; Shams, Ladan] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA.
[Thompson, Benjamin] Univ Auckland, Dept Optometry & Vis Sci, Auckland 1, New Zealand.
[Merabet, Lotfi B.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Vis Rehabil Ctr,Dept Ophthalmol, Boston, MA USA.
[Wu, Allan D.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA.
[Shams, Ladan] Univ Calif Los Angeles, Dept Bioengn, Los Angeles, CA 90095 USA.
RP Peters, MAK (reprint author), Univ Calif Los Angeles, Dept Psychol, 1285 Franz Hall, Los Angeles, CA 90095 USA.
EM meganakpeters@ucla.edu; b.thompson@auckland.ac.nz;
lotfi_merabet@meei.harvard.edu; allanwu@mednet.ucla.edu;
lshams@psych.ucla.edu
FU NSF [1057969]; Marsden Fund of New Zealand
FX We thank Felipe Fregni for helpful discussions. MP was supported by an
NSF graduate research fellowship. BT was supported by the Marsden Fund
of New Zealand. LS was supported by NSF Grant 1057969.
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PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0028-3932
J9 NEUROPSYCHOLOGIA
JI Neuropsychologia
PD JUN
PY 2013
VL 51
IS 7
BP 1234
EP 1239
DI 10.1016/j.neuropsychologia.2013.03.013
PG 6
WC Behavioral Sciences; Neurosciences; Psychology, Experimental
SC Behavioral Sciences; Neurosciences & Neurology; Psychology
GA 179RQ
UT WOS:000321539400011
PM 23562964
ER
PT J
AU Bernardino, I
Castelhano, J
Farivar, R
Silva, ED
Castelo-Branco, M
AF Bernardino, Ines
Castelhano, Joao
Farivar, Reza
Silva, Eduardo D.
Castelo-Branco, Miguel
TI Neural correlates of visual integration in Williams syndrome: Gamma
oscillation patterns in a model of impaired coherence
SO NEUROPSYCHOLOGIA
LA English
DT Article
DE Williams syndrome; Low-gamma oscillations; 3D integration; Visual
coherence; EEG/ERP
ID DORSAL-STREAM; BAND ACTIVITY; FROM-MOTION; BRAIN; COGNITION;
SYNCHRONIZATION; PERCEPTION; DISORDERS; ATTENTION; CHILDREN
AB Williams syndrome (WS) is a clinical model of dorsal stream vulnerability and impaired visual integration. However, little is still known about the neurophysiological correlates of perceptual integration in this condition. We have used a 3D structure-from-motion (SFM) integrative task to characterize the neuronal underpinnings of 3D perception in WS and to probe whether gamma oscillatory patterns reflect changed holistic perception. Coherent faces were parametrically modulated in 3D depth (three different depth levels) to vary levels of stimulus ambiguity. We have found that the electrophysiological (EEG/ERP) correlates of such holistic percepts were distinct across groups. Independent component analysis demonstrated the presence of a novel component with a late positivity around 200 ms that was absent in controls. Source localization analysis of ERP signals showed a posterior occipital shift in WS and reduced parietal dorsal stream sources. Interestingly, low gamma-band oscillations (20-40 Hz) induced by this 3D perceptual integration task were significantly stronger and sustained during the stimulus presentation in WS whereas high gamma-band oscillations (60-90 Hz) were reduced in this clinical model of impaired visual coherence, as compared to controls.
These observations suggest that dorsal stream processing of 3D SFM stimuli has distinct neural correlates in WS and different cognitive strategies are employed by these patients to reach visual coherence. Importantly, we found evidence for the presence of different sub-bands (20-40 Hz/60-90 Hz) within the gamma range which can be dissociated concerning the respective role On the coherent percept formation, both in typical and atypical development. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Bernardino, Ines; Castelhano, Joao; Silva, Eduardo D.; Castelo-Branco, Miguel] Univ Coimbra, IBILI, Visual Neurosci Lab, Fac Med, P-3000354 Coimbra, Portugal.
[Farivar, Reza] Harvard Univ, Sch Med, Charlestown, MA USA.
[Farivar, Reza] Massachusetts Gen Hosp, A Athinoula Martinos Ctr Biomed Imaging, Charlestown, MA USA.
[Silva, Eduardo D.] Univ Hosp Coimbra, Dept Ophthalmol, Ctr Hereditary Eye Dis, Coimbra, Portugal.
RP Castelo-Branco, M (reprint author), Univ Coimbra, IBILI, Visual Neurosci Lab, Fac Med, Azinhaga Santa Comba, P-3000354 Coimbra, Portugal.
EM mcbranco@ibili.uc.pt
RI Castelo-Branco, Miguel/E-5689-2010;
OI Bernardino, Ines/0000-0003-3123-008X; Silva,
Eduardo/0000-0002-2739-9854; Castelhano, Joao/0000-0002-8996-1515;
Castelo-Branco, Miguel/0000-0003-4364-6373
FU Portuguese Foundation for Science and Technology
[PTDC/SAU-NEU/68483/2006, PTDC/SAU-ORG/118380/2010, COMPETE,
PEst-C/SAU/UI3282/2011, PIC/IC/82986/2007]; [SRFH/BD/41401/2007];
[SFRH/BD/65341/2009]
FX We are grateful to the participants and their families for their
participation and support, and Eugenio Rodriguez for his support in data
analysis. This research was supported by the Portuguese Foundation for
Science and Technology grant numbers: PTDC/SAU-NEU/68483/2006,
PTDC/SAU-ORG/118380/2010, COMPETE, PEst-C/SAU/UI3282/2011 and
PIC/IC/82986/2007 to M.C.B. (PI); and individual
scholarships-SRFH/BD/41401/2007 to I.B. and SFRH/BD/65341/2009 to J.C.
NR 61
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U1 0
U2 8
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0028-3932
J9 NEUROPSYCHOLOGIA
JI Neuropsychologia
PD JUN
PY 2013
VL 51
IS 7
BP 1287
EP 1295
DI 10.1016/j.neuropsychologia.2013.03.020
PG 9
WC Behavioral Sciences; Neurosciences; Psychology, Experimental
SC Behavioral Sciences; Neurosciences & Neurology; Psychology
GA 179RQ
UT WOS:000321539400017
PM 23587664
ER
PT J
AU Chabner, BA
AF Chabner, Bruce A.
TI In This Issue: Personalized Medicine
SO ONCOLOGIST
LA English
DT Editorial Material
C1 [Chabner, Bruce A.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Chabner, Bruce A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
RP Chabner, BA (reprint author), 10 N Grove St,LRH 214, Boston, MA 02114 USA.
EM bchabner@partners.org
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ALPHAMED PRESS
PI DURHAM
PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA
SN 1083-7159
J9 ONCOLOGIST
JI Oncologist
PD JUN
PY 2013
VL 18
IS 6
BP 639
EP 639
DI 10.1634/theoncologist.2013-0211
PG 1
WC Oncology
SC Oncology
GA 172YL
UT WOS:000321043200001
PM 23814156
ER
PT J
AU Chabner, BA
Ellisen, LW
Iafrate, AJ
AF Chabner, Bruce A.
Ellisen, Leif W.
Iafrate, A. John
TI Personalized Medicine: Hype or Reality
SO ONCOLOGIST
LA English
DT Editorial Material
ID CELL LUNG-CANCER; PHILADELPHIA-CHROMOSOME; THERAPY; MUTATIONS; MELANOMA;
BRAF
C1 [Chabner, Bruce A.; Ellisen, Leif W.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Iafrate, A. John] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Iafrate, A. John] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
RP Chabner, BA (reprint author), 10 N Grove St,LRH 214, Boston, MA 02114 USA.
EM bchabner@partners.org
NR 21
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U1 0
U2 4
PU ALPHAMED PRESS
PI DURHAM
PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA
SN 1083-7159
J9 ONCOLOGIST
JI Oncologist
PD JUN
PY 2013
VL 18
IS 6
BP 640
EP 643
DI 10.1634/theoncologist.2013-0210
PG 4
WC Oncology
SC Oncology
GA 172YL
UT WOS:000321043200002
PM 23814157
ER
PT J
AU Doroshow, JH
Sleijfer, S
Stupp, R
Anderson, K
AF Doroshow, James H.
Sleijfer, Stefan
Stupp, Roger
Anderson, Kenneth
TI Cancer Clinical Trials-Do We Need a New Algorithm in the Age of
Stratified Medicine?
SO ONCOLOGIST
LA English
DT Editorial Material
C1 [Doroshow, James H.] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
[Sleijfer, Stefan] Erasmus Univ, Med Ctr, Inst Canc, Rotterdam, Netherlands.
[Sleijfer, Stefan] Netherlands Ctr, Rotterdam, Netherlands.
[Stupp, Roger] Univ Lausanne, Dept Clin Neurosci, Lausanne, Switzerland.
[Stupp, Roger] Univ Zurich Hosp, Ctr Canc, CH-8091 Zurich, Switzerland.
[Stupp, Roger] EORTC, Brussels, Belgium.
[Anderson, Kenneth] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Anderson, Kenneth] Dana Farber Canc Inst, Kraft Family Blood Ctr, Boston, MA 02115 USA.
RP Doroshow, JH (reprint author), NCI, NIH, Bldg 31,Room 3A-44,31 Ctr Dr, Bethesda, MD 20892 USA.
EM doroshoj@mail.nih.gov
NR 5
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U1 0
U2 3
PU ALPHAMED PRESS
PI DURHAM
PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA
SN 1083-7159
J9 ONCOLOGIST
JI Oncologist
PD JUN
PY 2013
VL 18
IS 6
BP 651
EP 652
DI 10.1634/theoncologist.2013-0190
PG 2
WC Oncology
SC Oncology
GA 172YL
UT WOS:000321043200006
PM 23814160
ER
PT J
AU Lautenschlaeger, T
George, A
Klimowicz, AC
Efstathiou, JA
Wu, CL
Sandler, H
Shipley, WU
Tester, WJ
Hagan, MP
Magliocco, AM
Chakravarti, A
AF Lautenschlaeger, Tim
George, Asha
Klimowicz, Alexander C.
Efstathiou, Jason A.
Wu, Chin-Lee
Sandler, Howard
Shipley, William U.
Tester, William J.
Hagan, Michael P.
Magliocco, Anthony M.
Chakravarti, Arnab
TI Bladder Preservation Therapy for Muscle-Invading Bladder Cancers on
Radiation Therapy Oncology Group Trials 8802, 8903, 9506, and 9706:
Vascular Endothelial Growth Factor B Overexpression Predicts for
Increased Distant Metastasis and Shorter Survival
SO ONCOLOGIST
LA English
DT Article
AB Background. From 1988 to 1999, the Radiation Therapy Oncology Group (RTOG) conducted four prospective studies (8802, 8903, 9506, 9706) of patients with clinical stage T2-4a muscle-invasive bladder cancer. Treatment was selective bladder preservation using transurethral surgery (TURBT) plus cisplatin-based induction and consolidation chemoradiation regimens, reserving radical cystectomy for invasive tumor recurrence. We investigated vascular endothelial growth factor (VEGF) pathway biomarkers in this unique clinical data-set (median follow-up of 3.1 years).
Methods. A total of 43 patients with tissue available from the entry TURBT were included in this analysis. Expression of VEGF ligands and receptors were quantified and scored by the AQUA platform (HistoRX, now Genoptix, Carlsbad, CA) and analyzed after median split.
Results. VEGF expression levels were not associated with increased rates of complete response to induction chemoradiation. Higher levels of cytoplasmic VEGF-B, VEGF-C, and VEGF-R2 were associated with decreased overall survival rates. The 3-year overall survival estimates for high and low expressers were 43.7% and 75% for VEGF-B cytoplasm (p = .01), 40.2% and 86.7% for VEGF-C cytoplasm (p = .01), and 49.7% and 66.7% for VEGF-R2 cytoplasm (p = .02). Higher expression levels of cytoplasm VEGF-B were associated with higher rates of distant failure (p = .01).
[GRAPHICS]
Conclusions. Although VEGF ligands and receptors do not appear to be associated with complete response to induction chemoradiation for muscle- invasive bladder cancer, we report significant associations with overall survival and distant failure for certain VEGF family members.
C1 [Lautenschlaeger, Tim; Chakravarti, Arnab] Ohio State Univ, Wexner Med Ctr, Dept Radiat Oncol, Columbus, OH 43210 USA.
[George, Asha] Ctr Stat, Radiat Therapy Oncol Grp, Philadelphia, PA USA.
[Klimowicz, Alexander C.] Univ Calgary, Translat Res Lab, Funct Tissue Imaging Unit, Calgary, AB, Canada.
[Efstathiou, Jason A.] Massachusetts Gen Hosp, Clark Ctr Radiat Oncol, Boston, MA 02114 USA.
[Wu, Chin-Lee] Massachusetts Gen Hosp, Urol Res Lab, Boston, MA 02114 USA.
[Shipley, William U.] Massachusetts Gen Hosp, Genitourinary Oncol Unit, Boston, MA 02114 USA.
[Sandler, Howard] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Dept Radiat Oncol, Los Angeles, CA 90048 USA.
[Tester, William J.] Einstein Med Ctr, Div Med Oncol, Philadelphia, PA USA.
[Hagan, Michael P.] Virginia Commonwealth Univ, Med Coll Virginia, Dept Radiat Oncol, Richmond, VA 23298 USA.
[Magliocco, Anthony M.] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Anat Pathol, Tampa, FL 33682 USA.
[Magliocco, Anthony M.] Res Inst, Tampa, FL USA.
RP Lautenschlaeger, T (reprint author), Ohio State Univ, Wexner Med Ctr, Arthur G James Comprehens Canc Ctr, Richard L Solove Res Inst,Dept Radiat Oncol, Wiseman Hall 385G,410 W 12th Ave, Columbus, OH 43210 USA.
EM TL@osumc.edu
FU RTOG [U10 CA21661]; CCOP from the National Cancer Institute (NCI) [U10
CA37422]; Pennsylvania Department of Health [4100054841]; Ohio State
University Comprehensive Cancer Center
FX This trial was conducted by the Radiation Therapy Oncology Group (RTOG),
and was supported by RTOG grant U10 CA21661 and CCOP grant U10 CA37422
from the National Cancer Institute (NCI). The publication was supported
by the 2010 Pennsylvania Department of Health Formula Grant 4100054841
(to AG), and funds from the Ohio State University Comprehensive Cancer
Center (to AC). This manuscript's contents are solely the responsibility
of the authors and do not necessarily represent the official views of
the National Cancer Institute. We thank Vaia Dedousi-Huebner for writing
and editorial assistance.
NR 0
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U2 2
PU ALPHAMED PRESS
PI DURHAM
PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA
SN 1083-7159
J9 ONCOLOGIST
JI Oncologist
PD JUN
PY 2013
VL 18
IS 6
BP 685
EP 686
DI 10.1634/theoncologist.2012-0461
PG 2
WC Oncology
SC Oncology
GA 172YL
UT WOS:000321043200013
PM 23728940
ER
PT J
AU Luke, JJ
Hodi, FS
AF Luke, Jason J.
Hodi, F. Stephen
TI Ipilimumab, Vemurafenib, Dabrafenib, and Trametinib: Synergistic
Competitors in the Clinical Management of BRAF Mutant Malignant Melanoma
SO ONCOLOGIST
LA English
DT Article
DE CTLA-4; Immunotherapy; BRAF; MEK; Resistance; Biomarker
ID T-LYMPHOCYTE ANTIGEN-4; DOSE-ESCALATION TRIAL; RAF INHIBITOR RESISTANCE;
UNRESECTABLE STAGE-III; METASTATIC MELANOMA; PHASE-II; CTLA-4 BLOCKADE;
OPEN-LABEL; COMBINATION IMMUNOTHERAPY; SELECTIVE INHIBITOR
AB There have been significant advances in the treatment of malignant melanoma with the U.S. Food and Drug Administration approval of two drugs in 2011, the first drugs approved in 13 years. The developments of immune checkpoint modulation via cytotoxic T-lymphocyte antigen-4 blockade, with ipilimumab, and targeting of BRAF(V600), with vemurafenib or dabrafenib, as well as MEK, with trametinib, have been paradigm changing both for melanoma clinical practice and for oncology therapeutic development. These advancements, however, reveal new clinical questions regarding combinations and optimal sequencing of these agents in patients with BRAF mutant disease. We review the development of these agents, putative biomarkers, and resistance mechanisms relevant to their use, and possibilities for sequencing and combining these agents.
C1 [Luke, Jason J.] Dana Farber Canc Inst, Melanoma Dis Ctr, Boston, MA 02215 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Luke, JJ (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA.
EM Jason_Luke@dfci.harvard.edu
FU Bristol-Myers Squibb; Genentech/Roche; Novartis; Pfizer; Synta
FX The authors are fully responsibility for the content of this publication
and confirm that it reflects their viewpoint and medical expertise. The
authors wish to acknowledge StemScientific for providing editorial
support. This support was funded by Bristol-Myers Squibb. Neither
Bristol-Myers Squibb nor StemScientific influenced the content of the
manuscript, nor did the authors receive financial compensation for
authoring the manuscript.; F. Stephen Hodi: Genentech/Roche,
Bristol-Myers Squibb, Novartis, Pfizer, and Synta (RF); Genentech/Roche,
Novartis, and Bristol-Myers Squibb (C/A). The other author indicated no
financial relationships.
NR 72
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U2 13
PU ALPHAMED PRESS
PI DURHAM
PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA
SN 1083-7159
J9 ONCOLOGIST
JI Oncologist
PD JUN
PY 2013
VL 18
IS 6
BP 717
EP 725
DI 10.1634/theoncologist.2012-0391
PG 9
WC Oncology
SC Oncology
GA 172YL
UT WOS:000321043200018
PM 23709751
ER
PT J
AU Postow, MA
Luke, JJ
Bluth, DJ
Ramaiya, N
Panageas, KS
Lawrence, DP
Ibrahim, N
Flaherty, KT
Sullivan, RJ
Ott, PA
Callahan, DK
Harding, JJ
D'Angelo, SP
Dickson, AA
Schwartz, GK
Chapman, PB
Gnjatic, S
Wolchok, JD
Hodi, FS
Carvajal, RD
AF Postow, Michael A.
Luke, Jason J.
Bluth, Mark J.
Ramaiya, Nikhil
Panageas, Katherine S.
Lawrence, Donald P.
Ibrahim, Nageatte
Flaherty, Keith T.
Sullivan, Ryan J.
Ott, Patrick A.
Callahan, Margaret K.
Harding, James J.
D'Angelo, Sandra P.
Dickson, Mark A.
Schwartz, Gary K.
Chapman, Paul B.
Gnjatic, Sacha
Wolchok, Jedd D.
Hodi, F. Stephen
Carvajal, Richard D.
TI Ipilimumab for Patients With Advanced Mucosal Melanoma
SO ONCOLOGIST
LA English
DT Article
DE Mucosal melanoma; Ipilimumab; CTLA-4; Immunotherapy; Cancer-testis
antigens
ID KIT PROTEIN EXPRESSION; METASTATIC MELANOMA; ANTIGEN CT45; HUMAN CANCER;
BIOCHEMOTHERAPY; MUTATIONS; DACARBAZINE; LYMPHOMAS; SURVIVAL; THERAPY
AB The outcome of patients with mucosal melanoma treated with ipilimumab is not defined. To assess the efficacy and safety of ipilimumab in this melanoma subset, we performed a multicenter, retrospective analysis of 33 patients with unresectable or metastatic mucosal melanoma treated with ipilimumab. The clinical characteristics, treatments, toxicities, radiographic assessment of disease burden by central radiology review at each site, and mutational profiles of the patients' tumors were recorded. Available peripheral blood samples were used to assess humoral immunity against a panel of cancer-testis antigens and other antigens. By the immune-related response criteria of the 30 patients who underwent radiographic assessment after ipilimumab at approximately week 12, there were 1 immune-related complete response, 1 immune-related partial response, 6 immune-related stable disease, and 22 immune-related progressive disease. By the modified World Health Organization criteria, there were 1 immune-related complete response, 1 immune-related partial response, 5 immune-related stable disease, and 23 immune-related progressive disease. Immune-related adverse events (as graded by Common Terminology Criteria for Adverse Events version 4.0) consisted of six patients with rash (four grade 1, two grade 2), three patients with diarrhea (one grade 1, two grade 3), one patient with grade 1 thyroiditis, one patient with grade 3 hepatitis, and 1 patient with grade 2 hypophysitis. The median overall survival from the time of the first dose of ipilimumab was 6.4 months (range: 1.8-26.7 months). Several patients demonstrated serologic responses to cancer-testis antigens and other antigens. Durable responses to ipilimumab were observed, but the overall response rate was low. Additional investigation is necessary to clarify the role of ipilimumab in patients with mucosal melanoma.
C1 [Postow, Michael A.; Callahan, Margaret K.; Harding, James J.; D'Angelo, Sandra P.; Dickson, Mark A.; Schwartz, Gary K.; Chapman, Paul B.; Wolchok, Jedd D.; Carvajal, Richard D.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA.
[Bluth, Mark J.] Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10021 USA.
[Panageas, Katherine S.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA.
[Luke, Jason J.; Ibrahim, Nageatte; Ott, Patrick A.; Hodi, F. Stephen] Dana Farber Canc Inst, Melanoma Dis Ctr, Dept Med Oncol, Boston, MA 02115 USA.
[Ramaiya, Nikhil] Dana Farber Brigham & Womens Canc Ctr, Dept Radiol, Boston, MA USA.
[Lawrence, Donald P.; Flaherty, Keith T.; Sullivan, Ryan J.] Massachusetts Gen Hosp Canc Ctr, Dept Med, Boston, MA USA.
[Gnjatic, Sacha] Ludwig Inst Canc Res, New York, NY USA.
[Gnjatic, Sacha] Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY USA.
RP Carvajal, RD (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med, Melanoma Sarcoma Oncol Serv, BAIC 1071, New York, NY 10021 USA.
EM carvajar@mskcc.org
FU National Institutes of Health [RC2CA148468]; Melanoma Research Alliance;
Swim Across America; Cancer Research Institute; Lita Annenberg Hazen
Foundation; Commonwealth Foundation for Cancer Research; Clinical and
Translational Science Center at Weill Cornell Medical College
[UL1-TR000457]; Bristol-Myers Squibb
FX This study was supported by grants from the National Institutes of
Health (RC2CA148468), the Melanoma Research Alliance, Swim Across
America, the Cancer Research Institute, the Lita Annenberg Hazen
Foundation, and the Commonwealth Foundation for Cancer Research. This
investigation was supported by grant UL1-TR000457 of the Clinical and
Translational Science Center at Weill Cornell Medical College.; Margaret
K. Callahan: Bristol-Myers Squibb (RF); Jedd D. Wolchok: Bristol-Myers
Squibb (C/A, RF); F. Stephen Hodi: Bristol-Myers Squibb (C/A, RF);
Richard D. Carvajal: Bristol-Myers Squibb (RF).
NR 29
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U1 0
U2 5
PU ALPHAMED PRESS
PI DURHAM
PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA
SN 1083-7159
J9 ONCOLOGIST
JI Oncologist
PD JUN
PY 2013
VL 18
IS 6
BP 726
EP 732
DI 10.1634/theoncologist.2012-0464
PG 7
WC Oncology
SC Oncology
GA 172YL
UT WOS:000321043200019
PM 23716015
ER
PT J
AU Fecher, LA
Agarwala, SS
Hodi, FS
Weber, JS
AF Fecher, Leslie A.
Agarwala, Sanjiv S.
Hodi, F. Stephen
Weber, Jeffrey S.
TI Ipilimumab and Its Toxicities: A Multidisciplinary Approach
SO ONCOLOGIST
LA English
DT Article
DE Ipilimumab; CTLA-4; Antibody; Melanoma; Immune-mediated toxicity;
immune-related adverse events; AEOSI
ID LYMPHOCYTE-ASSOCIATED ANTIGEN-4; METASTATIC MELANOMA; ANTI-CTLA-4
ANTIBODY; AUTOIMMUNE HYPOPHYSITIS; MONOCLONAL-ANTIBODY; INDUCED
SARCOIDOSIS; CLINICAL-RESPONSE; ADVERSE EVENTS; PHASE-II; CANCER
AB The treatment for metastatic melanoma has evolved significantly in the past few years. Ipilimumab, an immunotherapy, is now in mainstream oncology practice given that it has shown improved overall survival in randomized clinical trials. Other immune modulating agents, such as programmed death receptor-1 and programmed death receptor ligand-1 antibodies, are showing promise in early clinical trials. This manuscript will review ipilimumab and its most common side effects. Immune-related adverse events (irAEs) are important to recognize early, and their presentation, timing of onset, and general recommendations for workup and management will be reviewed. Assembling a multidisciplinary team, as well as thorough education of the patient, is recommended to optimize patient care.
C1 [Fecher, Leslie A.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA.
[Agarwala, Sanjiv S.] St Lukes Canc Ctr, Bethlehem, PA USA.
[Hodi, F. Stephen] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Weber, Jeffrey S.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA.
RP Fecher, LA (reprint author), Indiana Univ, Melvin & Bren Simon Canc Ctr, 535 Barnhill Dr,Room 473, Indianapolis, IN 46202 USA.
EM lafecher@iu.edu
FU Bristol-Myers Squibb; Genentech-Roche; sanofi-aventis
FX The authors take full responsibility for the content of this publication
and confirm that it reflects their viewpoint and medical expertise. The
authors also wish to acknowledge Jennifer Wietzke, Ph.D., and Rebecca
Goldstein, Ph.D., from StemScientific, funded by Bristol-Myers Squibb,
for providing editorial support. Neither Bristol-Myers Squibb nor
StemScientific influenced the content of the manuscript, nor did the
authors receive financial compensation for authoring the manuscript.;
Leslie Fecher: Genentech-Roche, Bristol-Myers Squibb (C/A); Imedex LLC,
Dava Oncology, First Consult LLC (H); Genentech-Roche, sanofi-aventis,
Bristol-Myers Squibb (RF); F. Stephen Hodi: Bristol-Myers Squibb (C/A,
RF); Jeffrey S. Weber: Bristol-Myers Squibb (RF, H).
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U2 11
PU ALPHAMED PRESS
PI DURHAM
PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA
SN 1083-7159
EI 1549-490X
J9 ONCOLOGIST
JI Oncologist
PD JUN
PY 2013
VL 18
IS 6
BP 733
EP 743
DI 10.1634/theoncologist.2012-0483
PG 11
WC Oncology
SC Oncology
GA 172YL
UT WOS:000321043200020
PM 23774827
ER
PT J
AU Taylor, JW
Chi, AS
Cahill, DP
AF Taylor, Jennie W.
Chi, Andrew S.
Cahill, Daniel P.
TI Tailored Therapy in Diffuse Gliomas: Using Molecular Classifiers to
Optimize Clinical Management
SO ONCOLOGY-NEW YORK
LA English
DT Review
ID BRAIN-TUMOR GROUP; IDH2 MUTATIONS; ISOCITRATE DEHYDROGENASE;
GLIOBLASTOMA-MULTIFORME; ONCOMETABOLITE 2-HYDROXYGLUTARATE; GRADE
GLIOMA; RESECTION; OLIGODENDROGLIOMA; SURVIVAL; EXTENT
AB Diffuse gliomas are the most common primary malignant brain tumors in adults and continue to be almost universally fatal. Nevertheless, a striking variability in outcome has long been observed, with a subset of patients having prolonged survival. Recent molecular discoveries have provided new insights into gliomagenesis and have enhanced clinical subclassification of gliomas. Mutations in the isocitrate dehydrogenase (IDH) genes occur frequently in low-grade astrocytomas and oligodendrogliomas (World Health Organization [WHO] grade II), and in higher-grade gliomas (WHO grades III and IV) that arise after malignant progression of low-grade tumors. IDH mutation has an established role as a favorable prognostic marker; however, the utility of IDH mutation in guiding treatment is still under investigation. A subset of IDH-mutant tumors, predominantly oligodendrogliomas, also harbor codeletion of chromosomes 1 p and 19q, a feature that predicts responsiveness to chemotherapy. Here, we review the current data regarding the prognostic and predictive value of IDH mutation and 1 p/19q codeletion in gliomas. We also discuss possible management algorithms using these biomarkers to tailor surgical and adjuvant therapy for specific diffuse gliomas. Ultimately, understanding the natural history of glioma subtypes and the predictive value of genetic markers may maximize survival and minimize treatment morbidity.
C1 [Taylor, Jennie W.; Chi, Andrew S.] Massachusetts Gen Hosp, Ctr Canc, Div Neurooncol, Dept Neurol,Stephen E & Catherine Pappas Ctr Neur, Boston, MA 02114 USA.
[Taylor, Jennie W.; Chi, Andrew S.] Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, Dept Neurol,Stephen E & Catherine Pappas Ctr Neur, Boston, MA 02114 USA.
[Cahill, Daniel P.] Massachusetts Gen Hosp, Ctr Canc, Dept Neurosurg, Stephen E & Catherine Pappas Ctr Neurooncol, Boston, MA 02114 USA.
[Taylor, Jennie W.; Chi, Andrew S.; Cahill, Daniel P.] Harvard Univ, Sch Med, Boston, MA USA.
RP Cahill, DP (reprint author), Massachusetts Gen Hosp, 55 Fruit St Yawkey 9E, Boston, MA 02114 USA.
EM dcahill@partners.org
NR 51
TC 7
Z9 8
U1 0
U2 1
PU UBM MEDICA
PI NORWALK
PA 535 CONNECTICUT AVE, STE 300, NORWALK, CT 06854 USA
SN 0890-9091
J9 ONCOLOGY-NY
JI Oncology-NY
PD JUN
PY 2013
VL 27
IS 6
BP 504
EP 514
PG 11
WC Oncology
SC Oncology
GA 174MH
UT WOS:000321159200002
PM 23909061
ER
PT J
AU Jeon, JY
Meyerhardt, JA
AF Jeon, Justin Y.
Meyerhardt, Jeffrey A.
TI Exercise After Cancer Diagnosis: Time to Get Moving THE
LEMANNE/CASSILETH/GUBILI ARTICLE REVIEWED
SO ONCOLOGY-NEW YORK
LA English
DT Editorial Material
ID PHYSICAL-ACTIVITY; POSTMENOPAUSAL WOMEN; SURVIVORS; INTERVENTION;
GUIDELINES; TRIAL; RISK; NUTRITION; INSULIN; IMPACT
C1 [Jeon, Justin Y.] Yonsei Univ, Dept Sport & Leisure Studies, Seoul 120749, South Korea.
[Meyerhardt, Jeffrey A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
RP Jeon, JY (reprint author), Yonsei Univ, Dept Sport & Leisure Studies, Seoul 120749, South Korea.
NR 18
TC 1
Z9 1
U1 0
U2 3
PU UBM MEDICA
PI NORWALK
PA 535 CONNECTICUT AVE, STE 300, NORWALK, CT 06854 USA
SN 0890-9091
J9 ONCOLOGY-NY
JI Oncology-NY
PD JUN
PY 2013
VL 27
IS 6
BP 585
EP +
PG 3
WC Oncology
SC Oncology
GA 174MH
UT WOS:000321159200015
PM 23909074
ER
PT J
AU Ciolino, JB
Belin, MW
Todani, A
Al-Arfaj, K
Rudnisky, CJ
AF Ciolino, Joseph B.
Belin, Michael W.
Todani, Amit
Al-Arfaj, Khalid
Rudnisky, Christopher J.
CA Boston Keratoprosthesis Type 1
TI Retention of the Boston Keratoprosthesis Type 1: Multicenter Study
Results
SO OPHTHALMOLOGY
LA English
DT Article
ID UNIVERSITY-OF-CALIFORNIA; COMPLICATIONS; OUTCOMES; DAVIS
AB Objective: To report the retention rate of the Boston keratoprosthesis type 1 and to identify risk factors for keratoprosthesis loss.
Design: Cohort study.
Participants: A total of 300 eyes of 300 patients who underwent implantation of the Boston keratoprosthesis type I device between January 2003 and July 2008 by 19 surgeons at 18 medical centers.
Methods: Forms reporting preoperative, intraoperative, and postoperative parameters were prospectively collected and subsequently analyzed at a central data collection site.
Main Outcome Measures: Keratoprosthesis retention.
Results: A total cumulative number of 422 life-years of device implantation are included in this analysis. The average duration of follow-up was 17.1+/-14.8 months, with a range of 1 week to >6.1 years. Ninety-three percent of the 300 Boston keratoprosthesis implants were retained at their last follow-up, corresponding to a retention time of 396 patient-years or 1.42 years/keratoprosthesis. The probability of retention after 1 year and 2 years was 94% and 89%, respectively. During the study period, 21 (7%) eyes failed to retain the device; the reasons for keratoprosthesis loss include sterile keratolysis (9), fungal infections (8), dense retroprosthetic membranes (3), and bacterial endophthalmitis (1). Multivariate analysis demonstrated 3 independent risk factors for keratoprosthesis loss: autoimmune cause (hazard ratio [HR], 11.94; 95% confidence interval [CI], 3.31-43.11), ocular surface exposure requiring a concomitant tarsorrhaphy (HR, 3.43; 95% CI, 1.05-11.22), and number of prior failed penetrating keratoplasties (HR, 1.64; 95% CI, 1.18-2.28).
Conclusions: The Boston keratoprosthesis type 1 seems to be a viable option for eyes that are not candidates for penetrating keratoplasty (PK). Ocular surface disease due to an autoimmune cause demonstrated the lowest retention rate. (C) 2013 by the American Academy of Ophthalmology.
C1 [Ciolino, Joseph B.; Todani, Amit; Al-Arfaj, Khalid] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA USA.
[Ciolino, Joseph B.; Belin, Michael W.; Todani, Amit] Albany Med Coll, Dept Ophthalmol, Albany Med Ctr, Albany, NY 12208 USA.
[Belin, Michael W.] Univ Arizona, Dept Ophthalmol, Tucson, AZ USA.
[Al-Arfaj, Khalid] Dammam Univ, Dept Ophthalmol, Dammam, Saudi Arabia.
[Rudnisky, Christopher J.] Univ Alberta, Dept Ophthalmol, Edmonton, AB, Canada.
RP Ciolino, JB (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA.
EM Joseph_Ciolino@meei.harvard.edu
FU National Eye Institute [1K08EY019686-03]; New England Cornea Transplant
Research Fund; Research to Prevent Blindness Career Development Award;
Lion's Club of Massachusetts
FX Supported by National Eye Institute 1K08EY019686-03 (J.B.C.), New
England Cornea Transplant Research Fund (J.B.C.), Research to Prevent
Blindness Career Development Award (J.B.C.), and Lion's Club of
Massachusetts (J.B.C.).
NR 13
TC 56
Z9 57
U1 0
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
J9 OPHTHALMOLOGY
JI Ophthalmology
PD JUN
PY 2013
VL 120
IS 6
BP 1195
EP 1200
DI 10.1016/j.ophtha.2012.11.025
PG 6
WC Ophthalmology
SC Ophthalmology
GA 167RJ
UT WOS:000320650700024
PM 23499061
ER
PT J
AU Colby, K
Pavan-Langston, D
AF Colby, Kathryn
Pavan-Langston, Deborah
TI Oral Acyclovir for Herpes Simplex Blepharoconjunctivitis in Children
Reply
SO OPHTHALMOLOGY
LA English
DT Letter
C1 [Colby, Kathryn; Pavan-Langston, Deborah] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02115 USA.
RP Colby, K (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02115 USA.
NR 1
TC 0
Z9 0
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
J9 OPHTHALMOLOGY
JI Ophthalmology
PD JUN
PY 2013
VL 120
IS 6
BP E28
EP E9
PG 2
WC Ophthalmology
SC Ophthalmology
GA 167RJ
UT WOS:000320650700002
PM 23732060
ER
PT J
AU Yoon, MK
McCulley, TJ
Horton, JC
AF Yoon, Michael K.
McCulley, Timothy J.
Horton, Jonathan C.
TI Brow Ptosis After Temporal Artery Biopsy
SO OPHTHALMOLOGY
LA English
DT Letter
C1 [Yoon, Michael K.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02115 USA.
[McCulley, Timothy J.] Johns Hopkins Sch Med, Wilmer Eye Inst, Baltimore, MD USA.
[Horton, Jonathan C.] Univ Calif San Francisco, Dept Ophthalmol, San Francisco, CA USA.
[Horton, Jonathan C.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA.
[Horton, Jonathan C.] Univ Calif San Francisco, Dept Physiol, San Francisco, CA USA.
RP Yoon, MK (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02115 USA.
NR 5
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
J9 OPHTHALMOLOGY
JI Ophthalmology
PD JUN
PY 2013
VL 120
IS 6
BP E34
EP E34
PG 1
WC Ophthalmology
SC Ophthalmology
GA 167RJ
UT WOS:000320650700010
PM 23732069
ER
PT J
AU Andrews, JR
Prajapati, KG
Eypper, E
Shrestha, P
Shakya, M
Pathak, KR
Joshi, N
Tiwari, P
Risal, M
Koirala, S
Karkey, A
Dongol, S
Wen, S
Smith, AB
Maru, D
Basnyat, B
Baker, S
Farrar, J
Ryan, ET
Hohmann, E
Arjyal, A
AF Andrews, Jason R.
Prajapati, Krishna G.
Eypper, Elizabeth
Shrestha, Poojan
Shakya, Mila
Pathak, Kamal R.
Joshi, Niva
Tiwari, Priyanka
Risal, Manisha
Koirala, Samir
Karkey, Abhilasha
Dongol, Sabina
Wen, Shawn
Smith, Amy B.
Maru, Duncan
Basnyat, Buddha
Baker, Stephen
Farrar, Jeremy
Ryan, Edward T.
Hohmann, Elizabeth
Arjyal, Amit
TI Evaluation of an Electricity-free, Culture-based Approach for Detecting
Typhoidal Salmonella Bacteremia during Enteric Fever in a High Burden,
Resource-limited Setting
SO PLOS NEGLECTED TROPICAL DISEASES
LA English
DT Article
ID BONE-MARROW; BLOOD CULTURE; DIAGNOSIS; TYPHI; EFFICACY; BROTH;
BACT/ALERT; PARATYPHI; KATHMANDU; COUNTRIES
AB Background: In many rural areas at risk for enteric fever, there are few data on Salmonella enterica serotypes Typhi (S. Typhi) and Paratyphi (S. Paratyphi) incidence, due to limited laboratory capacity for microbiologic culture. Here, we describe an approach that permits recovery of the causative agents of enteric fever in such settings. This approach involves the use of an electricity-free incubator based upon use of phase-change materials. We compared this against conventional blood culture for detection of typhoidal Salmonella.
Methodology/Principal Findings: Three hundred and four patients with undifferentiated fever attending the outpatient and emergency departments of a public hospital in the Kathmandu Valley of Nepal were recruited. Conventional blood culture was compared against an electricity-free culture approach. Blood from 66 (21.7%) patients tested positive for a Gram-negative bacterium by at least one of the two methods. Sixty-five (21.4%) patients tested blood culture positive for S. Typhi (30; 9.9%) or S. Paratyphi A (35; 11.5%). From the 65 individuals with culture-confirmed enteric fever, 55 (84.6%) were identified by the conventional blood culture and 60 (92.3%) were identified by the experimental method. Median time-to-positivity was 2 days for both procedures. The experimental approach was falsely positive due to probable skin contaminants in 2 of 239 individuals (0.8%). The percentages of positive and negative agreement for diagnosis of enteric fever were 90.9% (95% CI: 80.0%-97.0%) and 96.0% (92.7%-98.1%), respectively. After initial incubation, Salmonella isolates could be readily recovered from blood culture bottles maintained at room temperature for six months.
Conclusions/Significance: A simple culture approach based upon a phase-change incubator can be used to isolate agents of enteric fever. This approach could be used as a surveillance tool to assess incidence and drug resistance of the etiologic agents of enteric fever in settings without reliable local access to electricity or local diagnostic microbiology laboratories.
C1 [Andrews, Jason R.; Eypper, Elizabeth; Ryan, Edward T.; Hohmann, Elizabeth] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[Andrews, Jason R.; Maru, Duncan; Ryan, Edward T.; Hohmann, Elizabeth] Harvard Univ, Sch Med, Boston, MA USA.
[Prajapati, Krishna G.; Shrestha, Poojan; Shakya, Mila; Pathak, Kamal R.; Joshi, Niva; Tiwari, Priyanka; Risal, Manisha; Koirala, Samir; Karkey, Abhilasha; Dongol, Sabina; Basnyat, Buddha; Arjyal, Amit] Univ Oxford, Patan Hosp, Patan Acad Hlth Sci, Clin Res Unit, Kathmandu, Nepal.
[Wen, Shawn; Smith, Amy B.] MIT, Lab D, Cambridge, MA USA.
[Maru, Duncan] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Baker, Stephen; Farrar, Jeremy] Univ Oxford, Clin Res Unit, Wellcome Trust Major Overseas Programme, Hosp Trop Dis, Ho Chi Minh City, Vietnam.
[Baker, Stephen; Farrar, Jeremy] Univ Oxford, Ctr Trop Med, Oxford, England.
[Baker, Stephen] Univ London London Sch Hyg & Trop Med, London WC1E 7HT, England.
[Ryan, Edward T.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
RP Andrews, JR (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
EM jandrews6@partners.org
OI Farrar, Jeremy/0000-0002-2700-623X
FU Frederick Lovejoy Fund at Boston Children's Hospital; Harvard Global
Health Institute; Li Ka Shing Foundation; National Institute of Allergy
and Infectious Diseases [AI100023, AI077883]
FX This study was supported by the Frederick Lovejoy Fund at Boston
Children's Hospital, Harvard Global Health Institute, the Li Ka Shing
Foundation, and the National Institute of Allergy and Infectious
Diseases (AI100023 and AI077883). The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 40
TC 7
Z9 7
U1 0
U2 14
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1935-2735
J9 PLOS NEGLECT TROP D
JI Plos Neglect. Trop. Dis.
PD JUN
PY 2013
VL 7
IS 6
AR e2292
DI 10.1371/journal.pntd.0002292
PG 8
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA 175AL
UT WOS:000321201300043
PM 23853696
ER
PT J
AU Sinclair, SJ
Slavin-Mulford, J
Antonius, D
Stein, MB
Siefert, CJ
Haggerty, G
Malone, JC
O'Keefe, S
Blais, MA
AF Sinclair, Samuel Justin
Slavin-Mulford, Jenelle
Antonius, Daniel
Stein, Michelle B.
Siefert, Caleb J.
Haggerty, Greg
Malone, Johanna C.
O'Keefe, Sheila
Blais, Mark A.
TI Development and Preliminary Validation of the Level of Care Index (LOCI)
From the Personality Assessment Inventory (PAI) in a Psychiatric Sample
SO PSYCHOLOGICAL ASSESSMENT
LA English
DT Article
DE Level of Care Index; LOCI; psychiatric hospitalization; personality
assessment inventory; PAI
ID OBJECT RELATIONS SCALE; SUICIDE ATTEMPTERS; PSYCHOMETRIC PROPERTIES;
HOSPITAL UTILIZATION; SERVICE UTILIZATION; INPATIENT SERVICE; SOCIAL
COGNITION; CLINICAL UTILITY; SUBSTANCE-ABUSE; NORMATIVE DATA
AB Research over the last decade has been promising in terms of the incremental utility of psychometric tools in predicting important clinical outcomes, such as mental health service utilization and inpatient psychiatric hospitalization. The purpose of this study was to develop and validate a new Level of Care Index (LOCI) from the Personality Assessment Inventory (PAI). Logistic regression was initially used in a development sample (n = 253) of psychiatric patients to identify unique PAI indicators associated with inpatient (n = 75) as opposed to outpatient (n = 178) status. Five PAI variables were ultimately retained (Suicidal Ideation, Antisocial Personality-Stimulus Seeking, Paranoia-Persecution, Negative Impression Management, and Depression-Affective) and were then aggregated into a single LOCI and independently evaluated in a second validation sample (n = 252). Results indicated the LOCI effectively differentiated inpatients from outpatients after controlling for demographic variables and was significantly associated with both internalizing and externalizing risk factors for psychiatric admission (range of ds = 0.46 for history of arrests to 0.88 for history of suicidal ideation). The LOCI was additionally found to be meaningfully associated with measures of normal personality, performance-based tests of psychological functioning, and measures of neurocognitive (executive) functioning. The clinical implications of these findings and potential utility of the LOCI are discussed.
C1 [Sinclair, Samuel Justin; Slavin-Mulford, Jenelle; Stein, Michelle B.; Malone, Johanna C.; O'Keefe, Sheila; Blais, Mark A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Sinclair, Samuel Justin; Stein, Michelle B.; Malone, Johanna C.; O'Keefe, Sheila; Blais, Mark A.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Antonius, Daniel] SUNY Buffalo, Sch Med & Biomed Sci, Buffalo, NY USA.
[Antonius, Daniel] NYU, Dept Psychiat, Sch Med, New York, NY 10003 USA.
[Siefert, Caleb J.] Univ Michigan Dearborn, Dept Behav Sci, Dearborn, MI 48128 USA.
[Haggerty, Greg] Nassau Univ, Von Tauber Inst Global Psychiat, Med Ctr, E Meadow, NY USA.
RP Sinclair, SJ (reprint author), Massachusetts Gen Hosp, 1 Bowdoin Sq 7th Floor, Boston, MA 02114 USA.
EM SJSinclair@Partners.org
NR 63
TC 4
Z9 4
U1 1
U2 5
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 1040-3590
J9 PSYCHOL ASSESSMENT
JI Psychol. Assess.
PD JUN
PY 2013
VL 25
IS 2
BP 606
EP 617
DI 10.1037/a0032085
PG 12
WC Psychology, Clinical
SC Psychology
GA 173DR
UT WOS:000321058800027
PM 23458082
ER
PT J
AU Hartwell, KJ
Prisciandaro, JJ
Borckardt, J
Li, XB
George, MS
Brady, KT
AF Hartwell, Karen J.
Prisciandaro, James J.
Borckardt, Jeffery
Li, Xingbao
George, Mark S.
Brady, Kathleen T.
TI Real-Time fMRI in the Treatment of Nicotine Dependence: A Conceptual
Review and Pilot Studies
SO PSYCHOLOGY OF ADDICTIVE BEHAVIORS
LA English
DT Article
DE real-time fMRI; real-time fMRI feedback; neurofeedback; nicotine
dependence
ID CORTEX ACTIVITY; FUNCTIONAL MRI; ACTIVATION; SMOKERS; NEUROFEEDBACK;
BIOFEEDBACK; MODULATION; INTERFACE; RELAPSE
AB Technical advances allowing for the analysis of functional MRI (fMRI) results in real time have led to studies exploring the ability of individuals to use neural feedback signals to modify behavior and regional brain activation. The use of real-time fMRI (rtfMRI) feedback has been explored for therapeutic benefit in a number of disease states, but to our knowledge, the potential therapeutic benefit of rtfMRI feedback in the treatment of addictive disorders has not been explored. This article will provide an overview of the development of rtfMRI and discussion of its potential uses in the treatment of addictions. We also describe a series of pilot studies that highlight some of the technical challenges in developing a rtfMRI feedback paradigm for use in addictions, specifically in nicotine dependence. Because the use of rtfMRI feedback is in its infancy, the work described is focused on establishing some of the basic parameters in optimizing the rtfMRI feedback, such as the type of feedback signal, region of interest for feedback and predicting which subjects are most likely to respond well to training. While rtfMRI feedback remains an intriguing possibility for the treatment of addictions, much work remains to be done in establishing its efficacy.
C1 [Hartwell, Karen J.; Prisciandaro, James J.; Borckardt, Jeffery; Li, Xingbao; George, Mark S.; Brady, Kathleen T.] Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA.
[Hartwell, Karen J.; George, Mark S.; Brady, Kathleen T.] Ralph H Johnson VAMC, Charleston, SC USA.
RP Hartwell, KJ (reprint author), Med Univ S Carolina, 67 President St,MSC 861, Charleston, SC 29425 USA.
EM hartwelk@musc.edu
FU NIDA NIH HHS [R33 DA026085, R33 DA026085-04, R33 DA036085-03]
NR 45
TC 12
Z9 12
U1 2
U2 14
PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA
SN 0893-164X
J9 PSYCHOL ADDICT BEHAV
JI Psychol. Addict. Behav.
PD JUN
PY 2013
VL 27
IS 2
SI SI
BP 501
EP 509
DI 10.1037/a0028215
PG 9
WC Substance Abuse; Psychology, Multidisciplinary
SC Substance Abuse; Psychology
GA 170HS
UT WOS:000320841600017
PM 22564200
ER
PT J
AU Schellhammer, PF
Chodak, G
Whitmore, JB
Sims, R
Frohlich, MW
Kantoff, PW
AF Schellhammer, Paul F.
Chodak, Gerald
Whitmore, James B.
Sims, Robert
Frohlich, Mark W.
Kantoff, Philip W.
TI Lower Baseline Prostate-specific Antigen Is Associated With a Greater
Overall Survival Benefit From Sipuleucel-T in the Immunotherapy for
Prostate Adenocarcinoma Treatment (IMPACT) Trial
SO UROLOGY
LA English
DT Article
ID MITOXANTRONE PLUS PREDNISONE; CANCER; MEN; CORRELATE; ANEMIA
AB OBJECTIVE To explore the prognostic and predictive value of baseline variables in 512 patients with metastatic castration-resistant prostate cancer from the phase III Immunotherapy for Prostate Adenocarcinoma Treatment (IMPACT) trial who were randomized to receive sipuleucel-T or control.
METHODS The most powerful of these prognostic factors, baseline prostate-specific antigen (PSA), was subdivided into quartiles to evaluate treatment effect patterns. Cox regression analyses were used to assess predictors of overall survival (OS) and sipuleucel-T treatment effect within PSA quartiles. Median OS was estimated by the Kaplan-Meier method.
RESULTS PSA was the strongest baseline prognostic factor (P<.0001). Furthermore, the sipuleucel-T treatment effect appeared greater with decreasing baseline PSA. The OS hazard ratio for patients in the lowest baseline PSA quartile (<= 22.1 ng/mL) was 0.51 (95% confidence interval, 0.31-0.85) compared with 0.84 (95% confidence interval, 0.55-1.29) for patients in the highest PSA quartile (>134 ng/mL). Estimated improvement in median survival varied from 13.0 months in the lowest baseline PSA quartile to 2.8 months in the highest quartile. Estimated 3-year survival in the lowest PSA quartile was 62.6% for sipuleucel-T patients and 41.6% for control patients, representing a 50% relative increase.
CONCLUSION The greatest magnitude of benefit with sipuleucel-T treatment in this exploratory analysis was observed among patients with better baseline prognostic factors, particularly those with lower baseline PSA values. These findings suggest that patients with less advanced disease may benefit the most from sipuleucel-T treatment and provide a rationale for immunotherapy as an early treatment strategy in sequencing algorithms for metastatic castration-resistant prostate cancer. (C) 2013 Elsevier Inc.
C1 Eastern Virginia Med Sch, Dept Urol, Norfolk, VA 23501 USA.
Weiss Mem Hosp, Midwest Prostate & Urol Hlth Ctr, Chicago, IL USA.
Dendreon Corp, Seattle, WA USA.
[Kantoff, Philip W.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
RP Kantoff, PW (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02115 USA.
EM philip_kantoff@dfci.harvard.edu
FU Dendreon Corporation
FX This study was funded by Dendreon Corporation.
NR 24
TC 70
Z9 73
U1 0
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0090-4295
EI 1527-9995
J9 UROLOGY
JI Urology
PD JUN
PY 2013
VL 81
IS 6
BP 1297
EP 1302
DI 10.1016/j.urology.2013.01.061
PG 6
WC Urology & Nephrology
SC Urology & Nephrology
GA 167BN
UT WOS:000320605400061
PM 23582482
ER
PT J
AU Najafzadeh, M
Marra, CA
Lynd, L
Wiseman, S
AF Najafzadeh, Mehdi
Marra, Carlo A.
Lynd, Larry
Wiseman, Sam
TI Authors' Response to "Comparative Effectiveness and Personalized
Medicine" by Dr. JC Hornberger
SO VALUE IN HEALTH
LA English
DT Letter
C1 [Najafzadeh, Mehdi] Mass Gen Hosp, Mongan Inst, Boston, MA USA.
[Marra, Carlo A.; Lynd, Larry] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada.
[Wiseman, Sam] St Pauls Hosp, Vancouver, BC V6Z 1Y6, Canada.
RP Najafzadeh, M (reprint author), Mass Gen Hosp, Mongan Inst, Boston, MA USA.
NR 2
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 1098-3015
J9 VALUE HEALTH
JI Value Health
PD JUN
PY 2013
VL 16
IS 4
BP 697
EP 697
DI 10.1016/j.jval.2013.02.005
PG 1
WC Economics; Health Care Sciences & Services; Health Policy & Services
SC Business & Economics; Health Care Sciences & Services
GA 178IK
UT WOS:000321440900030
PM 23796305
ER
PT J
AU Patel, MS
Arron, MJ
Sinsky, TA
Green, EH
Baker, DW
Bowen, JL
Day, S
AF Patel, Mitesh S.
Arron, Martin J.
Sinsky, Thomas A.
Green, Eric H.
Baker, David W.
Bowen, Judith L.
Day, Susan
TI Estimating the Staffing Infrastructure for a Patient-Centered Medical
Home
SO AMERICAN JOURNAL OF MANAGED CARE
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; PRIMARY-CARE; HEALTH-CARE; GLYCEMIC
CONTROL; COST SAVINGS; INNOVATION; SERVICES; QUALITY; MODEL; MANAGEMENT
AB Background:The patient-centered medical home (PCMH) offers an innovative method of delivering primary care. However, the necessary staffing infrastructure is not well established.
Objectives: To evaluate the roles of personnel within a PCMH and to propose necessary staffing ratios and associated incremental costs to implement this model of care.
Methods: We sampled primary care clinical practices that either have successfully deployed or were in the process of implementing a PCMH practice model. We conducted targeted interviews of administrators from these practices and reviewed published literature on the personnel roles within a PCMH. Collectively, these data were compared with current staffing standards and used to inform an analytical model and sensitivity analysis.
Results: Primary care practices that successfully transitioned to a PCMH have incorporated a range of new staff and functionalities. Based on our model, we estimated that 4.25 full-time equivalents (FTEs) should be allocated to staffing personnel per 1 physician FTE. Compared with the base-case model of current staffing in the United States of 2.68 FTEs per physician FTE, this is a 59% increase. After applying sensitivity analysis for variability in staffing and compensation, the incremental staffing FTE per physician FTE was 1.57 (range 1.41-1.73) and the incremental associated cost per member per month was $4.68 (range $3.79-$6.43).
Conclusions: Our study suggests that additional staff with specific expertise and training is necessary to implement a PCMH. Further study and opportunities for funding additional staffing costs will be important for realizing the potential of the PCMH model of care.
C1 [Patel, Mitesh S.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA.
[Patel, Mitesh S.] Univ Penn, Robert Wood Johnson Clin Scholars Program, Philadelphia, PA 19104 USA.
[Day, Susan] Univ Penn, Div Gen Internal Med, Philadelphia, PA 19104 USA.
[Arron, Martin J.] Beth Israel Deaconess Med Ctr, New York, NY 10003 USA.
[Sinsky, Thomas A.] Med Associates, Dubuque, IA USA.
[Green, Eric H.] Mercy Catholic Med Ctr, Darby, PA USA.
[Baker, David W.] Northwestern Univ, Dept Med, Chicago, IL 60611 USA.
[Bowen, Judith L.] Oregon Hlth & Sci Univ, Div Gen Internal Med, Portland, OR 97201 USA.
RP Patel, MS (reprint author), Univ Penn, 423 Guardian Dr,13th Fl, Philadelphia, PA 19104 USA.
EM mpatel@mail.med.upenn.edu
NR 47
TC 19
Z9 19
U1 2
U2 10
PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC
PI PLAINSBORO
PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA
SN 1088-0224
J9 AM J MANAG CARE
JI Am. J. Manag. Care
PD JUN
PY 2013
VL 19
IS 6
BP 509
EP 516
PG 8
WC Health Care Sciences & Services; Health Policy & Services; Medicine,
General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA 171FO
UT WOS:000320910700005
PM 23844711
ER
PT J
AU Dukkipati, SR
Kuck, KH
Neuzil, P
Woollett, I
Kautzner, J
McElderry, HT
Schmidt, B
Gerstenfeld, EP
Doshi, SK
Horton, R
Metzner, A
d'Avila, A
Ruskin, JN
Natale, A
Reddy, VY
AF Dukkipati, Srinivas R.
Kuck, Karl-Heinz
Neuzil, Petr
Woollett, Ian
Kautzner, Josef
McElderry, H. Thomas
Schmidt, Boris
Gerstenfeld, Edward P.
Doshi, Shephal K.
Horton, Rodney
Metzner, Andreas
d'Avila, Andre
Ruskin, Jeremy N.
Natale, Andrea
Reddy, Vivek Y.
TI Pulmonary Vein Isolation Using a Visually Guided Laser Balloon Catheter:
The First 200-Patient Multicenter Clinical Experience
SO CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY
LA English
DT Article
DE atrial fibrillation; catheter ablation; lasers; pulmonary vein
isolation; visual guidance
ID PAROXYSMAL ATRIAL-FIBRILLATION; VENOUS ISOLATION; ABLATION; FEASIBILITY;
CRYOBALLOON
AB Background
Because of the technical difficulty with achieving pulmonary vein (PV) isolation in the treatment of patients with paroxysmal atrial fibrillation, novel catheter designs to facilitate the procedure are in development. A visually guided laser ablation (VGLA) catheter was designed to allow the operator to directly visualize target tissue for ablation and then deliver laser energy to perform point-to-point circumferential ablation. Single-center studies have demonstrated favorable safety and efficacy. We sought to determine the multicenter feasibility, efficacy, and safety of performing PV isolation using the VGLA catheter.
Methods and Results
This study includes the first 200 paroxysmal atrial fibrillation patients treated with the VGLA catheter (33 operators, 15 centers). After transseptal puncture, the VGLA catheter was used to perform PV isolation. Electric isolation was assessed using a circular mapping catheter. Using the VGLA catheter, 98.8% (95% confidence interval, 97.8%-99.5%) of targeted PVs were isolated using a mean of 1.07 catheters per patient. Fluoroscopy and procedure times were 31 +/- 21 (mean +/- SD) and 200 +/- 54 minutes, respectively, and improved with operator experience. There were no instances of stroke, transient ischemic attack, atrioesophageal fistulas, or significant PV stenosis. There was a 2% incidence of cardiac tamponade and a 2.5% incidence of phrenic nerve palsy. At 12 months, the drug-free rate of freedom from atrial arrhythmias after 1 or 2 procedures was 60.2% (95% confidence interval, 52.7%-67.4%).
Conclusions
In this multicenter experience of the first 200 patients treated with the VGLA catheter, PV isolation can be achieved in virtually all patients using a single VGLA catheter with an efficacy similar to radiofrequency ablation.
C1 [Dukkipati, Srinivas R.; d'Avila, Andre; Reddy, Vivek Y.] Mt Sinai Sch Med, Helmsley Electrophysiol Ctr, New York, NY 10029 USA.
[Kuck, Karl-Heinz; Metzner, Andreas] Asklepios Klin St Georg, Hamburg, Germany.
[Neuzil, Petr] Homolka Hosp, Prague, Czech Republic.
[Woollett, Ian] Sentara Cardiovasc Res Inst, Norfolk, VA USA.
[Kautzner, Josef] IKEM, Prague, Czech Republic.
[McElderry, H. Thomas] Univ Alabama Birmingham, Birmingham, AL USA.
[Schmidt, Boris] Cardioangiol Ctr Bethanien CCB, Frankfurt, Germany.
[Gerstenfeld, Edward P.] Univ Calif San Francisco, Sch Med, San Francisco, CA USA.
[Doshi, Shephal K.] Pacific Heart Inst, Santa Monica, CA USA.
[Horton, Rodney; Natale, Andrea] Texas Cardiac Arrhythmia Inst, Austin, TX USA.
[Ruskin, Jeremy N.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Reddy, VY (reprint author), Mt Sinai Sch Med, Helmsley Electrophysiol Ctr, 1 Gustave L Levy Pl,Box 1030, New York, NY 10029 USA.
EM vivek.reddy@mountsinai.org
RI d'Avila, Andre/F-8009-2010
OI d'Avila, Andre/0000-0001-8769-1411
FU CardioFocus, Inc.
FX This study was supported by CardioFocus, Inc.
NR 17
TC 32
Z9 35
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1941-3149
J9 CIRC-ARRHYTHMIA ELEC
JI Circ.-Arrhythmia Electrophysiol.
PD JUN
PY 2013
VL 6
IS 3
BP 467
EP 472
DI 10.1161/CIRCEP.113.000431
PG 6
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 169EH
UT WOS:000320760200012
PM 23559674
ER
PT J
AU Gao, XL
Wang, HZ
Yang, J
Liu, ZR
AF Gao, Xueliang
Wang, Haizhen
Yang, Jenny
Liu, Zhi-Ren
TI Prevent protein interactions to prevent cancer metastasis
SO EXPERT REVIEW OF PROTEOMICS
LA English
DT Editorial Material
DE cancer metastasis; drug discovery; drug targets; inhibitor;
protein-protein interaction
ID DRUG DISCOVERY; TUMOR-GROWTH; IN-VIVO; BREAST; ANGIOGENESIS; INHIBITION;
ACTIVATION; RECEPTOR; BIOLOGY
C1 [Gao, Xueliang; Wang, Haizhen] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Yang, Jenny] Georgia State Univ, Dept Chem, Atlanta, GA 30303 USA.
[Liu, Zhi-Ren] Georgia State Univ, Dept Biol, Atlanta, GA 30303 USA.
RP Gao, XL (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA.
EM xueliang_gao@dfci.harvard.edu
NR 21
TC 1
Z9 1
U1 1
U2 6
PU EXPERT REVIEWS
PI LONDON
PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB,
ENGLAND
SN 1478-9450
J9 EXPERT REV PROTEOMIC
JI Expert Rev. Proteomics
PD JUN
PY 2013
VL 10
IS 3
BP 207
EP 209
DI 10.1586/EPR.13.17
PG 3
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 168LU
UT WOS:000320708200001
PM 23777209
ER
PT J
AU Halczli, A
Woolley, AB
AF Halczli, Alyssa
Woolley, Adam B.
TI Medication underdosing and underprescribing: Issues that may contribute
to polypharmacy, poor outcomes
SO FORMULARY
LA English
DT Article
AB Medication underdosing and underprescribing are often overlooked and can result in poor patient outcomes. They can also contribute to polypharmacy and significant cost to the healthcare system. Pharmacists can play a key role in preventing underdosing and underprescribing of medications by ensuring that patient-specific pharmacotherapy is prescribed and administered, and by providing patient and provider education regarding appropriate use of medications. While numerous examples of effective pharmacist-led interventions to reduce medication underdosing and underprescribing are described in the literature, further research is needed to elucidate new ways to improve patient outcomes and reduce unnecessary cost to the healthcare system. This article describes the clinical consequences of medication underdosing and underprescribing and provides examples of pharmacist-led interventions to address these medication issues.
C1 [Halczli, Alyssa; Woolley, Adam B.] VA Boston Healthcare Syst, Boston, MA USA.
[Woolley, Adam B.] Northeastern Univ, Sch Pharm, Dept Pharm Serv, Bouve Coll Hlth Sci, Boston, MA 02115 USA.
RP Halczli, A (reprint author), VA Boston Healthcare Syst, Boston, MA USA.
NR 15
TC 2
Z9 2
U1 0
U2 0
PU ADVANSTAR COMMUNICATIONS INC
PI DULUTH
PA 131 W 1ST STREET, DULUTH, MN 55802 USA
SN 1082-801X
J9 FORMULARY
JI Formulary
PD JUN
PY 2013
VL 48
IS 6
BP 194
EP 196
PG 3
GA 170EH
UT WOS:000320832400010
ER
PT J
AU Thiagarajan, P
Afshar-Kharghan, V
AF Thiagarajan, Perumal
Afshar-Kharghan, Vahid
TI Platelet Transfusion Therapy
SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA
LA English
DT Article
DE Platelet transfusion; Alloimmunization; Transfusion triggers; Pathogen
reduction
ID THROMBOTIC THROMBOCYTOPENIC PURPURA; MEMBRANE PHOSPHOLIPID ASYMMETRY;
PATHOGEN INACTIVATION; STORED PLATELETS; CROSS-MATCH; PHOSPHATIDYLSERINE
EXPOSURE; APHERESIS PLATELETS; BLEEDING DIATHESIS; BLOOD-PLATELETS;
ACUTE-LEUKEMIA
AB Platelet transfusion therapy has become an integral part of the treatment of patients with hematological and solid tumor malignancy receiving chemotherapy. Since its introduction almost 60 years ago, several advances and refinements have been introduced in the collection, storage, and administration to improve the safety and efficacy of platelet transfusion. This review summarizes the current practice and clinical approach to patients with thrombocytopenia. Existing evidence-based guidelines for appropriate platelet transfusion is reviewed.
C1 [Thiagarajan, Perumal] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Dept Pathol, Houston, TX 77030 USA.
[Thiagarajan, Perumal] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Houston, TX 77030 USA.
[Afshar-Kharghan, Vahid] MD Anderson Canc Ctr, Sect Benign Hematol, Houston, TX 77030 USA.
RP Thiagarajan, P (reprint author), Michael E DeBakey VA Med Ctr, Mail Stop 113,2002 Holcombe Blvd, Houston, TX 77030 USA.
EM perumalt@bcm.edu
OI Thiagarajan, Perumal/0000-0003-2186-7036
FU Veterans Affairs Research Service
FX Supported by a grant from the Veterans Affairs Research Service (P.
Thiagarajan).
NR 103
TC 12
Z9 12
U1 0
U2 6
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0889-8588
J9 HEMATOL ONCOL CLIN N
JI Hematol. Oncol. Clin. North Am.
PD JUN
PY 2013
VL 27
IS 3
BP 629
EP +
DI 10.1016/j.hoc.2013.03.004
PG 16
WC Oncology; Hematology
SC Oncology; Hematology
GA 168XJ
UT WOS:000320740900012
PM 23714315
ER
PT J
AU Higgins, HW
Jenkins, J
Horn, TD
Kroumpouzos, G
AF Higgins, H. William
Jenkins, Jennifer
Horn, Thomas D.
Kroumpouzos, George
TI Pregnancy-Associated Hyperkeratosis of the Nipple A Report of 25 Cases
SO JAMA DERMATOLOGY
LA English
DT Article
ID NEVOID HYPERKERATOSIS; ACANTHOSIS NIGRICANS; HYPER-KERATOSIS; UNILATERAL
HYPERKERATOSIS; TOPICAL CALCIPOTRIOL; AREOLA
AB Importance: Reported physiologic nipple changes in pregnancy do not include hyperkeratosis and are expected to resolve or improve post partum. Hyperkeratosis of the nipple and/or areola can develop in the context of inflammatory diseases (such as atopic dermatitis), in acanthosis nigricans, as an extension of epidermal nevus, after estrogen treatment, and/or in nevoid hyperkeratosis of the nipple and areola. We performed a clinicopathologic analysis of cases of pregnancy-associated nipple hyperkeratosis.
Observations: Twenty-five cases of pregnancy-associated nipple hyperkeratosis identified during a 5-year period (January 1, 2007, through December 31, 2012) are reported. The lesions were bilateral and involved predominantly the top of the nipple. Lesions were symptomatic in 17 patients (68%), causing tenderness or discomfort, pruritus, sensitivity to touch, and/or discomfort with breastfeeding. Nine patients (36%) experienced symptomatic aggravation only during pregnancy or breastfeeding. The lesions persisted post partum in 22 patients (88%). Histopathologic features were conspicuous orthokeratotic hyperkeratosis, with papillomatosis and acanthosis being mild or absent.
Conclusions and Relevance: Pregnancy-associated hyperkeratosis of the nipple can be symptomatic and persist post partum. It may represent a physiologic change of pregnancy. The characteristic clinicopathologic features of this disorder allow differentiation from nevoid hyperkeratosis of the nipple and areola. We suggest that this distinctive clinicopathologic entity be called pregnancy-associated hyperkeratosis of the nipple.
C1 [Higgins, H. William; Kroumpouzos, George] Brown Univ, Warren Alpert Med Sch, Dept Dermatol, Providence, RI 02912 USA.
[Jenkins, Jennifer] Atrius Hlth, Dedham Med Associates, Div Dermatol, Dedham, MA USA.
[Horn, Thomas D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol, Boston, MA USA.
[Horn, Thomas D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA.
[Kroumpouzos, George] Atrius Hlth, South Shore Med Ctr, Norwell, MA USA.
RP Kroumpouzos, G (reprint author), Rhode Isl Hosp, Dept Dermatol, APC 10,593 Eddy St, Providence, RI 02903 USA.
EM gk@gkderm.com
OI Kroumpouzos, George/0000-0002-5915-4640
NR 31
TC 4
Z9 4
U1 0
U2 2
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 2168-6068
J9 JAMA DERMATOL
JI JAMA Dermatol.
PD JUN
PY 2013
VL 149
IS 6
BP 722
EP 726
DI 10.1001/jamadermatol.2013.128
PG 5
WC Dermatology
SC Dermatology
GA 170MY
UT WOS:000320857700011
PM 23616176
ER
PT J
AU Rogers, DJ
Cunnane, MB
Hartnick, CJ
AF Rogers, Derek J.
Cunnane, Mary Beth
Hartnick, Christopher J.
TI Vascular Compression of the Airway Establishing a Functional Diagnostic
Algorithm
SO JAMA OTOLARYNGOLOGY-HEAD & NECK SURGERY
LA English
DT Article
ID INNOMINATE-ARTERY COMPRESSION; SURGICAL-MANAGEMENT; COMPUTED-TOMOGRAPHY;
ANOMALIES; CHILDREN; TRACHEA; ANESTHESIA; EXPOSURE; RISKS
AB Importance: Pediatric imaging carries the risk of radiation exposure. Children frequently undergo computed tomography with angiography (CTA) for findings on bronchoscopy with limited knowledge regarding the necessity of such imaging.
Objective: To report our experience with all pediatric patients at our institution over an 8-year period with airway symptoms warranting bronchoscopy followed by CTA for potential vascular anomaly. Goals were to report the percentage of positive findings seen on CTA leading to surgery; discuss relative radiation exposure risk and sedation risk for additional radio-logic studies; and propose a functional diagnostic algorithm.
Design, Setting, and Participants: Retrospective chart review of 42 children aged 2 months to 11 years with tracheomalacia who underwent CTA between 2004 and 2012 in our tertiary aerodigestive center.
Interventions: Bronchoscopy and CTA.
Main Outcomes and Measures: Presence of vascular anomaly and need for thoracic surgery.
Results: Of these 42 children, 21 (50%) had a vascular anomaly identified on CTA. Of these 21, 17 (81%) had innominate artery compression; 1 (5%) had double aortic arch; 1 (5%) had right aortic arch; 3 (14%) had bronchial compression by pulmonary artery; and 1 (5%) had dextrocardia with duplicated vena cava. Six (29%) of these 21 had clinical symptoms and CTA findings requiring thoracic surgery. The most common symptoms in children requiring thoracic surgery were cough, cyanosis, and stridor.
Conclusions and Relevance: Deciding when to obtain imaging for bronchoscopic findings suggestive of vascular compression remains challenging. A diagnostic algorithm is proposed as a means to provide the best clinical care while weighing risks of additional radiation exposure vs sedation and exposure to general anesthesia.
C1 [Rogers, Derek J.; Hartnick, Christopher J.] Massachusetts Eye & Ear Infirm, Dept Pediat Otolaryngol, Boston, MA 02114 USA.
[Cunnane, Mary Beth] Massachusetts Eye & Ear Infirm, Dept Pediat Neuroradiol, Boston, MA 02114 USA.
[Cunnane, Mary Beth] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Cunnane, Mary Beth] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Hartnick, CJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Pediat Otolaryngol, 243 Charles St, Boston, MA 02114 USA.
EM Christopher_Hartnick@meei.harvard.edu
NR 22
TC 3
Z9 3
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 2168-6181
J9 JAMA OTOLARYNGOL
JI JAMA Otolaryngol-Head Neck Surg.
PD JUN
PY 2013
VL 139
IS 6
BP 586
EP 591
DI 10.1001/jamaoto.2013.3214
PG 6
WC Otorhinolaryngology; Surgery
SC Otorhinolaryngology; Surgery
GA 170MP
UT WOS:000320856300006
PM 23787416
ER
PT J
AU Sabatini, ME
Dizon, DS
AF Sabatini, Mary E.
Dizon, Don S.
TI Why DOMA is unconstitutional, beyond the traditional views of same sex
relationships
SO JOURNAL OF ASSISTED REPRODUCTION AND GENETICS
LA English
DT Letter
C1 [Sabatini, Mary E.] Massachusetts Gen Hosp, Div Reprod Endocrinol & Infertil, Vincent Mem Dept Obstet & Gynecol, Boston, MA 02114 USA.
[Dizon, Don S.] Massachusetts Gen Hosp, Ctr Canc, Oncol Sexual Hlth Clin, Gillette Ctr Gynecol Oncol, Boston, MA 02114 USA.
RP Sabatini, ME (reprint author), Massachusetts Gen Hosp, Div Reprod Endocrinol & Infertil, Vincent Mem Dept Obstet & Gynecol, Boston, MA 02114 USA.
EM msabatini@partners.org; ddizon@partners.org
NR 0
TC 0
Z9 0
U1 0
U2 3
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1058-0468
J9 J ASSIST REPROD GEN
JI J. Assist. Reprod. Genet.
PD JUN
PY 2013
VL 30
IS 6
BP 861
EP 861
DI 10.1007/s10815-013-0020-3
PG 1
WC Genetics & Heredity; Obstetrics & Gynecology; Reproductive Biology
SC Genetics & Heredity; Obstetrics & Gynecology; Reproductive Biology
GA 173EZ
UT WOS:000321062200020
PM 23722937
ER
PT J
AU Guitton, TG
Kinaci, A
Ring, D
AF Guitton, Thierry G.
Kinaci, Ahmet
Ring, David
TI Diagnostic accuracy of 2-and 3-dimensional computed tomography and solid
modeling of coronoid fractures
SO JOURNAL OF SHOULDER AND ELBOW SURGERY
LA English
DT Article
DE Computed tomography; coronoid fracture; fracture classification;
interobserver reliability; diagnostic performance characteristics
ID PROXIMAL HUMERUS; RADIAL HEAD; ELBOW; DISLOCATION; RELIABILITY;
CLASSIFICATION; AGREEMENT
AB Purpose: This study measured the diagnostic performance characteristics and reliability of 2-dimensional (2DCT) and 3-dimensional (3DCT) computed tomography images and modeling of coronoid fractures.
Method: The treating surgeon and first assistant evaluated 28 fractures for fracture type, specific characteristics, and proposed treatment. The observers evaluated the fractures 4 times: first based upon 2DCT computed images and radiographs; second with the addition of 3DCT images; third with the addition of 3D models; and finally based upon intra-operative exposure, which was considered the reference standard.
Results: The diagnostic performance characteristics did not improve with more sophisticate imaging and models. The addition of 3DCT reconstructions improved the inter-observer reliability for fracture classification, characteristics, and proposed treatment.
Conclusion: More sophisticated images and modeling improved reliability but not accuracy when characterizing coronoid fractures.
Level of evidence: Level II, Diagnostic Study. (C) 2013 Journal of Shoulder and Elbow Surgery Board of Trustees.
C1 [Guitton, Thierry G.; Kinaci, Ahmet; Ring, David] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA.
EM dring@partners.org
OI Guitton, Thierry/0000-0002-2599-1985
NR 23
TC 5
Z9 5
U1 0
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1058-2746
J9 J SHOULDER ELB SURG
JI J. Shoulder Elbow Surg.
PD JUN
PY 2013
VL 22
IS 6
BP 782
EP 786
DI 10.1016/j.jse.2013.02.009
PG 5
WC Orthopedics; Sport Sciences; Surgery
SC Orthopedics; Sport Sciences; Surgery
GA 172IP
UT WOS:000320995800016
PM 23594717
ER
PT J
AU Reuben, DB
Ganz, DA
Roth, CP
McCreath, HE
Ramirez, KD
Wenger, NS
AF Reuben, David B.
Ganz, David A.
Roth, Carol P.
McCreath, Heather E.
Ramirez, Karina D.
Wenger, Neil S.
TI Effect of Nurse Practitioner Comanagement on the Care of Geriatric
Conditions
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article
DE quality improvement; practice redesign; ACOVE; geriatric conditions
ID RANDOMIZED-CONTROLLED-TRIAL; GUIDED CARE; COLLABORATIVE CARE;
HEALTH-CARE; OLDER-PATIENTS; QUALITY; MANAGEMENT; INTERVENTION; ADULTS;
DEPRESSION
AB Objectives To determine whether community-based primary care physician (PCP)-nurse practitioner (NP) comanagement implementing the Assessing Care of Vulnerable Elders (ACOVE)-2 model: (case finding, delegation of data collection, structured visit notes, physician and patient education, and linkage to community resources) can improve the quality of care for geriatric conditions. Design Case study. Setting Two community-based primary care practices. Participants Patients aged 75 and older who screened positive for at least one condition: falls, urinary incontinence (UI), dementia, and depression. Intervention The ACOVE-2 model augmented by NP comanagement of conditions. Measurements Quality of care according to medical record review using ACOVE-3 quality indicators (QIs). Individuals receiving comanagement were compared with those who received PCP care alone in the same practices. Results Of 1,084 screened individuals, 658 (61%) screened positive for more than one condition; 485 of these were randomly selected for chart review and triggered a mean of seven QIs. A NP saw 49% for comanagement. Overall, individuals received 57% of recommended care. Quality scores for all conditions (falls, 80% vs 34%; UI, 66% vs 19%; dementia, 59% vs 38%) except depression (63% vs 60%) were higher for individuals who saw a NP. In analyses adjusted for sex and age of patient, number of conditions, site, and a NP estimate of medical management style, NP comanagement remained significantly associated with receiving recommended care (P<.001), as did NP estimate of medical management style (P=.02). Conclusion NP comanagement is associated with better quality of care for geriatric conditions in community-based primary care than usual care using the ACOVE-2 model.
C1 [Reuben, David B.; Ganz, David A.; McCreath, Heather E.; Ramirez, Karina D.] Univ Calif Los Angeles, David Geffen Sch Med, Multicampus Program Geriatr Med & Gerontol, Los Angeles, CA 90095 USA.
[Ganz, David A.] Vet Affairs Greater Los Angeles Healthcare Syst, Hlth Serv Res & Dev Ctr Excellence, Los Angeles, CA USA.
[Ganz, David A.] Vet Affairs Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, Los Angeles, CA USA.
[Ganz, David A.; Roth, Carol P.; Wenger, Neil S.] RAND Hlth, Santa Monica, CA USA.
[Wenger, Neil S.] Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90095 USA.
RP Reuben, DB (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Geriatr, 10945 Le Conte Ave,Suite 2339, Los Angeles, CA 90095 USA.
EM dreuben@mednet.ucla.edu
FU UniHealth Foundation; U.S. Department of Veterans Affairs, Veterans
Health Administration, Veterans Affairs Health Services Research &
Development Service (HSR&D) through the Veterans Affairs Greater Los
Angeles HSR&D Center of Excellence [VA CD2 08-012-1]; National Institute
on Aging [5P30AG028748]
FX This project was supported by a grant from the UniHealth Foundation to
DBR. DAG was supported by a Career Development Award from the U.S.
Department of Veterans Affairs, Veterans Health Administration, Veterans
Affairs Health Services Research & Development Service (HSR&D) through
the Veterans Affairs Greater Los Angeles HSR&D Center of Excellence
(Project VA CD2 08-012-1). Data collection and analysis was supported in
part by the University of California at Los Angeles Claude Pepper Older
Americans Independence Center funded by the National Institute on Aging
(5P30AG028748).
NR 23
TC 10
Z9 10
U1 7
U2 21
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0002-8614
EI 1532-5415
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD JUN
PY 2013
VL 61
IS 6
BP 857
EP 867
DI 10.1111/jgs.12268
PG 11
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 164KD
UT WOS:000320407100001
PM 23772723
ER
PT J
AU Pawloski, PA
Geiger, AM
Haque, R
Kamineni, A
Fouayzi, H
Ogarek, J
Petersen, HV
Bosco, JLF
Thwin, SS
Silliman, RA
Field, TS
AF Pawloski, Pamala A.
Geiger, Ann M.
Haque, Reina
Kamineni, Aruna
Fouayzi, Hassan
Ogarek, Jessica
Petersen, Hans V.
Bosco, Jaclyn L. F.
Thwin, Soe Soe
Silliman, Rebecca A.
Field, Terry S.
TI Fracture Risk in Older, Long-Term Survivors of Early-Stage Breast Cancer
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article
DE osteoporotic fractures; breast cancer survivors; postmenopausal women;
cohort study; pharmacoepidemiology
ID BONE-MINERAL DENSITY; POSTMENOPAUSAL WOMEN; INTERGROUP EXEMESTANE;
SAFETY ANALYSIS; UNITED-STATES; TAMOXIFEN; CARE; TRIAL; OSTEOPOROSIS;
MORTALITY
AB Objectives To examine the effect of breast cancer and its treatment on fracture risk in older breast cancer survivors. Design A 10-year prospective cohort study beginning 5years after a diagnosis of breast cancer for survivors and match date for comparison women. Setting Six integrated healthcare systems. Participants Women aged 65 and older (1,286 survivors, 1,286 comparison women, mean age 77.7 in both groups, white, non-Hispanic: survivors, 81.6%; comparison women, 85.2%) who were alive and recurrence free 5years after a diagnosis of early-stage breast cancer and matched on age, study site, and enrollment year to a comparison cohort without breast cancer. Measurements Cox proportional hazards models were used to estimate the association between fracture risk and survivor-comparison status, adjusting for drugs and risk factors associated with bone health. A subanalysis was used to evaluate the association between tamoxifen exposure and fracture risk. Results No difference was observed in fracture rates between groups (hazard ratio (HR)=1.1, 95% confidence interval (CI)=0.9-1.3). The protective effect of tamoxifen was not statistically significant (HR=0.9, 95% CI=0.6-1.2). Conclusion Long-term survivors of early-stage breast cancer diagnosed at age 65 and older are not at greater risk of osteoporotic fractures than age-matched women without breast cancer. There appears to be no long-term protection from fractures with tamoxifen use.
C1 [Pawloski, Pamala A.] HealthPartners Inst Educ & Res, Minneapolis, MN USA.
[Geiger, Ann M.] Wake Forest Sch Med, Winston Salem, NC USA.
[Haque, Reina] Kaiser Permanente So Calif, Dept Res & Evaluat, Pasadena, CA 91101 USA.
[Kamineni, Aruna] Grp Hlth Res Inst, Seattle, WA USA.
[Fouayzi, Hassan; Ogarek, Jessica; Field, Terry S.] Meyers Primary Care Inst, Worcester, MA USA.
[Petersen, Hans V.] Lovelace Resp Res Inst, Albuquerque, NM USA.
[Bosco, Jaclyn L. F.] Dana Farber Canc Inst, Phyllis F Cantor Ctr, Boston, MA 02115 USA.
[Bosco, Jaclyn L. F.; Thwin, Soe Soe; Silliman, Rebecca A.] Boston Univ, Sch Med, Sect Geriatr, Boston Med Ctr, Boston, MA 02118 USA.
[Thwin, Soe Soe] Vet Affairs Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA.
RP Pawloski, PA (reprint author), HealthPartners Inst Educ & Res, 8170 33rd Ave S,MS21111R, Bloomington, MN 55425 USA.
EM pamala.a.pawloski@healthpartners.com
FU Public Health Service from the National Cancer Institute, National
Institutes of Health, Department of Health and Human Services
[R01CA093772-05A2]; Novartis; International Serious Adverse Event
Consortium; GlaxoSmithKline; Astra Zenica; Amgen; Pfizer; Merck; Sanofia
Aventis
FX Supported by Public Health Service Grant R01CA093772-05A2 (R Silliman,
Principal Investigator) from the National Cancer Institute, National
Institutes of Health, Department of Health and Human Services. These
findings were in part accepted for presentation at the 18th HMO Research
Network Annual Conference, Seattle, Washington, May 2012.; The following
conflicts of interest are reported for this study: receipt of salary for
work performed on grants and contracts funded by commercial entities
including Novartis and the International Serious Adverse Event
Consortium (Pawloski); GlaxoSmithKline, Astra Zenica, Novartis, Amgen,
Pfizer, Merck, Sanofia Aventis, and others (Petersen).
NR 36
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U1 1
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0002-8614
EI 1532-5415
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD JUN
PY 2013
VL 61
IS 6
BP 888
EP 895
DI 10.1111/jgs.12269
PG 8
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 164KD
UT WOS:000320407100005
PM 23647433
ER
PT J
AU Espeland, MA
Rejeski, WJ
West, DS
Bray, GA
Clark, JM
Peters, AL
Chen, HY
Johnson, KC
Horton, ES
Hazuda, HP
AF Espeland, Mark A.
Rejeski, W. Jack
West, Delia S.
Bray, George A.
Clark, Jeanne M.
Peters, Anne L.
Chen, Haiying
Johnson, Karen C.
Horton, Edward S.
Hazuda, Helen P.
CA Action Hlth Diabet Res Grp
TI Intensive Weight Loss Intervention in Older Individuals: Results from
the Action for Health in Diabetes Type 2 Diabetes Mellitus Trial
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article
DE behavioral intervention; weight loss; physical activity; type 2 diabetes
mellitus; cardiovascular disease risk factors
ID LIFE-STYLE INTERVENTION; RANDOMIZED CONTROLLED-TRIAL; DISEASE
RISK-FACTORS; LOOK-AHEAD TRIAL; CARDIOVASCULAR-DISEASE; KNEE
OSTEOARTHRITIS; PHYSICAL-ACTIVITY; CLINICAL-TRIAL; ADULTS; OBESE
AB Objectives To compare the effects of 4years of intensive lifestyle intervention on weight, fitness, and cardiovascular disease risk factors in older and younger individuals. Design Randomized controlled clinical trial. Setting Sixteen U.S. clinical sites. Participants Individuals with type 2 diabetes mellitus: 1,053 aged 65 to 76 and 4,092 aged 45 to 64. Interventions An intensive behavioral intervention designed to promote and maintain weight loss through caloric restriction and increased physical activity was compared with diabetes mellitus support and education. Measurements Standardized assessments of weight, fitness (based on graded exercise testing), and cardiovascular disease risk factors. Results Over 4years, older individuals had greater intervention-related mean weight losses (6.2%) than younger participants (5.1%; interaction P=.006) and comparable relative mean increases in fitness (0.56 vs 0.53 metabolic equivalents; interaction P=.72). These benefits were seen consistently across subgroups of older adults formed according to many demographic and health factors. Of a panel of age-related health conditions, only self-reported worsening vision was associated with poorer intervention-related weight loss in older individuals. The intensive lifestyle intervention produced mean increases in high-density lipoprotein cholesterol (2.03mg/dL; P<.001) and decreases in glycated hemoglobin (0.21%; P<.001) and waist circumference (3.52cm; P<.001) over 4years that were at least as large in older as in younger individuals. Conclusion Intensive lifestyle intervention targeting weight loss and increased physical activity is effective in overweight and obese older individuals to produce sustained weight loss and improvements in fitness and cardiovascular risk factors.
C1 [Espeland, Mark A.; Chen, Haiying] Wake Forest Univ, Bowman Gray Sch Med, Dept Biostat Sci, Winston Salem, NC USA.
[Rejeski, W. Jack] Wake Forest Univ, Dept Hlth & Exercise Sci, Winston Salem, NC USA.
[West, Delia S.] Univ Arkansas Med Sci, Coll Publ Hlth, Little Rock, AR 72205 USA.
[Bray, George A.] Louisiana State Univ, Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA.
[Clark, Jeanne M.] Johns Hopkins Univ, Dept Med, Baltimore, MD USA.
[Clark, Jeanne M.] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA.
[Peters, Anne L.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA.
[Johnson, Karen C.] Univ Tennessee, Hlth Sci Ctr, Dept Prevent Med, Memphis, TN USA.
[Horton, Edward S.] Joslin Diabet Ctr, Boston, MA 02215 USA.
[Hazuda, Helen P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA.
RP Espeland, MA (reprint author), Wake Forest Sch Med, Dept Biostat Sci, Med Ctr Blvd, Winston Salem, NC 27157 USA.
EM mespelan@wfubmc.edu
OI Peters, Anne/0000-0003-0520-0776
FU National Institutes of Health; Department of Health and Human Services
through the NIH [DK57136, DK57149, DK56990, DK57177, DK57171, DK57151,
DK57182, DK57131, DK57002, DK57078, DK57154, DK57178, DK57219, DK57008,
DK57135, DK56992]; National Institute of Diabetes and Digestive and
Kidney Diseases; National Heart, Lung, and Blood Institute; National
Institute of Nursing Research; National Center on Minority Health and
Health Disparities; Office of Research on Women's Health; Centers for
Disease Control and Prevention; Department of Veterans Affairs; Johns
Hopkins Medical Institutions Bayview General Clinical Research Center
[M01RR02719]; Massachusetts General Hospital Mallinckrodt General
Clinical Research Center; Massachusetts Institute of Technology General
Clinical Research Center [M01RR01066]; University of Colorado Health
Sciences Center General Clinical Research Center [M01RR00051]; Clinical
Nutrition Research Unit [P30 DK48520]; University of Tennessee at
Memphis General Clinical Research Center [M01RR0021140]; University of
Pittsburgh General Clinical Research Center [M01RR000056]; Clinical
Translational Research Center; Clinical and Translational Science Award
[UL1 RR 024153]; NIH [DK 046204]; Frederic C. Bartter General Clinical
Research Center [M01RR01346]
FX This work was funded under a cooperative agreement by the National
Institutes of Health. The editor in chief has reviewed the conflict of
interest checklist provided by the authors and has determined that the
authors have no financial or any other kind of personal conflicts with
this paper.; This study is supported by the Department of Health and
Human Services through the following cooperative agreements from the
NIH: DK57136, DK57149, DK56990, DK57177, DK57171, DK57151, DK57182,
DK57131, DK57002, DK57078, DK57154, DK57178, DK57219, DK57008, DK57135,
and DK56992. The National Institute of Diabetes and Digestive and Kidney
Diseases; National Heart, Lung, and Blood Institute; National Institute
of Nursing Research; National Center on Minority Health and Health
Disparities; Office of Research on Women's Health; Centers for Disease
Control and Prevention; and Department of Veterans Affairs have
contributed support. This research was supported in part by the
Intramural Research Program of the National Institute of Diabetes and
Digestive and Kidney Diseases. The Indian Health Service provided
personnel, medical oversight, and use of facilities.; Additional support
was received from The Johns Hopkins Medical Institutions Bayview General
Clinical Research Center (M01RR02719), the Massachusetts General
Hospital Mallinckrodt General Clinical Research Center and the
Massachusetts Institute of Technology General Clinical Research Center
(M01RR01066), the University of Colorado Health Sciences Center General
Clinical Research Center (M01RR00051) and Clinical Nutrition Research
Unit (P30 DK48520), the University of Tennessee at Memphis General
Clinical Research Center (M01RR0021140), the University of Pittsburgh
General Clinical Research Center (M01RR000056), the Clinical
Translational Research Center funded by the Clinical and Translational
Science Award (UL1 RR 024153) and NIH grant (DK 046204), and the
Frederic C. Bartter General Clinical Research Center (M01RR01346).
NR 34
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PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0002-8614
EI 1532-5415
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD JUN
PY 2013
VL 61
IS 6
BP 912
EP 922
DI 10.1111/jgs.12271
PG 11
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 164KD
UT WOS:000320407100008
PM 23668423
ER
PT J
AU Hohman, MH
Lee, LN
Hadlock, TA
AF Hohman, Marc H.
Lee, Linda N.
Hadlock, Tessa A.
TI Two-Step Highly Selective Neurectomy for Refractory Periocular
Synkinesis
SO LARYNGOSCOPE
LA English
DT Editorial Material
DE Facial paralysis; synkinesis; neurectomy; facial nerve
ID BELLS-PALSY
C1 [Hohman, Marc H.] Massachusetts Eye & Ear Infirm, Div Facial Plast & Reconstruct Surg, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Dept Otol & Laryngol, Cambridge, MA 02138 USA.
RP Hohman, MH (reprint author), Massachusetts Eye & Ear Infirm, Div Facial Plast & Reconstruct Surg, 243 Charles St, Boston, MA 02114 USA.
EM marc_hohman@meei.harvard.edu
NR 10
TC 14
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U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0023-852X
J9 LARYNGOSCOPE
JI Laryngoscope
PD JUN
PY 2013
VL 123
IS 6
BP 1385
EP 1388
DI 10.1002/lary.23873
PG 4
WC Medicine, Research & Experimental; Otorhinolaryngology
SC Research & Experimental Medicine; Otorhinolaryngology
GA 169MI
UT WOS:000320784000013
PM 23315713
ER
PT J
AU Shampo, MA
Kyle, RA
Steensma, DP
AF Shampo, Marc A.
Kyle, Robert A.
Steensma, David P.
TI Jens Skou-Nobel Prize in Chemistry
SO MAYO CLINIC PROCEEDINGS
LA English
DT Editorial Material
C1 [Shampo, Marc A.; Kyle, Robert A.] Mayo Clin, Rochester, MN 55905 USA.
[Steensma, David P.] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Shampo, MA (reprint author), Mayo Clin, Rochester, MN 55905 USA.
OI Steensma, David/0000-0001-5130-9284
NR 0
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U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0025-6196
J9 MAYO CLIN PROC
JI Mayo Clin. Proc.
PD JUN
PY 2013
VL 88
IS 6
BP E55
EP E55
DI 10.1016/j.mayocp.2012.01.029
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 167TL
UT WOS:000320657600002
PM 23726407
ER
PT J
AU Sung, CK
Li, DW
Andrews, E
Drapkin, R
Benjamin, T
AF Sung, Chang K.
Li, Dawei
Andrews, Erik
Drapkin, Ronny
Benjamin, Thomas
TI Promoter methylation of the SALL2 tumor suppressor gene in ovarian
cancers
SO MOLECULAR ONCOLOGY
LA English
DT Article
DE SALL2; Ovarian cancer; Tumor suppressor; Promoter methylation; Polyoma T
antigen
ID RADIAL RAY SYNDROME; SV40-TRANSFORMED CELLS; CPG-ISLANDS; T-ANTIGEN;
CARCINOMA; MUTATIONS; SURVIVAL; SPALT; GLYCOPROTEIN; P150(SAL2)
AB The SALL2 gene product and transcription factor p150 were first identified in a search for tumor suppressors targeted for inactivation by the oncogenic mouse polyoma virus. SALL2 has also been identified as a cellular quiescence factor, essential for cells to enter and remain in a state of growth arrest under conditions of serum deprivation. p150 is a transcriptional activator of p21(Cip1/Waf1) and BAX, sharing important growth arrest and proapoptotic properties with p53. It also acts as a repressor of c-myc. Restoration of SALL2 expression in cells derived from a human ovarian carcinoma (OVCA) suppresses growth of the cells in immunodeficient mice. Here we examine the pattern of p150 expression in the normal human ovary, in OVCA-derived cell lines and in primary ovarian carcinomas. Immunohistochemical staining showed that p150 is highly expressed in surface epithelial cells of the normal human ovary. Expression is exclusively from the P2 promoter governing the E1A splice variant of p150. The P2 promoter is CpG-rich and susceptible to methylation silencing. p150 expression was restored in OVCA cell lines following growth in the presence of 5-azacytidine. In a survey of 210 cases of OVCA, roughly 90% across major and minor histological types failed to show expression of the protein. Immunological and biochemical approaches were used to show hypermethylation of the SALL2 P2 promoter in OVCA-derived cell lines and in a majority of primary tumors. These results bring together molecular biological and clinical evidence in support of a role of SALL2 as a suppressor of ovarian cancers. (C) 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
C1 [Sung, Chang K.; Li, Dawei; Andrews, Erik; Benjamin, Thomas] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02114 USA.
[Drapkin, Ronny] Dana Farber Canc Inst, Dept Med Oncol, Ctr Mol Oncol Pathol, Boston, MA 02115 USA.
[Drapkin, Ronny] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
RP Benjamin, T (reprint author), Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, NRB-939,77 Ave Louis Pasteur, Boston, MA 02114 USA.
EM thomas_benjamin@hms.harvard.edu
RI Drapkin, Ronny/E-9944-2016
OI Drapkin, Ronny/0000-0002-6912-6977
FU National Cancer Institute [RO1 CA-092520]; Ovarian Cancer Research Fund;
Mary Kay Foundation; Robert and Debra First Fund; Dana-Farber Women's
Executive Council Genetic Fingerprinting Award; [P50 CA105009]; [U01
CA152990]
FX This work has been supported by a grant from the National Cancer
Institute RO1 CA-092520 to TB, grants P50 CA105009 and U01 CA152990, the
Ovarian Cancer Research Fund, The Mary Kay Foundation, the Robert and
Debra First Fund, and the Dana-Farber Women's Executive Council Genetic
Finger-printing Award to RD.
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U2 7
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1574-7891
J9 MOL ONCOL
JI Mol. Oncol.
PD JUN
PY 2013
VL 7
IS 3
BP 419
EP 427
DI 10.1016/j.molonc.2012.11.005
PG 9
WC Oncology
SC Oncology
GA 175LY
UT WOS:000321233400011
PM 23273547
ER
PT J
AU Singh, A
Lun, XQ
Jayanthan, A
Obaid, H
Ruan, YB
Strother, D
Chi, SN
Smith, A
Forsyth, P
Narendran, A
AF Singh, Anjali
Lun, Xueqing
Jayanthan, Aarthi
Obaid, Halah
Ruan, Yibing
Strother, Douglas
Chi, Susan N.
Smith, Amy
Forsyth, Peter
Narendran, Aru
TI Profiling pathway-specific novel therapeutics in preclinical assessment
for central nervous system atypical teratoid rhabdoid tumors (CNS ATRT):
Favorable activity of targeting EGFR-ErbB2 signaling with lapatinib
SO MOLECULAR ONCOLOGY
LA English
DT Article
DE Lapatinib; Teratoid Rhabdoid tumors; Targeted therapeutics
ID GROWTH-FACTOR RECEPTOR; KINASE INHIBITOR LAPATINIB; BREAST-CANCER CELLS;
TERATOID/RHABDOID TUMOR; IN-VITRO; BRAIN-TUMORS; CYCLIN D1; FACTOR-II;
INSULIN; MIGRATION
AB Despite intensifying multimodal treatments, children with central nervous system atypical teratoid/rhabdoid tumor (CNS ATRT) continue to endure unacceptably high mortality rates. At present, concerted efforts are focusing on understanding the characteristic INI1 mutation and its implications for the growth and survival of these tumors. Additionally, pharmaceutical pipeline libraries constitute a significant source of potential agents that can be taken to clinical trials in a timely manner. However, this process requires efficient target validation and relevant preclinical studies. As an initial screening approach, a panel of 129 small molecule inhibitors from multiple pharmaceutical pipeline libraries was tested against three ATRT cell lines by in vitro cytotoxicity assays. Based on these data, agents that have strong activity and corresponding susceptible cellular pathways were identified. Target modulation, antibody array analysis, drug combination and in vivo xenograft studies were performed on one of the pathway inhibitors found in this screening. Approximately 20% of agents in the library showed activity with IC50 values of 1 mu M or less and many showed IC50 values less than 0.05 mu M. Intra cell line variability was also noted among some of the drugs. However, it was determined that agents capable of affecting pathways constituting ErbB2, mTOR, proteasomes, Hsp90, Polo like kinases and Aurora kinases were universally effective against the three ATRT cell lines. The first target selected for further analysis, the inhibition of ErbB2-EGFR pathway by the small molecule inhibitor lapatinib, indicated inhibition of cell migration properties and the initiation of apoptosis. Synergy between lapatinib and IGF-IR inhibition was also demonstrated by combination index (CI) values. Xenograft studies showed effective antitumor activity of lapatinib in vivo. We present an experimental approach to identifying agents and drug combinations for future clinical trials and provide evidence for the potential of lapatinib as an effective agent in the context of the biology and heterogeneity of its targets in ATRT. (C) 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
C1 [Singh, Anjali; Lun, Xueqing; Jayanthan, Aarthi; Obaid, Halah; Ruan, Yibing; Chi, Susan N.; Smith, Amy; Narendran, Aru] Univ Calgary, POETIC, Lab Preclin & Drug Discovery Studies, Calgary, AB, Canada.
[Strother, Douglas; Narendran, Aru] Alberta Childrens Prov Gen Hosp, Div Pediat Oncol & Transplant, Calgary, AB T3B 6A8, Canada.
[Chi, Susan N.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Smith, Amy] Arnold Palmer Hosp Children, MD Anderson Canc Ctr Orlando, Orlando, FL USA.
[Forsyth, Peter] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Neurooncol, Tampa, FL 33682 USA.
RP Narendran, A (reprint author), Alberta Childrens Prov Gen Hosp, Div Pediat Oncol, 2888 Shaganappi Trail NW, Calgary, AB T3B 6A8, Canada.
EM a.narendran@ucalgary.ca
FU Kids Cancer Care Foundation of Alberta (KCCFA) Alberta Children's
Hospital Foundation (ACHF); Brain Tumour Foundation of Canada; Canadian
Institutes for Health Research (CIHR) Training Program in Genetics;
Child Development and Health Graduate Studentship; Alberta Children's
Hospital for Child and Maternal Health (ACHRI); McCarthy Tetrault
Graduate Studentship; ACHF
FX This research was supported by grants from the Kids Cancer Care
Foundation of Alberta (KCCFA) Alberta Children's Hospital Foundation
(ACHF) and the Brain Tumour Foundation of Canada. AJ holds a Canadian
Institutes for Health Research (CIHR) Training Program in Genetics,
Child Development and Health Graduate Studentship awarded by Alberta
Children's Hospital for Child and Maternal Health (ACHRI) and a McCarthy
Tetrault Graduate Studentship awarded by ACHF.
NR 51
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U2 7
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1574-7891
J9 MOL ONCOL
JI Mol. Oncol.
PD JUN
PY 2013
VL 7
IS 3
BP 497
EP 512
DI 10.1016/j.molonc.2013.01.001
PG 16
WC Oncology
SC Oncology
GA 175LY
UT WOS:000321233400018
PM 23375777
ER
PT J
AU Middelbeek, RJW
Chambers, MA
Tantiwong, P
Treebak, JT
An, D
Hirshman, MF
Musi, N
Goodyear, LJ
AF Middelbeek, R. J. W.
Chambers, M. A.
Tantiwong, P.
Treebak, J. T.
An, D.
Hirshman, M. F.
Musi, N.
Goodyear, L. J.
TI Insulin stimulation regulates AS160 and TBC1D1 phosphorylation sites in
human skeletal muscle
SO NUTRITION & DIABETES
LA English
DT Article
DE obesity; insulin; diabetes; TBC1D1; AS160
ID TYPE-2 DIABETIC SUBJECTS; GLUT4 TRANSLOCATION; AKT SUBSTRATE;
CONTRACTION; SENSITIVITY; OBESITY
AB INTRODUCTION: Individuals with obesity and type 2 diabetes (T2D) are typically insulin resistant, exhibiting impaired skeletal muscle glucose uptake. Animal and cell culture experiments have shown that site-specific phosphorylation of the Rab-GTPase-activating proteins AS160 and TBC1D1 is critical for GLUT4 translocation facilitating glucose uptake, but their regulation in human skeletal muscle is not well understood.
METHODS: Here, lean, obese and T2D subjects underwent a euglycemic-hyperinsulinemic clamp, and vastus lateralis muscle biopsies were obtained before, and at 30 and 180 min post insulin infusion.
RESULTS: Obese and T2D subjects had higher body mass indexes and fasting insulin concentrations, and T2D subjects showed insulin resistance. Consistent with the clamp findings, T2D subjects had impaired insulin-stimulated phosphorylation of AS160 Thr(642), a site previously shown to be important in glucose uptake in rodents. Interestingly, insulin-stimulated phosphorylation of TBC1D1 Thr(590), a site shown to be regulated by insulin in rodents, was only increased in T2D subjects, although the functional significance of this difference is unknown.
CONCLUSION: These data show that insulin differentially regulates AS160 and TBC1D1 phosphorylation in human skeletal muscle. Impaired insulin-stimulated glucose uptake in T2D subjects is accompanied by dysregulation of AS160 and TBC1D1 phosphorylation in skeletal muscle, suggesting that these proteins may regulate glucose uptake in humans.
C1 [Middelbeek, R. J. W.; Chambers, M. A.; Treebak, J. T.; An, D.; Hirshman, M. F.; Goodyear, L. J.] Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA 02215 USA.
[Tantiwong, P.; Musi, N.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Diabet Div, San Antonio, TX 78229 USA.
[Tantiwong, P.; Musi, N.] South Texas Vet Healthcare Syst, San Antonio, TX USA.
[Goodyear, L. J.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Goodyear, L. J.] Harvard Univ, Sch Med, Boston, MA 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 Treebak, Jonas/B-4521-2017
OI Treebak, Jonas/0000-0003-1488-7012
FU National Institutes of Health [AR42238, K23-AG030979, RO1-DK80157,
RO1-DK089229]; American Diabetes Association; VSBfonds Beurs;
Scholten-Cordes Foundation; Haak Bastiaanse-Kuneman Foundation; NRSA
[F32DK083183]; Danish Agency for Science, Technology and Innovation,
Denmark
FX This research was supported by the National Institutes of Health Grant
AR42238 (to LJG). RJWM was supported by an American Diabetes Association
mentor-based fellowship (to LJG), the VSBfonds Beurs, the
Scholten-Cordes Foundation and the Haak Bastiaanse-Kuneman Foundation.
MAC was supported by the NRSA grant F32DK083183. JTT was supported by a
postdoctoral fellowship from The Danish Agency for Science, Technology
and Innovation, Denmark. NM was supported by grants from the National
Institutes of Health (K23-AG030979, RO1-DK80157 and RO1-DK089229) and
the American Diabetes Association. Special thanks to Cell Signaling
Technology (Danvers, MA, USA) for pan-TBC1D1 and TBC1D1 phospho-specific
antibodies. This study was supported by the National Institutes of
Health Grants AR42238 (to LJG) and K23-AG030979, RO1-DK80157,
RO1-DK089229 and the American Diabetes Association (to NM).
NR 20
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PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2044-4052
J9 NUTR DIABETES
JI Nutr. Diabetes
PD JUN
PY 2013
VL 3
AR UNSP e74
DI 10.1038/nutd.2013.13
PG 4
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 171JO
UT WOS:000320923000003
PM 23752133
ER
PT J
AU Hess, DR
AF Hess, Dean R.
TI Noninvasive Ventilation for Acute Respiratory Failure
SO RESPIRATORY CARE
LA English
DT Article
DE noninvasive ventilation; acute respiratory failure; COPD; acute
cardiogenic pulmonary edema
ID POSITIVE-PRESSURE VENTILATION; OBSTRUCTIVE PULMONARY-DISEASE; RANDOMIZED
CONTROLLED-TRIAL; OBESITY HYPOVENTILATION SYNDROME; COMMUNITY-ACQUIRED
PNEUMONIA; ACUTE LUNG INJURY; TOTAL FACE MASK; MECHANICAL VENTILATION;
AIRWAY PRESSURE; SUPPORT VENTILATION
AB Noninvasive ventilation (NW) for acute respiratory failure has gained much academic and clinical interest. Despite this, NIV is underutilized. The evidence strongly supports its use in patients presenting with an exacerbation of COPD and in patients with acute cardiogenic pulmonary edema. As reviewed in this paper, there is now evidence supporting or not supporting the use of NIV in various other presentations of acute respiratory failure. It is important not only to know when to initiate NIV, but also when this therapy is failing. Whether NW in the setting of acute respiratory failure can be managed appropriately outside the ICU setting is controversial. Although a variety of interfaces are available, the oronasal mask is the best initial interface in terms of leak prevention and patient comfort. Some critical care ventilators have NW modes that compensate well for leaks, but as a group the ventilators that are designed specifically for NW have better leak compensation. NW should be part of the armamentarium of all clinicians caring from patients with acute respiratory failure. (C) 2013 Daedalus Enterprises
C1 [Hess, Dean R.] Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA.
[Hess, Dean R.] Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA.
RP Hess, DR (reprint author), Massachusetts Gen Hosp, Ellison 401,55 Fruit St, Boston, MA 02114 USA.
EM dhess@partners.org
NR 187
TC 34
Z9 36
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 JUN
PY 2013
VL 58
IS 6
BP 950
EP 969
DI 10.4187/respcare.02319
PG 20
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 164PV
UT WOS:000320422900006
PM 23709194
ER
PT J
AU Mietto, C
Pinciroli, R
Patel, N
Berra, L
AF Mietto, Cristina
Pinciroli, Riccardo
Patel, Niti
Berra, Lorenzo
TI Ventilator Associated Pneumonia: Evolving Definitions and Preventive
Strategies
SO RESPIRATORY CARE
LA English
DT Article
DE ventilator-associated pneumonia; VAP; nosocomial infections; mechanical
ventilation; lung bacterial colonization; body positioning; endotracheal
tube; modification; medical devices
ID TRACHEAL TUBE CUFF; SUBGLOTTIC SECRETION DRAINAGE; COATED
ENDOTRACHEAL-TUBES; REQUIRING MECHANICAL VENTILATION; INTENSIVE-CARE
UNITS; RANDOMIZED-TRIAL; BACTERIAL-COLONIZATION; MUCUS SHAVER;
SEMIRECUMBENT POSITION; CONTINUOUS ASPIRATION
AB Ventilator-associated pneumonia (YAP) is one of the most frequent hospital-acquired infections occurring in intubated patients. Because YAP is associated with higher mortality, morbidity, and costs, there is a need to solicit further research for effective preventive measures. YAP has been proposed as an indicator of quality of care. Clinical diagnosis has been criticized to have poor accuracy and reliability. Thus, the Centers for Disease Control and Prevention has introduced a new definition based upon objective and recordable data. Institutions are nowadays reporting a YAP zero rate in surveillance programs, which is in discrepancy with clinical data. This reduction has been highlighted in epidemiological studies, but it can only be attributed to a difference in patient selection, since no additional intervention has been taken to modify pathogenic mechanisms in these studies. The principal determinant of YAP development is the presence of the endotracheal tube (ETT). Contaminated oropharyngeal secretions pool over the ETT cuff and subsequently leak down to the lungs through a hydrostatic gradient. Impairment of mucociliary motility and cough reflex cannot counterbalance with a proper clearance of secretions. Lastly, biofilm develops on the inner ETT surface and acts as a reservoir for microorganism inoculum to the lungs. New preventive strategies are focused on the improvement of secretions drainage and prevention of bacterial colonization. The influence of gravity on mucus flow and body positioning can facilitate the clearance of distal airways, with decreased colonization of the respiratory tract. A different approach proposes ETT modifications to limit the leakage of oropharyngeal secretions: subglottic secretion drainage and cuffs innovations have been addressed to reduce YAP incidence. Moreover, coated-ETTs have been shown to prevent biofilm formation, although there is evidence that ETT clearance devices (Mucus Shaver) are required to preserve the antimicrobial properties over time. Here, after reviewing the most noteworthy issues in YAP definition and pathophysiology, we will present the more interesting proposals for YAP prevention. (C) 2013 Daedalus Enterprises
C1 [Mietto, Cristina; Pinciroli, Riccardo; Patel, Niti; Berra, Lorenzo] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Medicine, Boston, MA 02114 USA.
RP Berra, L (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Medicine, 55 Fruit St, Boston, MA 02114 USA.
EM lberra@partners.org
NR 91
TC 33
Z9 38
U1 1
U2 18
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 JUN
PY 2013
VL 58
IS 6
BP 990
EP 1003
DI 10.4187/respcare.02380
PG 14
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 164PV
UT WOS:000320422900010
PM 23709196
ER
PT J
AU Piriyapatsom, A
Bittner, EA
Hines, J
Schmidt, UH
AF Piriyapatsom, Annop
Bittner, Edward A.
Hines, Jessica
Schmidt, Ulrich H.
TI Sedation and Paralysis
SO RESPIRATORY CARE
LA English
DT Article
DE sedation; sedatives; critical illness; mechanical ventilation;
neuromuscular blocking agent
ID CRITICALLY-ILL PATIENTS; INTENSIVE-CARE-UNIT; MECHANICALLY VENTILATED
PATIENTS; RESPIRATORY-DISTRESS-SYNDROME; NEUROMUSCULAR BLOCKING-AGENTS;
RANDOMIZED CONTROLLED-TRIAL; LONG-TERM SEDATION; ACUTE LUNG INJURY;
CLINICAL-PRACTICE GUIDELINES; BREATHING CONTROLLED-TRIAL
AB Sedation is used almost universally in the care of critically ill patients, especially in those who require mechanical ventilatory support or other life-saving invasive procedures. This review will focus on the sedation strategies for critically ill patients and the pharmacology of commonly used sedative agents. The role of neuromuscular blocking agents in the ICU will be examined and the pharmacology of commonly used agents is reviewed. Finally a strategy for rational use of these sedative and neuromuscular blocking agents in critically ill patients will be proposed. (C) 2013 Daedalus Enterprises
C1 [Piriyapatsom, Annop; Bittner, Edward A.; Hines, Jessica; Schmidt, Ulrich H.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02115 USA.
RP Schmidt, UH (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02115 USA.
EM Uschinidt@partners.org
NR 105
TC 2
Z9 2
U1 1
U2 4
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 JUN
PY 2013
VL 58
IS 6
BP 1024
EP 1035
DI 10.4187/respcare.02232
PG 12
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 164PV
UT WOS:000320422900014
PM 23709198
ER
PT J
AU Kacmarek, RM
AF Kacmarek, Robert M.
TI Mechanical Ventilation Competencies of the Respiratory Therapist in 2015
and Beyond
SO RESPIRATORY CARE
LA English
DT Article
DE respiratory care; respiratory therapist; manpower; education
competencies; protocols
ID HIGH-FREQUENCY OSCILLATION; INHALED NITRIC-OXIDE; DISTRESS-SYNDROME;
PROTOCOLS; SUPPORT; ASSIST
AB The evolution of critical care and mechanical ventilation has been dramatic and rapid over the last 10 years and can be expected to continue at this pace into the future. As a result, the competencies of the respiratory therapist regarding mechanical ventilation in 2015 and beyond are expected to also markedly increase. Respiratory therapists are expected to be the experts on the mechanical ventilator and all aspects of the application of mechanical ventilation. They will be considered consultants on all aspect of ventilatory support. This requires an expanded education in a number of areas. To achieve these levels of competency, as recommended by the third "2015 and Beyond" conference, the entry level education of the respiratory therapist of the future must be at the baccalaureate level. (C) 2013 Daedalus Enterprises
C1 [Kacmarek, Robert M.] Harvard Univ, Sch Med, Dept Anesthesiol, Cambridge, MA 02138 USA.
[Kacmarek, Robert M.] Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 01460 USA.
RP Kacmarek, RM (reprint author), Massachusetts Gen Hosp, Warren 1225,55 Fruit St, Boston, MA 01460 USA.
EM rkacmarek@partners.org
NR 23
TC 5
Z9 5
U1 0
U2 1
PU DAEDALUS ENTERPRISES INC
PI IRVING
PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA
SN 0020-1324
J9 RESP CARE
JI Respir. Care
PD JUN
PY 2013
VL 58
IS 6
BP 1087
EP 1092
DI 10.4187/respcare.02546
PG 6
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 164PV
UT WOS:000320422900022
PM 23709202
ER
PT J
AU Nurmi, EL
Spilman, SL
Whelan, F
Scahill, LL
Aman, MG
McDougle, CJ
Arnold, LE
Handen, B
Johnson, C
Sukhodolsky, DG
Posey, DJ
Lecavalier, L
Stigler, KA
Ritz, L
Tierney, E
Vitiello, B
McCracken, JT
AF Nurmi, E. L.
Spilman, S. L.
Whelan, F.
Scahill, L. L.
Aman, M. G.
McDougle, C. J.
Arnold, L. E.
Handen, B.
Johnson, C.
Sukhodolsky, D. G.
Posey, D. J.
Lecavalier, L.
Stigler, K. A.
Ritz, L.
Tierney, E.
Vitiello, B.
McCracken, J. T.
CA Res Units Pediat
TI Moderation of antipsychotic-induced weight gain by energy balance gene
variants in the RUPP autism network risperidone studies
SO TRANSLATIONAL PSYCHIATRY
LA English
DT Article
DE autistic disorder; children; CNR1; leptin; risperidone; weight gain
ID BODY-MASS INDEX; CB1 RECEPTOR ANTAGONIST; LEPTIN PROMOTER REGION; WHITE
ADIPOSE-TISSUE; FOOD-INTAKE; HUMAN OBESITY; FTO GENE; ENDOCANNABINOID
SYSTEM; SCHIZOPHRENIC-PATIENTS; LEPR POLYMORPHISMS
AB Second-generation antipsychotic exposure, in both children and adults, carries significant risk for excessive weight gain that varies widely across individuals. We queried common variation in key energy balance genes (FTO, MC4R, LEP, CNR1, FAAH) for their association with weight gain during the initial 8 weeks in the two NIMH Research Units on Pediatric Psychopharmacology Autism Network trials (N = 225) of risperidone for treatment of irritability in children/adolescents aged 4-17 years with autism spectrum disorders. Variants in the cannabinoid receptor (CNR)-1 promoter (P = 1.0 x 10(-6)), CNR1 (P = 9.6 x 10(-5)) and the leptin (LEP) promoter (P = 1.4 x 10(-4)) conferred robust-independent risks for weight gain. A model combining these three variants was highly significant (P = 1.3 x 10(-9)) with a 0.85 effect size between lowest and highest risk groups. All results survived correction for multiple testing and were not dependent on dose, plasma level or ethnicity. We found no evidence for association with a reported functional variant in the endocannabinoid metabolic enzyme, fatty acid amide hydrolase, whereas body mass index-associated single-nucleotide polymorphisms in FTO and MC4R showed only trend associations. These data suggest a substantial genetic contribution of common variants in energy balance regulatory genes to individual antipsychotic-associated weight gain in children and adolescents, which supersedes findings from prior adult studies. The effects are robust enough to be detected after only 8 weeks and are more prominent in this largely treatment naive population. This study highlights compelling directions for further exploration of the pharmacogenetic basis of this concerning multifactorial adverse event.
C1 [Nurmi, E. L.; Spilman, S. L.; Whelan, F.; McCracken, J. T.] UCLA Semel Inst, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA.
[Scahill, L. L.; Sukhodolsky, D. G.] Yale Univ, Ctr Child Study, New Haven, CT 06520 USA.
[Aman, M. G.; Lecavalier, L.] Ohio State Univ, Dept Psychol, Columbus, OH 43210 USA.
[McDougle, C. J.] Massachusetts Gen Hosp, Dept Psychiat, Lurie Autism Ctr, Boston, MA 02114 USA.
[Arnold, L. E.] Ohio State Univ, Dept Psychiat, Columbus, OH 43210 USA.
[Handen, B.; Johnson, C.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA.
[Posey, D. J.; Stigler, K. A.] Indiana Univ, Dept Psychiat, Indianapolis, IN 46204 USA.
[Ritz, L.] NINDS, NIH, Bethesda, MD 20892 USA.
[Tierney, E.] Kennedy Krieger Inst, Dept Psychiat, Baltimore, MD USA.
[Vitiello, B.] NIMH, NIH, Bethesda, MD 20892 USA.
RP McCracken, JT (reprint author), UCLA Semel Inst, Dept Psychiat & Biobehav Sci, 760 Westwood Plaza, Los Angeles, CA 90024 USA.
EM jmccracken@mednet.ucla.edu
RI Nurmi, Erika/P-4627-2014;
OI Nurmi, Erika/0000-0003-4893-8957; Sukhodolsky, Denis/0000-0002-5401-792X
FU NIMH [T32MH073517, K23 MH094613, K24 MH010805, N01MH70010, N01MH80011,
U10MH66768, N01MH70001, U10MH66766, N01MH70009, U10MH66764]; Korczak
Foundation
FX This work was partially supported by the following sources: NIMH grants
T32MH073517 (ELN), K23 MH094613 (ELN), K24 MH010805 (JTM) and N01MH70010
(JTM), N01MH80011 and U10MH66768 (MGA), N01MH70001 and U10MH66766 (CJM),
N01MH70009 and U10MH66764 (LLS) and a grant from the Korczak Foundation
(LLS). Study medications were donated by Janssen Pharmaceutica.
NR 87
TC 17
Z9 18
U1 2
U2 13
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 2158-3188
J9 TRANSL PSYCHIAT
JI Transl. Psychiatr.
PD JUN
PY 2013
VL 3
AR e274
DI 10.1038/tp.2013.26
PG 8
WC Psychiatry
SC Psychiatry
GA 174VL
UT WOS:000321184600008
PM 23799528
ER
PT J
AU Poelmans, G
Franke, B
Pauls, DL
Glennon, JC
Buitelaar, JK
AF Poelmans, G.
Franke, B.
Pauls, D. L.
Glennon, J. C.
Buitelaar, J. K.
TI AKAPs integrate genetic findings for autism spectrum disorders
SO TRANSLATIONAL PSYCHIATRY
LA English
DT Article
DE A-kinase anchor proteins; autism spectrum disorders; genetics;
genome-wide association studies
ID DE-NOVO MUTATIONS; PROTEIN-KINASE-A; PERVASIVE DEVELOPMENTAL DISORDERS;
COPY NUMBER VARIATION; LYMPHOBLASTOID CELL-LINES; MEDIAL PREFRONTAL
CORTEX; CANDIDATE GENES; CLINICAL-IMPLICATIONS; REPETITIVE BEHAVIOR;
EXPRESSION PROFILES
AB Autism spectrum disorders (ASDs) are highly heritable, and six genome-wide association studies (GWASs) of ASDs have been published to date. In this study, we have integrated the findings from these GWASs with other genetic data to identify enriched genetic networks that are associated with ASDs. We conducted bioinformatics and systematic literature analyses of 200 top-ranked ASD candidate genes from five published GWASs. The sixth GWAS was used for replication and validation of our findings. Further corroborating evidence was obtained through rare genetic variant studies, that is, exome sequencing and copy number variation (CNV) studies, and/or other genetic evidence, including candidate gene association, microRNA and gene expression, gene function and genetic animal studies. We found three signaling networks regulating steroidogenesis, neurite outgrowth and (glutamatergic) synaptic function to be enriched in the data. Most genes from the five GWASs were also implicated-independent of gene size-in ASDs by at least one other line of genomic evidence. Importantly, A-kinase anchor proteins (AKAPs) functionally integrate signaling cascades within and between these networks. The three identified protein networks provide an important contribution to increasing our understanding of the molecular basis of ASDs. In addition, our results point towards the AKAPs as promising targets for developing novel ASD treatments.
C1 [Poelmans, G.; Glennon, J. C.; Buitelaar, J. K.] Radboud Univ Nijmegen, Med Ctr, Dept Cognit Neurosci, Donders Inst Brain Cognit & Behav, NL-6500 HB Nijmegen, Netherlands.
[Poelmans, G.; Franke, B.] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6500 HB Nijmegen, Netherlands.
[Franke, B.] Radboud Univ Nijmegen, Med Ctr, Dept Psychiat, Donders Inst Brain Cognit & Behav, NL-6500 HB Nijmegen, Netherlands.
[Pauls, D. L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Psychiat & Neurodev Genet Unit,Ctr Human Genet Re, Boston, MA USA.
RP Poelmans, G (reprint author), Radboud Univ Nijmegen, Med Ctr, Dept Cognit Neurosci, Donders Inst Brain Cognit & Behav, POB 9101,HP 204, NL-6500 HB Nijmegen, Netherlands.
EM g.poelmans@donders.ru.nl
RI Franke, Barbara/D-4836-2009
OI Franke, Barbara/0000-0003-4375-6572
FU European Community's Seventh Framework Programme [278948]
FX The research leading to these results has received funding from the
European Community's Seventh Framework Programme (FP7/2007-2013) under
grant agreement no278948. We thank the families who made all the genetic
studies of ASDs possible and the many investigators whose work drives
the ASD genetics field forward. In particular, we are grateful to K
Wang, H Hakonarson, LA Weiss and their collaborators for providing us
with the detailed results from their GWASs.
NR 108
TC 22
Z9 22
U1 1
U2 27
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 2158-3188
J9 TRANSL PSYCHIAT
JI Transl. Psychiatr.
PD JUN
PY 2013
VL 3
AR e270
DI 10.1038/tp.2013.48
PG 11
WC Psychiatry
SC Psychiatry
GA 174VL
UT WOS:000321184600004
PM 23756379
ER
PT J
AU Knobe, M
Gradl, G
AF Knobe, M.
Gradl, G.
TI Transplantation of Bone: Prerequisites for Immunologic and Inflammatory
Conditions - an Overview
SO ACTA CHIRURGIAE ORTHOPAEDICAE ET TRAUMATOLOGIAE CECHOSLOVACA
LA English
DT Review
ID GRAFT SUBSTITUTES; FRACTURE REPAIR; GROWTH-FACTORS; TNF-ALPHA; TGF-BETA;
RESORPTION; OSTEOBLASTS; EXPRESSION; CYTOKINES; CELLS
AB In this review we have summarized the conditions under which bone grafts have a suitable environment for ingrowth into surrounding bone. Among the topics discussed are the immunological properties of bone and differences between bone grafting and organ transplants. Local osteogenic immune changes following fracture and bone graft transplants are outlined. Moreover, techniques of bone graft harvesting are summarized.
C1 [Knobe, M.; Gradl, G.] Univ Aachen, Med Ctr, Dept Trauma & Reconstruct Surg, D-52074 Aachen, Germany.
[Gradl, G.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Hand & Upper Extrem Serv, Boston, MA 02114 USA.
RP Gradl, G (reprint author), Univ Aachen, Med Ctr, Dept Trauma & Reconstruct Surg, Pauwelsstr 30, D-52074 Aachen, Germany.
EM ggradl@ukaachen.de
NR 47
TC 0
Z9 0
U1 0
U2 0
PU GALEN SRO
PI PRAGUE 5
PA NA BELIDLE 34, PRAGUE 5, 150 00, CZECH REPUBLIC
SN 0001-5415
J9 ACTA CHIR ORTHOP TR
JI Acta Chir. Orthop. Traumatol. Cechoslov.
PD JUN
PY 2013
VL 80
IS 3
BP 192
EP 196
PG 5
WC Orthopedics
SC Orthopedics
GA 175II
UT WOS:000321223800002
PM 23777943
ER
PT J
AU Shah, K
Quaas, J
Rolston, D
Bansal, S
Bania, T
Newman, D
Wiener, D
Lee, J
AF Shah, Kaushal
Quaas, Joshua
Rolston, Daniel
Bansal, Shalu
Bania, Theodore
Newman, David
Wiener, Dan
Lee, Jarone
TI Magnitude of D-dimer matters for diagnosing pulmonary embolus
SO AMERICAN JOURNAL OF EMERGENCY MEDICINE
LA English
DT Article
ID SIMPLE CLINICAL-MODEL; WHOLE-BLOOD ASSAY; COMPUTED-TOMOGRAPHY;
EMERGENCY-DEPARTMENT; PRETEST PROBABILITY; WORK-UP; MANAGEMENT;
ANGIOGRAPHY; THRESHOLD; INCREASE
AB Objective: The objective of this study is to determine whether the magnitude of the D-dimer correlates with a higher likelihood of pulmonary embolus (PE).
Methods: We performed an electronic chart review at our academic, tertiary care center, annual emergency department (ED) census greater than 100000. All patients with a chest computed tomographic (CT) scan with intravenous contrast and an elevated D-dimer level obtained in the ED between January 2001 and July 2008 were identified. Specific, predetermined, predefined data elements including sex, age, D-dimer level, and final ED diagnosis were recorded by a hypothesis-blinded extractor using a preformatted data form. D-dimer level less than 0.58 mu g/mL constitutes the normal laboratory reference range for our turbidometric D-dimer assay. Data were analyzed using standard statistical methods, and a linear regression analysis was performed for correlation analysis of D-dimer and diagnosis of PE.
Results: We identified 544 subjects who had both a chest CT scan performed and an elevated D-dimer level obtained in the ED. Fifty-eight subjects (10.7%; mean D-dimer, 4.9 mu g/mL) were diagnosed with PE, and 486 (89.3%; mean D-dimer, 2.0) did not have a PE. The percentages of PE diagnoses for D-dimers in the ranges 0.58 to 1.0, 1.0 to 2.0, 2.0 to 5.0, 5.0 to 20.0, and greater than 20.0 (n=11) were 3.6%, 8.0%, 16.2%, 35.3%, and 45.5%, respectively. The positive predictive value of PE for D-dimer level cutoffs of greater than 0.58, greater than 1.0, greater than 2.0, greater than 5.0, and greater than 20.0 was 10.7%, 14.6%, 22.2%, 37.8%, and 45.5%, respectively. Increasing D-dimer values were strongly correlated with the presence of PE (odds ratio, 1.1685 per stratum; P < .001).
Conclusion: Increasing magnitude of D-dimer correlates with increasing likelihood of PE diagnosed by CT angiography. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Shah, Kaushal; Newman, David] Mt Sinai Sch Med, Dept Emergency Med, New York, NY 10029 USA.
[Quaas, Joshua; Rolston, Daniel; Bania, Theodore; Wiener, Dan] St Lukes Roosevelt Hosp, Dept Emergency Med, New York, NY 10025 USA.
[Bansal, Shalu] Mayo Clin & Mayo Grad Sch Med, Rochester, MN 55905 USA.
[Lee, Jarone] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA.
RP Lee, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA.
EM lee.jarone@mgh.harvard.edu
OI Rolston, Daniel/0000-0001-7595-2418; Lee, Jarone/0000-0002-4532-8523
NR 32
TC 4
Z9 5
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 0735-6757
EI 1532-8171
J9 AM J EMERG MED
JI Am. J. Emerg. Med.
PD JUN
PY 2013
VL 31
IS 6
BP 942
EP 945
DI 10.1016/j.ajem.2013.03.009
PG 4
WC Emergency Medicine
SC Emergency Medicine
GA 167SO
UT WOS:000320655100009
PM 23685058
ER
PT J
AU Lee, DC
Peak, DA
Jones, JS
Domeier, RM
Hendry, PL
Rathlev, NK
Swor, RA
McLean, SA
AF Lee, David C.
Peak, David A.
Jones, Jeffrey S.
Domeier, Robert M.
Hendry, Phyllis L.
Rathlev, Niels K.
Swor, Robert A.
McLean, Samuel A.
TI Variations in institutional review board reviews of a multi-center,
Emergency Department (ED)-based genetic research protocol
SO AMERICAN JOURNAL OF EMERGENCY MEDICINE
LA English
DT Article
ID RESPONSES; STANDARD
AB Introduction: In the United States, institutional review boards (IRBs) oversee the scientific, ethical, and regulatory aspects of research conducted on human subjects. Institutional variations in the interpretation and application of federal and local regulations concerning genetic testing can have significant impact on the implementation of such studies.
Objective: We assessed variability in IRB review of a multi-center Emergency Department-based study examining genotypic and phenotypic predictors of pain and psychological outcomes after minor motor vehicle collision (Project CRASH). This is one of the first multi-center genetic research protocols based solely in the Emergency Department (ED).
Methods: We performed an observational study of sites participating in Project CRASH. We collected IRB information and correspondence from each site. We collected data that included information regarding institution demographics, original IRB application characteristics, subsequent IRB correspondence, and time interval between submission and approval. Descriptive statistics were used in analysis.
Results: All sites that initially agreed to participate in Project CRASH also participated in this study (n = 7). The time interval in receiving IRB approval varied between 20-760 days (median 105, IQR 21-225). One site appeared to be an outlier (760 days). The most commonly requested changes were changes to the consent form.
Conclusion: Institutional interpretation of regulations regarding our ED-based genetic study was highly variable. Although the majority of our results are consistent with other similar published studies, the mean time interval for approval for this genetic study is far greater than other reported studies. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Lee, David C.] N Shore Univ Hosp, Dept Emergency Med, Manhasset, NY 11030 USA.
[Peak, David A.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.
[Jones, Jeffrey S.] Spectrum Hlth, Dept Emergency Med, Grand Rapids, MI 49503 USA.
[Domeier, Robert M.] St Joseph Mercy Hosp, Dept Emergency Med, Ann Arbor, MI 48197 USA.
[Hendry, Phyllis L.] Univ Florida, Dept Emergency Med & Pediat, Jacksonville, FL 32608 USA.
[Rathlev, Niels K.] Baystate Med Ctr, Dept Emergency Med, Springfield, MA 01199 USA.
[Swor, Robert A.] William Beaumont Hosp, Dept Emergency Med, Royal Oak, MI 48073 USA.
[McLean, Samuel A.] Univ N Carolina, Dept Emergency Med, Chapel Hill, NC 27599 USA.
RP Lee, DC (reprint author), N Shore Univ Hosp, Dept Emergency Med, Manhasset, NY 11030 USA.
EM dlee@nshs.edu
OI McLean, Samuel/0000-0001-9482-3582
FU NIAMS NIH HHS [R01 AR056328]
NR 5
TC 1
Z9 1
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 0735-6757
J9 AM J EMERG MED
JI Am. J. Emerg. Med.
PD JUN
PY 2013
VL 31
IS 6
BP 967
EP 969
DI 10.1016/j.ajem.2013.03.003
PG 3
WC Emergency Medicine
SC Emergency Medicine
GA 167SO
UT WOS:000320655100015
PM 23623236
ER
PT J
AU Carr, CE
Rowedder, H
Lui, CS
Zlatkovsky, I
Papalias, CW
Bolander, J
Myers, JW
Bustillo, J
Rothberg, JM
Zuber, MT
Ruvkun, G
AF Carr, Christopher E.
Rowedder, Holli
Lui, Clarissa S.
Zlatkovsky, Ilya
Papalias, Chris W.
Bolander, Jarie
Myers, Jason W.
Bustillo, James
Rothberg, Jonathan M.
Zuber, Maria T.
Ruvkun, Gary
TI Radiation Resistance of Sequencing Chips for in situ Life Detection
SO ASTROBIOLOGY
LA English
DT Article
DE Laboratory simulation experiments; Life-detection instruments; Nucleic
acids; Mars; Panspermia
ID BURROWS-WHEELER TRANSFORM; MURCHISON METEORITE; SUBSURFACE OCEAN;
EXTRATERRESTRIAL NUCLEOBASES; CARBONACEOUS METEORITES; READ ALIGNMENT;
MARS; ENCELADUS; PLANETS; SIMULATION
AB Life beyond Earth may be based on RNA or DNA if such life is related to life on Earth through shared ancestry due to meteoritic exchange, such as may be the case for Mars, or if delivery of similar building blocks to habitable environments has biased the evolution of life toward utilizing nucleic acids. In this case, in situ sequencing is a powerful approach to identify and characterize such life without the limitations or expense of returning samples to Earth, and can monitor forward contamination. A new semiconductor sequencing technology based on sensing hydrogen ions released during nucleotide incorporation can enable massively parallel sequencing in a small, robust, optics-free CMOS chip format. We demonstrate that these sequencing chips survive several analogues of space radiation at doses consistent with a 2-year Mars mission, including protons with solar particle event-distributed energy levels and 1 GeV oxygen and iron ions. We find no measurable impact of irradiation at 1 and 5 Gy doses on sequencing quality nor on low-level hardware characteristics. Further testing is required to study the impacts of soft errors as well as to characterize performance under neutron and gamma irradiation and at higher doses, which would be expected during operation in environments with significant trapped energetic particles such as during a mission to Europa. Our results support future efforts to use in situ sequencing to test theories of panspermia and/or whether life has a common chemical basis.
C1 [Carr, Christopher E.; Lui, Clarissa S.; Zuber, Maria T.] MIT, Dept Earth Atmospher & Planetary Sci, Cambridge, MA USA.
[Carr, Christopher E.; Rowedder, Holli; Lui, Clarissa S.; Ruvkun, Gary] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
[Carr, Christopher E.; Rowedder, Holli; Lui, Clarissa S.; Ruvkun, Gary] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA.
[Zlatkovsky, Ilya; Papalias, Chris W.; Bolander, Jarie; Myers, Jason W.; Bustillo, James; Rothberg, Jonathan M.] Life Technol, San Francisco, CA USA.
RP Ruvkun, G (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Simches Res Bldg,185 Cambridge St,CPZN 7250, Boston, MA 02114 USA.
EM ruvkun@molbio.mgh.harvard.edu
OI Carr, Christopher/0000-0002-7946-5622
FU NASA's ASTID program [NNX08AX15G]
FX We thank Peter Guida, Adam Rusek, and the rest of the NSRL-associated
staff for assistance with the irradiations, and Alan Natapoff at MIT for
statistical advice. This work was funded by NASA's ASTID program
(NNX08AX15G).
NR 37
TC 1
Z9 1
U1 4
U2 16
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1531-1074
J9 ASTROBIOLOGY
JI Astrobiology
PD JUN
PY 2013
VL 13
IS 6
BP 560
EP 569
DI 10.1089/ast.2012.0923
PG 10
WC Astronomy & Astrophysics; Biology; Geosciences, Multidisciplinary
SC Astronomy & Astrophysics; Life Sciences & Biomedicine - Other Topics;
Geology
GA 168LO
UT WOS:000320707500006
PM 23734755
ER
PT J
AU Klosky, JL
Hum, AM
Zhang, N
Ali, KS
Srivastava, DK
Klesges, RC
Emmons, KM
Ness, KK
Stovall, M
Robison, LL
Hudson, MM
AF Klosky, James L.
Hum, Ashley M.
Zhang, Nan
Ali, Khatidja S.
Srivastava, D. Kumar
Klesges, Robert C.
Emmons, Karen M.
Ness, Kirsten K.
Stovall, Marilyn
Robison, Leslie L.
Hudson, Melissa M.
TI Smokeless and Dual Tobacco Use Among Males Surviving Childhood Cancer: A
Report From the Childhood Cancer Survivor Study
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID SMOKING-CESSATION; ADULT SURVIVORS
AB Cancer survivors experience treatment-related complications that can be exacerbated by tobacco use. This study reports the prevalence of smokeless and dual tobacco use, compares these rates to the U. S. population, and examines tobacco risk factors among males surviving childhood cancer. Data from the Childhood Cancer Survivor Study (CCSS) 2007 survey were used (N 3378). Standardized incidence ratios (SIR) were obtained by comparing CCSS data with the National Survey on Drug Use and Health. Logistic regression was used to evaluate associations between risk factors and tobacco use. Amongmale survivors, 8.3% and 2.3% were current smokeless tobacco and dual tobacco users, respectively. Survivors were less likely than population males to report smokeless tobacco [SIR=0.64; 95% confidence interval (CI), 0.57-0.72) or dual tobacco (SIR=0.37; CI, 0.29-0.46) use; however, non-White survivors aged 35 to 49 years were more likely to use smokeless tobacco (SIR=2.32; CI, 1.27-3.90). Smokeless tobacco use was associated (P < 0.05) with younger age at diagnosis, lower education, being married or divorced/separated, and not living in the Northeastern United State, whereas history of cardiovascular-and/or pulmonary-toxic treatment was protective. Dual tobacco use was associated with younger age at diagnosis, lower education, divorce/separation, and high psychologic distress. Having active heart or circulatory conditions was protective. Although smokeless tobacco/dual tobacco use is generally low among childhood cancer survivors, these findings suggest that tobacco use screening should be expanded to include smokeless tobacco use, and that smokeless tobacco-specific education and cessation interventions should be provided to users. Screening and intervening for smokeless tobacco/dual tobacco use in childhood cancer survivors will reduce tobacco-related morbidity and mortality. (C) 2013 AACR.
C1 [Klosky, James L.; Hum, Ashley M.; Ali, Khatidja S.] St Jude Childrens Res Hosp, Dept Psychol, Memphis, TN 38105 USA.
[Zhang, Nan; Srivastava, D. Kumar] St Jude Childrens Res Hosp, Dept Biostat, Memphis, TN 38105 USA.
[Klesges, Robert C.; Ness, Kirsten K.; Robison, Leslie L.; Hudson, Melissa M.] St Jude Childrens Res Hosp, Dept Epidemiol & Canc Control, Memphis, TN 38105 USA.
[Hudson, Melissa M.] St Jude Childrens Res Hosp, Dept Oncol, Memphis, TN 38105 USA.
[Klesges, Robert C.] Univ Tennessee, Hlth Sci Ctr, Dept Prevent Med, Memphis, TN USA.
[Emmons, Karen M.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Emmons, Karen M.] Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Stovall, Marilyn] Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA.
RP Klosky, JL (reprint author), St Jude Childrens Res Hosp, Dept Psychol, 262 Danny Thomas Pl, Memphis, TN 38105 USA.
EM james.klosky@stjude.org
OI Clawson, Ashley/0000-0003-4290-5310
FU National Cancer Institute [CA55727]; NIH Cancer Support (CORE) grant;
American Lebanese Syrian Associated Charities
FX This work was supported by National Cancer Institute grant CA55727 (to
L. L. Robison, Principal Investigator), NIH Cancer Support (CORE) grant
(to R. Gilbertson, Principal Investigator), and the American Lebanese
Syrian Associated Charities.
NR 25
TC 2
Z9 2
U1 0
U2 5
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD JUN
PY 2013
VL 22
IS 6
BP 1025
EP 1029
DI 10.1158/1055-9965.EPI-12-1302
PG 5
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 167PF
UT WOS:000320643200003
PM 23580700
ER
PT J
AU Yamauchi, M
Lochhead, P
Imamura, Y
Kuchiba, A
Liao, XY
Qian, ZR
Nishihara, R
Morikawa, T
Shima, K
Wu, KN
Giovannucci, E
Meyerhardt, JA
Fuchs, CS
Chan, AT
Ogino, S
AF Yamauchi, Mai
Lochhead, Paul
Imamura, Yu
Kuchiba, Aya
Liao, Xiaoyun
Qian, Zhi Rong
Nishihara, Reiko
Morikawa, Teppei
Shima, Kaori
Wu, Kana
Giovannucci, Edward
Meyerhardt, Jeffrey A.
Fuchs, Charles S.
Chan, Andrew T.
Ogino, Shuji
TI Physical Activity, Tumor PTGS2 Expression, and Survival in Patients with
Colorectal Cancer
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID BODY-MASS INDEX; ISLAND METHYLATOR PHENOTYPE; MOLECULAR PATHOLOGICAL
EPIDEMIOLOGY; OF-THE-LITERATURE; III COLON-CANCER; MICROSATELLITE
INSTABILITY; ACTIVITY QUESTIONNAIRE; PERSONALIZED MEDICINE; SIGNALING
PATHWAY; MODERATE EXERCISE
AB Background: Higher levels of physical activity are associated with lower colorectal carcinoma incidence and mortality, perhaps through influencing energy balance, cellular prosta7 systemic inflammation. Although evidence suggests interactive effects of energetics, sedentary lifestyle, and tumor CTNNB1 (beta-catenin) or CDKN1B (p27) status on colon cancer prognosis, interactive effects of physical activity and tumor PTGS2 (the official symbol for COX-2) status on clinical outcome remain unknown.
Methods: Using molecular pathological epidemiology database of 605 stage I-III colon and rectal cancers in two prospective cohort studies (the Nurse's Health Study and the Health Professionals Follow-up Study), we examined patient survival according to postdiagnosis physical activity and tumor PTGS2 status (with 382 PTGS2-positive and 223 PTGS2-negative tumors by immunohistochemistry). Cox proportional hazards models were used to calculate colorectal cancer-specific mortality HR, adjusting for clinical and other tumor variables including microsatellite instability status.
Results: Among PTGS2-positive cases, compared with the least active first quartile, the multivariate HRs (95% confidence interval) were 0.30 (0.14-0.62) for the second, 0.38 (0.20-0.71) for the third, and 0.18 (0.08-0.41) for the fourth quartile of physical activity level (P-trend = 0.0002). In contrast, among PTGS2-negative cases, physical activity level was not significantly associated with survival (P-trend = 0.84; P-interaction = 0.024, between physical activity and tumor PTGS2 status).
Conclusions: Postdiagnosis physical activity is associated with better survival among patients with PTGS2-positive tumors but not among patients with PTGS2-negative tumors.
Impact: Immunohistochemical PTGS2 expression in colorectal carcinoma may serve as a predictive biomarker in pathology practice, which may predict stronger benefit from exercise. (c) 2013 AACR.
C1 [Yamauchi, Mai; Lochhead, Paul; Imamura, Yu; Kuchiba, Aya; Liao, Xiaoyun; Qian, Zhi Rong; Nishihara, Reiko; Meyerhardt, Jeffrey A.; Fuchs, Charles S.; Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Yamauchi, Mai; Lochhead, Paul; Imamura, Yu; Kuchiba, Aya; Liao, Xiaoyun; Qian, Zhi Rong; Nishihara, Reiko; Meyerhardt, Jeffrey A.; Fuchs, Charles S.; Ogino, Shuji] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Lochhead, Paul] Univ Aberdeen, Gastrointestinal Res Grp, Inst Med Sci, Aberdeen, Scotland.
[Kuchiba, Aya; Nishihara, Reiko; Wu, Kana; Giovannucci, Edward] Harvard Univ, Dept Nutr, Sch Publ Hlth, Boston, MA 02114 USA.
[Giovannucci, Edward; Ogino, Shuji] Harvard Univ, Dept Epidemiol, Sch Publ Hlth, Boston, MA 02114 USA.
[Morikawa, Teppei] Tokyo Univ Hosp, Dept Pathol, Tokyo 113, Japan.
[Shima, Kaori] Kagoshima Univ, Dept Oral Pathol, Kagoshima 890, Japan.
[Giovannucci, Edward; Fuchs, Charles S.; Chan, Andrew T.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA.
[Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA.
RP Chan, AT (reprint author), Harvard Univ, Brigham & Womens Hosp, Massachusetts Gen Hosp, Div Gastroenterol,Channing Div Network Med,Med Sc, 55 Fruit St, Boston, MA 02114 USA.
EM achan@partners.org; shuji_ogino@dfci.harvard.edu
OI Qian, Zhi rong/0000-0003-1633-4120
FU NIH [P01 CA87969, P01 CA55075, 1UM1 CA167552, P50 CA127003, R01
CA151993, R01 CA137178]; Harvard University Knox Memorial Fellowship
FX This work was supported by NIH grants [P01 CA87969 (to S.E. Hankinson),
P01 CA55075 (to W.C. Willett), 1UM1 CA167552 (to W.C. Willett), P50
CA127003 (to C.S. Fuchs), R01 CA151993 (to S. Ogino), and R01 CA137178
(to A.T. Chan)]. P. Lochhead is a Scottish Government Clinical Academic
Fellow and was supported by a Harvard University Knox Memorial
Fellowship. A.T. Chan is a Damon Runyon Cancer Foundation Clinical
Investigator.
NR 89
TC 17
Z9 17
U1 0
U2 15
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD JUN
PY 2013
VL 22
IS 6
BP 1142
EP 1152
DI 10.1158/1055-9965.EPI-13-0108
PG 11
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 167PF
UT WOS:000320643200018
PM 23629521
ER
PT J
AU Valente, AM
Lakdawala, NK
Powell, AJ
Evans, SP
Cirino, AL
Orav, EJ
MacRae, CA
Colan, SD
Ho, CY
AF Valente, Anne Marie
Lakdawala, Neal K.
Powell, Andrew J.
Evans, Sarah P.
Cirino, Allison L.
Orav, E. John.
MacRae, Calum A.
Colan, Steven D.
Ho, Carolyn Y.
TI Comparison of Echocardiographic and Cardiac Magnetic Resonance Imaging
in Hypertrophic Cardiomyopathy Sarcomere Mutation Carriers Without Left
Ventricular Hypertrophy
SO CIRCULATION-CARDIOVASCULAR GENETICS
LA English
DT Article
DE cardiac MRI; cardiomyopathy, hypertrophic; echocardiography; genetics;
humans
ID LATE GADOLINIUM ENHANCEMENT; DILATED CARDIOMYOPATHY; HEART-ASSOCIATION;
OF-CARDIOLOGY; ABNORMALITIES; PHENOTYPE; GUIDELINES; DIAGNOSIS;
COMMITTEE; FAMILIES
AB Background- Left ventricular hypertrophy (LVH) typically manifests during or after adolescence in sarcomere mutation carriers at risk for developing hypertrophic cardiomyopathy. Guidelines recommend serial imaging of mutation carriers without LVH (G+/LVH-) to monitor for phenotypic evolution, but the optimal strategy is undefined. Compared with echocardiography (echo), cardiac MRI (CMR) offers improved endocardial visualization and potential to assess scar. However, the incremental advantage offered by CMR for early diagnosis of hypertrophic cardiomyopathy is unclear. Therefore, we systematically compared echo and CMR in G+/LVH- subjects.
Methods and Results- A total of 40 sarcomere mutation carriers with normal echo wall thickness (<12 mm or z score <2.5 in children) underwent concurrent CMR. Mean age was 21.7 +/- 11.1 years, 55% were female. If left ventricular wall thickness seemed nonuniform, the size and location of relatively thickened segments were noted. Late gadolinium enhancement was assessed with CMR. Diagnostic agreement between echo and CMR was good (90%), although CMR measurements of left ventricular wall thickness were approximate to 19% lower than echo. Four subjects had mild hypertrophy (12.6-14 mm; <= 2 segments) appreciated by CMR but not echo. No subjects had late gadolinium enhancement. During median 35-month follow-up, 2 subjects developed overt hypertrophic cardiomyopathy, including 1 with mild LVH by CMR at baseline.
Conclusions- Echo is unlikely to miss substantial LVH; however, CMR identified mild hypertrophy in approximate to 10% of mutation carriers with normal echo wall thickness. CMR may be a useful adjunct in hypertrophic cardiomyopathy family screening, particularly in higher risk situations, or if echocardiographic images are suboptimal or suggest borderline LVH.
C1 [Valente, Anne Marie; Lakdawala, Neal K.; Cirino, Allison L.; MacRae, Calum A.; Ho, Carolyn Y.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA.
[Valente, Anne Marie; Powell, Andrew J.; Evans, Sarah P.; Colan, Steven D.] Boston Childrens Hosp, Dept Cardiol, Boston, MA USA.
[Orav, E. John.] Brigham & Womens Hosp, Div Gen Med & Primary Care, Boston, MA 02115 USA.
[Lakdawala, Neal K.] VA Boston Healthcare Syst, Boston, MA USA.
RP Ho, CY (reprint author), Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA.
EM cho@partners.org
OI Ho, Carolyn/0000-0002-7334-7924
FU National Heart, Lung, and Blood Institute at the National Institutes of
Health [5K23HL078901, 1P20HL101408]
FX This work was supported by the National Heart, Lung, and Blood Institute
at the National Institutes of Health [5K23HL078901 and 1P20HL101408 to
C.Y. Ho].
NR 33
TC 13
Z9 15
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1942-325X
J9 CIRC-CARDIOVASC GENE
JI Circ.-Cardiovasc. Genet.
PD JUN
PY 2013
VL 6
IS 3
BP 230
EP 237
DI 10.1161/CIRCGENETICS.113.000037
PG 8
WC Cardiac & Cardiovascular Systems; Genetics & Heredity
SC Cardiovascular System & Cardiology; Genetics & Heredity
GA 166TL
UT WOS:000320580700003
PM 23690394
ER
PT J
AU Hedrich, CM
Tsokos, GC
AF Hedrich, Christian M.
Tsokos, George C.
TI Bridging the gap between autoinflammation and autoimmunity
SO CLINICAL IMMUNOLOGY
LA English
DT Editorial Material
ID EXONUCLEASE TREX1; IL-10 EXPRESSION; MUTATIONS; DISEASE; GENE; DNA
C1 [Hedrich, Christian M.; Tsokos, George C.] Harvard Univ, Beth Israel Deaconess Med Ctr, Div Rheumatol, Dept Med,Med Sch, Boston, MA 02215 USA.
RP Hedrich, CM (reprint author), Beth Israel Deaconess Med Ctr CLS 937, Div Rheumatol, Dept Med, 330 Brookline Ave, Boston, MA 02115 USA.
EM chedrich@bidmc.harvard.edu
NR 28
TC 3
Z9 3
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 1521-6616
J9 CLIN IMMUNOL
JI Clin. Immunol.
PD JUN
PY 2013
VL 147
IS 3
SI SI
BP 151
EP 154
DI 10.1016/j.clim.2013.03.006
PG 4
WC Immunology
SC Immunology
GA 168EO
UT WOS:000320688700001
PM 23587745
ER
PT J
AU Luo, S
Cha, JS
Wilke, C
Breen, C
Zhou, LDH
AF Luo, Su
Cha, Jisun
Wilke, Caroline
Breen, Catherine
Zhou, Linda Hua
TI What Is Your Diagnosis? Primary Localized Cutaneous Nodular Amyloidosis
SO CUTIS
LA English
DT Editorial Material
ID OF-THE-LITERATURE; TERM-FOLLOW-UP; EXCISION
C1 [Luo, Su; Cha, Jisun; Wilke, Caroline; Breen, Catherine; Zhou, Linda Hua] Roger Williams Med Ctr, Providence, RI 02908 USA.
[Luo, Su; Cha, Jisun; Zhou, Linda Hua] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol & Skin Surg, Boston, MA USA.
[Wilke, Caroline; Breen, Catherine] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA.
RP Zhou, LDH (reprint author), Roger Williams Med Ctr, Dept Dermatol & Skin Surg, 50 Maude St, Providence, RI 02908 USA.
EM lindahuazhou@yahoo.com
NR 19
TC 0
Z9 0
U1 0
U2 0
PU QUADRANT HEALTHCOM INC
PI PARSIPPANY
PA 7 CENTURY DRIVE, STE 302, PARSIPPANY, NJ 07054-4603 USA
SN 0011-4162
J9 CUTIS
JI Cutis
PD JUN
PY 2013
VL 91
IS 6
BP 271
EP +
PG 3
WC Dermatology
SC Dermatology
GA 166PL
UT WOS:000320569400002
PM 23837156
ER
PT J
AU Matsumoto, AM
AF Matsumoto, Alvin M.
TI Testosterone Administration in Older Men
SO ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA
LA English
DT Article
DE Hypogonadism; Aging; Diagnosis; Testosterone; Treatment
ID CLINICAL-PRACTICE GUIDELINE; SEX-HORMONE LEVELS; SERUM TESTOSTERONE;
ANDROGEN DEFICIENCY; ELDERLY-MEN; HYPOGONADAL MEN; HEALTHY-YOUNG; ADULT
MEN; PROSTATE; THERAPY
AB The only indication for testosterone administration in older men is testosterone replacement therapy for male hypogonadism. Compared with young hypogonadal men, the diagnosis and management of male hypogonadism in older men is more challenging. Both the clinical manifestations of androgen deficiency and low testosterone levels may be caused or modified by comorbid illnesses that occur and medications taken more frequently by older men, resulting in a greater likelihood for overdiagnosis of hypogonadism and subsequent inappropriate use of and inadequate response to testosterone treatment. It is important to use a systematic, holistic approach to the diagnosis and management of older men with hypogonadism.
C1 [Matsumoto, Alvin M.] VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA.
[Matsumoto, Alvin M.] VA Puget Sound Hlth Care Syst, Clin Res Unit, Seattle, WA 98108 USA.
[Matsumoto, Alvin M.] Univ Washington, Sch Med, Div Gerontol & Geriatr Med, Dept Med, Seattle, WA 98195 USA.
[Matsumoto, Alvin M.] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA.
RP Matsumoto, AM (reprint author), VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, 1660 South Columbian Way S-182-GRECC, Seattle, WA 98108 USA.
EM alvin.matsumoto@va.gov
NR 32
TC 7
Z9 8
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 0889-8529
J9 ENDOCRIN METAB CLIN
JI Endocrinol. Metabol. Clin. North Amer.
PD JUN
PY 2013
VL 42
IS 2
BP 271
EP +
DI 10.1016/j.ecl.2013.02.011
PG 17
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 168XK
UT WOS:000320741000007
PM 23702401
ER
PT J
AU Rozman, PA
Eskandar, E
Madsen, JR
Thesen, T
Carlson, C
Devinsky, O
Kuzniecky, R
Doyle, WK
Ulbert, I
Halgren, E
Cash, SS
AF Rozman, P. A.
Eskandar, E.
Madsen, J. R.
Thesen, T.
Carlson, C.
Devinsky, O.
Kuzniecky, R.
Doyle, W. K.
Ulbert, I
Halgren, E.
Cash, S. S.
TI MULTI-UNIT ACTIVITY IN THE HUMAN NEOCORTEX AS A PREDICTOR OF SEIZURE
ONSET
SO EPILEPSIA
LA English
DT Meeting Abstract
CT 30th International Epilepsy Congress
CY JUN 23-27, 2013
CL Montreal, CANADA
SP Int Bur Epilepsy (IBE), Int League Against Epilepsy (ILAE)
C1 [Rozman, P. A.; Cash, S. S.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Rozman, P. A.; Eskandar, E.; Cash, S. S.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[Eskandar, E.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA.
[Madsen, J. R.] Boston Childrens Hosp, Dept Neurosurg, Boston, MA USA.
[Madsen, J. R.] Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA.
[Thesen, T.; Carlson, C.; Devinsky, O.; Kuzniecky, R.; Doyle, W. K.] NYU, Med Ctr, Comprehens Epilepsy Ctr, New York, MA USA.
[Ulbert, I] Natl Inst Neurosci, Budapest, Hungary.
[Ulbert, I] Hungarian Acad Sci, Inst Psychol, Budapest, Hungary.
[Ulbert, I] Peter Pazmany Catholic Univ, Dept Informat Technol, Budapest, Hungary.
[Halgren, E.] Univ Calif San Diego, Dept Radiol, San Diego, CA 92103 USA.
[Halgren, E.] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA.
[Halgren, E.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0013-9580
J9 EPILEPSIA
JI Epilepsia
PD JUN
PY 2013
VL 54
SU 3
SI SI
BP 9
EP 10
PG 2
WC Clinical Neurology
SC Neurosciences & Neurology
GA 165GS
UT WOS:000320472000019
ER
PT J
AU Moura, LMVR
Almeida, KT
Bezerra, MP
Kilbride, RD
AF Moura, L. M. V. R.
Almeida, K. T.
Bezerra, M. P.
Kilbride, R. D.
TI TIME TO SPECIALIST EPILEPSY EVALUATION AND ITS RELATION TO SEIZURE
CONTROL
SO EPILEPSIA
LA English
DT Meeting Abstract
CT 30th International Epilepsy Congress
CY JUN 23-27, 2013
CL Montreal, CANADA
SP Int Bur Epilepsy (IBE), Int League Against Epilepsy (ILAE)
C1 [Moura, L. M. V. R.; Kilbride, R. D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Epilepsy Serv, Boston, MA USA.
[Almeida, K. T.; Bezerra, M. P.] Univ Estado Rio De Janeiro, Hosp Univ Pedro Ernesto, Dept Neurol, Rio De Janeiro, Brazil.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0013-9580
J9 EPILEPSIA
JI Epilepsia
PD JUN
PY 2013
VL 54
SU 3
SI SI
BP 57
EP 57
PG 1
WC Clinical Neurology
SC Neurosciences & Neurology
GA 165GS
UT WOS:000320472000165
ER
PT J
AU Moura, LMVR
Almeida, KT
Kilbride, RD
Cole, AJ
Hoch, DB
AF Moura, L. M. V. R.
Almeida, K. T.
Kilbride, R. D.
Cole, A. J.
Hoch, D. B.
TI ADHERENCE TO EPILEPSY QUALITY INDICATORS IN SPECIALIZED EPILEPSY CARE
CENTERS: A COMPARISON BETWEEN DISPARATE HEALTH CARE SYSTEMS
SO EPILEPSIA
LA English
DT Meeting Abstract
CT 30th International Epilepsy Congress
CY JUN 23-27, 2013
CL Montreal, CANADA
SP Int Bur Epilepsy (IBE), Int League Against Epilepsy (ILAE)
C1 [Moura, L. M. V. R.; Kilbride, R. D.; Cole, A. J.; Hoch, D. B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Epilepsy Serv, Boston, MA USA.
[Almeida, K. T.] Univ Estado Rio De Janeiro, Hosp Univ Pedro Ernesto, Dept Neurol, Rio De Janeiro, Brazil.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0013-9580
J9 EPILEPSIA
JI Epilepsia
PD JUN
PY 2013
VL 54
SU 3
SI SI
BP 58
EP 58
PG 1
WC Clinical Neurology
SC Neurosciences & Neurology
GA 165GS
UT WOS:000320472000166
ER
PT J
AU Almeida, KT
Moura, LMVR
Bezerra, MP
Kilbride, RD
AF Almeida, K. T.
Moura, L. M. V. R.
Bezerra, M. P.
Kilbride, R. D.
TI AVAILABILITY OF THE NEWER GENERATION OF ANTI-EPILEPTIC DRUGS IN TWO
TERTIARY REFERRAL EPILEPSY CENTERS
SO EPILEPSIA
LA English
DT Meeting Abstract
CT 30th International Epilepsy Congress
CY JUN 23-27, 2013
CL Montreal, CANADA
SP Int Bur Epilepsy (IBE), Int League Against Epilepsy (ILAE)
C1 [Almeida, K. T.; Bezerra, M. P.] Univ Estado Rio de Janeiro, Hosp Univ Pedro Ernesto, Dept Neurol, BR-20550011 Rio De Janeiro, Brazil.
[Moura, L. M. V. R.; Kilbride, R. D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Epilepsy Serv, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0013-9580
J9 EPILEPSIA
JI Epilepsia
PD JUN
PY 2013
VL 54
SU 3
SI SI
BP 59
EP 59
PG 1
WC Clinical Neurology
SC Neurosciences & Neurology
GA 165GS
UT WOS:000320472000171
ER
PT J
AU Gill, SN
Duron, RM
Medina, MT
Martinez-Juarez, I
Alonso, MA
Ochoa, A
Jara-Prado, A
Machado-Salas, J
Tanaka, M
Bailey, JN
Delgado-Escueta, A
AF Gill, S. N.
Duron, R. M.
Medina, M. T.
Martinez-Juarez, I
Alonso, M. A.
Ochoa, A.
Jara-Prado, A.
Machado-Salas, J.
Tanaka, M.
Bailey, J. N.
Delgado-Escueta, A.
TI FOCAL SPIKES IN ASYMPTOMATIC MEMBERS OF JUVENILE MYOCLONIC EPILEPSY
FAMILIES WITH MUTATED EPILEPSY GENES
SO EPILEPSIA
LA English
DT Meeting Abstract
CT 30th International Epilepsy Congress
CY JUN 23-27, 2013
CL Montreal, CANADA
SP Int Bur Epilepsy (IBE), Int League Against Epilepsy (ILAE)
C1 [Gill, S. N.; Tanaka, M.; Delgado-Escueta, A.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Gill, S. N.; Duron, R. M.; Tanaka, M.; Bailey, J. N.; Delgado-Escueta, A.] VA Greater Los Angeles Healthcare Syst, Neurol Serv, Epilepsy Genet Genom Lab, Los Angeles, CA USA.
[Gill, S. N.; Duron, R. M.; Tanaka, M.; Bailey, J. N.; Delgado-Escueta, A.] VA Greater Los Angeles Healthcare Syst, Res Serv, Epilepsy Genet Genom Lab, Los Angeles, CA USA.
[Gill, S. N.; Duron, R. M.; Medina, M. T.; Martinez-Juarez, I; Alonso, M. A.; Ochoa, A.; Jara-Prado, A.; Machado-Salas, J.; Tanaka, M.; Bailey, J. N.; Delgado-Escueta, A.] Int GENESS Consortium, Los Angeles, CA USA.
[Duron, R. M.] Lucas Med Ctr, Dept Neurol, Tegucigalpa, Honduras.
[Duron, R. M.; Medina, M. T.] Natl Autonomous Univ, Dept Neurol, Tegucigalpa, Honduras.
[Martinez-Juarez, I; Alonso, M. A.; Ochoa, A.; Jara-Prado, A.] Natl Inst Neurol & Neurosurg, Dept Neurol, Mexico City, DF, Mexico.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0013-9580
J9 EPILEPSIA
JI Epilepsia
PD JUN
PY 2013
VL 54
SU 3
SI SI
BP 194
EP 194
PG 1
WC Clinical Neurology
SC Neurosciences & Neurology
GA 165GS
UT WOS:000320472000616
ER
PT J
AU Ng, MC
Kilbride, R
Simon, MV
Eskandar, E
Cole, AJ
AF Ng, M. C.
Kilbride, R.
Simon, M., V
Eskandar, E.
Cole, A. J.
TI HIPPOCAMPOGRAPHY AND HIPPOCAMPECTOMY IN DOMINANT LESIONAL
EXTRAHIPPOCAMPAL TEMPORAL LOBE EPILEPSY
SO EPILEPSIA
LA English
DT Meeting Abstract
CT 30th International Epilepsy Congress
CY JUN 23-27, 2013
CL Montreal, CANADA
SP Int Bur Epilepsy (IBE), Int League Against Epilepsy (ILAE)
C1 [Ng, M. C.; Kilbride, R.; Simon, M., V; Eskandar, E.; Cole, A. J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0013-9580
J9 EPILEPSIA
JI Epilepsia
PD JUN
PY 2013
VL 54
SU 3
SI SI
BP 265
EP 265
PG 1
WC Clinical Neurology
SC Neurosciences & Neurology
GA 165GS
UT WOS:000320472001140
ER
PT J
AU Mosher, JC
Hamalainen, MS
Nair, DR
Alexopoulos, AV
Burgess, RC
So, NK
Najm, IM
AF Mosher, J. C.
Haemaelaeinen, M. S.
Nair, D. R.
Alexopoulos, A., V
Burgess, R. C.
So, N. K.
Najm, I. M.
TI WIDE-BAND DETECTION AND LOCALIZATION OF NORMAL HIGH FREQUENCY
OSCILLATIONS IN EVOKED RESPONSE MAGNETIC FIELDS
SO EPILEPSIA
LA English
DT Meeting Abstract
CT 30th International Epilepsy Congress
CY JUN 23-27, 2013
CL Montreal, CANADA
SP Int Bur Epilepsy (IBE), Int League Against Epilepsy (ILAE)
C1 [Mosher, J. C.; Nair, D. R.; Alexopoulos, A., V; Burgess, R. C.; So, N. K.; Najm, I. M.] Cleveland Clin, Epilepsy Ctr, Cleveland, OH 44106 USA.
[Haemaelaeinen, M. S.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA.
RI Hamalainen, Matti/C-8507-2013
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0013-9580
J9 EPILEPSIA
JI Epilepsia
PD JUN
PY 2013
VL 54
SU 3
SI SI
BP 266
EP 266
PG 1
WC Clinical Neurology
SC Neurosciences & Neurology
GA 165GS
UT WOS:000320472001143
ER
PT J
AU San-Juan, D
Maldonado, LB
Garduno, AJO
Gonzalez-Aragon, MF
Pathmanathan, JS
Trenado, C
Fregni, F
AF San-Juan, D.
Maldonado, L. B.
Garduno, A. J. O.
Gonzalez-Aragon, M. F.
Pathmanathan, J. S.
Trenado, C.
Fregni, F.
TI A RANDOMIZED CONTROLLED TRIAL OF CATHODAL TRANSCRANIAL DIRECT CURRENT
STIMULATION IN PATIENTS WITH MULTIFOCAL EPILEPSY REFRACTORY TO
PHARMACOLOGICAL TREATMENT
SO EPILEPSIA
LA English
DT Meeting Abstract
CT 30th International Epilepsy Congress
CY JUN 23-27, 2013
CL Montreal, CANADA
SP Int Bur Epilepsy (IBE), Int League Against Epilepsy (ILAE)
C1 [San-Juan, D.; Maldonado, L. B.; Garduno, A. J. O.; Gonzalez-Aragon, M. F.] Inst Nacl Neurol & Neurocirug, Mexico City, DF, Mexico.
[Pathmanathan, J. S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Epilepsy Serv, Boston, MA USA.
[Trenado, C.] Freiburg Univ Hosp, Freiburg, Germany.
[Fregni, F.] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Spaulding Rehabil Hosp, Boston, MA USA.
[Fregni, F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0013-9580
J9 EPILEPSIA
JI Epilepsia
PD JUN
PY 2013
VL 54
SU 3
SI SI
BP 289
EP 290
PG 2
WC Clinical Neurology
SC Neurosciences & Neurology
GA 165GS
UT WOS:000320472001219
ER
PT J
AU Bartnikas, TB
Steinbicker, AU
Campagna, DR
Blevins, S
Woodward, LS
Herrera, C
Bloch, KD
Justice, MJ
Fleming, MD
AF Bartnikas, Thomas B.
Steinbicker, Andrea U.
Campagna, Dean R.
Blevins, Sherika
Woodward, Lanette S.
Herrera, Carolina
Bloch, Kenneth D.
Justice, Monica J.
Fleming, Mark D.
TI Identification and characterization of a novel murine allele of Tmprss6
SO HAEMATOLOGICA
LA English
DT Article
ID IRON-DEFICIENCY ANEMIA; TRANSMEMBRANE SERINE-PROTEASE; GENOME-WIDE
ASSOCIATION; MATRIPTASE-2 TMPRSS6; HEPCIDIN EXPRESSION; MICROCYTIC
ANEMIA; COMMON VARIANTS; MUTATIONS; GENE; MICE
AB Mutagenesis screens can establish mouse models of utility for the study of critical biological processes such as iron metabolism. Such screens can produce mutations in novel genes or establish novel alleles of known genes, both of which can be useful tools for study. In order to identify genes of relevance to hematologic as well as other phenotypes, we performed N-ethyl-N-nitrosourea mutagenesis in C57BL/6J mice. An anemic mouse was identified and a putative mutation was characterized by mapping, sequencing and in vitro activity analysis. The mouse strain was backcrossed for ten generations then phenotypically characterized with respect to a previously established null mouse strain. Potential modifying loci were identified by quantitative trait locus analysis. Mapping and sequencing in an anemic mouse termed hem8 identified an I286F substitution in Tmprss6, a serine protease essential for iron metabolism; this substitution impaired in vitro protease activity. After backcrossing to C57BL6/J for ten generations, the hem8(-/-) strain exhibited a phenotype similar in some but not all aspects to that of Tmprss6(-/-) mice. The hem8 and Tmprss6-null mutations were allelic. Both hem8(-/-) and Tmprss6(-/-) mice responded similarly to pharmacological modulators of bone morphogenetic protein signaling, a key regulator of iron metabolism. Quantitative trait locus analysis in the hem8 strain identified potential modifying loci on chromosomes 2, 4, 7 and 10. In conclusion, the hem8 mouse model carries a novel allele of Tmprss6. Potential uses for this strain in the study of iron metabolism are discussed.
C1 [Bartnikas, Thomas B.; Herrera, Carolina] Brown Univ, Dept Pathol & Lab Med, Providence, RI 02912 USA.
[Steinbicker, Andrea U.; Bloch, Kenneth D.] Massachusetts Gen Hosp, Anesthesia Ctr Crit Care Res, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
[Steinbicker, Andrea U.] Univ Munster, Dept Anesthesiol Intens Care & Pain Med, D-48149 Munster, Germany.
[Campagna, Dean R.; Blevins, Sherika; Fleming, Mark D.] Childrens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Woodward, Lanette S.; Justice, Monica J.] Baylor Coll Med, Dept Genet, Houston, TX 77030 USA.
RP Bartnikas, TB (reprint author), Brown Univ, Dept Pathol & Lab Med, Providence, RI 02912 USA.
EM Thomas_Bartnikas@brown.edu
FU National Institutes of Health [K99DK084122, R01DK082971, U01HD039372,
R01CA115503, R01DK080011]; Deutsche Forschungsgemeinschaft [DFG SW
119/3-1]; Fondation Leducq
FX This work was supported by National Institutes of Health grants
K99DK084122 (to TBB), R01DK082971 (to KDB), U01HD039372 and R01CA115503
(to MJJ) and R01DK080011 (to MDF), Deutsche Forschungsgemeinschaft DFG
SW 119/3-1 (to AUS) and a grant from the Fondation Leducq (to KDB).
NR 48
TC 2
Z9 2
U1 0
U2 6
PU FERRATA STORTI FOUNDATION
PI PAVIA
PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY
SN 0390-6078
J9 HAEMATOLOGICA
JI Haematologica
PD JUN
PY 2013
VL 98
IS 6
BP 854
EP 861
DI 10.3324/haematol.2012.074617
PG 8
WC Hematology
SC Hematology
GA 157MH
UT WOS:000319899800010
PM 23300183
ER
PT J
AU Brown, JR
Messmer, B
Werner, L
Davids, MS
Mikler, E
Supko, JG
Fisher, DC
LaCasce, AS
Armand, P
Jacobsen, E
Dalton, V
Tesar, B
Fernandes, SM
McDonough, S
Ritz, J
Rassenti, L
Kipps, TJ
Neuberg, D
Freedman, AS
AF Brown, Jennifer R.
Messmer, Bradley
Werner, Lillian
Davids, Matthew S.
Mikler, Evgeny
Supko, Jeffrey G.
Fisher, David C.
LaCasce, Ann S.
Armand, Philippe
Jacobsen, Eric
Dalton, Virginia
Tesar, Bethany
Fernandes, Stacey M.
McDonough, Sean
Ritz, Jerome
Rassenti, Laura
Kipps, Thomas J.
Neuberg, Donna
Freedman, Arnold S.
TI A phase I study of escalated dose subcutaneous alemtuzumab given weekly
with rituximab in relapsed chronic lymphocytic leukemia/small
lymphocytic lymphoma
SO HAEMATOLOGICA
LA English
DT Article
ID SALVAGE THERAPY; FLUDARABINE; METHYLPREDNISOLONE; CYCLOPHOSPHAMIDE;
COMBINATION; TRIAL; GUIDELINES; CAMPATH-1H; DIAGNOSIS
AB This study assessed the safety and preliminary efficacy of escalated dose subcutaneous alemtuzumab in combination with rituximab in chronic lymphocytic leukemia. Twenty-eight patients with relapsed refractory chronic lymphocytic leukemia were treated on four dosing cohorts of weekly rituximab at 375 mg/m(2) and alemtuzumab doses that started at 30 mg three times per week and escalated to weekly dosing over four weeks, culminating with 90 mg weekly. One dose limiting toxicity of a rituximab infusion reaction was seen in cohort 2, but the regimen was otherwise well tolerated without evidence of differential toxicity by cohort. The overall response rate by National Cancer Institute-Working Group criteria was 61%, and the rate of complete bone marrow response was 43%, most of whom were negative for minimal residual disease. The addition of CT scan evaluation per International Workshop on Chronic Lymphocytic Leukemia 2008 criteria reduced the overall response rate to 14%. Median overall survival was 35 months, with 12 patients able to proceed to stem cell transplantation. Pharmacokinetic studies showed that chronic lymphocytic leukemia involving more than 80% of the bone marrow at study start was associated with lower trough concentrations of alemtuzumab and rituximab, and that higher trough serum concentrations of alemtuzumab were associated with complete bone marrow clearance. We conclude that escalated subcutaneous doses of alemtuzumab given weekly are well tolerated and result in excellent bone marrow clearance of chronic lymphocytic leukemia, helping patients to proceed to stem cell transplantation. This study is registered at ClinicalTrials.gov (Identifier:00330252).
C1 [Brown, Jennifer R.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Dept Med Oncol, Boston, MA 02115 USA.
Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA USA.
Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
RP Brown, JR (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, Dept Med Oncol, Boston, MA 02115 USA.
EM jbrown2@partners.org
FU NIH [K23 CA115682-01]
FX JRB was supported by NIH grant K23 CA115682-01 and is a Scholar of the
American Society of Hematology as well as a Scholar in Clinical Research
of the Leukemia and Lymphoma Society.
NR 28
TC 7
Z9 7
U1 0
U2 3
PU FERRATA STORTI FOUNDATION
PI PAVIA
PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY
SN 0390-6078
J9 HAEMATOLOGICA
JI Haematologica
PD JUN
PY 2013
VL 98
IS 6
BP 964
EP 970
DI 10.3324/haematol.2013.086207
PG 7
WC Hematology
SC Hematology
GA 157MH
UT WOS:000319899800025
PM 23645694
ER
PT J
AU Ioannou, GN
Bryson, CL
Weiss, NS
Scott, JD
Boyko, EJ
AF Ioannou, George N.
Bryson, Christopher L.
Weiss, Noel S.
Scott, John D.
Boyko, Edward J.
TI The prevalence of cirrhosis and hepatocellular carcinoma in patients
with human immunodeficiency virus infection: Are the data found in this
sample applicable to other settings? Reply
SO HEPATOLOGY
LA English
DT Letter
C1 [Ioannou, George N.] Vet Affairs Puget Sound Hlth Care Syst, Div Gastroenterol, Seattle, WA USA.
[Bryson, Christopher L.; Boyko, Edward J.] Vet Affairs Puget Sound Hlth Care Syst, Div Internal Med, Seattle, WA USA.
Univ Washington, Seattle, WA 98195 USA.
[Weiss, Noel S.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Scott, John D.] Univ Washington, Div Infect Dis, Seattle, WA 98195 USA.
RP Ioannou, GN (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Div Gastroenterol, Seattle, WA USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD JUN
PY 2013
VL 57
IS 6
BP 2545
EP 2545
DI 10.1002/hep.26171
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 162PC
UT WOS:000320276400053
PM 23197437
ER
PT J
AU Bleier, BS
Nocera, AL
Iqbal, H
Hoang, JD
Feldman, RE
Han, X
AF Bleier, Benjamin S.
Nocera, Angela L.
Iqbal, Hufsa
Hoang, John D.
Feldman, Rachel E.
Han, Xue
TI P-glycoprotein functions as an immunomodulator in healthy human primary
nasal epithelial cells
SO INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY
LA English
DT Article
DE P-glycoprotein; multidrug resistance; nasal epithelium; cell culture;
cytokine secretion; immunomodulator; PSC 833; verapamil; rhodamine 123;
sinusitis
ID CHRONIC RHINOSINUSITIS; EXPRESSION; TRANSPORT; POLYPS; MRP1
AB Background P-glycoprotein (P-gp) is an adenosine triphosphate (ATP)-dependent efflux pump that confers chemotherapeutic resistance in cancer cells. Recent studies suggest that P-gp may also function as an immunomodulator through regulation of cytokine transport. Sinonasal epithelial cells have been recognized as drivers of local innate and adaptive immunity and are known to overexpress P-gp in the setting of inflammation. The objective of this study is to therefore determine whether P-gp participates in the regulation of cytokine secretion in sinonasal epithelial cells. Methods Primary nasal epithelial cell cultures (PNECCs) were cultivated from 5 healthy patients. Membranous P-gp was quantified through quantitative fluorescent immunohistochemistry (Q-FIHC) and confirmed by enzyme-linked immunosorbent assay (ELISA). Sensitivity to inhibition was determined using a rhodamine 123 accumulation assay. Baseline and lipopolysaccharide (LPS)-stimulated cytokine secretion of interleukin 6 (IL-6), IL-8, granulocyte macrophage colony stimulating factor (GM-CSF), and thymic stromal lymphopoietin (TSLP) were quantified by ELISA and compared to LPS stimulated secretion in the setting of P-gp-specific inhibition. Differences in P-gp expression and cytokine secretion were compared using 2-tailed Student t tests with post hoc testing using the Bonferroni procedure. Results Membranous P-gp is detectable in PNECCs and upregulated following LPS exposure. P-gp is sensitive to inhibition by both PSC 833 and verapamil in a dose-dependent fashion. LPS stimulated secretion of normalized IL-6 (mean, 95% confidence interval [CI]) (79.67, 42.26-117.07), GM-CSF (39.92, 7.90-71.94), and TSLP (6.65, 5.35-7.96) was significantly reduced following P-gp inhibition (37.60, 11.54-63.65, p = 0.023; 7.64, 2.25-13.03, p = 0.044; and 5.13, 4.44-5.82, p = 0.038; respectively). Conclusion P-gp is functionally active in PNECCs. P-gp participates in modulation of epithelial secretion of LPS stimulated IL-6, GM-CSF, and TSLP.
C1 [Bleier, Benjamin S.; Feldman, Rachel E.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA.
[Nocera, Angela L.; Iqbal, Hufsa; Hoang, John D.; Han, Xue] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA.
RP Bleier, BS (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02115 USA.
EM benjamin_bleier@meei.harvard.edu
FU American Rhinologic Society
FX Funding sources for the study: Funded in part by a American Rhinologic
Society New Investigator Grant.
NR 16
TC 13
Z9 13
U1 0
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2042-6976
J9 INT FORUM ALLERGY RH
JI Int. Forum Allergy Rhinol.
PD JUN
PY 2013
VL 3
IS 6
BP 433
EP 438
DI 10.1002/alr.21166
PG 6
WC Otorhinolaryngology
SC Otorhinolaryngology
GA 171LG
UT WOS:000320929300002
PM 23520057
ER
PT J
AU Klein, C
Krainc, D
AF Klein, Christine
Krainc, Dimitri
TI Glucocerebrosidase Mutations Tipping Point Toward Parkinson Disease and
Dementia?
SO JAMA NEUROLOGY
LA English
DT Editorial Material
ID LEWY BODY DISEASE; SYNUCLEIN; ALPHA; EXPRESSION; PATHOLOGY
C1 [Klein, Christine] Univ Lubeck, Inst Neurogenet, D-23562 Lubeck, Germany.
[Krainc, Dimitri] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Neurodegenerat Dis,Dept Neurol, Boston, MA USA.
RP Klein, C (reprint author), Univ Lubeck, Inst Neurogenet, Maria Goeppert Str 1, D-23562 Lubeck, Germany.
EM christine.klein@neuro.uni-luebeck.de
NR 11
TC 0
Z9 0
U1 2
U2 3
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 2168-6149
J9 JAMA NEUROL
JI JAMA Neurol.
PD JUN
PY 2013
VL 70
IS 6
BP 686
EP 688
DI 10.1001/jamaneurol.2013.87
PG 3
WC Clinical Neurology
SC Neurosciences & Neurology
GA 160PV
UT WOS:000320132600002
PM 23588619
ER
PT J
AU Dombroski, BA
Galasko, DR
Mata, IF
Zabetian, CP
Craig, UK
Garruto, RM
Oyanagi, K
Schellenberg, GD
AF Dombroski, Beth A.
Galasko, Douglas R.
Mata, Ignacio F.
Zabetian, Cyrus P.
Craig, Ulla-Katrina
Garruto, Ralph M.
Oyanagi, Kiyomitsu
Schellenberg, Gerard D.
TI C9orf72 Hexanucleotide Repeat Expansion and Guam Amyotrophic Lateral
Sclerosis-Parkinsonism-Dementia Complex
SO JAMA NEUROLOGY
LA English
DT Article
ID KII PENINSULA; JAPAN; DISEASE; RISK; TAU; MUTATIONS; REGION; GENE; FTD;
ALS
AB Importance: High-prevalence foci of amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia complex (PDC) exist in Japanese on the Kii Peninsula of Japan and in the Chamorros of Guam. Clinical and neuropathologic similarities suggest that the disease in these 2 populations may be related. Recent findings showed that some of the Kii Peninsula ALS cases had pathogenic C9orf72 repeat expansions, a genotype that causes ALS in Western populations.
Objectives: To perform genotyping among Guam residents to determine if the C9orf72 expanded repeat allele contributes to ALS-PDC in this population and to evaluate LRRK2 for mutations in the same population.
Design and Setting: Case-control series from neurodegenerative disease research programs on Guam that screened residents for ALS, PDC, and dementia.
Participants: Study participants included 24 with ALS and 22 with PDC and 43 older control subjects with normal cognition ascertained between 1956 and 2006. All but one participant were Chamorro, the indigenous people of Guam. A single individual of white race/ethnicity with ALS was ascertained on Guam during the study.
Main Outcomes and Measures: Participants were screened for C9orf72 hexanucleotide repeat length. Participants with repeat numbers in great excess of 30 were considered to have pathogenic repeat expansions. LRRK2 was screened for point mutations by DNA sequencing.
Results: We found a single individual with an expanded pathogenic hexanucleotide repeat. This individual of white race/ethnicity with ALS was living on Guam at the time of ascertainment but had been born in the United States. All Chamorro participants with ALS and PDC and control subjects had normal repeats, ranging from 2 to 17 copies. No pathogenic LRRK2 mutations were found.
Conclusions and Relevance: Unlike participants with ALS from the Kii Peninsula, C9orf72 expansions do not cause ALS-PDC in Chamorros. Likewise, LRRK2 mutations do not cause Guam ALS-PDC.
C1 [Dombroski, Beth A.; Schellenberg, Gerard D.] Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
[Galasko, Douglas R.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA.
[Mata, Ignacio F.; Zabetian, Cyrus P.] Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98195 USA.
[Mata, Ignacio F.; Zabetian, Cyrus P.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA.
[Garruto, Ralph M.] SUNY Binghamton, Lab Biomed Anthropol & Neurosci, Grad Program Biomed Anthropol, Binghamton, NY USA.
[Oyanagi, Kiyomitsu] Tokyo Metropolitan Inst Neurosci, Dept Neuropathol, Tokyo, Japan.
RP Schellenberg, GD (reprint author), Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Stellar Chance Labs, Room 609B,422 Curie Blvd, Philadelphia, PA 19104 USA.
EM gerardsc@mail.med.upenn.edu
OI Fernandez Mata, Ignacio/0000-0003-1198-0633; Zabetian,
Cyrus/0000-0002-7739-4306
FU National Institute on Aging [AG14382, P01-AG-017586, R37 AG11762];
National Institute of Neurological Disorders and Stroke [R01 NS065070]
FX This work was supported by grants AG14382, P01-AG-017586, and R37
AG11762 from the National Institute on Aging and by grant R01 NS065070
from the National Institute of Neurological Disorders and Stroke.
NR 20
TC 10
Z9 11
U1 0
U2 7
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 2168-6149
J9 JAMA NEUROL
JI JAMA Neurol.
PD JUN
PY 2013
VL 70
IS 6
BP 742
EP 745
DI 10.1001/jamaneurol.2013.1817
PG 4
WC Clinical Neurology
SC Neurosciences & Neurology
GA 160PV
UT WOS:000320132600010
PM 23588498
ER
PT J
AU Jadhav, AP
Zenonos, G
Pless, M
Jovin, TG
Wechsler, L
AF Jadhav, Ashutosh P.
Zenonos, Georgios
Pless, Misha
Jovin, Tudor G.
Wechsler, Lawrence
TI A Variant of the Anterior Opercular Syndrome With Supranuclear Gaze
Palsy
SO JAMA NEUROLOGY
LA English
DT Editorial Material
C1 [Jadhav, Ashutosh P.; Jovin, Tudor G.; Wechsler, Lawrence] Univ Pittsburgh, Med Ctr, Dept Neurol, Pittsburgh, PA 15213 USA.
[Zenonos, Georgios] Univ Pittsburgh, Med Ctr, Dept Neurosurg, Pittsburgh, PA 15213 USA.
[Pless, Misha] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA.
RP Jadhav, AP (reprint author), Univ Pittsburgh, Med Ctr, Dept Neurol, Kaufmann Med Bldg,Ste 811,3471 5th Ave, Pittsburgh, PA 15213 USA.
EM jadhavap@upmc.edu
NR 3
TC 2
Z9 2
U1 0
U2 1
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 2168-6149
J9 JAMA NEUROL
JI JAMA Neurol.
PD JUN
PY 2013
VL 70
IS 6
BP 800
EP 801
PG 2
WC Clinical Neurology
SC Neurosciences & Neurology
GA 160PV
UT WOS:000320132600023
PM 23753964
ER
PT J
AU Amparo, F
Dastjerdi, MH
Okanobo, A
Ferrari, G
Smaga, L
Hamrah, P
Jurkunas, U
Schaumberg, DA
Dana, R
AF Amparo, Francisco
Dastjerdi, Mohammad H.
Okanobo, Andre
Ferrari, Giulio
Smaga, Leila
Hamrah, Pedram
Jurkunas, Ula
Schaumberg, Debra A.
Dana, Reza
TI Topical Interleukin 1 Receptor Antagonist for Treatment of Dry Eye
Disease
SO JAMA OPHTHALMOLOGY
LA English
DT Article
ID KERATOCONJUNCTIVITIS SICCA; OPHTHALMIC EMULSION; CORNEAL EPITHELIUM;
DESICCATING STRESS; TEAR FLUID; CYCLOSPORINE; PREVALENCE; CELLS;
CONJUNCTIVA; EXPRESSION
AB Importance: The immunopathogenic mechanisms of dry eye disease (DED), one of the most common ophthalmic conditions, is incompletely understood. Data from this prospective, double-masked, randomized trial demonstrate that targeting interleukin 1 (IL-1) by topical application of an IL-1 antagonist is efficacious in significantly reducing DED-related patient symptoms and corneal epitheliopathy.
Objective: To evaluate the safety and efficacy of treatment with the topical IL-1 receptor antagonist anakinra (Kineret; Amgen Inc) in patients having DED associated with meibomian gland dysfunction.
Design and Setting: Prospective phase 1/2, randomized, double-masked, vehicle-controlled clinical trial.
Participants: Seventy-five patients with refractory DED.
Interventions: Participants were randomized to receive treatment with topical anakinra, 2.5% (n = 30), anakinra, 5% (n = 15), or vehicle (1% carboxymethylcellulose) (n = 30) 3 times daily for 12 weeks.
Main Outcomes and Measures: Primary outcomes were corneal fluorescein staining (CFS), complete bilateral CFS clearance, dry eye-related symptoms as measured by the Ocular Surface Disease Index, tear film breakup time, and meibomian gland secretion quality.
Results: Topical anakinra was well tolerated compared with vehicle, with no reports of serious adverse reactions attributable to the therapy. After 12 weeks of therapy, participants treated with anakinra, 2.5%, achieved a 46% reduction in their mean CFS score (P = .12 compared with vehicle and P < .001 compared with baseline); participants treated with anakinra, 5%, achieved a 17% reduction in their mean CFS score (P = .88 compared with vehicle and P = .33 compared with baseline); and patients treated with vehicle achieved a 19% reduction in their mean CFS score (P = .11). Complete bilateral CFS clearance was noted in 8 of 28 patients (29%) treated with anakinra, 2.5%, vs in 2 of 29 patients (7%) treated with vehicle (P = .03). By week 12, treatment with anakinra, 2.5%, and treatment with anakinra, 5%, led to significant reductions in symptoms of 30% and 35%, respectively (P = .02 and P = .01, respectively, compared with vehicle); treatment with vehicle led to a 5% reduction in symptoms.
Conclusions and Relevance: Treatment with topical anakinra, 2.5%, for 12 weeks was safe and significantly reduced symptoms and corneal epitheliopathy in patients with DED. These data suggest that the use of an IL-1 antagonist may have a role as a novel therapeutic option for patients with DED.
C1 [Amparo, Francisco; Dastjerdi, Mohammad H.; Okanobo, Andre; Ferrari, Giulio; Smaga, Leila; Hamrah, Pedram; Jurkunas, Ula; Dana, Reza] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA.
[Schaumberg, Debra A.] Harvard Univ, Brigham & Womens Hosp, Div Prevent Med, Sch Med, Boston, MA 02115 USA.
RP Dana, R (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA.
EM reza_dana@meei.harvard.edu
RI ferrari, giulio/J-9260-2016
OI ferrari, giulio/0000-0001-6474-9908
FU Pfizer Inc; National Institutes of Health [K24 EY019098]
FX Drs Dastjerdi and Dana report being listed as coinventors in a patent
application pertaining to use of IL-1 blockers for ophthalmic use,
licensed by Schepens Eye Research Institute and Massachusetts Eye and
Ear Infirmary to Eleven Biotherapeutics Inc. Dr Schaumberg reports
receiving support from Pfizer Inc; holding investments in Mimetogen and
TearLab; being a consultant to Alcon, Allergan, Celtic, Eleven
Biotherapeutics Inc, Inspire, Mimetogen, Pfizer Inc, and SARcode
Bioscience; holding a proprietary interest in patent 11873478 covering
compositions and methods for treating eye disorders and conditions; and
receiving honoraria from Allergan and Pfizer Inc. Dr Dana reports
holding equity in Eleven Biotherapeutics Inc.; This study was supported
in part by grant K24 EY019098 from the National Institutes of Health
(Drs Amparo, Dastjerdi, Okanobo, Ferrari, and Dana and Ms Smaga).
NR 43
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U1 1
U2 1
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 2168-6165
J9 JAMA OPHTHALMOL
JI JAMA Ophthalmol.
PD JUN
PY 2013
VL 131
IS 6
BP 715
EP 723
DI 10.1001/jamaophthalmol.2013.195
PG 9
WC Ophthalmology
SC Ophthalmology
GA 170LR
UT WOS:000320852700001
PM 23599118
ER
PT J
AU Schmidt, TA
Sullivan, DA
Knop, E
Richards, SM
Knop, N
Liu, SH
Sahin, A
Darabad, RR
Morrison, S
Kam, WR
Sullivan, BD
AF Schmidt, Tannin A.
Sullivan, David A.
Knop, Erich
Richards, Stephen M.
Knop, Nadja
Liu, Shaohui
Sahin, Afsun
Darabad, Raheleh Rahimi
Morrison, Sheila
Kam, Wendy R.
Sullivan, Benjamin D.
TI Transcription, Translation, and Function of Lubricin, a Boundary
Lubricant, at the Ocular Surface
SO JAMA OPHTHALMOLOGY
LA English
DT Article
ID DRY EYE DISEASE; ARTICULAR-CARTILAGE; SYNOVIAL-FLUID; HYALURONIC-ACID;
PROTEOGLYCAN 4; WORKSHOP 2007; ZONE PROTEIN; RECOMBINANT LUBRICIN;
ARTIFICIAL MOUTH; LID WIPER
AB Importance: Lubricin may be an important barrier to the development of corneal and conjunctival epitheliopathies that may occur in dry eye disease and contact lens wear.
Objective: To test the hypotheses that lubricin (ie, proteoglycan 4 [PRG4]), a boundary lubricant, is produced by ocular surface epithelia and acts to protect the cornea and conjunctiva against significant shear forces generated during an eyelid blink and that lubricin deficiency increases shear stress on the ocular surface and promotes corneal damage.
Design, Setting, and Participants: Human, porcine, and mouse tissues and cells were processed for molecular biological, immunohistochemical, and tribological studies, and wild-type and PRG4 knockout mice were evaluated for corneal damage.
Results: Our findings demonstrate that lubricin is transcribed and translated by corneal and conjunctival epithelial cells. Lubricin messenger RNA is also present in lacrimal and meibomian glands, as well as in a number of other tissues. Absence of lubricin in PRG4 knockout mice is associated with a significant increase in corneal fluorescein staining. Our studies also show that lubricin functions as an effective friction-lowering boundary lubricant at the human cornea-eyelid interface. This effect is specific and cannot be duplicated by the use of hyaluronate or bovine serum albumin solutions.
Conclusions and Relevance: Our results show that lubricin is transcribed, translated, and expressed by ocular surface epithelia. Moreover, our findings demonstrate that lubricin presence significantly reduces friction between the cornea and conjunctiva and that lubricin deficiency may play a role in promoting corneal damage.
C1 [Schmidt, Tannin A.; Morrison, Sheila] Univ Calgary, Fac Kinesiol, Human Performance Lab, Calgary, AB, Canada.
[Schmidt, Tannin A.] Univ Calgary, Schulich Sch Engn, Ctr Bioengn Res & Educ, Calgary, AB, Canada.
[Sullivan, David A.; Richards, Stephen M.; Liu, Shaohui; Sahin, Afsun; Darabad, Raheleh Rahimi; Kam, Wendy R.] Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, Boston, MA 02114 USA.
[Sullivan, David A.; Richards, Stephen M.; Liu, Shaohui; Sahin, Afsun; Darabad, Raheleh Rahimi; Kam, Wendy R.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA.
[Knop, Erich; Knop, Nadja] Charite, Dept Anat, OSCB, D-13353 Berlin, Germany.
[Sullivan, Benjamin D.] TearLab Corp, San Diego, CA USA.
RP Sullivan, DA (reprint author), Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA.
EM david.sullivan@schepens.harvard.edu
FU National Institutes of Health [R01EY05612, 5 U42 RR006042]; Margaret S.
Sinon Scholar in Ocular Surface Research fund; Natural Sciences and
Engineering Research Council of Canada; Canadian Arthritis Network;
Faculty of Kinesiology at the University of Calgary; Schulich School of
Engineering Centre for Bioengineering Research and Education at the
University of Calgary
FX This research was supported by National Institutes of Health grant
R01EY05612, the Margaret S. Sinon Scholar in Ocular Surface Research
fund, and funding from the Natural Sciences and Engineering Research
Council of Canada, the Canadian Arthritis Network, and the Faculty of
Kinesiology and the Schulich School of Engineering Centre for
Bioengineering Research and Education at the University of Calgary. We
acknowledge use of tissues procured by the National Disease Research
Interchange with support from National Institutes of Health grant 5 U42
RR006042.
NR 63
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Z9 20
U1 2
U2 11
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 2168-6165
J9 JAMA OPHTHALMOL
JI JAMA Ophthalmol.
PD JUN
PY 2013
VL 131
IS 6
BP 766
EP 776
DI 10.1001/jamaophthalmol.2013.2385
PG 11
WC Ophthalmology
SC Ophthalmology
GA 170LR
UT WOS:000320852700008
PM 23599181
ER
PT J
AU Palioura, S
Piris, A
Chodosh, J
AF Palioura, Sotiria
Piris, Adriano
Chodosh, James
TI Conjunctivitis, Fever, and Tender Skin Nodules
SO JAMA OPHTHALMOLOGY
LA English
DT Editorial Material
ID FEBRILE NEUTROPHILIC DERMATOSIS; SWEETS-SYNDROME; INVOLVEMENT
C1 [Palioura, Sotiria; Chodosh, James] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA.
[Piris, Adriano] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA.
RP Chodosh, J (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA.
EM james_chodosh@meei.harvard.edu
NR 9
TC 0
Z9 0
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 2168-6165
J9 JAMA OPHTHALMOL
JI JAMA Ophthalmol.
PD JUN
PY 2013
VL 131
IS 6
BP 791
EP 793
PG 3
WC Ophthalmology
SC Ophthalmology
GA 170LR
UT WOS:000320852700015
PM 23764707
ER
PT J
AU Afshar, R
Strassner, JP
Seung, E
Causton, B
Cho, JL
Harris, RS
Hamilos, DL
Medoff, BD
Luster, AD
AF Afshar, Roshi
Strassner, James P.
Seung, Edward
Causton, Benjamin
Cho, Josalyn L.
Harris, R. Scott
Hamilos, Daniel L.
Medoff, Benjamin D.
Luster, Andrew D.
TI Compartmentalized chemokine-dependent regulatory T-cell inhibition of
allergic pulmonary inflammation
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE Asthma; regulatory T cells; chemokines; CCR4; CCR7; segmental allergen
challenge
ID RECEPTOR EXPRESSION; AIRWAY INFLAMMATION; ASTHMA; CCR7; DISEASE;
HYPERRESPONSIVENESS; INDUCTION; TOLERANCE; MIGRATION; SUBSETS
AB Background: Induction of endogenous regulatory T (Treg) cells represents an exciting new potential modality for treating allergic diseases, such as asthma. Treg cells have been implicated in the regulation of asthma, but the anatomic location in which they exert their regulatory function and the mechanisms controlling the migration necessary for their suppressive function in asthma are not known. Understanding these aspects of Treg cell biology will be important for harnessing their power in the clinic.
Objective: We sought to determine the anatomic location at which Treg cells exert their regulatory function in the sensitization and effector phases of allergic asthma and to determine the chemokine receptors that control the migration of Treg cells to these sites in vivo in both mice and human subjects.
Methods: The clinical efficacy and anatomic location of adoptively transferred chemokine receptor-deficient CD4(+)CD25(+) forkhead box protein 3-positive Treg cells was determined in the sensitization and effector phases of allergic airway inflammation in mice. The chemokine receptor expression profile was determined on Treg cells recruited into the human airway after bronchoscopic segmental allergen challenge of asthmatic patients.
Results: We show that CCR7, but not CCR4, is required on Treg cells to suppress allergic airway inflammation during the sensitization phase. In contrast, CCR4, but not CCR7, is required on Treg cells to suppress allergic airway inflammation during the effector phase. Consistent with our murine studies, human subjects with allergic asthma had an increase in CCR4-expressing functional Treg cells in the lungs after segmental allergen challenge.
Conclusion: The location of Treg cell function differs during allergic sensitization and allergen-induced recall responses in the lung, and this differential localization is critically dependent on differential chemokine function.
C1 [Afshar, Roshi; Strassner, James P.; Seung, Edward; Causton, Benjamin; Cho, Josalyn L.; Hamilos, Daniel L.; Medoff, Benjamin D.; Luster, Andrew D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol,Ctr Immunol & Inf, Cambridge, MA 02138 USA.
[Causton, Benjamin; Cho, Josalyn L.; Harris, R. Scott; Medoff, Benjamin D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pulm & Crit Care Unit, Cambridge, MA 02138 USA.
RP Luster, AD (reprint author), Massachusetts Gen Hosp, 149,13th St, Charlestown, MA 02129 USA.
EM aluster@mgh.harvard.edu
FU National Institutes of Health [R37AI0406, U19AI095261, T32 AI060548];
Merck; United Therapeutics
FX Supported by grants from the National Institutes of Health (R37AI0406,
U19AI095261, and T32 AI060548 to A.D.L.).; Disclosure of potential
conflict of interest: D. L. Hamilos has consultant arrangements with and
has received grants from Merck. R. S. Harris has consultant arrangements
with Merck and has received grants from United Therapeutics. A. D.
Luster has consultant arrangements with Amgen, Idera, Lilly, and Merck.
The rest of the authors declare that they have no relevant conflicts of
interest.
NR 32
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U1 0
U2 7
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD JUN
PY 2013
VL 131
IS 6
BP 1644
EP +
DI 10.1016/j.jaci.2013.03.002
PG 13
WC Allergy; Immunology
SC Allergy; Immunology
GA 166CT
UT WOS:000320532800025
PM 23632297
ER
PT J
AU Hernandez, AF
Hammill, BG
Kociol, RD
Eapen, ZJ
Fonarow, GC
Klaskala, W
Mills, RM
Curtis, LH
AF Hernandez, Adrian F.
Hammill, Bradley G.
Kociol, Robb D.
Eapen, Zubin J.
Fonarow, Gregg C.
Klaskala, Winslow
Mills, Roger M.
Curtis, Lesley H.
TI Clinical Effectiveness of Anticoagulation Therapy Among Older Patients
With Heart Failure and Without Atrial Fibrillation: Findings From the
ADHERE Registry Linked to Medicare Claims
SO JOURNAL OF CARDIAC FAILURE
LA English
DT Article
DE Atrial fibrillation; anticoagulants; heart failure; outcome assessment
(health care)
ID LEFT-VENTRICULAR DYSFUNCTION; SYSTOLIC DYSFUNCTION; SINUS RHYTHM;
ANTITHROMBOTIC THERAPY; RANDOMIZED-TRIAL; RISK; BENEFICIARIES; WARFARIN;
OUTCOMES; STROKE
AB Background: Patients with heart failure are at higher risk for thromboembolic events, even in the absence of atrial fibrillation, but the effect of anticoagulation therapy on outcomes is uncertain.
Methods and Results: With data from a clinical registry linked to Medicare claims, we estimated the adjusted associations between anticoagulation and 1-year outcomes with the use of inverse probability of treatment weighting. Eligible patients had an ejection fraction <= 35%, had no concurrent atrial fibrillation, were alive at discharge, and had not received anticoagulation therapy before admission. Of 13,217 patients in 276 hospitals, 1,140 (8.6%) received anticoagulation therapy at discharge. Unadjusted rates of thromboembolic events and major adverse cardiovascular events did not differ by receipt of anticoagulation therapy. Patients discharged on anticoagulation therapy had lower unadjusted rates of all-cause mortality (27.2% vs 32.3%; P < .001) and readmission for heart failure (29.4% vs 35.4%; P < .001) and higher rates of bleeding events (5.2% vs 2.8%; P < .001). After adjustment for probability of treatment and discharge medications, there were no differences in all-cause mortality (hazard ratio 0.92; 95% confidence interval 0.80-1.06) or readmission for heart failure (0.91, 0.81-1.02), but patients receiving anticoagulation therapy were at higher risk for bleeding events (2.09, 1.47-2.97).
Conclusions: Anticoagulation therapy at discharge is infrequent among older patients with heart failure and without atrial fibrillation. There were no statistically significant propensity-weighted associations between anticoagulation therapy and 1-year outcomes, except for a higher risk of bleeding.
C1 [Hernandez, Adrian F.; Hammill, Bradley G.; Eapen, Zubin J.; Curtis, Lesley H.] Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA.
[Hernandez, Adrian F.; Eapen, Zubin J.; Curtis, Lesley H.] Duke Univ, Sch Med, Dept Med, Durham, NC 27706 USA.
[Kociol, Robb D.] Beth Israel Deaconess Med Ctr, Div Cardiovasc Med, Boston, MA 02215 USA.
[Kociol, Robb D.] Beth Israel Deaconess Med Ctr, CardioVasc Inst, Boston, MA 02215 USA.
[Fonarow, Gregg C.] Ronald Reagan UCLA Med Ctr, Ahmanson UCLA Cardiomyopathy Ctr, Los Angeles, CA USA.
[Klaskala, Winslow; Mills, Roger M.] Janssen Res & Dev LLC, Raritan, NJ USA.
RP Hernandez, AF (reprint author), Duke Clin Res Inst, POB 17969, Durham, NC 27715 USA.
EM adrian.hernandez@duke.edu
RI Hernandez, Adrian F./A-7818-2016
OI Hernandez, Adrian F./0000-0003-3387-9616
FU Duke University; Johnson Johnson; Amylin; American Heart Association
Pharmaceutical Roundtable
FX Funding: Research agreement between Duke University and Johnson &
Johnson.; Dr Hernandez has received research funding (>$10,000) from
Amylin and Johnson & Johnson and honoraria (<$10,000) from Corthera. Dr
Eapen has received research fellowship funding (>$10,000) from the
American Heart Association Pharmaceutical Roundtable. Dr Fonarow is a
consultant or advisory board member with Novartis (>$10,000), Medtronic
(<$10,000), and Gambro (<$10,000). Dr Mills is a full-time employee of
Janssen Research and Development, a subsidiary of Johnson & Johnson. Dr
Curtis has received research funding (>$10,000) from Johnson & Johnson.
Drs Hernandez and Curtis have made available online detailed listings of
financial disclosures
(http://www.dcri.duke.edu/about-us/conflict-of-interest/).
NR 26
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U1 0
U2 4
PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS
PI PHILADELPHIA
PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA
SN 1071-9164
J9 J CARD FAIL
JI J. Card. Fail.
PD JUN
PY 2013
VL 19
IS 6
BP 401
EP 407
DI 10.1016/j.cardfail.2013.04.004
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 167NX
UT WOS:000320639800004
PM 23743489
ER
PT J
AU Jaussaud, N
Chitsaz, S
Meadows, A
Wintermark, M
Cambronero, N
Azadani, AN
Saloner, DA
Chuter, TA
Tseng, EE
AF Jaussaud, N.
Chitsaz, S.
Meadows, A.
Wintermark, M.
Cambronero, N.
Azadani, A. N.
Saloner, D. A.
Chuter, T. A.
Tseng, E. E.
TI Acute type A aortic dissection intimal tears by 64-slice computed
tomography: a role for endovascular stent-grafting?
SO JOURNAL OF CARDIOVASCULAR SURGERY
LA English
DT Article
DE Aorta; Tomography, spiral computed; Lacerations
ID INTERNATIONAL REGISTRY; SURGICAL-TREATMENT; THORACIC AORTA; MANAGEMENT;
REPAIR; ANEURYSM; OUTCOMES; DISEASE; CT; PLACEMENT
AB Aim. The goal of this study was to identify physical characteristics of primary intimal tears in patients arriving to the hospital alive with acute type A aortic dissection using 64-multislice computerized tomography (MSCT) in order to determine anatomic feasibility of endovascular stent-grafting (ESG) for future treatment.
Methods. Radiology database was screened for acute type A aortic dissection since the time of acquisition of the 64-slice CT scanner and cross-referenced with surgical database. Seventeen patients met inclusion criteria. Images were reviewed for number, location, and size of intimal tears and aortic dimensions. Potential obstacles for ESG were determined.
Results. Ascending aorta (29%) and sinotubular junction (29%) were the most frequent regions where intimal tears originated. Location of intimal tears in nearly 75% of patients was inappropriate for ESG, and 94% of patients did not have sufficient proximal or distal landing zone required for secure fixation. Only 71% of patients underwent surgical aortic dissection repair after imaging and 86% of entry tears detected on MSCT were confirmed on intraoperative documentation. Only one patient would have met all technical criteria for ESG using currently available devices.
Conclusion. Location of intimal tear, aortic valve insufficiency, aortic diameter>38mm are major factors limiting use of ESG for acute type A dissection. Available stents used to treat type B aortic dissection do not address anatomic constraints present in type A aortic dissection in the majority of cases, such that development of new devices would be required.
C1 [Jaussaud, N.; Chitsaz, S.; Cambronero, N.; Azadani, A. N.; Chuter, T. A.; Tseng, E. E.] Univ Calif San Francisco, Dept Surg, Med Ctr, Div Cardiothorac Surg, San Francisco, CA USA.
[Jaussaud, N.; Chitsaz, S.; Meadows, A.; Wintermark, M.; Cambronero, N.; Azadani, A. N.; Saloner, D. A.; Chuter, T. A.; Tseng, E. E.] San Francisco VA Med Ctr, San Francisco, CA USA.
[Meadows, A.; Wintermark, M.; Saloner, D. A.] Univ Calif San Francisco, Med Ctr, Dept Radiol, San Francisco, CA USA.
RP Tseng, EE (reprint author), UCSF Med Ctr, 500 Parnassus Ave Suite 405W Box 0118, San Francisco, CA 94143 USA.
EM Elaine.Tseng@ucsfmedctr.org
RI Chitsaz, Sam/C-4586-2008;
OI Wintermark, Max/0000-0002-6726-3951
FU American Heart Association; Northern California Institute for Research
and Education; Federation Francaise de Cardiologie/Societe Frangaise de
Cardiologie, Societe Francaise de Chirurugie Thoracique et
Cardio-Vasculaire
FX This work was supported by American Heart Association, Northern
California Institute for Research and Education, and Federation
Francaise de Cardiologie/Societe Francaise de Cardiologie, Societe
Francaise de Chirurugie Thoracique et Cardio-Vasculaire.
NR 36
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Z9 5
U1 0
U2 0
PU EDIZIONI MINERVA MEDICA
PI TURIN
PA CORSO BRAMANTE 83-85 INT JOURNALS DEPT., 10126 TURIN, ITALY
SN 0021-9509
J9 J CARDIOVASC SURG
JI J. Cardiovasc. Surg.
PD JUN
PY 2013
VL 54
IS 3
BP 373
EP 381
PG 9
WC Cardiac & Cardiovascular Systems; Surgery; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology; Surgery
GA 168YF
UT WOS:000320743200008
PM 22820738
ER
PT J
AU Guddati, AK
Shaheen, S
AF Guddati, Achuta K.
Shaheen, Shagufta
TI Characterization of disease progression in ovarian cancer by utilizing
'chemograms' of ovarian cancer stem cells
SO JOURNAL OF CHEMOTHERAPY
LA English
DT Article
DE Chemogram; Ovarian cancer; Cancer stem cells; Chemotherapy
ID GENE-EXPRESSION PROFILE; MULLERIAN-INHIBITING SUBSTANCE; ACUTE
MYELOID-LEUKEMIA; LABEL-RETAINING CELLS; SIDE-POPULATION CELLS;
CISPLATIN RESISTANCE; INITIATING CELLS; PROGNOSTIC VALUE; LOW-GRADE;
STEM/PROGENITOR CELLS
AB Introduction: Ovarian cancer is one of the leading causes of death in women with cancer. First-line chemotherapy with platinum compounds and taxane compounds has been effective, but most patients develop a relapse of the disease due to drug resistance. There is growing evidence that this resistance may be due to the presence of ovarian cancer stem cells.
Discussion: Cells with properties of cancer stem cells have been isolated from the ascitic fluid of ovarian cancer patients. This subset of cells is highly tumourigenic compared to the rest of the cells in the ascitic fluid. They are known to exude harmful chemicals from their cytoplasm and have been found to be resistant to chemotherapeutic agents. This property has been utilized to purify them by fluorescence assisted cytometry to yield a subset of cells which are called 'side population'. These cells exhibit the properties of cancer stem cells and their role in disease progression is being currently investigated. The course of the disease can be potentially characterized at the cellular level by closely studying this cell population. They can also be cultured in different combinations of chemotherapeutic agents at varying concentrations to obtain 'chemograms' which are sensitivity charts. Chemotherapeutic agents which produce the most effective kill curves can then be rationally used as a second-line chemotherapy if the disease relapses. These sensitivity charts can provide insight into emerging patterns of chemoresistance and also help discover surface markers that accurately identify ovarian cancer stem cells.
Conclusion: The high rate of disease relapse in patients with ovarian cancer requires a new and different approach utilizing the sensitivity of cancer stem cells. Isolating and characterizing the resistance patterns of ovarian cancer stem cells may provide a rational approach towards an effective and individualized chemotherapeutic regimen.
C1 [Guddati, Achuta K.; Shaheen, Shagufta] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Internal Med, Boston, MA USA.
RP Guddati, AK (reprint author), Massachusetts Gen Hosp, 50 Fruit St, Boston, MA 02114 USA.
EM aguddati@partners.org
NR 90
TC 0
Z9 0
U1 0
U2 5
PU MANEY PUBLISHING
PI LEEDS
PA STE 1C, JOSEPHS WELL, HANOVER WALK, LEEDS LS3 1AB, W YORKS, ENGLAND
SN 1120-009X
J9 J CHEMOTHERAPY
JI J. Chemother.
PD JUN
PY 2013
VL 25
IS 3
BP 184
EP 191
DI 10.1179/1973947812Y.0000000058
PG 8
WC Oncology; Infectious Diseases; Pathology; Pharmacology & Pharmacy
SC Oncology; Infectious Diseases; Pathology; Pharmacology & Pharmacy
GA 152AB
UT WOS:000319500400009
PM 23783145
ER
PT J
AU McCarthy, A
Farrell, M
Hedley-Whyte, T
McGuone, D
Kavanagh, E
McNally, S
Keogan, M
Horgan, N
Lynch, T
O'Rourke, K
AF McCarthy, A.
Farrell, M.
Hedley-Whyte, T.
McGuone, D.
Kavanagh, E.
McNally, S.
Keogan, M.
Horgan, N.
Lynch, T.
O'Rourke, K.
TI Granulomatosis with polyangiitis masquerading as giant cell arteritis
SO JOURNAL OF NEUROLOGY
LA English
DT Letter
ID WEGENERS-GRANULOMATOSIS
C1 [McCarthy, A.; Lynch, T.; O'Rourke, K.] Mater Misericordiae Univ Hosp, Dublin Neurol Inst, Dublin 7, Ireland.
[Farrell, M.] Beaumont Hosp, Dept Neuropathol, Dublin 9, Ireland.
[Hedley-Whyte, T.; McGuone, D.] Massachusetts Gen Hosp, Dept Pathol, Charles S Kubik Lab Neuropathol, Boston, MA 02114 USA.
[Hedley-Whyte, T.; McGuone, D.] Harvard Univ, Sch Med, Boston, MA USA.
[Kavanagh, E.] Mater Misericordiae Univ Hosp, Dept Radiol, Dublin 7, Ireland.
[McNally, S.] Beaumont Hosp, Dept Neurosurg, Dublin 9, Ireland.
[Keogan, M.] Beaumont Hosp, Dept Immunol, Dublin 9, Ireland.
[Horgan, N.] Royal Victoria Eye & Ear Hosp, Dublin, Ireland.
RP O'Rourke, K (reprint author), Mater Misericordiae Univ Hosp, Dublin Neurol Inst, 57 Eccles St, Dublin 7, Ireland.
EM killian.orourke@gmail.com
NR 7
TC 0
Z9 0
U1 0
U2 1
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 0340-5354
J9 J NEUROL
JI J. Neurol.
PD JUN
PY 2013
VL 260
IS 6
BP 1661
EP 1663
DI 10.1007/s00415-013-6913-3
PG 3
WC Clinical Neurology
SC Neurosciences & Neurology
GA 159LJ
UT WOS:000320046600028
PM 23579235
ER
PT J
AU Serrano-Pozo, A
Muzikansky, A
Gomez-Isla, T
Growdon, JH
Betensky, RA
Frosch, MP
Hyman, BT
AF Serrano-Pozo, Alberto
Muzikansky, Alona
Gomez-Isla, Teresa
Growdon, John H.
Betensky, Rebecca A.
Frosch, Matthew P.
Hyman, Bradley T.
TI Differential Relationships of Reactive Astrocytes and Microglia to
Fibrillar Amyloid Deposits in Alzheimer Disease
SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
LA English
DT Article
DE Alzheimer disease; Amyloid plaques; Apolipoprotein E; Astrocytes;
Microglia
ID APOLIPOPROTEIN-E GENOTYPE; SENILE PLAQUES; A-BETA; CEREBRAL-CORTEX; SIZE
DISTRIBUTION; APOE GENOTYPE; PROTEIN; RECEPTOR; BRAIN; ACCUMULATION
AB Although it is clear that astrocytes and microglia cluster around dense-core amyloid plaques in Alzheimer disease (AD), whether they are primarily attracted to amyloid deposits or are just reacting to plaque-associated neuritic damage remains elusive. We postulate that astrocytes and microglia may differentially respond to fibrillar amyloid beta. Therefore, we quantified the size distribution of dense-core thioflavin-S (ThioS)-positive plaques in the temporal neocortex of 40 AD patients and the microglial and astrocyte responses in their vicinity (<= 50 mu m) and performed correlations between both measures. As expected, both astrocytes and microglia were clearly spatially associated with ThioS-positive plaques (p = 0.0001, <= 50 mu m vs >= 50 mu m from their edge), but their relationship to ThioS-positive plaque size differed: larger ThioS-positive plaques were associated with more surrounding activated microglia (p = 0.0026), but this effect was not observed with reactive astrocytes. Microglial response to dense-core plaques seems to be proportional to their size, which we postulate reflects a chemotactic effect of amyloid beta. By contrast, plaque-associated astrocytic response does not correlate with plaque size and seems to parallel the behavior of plaque-associated neuritic damage.
C1 [Serrano-Pozo, Alberto; Gomez-Isla, Teresa; Growdon, John H.; Betensky, Rebecca A.; Frosch, Matthew P.; Hyman, Bradley T.] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Massachusetts Alzheimer Dis Res Ctr, Charlestown, MA USA.
[Serrano-Pozo, Alberto; Gomez-Isla, Teresa; Growdon, John H.; Betensky, Rebecca A.; Frosch, Matthew P.; Hyman, Bradley T.] Harvard Univ, Sch Med, Charlestown, MA USA.
[Muzikansky, Alona] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA.
[Betensky, Rebecca A.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Frosch, Matthew P.] Massachusetts Gen Hosp, CS Kubik Lab Neuropathol, Boston, MA 02114 USA.
RP Hyman, BT (reprint author), Bldg 114,16th St 2009, Charlestown, MA 02129 USA.
EM bhyman@partners.org
OI SERRANO-POZO, ALBERTO/0000-0003-0899-7530
FU National Institutes of Health [P50AG05134, AG08487]; Fundacion Alfonso
Martin Escudero (Madrid, Spain)
FX This work was funded by the National Institutes of Health (grants
P50AG05134 and AG08487). Dr. Alberto Serrano-Pozo was funded by a
Research Fellowship from Fundacion Alfonso Martin Escudero (Madrid,
Spain).
NR 64
TC 31
Z9 31
U1 1
U2 12
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0022-3069
J9 J NEUROPATH EXP NEUR
JI J. Neuropathol. Exp. Neurol.
PD JUN
PY 2013
VL 72
IS 6
BP 462
EP 471
DI 10.1097/NEN.0b013e3182933788
PG 10
WC Clinical Neurology; Neurosciences; Pathology
SC Neurosciences & Neurology; Pathology
GA 151IR
UT WOS:000319454400002
PM 23656989
ER
PT J
AU Rahgozar, K
Wright, E
Carrithers, LM
Carrithers, MD
AF Rahgozar, Kusha
Wright, Erik
Carrithers, Lisette M.
Carrithers, Michael D.
TI Mediation of Protection and Recovery From Experimental Autoimmune
Encephalomyelitis by Macrophages Expressing the Human Voltage-Gated
Sodium Channel NaV1.5
SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
LA English
DT Article
DE Alternative activation; Experimental autoimmune encephalomyelitis;
Macrophage; Multiple sclerosis; Sodium channel
ID CENTRAL-NERVOUS-SYSTEM; MULTIPLE-SCLEROSIS; IMMUNE SURVEILLANCE;
ARGINASE-I; INFLAMMATION; ACTIVATION; CELLS; POLARIZATION; REGENERATION;
PLASTICITY
AB Multiple sclerosis (MS) is the most common nontraumatic cause of neurologic disability in young adults. Despite treatment, progressive tissue injury leads to accumulation of disability in many patients. Here, our goal was to develop an immune-mediated strategy to promote tissue repair and clinical recovery in an MS animal model. We previously demonstrated that a variant of the voltage-gated sodium channel NaV1.5 is expressed intracellularly in human macrophages, and that it regulates cellular signaling. This channel is not expressed in mouse macrophages, which has limited the study of its functions. To overcome this obstacle, we developed a novel transgenic mouse model (C57BL6(c-fms-hSCN5A)), in which the human macrophage NaV1.5 splice variant is expressed in vivo in mouse macrophages. These mice were protected from experimental autoimmune encephalomyelitis, the mouse model of MS. During active inflammatory disease, NaV1.5-positive macrophages were found in spinal cord lesions where they formed phagocytic cell clusters; they expressed markers of alternative activation during recovery. NaV1.5-positive macrophages that were adoptively transferred into wild-type recipients with established experimental autoimmune encephalomyelitis homed to lesions and promoted recovery. These results suggest that NaV1.5-positive macrophages enhance recovery from CNS inflammatory disease and could potentially be developed as a cell-based therapy for the treatment of MS.
C1 [Carrithers, Michael D.] Univ Wisconsin, Sch Med & Publ Hlth, William S Middleton Mem Vet Hosp, Madison, WI 53706 USA.
[Rahgozar, Kusha; Wright, Erik; Carrithers, Lisette M.; Carrithers, Michael D.] Univ Wisconsin, Dept Neurol, Sch Med & Publ Hlth, Madison, WI 53706 USA.
[Carrithers, Michael D.] Univ Wisconsin, Program Cellular & Mol Pathol, Madison, WI 53706 USA.
RP Carrithers, MD (reprint author), Univ Wisconsin, Dept Neurol, Sch Med & Publ Hlth, 1300 Univ Ave,Room 2679, Madison, WI 53706 USA.
EM carrithers@neurology.wisc.edu
FU VA Merit Award from the BLRD service; University of Wisconsin
FX This work was supported by a VA Merit Award from the BLR&D service to
Michael Carrithers and the University of Wisconsin.
NR 42
TC 4
Z9 4
U1 1
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0022-3069
J9 J NEUROPATH EXP NEUR
JI J. Neuropathol. Exp. Neurol.
PD JUN
PY 2013
VL 72
IS 6
BP 489
EP 504
DI 10.1097/NEN.0b013e318293eb08
PG 16
WC Clinical Neurology; Neurosciences; Pathology
SC Neurosciences & Neurology; Pathology
GA 151IR
UT WOS:000319454400005
PM 23656992
ER
PT J
AU Edlow, BL
Haynes, RL
Takahashi, E
Klein, JP
Cummings, P
Benner, T
Greer, DM
Greenberg, SM
Wu, O
Kinney, HC
Folkerth, RD
AF Edlow, Brian L.
Haynes, Robin L.
Takahashi, Emi
Klein, Joshua P.
Cummings, Peter
Benner, Thomas
Greer, David M.
Greenberg, Steven M.
Wu, Ona
Kinney, Hannah C.
Folkerth, Rebecca D.
TI Disconnection of the Ascending Arousal System in Traumatic Coma
SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
LA English
DT Article
DE ARAS; Ascending reticular activating system; Coma; Consciousness; HARDI;
High angular resolution diffusion imaging; TAI; TBI; Tractography;
Traumatic axonal injury; Traumatic brain injury
ID DIFFUSE AXONAL INJURY; PERSISTENT VEGETATIVE STATE; AMYLOID PRECURSOR
PROTEIN; MINIMALLY CONSCIOUS STATE; CLOSED-HEAD INJURY; BRAIN-INJURY;
ALZHEIMERS-DISEASE; NERVOUS-TISSUE; WATER RELAXATION; LATE RECOVERY
AB Traumatic coma is associated with disruption of axonal pathways throughout the brain, but the specific pathways involved in humans are incompletely understood. In this study, we used high angular resolution diffusion imaging to map the connectivity of axonal pathways that mediate the 2 critical components of consciousness-arousal and awareness-in the postmortem brain of a 62-year-old woman with acute traumatic coma and in 2 control brains. High angular resolution diffusion imaging tractography guided tissue sampling in the neuropathologic analysis. High angular resolution diffusion imaging tractography demonstrated complete disruption of white matter pathways connecting brainstem arousal nuclei to the basal forebrain and thalamic intralaminar and reticular nuclei. In contrast, hemispheric arousal pathways connecting the thalamus and basal forebrain to the cerebral cortex were only partially disrupted, as were the cortical "awareness pathways." Neuropathologic examination, which used beta-amyloid precursor protein and fractin immunomarkers, revealed axonal injury in the white matter of the brainstem and cerebral hemispheres that corresponded to sites of high angular resolution diffusion imaging tract disruption. Axonal injury was also present within the gray matter of the hypothalamus, thalamus, basal forebrain, and cerebral cortex. We propose that traumatic coma may be a subcortical disconnection syndrome related to the disconnection of specific brainstem arousal nuclei from the thalamus and basal forebrain.
C1 [Edlow, Brian L.; Klein, Joshua P.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurol, Boston, MA 02115 USA.
[Klein, Joshua P.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA.
[Folkerth, Rebecca D.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Edlow, Brian L.; Takahashi, Emi; Benner, Thomas; Wu, Ona] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA.
[Edlow, Brian L.; Greer, David M.; Greenberg, Steven M.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp,J Philip Kistler Stroke Re, Boston, MA 02115 USA.
[Takahashi, Emi] Harvard Univ, Sch Med, Div Newborn Med, Boston Childrens Hosp, Boston, MA USA.
[Takahashi, Emi] Harvard Univ, Sch Med, Fetal Neonatal Neuroimaging & Dev Sci Ctr, Boston Childrens Hosp, Boston, MA USA.
[Cummings, Peter] Off Chief Med Examiner, Boston, MA USA.
[Wu, Ona] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Greer, David M.] Yale Univ, Sch Med, Dept Neurol, Yale New Haven Hosp, New Haven, CT 06510 USA.
[Haynes, Robin L.; Kinney, Hannah C.; Folkerth, Rebecca D.] Harvard Univ, Sch Med, Dept Pathol, Boston Childrens Hosp, Boston, MA 02115 USA.
RP Edlow, BL (reprint author), Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St Lunder 650, Boston, MA 02114 USA.
EM bedlow@partners.org
RI Haynes, Robin/M-4401-2016
OI Haynes, Robin/0000-0003-4909-9585
FU National Institutes of Health [R25NS065743, R01HD20991, R21HD069001,
P41EB015896]; Center for Integration of Medicine & Innovative
Technology; Neuropathology Division, Department of Pathology; Department
of Neurology, Brigham; Women's Hospital, Boston, Mass; National Center
for Research Resources [1S10RR016811-01]
FX This work was supported by grants from the National Institutes of Health
(R25NS065743 to Brian Edlow, R01HD20991 to Hannah Kinney, R21HD069001 to
Emi Takahashi, and P41EB015896 to the Athinoula A. Martinos Center for
Biomedical Imaging) and the Center for Integration of Medicine &
Innovative Technology (to Brian Edlow). This work was also supported by
the Neuropathology Division, Department of Pathology, and the Department
of Neurology, Brigham and Women's Hospital, Boston, Mass. This work
involved the use of instrumentation supported by the National Center for
Research Resources (1S10RR016811-01 to the Athinoula A. Martinos Center
for Biomedical Imaging).
NR 87
TC 28
Z9 28
U1 0
U2 9
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0022-3069
J9 J NEUROPATH EXP NEUR
JI J. Neuropathol. Exp. Neurol.
PD JUN
PY 2013
VL 72
IS 6
BP 505
EP 523
DI 10.1097/NEN.0b013e3182945bf6
PG 19
WC Clinical Neurology; Neurosciences; Pathology
SC Neurosciences & Neurology; Pathology
GA 151IR
UT WOS:000319454400006
PM 23656993
ER
PT J
AU Suva, M
Rheinbay, E
Louis, D
Bernstein, B
AF Suva, Mario
Rheinbay, Esther
Louis, David
Bernstein, Bradley
TI Epigenetic Determinants of Cellular State in Glioblastoma
SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
LA English
DT Meeting Abstract
CT 89th Annual Meeting of the American-Association-of-Neuropathologists-Inc
CY JUN 20-23, 2013
CL Charleston, SC
SP Amer Assoc Neuropathologists Inc
C1 [Suva, Mario; Rheinbay, Esther; Louis, David; Bernstein, Bradley] Massachusetts Gen Hosp, Boston, MA 02114 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 0022-3069
J9 J NEUROPATH EXP NEUR
JI J. Neuropathol. Exp. Neurol.
PD JUN
PY 2013
VL 72
IS 6
MA 4
BP 541
EP 541
PG 1
WC Clinical Neurology; Neurosciences; Pathology
SC Neurosciences & Neurology; Pathology
GA 151IR
UT WOS:000319454400012
ER
PT J
AU Bit-Ivan, E
Weintraub, S
Hyman, B
Arnold, S
McCarty-Wood, E
Shim, H
Suh, E
Van Deerlin, V
Schneider, J
Trojanowski, J
Frosch, M
Baker, M
Rademakers, R
Mesulam, MM
Bigio, E
AF Bit-Ivan, Esther
Weintraub, Sandra
Hyman, Bradley
Arnold, Steven
McCarty-Wood, Elisabeth
Shim, HyungSub
Suh, Eunran
Van Deerlin, Vivianna
Schneider, Julie
Trojanowski, John
Frosch, Matthew
Baker, Matt
Rademakers, Rosa
Mesulam, M. Marsel
Bigio, Eileen
TI A Novel GRN Mutation: Clinicopathologic Report of Four Cases
SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
LA English
DT Meeting Abstract
CT 89th Annual Meeting of the American-Association-of-Neuropathologists-Inc
CY JUN 20-23, 2013
CL Charleston, SC
SP Amer Assoc Neuropathologists Inc
C1 [Bit-Ivan, Esther; Weintraub, Sandra; Shim, HyungSub; Mesulam, M. Marsel; Bigio, Eileen] Northwestern Univ, Feinberg Sch Med, Evanston, IL 60208 USA.
[Hyman, Bradley; Frosch, Matthew] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Arnold, Steven; McCarty-Wood, Elisabeth; Suh, Eunran; Van Deerlin, Vivianna; Trojanowski, John] Univ Penn, Philadelphia, PA 19104 USA.
[Schneider, Julie] Rush Univ, Med Ctr, Chicago, IL USA.
[Baker, Matt; Rademakers, Rosa] Mayo Clin Jacksonville, Jacksonville, FL USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0022-3069
J9 J NEUROPATH EXP NEUR
JI J. Neuropathol. Exp. Neurol.
PD JUN
PY 2013
VL 72
IS 6
MA 48
BP 552
EP 553
PG 2
WC Clinical Neurology; Neurosciences; Pathology
SC Neurosciences & Neurology; Pathology
GA 151IR
UT WOS:000319454400056
ER
PT J
AU Kinney, H
Edlow, B
Witzel, T
Wald, L
McNab, J
AF Kinney, Hannah
Edlow, Brian
Witzel, Thomas
Wald, Lawrence
McNab, Jennifer
TI Human Hippocampal-caudal Brainstem Connectivity Determined by the
Connectome: Implications for Seizure-Related, Sudden Death
SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
LA English
DT Meeting Abstract
CT 89th Annual Meeting of the American-Association-of-Neuropathologists-Inc
CY JUN 20-23, 2013
CL Charleston, SC
SP Amer Assoc Neuropathologists Inc
C1 [Kinney, Hannah; Edlow, Brian; Witzel, Thomas; Wald, Lawrence; McNab, Jennifer] Harvard Univ, Sch Med, Boston, MA USA.
[Edlow, Brian; Witzel, Thomas; Wald, Lawrence; McNab, Jennifer] Mass Gen Hosp, Boston, MA USA.
[McNab, Jennifer] Stanford Univ, Stanford, CA 94305 USA.
RI Witzel, Thomas/P-1402-2014
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0022-3069
J9 J NEUROPATH EXP NEUR
JI J. Neuropathol. Exp. Neurol.
PD JUN
PY 2013
VL 72
IS 6
MA 110
BP 570
EP 570
PG 1
WC Clinical Neurology; Neurosciences; Pathology
SC Neurosciences & Neurology; Pathology
GA 151IR
UT WOS:000319454400118
ER
PT J
AU Davidson, C
Liu, CH
Vitte, J
Giovannini, M
McClatchey, A
AF Davidson, Christian
Liu, Ching-Hui
Vitte, Jeremie
Giovannini, Marco
McClatchey, Andrea
TI Heterogeneity Dictates Therapeutic Response In Nf2-Mutant Schwann Cells
SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
LA English
DT Meeting Abstract
CT 89th Annual Meeting of the American-Association-of-Neuropathologists-Inc
CY JUN 20-23, 2013
CL Charleston, SC
SP Amer Assoc Neuropathologists Inc
C1 [Davidson, Christian; Liu, Ching-Hui; McClatchey, Andrea] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Vitte, Jeremie; Giovannini, Marco] House Ear Res Inst, Los Angeles, CA USA.
RI Vitte, Jeremie/B-9874-2017
OI Vitte, Jeremie/0000-0002-2567-7988
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0022-3069
J9 J NEUROPATH EXP NEUR
JI J. Neuropathol. Exp. Neurol.
PD JUN
PY 2013
VL 72
IS 6
MA 129
BP 575
EP 575
PG 1
WC Clinical Neurology; Neurosciences; Pathology
SC Neurosciences & Neurology; Pathology
GA 151IR
UT WOS:000319454400137
ER
PT J
AU Santagata, S
Eberlin, L
Norton, I
Ide, J
Feldman, D
Liu, XH
Wiley, J
Orringer, D
Gill, K
Dunn, I
Dias-Santagata, D
Ligon, K
Jolesz, F
Golby, A
Cooks, R
Agar, N
AF Santagata, Sandro
Eberlin, Livia
Norton, Isaiah
Ide, Jennifer
Feldman, Daniel
Liu, Xiaohui
Wiley, Joshua
Orringer, Daniel
Gill, Kristen
Dunn, Ian
Dias-Santagata, Dora
Ligon, Keith
Jolesz, Ferencc
Golby, Alexandra
Cooks, R.
Agar, Nathalie
TI Metabolite-imaging Mass Spectrometry to Guide Brain Surgery
SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
LA English
DT Meeting Abstract
CT 89th Annual Meeting of the American-Association-of-Neuropathologists-Inc
CY JUN 20-23, 2013
CL Charleston, SC
SP Amer Assoc Neuropathologists Inc
C1 [Santagata, Sandro; Feldman, Daniel; Gill, Kristen; Ligon, Keith] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Norton, Isaiah; Ide, Jennifer; Liu, Xiaohui; Orringer, Daniel; Dunn, Ian; Agar, Nathalie] Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA.
[Jolesz, Ferencc; Golby, Alexandra] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA.
[Eberlin, Livia; Wiley, Joshua; Cooks, R.] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA.
[Dias-Santagata, Dora] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
RI Cooks, R/G-1051-2015
OI Cooks, R/0000-0002-9581-9603
NR 0
TC 0
Z9 0
U1 0
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0022-3069
J9 J NEUROPATH EXP NEUR
JI J. Neuropathol. Exp. Neurol.
PD JUN
PY 2013
VL 72
IS 6
MA 131
BP 575
EP 576
PG 2
WC Clinical Neurology; Neurosciences; Pathology
SC Neurosciences & Neurology; Pathology
GA 151IR
UT WOS:000319454400139
ER
PT J
AU Holschneider, DP
Guo, YM
Wang, Z
Roch, M
Scremin, OU
AF Holschneider, Daniel P.
Guo, Yumei
Wang, Zhuo
Roch, Margareth
Scremin, Oscar U.
TI Remote Brain Network Changes after Unilateral Cortical Impact Injury and
Their Modulation by Acetylcholinesterase Inhibition
SO JOURNAL OF NEUROTRAUMA
LA English
DT Article
DE cholinergic; diaschisis; functional brain mapping; functional
connectivity; traumatic brain injury
ID CEREBRAL BLOOD-FLOW; CENTRAL-NERVOUS-SYSTEM; PARKINSONS-DISEASE;
FUNCTIONAL CONNECTIVITY; MOTOR CORTEX; BASAL GANGLIA; RESTING-STATE;
RAT-BRAIN; INDICATOR FRACTIONATION; SPATIAL NORMALIZATION
AB We explored whether cerebral cortical impact injury (CCI) effects extend beyond direct lesion sites to affect remote brain networks, and whether acetylcholinesterase (AChE) inhibition elicits discrete changes in functional activation of motor circuits following CCI. Adult male rats underwent unilateral motor-sensory CCI or sham injury. Physostigmine (AChE inhibitor) or saline were administered subcutaneously continuously via implanted minipumps (1.6 micromoles/kg/day) for 3 weeks, followed by cerebral perfusion mapping during treadmill walking using [C-14]-iodoantipyrine. Quantitative autoradiographs were analyzed by statistical parametric mapping and functional connectivity (FC) analysis. CCI resulted in functional deficits in the ipsilesional basal ganglia, with increased activation contralesionally. Recruitment was also observed, especially contralesionally, of the red nucleus, superior colliculus, pedunculopontine tegmental nucleus, thalamus (ventrolateral n., central medial n.), cerebellum, and sensory cortex. FC decreased significantly within ipsi- and contralesional motor circuits and between hemispheres, but increased between midline cerebellum and select regions of the basal ganglia within each hemisphere. Physostigmine significantly increased functional brain activation in the cerebellar thalamocortical pathway (midline cerebellum -> ventrolateral thalamus -> motor cortex), subthalamic nucleus/zona incerta, and red nucleus and bilateral sensory cortex. In conclusion, CCI resulted in increased functional recruitment of contralesional motor cortex and bilateral subcortical motor regions, as well as recruitment of the cerebellar-thalamocortical circuit and contralesional sensory cortex. This phenomenon, augmented by physostigmine, may partially compensate motor deficits. FC decreased inter-hemispherically and in negative, but not positive, intra-hemispherical FC, and it was not affected by physostigmine. Circuit-based approaches into functional brain reorganization may inform future behavioral or molecular strategies to augment targeted neurorehabilitation.
C1 [Holschneider, Daniel P.; Guo, Yumei; Wang, Zhuo] Univ So Calif, Keck Sch Med, Dept Psychiat, Los Angeles, CA 90033 USA.
[Holschneider, Daniel P.; Guo, Yumei; Wang, Zhuo] Univ So Calif, Keck Sch Med, Dept Behav Sci, Los Angeles, CA 90033 USA.
[Holschneider, Daniel P.] Univ So Calif, Dept Neurol, Los Angeles, CA 90033 USA.
[Holschneider, Daniel P.] Univ So Calif, Dept Biomed Engn, Los Angeles, CA 90033 USA.
[Holschneider, Daniel P.] Univ So Calif, Dept Cell & Neurobiol, Los Angeles, CA 90033 USA.
[Holschneider, Daniel P.; Roch, Margareth; Scremin, Oscar U.] Vet Affairs Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA USA.
[Scremin, Oscar U.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90095 USA.
RP Holschneider, DP (reprint author), Univ So Calif, Dept Psychiat & Behav Sci, 1333 San Pablo St,MCH 51A,MC9151, Los Angeles, CA 90033 USA.
EM holschne@usc.edu
FU Department of Veterans Affairs Rehabilitation Research & Development
Merit Review (VARRD) [B5089R]; VARR&D Research Career Scientist award
(OUS)
FX This study was supported by a Department of Veterans Affairs
Rehabilitation Research & Development Merit Review (VARR&D) #B5089R and
a VARR&D Research Career Scientist award (OUS).
NR 93
TC 6
Z9 6
U1 0
U2 3
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0897-7151
J9 J NEUROTRAUM
JI J. Neurotrauma
PD JUN
PY 2013
VL 30
IS 11
BP 907
EP 919
DI 10.1089/neu.2012.2657
PG 13
WC Critical Care Medicine; Clinical Neurology; Neurosciences
SC General & Internal Medicine; Neurosciences & Neurology
GA 166WD
UT WOS:000320589300002
PM 23343118
ER
PT J
AU Durazzo, TC
Abadjian, L
Kincaid, A
Bilovsky-Muniz, T
Boreta, L
Gauger, GE
AF Durazzo, Timothy C.
Abadjian, Linda
Kincaid, Adam
Bilovsky-Muniz, Tobias
Boreta, Lauren
Gauger, Grant E.
TI The Influence of Chronic Cigarette Smoking on Neurocognitive Recovery
after Mild Traumatic Brain Injury
SO JOURNAL OF NEUROTRAUMA
LA English
DT Article
DE cigarette smoking; cognition; mild traumatic brain injury; recovery
ID ALCOHOL-DEPENDENT INDIVIDUALS; OXIDATIVE STRESS; NICOTINE ADDICTION;
ANTIOXIDANT STATUS; TOBACCO-SMOKE; TEENAGE GIRLS; VITAMIN-C; IN-VITRO;
HISTORY; DAMAGE
AB The majority of the approximately 1.7 million civilians in the United States who seek emergency care for traumatic brain injury (TBI) are classified as mild (MTBI). Premorbid and comorbid conditions that commonly accompany MTBI may influence neurocognitive and functional recovery. This study assessed the influence of chronic smoking and hazardous alcohol consumption on neurocognitive recovery after MTBI. A comprehensive neurocognitive battery was administered to 25 non-smoking MTBI participants (nsMTBI), 19 smoking MTBI (sMTBI) 38 +/- 22 days (assessment point 1: AP1) and 230 +/- 36 (assessment point 2: AP2) days after injury. Twenty non-smoking light drinkers served as controls (CON). At AP1, nsMTBI and sMTBI were inferior to CON on measures of auditory-verbal learning and memory; nsMTBI performed more poorly than CON on processing speed and global neurocognition, and sMTBI performed worse than CON on working memory measures; nsMTBI were inferior to sMTBI on visuospatial memory. Over the AP1-AP2 interval, nsMTBI showed significantly greater improvement than sMTBI on measures of processing speed, visuospatial learning and memory, visuospatial skills, and global neurocognition, whereas sMTBI only showed significant improvement on executive skills. At AP2, sMTBI remained inferior to CON on auditory-verbal learning and auditory-verbal memory; there were no significant differences between nsMTBI and CON or among nsMTBI and sMTBI on any domain at AP2. Hazardous alcohol consumption was not significantly associated with change in any neurocognitive domain. For sMTBI, over the AP1-AP2 interval, greater lifetime duration of smoking and pack-years were related to significantly less improvement on multiple domains. Results suggest consideration of the effects of chronic cigarette smoking is necessary to understand the potential factors influencing neurocognitive recovery after MTBI.
C1 [Durazzo, Timothy C.; Abadjian, Linda; Bilovsky-Muniz, Tobias; Boreta, Lauren; Gauger, Grant E.] San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis, San Francisco, CA 94121 USA.
[Durazzo, Timothy C.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA.
[Kincaid, Adam; Gauger, Grant E.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA USA.
RP Durazzo, TC (reprint author), San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis 114M, 4150 Clement St, San Francisco, CA 94121 USA.
EM timothy.durazzo@ucsf.edu
FU Department of Defense [W81XWII-05-2-0094]; National Institute on Drug
Abuse [DA24136]; National Institute on Alcohol and Alcoholism [AA10788]
FX This material is the result of work supported by the Department of
Defense (W81XWII-05-2-0094 to TCD and GEG), National Institute on Drug
Abuse (DA24136 to TCD), National Institute on Alcohol and Alcoholism
(AA10788 to Dieter J. Meyerhoff), and with resources and the use of
facilities at the San Francisco Veterans Affairs Medical Center, San
Francisco, CA. We thank Dr. Geoffrey Manley and Michelle Meeker for
invaluable assistance in recruitment, Hana Lee for assistance with
neurocognitive assessment, and Dr. Dieter J. Meyerhoff for providing a
portion of the neurocognitive data for control participants. We also
wish to extend our gratitude to the study participants, who made this
research possible.
NR 74
TC 5
Z9 5
U1 0
U2 9
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0897-7151
J9 J NEUROTRAUM
JI J. Neurotrauma
PD JUN
PY 2013
VL 30
IS 11
BP 1013
EP 1022
DI 10.1089/neu.2012.2676
PG 10
WC Critical Care Medicine; Clinical Neurology; Neurosciences
SC General & Internal Medicine; Neurosciences & Neurology
GA 166WD
UT WOS:000320589300012
PM 23421788
ER
PT J
AU Dreyer, KJ
Dreyer, JL
AF Dreyer, Keith J.
Dreyer, Jonathon L.
TI Imaging Informatics: Lead, Follow, or Become Irrelevant
SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY
LA English
DT Editorial Material
C1 [Dreyer, Keith J.; Dreyer, Jonathon L.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Dreyer, KJ (reprint author), Massachusetts Gen Hosp, Dept Radiol, 25 New Chardon St, Boston, MA 02114 USA.
EM kdreyer@partners.org
NR 5
TC 3
Z9 3
U1 2
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1546-1440
J9 J AM COLL RADIOL
JI J. Am. Coll. Radiol.
PD JUN
PY 2013
VL 10
IS 6
BP 394
EP 396
DI 10.1016/j.jacr.2012.11.011
PG 3
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 168EK
UT WOS:000320688300003
PM 23735267
ER
PT J
AU Lalani, T
Couto, CA
Rosen, MP
Baker, ME
Blake, MA
Cash, BD
Fidler, JL
Greene, FL
Hindman, NM
Katz, DS
Kaur, H
Miller, FH
Qayyum, A
Small, WC
Sudakoff, GS
Yaghmai, V
Yarmish, GM
Yee, J
AF Lalani, Tasneem
Couto, Corey A.
Rosen, Max P.
Baker, Mark E.
Blake, Michael A.
Cash, Brooks D.
Fidler, Jeff L.
Greene, Frederick L.
Hindman, Nicole M.
Katz, Douglas S.
Kaur, Harmeet
Miller, Frank H.
Qayyum, Aliya
Small, William C.
Sudakoff, Gary S.
Yaghmai, Vahid
Yarmish, Gail M.
Yee, Judy
TI ACR Appropriateness Criteria Jaundice
SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY
LA English
DT Article
DE Appropriateness criteria; jaundice; cholelithiasis; cholangitis; biliary
tract; pancreatic malignancy
ID BILE-DUCT STONES; ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY;
MAGNETIC-RESONANCE CHOLANGIOPANCREATOGRAPHY; ROW COMPUTED-TOMOGRAPHY; MR
CHOLANGIOPANCREATOGRAPHY; HILAR CHOLANGIOCARCINOMA; PREOPERATIVE
EVALUATION; DIRECT CHOLANGIOGRAPHY; OBSTRUCTIVE-JAUNDICE; SUSPECTED
CHOLEDOCHOLITHIASIS
AB A fundamental consideration in the workup of a jaundiced patient is the pretest probability of mechanical obstruction. Ultrasound is the first-line modality to exclude biliary tract obstruction. When mechanical obstruction is present, additional imaging with CT or MRI can clarify etiology, define level of obstruction, stage disease, and guide intervention. When mechanical obstruction is absent, additional imaging can evaluate liver parenchyma for fat and iron deposition and help direct biopsy in cases where underlying parenchymal disease or mass is found.
Imaging techniques are reviewed for the following clinical scenarios: (1) the patient with painful jaundice, (2) the patient with painless jaundice, and (3) the patient with a nonmechanical cause for jaundice.
The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.
C1 [Lalani, Tasneem] Inland Imaging Associates, Seattle, WA USA.
[Lalani, Tasneem] Univ Washington, Seattle, WA 98195 USA.
[Couto, Corey A.] Spectrum Med Grp, South Portland, ME USA.
[Rosen, Max P.] UMass Mem Med Sch, Worcester, MA USA.
[Rosen, Max P.] UMass Sch Med, Worcester, MA USA.
[Baker, Mark E.] Cleveland Clin, Cleveland, OH 44106 USA.
[Blake, Michael A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Cash, Brooks D.] Walter Reed Natl Mil Med Ctr, Bethesda, MD USA.
[Cash, Brooks D.] Amer Gastroenterol Assoc, Bethesda, MD USA.
[Fidler, Jeff L.] Mayo Clin, Rochester, MN USA.
[Greene, Frederick L.] Carolinas Med Ctr, Charlotte, NC 28203 USA.
[Hindman, Nicole M.] NYU, Med Ctr, New York, NY 10016 USA.
[Katz, Douglas S.] Winthrop Univ Hosp, Mineola, NY 11501 USA.
[Kaur, Harmeet] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Miller, Frank H.] Northwestern Univ, Feinberg Sch Med NMH, Chicago, IL 60611 USA.
[Qayyum, Aliya; Yee, Judy] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Small, William C.] Emory Univ, Atlanta, GA 30322 USA.
[Sudakoff, Gary S.] Med Coll Wisconsin, Milwaukee, WI 53226 USA.
[Yaghmai, Vahid] Northwestern Univ, Chicago, IL 60611 USA.
[Yarmish, Gail M.] Staten Isl Univ Hosp, Staten Isl, NY USA.
RP Lalani, T (reprint author), Amer Coll Radiol, 1891 Preston White Dr, Reston, VA 20191 USA.
EM tlalani@inlandimaging.com
OI Hindman, Nicole/0000-0003-4762-8041
NR 46
TC 10
Z9 10
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1546-1440
J9 J AM COLL RADIOL
JI J. Am. Coll. Radiol.
PD JUN
PY 2013
VL 10
IS 6
BP 402
EP 409
DI 10.1016/j.jacr.2013.02.020
PG 8
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 168EK
UT WOS:000320688300008
PM 23632132
ER
PT J
AU Ghoshhajra, BB
Lee, AM
Ferencik, M
Elmariah, S
Margey, RJP
Onuma, O
Panagia, M
Abbara, S
Hoffmann, U
AF Ghoshhajra, Brian B.
Lee, Ashley M.
Ferencik, Maros
Elmariah, Sammy
Margey, Ronan J. P.
Onuma, Oyere
Panagia, Marcello
Abbara, Suhny
Hoffmann, Udo
TI Interpreting the Interpretations: The Use of Structured Reporting
Improves Referring Clinicians' Comprehension of Coronary CT Angiography
Reports
SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY
LA English
DT Article
DE Structured reporting; coronary CT angiography; referring clinicians
ID COMPUTED-TOMOGRAPHY ANGIOGRAPHY; ACUTE CHEST-PAIN; PROGNOSTIC VALUE;
ARTERY-DISEASE; COMMUNICATION; METAANALYSIS; MORTALITY; OUTCOMES
AB Background: Efficiency of coronary CT angiography (CCTA) in clinical practice depends on precise reporting and accurate result interpretation.
Objective: We sought to assess referring clinicians' understanding of patients' coronary artery disease (CAD) severity and to compare satisfactions of the free-form impression (FFI) with satisfactions of the structured impression (SI section of CCTA reports.
Materials and Methods: Fifty clinical CCTA reports from May 2011 to April 2012 were retrospectively selected (25 FFI and 25 SI), to include cases with the entire spectrum of CAD (6 categories encompassing normal, minimal, mild, moderate, severe stenosis, and occlusion). A survey containing only randomized blinded impressions was distributed to 4 cardiologists and 2 cardiac imaging specialists. Clinician interpretation was examined regarding (Q1) worst stenosis severity, (Q2) number of vessels with significant stenosis, and (Q3) the presence of nonevaluable segments. Agreement proportions and Cohen's kappa were evaluated between FFI versus SI. Satisfactions were measured with respect to content, clarity, and clinical effectiveness.
Results: Q1 agreement was excellent for both FFI and SI (by 6 categories: 80% versus 85%; P > .05; kappa: 0.87 versus 0.89; by no CAD versus nonsignificant versus significant CAD: 99% versus 97%; P > .05; kappa: 0.99 versus 0.94). Q2 agreement improved from fair to moderate (53% versus 68%; P = .04; kappa 0.31 versus 0.52). Q3 agreement was moderate (90% versus 87%; P > .05; kappa 0.57 versus 0.58). Satisfactions with impressions were high and similar for FFI and SI for clinicians.
Conclusion: Structured impressions were shown to improve result interpretation agreement from fair to moderate with regard to the number of vessels with significant stenosis.
C1 [Lee, Ashley M.] Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET CT Program, Boston, MA 02114 USA.
[Lee, Ashley M.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Lee, Ashley M.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Lee, AM (reprint author), Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET CT Program, 165 Cambridge St,Suite 400, Boston, MA 02114 USA.
EM amlee@partners.org
FU NHLBI NIH HHS [T32 HL076136]
NR 24
TC 9
Z9 9
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1546-1440
J9 J AM COLL RADIOL
JI J. Am. Coll. Radiol.
PD JUN
PY 2013
VL 10
IS 6
BP 432
EP 438
DI 10.1016/j.jacr.2012.11.012
PG 7
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 168EK
UT WOS:000320688300012
PM 23485747
ER
PT J
AU Ahmed, FS
Miller, LS
AF Ahmed, Fayeza S.
Miller, L. Stephen
TI Relationship Between Theory of Mind and Functional Independence Is
Mediated by Executive Function
SO PSYCHOLOGY AND AGING
LA English
DT Article
DE theory of mind; executive function; functional independence
ID MILD COGNITIVE IMPAIRMENT; STRANGE STORIES TEST; OLDER-ADULTS;
ASPERGER-SYNDROME; FRONTOTEMPORAL DEMENTIA; INSTRUMENTAL ACTIVITIES;
ALZHEIMERS-DISEASE; INHIBITORY CONTROL; WORKING-MEMORY; MENTAL-STATE
AB Theory of mind (ToM) is the ability to comprehend another person's perspective. Although there is much literature of ToM in children, there is a limited and somewhat inconclusive amount of studies examining ToM in a geriatric population. This study examined ToM's relationship to functional independence. Two tests of ToM, tests of executive function, and a measure of functional ability were administered to cognitively intact older adults. Results showed that 1 test of ToM (Strange Stories test) significantly accounted for variance in functional ability, whereas the other did not (Faux Pas test). In addition, Strange Stories test performance was partially driven by a verbal abstraction-based executive function: proverb interpretation. A multiple mediation model was employed to examine whether executive functions explained the relationship between the Strange Stories test and functional ability. Results showed that both the combined and individual indirect effects of the executive function measures mediated the relationship. We argue that, although components of ToM are associated with functional independence, ToM does not appear to account for additional variance in functional independence beyond executive function measures.
C1 [Ahmed, Fayeza S.; Miller, L. Stephen] Univ Georgia, Dept Psychol, Athens, GA 30602 USA.
RP Ahmed, FS (reprint author), VA Puget Sound, Seattle, WA USA.
EM ahmedfs@gmail.com
NR 95
TC 2
Z9 2
U1 8
U2 30
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0882-7974
J9 PSYCHOL AGING
JI Psychol. Aging
PD JUN
PY 2013
VL 28
IS 2
BP 293
EP 303
DI 10.1037/a0031365
PG 11
WC Gerontology; Psychology, Developmental
SC Geriatrics & Gerontology; Psychology
GA 165OB
UT WOS:000320492100001
PM 23795763
ER
PT J
AU Miao, J
Wang, SB
Park, WM
Xia, Q
Fang, XT
Torriani, MP
Wood, KB
Li, GA
AF Miao, Jun
Wang, Shaobai
Park, Won Man
Xia, Qun
Fang, Xiutong
Torriani, Martin P.
Wood, Kirkham B.
Li, Guoan
TI Segmental spinal canal volume in patients with degenerative
spondylolisthesis
SO SPINE JOURNAL
LA English
DT Article
DE Lumbar degenerative spondylolisthesis; Spinal canal volume; Kinematics;
Lumbar spine; Fluoroscopy
ID LUMBAR SPINE; ASYMPTOMATIC INDIVIDUALS; SURGICAL-TREATMENT; INTERBODY
FUSION; STENOSIS; ALIGNMENT; POSITION; TRENDS; IMAGE; ANGLE
AB BACKGROUND CONTEXT: Lumbar degenerative spondylolisthesis (DS), typically characterized by the forward slippage of the superior vertebra of a lumbar motion segment, is a common spinal pathological condition in elderly individuals. Significant deformation and volume changes of the spinal canal can occur because of the vertebral slippage, but few data have been reported on these anatomic variations in DS patients. Whether to restore normal anatomy, such as reduction of the slippage and restoration of disc height, is still not clear in surgery.
PURPOSE: This study was designed to determine the volume change of the spinal canal and detect specific anatomic factors affecting the spinal canal volume in DS patients.
STUDY DESIGN/SETTING: A case-control study.
METHODS: Nine asymptomatic volunteers (mean age 54.4) and 9 patients with L4/L5 DS (mean age 73.4) were recruited. All patients had intermittent claudication and different extent low back pain, and two patients also had leg pain. L4/L5 vertebral motion segment unit of each subject was reconstructed using three-dimensional computed tomography or magnetic resonance images in a solid modeling software. In vivo lumbar vertebral motion during functional postures (supine, standing upright, flexion, and extension) was determined using a dual fluoroscopic imaging technique. The volume of the spinal canal was measured at each functional posture. Various anatomic parameters (disc height, cross-sectional area of the canal, left-right diameter of the canal, anterior-posterior diameter of the canal, slippage, posture, intervertebral disc angle [ DA], etc.) that may potentially affect the canal volume were also measured, and their correlations with the volume change of spinal canal were analyzed. This study was funded by a 2-year, $275,000 grant from the National Institutes of Health.
RESULTS: On average, spinal canal volume was larger at supine and flexion postures than at stand and extension postures in both the DS and the asymptomatic groups. Spinal canal volume of the DS patients were significantly lower than that of the asymptomatic subjects under all the four postures (p<.05). Correlation analysis showed that spinal canal volume was strongly affected by the posterior disc height (Pearson correlation coefficient gamma(b)=0.822) and the slippage percentage (gamma(b)=-0.593) and moderately affected by the anterior disc height (gamma(b)=0.300) and the DA (gamma(b)=-0.237).
CONCLUSIONS: The volume of spinal canal is affected by multiple factors. Increased spinal canal volume at supine and flexion positions may explain the clinical observations of relief of symptoms at these postures in DS patients. The data also suggest that reduction of slipped vertebral body, decrease of DA, intervertebral distraction, and decompression could all be effective to increase the canal volume of DS patients thus to relieve clinical symptoms. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Miao, Jun; Wang, Shaobai; Park, Won Man; Fang, Xiutong; Torriani, Martin P.; Wood, Kirkham B.; Li, Guoan] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg,Bioengn Lab, Boston, MA 02114 USA.
[Miao, Jun; Xia, Qun] Tianjin Hosp, Dept Spinal Surg, Tianjin 300210, Peoples R China.
[Wang, Shaobai] MIT, Dept Mech Engn, Cambridge, MA 02139 USA.
[Park, Won Man] Kyung Hee Univ, Dept Mech Engn, Yongin 446701, South Korea.
[Fang, Xiutong] Beijing Capital Med Univ, Beijing Shijitan Hosp, Dept Orthoped, Beijing 100038, Peoples R China.
RP Li, GA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg,Bioengn Lab, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA.
EM gli1@partner.org
FU National Institutes of Health [R21AR057989]; NASS (North American Spine
Society); SRS (Scoliosis Research Society); China Scholarship Council
[2009912008]
FX This study was supported by National Institutes of Health (R21AR057989),
NASS (North American Spine Society), SRS (Scoliosis Research Society),
and China Scholarship Council (2009912008).
NR 30
TC 8
Z9 11
U1 4
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1529-9430
J9 SPINE J
JI Spine Journal
PD JUN
PY 2013
VL 13
IS 6
BP 706
EP 712
DI 10.1016/j.spinee.2013.02.017
PG 7
WC Clinical Neurology; Orthopedics
SC Neurosciences & Neurology; Orthopedics
GA 166XY
UT WOS:000320595200015
PM 23541448
ER
PT J
AU Grabowski, EF
Kushak, RI
Liu, BH
Ingelfinger, JR
AF Grabowski, Eric F.
Kushak, Rafail I.
Liu, Bohan
Ingelfinger, Julie R.
TI Shiga toxin downregulates tissue factor pathway inhibitor, modulating an
increase in the expression of functional tissue factor on endothelium
SO THROMBOSIS RESEARCH
LA English
DT Article
DE Endothelial cells; Hemolytic uremic syndrome (HUS); Shiga toxin (Stx);
Tissue factor (TF); Tissue factor pathway inhibitor (TFPI)
ID HEMOLYTIC-UREMIC SYNDROME; TUMOR-NECROSIS-FACTOR; ESCHERICHIA-COLI;
CELLS; ALPHA; PATHOGENESIS; VEROTOXIN; RECEPTOR; IDENTIFICATION;
CYTOKINES
AB Introduction: Endothelial expression of tissue factor (TF) may play a major role in (Stx)-related hemolytic uremic syndrome. We examined human umbilical vein endothelial cell (HUVEC) monolayers to determine the interaction between TF and TF pathway inhibitor (TFPI), hypothesizing that changes in TFPI modulate TF expression.
Materials and Methods: We studied 1) cell surface expression of globotriasylceramide (Gb3, the receptor for Stx) with Stx-1 (10 pM), TNF alpha (20 Ng/ml), or Stx-1 plus TNFa compared to control, 2) gene expression of TF and TFPI, 3) total cellular and cell surface antigenic TF and TFPI, 4) TFPI secretion into supernatant, and 5) factor Xa production.
Results and Conclusions: Gb3 expression, negligible with control and Stx-1 alone, increased significantly with TNFa and with Stx-1 plus TNF alpha. TF mRNA increased 1.25 +/- 0.32-fold (N = 9; p = 0.041) with Stx-1 alone vs. 2.82 +/- 0.92-fold (N = 13; p < 0.0005) with TNFa alone. However, Stx-1 plus TNFa yielded a 6.51 +/- 3.48-fold increase (N = 17; p < 0.0005). TFPI mRNA decreased with TNFa (p < 0.001) and Stx-1 plus TNF alpha (p < 0.0005). Total cellular and cell surface TF antigen increased significantly with TNF alpha, but no further with Stx-1 plus TNF alpha. Total TFPI cellular and cell surface antigen levels, and TFPI secretion decreased significantly with Stx-1 plus TNF alpha. Median factor Xa production for Stx-1 plus TNF alpha vs TNF alpha alone increased (p < 0.001) 3.24-fold. Our results indicate that a subinhibitory concentration of Stx-1 plus TNFa impairs TFPI gene expression, synthesis, cell-surface association, and secretion, leading to augmented functional TF. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Grabowski, Eric F.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Grabowski, EF (reprint author), Massachusetts Gen Hosp, Yawkey 8B,55 Fruit St, Boston, MA 02114 USA.
EM Grabowski.Eric@MGH.Harvard.edu
FU NHLBI [R01HL089332]
FX This work was supported by NHLBI R01HL089332, "Tissue Factor, Flow, and
Platelet Adhesion/Aggregation on Activated Endothelium." EG, RK, and JI
designed the experiments and wrote the paper, while EG and RK directed
and conducted the experiments. BL performed special data analysis and
Figure revision. We thank Kylee Yam, Ming Cheung, Emily Bilouris, and
Amy Skaria for expert technical help with the experiments and data
analysis. We are grateful to Brian Healy of the MGH Biostatistics Center
for help with the statistical analyses.
NR 35
TC 4
Z9 5
U1 1
U2 7
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0049-3848
J9 THROMB RES
JI Thromb. Res.
PD JUN
PY 2013
VL 131
IS 6
BP 521
EP 528
DI 10.1016/j.thromres.2013.03.006
PG 8
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 166ZI
UT WOS:000320599400022
PM 23642803
ER
PT J
AU Morinelli, TA
Lee, MH
Kendall, RT
Luttrell, LM
Walker, LP
Ullian, ME
AF Morinelli, Thomas A.
Lee, Mi-Hye
Kendall, Ryan T.
Luttrell, Louis M.
Walker, Linda P.
Ullian, Michael E.
TI Angiotensin II activates NF-kappa B through AT(1A) receptor recruitment
of beta-arrestin in cultured rat vascular smooth muscle cells
SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
LA English
DT Article
DE angiotensin receptor; NF-kappa B; beta-arrestins; signal transduction;
vascular smooth muscle cells; cyclooxygenase-2
ID NUCLEAR-LOCALIZATION SEQUENCE; SIGNAL-TRANSDUCTION; TYROSINE KINASES;
EXPRESSION; PATHWAY; CYCLOOXYGENASE-2; IDENTIFICATION; TRANSCRIPTION;
PHOSPHORYLATION; MOLECULE
AB Activation of the angiotensin type 1A receptor (AT(1A)R) in rat aorta vascular smooth muscle cells (RASMC) results in increased synthesis of the proinflammatory enzyme cyclooxygenase-2 (COX-2). We previously showed that nuclear localization of internalized AT(1A)R results in activation of transcription of the gene for COX-2, i.e., prostaglandin-endoperoxide synthase-2. Others have suggested that ANG II stimulation of COX-2 protein synthesis is mediated by NF-kappa B. The purpose of the present study was to examine the interrelationship between AT(1A)R activation, beta-arrestin recruitment, and NF-kappa B activation in the ability of ANG II to increase COX-2 protein synthesis in RASMC. In the present study we utilized RASMC, inhibitors of the NF-kappa B pathway, beta-arrestin knockdown, radioligand binding, immunoblotting, and immunofluorescence to characterize the roles of AT(1A)R internalization, NF-kappa B activation, and beta-arrestin in ANG II-induced COX-2 synthesis. Ro-106-9920 or parthenolide, agents that inhibit the initial steps of NF-kappa B activation, blocked ANG II-induced p65 NF-kappa B nuclear localization, COX-2 protein expression, beta-arrestin recruitment, and AT(1A)R internalization without inhibiting ANG II-induced p42/44 ERK activation. Curcumin, an inhibitor of NF-kappa B-induced transcription, blocked ANG II-induced COX-2 protein expression without altering AT(1A)R internalization, ANG II-induced p65 NF-kappa B nuclear localization, or p42/44 ERK activation. Small interfering RNA-induced knockdown of beta-arrestin-1 and -2 inhibited ANG II-induced p65 NF-kappa B nuclear localization. In vascular smooth muscle cells, internalization of the activated AT(1A)R mediated by beta-arrestins activates the NF-kappa B pathway, producing nuclear localization of the transcription factor and initiation of COX-2 protein synthesis, thereby linking internalization of the receptor with the NF-kappa B pathway.
C1 [Morinelli, Thomas A.; Walker, Linda P.; Ullian, Michael E.] Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA.
[Lee, Mi-Hye; Kendall, Ryan T.; Luttrell, Louis M.] Med Univ S Carolina, Dept Med, Div Endocrinol, Charleston, SC 29425 USA.
[Luttrell, Louis M.; Ullian, Michael E.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA.
RP Morinelli, TA (reprint author), Med Univ S Carolina, Dept Med, Div Nephrol, 96 Jonathan Lucas St,MSC 629, Charleston, SC 29425 USA.
EM morinelt@musc.edu
FU Dialysis Clinic, Incorporated; National Institute of Diabetes and
Digestive and Kidney Diseases [DK-055524]; National Center for Research
Resources [1S10 RR-027777-01]; Research Service of the Veterans Affairs
Medical Center of Charleston, SC
FX This project was supported by Dialysis Clinic, Incorporated, National
Institute of Diabetes and Digestive and Kidney Diseases Grant DK-055524
(L. M. Luttrell), National Center for Research Resources Grant 1S10
RR-027777-01 (FLIPR Tetra, L. M. Luttrell and T. A. Morinelli), and the
Research Service of the Veterans Affairs Medical Center of Charleston,
SC.
NR 33
TC 7
Z9 7
U1 0
U2 5
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0363-6143
J9 AM J PHYSIOL-CELL PH
JI Am. J. Physiol.-Cell Physiol.
PD JUN
PY 2013
VL 304
IS 12
BP C1176
EP C1186
DI 10.1152/ajpcell.00235.2012
PG 11
WC Cell Biology; Physiology
SC Cell Biology; Physiology
GA 164XJ
UT WOS:000320445300009
PM 23576578
ER
PT J
AU Miller, MW
Knaub, LA
Olivera-Fragoso, LF
Keller, AC
Balasubramaniam, V
Watson, PA
Reusch, JEB
AF Miller, Matthew W.
Knaub, Leslie A.
Olivera-Fragoso, Luis F.
Keller, Amy C.
Balasubramaniam, Vivek
Watson, Peter A.
Reusch, Jane E. B.
TI Nitric oxide regulates vascular adaptive mitochondrial dynamics
SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
LA English
DT Article
DE endothelial nitric oxide synthase; vascular mitochondria
ID SMOOTH-MUSCLE-CELLS; ENDOTHELIAL-CELLS; SUPEROXIDE-DISMUTASE;
DIABETES-MELLITUS; OXIDATIVE STRESS; SKELETAL-MUSCLE;
PULMONARY-HYPERTENSION; IN-VIVO; DYSFUNCTION; SYNTHASE
AB Cardiovascular disease risk factors, such as diabetes, hypertension, dyslipidemia, obesity, and physical inactivity, are all correlated with impaired endothelial nitric oxide synthase (eNOS) function and decreased nitric oxide (NO) production. NO-mediated regulation of mitochondrial biogenesis has been established in many tissues, yet the role of eNOS in vascular mitochondrial biogenesis and dynamics is unclear. We hypothesized that genetic eNOS deletion and 3-day nitric oxide synthase (NOS) inhibition in rodents would result in impaired mitochondrial biogenesis and defunct fission/fusion and autophagy profiles within the aorta. We observed a significant, eNOS expression-dependent decrease in mitochondrial electron transport chain (ETC) protein subunits from complexes I, II, III, and V in eNOS heterozygotes and eNOS null mice compared with age-matched controls. In response to NOS inhibition with N-G-nitro-L-arginine methyl ester (L-NAME) treatment in Sprague Dawley rats, significant decreases were observed in ETC protein subunits from complexes I, III, and IV as well as voltage-dependent anion channel 1. Decreased protein content of upstream regulators of mitochondrial biogenesis, cAMP response element-binding protein and peroxisome proliferator-activated receptor-gamma coactivator-1 alpha, were observed in response to 3-day L-NAME treatment. Both genetic eNOS deletion and NOS inhibition resulted in decreased manganese superoxide dismutase protein. L-NAME treatment resulted in significant changes to mitochondrial dynamic protein profiles with decreased fusion, increased fission, and minimally perturbed autophagy. In addition, L-NAME treatment blocked mitochondrial adaptation to an exercise intervention in the aorta. These results suggest that eNOS/NO play a role in basal and adaptive mitochondrial biogenesis in the vasculature and regulation of mitochondrial turnover.
C1 [Miller, Matthew W.; Knaub, Leslie A.; Keller, Amy C.; Balasubramaniam, Vivek; Watson, Peter A.; Reusch, Jane E. B.] Univ Colorado, Aurora, CO USA.
[Miller, Matthew W.; Knaub, Leslie A.; Keller, Amy C.; Watson, Peter A.; Reusch, Jane E. B.] Denver Vet Affairs Med Ctr, Denver, CO USA.
[Olivera-Fragoso, Luis F.] Univ Puerto Rico, San Juan, PR 00936 USA.
[Balasubramaniam, Vivek] Childrens Hosp, Aurora, CO USA.
RP Reusch, JEB (reprint author), Univ Colorado Denver, Div Endocrinol Diabet & Metab, Anschutz Med Campus,12801 E 17th Ave,MS8106, Aurora, CO 80045 USA.
EM jane.reusch@ucdenver.edu
FU National Heart, Lung, and Blood Institute [1R25-HL-103286-02]
FX This work was supported by National Heart, Lung, and Blood Institute
Grant 1R25-HL-103286-02.
NR 68
TC 22
Z9 24
U1 2
U2 27
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0363-6135
J9 AM J PHYSIOL-HEART C
JI Am. J. Physiol.-Heart Circul. Physiol.
PD JUN
PY 2013
VL 304
IS 12
BP H1624
EP H1633
DI 10.1152/ajpheart.00987.2012
PG 10
WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Physiology
GA 164XB
UT WOS:000320444300004
PM 23585138
ER
PT J
AU Trivedi, MH
Morris, DW
Wisniewski, SR
Lesser, I
Nierenberg, AA
Daly, E
Kurian, BT
Gaynes, BN
Balasubramani, GK
Rush, AJ
AF Trivedi, Madhukar H.
Morris, David W.
Wisniewski, Stephen R.
Lesser, Ira
Nierenberg, Andrew A.
Daly, Ella
Kurian, Benji T.
Gaynes, Bradley N.
Balasubramani, G. K.
Rush, A. John
TI Increase in Work Productivity of Depressed Individuals With Improvement
in Depressive Symptom Severity
SO AMERICAN JOURNAL OF PSYCHIATRY
LA English
DT Article
ID STAR-ASTERISK-D; SEQUENCED TREATMENT ALTERNATIVES; DIAGNOSTIC SCREENING
QUESTIONNAIRE; MEASUREMENT-BASED CARE; ILLNESS RATING-SCALE; FORM HEALTH
SURVEY; REPORT QIDS-SR; QUICK INVENTORY; PSYCHOMETRIC EVALUATION;
CLINICAL-PRACTICE
AB Objective: The authors sought to identify baseline clinical and sociodemographic characteristics associated with work productivity in depressed outpatients and to assess the effect of treatment on work productivity.
Method: Employed depressed outpatients 18-75 years old who completed the Work Productivity and Activity Impairment scale (N=1,928) were treated with citalopram (20-40 mg/day) in the Sequenced Treatment Alternatives to Relieve Depression study. For patients who did not remit after an initial adequate antidepressant trial (level 1), either a switch to sertraline, sustained-release bupropion, or extended-release venlafaxine or an augmentation with sustained-release bupropion or buspirone was provided (level 2). Participants' clinical "and demographic characteristics and treatment outcomes were analyzed for associations with baseline work productivity and change in productivity over time.
Results: Education, baseline depression severity, and melancholic, atypical, and recurrent depression subtypes were all independently associated with lower benefit to work productivity domains. During level 1 treatment, work productivity in several domains improved with reductions in depressive symptom severity. However, these findings did not hold true for level 2 outcomes; there was no significant association between treatment response and reduction in work impairment. Results were largely confirmed when multiple imputations were employed to address missing data. During this additional analysis, an association was also observed between greater impairment in work productivity and higher levels of anxious depression.
Conclusions: Patients with clinically significant reductions in symptom severity during initial treatment were more likely than nonresponders to experience significant improvements in work productivity. In contrast, patients who achieved symptom remission in second-step treatment continued to have impairment at work. Patients who have demonstrated some degree of treatment resistance are more prone to persistent impairment in occupational productivity, implying a need for additional, possibly novel, treatments.
C1 [Trivedi, Madhukar H.] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75235 USA.
Univ Pittsburgh, Grad Sch Publ Hlth, Epidemiol Data Ctr, Pittsburgh, PA USA.
Univ Calif Los Angeles, Dept Psychiat, Geffen Sch Med, Los Angeles, CA USA.
Massachusetts Gen Hosp, Clin Psychopharmacol Unit, Boston, MA 02114 USA.
Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA.
Duke Natl Univ Singapore, Grad Sch Med, Singapore, Singapore.
Johnson & Johnson Pharmaceut Res & Dev, Titusville, NJ USA.
RP Trivedi, MH (reprint author), Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75235 USA.
EM madhukar.trivedi@utsouthwestern.edu
OI Wisniewski, Stephen/0000-0002-3877-9860; Gaynes,
Bradley/0000-0002-8283-5030; Rush, Augustus/0000-0003-2004-2382
FU Abbott Laboratories; Abdi Ibrahim; Agency for Healthcare Research and
Quality; Akzo (Organon Pharmaceuticals); Alkermes; AstraZeneca; Axon
Advisors; Bristol-Myers Squibb; Cephalon; Corcept Therapeutics;
Cyberonics; Eli Lilly; Evotec; Fabre Kramer Pharmaceuticals; Forest
Pharmaceuticals; GlaxoSmithKline; Janssen Pharmaceutica Products;
Johnson Johnson PRD; Libby; Lundbeck; Mead Johnson; MedAvante;
Medtronic; Merck; National Institute on Drug Abuse; NARSAD; Naurex;
Neuronetics; NIMH; Novartis; Otsuka Pharmaceuticals; Pamlab; Parke-Davis
Pharmaceuticals; Pfizer; PgxHealth; Pharmacia Upjohn; Predix
Pharmaceuticals (Epix); Rexahn Pharmaceuticals; Roche Products;
Sepracor; Shire Development; Sierra; SK Life and Science; Solvay
Pharmaceuticals; Takeda; Transcept; Vantage Point; Wyeth-Ayerst
Laboratories; Basilea Pharmaceutica; Brain Cells; Cederroth; Dainippon
Sumitomo; EpiQ; Genaissance; Janssen Pharmaceutica; Jazz
Pharmaceuticals; Innapharma; Lichtwer Pharma; Massachusetts General
Psychiatry Academy; Janssen Pharmaceuticals; Johnson Johnson; Rexahn;
Targacept; M-3 Corporation; Robert Wood Johnson Foundation; Shire
Pharmaceuticals; Wyeth-Ayerst; Duke-National University of Singapore
Graduate Medical School; Brain Resource; Otsuka; University of Michigan;
Singapore College of Family Physicians; NIMH [N01MH90003]
FX Dr. Trivedi has received research support from or served as an adviser,
consultant, or speaker for Abbott Laboratories, Abdi Ibrahim, Agency for
Healthcare Research and Quality, Akzo (Organon Pharmaceuticals),
Alkermes, AstraZeneca, Axon Advisors, Bristol-Myers Squibb, Cephalon,
Corcept Therapeutics, Cyberonics, Eli Lilly, Evotec, Fabre Kramer
Pharmaceuticals, Forest Pharmaceuticals, GlaxoSmithKline, Janssen
Pharmaceutica Products, Johnson & Johnson PRD, Libby, Lundbeck, Mead
Johnson, MedAvante, Medtronic, Merck, National Institute on Drug Abuse,
NARSAD, Naurex, Neuronetics, NIMH, Novartis, Otsuka Pharmaceuticals,
Pamlab, Parke-Davis Pharmaceuticals, Pfizer, PgxHealth, Pharmacia &
Upjohn, Predix Pharmaceuticals (Epix), Rexahn Pharmaceuticals, Roche
Products, Sepracor, Shire Development, Sierra, SK Life and Science,
Solvay Pharmaceuticals, Takeda, Transcept, Vantage Point, and
Wyeth-Ayerst Laboratories. Dr. Wisniewski has served as a consultant for
Dey Pharmaceuticals and Venebio and has received grant support from Eli
Lilly. Dr. Lesser has received grant support from NIMH. Dr. Nierenberg
has received research support from or served as an adviser, consultant,
or speaker for AstraZeneca, Basilea Pharmaceutica, Brain Cells,
Bristol-Myers Squibb, Cederroth, Cyberonics, Dainippon Sumitomo, Eli
Lilly, EpiQ, Forest Pharmaceuticals, Genaissance, GlaxoSmithKline,
Janssen Pharmaceutica, Jazz Pharmaceuticals, Innapharma, Lichtwer
Pharma, Eli Lilly, Merck, Neuronetics, Novartis, Organon, Pamlab,
Pfizer, PGx Health, NIMH, NARSAD, Sepracor, Shire, Stanley Foundation,
Targacept, Takeda, Wyeth-Ayerst Laboratories, and Massachusetts General
Psychiatry Academy (MGHPA talks are supported through Independent
Medical Education grants from AstraZeneca, Eli Lilly, and Janssen
Pharmaceuticals); he has equity holdings (excluding mutual funds/blind
trusts) in Appliance Computing. Dr. Daly is currently a full-time
employee and stockholder of Johnson & Johnson PRD; at the time of this
study, she was an assistant professor at the University of Texas Medical
Center, Dallas, where she continues to hold a position as adjunct
faculty. Dr. Kurian has received research grant support from Evotec,
Forest Pharmaceuticals, Johnson & Johnson, Naurex, NIMH, Pfizer, Rexahn,
and Targacept. Dr. Gaynes has received research support from or served
as an adviser, consultant, or speaker for the Agency for Healthcare
Research and Quality, Bristol-Myers Squibb, GlaxoSmithKline, M-3
Corporation, NImH, Novartis, Ovation Pharmaceuticals, Pfizer, Robert
Wood Johnson Foundation, Shire Pharmaceuticals, and Wyeth-Ayerst. Dr.
Rush has received research support from Duke-National University of
Singapore Graduate Medical School and NIMH; consulting fees from Brain
Resource, Otsuka, and University of Michigan; speaking fees from
Singapore College of Family Physicians; royalties from Guilford
Publications and the University of Texas Southwestern Medical Center;
and travel support from Collegium Internationale
Neuro-PsychoPharmacologicum. The other authors report no financial
relationships with commercial interests.; Supported by NIMH contract
N01MH90003 to University of Texas Southwestern Medical Center at Dallas
(principal investigator, Dr. Rush). Medications for this trial were
provided at no cost by Bristol-Myers Squibb, Forest Laboratories,
GlaxoSmithKline, King Pharmaceuticals, Organon, Pfizer, and Wyeth.
NR 39
TC 24
Z9 24
U1 0
U2 10
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 JUN
PY 2013
VL 170
IS 6
BP 633
EP 641
DI 10.1176/appi.ajp.2012.12020250
PG 9
WC Psychiatry
SC Psychiatry
GA 159VG
UT WOS:000320074800013
PM 23558394
ER
PT J
AU Merkow, RP
Bentrem, DJ
Winchester, DP
Stewart, AK
Ko, CY
Bilimoria, KY
AF Merkow, Ryan P.
Bentrem, David J.
Winchester, David P.
Stewart, Andrew K.
Ko, Clifford Y.
Bilimoria, Karl Y.
TI Effect of Including Cancer-Specific Variables on Risk-Adjusted Hospital
Surgical Quality Comparisons
SO ANNALS OF SURGICAL ONCOLOGY
LA English
DT Article; Proceedings Paper
CT Endocrine Cancer Parallel Session at the 65th Annual Cancer Symposium of
the Society-of-Surgical-Oncology (SSO) / Presidential Plenary Session
CY MAR 21-24, 2012
CL Orlando, FL
SP Soc Surg Oncol (SSO)
ID IMPROVEMENT PROGRAM; SURGERY; MORTALITY; SAFETY; CARE
AB Quality initiatives are increasingly focusing on the quality of oncologic surgery. However, there is concern that a lack of cancer-specific variables may make risk-adjusted hospital quality comparisons inadequate. Our objective was to assess whether hospital quality rankings for cancer surgery are influenced by the addition of cancer-specific variables to the risk-adjusted models.
Patients from the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) and National Cancer Data Base (NCDB) who underwent colon or rectal resection for cancer were linked (2006-2008). Hierarchical models were developed predicting ACS NSQIP outcomes based on ACS NSQIP only vs a model using NSQIP and NCDB-derived cancer variables (e.g., stage and neoadjuvant therapy). Changes in hospital quality rankings were compared.
A total of 11,405 patients underwent colon (n = 9,678, 146 hospitals) or rectal (n = 1,727, 135 hospitals) resection for cancer (2006-2008). Hospital-level complication rates (and standard deviation) after colon surgery were 2.2 % (+/- 2.7 %) for mortality and 17.2 % (+/- 8.7 %) for serious morbidity. After rectal cancer resection, complication rates were 0.9 % (+/- 3.8 %) for mortality and 22.3 % (+/- 20.4 %) for serious morbidity. When cancer-specific variables were included in risk-adjustment, outlier agreement was very good (kappa > 0.85), and hospital odds ratio correlations were nearly identical (R > 0.98) for all outcomes assessed. Median changes in hospital rankings with the addition of the cancer-specific variables ranged from 1 to 2 after colon resection to 2-4 after rectal resection.
Addition of the available cancer-specific variables to risk-adjustment models did not affect hospital quality rankings for cancer surgery. Existing ACS NSQIP risk-adjustment variables appears to be sufficient for accurate comparisons of hospital quality.
C1 [Merkow, Ryan P.; Winchester, David P.; Stewart, Andrew K.; Ko, Clifford Y.; Bilimoria, Karl Y.] Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL USA.
[Merkow, Ryan P.; Bentrem, David J.; Bilimoria, Karl Y.] Northwestern Univ, Feinberg Sch Med, Dept Surg, Surg Outcomes & Qual Improvement Ctr, Chicago, IL 60611 USA.
[Merkow, Ryan P.; Bentrem, David J.; Bilimoria, Karl Y.] Northwestern Univ, Feinberg Sch Med, Northwestern Inst Comparat Effectiveness Res NICE, Chicago, IL 60611 USA.
[Merkow, Ryan P.] Univ Colorado Denver, Dept Surg, Aurora, CO USA.
[Ko, Clifford Y.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA.
[Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
RP Merkow, RP (reprint author), Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL USA.
EM kbilimoria@facs.org
NR 18
TC 6
Z9 6
U1 2
U2 6
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1068-9265
J9 ANN SURG ONCOL
JI Ann. Surg. Oncol.
PD JUN
PY 2013
VL 20
IS 6
BP 1766
EP 1773
DI 10.1245/s10434-013-2867-z
PG 8
WC Oncology; Surgery
SC Oncology; Surgery
GA 147LS
UT WOS:000319169100004
PM 23354565
ER
PT J
AU Win, AK
Parry, S
Parry, B
Kalady, MF
Macrae, FA
Ahnen, DJ
Young, GP
Lipton, L
Winship, I
Boussioutas, A
Young, JP
Buchanan, DD
Arnold, J
Le Marchand, L
Newcomb, PA
Haile, RW
Lindor, NM
Gallinger, S
Hopper, JL
Jenkins, MA
AF Win, Aung Ko
Parry, Susan
Parry, Bryan
Kalady, Matthew F.
Macrae, Finlay A.
Ahnen, Dennis J.
Young, Graeme P.
Lipton, Lara
Winship, Ingrid
Boussioutas, Alex
Young, Joanne P.
Buchanan, Daniel D.
Arnold, Julie
Le Marchand, Loic
Newcomb, Polly A.
Haile, Robert W.
Lindor, Noralane M.
Gallinger, Steven
Hopper, John L.
Jenkins, Mark A.
TI Risk of Metachronous Colon Cancer Following Surgery for Rectal Cancer in
Mismatch Repair Gene Mutation Carriers
SO ANNALS OF SURGICAL ONCOLOGY
LA English
DT Article
ID NONPOLYPOSIS COLORECTAL-CANCER; POUCH-ANAL ANASTOMOSIS; QUALITY-OF-LIFE;
LYNCH-SYNDROME; FAMILY
AB Despite regular surveillance colonoscopy, the metachronous colorectal cancer risk for mismatch repair (MMR) gene mutation carriers after segmental resection for colon cancer is high and total or subtotal colectomy is the preferred option. However, if the index cancer is in the rectum, management decisions are complicated by considerations of impaired bowel function. We aimed to estimate the risk of metachronous colon cancer for MMR gene mutation carriers who underwent a proctectomy for index rectal cancer.
This retrospective cohort study comprised 79 carriers of germline mutation in a MMR gene (18 MLH1, 55 MSH2, 4 MSH6, and 2 PMS2) from the Colon Cancer Family Registry who had had a proctectomy for index rectal cancer. Cumulative risks of metachronous colon cancer were calculated using the Kaplan-Meier method.
During median 9 years (range 1-32 years) of observation since the first diagnosis of rectal cancer, 21 carriers (27 %) were diagnosed with metachronous colon cancer (incidence 24.25, 95 % confidence interval [CI] 15.81-37.19 per 1,000 person-years). Cumulative risk of metachronous colon cancer was 19 % (95 % CI 9-31 %) at 10 years, 47 (95 % CI 31-68 %) at 20 years, and 69 % (95 % CI 45-89 %) at 30 years after surgical resection. The frequency of surveillance colonoscopy was 1 colonoscopy per 1.16 years (95 % CI 1.01-1.31 years). The AJCC stages of the metachronous cancers, where available, were 72 % stage I, 22 % stage II, and 6 % stage III.
Given the high metachronous colon cancer risk for MMR gene mutation carriers diagnosed with an index rectal cancer, proctocolectomy may need to be considered.
C1 [Win, Aung Ko; Hopper, John L.; Jenkins, Mark A.] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Parkville, Vic 3052, Australia.
[Parry, Susan; Arnold, Julie] Auckland City Hosp, New Zealand Familial Gastrointestinal Canc Regist, Auckland, New Zealand.
[Parry, Susan] Middlemore Hosp, Dept Gastroenterol, Auckland 6, New Zealand.
[Parry, Bryan] Auckland City Hosp, Colorectal Surg Unit, Auckland, New Zealand.
[Kalady, Matthew F.] Cleveland Clin, Inst Digest Dis, Dept Colorectal Surg, Cleveland, OH 44106 USA.
[Macrae, Finlay A.; Winship, Ingrid] Royal Melbourne Hosp, Parkville, Vic 3050, Australia.
[Ahnen, Dennis J.] Univ Colorado, Sch Med, Denver VA Med Ctr, Denver, CO 80202 USA.
[Young, Graeme P.] Flinders Univ S Australia, Flinders Ctr Innovat Canc, Adelaide, SA 5001, Australia.
[Lipton, Lara] Royal Melbourne Hosp, Ludwig Inst Canc Res, Parkville, Vic 3050, Australia.
[Winship, Ingrid] Univ Melbourne, Dept Med, Parkville, Vic 3052, Australia.
[Boussioutas, Alex] Univ Melbourne, Royal Melbourne Hosp, Dept Med, Parkville, Vic, Australia.
[Boussioutas, Alex] Peter MacCallum Canc Ctr, East Melbourne, Vic, Australia.
[Boussioutas, Alex] Univ Melbourne, Sir Peter MacCallum Dept Oncol, Parkville, Vic 3052, Australia.
[Young, Joanne P.; Buchanan, Daniel D.] Queensland Inst Med Res, Canc & Populat Studies Grp, Bancroft Ctr, Herston, Qld 4006, Australia.
[Le Marchand, Loic] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA.
[Newcomb, Polly A.] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98104 USA.
[Haile, Robert W.] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA.
[Lindor, Noralane M.] Mayo Clin Arizona, Dept Hlth Sci Res, Scottsdale, AZ USA.
[Gallinger, Steven] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada.
[Gallinger, Steven] Canc Care Ontario, Toronto, ON, Canada.
RP Win, AK (reprint author), Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Parkville, Vic 3052, Australia.
EM SParry@adhb.govt.nz
RI Jenkins, Mark/P-7803-2015;
OI Jenkins, Mark/0000-0002-8964-6160; Boussioutas,
Alex/0000-0002-8109-6897; Win, Aung Ko/0000-0002-2794-5261; Buchanan,
Daniel/0000-0003-2225-6675; Winship, Ingrid/0000-0001-8535-6003
FU National Cancer Institute, National Institutes of Health under RFA
[CA-95-011]; Picchi Brothers Foundation Cancer Council Victoria Cancer
Research Scholarship, Australia
FX This work was supported by the National Cancer Institute, National
Institutes of Health under RFA #CA-95-011 and through cooperative
agreements with members of the Colon Cancer Family Registry and
Principal Investigators. Collaborating centers include Australasian
Colorectal Cancer Family Registry (U01 CA097735), Familial Colorectal
Neoplasia Collaborative Group (U01 CA074799) [USC], Mayo Clinic
Cooperative Family Registry for Colon Cancer Studies (U01 CA074800),
Ontario Registry for Studies of Familial Colorectal Cancer (U01
CA074783), Seattle Colorectal Cancer Family Registry (U01 CA074794), and
University of Hawaii Colorectal Cancer Family Registry (U01 CA074806).
AKW is supported by the Picchi Brothers Foundation Cancer Council
Victoria Cancer Research Scholarship, Australia. MAJ is a Senior
Research Fellow and JLH is an Australia Fellow of the National Health
and Medical Research Council, Australia.
NR 24
TC 29
Z9 31
U1 0
U2 7
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1068-9265
J9 ANN SURG ONCOL
JI Ann. Surg. Oncol.
PD JUN
PY 2013
VL 20
IS 6
BP 1829
EP 1836
DI 10.1245/s10434-012-2858-5
PG 8
WC Oncology; Surgery
SC Oncology; Surgery
GA 147LS
UT WOS:000319169100011
PM 23358792
ER
PT J
AU In, H
Jiang, W
Lipsitz, SR
Neville, BA
Weeks, JC
Greenberg, CC
AF In, Haejin
Jiang, Wei
Lipsitz, Stuart R.
Neville, Bridget A.
Weeks, Jane C.
Greenberg, Caprice C.
TI Variation in the Utilization of Reconstruction Following Mastectomy in
Elderly Women
SO ANNALS OF SURGICAL ONCOLOGY
LA English
DT Article
ID LINEAR MIXED MODELS; BREAST RECONSTRUCTION; COMORBIDITY INDEX; CANCER;
SURGERY; DETERMINANTS; POPULATION; DATABASES; IMMEDIATE; REASONS
AB Regardless of their age, women who choose to undergo postmastectomy reconstruction report improved quality of life as a result. However, actual use of reconstruction decreases with increasing age. Whereas this may reflect patient preference and clinical factors, it may also represent age-based disparity.
Women aged 65 years or older who underwent mastectomy for DCIS/stage I/II breast cancer (2000-2005) were identified in the SEER-Medicare database. Overall and institutional rates of reconstruction were calculated. Characteristics of hospitals with higher and lower rates of reconstruction were compared. Pseudo-RA(2) statistics utilizing a patient-level logistic regression model estimated the relative contribution of institution and patient characteristics.
A total of 19,234 patients at 716 institutions were examined. Overall, 6 % of elderly patients received reconstruction after mastectomy. Institutional rates ranged from zero to > 40 %. Whereas 53 % of institutions performed no reconstruction on elderly patients, 5.6 % performed reconstructions on more than 20 %. Although patient characteristics (%Delta RA(2)A = 70 %), and especially age (%Delta RA(2)A = 34 %), were the primary determinants of reconstruction, institutional characteristics also explained some of the variation (%Delta RA(2)A = 16 %). This suggests that in addition to appropriate factors, including clinical characteristics and patient preferences, the use of reconstruction among older women also is influenced by the institution at which they receive care.
Variation in the likelihood of reconstruction by institution and the association with structural characteristics suggests unequal access to this critical component of breast cancer care. Increased awareness of a potential age disparity is an important first step to improve access for elderly women who are candidates and desire reconstruction.
C1 [In, Haejin; Jiang, Wei; Lipsitz, Stuart R.; Greenberg, Caprice C.] Brigham & Womens Hosp, Dept Surg, Ctr Surg & Publ Hlth, Boston, MA 02115 USA.
[In, Haejin] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA.
[In, Haejin] Univ Chicago, Med Ctr, Dept Surg, Chicago, IL 60637 USA.
[Neville, Bridget A.; Weeks, Jane C.; Greenberg, Caprice C.] Dana Farber Canc Inst, Dept Med Oncol, Ctr Outcomes & Policy Res, Boston, MA 02115 USA.
[Greenberg, Caprice C.] Univ Wisconsin, Dept Surg, Wisconsin Surg Outcomes Res Program, Madison, WI USA.
RP In, H (reprint author), Brigham & Womens Hosp, Dept Surg, Ctr Surg & Publ Hlth, 75 Francis St, Boston, MA 02115 USA.
EM Haejin.In@uchospitals.edu
RI JIANG, WEI /F-3930-2015
FU National Cancer Institute [R25 CA92203]
FX This study used the linked Surveillance, Epidemiology, and End Results
(SEER) - Medicare database. This resource has been made available to the
research community through collaborative efforts of the National Cancer
Institute (NCI) and Centers for Medicare and Medicaid Services (CMS). We
acknowledge the efforts of the Applied Research Program, NCI; the Office
of Research, Development and Information, CMS; Information Management
Services; and the SEER Program tumor registries in the creation of the
SEER-Medicare database. Haejin In was supported by a National Cancer
Institute training grant (R25 CA92203), titled "Program in Cancer
Outcomes Research Training".
NR 27
TC 17
Z9 17
U1 1
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1068-9265
J9 ANN SURG ONCOL
JI Ann. Surg. Oncol.
PD JUN
PY 2013
VL 20
IS 6
BP 1872
EP 1879
DI 10.1245/s10434-012-2821-5
PG 8
WC Oncology; Surgery
SC Oncology; Surgery
GA 147LS
UT WOS:000319169100017
PM 23263733
ER
PT J
AU Svensson, LG
Adams, DH
Bonow, RO
Kouchoukos, NT
Miller, DC
O'Gara, PT
Shahian, DM
Schaff, HV
Akins, CW
Bavaria, JE
Blackstone, EH
David, TE
Desai, ND
Dewey, TM
D'Agostino, RS
Gleason, TG
Harrington, KB
Kodali, S
Kapadia, S
Leon, MB
Lima, B
Lytle, BW
Mack, MJ
Reardon, M
Reece, TB
Reiss, GR
Roselli, EE
Smith, CR
Thourani, VH
Tuzcu, EM
Webb, J
Williams, MR
AF Svensson, Lars G.
Adams, David H.
Bonow, Robert O.
Kouchoukos, Nicholas T.
Miller, D. Craig
O'Gara, Patrick T.
Shahian, David M.
Schaff, Hartzell V.
Akins, Cary W.
Bavaria, Joseph E.
Blackstone, Eugene H.
David, Tirone E.
Desai, Nimesh D.
Dewey, Todd M.
D'Agostino, Richard S.
Gleason, Thomas G.
Harrington, Katherine B.
Kodali, Susheel
Kapadia, Samir
Leon, Martin B.
Lima, Brian
Lytle, Bruce W.
Mack, Michael J.
Reardon, Michael
Reece, T. Brett
Reiss, G. Russell
Roselli, Eric E.
Smith, Craig R.
Thourani, Vinod H.
Tuzcu, E. Murat
Webb, John
Williams, Mathew R.
CA Writing Comm Members
TI Aortic Valve and Ascending Aorta Guidelines for Management and Quality
Measures
SO ANNALS OF THORACIC SURGERY
LA English
DT Article
ID PROSTHESIS-PATIENT MISMATCH; COREVALVE REVALVING SYSTEM; VALVULAR
HEART-DISEASE; HYPOTHERMIC CIRCULATORY ARREST; LEFT-VENTRICULAR
DYSFUNCTION; HIGH-RISK PATIENTS; ANTEGRADE CEREBRAL PERFUSION; LONG-TERM
SURVIVAL; EDWARDS SAPIEN VALVE; PROSPECTIVE RANDOMIZED-TRIAL
C1 [Svensson, Lars G.] Cleveland Clin, Cleveland, OH 44195 USA.
Mt Sinai Med Ctr, New York, NY 10029 USA.
Northwestern Univ, Sch Med, Chicago, IL USA.
Cardiac Thoracic & Vasc Surg Inc, St Louis, MO USA.
Falk Cardiovasc Res Ctr, Palo Alto, CA USA.
Brigham & Womens Hosp, Boston, MA 02115 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
Mayo Clin, Rochester, MN USA.
Hosp Univ Penn, Philadelphia, PA 19104 USA.
Toronto Gen Hosp, Toronto, ON, Canada.
Inst Technol, Dallas, TX USA.
Lahey Clin Med Ctr, Burlington, MA 01803 USA.
Univ Pittsburgh, Sch Med, Pittsburgh, PA USA.
Stanford Univ, Ctr Med, Stanford, CA 94305 USA.
Columbia Univ, Med Ctr, New York Presbyterian Hosp, New York, NY USA.
Columbia Univ, Med Ctr, New York, NY USA.
Baylor Hlth Care Syst, Dallas, TX USA.
Methodist Hosp, Houston, TX 77030 USA.
Univ Colorado, Boulder, CO 80309 USA.
Dean Hlth Syst, Madison, WI USA.
Emory Univ, Sch Med, Atlanta, GA USA.
St Pauls Hosp, Vancouver, BC V6Z 1Y6, Canada.
RP Svensson, LG (reprint author), Cleveland Clin, 9500 Euclid Ave,Desk F-25 CT Surg, Cleveland, OH 44195 USA.
OI Schaff, Hartzell/0000-0003-0994-027X
NR 462
TC 37
Z9 39
U1 3
U2 17
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 JUN
PY 2013
VL 95
IS 6
SU S
BP S1
EP S66
DI 10.1016/j.athoracsur.2013.01.083
PG 66
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA 162ZD
UT WOS:000320303900001
PM 23688839
ER
PT J
AU Kanda, M
Sadakari, Y
Borges, M
Topazian, M
Farrell, J
Syngal, S
Lee, J
Kamel, I
Lennon, AM
Knight, S
Fujiwara, S
Hruban, RH
Canto, MI
Goggins, M
AF Kanda, Mitsuro
Sadakari, Yoshihiko
Borges, Michael
Topazian, Mark
Farrell, James
Syngal, Sapna
Lee, Jeffrey
Kamel, Ihab
Lennon, Anne Marie
Knight, Spencer
Fujiwara, Sho
Hruban, Ralph H.
Canto, Marcia Irene
Goggins, Michael
TI Mutant TP53 in Duodenal Samples of Pancreatic Juice From Patients With
Pancreatic Cancer or High-Grade Dysplasia
SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
LA English
DT Article
DE Tumor; Biomarker; Diagnostic; Early Detection
ID HIGH-RISK INDIVIDUALS; INTRAEPITHELIAL NEOPLASIA; K-RAS; FAMILY-HISTORY;
MUTATIONS; P53; DIAGNOSIS; PROGRESSION; CARCINOMA; LESIONS
AB BACKGROUND & AIMS: Imaging tests can identify patients with pancreatic neoplastic cysts but not microscopic dysplasia. We investigated whether mutant TP53 can be detected in duodenal samples of secretin-stimulated pancreatic juice, and whether this assay can be used to screen for high-grade dysplasia and invasive pancreatic cancer.
METHODS: We determined the prevalence of mutant TP53 in microdissected pancreatic intraepithelial neoplasias (PanINs), intraductal papillary mucinous neoplasms (IPMNs), and invasive adenocarcinomas. TP53 mutations were quantified by digital high-resolution melt-curve analysis and sequencing of secretin-stimulated pancreatic juice samples, collected from duodena of 180 subjects enrolled in Cancer of the Pancreas Screening trials; patients were enrolled because of familial and/or inherited predisposition to pancreatic cancer, or as controls.
RESULTS: TP53 mutations were identified in 9.1% of intermediate-grade IPMNs (2 of 22), 17.8% of PanIN-2 (8 of 45), 38.1% of high-grade IPMNs (8 of 21), 47.6% of PanIN-3 (10 of 21), and 75% of invasive pancreatic adenocarcinomas (15 of 20); no TP53 mutations were found in PanIN-1 lesions or low-grade IPMNs. TP53 mutations were detected in duodenal samples of pancreatic juice from 29 of 43 patients with pancreatic ductal adenocarcinoma (67.4% sensitivity; 95% confidence interval, 0.52-0.80) and 4 of 8 patients with high-grade lesions (PanIN-3 and high-grade IPMN). No TP53 mutations were identified in samples from 58 controls or 55 screened individuals without evidence of advanced lesions.
CONCLUSIONS: We detected mutant TP53 in secretin-stimulated pancreatic juice samples collected from duodena of patients with high-grade dysplasia or invasive pancreatic cancer. Tests for mutant TP53 might be developed to improve the diagnosis of and screening for pancreatic cancer and high-grade dysplasia. Clinical Trial numbers: NCT00438906 and NCT00714701.
C1 [Kanda, Mitsuro; Sadakari, Yoshihiko; Borges, Michael; Knight, Spencer; Fujiwara, Sho; Hruban, Ralph H.; Goggins, Michael] Johns Hopkins Med Inst, Dept Pathol, Sol Goldman Pancreat Canc Res Ctr, Baltimore, MD 21231 USA.
[Kamel, Ihab] Johns Hopkins Med Inst, Dept Radiol, Sol Goldman Pancreat Canc Res Ctr, Baltimore, MD 21231 USA.
[Lennon, Anne Marie] Johns Hopkins Med Inst, Dept Med, Sol Goldman Pancreat Canc Res Ctr, Baltimore, MD 21231 USA.
[Hruban, Ralph H.; Goggins, Michael] Johns Hopkins Med Inst, Dept Oncol, Sol Goldman Pancreat Canc Res Ctr, Baltimore, MD 21231 USA.
[Topazian, Mark] Mayo Clin, Rochester, MI USA.
[Farrell, James] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Lee, Jeffrey] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Syngal, Sapna] Univ Calif Los Angeles, Los Angeles, CA USA.
RP Goggins, M (reprint author), Johns Hopkins Med Inst, Dept Pathol, 1550 Orleans St, Baltimore, MD 21231 USA.
EM mgoggins@jhmi.edu
RI Kanda, Mitsuro/M-4891-2014
FU National Institutes of Health [CA62924, R01CA120432, RC2CA148376];
Lustgarten Foundation for Pancreatic Cancer Research; Jimmy V
Foundation; Michael Rolfe Foundation; Alan Graff Foundation; Karp Family
H.H. Metals, Inc; Fund for Cancer Research; Susan Wojcicki and Dennis
Troper; Michael Hooven and Susan Spies; Hugh and Rachel Victor
FX Supported by National Institutes of Health grants (CA62924, R01CA120432,
and RC2CA148376), the Lustgarten Foundation for Pancreatic Cancer
Research, the Jimmy V Foundation, Susan Wojcicki and Dennis Troper, the
Michael Rolfe Foundation, the Alan Graff Foundation, Karp Family H.H.
Metals, Inc, Fund for Cancer Research, Michael Hooven and Susan Spies,
and Hugh and Rachel Victor. Recombinant secretin was provided for this
study by ChiRhoClin, Inc, and Repligen.
NR 31
TC 35
Z9 35
U1 0
U2 5
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 JUN
PY 2013
VL 11
IS 6
BP 719
EP +
DI 10.1016/j.cgh.2012.11.016
PG 17
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 162ZZ
UT WOS:000320306400024
PM 23200980
ER
PT J
AU Yeh, DD
Velmahos, GC
AF Yeh, D. D.
Velmahos, G. C.
TI Disease-specific nutrition therapy: one size does not fit all
SO EUROPEAN JOURNAL OF TRAUMA AND EMERGENCY SURGERY
LA English
DT Review
DE Nutrition; Immunonutrition; Renal failure; Hepatic failure; Obesity;
Pulmonary failure
ID CRITICALLY-ILL PATIENTS; INTENSIVE-CARE-UNIT; SEVERE ACUTE-PANCREATITIS;
EARLY ENTERAL NUTRITION; GAMMA-LINOLENIC ACID; SYSTEMIC INFLAMMATORY
RESPONSE; TOTAL PARENTERAL-NUTRITION; SHORT-BOWEL SYNDROME; MECHANICALLY
VENTILATED PATIENTS; ACUTE LUNG INJURY
AB The delivery of adequate nutrition is an integral part of the care of the critically ill surgical patient, and the provision of nutrition may have a greater impact on outcome than many other therapies commonly employed in the treatment of certain disease states.
A review of the existing literature was performed to summarize the evidence for utilizing disease-specific nutrition in critically ill surgical patients.
Enteral nutrition, unless specifically contraindicated, is always preferable to parenteral nutrition. Methodological heterogeneity and conflicting results plague research in immunonutrition, and routine use is not currently recommended in critically ill patients.
There is currently insufficient evidence to recommend the routine initial use of most disease-specific formulas, as most patients with the disease in question will tolerate standard enteral formulas. However, the clinician should closely monitor for signs of intolerance and utilize disease-specific formulas when appropriate.
C1 [Yeh, D. D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Trauma Emergency Surg & Surg Crit C, Boston, MA 02114 USA.
[Velmahos, G. C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Chief Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA.
RP Yeh, DD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Trauma Emergency Surg & Surg Crit C, Boston 165 Cambridge St 810, Boston, MA 02114 USA.
EM Dyeh2@partners.org
NR 171
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Z9 1
U1 0
U2 10
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 1863-9933
J9 EUR J TRAUMA EMERG S
JI Eur. J. Trauma Emerg. Surg.
PD JUN
PY 2013
VL 39
IS 3
BP 215
EP 233
DI 10.1007/s00068-013-0264-8
PG 19
WC Emergency Medicine
SC Emergency Medicine
GA 159MR
UT WOS:000320050000003
PM 26815228
ER
PT J
AU Surman, CBH
Hammerness, PG
Pion, K
Faraone, SV
AF Surman, Craig B. H.
Hammerness, Paul G.
Pion, Katie
Faraone, Stephen V.
TI Do stimulants improve functioning in adults with ADHD? A review of the
literature
SO EUROPEAN NEUROPSYCHOPHARMACOLOGY
LA English
DT Review
DE Attention deficit hyperactivity isorder; ADHD; Pharmacotherapy;
Stimulant; Function; Quality of life
ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY
DISORDER; SALTS EXTENDED-RELEASE; DOUBLE-BLIND; EFFICACY; QUALITY; LIFE;
PREVALENCE; SAFETY; METHYLPHENIDATE
AB ADHD is prevalent in adulthood and stimulant pharmacotherapy is the primary treatment for uncomplicated presentations. ADHD is associated with significant functional impairment in major life roles. Measurement of the efficacy of stimulant treatment for adult ADHD therefore should include assessment of improvement in role function. A literature search was conducted to identify studies that measured change in function with stimulant treatment in adult ADHD using measures other than global clinical impression or global assessment of function ratings. Five studies were identified that met our search criteria. Evidence of functional improvement with stimulant treatment was found with the following validated self-report measures of functional wellbeing employed across these studies: the Medical Outcome Study 36-item Short Form Health Survey; ADHD Impact Module for Adults; Quality of Life Enjoyment and Satisfaction scale-Short Form; Sheehan Disability Scale, and Social Adjustment Scale-Self-Report. We conclude that investigations using self-report scales provide evidence that stimulant treatment translates into measurable improvement in daily function for adults with ADHD. Further investigation could better characterize the mediators and moderators of individual improvement, an important step towards the personalization of treatment for ADHD in adulthood. (c) 2012 Elsevier B.V. and ECNP. All rights reserved.
C1 [Surman, Craig B. H.; Hammerness, Paul G.; Pion, Katie] Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol & Adult, Boston, MA 02114 USA.
[Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY 13210 USA.
[Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY 13210 USA.
RP Surman, CBH (reprint author), Massachusetts Gen Hosp, Suite 2000,185 Alewife Brook Pkwy, Cambridge, MA 02138 USA.
EM csurman@partners.org
OI Faraone, Stephen/0000-0002-9217-3982
FU Abbott; Alza; Cephalon; Eli Lilly; Hilda and Preston Davis Foundation;
McNeil; Merck; National Institutes of Health; New River; Nordic
Naturals; Organon; Pfizer; Shire; Takeda; Ortho-McNeil Janssen; Elminda
Ltd.; GlaxoSmithKline; Johnson Johnson; Novartis; Alcobra; National
Institutes of Health (NIH); Humana/Springer; Guilford Press; Oxford
University Press
FX Dr. Surman has received research support from Abbott, Alza, Cephalon,
Eli Lilly, the Hilda and Preston Davis Foundation, McNeil, Merck,
National Institutes of Health, New River, Nordic Naturals, Organon,
Pfizer, Shire, and Takeda; has been a speaker for Janssen-Ortho, McNeil,
Novartis, and Shire; and has been a consultant/advisor for McNeil,
Shire, Somaxon and Takeda. Dr. Surman has also received honoraria from
Reed Medical Education (a logistics collaborator for the MGH Psychiatry
Academy). Commercial entities supporting the MGH Psychiatry Academy are
listed on the Academy's website, http://www.mghcme.org. Dr Surman
receives royalties from books: "ADHD in Adults: A Practical Guide to
Evaluation and Management" (Humana/Springer) and "FAST MINDS: How To
Thrive If You Have ADHD (Or Think You Might)".; In the past 2 years, Dr.
Hammerness has participated in CME activities/professional talks
supported by the following pharmaceutical companies: Ortho-McNeil
Janssen, Shire. Dr. Hammerness has served on the advisory board for
Shire. In the past 2 years, Dr. Hammerness has participated, as an
investigator/principal investigator, in research studies funded by the
following pharmaceutical companies/companies: Cephalon, Eli Lilly,
Elminda Ltd., GlaxoSmithKline, Johnson & Johnson, McNeil, Merck, New
River, Novartis, Ortho-McNeil Janssen, Pfizer, Shire, Takeda. Dr.
Hammerness has also received honoraria from Reed Medical Education (a
logistics collaborator for the MGH Psychiatry Academy). Commercial
entities supporting the MGH Psychiatry Academy are listed on the
Academy's website, http://www.mghcme.org.; In the past year, Dr. Faraone
received consulting income and research support from Shire and Alcobra
and research support from the National Institutes of Health (NIH). In
previous years, he received consulting fees or was on Advisory Boards or
participated in continuing medical education programs sponsored by:
Shire, McNeil, Janssen, Novartis, Pfizer and Eli Lilly. Dr. Faraone
receives royalties from books published by Guilford Press: Straight Talk
about Your Child's Mental Health and Genetics of Mental Disorders and
from Oxford University Press: Schizophrenia: The Facts.
NR 36
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Z9 18
U1 2
U2 23
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0924-977X
J9 EUR NEUROPSYCHOPHARM
JI Eur. Neuropsychopharmacol.
PD JUN
PY 2013
VL 23
IS 6
BP 528
EP 533
DI 10.1016/j.euroneuro.2012.02.010
PG 6
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 159US
UT WOS:000320073400011
PM 23391411
ER
PT J
AU Reardon, DA
Wucherpfennig, KW
Freeman, G
Wu, CJ
Chiocca, EA
Wen, PY
Curry, WT
Mitchell, DA
Fecci, PE
Sampson, JH
Dranoff, G
AF Reardon, David A.
Wucherpfennig, Kai W.
Freeman, Gordon
Wu, Catherine J.
Chiocca, E. Antonio
Wen, Patrick Y.
Curry, William T., Jr.
Mitchell, Duane A.
Fecci, Peter E.
Sampson, John H.
Dranoff, Glenn
TI An update on vaccine therapy and other immunotherapeutic approaches for
glioblastoma
SO EXPERT REVIEW OF VACCINES
LA English
DT Review
DE dendritic cells; glioblastoma; immunosuppression; immunotherapy; vaccine
ID GROWTH-FACTOR RECEPTOR; CENTRAL-NERVOUS-SYSTEM; REGULATORY T-CELLS;
COLONY-STIMULATING FACTOR; PULSED DENDRITIC CELLS; ANTITUMOR
IMMUNE-RESPONSES; RESISTANT PROSTATE-CANCER; PROGRESSION-FREE SURVIVAL;
HIGH-GRADE GLIOMAS; NEWLY-DIAGNOSED GLIOBLASTOMA
AB Outcome for glioblastoma (GBM), the most common primary CNS malignancy, remains poor. The overall survival benefit recently achieved with immunotherapeutics for melanoma and prostate cancer support evaluation of immunotherapies for other challenging cancers, including GBM. Much historical dogma depicting the CNS as immunoprivileged has been replaced by data demonstrating CNS immunocompetence and active interaction with the peripheral immune system. Several glioma antigens have been identified for potential immunotherapeutic exploitation. Active immunotherapy studies for GBM, supported by preclinical data, have focused on tumor lysate and synthetic antigen vaccination strategies. Results to date confirm consistent safety, including a lack of autoimmune reactivity; however, modest efficacy and variable immunogenicity have been observed. These findings underscore the need to optimize vaccination variables and to address challenges posed by systemic and local immunosuppression inherent to GBM tumors. Additional immunotherapy strategies are also in development for GBM. Future studies may consider combinatorial immunotherapy strategies with complimentary actions.
C1 [Reardon, David A.; Wen, Patrick Y.] Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA USA.
[Wucherpfennig, Kai W.; Freeman, Gordon; Wu, Catherine J.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
[Wu, Catherine J.] Dana Farber Brigham & Womens Canc Ctr, Dept Med Oncol, Boston, MA USA.
[Chiocca, E. Antonio] Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA.
[Wen, Patrick Y.] Brigham & Womens Hosp, Dept Neurol, Div Neurooncol, Boston, MA 02115 USA.
[Curry, William T., Jr.; Fecci, Peter E.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA.
[Mitchell, Duane A.; Sampson, John H.] Duke Univ, Med Ctr, Dept Surg, Div Neurosurg, Durham, NC 27710 USA.
[Dranoff, Glenn] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
[Dranoff, Glenn] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02215 USA.
[Dranoff, Glenn] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Dranoff, Glenn] Harvard Univ, Sch Med, Boston, MA USA.
RP Reardon, DA (reprint author), Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA USA.
EM david_reardon@dfci.harvard.edu
FU Celldex Therapeutics
FX JH Sampson has a consultancy, honoraria and research funding with
Celldex Therapeutics. G Freeman has a consultancy with CoStim
Pharmaceuticals and grants/patents/pending royalties with Bristol-Myers
Squibb/Medarex, Roche/Genentech, Merck, EMD-Serono,
Boehringer-Ingelheim, GlaxoSmithKline and CoStim Pharmaceuticals. DA
Mitchell and JH Sampson have grants/patents/pending royalties through
Celldex Therapeutics and Annias Immunotherapeutics. The authors have no
other relevant affiliations or financial involvement with any
organization or entity with a financial interest in or financial
conflict with the subject matter or materials discussed in the
manuscript apart from those disclosed.
NR 241
TC 26
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U1 0
U2 14
PU EXPERT REVIEWS
PI LONDON
PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB,
ENGLAND
SN 1476-0584
J9 EXPERT REV VACCINES
JI Expert Rev. Vaccines
PD JUN
PY 2013
VL 12
IS 6
BP 597
EP 615
DI 10.1586/ERV.13.41
PG 19
WC Immunology
SC Immunology
GA 161CO
UT WOS:000320169300008
PM 23750791
ER
PT J
AU Fusco, DN
Brisac, C
John, SP
Huang, YW
Chin, CR
Xie, T
Zhao, H
Jilg, N
Zhang, LL
Chevaliez, S
Wambua, D
Lin, WY
Peng, L
Chung, RT
Brass, AL
AF Fusco, Dahlene N.
Brisac, Cynthia
John, Sinu P.
Huang, Yi-Wen
Chin, Christopher R.
Xie, Tiao
Zhao, Hong
Jilg, Nikolaus
Zhang, Leiliang
Chevaliez, Stephane
Wambua, Daniel
Lin, Wenyu
Peng, Lee
Chung, Raymond T.
Brass, Abraham L.
TI A Genetic Screen Identifies Interferon-alpha Effector Genes Required to
Suppress Hepatitis C Virus Replication
SO GASTROENTEROLOGY
LA English
DT Article
DE Treatment; Gene Regulation; Virology; Mechanism
ID RAT-LIVER; PATHWAYS; PROTEINS; CELLS; EXPRESSION; COFACTOR; GAMMA
AB BACKGROUND & AIMS: Hepatitis C virus (HCV) infection is a leading cause of end-stage liver disease. Interferon-alpha (IFN alpha) is an important component of anti-HCV therapy; it up-regulates transcription of IFN-stimulated genes, many of which have been investigated for their antiviral effects. However, all of the genes required for the antiviral function of IFN alpha (IFN effector genes [IEGs]) are not known. IEGs include not only IFN-stimulated genes, but other nontranscriptionally induced genes that are required for the antiviral effect of IFN alpha. In contrast to candidate approaches based on analyses of messenger RNA (mRNA) expression, identification of IEGs requires a broad functional approach. METHODS: We performed an unbiased genome-wide small interfering RNA screen to identify IEGs that inhibit HCV. Huh7.5.1 hepatoma cells were transfected with small interfering RNAs incubated with IFN alpha and then infected with JFH1 HCV. Cells were stained using HCV core antibody, imaged, and analyzed to determine the percent infection. Candidate IEGs detected in the screen were validated and analyzed further. RESULTS: The screen identified 120 previously unreported IEGs. From these, we more fully evaluated the following: asparagine-linked glycosylation 10 homolog (yeast, alpha-1,2-glucosyltransferase); butyrylcholinesterase; dipeptidylpeptidase 4 (CD26, adenosine deaminase complexing protein 2); glucokinase (hexokinase 4) regulator; guanylate cyclase 1, soluble, beta 3; MYST histone acetyltransferase 1; protein phosphatase 3 (formerly 2B), catalytic subunit, beta isoform; peroxisomal proliferator-activated receptor-gamma-DBD-interacting protein 1; and solute carrier family 27 (fatty acid transporter), member 2; and demonstrated that they enabled IFN alpha-mediated suppression of HCV at multiple steps of its life cycle. Expression of these genes had more potent effects against flaviviridae because a subset was required for IFN alpha to suppress dengue virus but not influenza A virus. In addition, many of the host genes detected in this screen (92%) were not transcriptionally stimulated by IFN alpha; these genes represent a heretofore unknown class of non-IFN-stimulated gene IEGs. CONCLUSIONS: We performed a whole-genome loss-of-function screen to identify genes that mediate the effects of IFN alpha against human pathogenic viruses. We found that IFN alpha restricts HCV via actions of general and specific IEGs.
C1 [Fusco, Dahlene N.; Brisac, Cynthia; Jilg, Nikolaus; Chevaliez, Stephane; Wambua, Daniel; Lin, Wenyu; Peng, Lee; Chung, Raymond T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
[John, Sinu P.] NIAID, Lab Syst Biol, NIH, Bethesda, MD 20892 USA.
[Huang, Yi-Wen] Natl Taiwan Univ, Coll Med, Dept Internal Med, Taipei, Taiwan.
[Huang, Yi-Wen] Cathay Gen Hosp, Med Ctr, Hosp Liver Ctr, Taipei, Taiwan.
[Huang, Yi-Wen] Taipei Med Univ, Sch Med, Taipei, Taiwan.
[Chin, Christopher R.; Brass, Abraham L.] Univ Massachusetts, Sch Med, Dept Microbiol & Physiol Syst, Worcester, MA 01605 USA.
[Xie, Tiao] Harvard Univ, Sch Med, Image & Data Anal Core, Boston, MA USA.
[Zhao, Hong] Peking Univ, Hosp Beijing 1, Dept Infect Dis, Beijing, Peoples R China.
[Zhang, Leiliang] Chinese Acad Med Sci, Inst Pathogen Biol, MOH Key Lab Syst Biol Pathogens, Beijing 100730, Peoples R China.
[Zhang, Leiliang] Peking Union Med Coll, Beijing 100021, Peoples R China.
[Chevaliez, Stephane] Univ Paris Est, Dept Virol, Hosp Univ Henri Mondor, Creteil, France.
[John, Sinu P.; Chin, Christopher R.; Brass, Abraham L.] Ragon Inst, Charlestown, MA USA.
RP Brass, AL (reprint author), Univ Massachusetts, Sch Med, Dept Microbiol & Physiol Syst, 55 Lake Ave North, Worcester, MA 01605 USA.
EM rtchung@partners.org; abraham.brass@umassmed.edu
FU NIH [U19 AI082630, 1R01AI091786]; American Association for the Study of
Liver Disease; ANRS (French National Agency for Research on AIDS and
Viral Hepatitis); Gilead
FX This work was supported by NIH U19 AI082630 (R. T. Chung, A. L. Brass,
and D. N. Fusco). D. N. Fusco is grateful for support from a Clinical
and Translational Research Award from the American Association for the
Study of Liver Disease. S. Chevalier is grateful for support from ANRS
(French National Agency for Research on AIDS and Viral Hepatitis) and
Gilead. A. L. Brass is grateful to the Charles H. Hood Foundation, the
Bill and Melinda Gates Foundation, the Phillip T. and Susan M. Ragon
Foundation, the University of Massachusetts Medical School Center for
AIDS Research, and the NIH (1R01AI091786) for their generous support.
NR 30
TC 21
Z9 21
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 0016-5085
J9 GASTROENTEROLOGY
JI Gastroenterology
PD JUN
PY 2013
VL 144
IS 7
BP 1438
EP U210
DI 10.1053/j.gastro.2013.02.026
PG 21
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 151ZI
UT WOS:000319498500027
PM 23462180
ER
PT J
AU Gao, T
Zhou, DW
Yang, CH
Singh, T
Penzo-Mendez, A
Maddipati, R
Tzatsos, A
Bardeesy, N
Avruch, J
Stanger, BZ
AF Gao, Tao
Zhou, Dawang
Yang, Chenghua
Singh, Tarjinder
Penzo-Mendez, Alfredo
Maddipati, Ravikanth
Tzatsos, Alexandros
Bardeesy, Nabeel
Avruch, Joseph
Stanger, Ben Z.
TI BASIC AND TRANSLATIONAL-PANCREAS
SO GASTROENTEROLOGY
LA English
DT Editorial Material
DE Mouse Model; Signal Transduction; Hpo; Wts
ID HIPPO SIGNALING PATHWAY; ORGAN SIZE CONTROL; YAP; KINASES; LIVER; MST1;
PROLIFERATION; INACTIVATION; REGENERATION; MAMMALS
AB BACKGROUND & AIMS: The Hippo signaling pathway is a context-dependent regulator of cell proliferation, differentiation, and apoptosis in species ranging from Drosophila to humans. In this study, we investigated the role of the core Hippo kinases-Mst1 and Mst2-in pancreatic development and homeostasis. METHODS: We used a Cre/LoxP system to create mice with pancreas-specific disruptions in Mst1 and Mst2 (Pdx1-Cre; Mst1(-/-); Mst2(fl/fl) mice), the mammalian orthologs of Drosophila Hippo. We used a transgenic approach to overexpress Yap, the downstream mediator of Hippo signaling, in the developing pancreas of mice. RESULTS: Contrary to expectations, the pancreatic mass of Pdx1-Cre; Mst1(-/-); Mst2(fl/fl) mice was reduced compared with wild-type mice, largely because of postnatal de-differentiation of acinar cells into duct-like cells. Development of this phenotype coincided with postnatal reactivation of YAP expression. Ectopic expression of YAP during the secondary transition (a stage at which YAP is normally absent) blocked differentiation of the endocrine and exocrine compartments, whereas loss of a single Yap allele reduced acinar de-differentiation. The phenotype of Pdx1-Cre; Mst1(-/-); Mst2(fl/fl) mice recapitulated cellular and molecular changes observed during chemicalinduced pancreatitis in mice. CONCLUSIONS: The mammalian Hippo kinases, and YAP, maintain postnatal pancreatic acinar differentiation in mice.
C1 [Gao, Tao; Yang, Chenghua; Singh, Tarjinder; Penzo-Mendez, Alfredo; Maddipati, Ravikanth; Stanger, Ben Z.] Univ Penn, Perelman Sch Med, Dept Med, Div Gastroenterol, Philadelphia, PA 19104 USA.
[Stanger, Ben Z.] Univ Penn, Perelman Sch Med, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA.
[Stanger, Ben Z.] Univ Penn, Perelman Sch Med, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA.
[Gao, Tao; Yang, Chenghua; Penzo-Mendez, Alfredo; Maddipati, Ravikanth; Stanger, Ben Z.] Univ Penn, Perelman Sch Med, Abramson Canc Ctr, Philadelphia, PA 19104 USA.
[Zhou, Dawang; Tzatsos, Alexandros; Bardeesy, Nabeel; Avruch, Joseph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
[Zhou, Dawang] Xiamen Univ, Sch Life Sci, State Key Lab Stress Cell Biol, Xiamen, Fujian, Peoples R China.
RP Stanger, BZ (reprint author), Univ Penn, Perelman Sch Med, 421 Curie Blvd, Philadelphia, PA 19104 USA.
EM bstanger@exchange.upenn.edu
FU NCI NIH HHS [K99 CA158582, P30 CA016520, R01 CA133557, R01 CA136567];
NIDDK NIH HHS [P30 DK043351, DK083111, DP2 DK083111, P30 DK040561, P30
DK050306, P30-DK050306, R01 DK083355, T32 DK007066]; PHS HHS [GSE35004]
NR 23
TC 37
Z9 37
U1 1
U2 17
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0016-5085
J9 GASTROENTEROLOGY
JI Gastroenterology
PD JUN
PY 2013
VL 144
IS 7
BP 1543
EP U380
DI 10.1053/j.gastro.2013.02.037
PG 12
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 151ZI
UT WOS:000319498500037
PM 23454691
ER
PT J
AU Press, MJ
Scanlon, DP
Ryan, AM
Zhu, JS
Navathe, AS
Mittler, JN
Volpp, KG
AF Press, Matthew J.
Scanlon, Dennis P.
Ryan, Andrew M.
Zhu, Jingsan
Navathe, Amol S.
Mittler, Jessica N.
Volpp, Kevin G.
TI Limits Of Readmission Rates In Measuring Hospital Quality Suggest The
Need For Added Metrics
SO HEALTH AFFAIRS
LA English
DT Article
ID ACUTE MYOCARDIAL-INFARCTION; MORTALITY-RATES; HEALTH-CARE;
PERFORMANCE-MEASURES; TEACHING STATUS; TRIAL
AB Recent national policies use risk-standardized readmission rates to measure hospital performance on the theory that readmissions reflect dimensions of the quality of patient care that are influenced by hospitals. In this article our objective was to assess readmission rates as a hospital quality measure. First we compared quartile rankings of hospitals based on readmission rates in 2009 and 2011 to see whether hospitals maintained their relative performance or whether shifts occurred that suggested either changes in quality or random variation. Next we examined the relationship between readmission rates and several commonly used hospital quality indicators, including risk-standardized mortality rates, volume, teaching status, and process-measure performance. We found that quartile rankings fluctuated and that readmission rates for lower-performing hospitals in 2009 tended to improve by 2011, while readmission rates for higher-performing hospitals tended to worsen. Regression to the mean (a form of statistical noise) accounted for a portion of the changes in hospital performance. We also found that readmission rates were higher in teaching hospitals and were weakly correlated with the other indicators of hospital quality. Policy makers should consider augmenting the use of readmission rates with other measures of hospital performance during care transitions and should build on current efforts that take a communitywide approach to the readmissions issue.
C1 [Press, Matthew J.] Weill Cornell Med Coll, New York, NY USA.
[Scanlon, Dennis P.] Penn State Univ, Hlth Policy & Adm, Coll Hlth & Human Dev, State Coll, PA USA.
[Ryan, Andrew M.] Weill Cornell Med Coll, Div Outcomes & Effectiveness Res, New York, NY USA.
[Zhu, Jingsan] Univ Penn, Leonard Davis Inst Hlth Econ, Ctr Hlth Incent & Behav Econ, Philadelphia, PA 19104 USA.
[Navathe, Amol S.] Harvard Univ, Sch Med, Boston, MA USA.
[Navathe, Amol S.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Navathe, Amol S.] Harvard Vanguard Med Associates, Boston, MA USA.
[Mittler, Jessica N.] Penn State Univ, Dept Hlth Policy Adm, State Coll, PA USA.
[Volpp, Kevin G.] Philadelphia Vet Affairs Med Center, Philadelphia, PA USA.
RP Press, MJ (reprint author), Weill Cornell Med Coll, New York, NY USA.
EM map9069@med.cornell.edu
FU Commonwealth Fund; Department of Veterans Affairs Health Services
Research and Development (VA HSRD); Agency for Healthcare Research and
Quality [K01HS018546-01]
FX Some results from this study were presented at the Society of General
Internal Medicine Annual Meeting, Orlando, Florida, May 2012. This
project was funded by the Commonwealth Fund (principal investigator:
Dennis Scanlon). The authors thank the Department of Veterans Affairs
Health Services Research and Development (VA HSR&D) for the support of
Kevin Volpp. Matthew Press is supported in part by funds provided to him
as a Nanette Laitman Clinical Scholar in Public Health at Weill Cornell
Medical College. Andrew Ryan is supported by Grant No. K01HS018546-01
from the Agency for Healthcare Research and Quality. The authors also
thank Andrea Troxel of the University of Pennsylvania for statistical
advice.
NR 36
TC 23
Z9 23
U1 4
U2 13
PU PROJECT HOPE
PI BETHESDA
PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA
SN 0278-2715
J9 HEALTH AFFAIR
JI Health Aff.
PD JUN
PY 2013
VL 32
IS 6
BP 1083
EP 1091
DI 10.1377/hlthaff.2012.0518
PG 9
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA 163XV
UT WOS:000320372800010
PM 23733983
ER
PT J
AU Olfson, M
Marcus, SC
AF Olfson, Mark
Marcus, Steven C.
TI Decline In Placebo-Controlled Trial Results Suggests New Directions For
Comparative Effectiveness Research
SO HEALTH AFFAIRS
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIALS; ACUTE MYOCARDIAL-INFARCTION;
RESEARCH-AND-DEVELOPMENT; ACTIVE-CONTROL TRIALS; BIOMEDICAL-RESEARCH;
OUTCOMES; DESIGN; TRENDS; ISSUES; SIZE
AB The Affordable Care Act offers strong support for comparative effectiveness research, which entails comparisons among active treatments, to provide the foundation for evidence-based practice. Traditionally, a key form of research into the effectiveness of therapeutic treatments has been placebo-controlled trials, in which a specified treatment is compared to placebo. These trials feature high-contrast comparisons between treatments. Historical trends in placebo-controlled trials have been evaluated to help guide the comparative effectiveness research agenda. We investigated placebo-controlled trials reported in four leading medical journals between 1966 and 2010. We found that there was a significant decline in average effect size or average difference in efficacy (the ability to produce a desired effect) between the active treatment and placebo. On average, recently studied treatments offered only small benefits in efficacy over placebo. A decline in effect sizes in conventional placebo-controlled trials supports an increased emphasis on other avenues of research, including comparative studies on the safety, tolerability, and cost of treatments with established efficacy.
C1 [Olfson, Mark] Columbia Univ, New York, NY 10027 USA.
[Olfson, Mark] New York State Psychiat Inst & Hosp, New York, NY 10032 USA.
[Marcus, Steven C.] Univ Penn, Ctr Hlth Equity Res & Promot, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA.
[Marcus, Steven C.] Univ Penn, Sch Social Policy & Practice, Philadelphia, PA 19104 USA.
RP Olfson, M (reprint author), Columbia Univ, New York, NY 10027 USA.
EM mo49@columbia.edu
FU Agency for Healthcare Research and Quality [U19 HS021112]; New York
State Psychiatric Institute
FX Mark Olfson's work on this project was supported by the Agency for
Healthcare Research and Quality (Grant No. U19 HS021112) and the New
York State Psychiatric Institute. The sponsors had no role in the design
and conduct of the study; collection, management, analysis, and
interpretation of the data; and preparation, review, or approval of the
manuscript. No human subjects were involved in the conduct of this
study. Steven Marcus had access to all of the extracted data in the
study and takes responsibility for the accuracy of the data analysis. A
bibliography of the 315 articles selected for review is available from
Olfson on request.
NR 48
TC 7
Z9 7
U1 1
U2 5
PU PROJECT HOPE
PI BETHESDA
PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA
SN 0278-2715
J9 HEALTH AFFAIR
JI Health Aff.
PD JUN
PY 2013
VL 32
IS 6
BP 1116
EP 1125
DI 10.1377/hlthaff.2012.1353
PG 10
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA 163XV
UT WOS:000320372800014
PM 23733987
ER
PT J
AU Morrison, P
Nikolajski, C
Zickmund, S
AF Morrison, Penelope
Nikolajski, Cara
Zickmund, Susan
TI 'When we think about risk, we think about rights': community-based
organisations' staff members' perspectives on risk, resiliency and
rights in Juiz de Fora, Brazil
SO HEALTH RISK & SOCIETY
LA English
DT Article
DE public health; risk; risk perception; young people; Brazil
ID SAO-PAULO; PROTECTIVE FACTORS; SEXUAL-BEHAVIOR; DRUG-USE; HEALTH;
ADOLESCENTS; YOUTH; CHILDREN; CONFLICT; STUDENTS
AB In this article, we draw on a qualitative case study undertaken in 2008 and 2009 of staff working at community-based organisations for at-risk youth in Juiz de Fora, Brazil, to examine staff members' perspectives of adolescent health-risk behaviours and resiliency. We use these data to explore how recent policy changes in Brazil have led to a shift in the ways in which adolescent risk taking is perceived by those working in youth services, and to suggest the influence that this has had on the way in which these entities promote resiliency among the population they serve. Specifically, we argue that Brazil's Child and Adolescent Act of 1990, a policy derived from the United Nations Convention on the Rights of the Child, has been instrumental in reframing for the community-based organisations the question of adolescent health-risk behaviours into a rights-based framework and has shifted the perceptions of those working at such organisations as to who a youth at-risk' is, why young people engage in risk taking and how best to promote resiliency. This work has implications for understanding both how risk and resiliency are constructed in different social and cultural contexts and how such concepts may change over time due to shifting socio-political climates.
C1 [Morrison, Penelope] Univ Pittsburgh, RAND Univ Pittsburgh Hlth Inst, Pittsburgh, PA 15260 USA.
[Nikolajski, Cara] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA.
[Zickmund, Susan] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA.
RP Morrison, P (reprint author), Univ Pittsburgh, RAND Univ Pittsburgh Hlth Inst, Pittsburgh, PA 15260 USA.
EM morrisonpk@upmc.edu
NR 62
TC 0
Z9 0
U1 1
U2 6
PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND
SN 1369-8575
J9 HEALTH RISK SOC
JI Health Risk Soc.
PD JUN 1
PY 2013
VL 15
IS 4
BP 347
EP 362
DI 10.1080/13698575.2013.796347
PG 16
WC Public, Environmental & Occupational Health; Social Sciences, Biomedical
SC Public, Environmental & Occupational Health; Biomedical Social Sciences
GA 160DV
UT WOS:000320098100004
ER
PT J
AU Pretorius, E
Lipinski, B
AF Pretorius, E.
Lipinski, B.
TI Differences in Morphology of Fibrin Clots Induced with Thrombin and
Ferric Ions and Its Pathophysiological Consequences
SO HEART LUNG AND CIRCULATION
LA English
DT Article
DE Scanning electron microscopy; Fibrin; Ferric iron
AB The activation of blood coagulation leads to the formation of thrombin that, in turn, converts soluble plasma fibrinogen into insoluble fibrin clot. In healthy individuals, fibrin is effectively degraded; however, in prothrombotic states, proteolysis of fibrin clots are often delayed or even inhibited, and is associated with altered fibrin structure. We have previously shown that in inflammatory conditions like stroke and diabetes, this fibrin forms dense matted deposits. Although there are several factors that modify fibrin structure and delay fibrinolysis in these conditions, no mechanism is yet known to be responsible for a persistent presence of thrombi in the coronary and/or cerebral circulations. It seems, therefore, desirable to better understand this phenomenon in order to improve the effectiveness of thrombolytic therapies. Here, we show that ferric ions can activate non-enzymatic blood coagulation resulting in the formation of fibrin-like dense matted deposits (DMD) demonstrable by electron scanning microscopy (SEM). These DMDs are similar to those found in stroke and diabetes. On the basis of these findings we can conclude that the spontaneous formation of fibrin-like dense deposits in patients' blood may be a consequence of what is known as iron overload. Therefore, it is possible that inactivation of unbound iron in blood by small molecular weight chelating agents may prevent thrombotic consequences of the excessive accumulation of iron in the circulation. (c) 2012 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier Inc. All rights reserved.
C1 [Pretorius, E.] Univ Pretoria, Fac Hlth Sci, Dept Physiol, ZA-0007 Arcadia, South Africa.
[Lipinski, B.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA.
RP Pretorius, E (reprint author), Univ Pretoria, Fac Hlth Sci, Dept Physiol, Private Bag X323, ZA-0007 Arcadia, South Africa.
EM resia.pretorius@up.ac.za
OI Pretorius, Etheresia/0000-0002-9108-2384
NR 9
TC 9
Z9 9
U1 1
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1443-9506
J9 HEART LUNG CIRC
JI Heart Lung Circ.
PD JUN
PY 2013
VL 22
IS 6
BP 447
EP 449
DI 10.1016/j.hlc.2012.10.010
PG 3
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 162WA
UT WOS:000320295500008
PM 23219312
ER
PT J
AU Souter, I
Smith, KW
Williams, PL
Ehrlich, S
Hauser, R
AF Souter, I.
Smith, K. W.
Williams, P. L.
Ehrlich, S.
Hauser, R.
TI Association of urinary phthalate (UrP) metabolite concentrations with
ovarian response and early in-vitro fertilization (IVF) outcomes
SO HUMAN REPRODUCTION
LA English
DT Meeting Abstract
CT 29th Annual Meeting of the
European-Society-of-Human-Reproduction-and-Embryology (ESHRE)
CY JUL 07-10, 2013
CL London, ENGLAND
SP European Soc Human Reprod & Embryol (ESHRE)
C1 [Souter, I.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
[Smith, K. W.; Williams, P. L.; Ehrlich, S.; Hauser, R.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
RI Ehrlich , Shelley/L-6991-2015
NR 0
TC 0
Z9 0
U1 0
U2 5
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0268-1161
J9 HUM REPROD
JI Hum. Reprod.
PD JUN
PY 2013
VL 28
SU 1
BP 36
EP 37
PG 3
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 165FD
UT WOS:000320467700080
ER
PT J
AU Anderson, RA
McLaughlin, M
Woods, DC
Tilly, JL
Telfer, EE
AF Anderson, R. A.
McLaughlin, M.
Woods, D. C.
Tilly, J. L.
Telfer, E. E.
TI Evaluation of oogonial stem cells and neo-oogenesis in ovaries of girls
and women with Turner Syndrome: a pilot study
SO HUMAN REPRODUCTION
LA English
DT Meeting Abstract
CT 29th Annual Meeting of the
European-Society-of-Human-Reproduction-and-Embryology (ESHRE)
CY JUL 07-10, 2013
CL London, ENGLAND
SP European Soc Human Reprod & Embryol (ESHRE)
C1 [Anderson, R. A.] Univ Edinburgh, MRC Ctr Reprod Hlth, Edinburgh, Midlothian, Scotland.
[McLaughlin, M.; Telfer, E. E.] Univ Edinburgh, Ctr Integrat Physiol, Edinburgh, Midlothian, Scotland.
[Woods, D. C.; Tilly, J. L.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Woods, D. C.; Tilly, J. L.] Harvard Univ, Sch Med, Dept OB GYN & Reprod Biol, Boston, MA USA.
NR 0
TC 1
Z9 1
U1 1
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0268-1161
J9 HUM REPROD
JI Hum. Reprod.
PD JUN
PY 2013
VL 28
SU 1
BP 52
EP 52
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 165FD
UT WOS:000320467700115
ER
PT J
AU Sawicki, DE
Machado, MA
AF Sawicki, Darlene E.
Machado, Monique A.
TI NANDA-I With NIC NOC'n on Heaven's Door
SO INTERNATIONAL JOURNAL OF NURSING KNOWLEDGE
LA English
DT Article
DE NANDA-I; NNN; nursing language
C1 [Machado, Monique A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Machado, MA (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.
EM m.a.machado81@gmail.com
NR 0
TC 0
Z9 0
U1 0
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2047-3087
J9 INT J NURS KNOWL
JI Int. J. Nurs. Knowl.
PD JUN
PY 2013
VL 24
IS 2
BP 64
EP 65
DI 10.1111/j.2047-3095.2013.01238.x
PG 2
WC Nursing
SC Nursing
GA 161LU
UT WOS:000320195300002
PM 23556468
ER
PT J
AU Barbesino, G
Tomer, Y
AF Barbesino, Giuseppe
Tomer, Yaron
TI Clinical Utility of TSH Receptor Antibodies
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Review
ID THYROID-STIMULATING-ANTIBODY; AMIODARONE-INDUCED THYROTOXICOSIS;
GRAVES-DISEASE; THYROTROPIN RECEPTOR; NEONATAL HYPERTHYROIDISM; BLOCKING
AUTOANTIBODIES; PAINLESS THYROIDITIS; RADIOIODINE THERAPY;
POLYETHYLENE-GLYCOL; SILENT THYROIDITIS
AB Context: TSH receptor antibodies (TRAb) cause Graves' disease (GD) hyperthyroidism. Widely available TRAb measurement methods have been significantly improved recently. However, the role of TRAb measurement in the differential diagnosis of hyperthyroidism, the prediction of remission of GD hyperthyroidism, the prediction of fetal/neonatal thyrotoxicosis, and the clinical assessment of Graves' ophthalmopathy (GO) are controversial.
Evidence Acquisition: We reviewed and analyzed the literature reporting primary data on the clinical use of TRAb. We focused our analyses on clinical studies analyzing third-generation TRAb assays.
Evidence Synthesis: The performance of TRAb in the differential diagnosis of overt hyperthyroidism is excellent, with sensitivity and specificity in the upper 90%. TRAb can accurately predict short-term relapses of hyperthyroidism after a course of antithyroid drugs but are less effective in predicting long-term relapses or remissions. Pregnancies in women with GD with negative TRAb are highly unlikely to result in fetal hyperthyroidism, whereas high titers of TRAb in pregnancy require careful fetal monitoring. GD patients with GO frequently have high TRAb levels. However, there are insufficient data to use the test to predict the clinical course of GO and response to treatment.
Conclusions: Third-generation TRAb assays are suitable in the differential diagnosis of hyperthyroidism. In GD, TRAbshould be tested before deciding whether methimazole can be stopped. TRAb should be used in pregnant women with GD to assess the risk of fetal thyrotoxicosis. The use of TRAb in GO requires further studies.
C1 [Barbesino, Giuseppe] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Endocrinol,Thyroid Unit, Boston, MA 02114 USA.
[Tomer, Yaron] Mt Sinai Sch Med, Div Endocrinol, New York, NY 10029 USA.
[Tomer, Yaron] James J Peters VA Med Ctr, Bronx, NY 10468 USA.
RP Barbesino, G (reprint author), Massachusetts Gen Hosp, Thyroid Unit, Div Endocrinol, Boston, MA 02114 USA.
EM gbarbesino@partners.org
FU National Institute of Diabetes and Digestive and Kidney Diseases
[DK061659, DK067555, DK073681]
FX This work was supported by Grants DK061659, DK067555, and DK073681 from
National Institute of Diabetes and Digestive and Kidney Diseases ( to
Y.T.).
NR 86
TC 38
Z9 39
U1 3
U2 16
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0021-972X
EI 1945-7197
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD JUN
PY 2013
VL 98
IS 6
BP 2247
EP 2255
DI 10.1210/jc.2012-4309
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 155GS
UT WOS:000319736500026
PM 23539719
ER
PT J
AU Rhee, CM
Curhan, GC
Alexander, EK
Bhan, I
Brunelli, SM
AF Rhee, Connie M.
Curhan, Gary C.
Alexander, Erik K.
Bhan, Ishir
Brunelli, Steven M.
TI Subclinical Hypothyroidism and Survival: The Effects of Heart Failure
and Race
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID ALL-CAUSE MORTALITY; MILD THYROID-DYSFUNCTION; RISK-FACTORS;
CARDIOVASCULAR-DISEASE; COGNITIVE FUNCTION; REFERENCE LIMITS;
NATIONAL-HEALTH; SERUM TSH; AGE; ADULTS
AB Context: Studies examining the association between subclinical hypothyroidism and mortality have yielded conflicting results. Emerging data suggest these associations may depend upon underlying congestive heart failure (CHF) and/or race, but this has not been empirically determined.
Objective: Our objective was to examine the association between subclinical hypothyroidism and hypothyroidism overall with mortality according to pre-existing CHF and race.
Design and Participants: We examined the associations of subclinical hypothyroidism (TSH higher than assay upper limit of normal; total T-4 within reference) and hypothyroidism overall (TSH higher than assay upper limit of normal; total T-4 below lower limit of normal or within reference) with all-cause mortality among Third National Health and Nutrition Examination Survey participants stratified by CHF and race using multivariable Cox models. To confirm whether differences between strata were statistically significant, we tested for interaction on the basis of CHF (separately) and race by likelihood ratio testing.
Results: There were 14 130 (95.0%) euthyroid controls and 749 (5.0%) participants with hypothyroidism, 691 (4.6%) of whom had subclinical disease. Subclinical hypothyroidism vs euthyroidism was associated with greater mortality in those with CHF but not in those without: adjusted hazard ratios (HRs) (95% confidence intervals [CIs]) = 1.44 (1.01-2.06) and 0.97 (0.85-1.11), respectively (P interaction = .03). Similar findings were observed for hypothyroidism overall. Hypothyroidism overall vs euthyroidism was associated with greater mortality in Black participants (HR = 1.44 [95% CI = 1.03-2.03]) but not in non-Blacks (HR = 0.95 [95% CI = 0.83-1.08]) (P interaction = .03).
Conclusion: Among participants with CHF, subclinical hypothyroidism and hypothyroidism overall are associated with greater death risk. Additional studies are needed to confirm findings and explore possible mechanisms for the differential hypothyroidism-mortality association across race.
C1 [Rhee, Connie M.; Curhan, Gary C.; Brunelli, Steven M.] Brigham & Womens Hosp, Div Renal, Dept Med, Boston, MA 02115 USA.
[Curhan, Gary C.] Brigham & Womens Hosp, Channing Div Network Med, Dept Med, Boston, MA 02115 USA.
[Alexander, Erik K.] Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Dept Med, Boston, MA 02115 USA.
[Brunelli, Steven M.] Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, Dept Med, Boston, MA 02115 USA.
[Rhee, Connie M.; Curhan, Gary C.; Alexander, Erik K.; Bhan, Ishir; Brunelli, Steven M.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Curhan, Gary C.] Harvard Univ, Dept Epidemiol, Sch Publ Hlth, Boston, MA 02115 USA.
[Bhan, Ishir] Massachusetts Gen Hosp, Dept Med, Div Renal, Boston, MA 02114 USA.
[Brunelli, Steven M.] DaVita Clin Res, Minneapolis, MN 55404 USA.
RP Rhee, CM (reprint author), Brigham & Womens Hosp, 75 Francis St,MRB-4, Boston, MA 02115 USA.
EM crhee@partners.org
FU National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health [DK093201, DK079056, DK91417]; Veracyte,
Inc; Asuragen, Inc; Genzyme, Inc.
FX This work was supported by grants from the National Institute of
Diabetes and Digestive and Kidney Diseases, National Institutes of
Health: DK093201 (to C.M.R.) and DK079056 (to S.M.B.), and DK91417 (to
G.C.C.).; Disclosure Summary: C.M.R., G.C.C., and I.B. have nothing to
declare. E.K.A. receives research support from Veracyte, Inc; Asuragen,
Inc; and Genzyme, Inc. Since completing work on this study, S.M.B. has
become a full-time employee at DaVita Clinical Research.
NR 44
TC 20
Z9 21
U1 0
U2 1
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0021-972X
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD JUN
PY 2013
VL 98
IS 6
BP 2326
EP 2336
DI 10.1210/jc.2013-1039
PG 11
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 155GS
UT WOS:000319736500037
PM 23720788
ER
PT J
AU Garcia, JM
Swerdloff, R
Wang, C
Kyle, M
Kipnes, M
Biller, BMK
Cook, D
Yuen, KCJ
Bonert, V
Dobs, A
Molitch, ME
Merriam, GR
AF Garcia, J. M.
Swerdloff, R.
Wang, C.
Kyle, M.
Kipnes, M.
Biller, B. M. K.
Cook, D.
Yuen, K. C. J.
Bonert, V.
Dobs, A.
Molitch, M. E.
Merriam, G. R.
TI Macimorelin (AEZS-130)-Stimulated Growth Hormone (GH) Test: Validation
of a Novel Oral Stimulation Test for the Diagnosis of Adult GH
Deficiency
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID BODY-COMPOSITION; GHRELIN-STIMULATION; ENDOCRINE-SOCIETY; DOUBLE-BLIND;
SECRETAGOGUE; MEN; REPLACEMENT; SECRETION; SAFETY; MASS
AB Context: In the absence of panhypopituitarism and low serum IGF-I levels, the diagnosis of adult GH deficiency (AGHD) requires confirmation with a GH stimulation test. Macimorelin is a novel, orally active ghrelin mimetic that stimulates GH secretion.
Objective: The objective of the study was to determine the diagnostic efficacy and safety of macimorelin in AGHD.
Design: This was a multicenter open-label study comparing the diagnostic accuracy of oral macimorelin with that of arginine+GHRH in AGHD patients and healthy, matched controls. After 43 AGHD patients and 10 controls were tested, the GHRH analog Geref Diagnostic [GHRH(1-29) NH2] became unavailable in the United States. The study was completed by testing 10 additional AGHD patients and 38 controls with macimorelin alone.
Main Outcome Measure: Peak GH area under the receiver operating characteristic curve after macimorelin was measured.
Results: Fifty AGHD subjects and 48 controls were evaluated. Peak GH levels in AGHD patients and controls after macimorelin were 2.36 +/- 5.69 and 17.71 +/- 19.11 ng/mL, respectively (P < .0001). With macimorelin, the receiver operating characteristic analysis yielded an optimal GH cut point of 2.7 ng/mL, with82% sensitivity, 92% specificity, and13% misclassification rate. For subjects receiving both tests, macimorelin showed discrimination comparable with arginine+GHRH (area under the receiver operating characteristic curve 0.99 vs 0.94, respectively, P = .29). Obesity (body mass index > 30 kg/m(2)) was present in 58% of subjects, and peak GH levels were inversely associated with body mass index in controls (r = -0.37, P = .01). Using the separate cut points of 6.8 ng/mL for nonobese and 2.7 for obese subjects reduced the misclassification rate to 11%. Only 1 drug-related serious adverse event, an asymptomatic QT interval prolongation on the electrocardiogram, was reported.
Conclusion: Oral macimorelin is safe, convenient, and effective in diagnosing AGHD with accuracy comparable with the arginine+GHRH test.
C1 [Garcia, J. M.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA.
[Swerdloff, R.; Wang, C.] Harbor UCLA Med Ctr, Torrance, CA 90502 USA.
[Swerdloff, R.; Wang, C.] Los Angeles Biomed Res Inst, Torrance, CA 90502 USA.
[Kyle, M.] Radiant Res Inc, Chicago, IL 60654 USA.
[Kipnes, M.] DGD Clin, San Antonio, TX 78229 USA.
[Biller, B. M. K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02215 USA.
[Cook, D.; Yuen, K. C. J.] Oregon Hlth & Sci Univ, Portland, OR 97239 USA.
[Bonert, V.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA.
[Dobs, A.] Johns Hopkins Med Inst, Baltimore, MD 21205 USA.
[Molitch, M. E.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Merriam, G. R.] Univ Washington, Vet Affairs Puget Sound HCS, Seattle, WA 98108 USA.
[Merriam, G. R.] Univ Washington, Vet Affairs Puget Sound HCS, Tacoma, WA 98108 USA.
RP Garcia, JM (reprint author), Baylor Coll Med, Div Endocrinol Diabet & Metab, Michael E DeBakey Vet Affairs Med Ctr, 2002 Holcombe Blvd,Bldg 109,Room 210, Houston, TX 77030 USA.
EM jgarcia1@bcm.edu
FU Ardana Biosciences Ltd and later; AEterna Zentaris Inc; facilities and
services of the Michael E. DeBakey Veterans Affairs Medical Center and
the Veterans Affairs Puget Sound Health Care System; Ardana Biosciences
and/or terna Zentaris Inc.; Helsinn Therapeutics, Inc.; consulted for
Novo Nordisk and Pfizer; Eli Lilly; Genentech; Pfizer; consulted for
Novo Nordisk and Teva; Ipsen; Eli Lilly Co; Novo Nordisk; Novartis;
Corcept and has consulted for Novo Nordisk; Corcept
FX This work was supported by Ardana Biosciences Ltd and later by AEterna
Zentaris Inc and by the facilities and services of the Michael E.
DeBakey Veterans Affairs Medical Center and the Veterans Affairs Puget
Sound Health Care System. All investigators received research support
from Ardana Biosciences and/or terna Zentaris Inc.; J.M.G. is a
consultant for AEterna Zentaris Inc and Helsinn Therapeutics Inc and
receives research support from Helsinn Therapeutics, Inc. B.M.K.B. has
served as a consultant to terna Zentaris Inc and received research
support from and consulted for Novo Nordisk and Pfizer. K.C.J.Y. has
received research support from and consulted for Novo Nordisk and
Pfizer. G.R.M. has received research support from Eli Lilly, Genentech,
and Pfizer and consulted for Novo Nordisk and Teva. M. E. M. received
research support from Ipsen, Eli Lilly & Co, Novo Nordisk, Novartis, and
Corcept and has consulted for Novo Nordisk, Corcept, and Novartis. The
other authors have nothing to declare.
NR 27
TC 11
Z9 11
U1 1
U2 6
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0021-972X
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD JUN
PY 2013
VL 98
IS 6
BP 2422
EP 2429
DI 10.1210/jc.2013-1157
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 155GS
UT WOS:000319736500049
PM 23559086
ER
PT J
AU Yuen, KCJ
Conway, GS
Popovic, V
Merriam, GR
Bailey, T
Hamrahian, AH
Biller, BMK
Kipnes, M
Moore, JA
Humphriss, E
Bright, GM
Cleland, JL
AF Yuen, Kevin C. J.
Conway, Gerard S.
Popovic, Vera
Merriam, George R.
Bailey, Timothy
Hamrahian, Amir H.
Biller, Beverly M. K.
Kipnes, Mark
Moore, Jerome A.
Humphriss, Eric
Bright, George M.
Cleland, Jeffrey L.
TI A Long-Acting Human Growth Hormone With Delayed Clearance (VRS-317):
Results of a Double-Blind, Placebo-Controlled, Single Ascending Dose
Study in Growth Hormone-Deficient Adults
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID PREPARATION NUTROPIN DEPOT; GH DEFICIENCY; REPLACEMENT THERAPY;
PHARMACODYNAMIC CHARACTERISTICS; INSULIN SENSITIVITY;
GLUCOSE-METABOLISM; ENDOCRINE-SOCIETY; BODY-COMPOSITION; VISCERAL FAT;
HALF-LIFE
AB Background: Administration of daily recombinant human GH (rhGH) poses a considerable challenge to patient compliance. Reduced dosing frequency may improve treatment adherence and potentially overall treatment outcomes.
Objectives: This study assessed the safety and tolerability and the potential for achieving IGF-I levels within the target range in adults with GH deficiency after a single dose of the long-acting rhGH analog, VRS-317.
Design: This was a randomized, double-blind, placebo-controlled, single ascending dose study.
Patients: Fifty adults with growth hormone deficiency (mean age, 45 years) were studied in 5 treatment groups of 10 subjects each (8 active drug and 2 placebo). Setting: The study was conducted in 17 adult endocrinology centers in North America and Europe.
Main Outcome Measures: Adverse events, laboratory safety assessments, and VRS-317 pharmacokinetics and pharmacodynamics (IGF-I and IGF binding protein-3) were analyzed.
Results: At 0.80 mg/kg, VRS-317 had a mean terminal elimination half-life of 131 hours. Single VRS-317 doses of 0.05, 0.10, 0.20, 0.40, and 0.80 mg/kg (approximately equivalent to daily rhGH doses of 0.3-5.0 mu g/kg over 30 d) safely increased the amplitude and duration of IGF-I responses in a dose-dependent manner. After a single 0.80 mg/kg dose, serum IGF-I was maintained in the normal range between -1.5 and 1.5 SD values for a mean of 3 weeks. No unexpected or serious adverse events were observed.
Conclusions: The elimination half-life for VRS-317 is 30- to 60-fold longer and stimulates more durable IGF-I responses than previously studied rhGH products. Prolonged IGF-I responses do not come at the expense of overexposure to high IGF-I levels. The pharmacokinetics and pharmacodynamics combined with the observed safety profile indicate the potential for safe and effective monthly dosing.
C1 [Yuen, Kevin C. J.] Oregon Hlth & Sci Univ, Portland, OR 97239 USA.
[Conway, Gerard S.] Univ Coll London Hosp, London NW1 2BU, England.
[Popovic, Vera] Univ Belgrade, Fac Med, Belgrade 11000, Serbia.
Clin Ctr Serbia, Dept Neuroendocrinol, Belgrade 11000, Serbia.
[Merriam, George R.] Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst & Metab Endocrinol, Seattle, WA 98493 USA.
[Merriam, George R.] Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst & Metab Endocrinol, Tacoma, WA 98493 USA.
[Bailey, Timothy] AMCR Inst, Escondido, CA 92026 USA.
[Hamrahian, Amir H.] Cleveland Clin Fdn, Cleveland, OH 44195 USA.
[Biller, Beverly M. K.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA.
[Kipnes, Mark] Endocrinol Diabet & Glandular Dis Clin, San Antonio, TX 78229 USA.
[Moore, Jerome A.] Pacific Biodev LLC, Emeryville, CA 94608 USA.
[Humphriss, Eric; Bright, George M.; Cleland, Jeffrey L.] Versartis Inc, Redwood City, CA 94065 USA.
RP Bright, GM (reprint author), Versartis Inc, 275 Shoreline Dr,Suite 450, Redwood City, CA 94065 USA.
EM gbright@versartis.com
FU Versartis, Inc.; National Center for Advancing Translational Sciences at
the National Institutes of Health [UL1RR024140]; Harvard Clinical and
Translational Science Center from the National Center for Research
Resources [1 UL1 RR025758-04]
FX This work was supported by Versartis, Inc., the National Center for
Advancing Translational Sciences at the National Institutes of Health
(grant UL1RR024140 to K.C.J.Y.) and the Harvard Clinical and
Translational Science Center from the National Center for Research
Resources (grant 1 UL1 RR025758-04 to B.M.K.B.).
NR 38
TC 17
Z9 19
U1 0
U2 15
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0021-972X
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD JUN
PY 2013
VL 98
IS 6
BP 2595
EP 2603
DI 10.1210/jc.2013-1437
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 155GS
UT WOS:000319736500069
PM 23585663
ER
PT J
AU Prudente, S
Morini, E
Marselli, L
Baratta, R
Copetti, M
Mendonca, C
Andreozzi, F
Chandalia, M
Pellegrini, F
Bailetti, D
Alberico, F
Shah, H
Abate, N
Sesti, G
Frittitta, L
Marchetti, P
Doria, A
Trischitta, V
AF Prudente, Sabrina
Morini, Eleonora
Marselli, Lorella
Baratta, Roberto
Copetti, Massimiliano
Mendonca, Christine
Andreozzi, Francesco
Chandalia, Manisha
Pellegrini, Fabio
Bailetti, Diego
Alberico, Federica
Shah, Hetal
Abate, Nicola
Sesti, Giorgio
Frittitta, Lucia
Marchetti, Piero
Doria, Alessandro
Trischitta, Vincenzo
TI Joint Effect of Insulin Signaling Genes on Insulin Secretion and Glucose
Homeostasis
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID HUMAN ENDOTHELIAL-CELLS; CARDIOVASCULAR RISK; RESISTANCE; POLYMORPHISM;
RECEPTOR; VARIANT; ISLETS; TISSUE; ONSET
AB Context: Reduced insulin signaling in insulin secreting beta-cells causes defective insulin secretion and hyperglycemia in mice.
Objective: We investigated whether functional polymorphisms affecting insulin signaling (ie, ENPP1 K121Q, rs1044498; IRS1 G972R, rs1801278; and TRIB3 Q84R, rs2295490) exert a joint effect on insulin secretion and abnormal glucose homeostasis (AGH).
Design: Insulin secretion was evaluated by 1) the disposition index (DI) from an oral glucose tolerance test (OGTT) in 829 individuals; 2) insulin secretion stimulation index (SI) in islets from nondiabetic donors after glucose (n = 92) or glibenclamide (n = 89) stimulation. AGH (including impaired fasting glucose and/or impaired glucose tolerance or type 2 diabetes; T2D) was evaluated in case-control studies from the GENetics of Type 2 Diabetes in Italy and the United States (GENIUS T2D) Consortium (n = 6607).
Results: Genotype risk score, obtained by totaling individual weighted risk allele effects, was associated with the following: 1) DI (P = .005); 2) glucose and glibenclamide SI (P = .46 and P = .009); or 3) AGH(odds ratio 1.08, 95% confidence interval 1.03-1.13; P = .001). We observed an inverse relationship between genetic effect and age at AGH onset, as indicated by a linear correlation between AGH-genotype risk score odds ratios and age-at-diagnosis cutoffs (R-2 = 0.80, P < .001).
Conclusions: Functional polymorphisms affecting insulin signaling exert a joint effect on both in vivo and in vitro insulin secretion as well as on early-onset AGH. Our data provide further evidence that abnormal insulin signaling reduces beta-cell function and impairs glucose homeostasis.
C1 [Prudente, Sabrina; Bailetti, Diego; Alberico, Federica; Trischitta, Vincenzo] Ist Ricovero Cura Carattere Sci, Casa Sollievo Sofferenza Mendel Lab, I-71013 San Giovanni Rotondo, Italy.
[Copetti, Massimiliano; Pellegrini, Fabio] Ist Ricovero Cura Carattere Sci, Unit Biostat, I-71013 San Giovanni Rotondo, Italy.
[Trischitta, Vincenzo] Ist Ricovero Cura Carattere Sci, Res Unit Diabet & Endocrine Dis, I-71013 San Giovanni Rotondo, Italy.
[Morini, Eleonora; Trischitta, Vincenzo] Univ Roma La Sapienza, Dept Expt Med, I-00161 Rome, Italy.
[Marselli, Lorella; Marchetti, Piero] Univ Pisa, Dept Endocrinol & Metab, Pisa, Italy.
[Baratta, Roberto; Frittitta, Lucia] Univ Catania, Dept Mol & Clin Biomed, I-95125 Catania, Italy.
[Mendonca, Christine; Shah, Hetal; Doria, Alessandro] Joslin Diabet Ctr, Boston, MA 02215 USA.
[Andreozzi, Francesco; Sesti, Giorgio] Magna Graecia Univ Catanzaro, Catanzaro, Italy.
[Copetti, Massimiliano; Abate, Nicola] Univ Texas SW Med Ctr Dallas, Dept Med, Div Endocrinol & Metab, Dallas, TX 75390 USA.
Univ Texas SW Med Ctr Dallas, Ctr Human Nutr, Dallas, TX 75390 USA.
[Pellegrini, Fabio] Consorzio Mario Negri Sud, Unit Biostat, Chieti, Italy.
[Doria, Alessandro] Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA.
[Doria, Alessandro] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
RP Prudente, S (reprint author), CSS Mendel Inst, Viale Regina Margherita 261, I-00198 Rome, Italy.
EM s.prudente@css-mendel.it; vincenzo.trischitta@uniroma1.it
RI Sesti, Giorgio/B-1509-2012; Marchetti, Piero/J-7439-2013; Prudente,
Sabrina/H-2886-2016; Trischitta, Vincenzo/K-1487-2016; Copetti,
Massimiliano/K-3186-2016;
OI Marchetti, Piero/0000-0003-4907-0635; Prudente,
Sabrina/0000-0001-9220-8981; Sesti, Giorgio/0000-0002-1618-7688;
Trischitta, Vincenzo/0000-0003-1174-127X; Copetti,
Massimiliano/0000-0002-7960-5947; Andreozzi,
Francesco/0000-0001-9375-1513
FU Italian Ministry of Health; European Union [LSHM-CT-2004-512013];
University of Rome "Sapienza"
FX This work was partly supported by the Italian Ministry of Health
(Ricerca Corrente 2011 and 2012, to S.P., F.P., and V.T) and by the
European Union (FP6 EUGENE2 Grant LSHM-CT-2004-512013, to G.S.). The
source of funding for our manuscript is the University of Rome
"Sapienza".
NR 24
TC 8
Z9 8
U1 0
U2 5
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0021-972X
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD JUN
PY 2013
VL 98
IS 6
BP E1143
EP E1147
DI 10.1210/jc.2012-4282
PG 5
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 155GS
UT WOS:000319736500016
PM 23633196
ER
PT J
AU Serra, V
Eichhorn, PJA
Garcia-Garcia, C
Ibrahim, YH
Prudkin, L
Sanchez, G
Rodriguez, O
Anton, P
Parra, JL
Marlow, S
Scaltriti, M
Perez-Garcia, J
Prat, A
Arribas, J
Hahn, WC
Kim, SY
Baselga, J
AF Serra, Violeta
Eichhorn, Pieter J. A.
Garcia-Garcia, Celina
Ibrahim, Yasir H.
Prudkin, Ludmila
Sanchez, Gertrudis
Rodriguez, Olga
Anton, Pilar
Parra, Josep-Lluis
Marlow, Sara
Scaltriti, Maurizio
Perez-Garcia, Jose
Prat, Aleix
Arribas, Joaquin
Hahn, William C.
Kim, So Young
Baselga, Jose
TI RSK3/4 mediate resistance to PI3K pathway inhibitors in breast cancer
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID RIBOSOMAL S6 KINASE; CAP-DEPENDENT TRANSLATION; DUAL PI3K/MTOR
INHIBITOR; VIVO ANTITUMOR-ACTIVITY; PROTEIN-KINASE;
FUNCTIONAL-CHARACTERIZATION; CELL-PROLIFERATION; INDUCED SENESCENCE;
RNAI SCREEN; PHASE-I
AB The PI3K signaling pathway regulates diverse cellular processes, including proliferation, survival, and metabolism, and is aberrantly activated in human cancer. As such, numerous compounds targeting the PI3K pathway are currently being clinically evaluated for the treatment of cancer, and several have shown some early indications of efficacy in breast cancer. However, resistance against these agents, both de novo and acquired, may ultimately limit the efficacy of these compounds. Here, we have taken a systematic functional approach to uncovering potential mechanisms of resistance to PI3K inhibitors and have identified several genes whose expression promotes survival under conditions of PI3K/mammalian target of rapamycin (PI3K/mTOR) blockade, including the ribosomal S6 kinases RPS6KA2 (RSK3) and RPS6KA6 (RSK4). We demonstrate that overexpression of RSK3 or RSK4 supports proliferation upon PI3K inhibition both in vitro and in vivo, in part through the attenuation of the apoptotic response and upregulation of protein translation. Notably, the addition of MEK- or RSK-specific inhibitors can overcome these resistance phenotypes, both in breast cancer cell lines and patient-derived xenograft models with elevated levels of RSK activity. These observations provide a strong rationale for the combined use of RSK and PI3K pathway inhibitors to elicit favorable responses in breast cancer patients with activated RSK.
C1 [Serra, Violeta; Garcia-Garcia, Celina; Ibrahim, Yasir H.; Rodriguez, Olga; Anton, Pilar; Baselga, Jose] Vall dHebron Inst Oncol, Barcelona, Spain.
[Eichhorn, Pieter J. A.] Natl Univ Singapore, Canc Sci Inst Singapore, Singapore 117548, Singapore.
[Prudkin, Ludmila; Sanchez, Gertrudis] Vall dHebron Inst Oncol, Mol Pathol Grp, Barcelona, Spain.
[Parra, Josep-Lluis; Arribas, Joaquin] Vall dHebron Inst Oncol, Growth Factors Grp, Barcelona, Spain.
[Marlow, Sara] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
[Scaltriti, Maurizio; Baselga, Jose] Human Oncol & Pathogenesis Program, New York, NY USA.
[Scaltriti, Maurizio; Baselga, Jose] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA.
[Perez-Garcia, Jose] Vall dHebron Inst Oncol, Breast Canc & Melanoma Grp, Barcelona, Spain.
[Prat, Aleix] Vall dHebron Inst Oncol, Translat Genom Unit, Barcelona, Spain.
[Hahn, William C.] Dana Farber Canc Inst, Dept Med Oncol, Ctr Canc Genome Discovery, Boston, MA 02115 USA.
[Hahn, William C.] Harvard Univ, Sch Med, Boston, MA USA.
[Hahn, William C.] Broad Inst Harvard & MIT, Cambridge, MA USA.
[Kim, So Young] Duke Univ, Med Ctr, Duke RNAi Screening Facil, Dept Mol Genet & Microbiol, Durham, NC 27710 USA.
RP Kim, SY (reprint author), Duke Univ, Med Ctr, Box 3053, Durham, NC 27710 USA.
EM soyoung.kim@duke.edu; baselgaj@mskcc.org
RI Arribas, Joaquin/M-4482-2014; Prat, Aleix/P-8561-2014
OI Arribas, Joaquin/0000-0002-0504-0664; Prat, Aleix/0000-0003-2377-540X
FU Breast Cancer Research Foundation; European Research Council
[AdG09250244]; Instituto de Salud Carlos III [Intrasalud PSO9/00623];
Novartis; FERO foundation; DFCI-Novartis Drug Discovery Program [R01
CA130988, RC2 CA148268, U54CA112962]; Snyder Medical Research Foundation
FX The authors thank Anna Schinzel of the DFCI RNAi facility for assistance
with reagents and Sadhna Vora and Jeff Engelman for helpful discussion.
The authors also thank Emmanuelle Di Tomaso and Michel Maira (Novartis
Institutes for Biomedical Research, Cambridge, Massachusetts, USA, and
Basel, Switzerland) for the supply of BEZ235 and BKM120. S.Y. Kim thanks
Joseph Nevins for advice and generous support. This research was
supported by the Breast Cancer Research Foundation (to J. Baselga), the
European Research Council (AdG09250244 to J. Baselga), the Instituto de
Salud Carlos III (Intrasalud PSO9/00623 to J. Baselga), a noncommercial
research agreement with Novartis (to J. Baselga), FERO foundation
supporting research grants (to J. Baselga), the DFCI-Novartis Drug
Discovery Program (to W.C. Hahn), R01 CA130988 (to W.C. Hahn), RC2
CA148268 (to W.C. Hahn), U54CA112962 (to W.C. Hahn), and the Snyder
Medical Research Foundation (to W.C. Hahn)
NR 70
TC 35
Z9 36
U1 3
U2 18
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 JUN
PY 2013
VL 123
IS 6
BP 2551
EP 2563
DI 10.1172/JCI66343
PG 13
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 160CD
UT WOS:000320093100026
PM 23635776
ER
PT J
AU Nemlich, Y
Greenberg, E
Ortenberg, R
Besser, MJ
Barshack, I
Jacob-Hirsch, J
Jacoby, E
Eyal, E
Rivkin, L
Prieto, VG
Chakravarti, N
Duncan, LM
Kallenberg, DM
Galun, E
Bennett, DC
Amariglio, N
Bar-Eli, M
Schachter, J
Rechavi, G
Markel, G
AF Nemlich, Yael
Greenberg, Eyal
Ortenberg, Rona
Besser, Michal J.
Barshack, Iris
Jacob-Hirsch, Jasmine
Jacoby, Elad
Eyal, Eran
Rivkin, Ludmila
Prieto, Victor G.
Chakravarti, Nitin
Duncan, Lyn M.
Kallenberg, David M.
Galun, Eitan
Bennett, Dorothy C.
Amariglio, Ninette
Bar-Eli, Menashe
Schachter, Jacob
Rechavi, Gideon
Markel, Gal
TI MicroRNA-mediated loss of ADAR1 in metastatic melanoma promotes tumor
growth
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID DOUBLE-STRANDED-RNA; TO-INOSINE RNA; GENE-EXPRESSION; SYSTEMATIC
IDENTIFICATION; ADENOSINE-DEAMINASE; CELL-PROLIFERATION; HUMAN CANCER;
HUMAN BRAIN; TARGETS; DICER
AB Some solid tumors have reduced posttranscriptional RNA editing by adenosine deaminase acting on RNA (ADAR) enzymes, but the functional significance of this alteration has been unclear. Here, we found the primary RNA-editing enzyme ADAR1 is frequently reduced in metastatic melanomas. In situ analysis of melanoma samples using progression tissue microarrays indicated a substantial downregulation of ADAR1 during the metastatic transition. Further, ADAR1 knockdown altered cell morphology, promoted in vitro proliferation, and markedly enhanced the tumorigenicity in vivo. A comparative whole genome expression microarray analysis revealed that ADAR1 controls the expression of more than 100 microRNAs (miRNAs) that regulate many genes associated with the observed phenotypes. Importantly, we discovered that ADAR1 fundamentally regulates miRNA processing in an RNA binding-dependent, yet RNA editing-independent manner by regulating Dicer expression at the translational level via let-7. In addition, ADAR1 formed a complex with DGCR8 that was mutually exclusive with the DGCR8-Drosha complex that processes pri-miRNAs in the nucleus. We found that cancer cells silence ADAR1 by overexpressing miR-17 and miR-432, which both directly target the ADAR1 transcript. We further demonstrated that the genes encoding miR-17 and miR-432 are frequently amplified in melanoma and that aberrant hypomethylation of the imprinted DLK1-DIO3 region in chromosome 14 can also drive miR-432 overexpression.
C1 [Nemlich, Yael; Greenberg, Eyal; Ortenberg, Rona; Besser, Michal J.; Schachter, Jacob; Markel, Gal] Ella Inst Melanoma, Ramat Gan, Israel.
[Nemlich, Yael; Greenberg, Eyal; Ortenberg, Rona; Besser, Michal J.; Rechavi, Gideon; Markel, Gal] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel.
[Barshack, Iris] Sheba Med Ctr, Inst Pathol, Ramat Gan, Israel.
[Jacob-Hirsch, Jasmine; Jacoby, Elad; Eyal, Eran; Amariglio, Ninette; Rechavi, Gideon] Sheba Med Ctr, Canc Res Ctr, Ramat Gan, Israel.
[Jacoby, Elad] Sheba Med Ctr, Dept Pediat Hematooncol, Ramat Gan, Israel.
[Rivkin, Ludmila; Galun, Eitan] Hadassah Hebrew Univ Hosp, Goldyne Savad Inst Gene Therapy, Jerusalem, Israel.
[Prieto, Victor G.; Chakravarti, Nitin] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA.
[Duncan, Lyn M.] Massachusetts Gen Hosp, Dermatopathol Unit, Boston, MA 02114 USA.
[Kallenberg, David M.; Bennett, Dorothy C.] Univ London, Biomed Sci Res Ctr, London, England.
[Bar-Eli, Menashe] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA.
[Markel, Gal] Sheba Med Ctr, Talpiot Med Leadership Program, Ramat Gan, Israel.
RP Markel, G (reprint author), Sheba Med Ctr, Ella Inst Melanoma, IL-52621 Ramat Gan, Israel.
EM markel@post.tau.ac.il
RI Bennett, Dorothy/C-2418-2008
OI Bennett, Dorothy/0000-0002-3639-7527
FU Israel Science Foundation [1489/10, 41/11.1]; Carol Fingerut Foundation
for Cancer Research; Wellcome Trust [078327]; Planning and Budgeting
Committee; Flight Attendants Medical Research Institute (FAMRI); Israel
Ministry for Science and Technology; I-CORE ISF [41/11.1]; SFB DFG [841]
FX G. Markel is supported by the Israel Science Foundation (grant 1489/10)
and the Carol Fingerut Foundation for Cancer Research (grant 2008). D.M.
Kallenberg is supported by Wellcome Trust (grant 078327). G. Rechavi is
supported by the I-CORE Program of the Planning and Budgeting Committee
and the Israel Science Foundation (grant no. 41/11.1), the Flight
Attendants Medical Research Institute (FAMRI), the I-CORE Program of the
Planning and Budgeting Committee and the Israel Science Foundation
(grant no. 41/11.1), and the Israel Ministry for Science and Technology
(Scientific Infrastructure Program, grant 2010). G. Rechavi holds the
Djerassi Chair in Oncology, Tel Aviv University. E. Galun is supported
by an I-CORE ISF grant (grant no. 41/11.1) and an SFB DFG grant (grant
no. 841). The authors would like to thank Michael Aronson for his
support in this work. This work was performed in partial fulfillment of
the requirements for a Ph.D. degree for Yael Nemlich, Sackler Faculty of
Medicine, Tel Aviv University.
NR 63
TC 47
Z9 49
U1 1
U2 9
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 JUN
PY 2013
VL 123
IS 6
BP 2703
EP 2718
DI 10.1172/JCI62980
PG 16
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 160CD
UT WOS:000320093100039
PM 23728176
ER
PT J
AU Imel, ZE
Laska, K
Jakupcak, M
Simpson, TL
AF Imel, Zac E.
Laska, Kevin
Jakupcak, Matthew
Simpson, Tracy L.
TI Meta-Analysis of Dropout in Treatments for Posttraumatic Stress Disorder
SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY
LA English
DT Article
DE PTSD; clinical trials; dropout; psychotherapy
ID RANDOMIZED CONTROLLED-TRIAL; EYE-MOVEMENT DESENSITIZATION; NARRATIVE
EXPOSURE THERAPY; COGNITIVE PROCESSING THERAPY; AFRICAN REFUGEE
SETTLEMENT; BONA-FIDE PSYCHOTHERAPIES; SUBSTANCE USE DISORDERS;
CHILDHOOD SEXUAL-ABUSE; PROLONGED EXPOSURE; IMAGINAL EXPOSURE
AB Objective: Many patients drop out of treatments for posttraumatic stress disorder (PTSD); some clinicians believe that trauma-focused treatments increase dropout. Method: We conducted a meta-analysis of dropout among active treatments in clinical trials for PTSD (42 studies; 17 direct comparisons). Results: The average dropout rate was 18%, but it varied significantly across studies. Group modality and greater number of sessions, but not trauma focus, predicted increased dropout. When the meta-analysis was restricted to direct comparisons of active treatments, there were no differences in dropout. Differences in trauma focus between treatments in the same study did not predict dropout. However, trauma-focused treatments resulted in higher dropout compared with present-centered therapy (PCT), a treatment originally designed as a control but now listed as a research-supported intervention for PTSD. Conclusion: Dropout varies between active interventions for PTSD across studies, but variability is primarily driven by differences between studies. There do not appear to be systematic differences across active interventions when they are directly compared in the same study. The degree of clinical attention placed on the traumatic event does not appear to be a primary cause of dropout from active treatments. However, comparisons of PCT may be an exception to this general pattern, perhaps because of a restriction of variability in trauma focus among comparisons of active treatments. More research is needed comparing trauma-focused interventions to trauma-avoidant treatments such as PCT.
C1 [Imel, Zac E.] Univ Utah, Dept Educ Psychol, Salt Lake City, UT 84112 USA.
[Imel, Zac E.; Jakupcak, Matthew; Simpson, Tracy L.] VA Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA USA.
[Laska, Kevin] Bedford VA Med Ctr, Bedford, MA USA.
RP Imel, ZE (reprint author), Univ Utah, Dept Educ Psychol, 1705 Campus Ctr Dr RM 327, Salt Lake City, UT 84112 USA.
EM zac.imel@utah.edu
OI imel, zachary/0000-0001-9645-7184
FU NCRR NIH HHS [UL1 RR025014, UL1RR025014]; NIDA NIH HHS [R34 DA034860]
NR 73
TC 50
Z9 50
U1 12
U2 44
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0022-006X
J9 J CONSULT CLIN PSYCH
JI J. Consult. Clin. Psychol.
PD JUN
PY 2013
VL 81
IS 3
BP 394
EP 404
DI 10.1037/a0031474
PG 11
WC Psychology, Clinical
SC Psychology
GA 150RA
UT WOS:000319407300003
PM 23339535
ER
PT J
AU Suvak, MK
Taft, CT
Goodman, LA
Dutton, MA
AF Suvak, Michael K.
Taft, Casey T.
Goodman, Lisa A.
Dutton, Mary Ann
TI Dimensions of Functional Social Support and Depressive Symptoms: A
Longitudinal Investigation of Women Seeking Help for Intimate Partner
Violence
SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY
LA English
DT Article
DE intimate partner violence; social support; depression; multilevel
modeling; longitudinal
ID POSTTRAUMATIC-STRESS-DISORDER; DOMESTIC VIOLENCE; BATTERED WOMEN;
ADVOCACY INTERVENTION; PROTECTIVE FACTORS; ABUSIVE PARTNERS;
MENTAL-HEALTH; METAANALYSIS; ADULTS; RISK
AB Objective: We examined 4 separate dimensions of functional social support (tangible, appraisal, self-esteem, and belonging) as predictors of change in depression over 4.5 years in a sample of women reporting intimate partner violence. Method: Participants were recruited as they sought help for violence perpetrated by a current or former male partner. Three hundred eighty-eight participants completed the Interpersonal Support Evaluation List (Cohen, Mermelstein, Kamarck, & Hoberman, 1985), the Conflict Tactics Scale-2 (Straus, Hamby, Boney-McCoy, & Sugarman, 1996), and the Center for Epidemiologic Studies Depression Scale (CES-D; Radloff, 1977) at the baseline assessment. Participants were reevaluated on 9 follow-up assessment occasions over approximately 4.5 years, during which they completed the CES-D. Results: Growth curve analyses revealed that belonging, or the perceived availability of people one can do things with, was the only dimension that predicted changes in depressive symptoms when controlling for initial depressive symptom levels. Higher levels of belonging support reported at the baseline assessment were associated with larger decreases in depression. Conclusions: The findings of the current study suggest that interventions should consider ways to get survivors connected to informal social networks. Neither perceived availability of material aid nor availability of someone to talk about one's problems or serve as a positive comparison when comparing oneself to others was associated with decreased depression over time. Only perceived availability of people one can do things with (i.e., belonging support) exhibited salutary effects.
C1 [Suvak, Michael K.] Suffolk Univ, Dept Psychol, Boston, MA 02114 USA.
[Taft, Casey T.] VA Boston Healthcare Syst, Behav Sci Div, Natl Ctr PTSD, Boston, MA USA.
[Taft, Casey T.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA.
[Goodman, Lisa A.] Boston Coll, Dept Counseling & Dev Psychol, Sch Educ, Chestnut Hill, MA 02167 USA.
[Dutton, Mary Ann] Georgetown Univ, Med Ctr, Dept Psychiat, Washington, DC 20057 USA.
RP Suvak, MK (reprint author), Suffolk Univ, Dept Psychol, 41 Temple St D609, Boston, MA 02114 USA.
EM msuvak@suffolk.edu
FU NIMH NIH HHS [1F32MH071011-1, F32 MH071011]
NR 54
TC 4
Z9 4
U1 6
U2 28
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0022-006X
J9 J CONSULT CLIN PSYCH
JI J. Consult. Clin. Psychol.
PD JUN
PY 2013
VL 81
IS 3
BP 455
EP 466
DI 10.1037/a0031787
PG 12
WC Psychology, Clinical
SC Psychology
GA 150RA
UT WOS:000319407300009
PM 23398492
ER
PT J
AU Palli, MBA
Reyes-Habito, CM
Lima, XT
Kimball, AB
AF Palli, Ma Beatrice Alora
Reyes-Habito, Claire Marie
Lima, Xinaida T.
Kimball, Alexa B.
TI A Single-Center, Randomized Double-Blind, Parallel-Group Study to
Examine the Safety and Efficacy of 3mg Drospirenone/0.02mg Ethinyl
Estradiol Compared With Placebo in the Treatment of Moderate Truncal
Acne Vulgaris
SO JOURNAL OF DRUGS IN DERMATOLOGY
LA English
DT Article
ID CONTROLLED-TRIAL; 24/4 REGIMEN; NORGESTIMATE
AB Background: Acne is a common disease of the face, chest and back, initially triggered by androgens. 3mg Drospirenone (DRSP)/0.02mg ethinyl estradiol (EE), an oral contraceptive and antiandrogen, has been effective in treatment studies of facial acne in women, but investigations on its efficacy for truncal acne are limited.
Objective: In this study, we sought to evaluate the safety and efficacy of 3mg DRSP/0.02mg EE versus placebo in the treatment of truncal acne in women.
Methods: Females, age 18-45, with 10 to 50 truncal acne lesions, were randomized in this double-blind study to 3mg DRSP/0.02mg EE (n=15) or placebo (n=10) administered in a 24/4 regimen given for 24 weeks. Noninflammatory, inflammatory and total truncal acne lesion counts were assessed from baseline to endpoint and mean percent change compared. Investigator Global Assessment (IGA) and Subject Global Assessment (SGA) were assessed based on scoring scales, and the percentage of subjects rated as success with clear (score 0) or almost clear (score 1) were computed.
Results: The 3mg DRSP/0.02mg EE group had significant reductions in mean percent change in noninflammatory, inflammatory and total lesions by 52.1%, 53.2%, and 57.3%, respectively, compared to placebo with -9.2%, 18.2% and 17.0%, respectively, by week 24 (p = 0.02, 0.05 and 0.02, respectively). The percentage of subjects on 3mg DRSP/0.02mg EE rated as treatment success were 53.3% and 60% based on IGA and SGA respectively. The regimen was also well tolerated by patients.
Conclusions: 3mg DRSP/0.02 mg EE is a safe and significantly effective treatment for moderate truncal acne.
C1 [Palli, Ma Beatrice Alora; Kimball, Alexa B.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Palli, Ma Beatrice Alora; Kimball, Alexa B.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA.
[Palli, Ma Beatrice Alora; Reyes-Habito, Claire Marie; Kimball, Alexa B.] Massachusetts Gen Hosp, Clin Unit Res Trials & Outcomes Skin CURTIS, Boston, MA 02114 USA.
[Lima, Xinaida T.] Univ Estadual Campinas, Dept Dermatol, Sao Paulo, Brazil.
RP Kimball, AB (reprint author), Harvard Univ, Sch Med, Boston, MA 02114 USA.
EM harvardskinstudies@partners.org
FU Bayer
FX This research was funded by Bayer. A.B.K. was a consultant of Bayer at
the time of the study.
NR 13
TC 10
Z9 11
U1 0
U2 1
PU JOURNAL OF DRUGS IN DERMATOLOGY
PI NEW YORK
PA 377 PARK AVE SOUTH, 6TH FLOOR, NEW YORK, NY 10016 USA
SN 1545-9616
J9 J DRUGS DERMATOL
JI J. Drugs Dermatol.
PD JUN
PY 2013
VL 12
IS 6
BP 633
EP 637
PG 5
WC Dermatology
SC Dermatology
GA 163NP
UT WOS:000320344500005
PM 23839178
ER
PT J
AU Ladizinski, B
Carter, JB
Lee, KC
Aaron, DM
AF Ladizinski, Barry
Carter, Joi B.
Lee, Kachiu C.
Aaron, Denise M.
TI Diagnosis of Herpes Simplex Virus-Induced Erythema Multiforme Confounded
by Previous Infection With Mycoplasma Pneumonia
SO JOURNAL OF DRUGS IN DERMATOLOGY
LA English
DT Article
ID GENITAL HERPES; SEROLOGY; ASSAY
AB Erythema multiforme (EM) is an immune-mediated hypersensitivity reaction often related to viral infection or medications. Infection-induced EM is typically self-limited and commonly caused by herpes simplex virus (HSV) or Mycoplasma pneumoniae (MP); recurrent EM is almost always associated with HSV. We present a concise overview of diagnostic techniques for HSV and MR as repeatedly elevated MP titers in our case led to a delayed diagnosis of HSV-induced EM.
C1 [Ladizinski, Barry] Duke Univ Hosp, Dept Dermatol, Durham, NC 27708 USA.
[Carter, Joi B.] Mass Gen Hosp, Dept Dermatol, Boston, MA USA.
[Lee, Kachiu C.] Brown Univ Hosp, Dept Dermatol, Providence, RI USA.
[Aaron, Denise M.] Dartmouth Hitchcock Med Ctr, Dept Dermatol, Lebanon, NH 03766 USA.
RP Ladizinski, B (reprint author), Duke Univ Hosp, Dept Dermatol, Durham, NC 27708 USA.
EM barryladizinski@gmail.com
NR 8
TC 3
Z9 3
U1 0
U2 0
PU JOURNAL OF DRUGS IN DERMATOLOGY
PI NEW YORK
PA 377 PARK AVE SOUTH, 6TH FLOOR, NEW YORK, NY 10016 USA
SN 1545-9616
J9 J DRUGS DERMATOL
JI J. Drugs Dermatol.
PD JUN
PY 2013
VL 12
IS 6
BP 707
EP 709
PG 3
WC Dermatology
SC Dermatology
GA 163NP
UT WOS:000320344500019
PM 23839193
ER
PT J
AU Martindale, JL
AF Martindale, Jennifer L.
TI IMAGING ABNORMALITIES ASSOCIATED WITH CARBON MONOXIDE TOXICITY
SO JOURNAL OF EMERGENCY MEDICINE
LA English
DT Editorial Material
ID BRAIN
C1 [Martindale, Jennifer L.] Brigham & Womens Hosp, Harvard Affiliated Emergency Med Residency Progra, Massachusetts Gen Hosp, Boston, MA 02115 USA.
RP Martindale, JL (reprint author), Massachusetts Gen Hosp, Harvard Affiliated Emergency Med Residency Progra, 55 Fruit St, Boston, MA 02114 USA.
NR 4
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 JUN
PY 2013
VL 44
IS 6
BP 1140
EP 1141
DI 10.1016/j.jemermed.2012.07.069
PG 2
WC Emergency Medicine
SC Emergency Medicine
GA 161TX
UT WOS:000320217300014
PM 23478185
ER
PT J
AU Wen, LS
Xu, J
Steptoe, AP
Sullivan, AF
Walline, JH
Yu, XZ
Camargo, CA
AF Wen, Leana S.
Xu, Jun
Steptoe, Anne P.
Sullivan, Ashley F.
Walline, Joseph H.
Yu, Xuezhong
Camargo, Carlos A., Jr.
TI EMERGENCY DEPARTMENT CHARACTERISTICS AND CAPABILITIES IN BEIJING, CHINA
SO JOURNAL OF EMERGENCY MEDICINE
LA English
DT Article
DE international emergency medicine; China; Emergency Department
classification; health policy; Emergency Department crowding
ID MEDICINE
AB Background: Emergency Departments (EDs) are a critical, yet heterogeneous, part of international emergency care. Objectives: We sought to describe the characteristics, resources, capabilities, and capacity of EDs in Beijing, China. Methods: Beijing EDs accessible to the general public 24 h per day/7 days per week were surveyed using the National ED Inventories survey instrument (vvvvvv.emnet-nedi.org). ED staff were asked about ED characteristics during the calendar year 2008. Results: Thirty-six EDs participated (88% response rate). All were located in hospitals and were independent hospital departments. Participating EDs saw a median of 80,000 patients (interquartile range 40,000-118,508). The vast majority (91%; 95% confidence interval [CI] 78-98%) had a contiguous layout, with medical and surgical care provided in one area. Most EDs (55%) saw only adults; 39% saw both adults and children, and 6% saw only children. Availability of technological and consultant resource in EDs was high. The typical ED length of stay was between land 6 h in 49% of EDs (95% CI 32-67%), whereas in the other half, patients reportedly remained for over 6 h; 36% (95% CI 21-54%) of respondents considered their ED over capacity. Conclusions: Beijing EDs have high volume, long length of stay, and frequent reports of EDs being over capacity. To meet its rapidly growing health needs in urban areas, China should consider improving urban ED capacity and training more Emergency Medicine specialists capable of efficiently staffing its crowded EDs. (C) 2013 Elsevier Inc.
C1 [Wen, Leana S.] Massachusetts Gen Hosp, Brigham & Womens Hosp, Harvard Affiliated Emergency Med Residency, Dept Emergency Med, Boston, MA 02114 USA.
[Xu, Jun; Yu, Xuezhong] Beijing Union Med Coll Hosp, Dept Emergency Med, Beijing, Peoples R China.
[Steptoe, Anne P.; Sullivan, Ashley F.; Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.
[Walline, Joseph H.] St Louis Univ, Div Emergency Med, St Louis, MO 63103 USA.
RP Xu, J (reprint author), Beijing Union Med Coll Hosp, Dept Emergency Med, 1 Shuaifuyuan, Beijing, Peoples R China.
OI Wen, Leana/0000-0003-0259-0537
NR 14
TC 2
Z9 2
U1 2
U2 7
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 JUN
PY 2013
VL 44
IS 6
BP 1174
EP 1179
DI 10.1016/j.jemermed.2012.07.083
PG 6
WC Emergency Medicine
SC Emergency Medicine
GA 161TX
UT WOS:000320217300023
PM 23473821
ER
PT J
AU Chung, KC
Kim, HM
Haase, SC
Lawton, J
Ozer, K
Waljee, JF
Nellans, K
Malay, S
Shauver, MJ
Rozental, TD
Appleton, P
Rodriguez, E
Herder, L
Wagner, K
Blazar, P
Earn, B
Floyd, WE
Leversedge, F
Pico, KS
Richards, MJ
Ruch, DS
Finley, S
Kalliainen, LK
Fletcher, JW
Heinrich, CA
Ward, CM
Hill, BW
Bamberger, B
Robinson, C
Palmer, B
Ring, D
Jupiter, JB
Reddy, R
Dennison, D
Kakar, S
Shin, A
Scrabeck, T
Hoyen, H
Malone, K
Sebastin, S
Tay, PL
Gaston, G
Connell, B
Neumeister, M
Berry, NN
Bueno, RA
McAndrew, M
Koechle, J
Perey, B
Zomar, M
Wolf, JM
Rodner, CM
Cote, M
Clark, T
Lehman, T
Carl, K
Bozentka, D
Levin, S
Steinberg, D
Horan, A
Knox, D
Hammert, W
McIntyre, AW
Friedrich, JB
Allan, CH
Hanel, DP
Huang, JI
Ko, JH
Vedder, NB
Boman, D
Cooper, CL
Grewal, R
MacDermid, J
Kelly, K
Millman, K
Li, ZY
Koman, A
Smith, B
Bullard, D
AF Chung, Kevin C.
Kim, H. Myra
Haase, Steven C.
Lawton, Jeffrey
Ozer, Kagan
Waljee, Jennifer F.
Nellans, Kate
Malay, Sunitha
Shauver, Melissa J.
Rozental, Tamara D.
Appleton, Paul
Rodriguez, Edward
Herder, Lindsay
Wagner, Katiri
Blazar, Philip
Earn, Brandon
Floyd, W. Emerson
Leversedge, Fraser
Pico, Katherine S.
Richards, Marc J.
Ruch, David S.
Finley, Suzanne
Kalliainen, Loree K.
Fletcher, James W.
Heinrich, Cherrie A.
Ward, Christian M.
Hill, Brian W.
Bamberger, Brent
Robinson, Carla
Palmer, Brandi
Ring, David
Jupiter, Jesse B.
Reddy, Rajesh
Dennison, David
Kakar, Sanjeev
Shin, Alexander
Scrabeck, Tyson
Hoyen, Harry
Malone, Kevin
Sebastin, Sandeep
Tay, Pub Ling
Gaston, Glenn
Connell, Benjamin
Neumeister, Michael
Berry, Nada N.
Bueno, Reuben A., Jr.
McAndrew, Mark
Koechle, Jennifer
Perey, Bertrand
Zomar, Mauri
Wolf, Jennifer Moriatis
Rodner, Craig M.
Cote, Mark
Clark, Tod
Lehman, Thomas
Carl, Kathy
Bozentka, David
Levin, Scott
Steinberg, David
Horan, Annamarie
Knox, Denise
Hammert, Warren
McIntyre, Allison W.
Friedrich, Jeffrey B.
Allan, Christopher H.
Hanel, Douglas P.
Huang, Jerry I.
Ko, Jason H.
Vedder, Nicholas B.
Boman, David
Cooper, Claudette L.
Grewal, Ruby
MacDermid, Joy
Kelly, Kate
Millman, Kristie
Li, Zhongyu
Koman, Andrew
Smith, Beth
Bullard, Debra
CA Wrist Radius Injury Surgical Trial
TI Reflections 1 Year Into the 21-Center National Institutes of
Health-Funded WRIST Study: A Primer on Conducting a Multicenter Clinical
Trial
SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME
LA English
DT Article
DE Distal radius fracture; randomized clinical trials; multicenter trials
ID DISTAL RADIUS FRACTURES; STATES MEDICARE POPULATION; UNITED-STATES;
SEASONAL-VARIATION; OLDER-PEOPLE; EXPERIENCE; BARRIERS; OUTCOMES; WOMEN;
RECRUITMENT
AB The Wrist and Radius Injury Surgery Trial (WRIST) study group is a collaboration of 21 hand surgery centers in the United States, Canada, and Singapore, to showcase the interest and capability of hand surgeons to conduct a multicenter clinical trial. The WRIST study group was formed in response to the seminal systematic review by Margaliot et al and the Cochrane report that indicated marked deficiency in the quality of evidence in the distal radius fracture literature. Since the initial description of this fracture by Cones in 1814, over 2,000 studies have been published on this subject; yet, high-level studies based on the principles of evidence-based medicine are lacking. As we continue to embrace evidence-based medicine to raise the quality of research, the lessons learned during the organization and conduct of WRIST can serve as a template for others contemplating similar efforts. This article traces the course of WRIST by sharing the triumphs and, more important, the struggles faced in the first year of this study. (Copyright (C) 2013 by the American Society for Surgery of the Hand All rights reserved.)
C1 [Chung, Kevin C.; Kim, H. Myra; Haase, Steven C.; Lawton, Jeffrey; Ozer, Kagan; Waljee, Jennifer F.; Nellans, Kate; Malay, Sunitha; Shauver, Melissa J.] Univ Michigan, Ann Arbor, MI 48109 USA.
[Rozental, Tamara D.; Appleton, Paul; Rodriguez, Edward; Herder, Lindsay; Wagner, Katiri] Beth Israel Deaconess Med Ctr, Boston, MA USA.
[Blazar, Philip; Earn, Brandon; Floyd, W. Emerson] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Leversedge, Fraser; Pico, Katherine S.; Richards, Marc J.; Ruch, David S.; Finley, Suzanne] Duke Univ, Durham, NC 27706 USA.
[Bamberger, Brent; Robinson, Carla; Palmer, Brandi] Kettering Hlth Network, Kettering, England.
[Ring, David; Jupiter, Jesse B.; Reddy, Rajesh] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Dennison, David; Kakar, Sanjeev; Shin, Alexander; Scrabeck, Tyson] Mayo Clin, Rochester, MN USA.
[Sebastin, Sandeep; Tay, Pub Ling] Natl Univ Singapore, Singapore 117548, Singapore.
[Neumeister, Michael; Berry, Nada N.; Bueno, Reuben A., Jr.; McAndrew, Mark; Koechle, Jennifer] So Illinois Univ, Carbondale, IL 62901 USA.
[Perey, Bertrand; Zomar, Mauri] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada.
[Wolf, Jennifer Moriatis; Rodner, Craig M.; Cote, Mark] Univ Connecticut, Storrs, CT USA.
[Clark, Tod] Univ Manitoba, Winnipeg, MB R3T 2N2, Canada.
[Lehman, Thomas; Carl, Kathy] Univ Oklahoma, Norman, OK 73019 USA.
[Bozentka, David; Levin, Scott; Steinberg, David; Horan, Annamarie; Knox, Denise] Univ Penn, Philadelphia, PA 19104 USA.
[Hammert, Warren; McIntyre, Allison W.] Univ Rochester, Rochester, NY 14627 USA.
[Friedrich, Jeffrey B.; Allan, Christopher H.; Hanel, Douglas P.; Huang, Jerry I.; Ko, Jason H.; Vedder, Nicholas B.; Boman, David; Cooper, Claudette L.] Univ Washington, Seattle, WA 98195 USA.
[Grewal, Ruby; MacDermid, Joy; Kelly, Kate; Millman, Kristie] Univ Western Ontario, London, ON N6A 3K7, Canada.
[Li, Zhongyu; Koman, Andrew; Smith, Beth; Bullard, Debra] Wake Forest Univ, Winston Salem, NC 27109 USA.
RP Chung, KC (reprint author), Univ Michigan Hlth Syst, Sect Plast Surg, Taubman Ctr 2130, SPC 5340,1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA.
EM kecchung@med.umich.edu
RI MacDermid, Joy/H-7837-2013; Waljee, Jennifer/A-1319-2014;
OI MacDermid, Joy/0000-0001-9311-7379; Shauver,
Melissa/0000-0001-5882-5986; Shin, Alexander/0000-0001-9658-8192
FU National Institute of Arthritis and Musculoskeletal and Skin Diseases;
National Institute on Aging [R01 AR062066]; Midcareer Investigator Award
in Patient-Oriented Research [K24 AR053120]
FX Supported in part by grants from the National Institute of Arthritis and
Musculoskeletal and Skin Diseases and National Institute on Aging (R01
AR062066) and a Midcareer Investigator Award in Patient-Oriented
Research (K24 AR053120) (to K.C.C.).
NR 33
TC 0
Z9 0
U1 1
U2 13
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0363-5023
J9 J HAND SURG-AM
JI J. Hand Surg.-Am. Vol.
PD JUN
PY 2013
VL 38A
IS 6
BP 1194
EP 1201
DI 10.1016/j.jhsa.2013.02.027
PG 8
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA 163MV
UT WOS:000320342500022
ER
PT J
AU Hageman, MGJS
Guitton, TG
Ring, D
AF Hageman, Michiel G. J. S.
Guitton, Thierry G.
Ring, David
CA Sci Variation Grp
TI How Surgeons Make Decisions When the Evidence Is Inconclusive
SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME
LA English
DT Article
DE Decision making; evidence-based medicine; treatment
ID TRIAL
AB Purpose To address the factors that surgeons use to decide between 2 options for treatment when the evidence is inconclusive.
Methods We tested the null hypothesis that the factors surgeons use do not vary by training, demographics, and practice. A total of 337 surgeons rated the importance of 7 factors when deciding between treatment and following the natural history of the disease and 12 factors when deciding between 2 operative treatments using a 5-point Likert scale between "very important" and "very unimportant."
Results According to the percentages of statements rated very important or somewhat important, the most popular factors influencing recommendations when evidence is inconclusive between treatment and following the natural course of the illness were "works in my hands," "familiarity with the treatment," and "what my mentor taught me." The most important factors when evidence shows no difference between 2 surgeries were "fewer complications," "quicker recovery," "burns fewer bridges," "works in my hands" and "familiarity with the procedure." Europeans rated "works in my hands" and "cheapest/most resourceful" of significantly greater importance and "what others are doing," "highest reimbursement," and "shorter procedure" of significantly lower importance than surgeons in the United States. Observers with fewer than 10 years in independent practice rated "what my mentor taught me," "what others are doing" and "highest reimbursement" of significantly lower importance compared to observers with 10 or more years in independent practice.
Conclusions Surgeons deciding between 2 treatment options, when the evidence is inconclusive, fall back to factors that relate to their perspective and reflect their culture and circumstances, more so than factors related to the patient's perspective, although this may be different for younger surgeons.
Clinical relevance Hand surgeons might benefit from consensus fallback preferences when evidence is inconclusive. It is possible that falling back to personal comfort makes us vulnerable to unhelpful commercial and societal influences. (Copyright (C) 2013 by the American Society for Surgery of the Hand. All rights reserved.)
C1 [Hageman, Michiel G. J. S.; Guitton, Thierry G.; Ring, David; Sci Variation Grp] Massachusetts Gen Hosp, Orthopaed Hand Serv, Boston, MA 02114 USA.
RP Ring, D (reprint author), Massachusetts Gen Hosp, Orthopaed Hand Serv, Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA.
EM dring@partners.org
RI Fernandes, C/F-9839-2012; Page, Richard/K-6327-2015;
OI Miller, Anna/0000-0002-7056-8502; Beeres, Frank/0000-0002-7277-3438;
harvey, edward/0000-0003-3934-8920; Swiontkowski,
Marc/0000-0001-7036-1782; Aita, Marcio Aurelio Aita/0000-0002-9062-265X;
Jubel, Axel/0000-0003-4402-4816; Goldfarb, Charles/0000-0001-9672-8853;
Borris, Lars/0000-0002-0527-1518; Guitton, Thierry/0000-0002-2599-1985;
Streubel, Philipp/0000-0002-4585-1779; Fernandes, C/0000-0003-0146-6091;
Page, Richard/0000-0002-2225-7144; Kanakaris,
Nikolaos/0000-0002-1695-1519; Frihagen, Frede/0000-0002-4811-669X; Ladd,
Amy/0000-0003-0948-1034
FU Marti-Keunig Eckhart Stichting; Anna Foundation
FX M.G.H. is supported by Dutch research grants from Marti-Keunig Eckhart
Stichting and Anna Foundation.
NR 12
TC 11
Z9 11
U1 0
U2 12
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0363-5023
J9 J HAND SURG-AM
JI J. Hand Surg.-Am. Vol.
PD JUN
PY 2013
VL 38A
IS 6
BP 1202
EP 1208
DI 10.1016/j.jhsa.2013.02.032
PG 7
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA 163MV
UT WOS:000320342500023
PM 23647639
ER
PT J
AU Raizman, NM
Ring, D
Hammert, WC
AF Raizman, Noah M.
Ring, David
Hammert, Warren C.
TI Evidence-Based Reviews of Hand and Upper Extremity Surgery
SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME
LA English
DT Editorial Material
C1 Hand & Upper Extrem Inst Greater Washington, Washington, DC USA.
Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA.
[Hammert, Warren C.] Univ Rochester, Med Ctr, Dept Orthopaed Surg, Rochester, NY 14642 USA.
RP Hammert, WC (reprint author), Univ Rochester, Med Ctr, Dept Orthopaed Surg, 601 Elmwood Ave,Box 665, Rochester, NY 14642 USA.
EM warren_hammert@urmcrochester.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0363-5023
J9 J HAND SURG-AM
JI J. Hand Surg.-Am. Vol.
PD JUN
PY 2013
VL 38A
IS 6
BP 1247
EP 1251
DI 10.1016/j.jhsa.2013.02.031
PG 5
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA 163MV
UT WOS:000320342500034
PM 23591022
ER
PT J
AU Suswam, EA
Shacka, JJ
Walker, K
Lu, L
Li, XL
Si, Y
Zhang, XW
Zheng, L
Nabors, LB
Cao, HP
King, PH
AF Suswam, Esther A.
Shacka, John J.
Walker, Kiera
Lu, Liang
Li, Xuelin
Si, Ying
Zhang, Xiaowen
Zheng, Lei
Nabors, L. Burt
Cao, Heping
King, Peter H.
TI Mutant tristetraprolin: a potent inhibitor of malignant glioma cell
growth
SO JOURNAL OF NEURO-ONCOLOGY
LA English
DT Article
DE RNA stability; VEGF; IL-6; IL-8; Post-transcriptional gene regulation
ID MESSENGER-RNA STABILITY; ACTIVATED PROTEIN-KINASE;
TUMOR-NECROSIS-FACTOR; SIGNALING PATHWAY; RICH ELEMENTS; UP-REGULATION;
BRF PROTEINS; CANCER CELLS; BINDING; HUR
AB Malignant gliomas rely on the production of certain critical growth factors including VEGF, interleukin (IL)-6 and IL-8, to fuel rapid tumor growth, angiogenesis, and treatment resistance. Post-transcriptional regulation through adenine and uridine-rich elements of the 3' untranslated region is one mechanism for upregulating these and other growth factors. In glioma cells, we have shown that the post-transcriptional machinery is optimized for growth factor upregulation secondary to overexpression of the mRNA stabilizer, HuR. The negative regulator, tristetraprolin (TTP), on the other hand, may be suppressed because of extensive phosphorylation. Here we test that possibility by analyzing the phenotypic effects of a mutated form of TTP (mt-TTP) in which 8 phosphoserine residues were converted to alanines. We observed a significantly enhanced negative effect on growth factor expression in glioma cells at the post-transcriptional and transcriptional levels. The protein became stabilized and displayed significantly increased antiproliferative effects compared to wild-type TTP. Macroautophagy was induced with both forms of TTP, but inhibition of autophagy did not affect cell viability. We conclude that glioma cells suppress TTP function through phosphorylation of critical serine residues which in turn contributes to growth factor upregulation and tumor progression.
C1 [Suswam, Esther A.; Walker, Kiera; Lu, Liang; Li, Xuelin; Si, Ying; Zheng, Lei; Nabors, L. Burt; King, Peter H.] Univ Alabama Birmingham, Dept Neurol, Birmingham, AL 35294 USA.
[Shacka, John J.] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA.
[Shacka, John J.; Lu, Liang; Li, Xuelin; Si, Ying; King, Peter H.] Birmingham Vet Affairs Med Ctr, Birmingham, AL 35233 USA.
[Zhang, Xiaowen] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA.
[Cao, Heping] ARS, Utilizat Res Unit, So Reg Res Ctr, USDA, New Orleans, LA 70124 USA.
[King, Peter H.] Univ Alabama Birmingham, Dept Genet, Birmingham, AL 35294 USA.
[King, Peter H.] Univ Alabama Birmingham, Dept Cell Dev & Integrat Biol, Birmingham, AL 35294 USA.
RP Suswam, EA (reprint author), Univ Alabama Birmingham, Dept Neurol, 1720 2nd Ave South,WTI410C, Birmingham, AL 35294 USA.
EM easuswam@uab.edu; pking@uab.edu
FU Department of Veterans Affairs Research; National Institutes of Health
[RO1 NS064133, CA131468, NS057664]
FX Grant support: Department of Veterans Affairs Research, Merit Review
grants (PHK and JJS), National Institutes of Health grants (RO1 NS064133
to PHK, CA131468 to EAS, and NS057664 to LL). The sponsors played no
role in the design of experiments, interpretation of results, or writing
this manuscript.
NR 50
TC 11
Z9 11
U1 0
U2 13
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 JUN
PY 2013
VL 113
IS 2
BP 195
EP 205
DI 10.1007/s11060-013-1112-8
PG 11
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA 162CD
UT WOS:000320241100005
PM 23525947
ER
PT J
AU Backes, DM
Siddiq, A
Cox, DG
Calboli, FCF
Gaziano, JM
Ma, J
Stampfer, M
Hunter, DJ
Camargo, CA
Michaud, DS
AF Backes, Danielle M.
Siddiq, Afshan
Cox, David G.
Calboli, Federico C. F.
Gaziano, J. Michael
Ma, Jing
Stampfer, Meir
Hunter, David J.
Camargo, Carlos A.
Michaud, Dominique S.
TI Single-nucleotide polymorphisms of allergy-related genes and risk of
adult glioma
SO JOURNAL OF NEURO-ONCOLOGY
LA English
DT Article
DE Brain tumors; Glioma; Allergies; Single-nucleotide polymorphisms; Cohort
studies
ID IGE LEVELS; INNATE IMMUNITY; ASTHMA; SUSCEPTIBILITY; GLIOBLASTOMA;
METAANALYSIS; ASSOCIATION; VARIANTS
AB Previous studies have shown an inverse association between allergies and glioma risk; however, results for associations between single nucleotide polymorphisms (SNPs) of allergy-related genes and glioma risk have been inconsistent and restricted to a small number of SNPs. The objective of this study was to examine the association between 166 SNPs of 21 allergy-related genes and glioma risk in a nested case-control study of participants from three large US prospective cohort studies. Blood collection took place between 1982 and 1994 among the 562 included Caucasian participants (143 cases and 419 matched controls) prior to case diagnosis. Custom Illumina assay chips were used for genotyping. Logistic regression analyses, controlling for age and study cohort, were used to determine associations between each SNP and glioma risk. Statistically significant associations were found between rs2494262 and rs2427824 of the FCER1A gene, which encodes the alpha chain of the high affinity immunoglobulin E receptor, and glioma risk (nominal trend p values 0.01 and 0.03, respectively). Significant associations were also found between SNPs in IL10, ADAM33, NOS1 and IL4R and glioma risk. However, our analyses were not corrected for multiple comparisons and need to be interpreted with caution. Our findings with FCER1A SNPs provide further support for the link between allergies and risk of glioma.
C1 [Backes, Danielle M.; Michaud, Dominique S.] Brown Univ, Brown Publ Hlth, Dept Epidemiol, Providence, RI 02912 USA.
[Siddiq, Afshan; Cox, David G.; Calboli, Federico C. F.; Michaud, Dominique S.] Univ London Imperial Coll Sci Technol & Med, Fac Med, Sch Publ Hlth, London SW7 2AZ, England.
[Cox, David G.] UCBL1, CNRS, INSERM, U1052,UMR 5286,Lyon Canc Res Ctr, F-69008 Lyon, France.
[Gaziano, J. Michael] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA.
[Ma, Jing; Stampfer, Meir; Hunter, David J.; Camargo, Carlos A.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA.
[Ma, Jing; Stampfer, Meir; Hunter, David J.; Camargo, Carlos A.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Stampfer, Meir; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Stampfer, Meir; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Camargo, Carlos A.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.
RP Michaud, DS (reprint author), Brown Univ, Brown Publ Hlth, Dept Epidemiol, POB G-S121-2, Providence, RI 02912 USA.
EM dominique_michaud@brown.edu
RI Michaud, Dominique/I-5231-2014; Cox, David/A-2023-2009
OI Cox, David/0000-0002-2152-9259
FU National Institutes of Health [R01 CA114205, P01 CA097193, P01 CA087969,
P01 CA055075]
FX We thank the following state cancer registries for their help: AL, AZ,
AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE,
NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. This
work was supported by the National Institutes of Health [grant numbers
R01 CA114205 to DSM, P01 CA097193 to JMG, P01 CA087969 to MS, P01
CA055075 to Dr. Willett]. This research complies with the current laws
of the country in which it was performed.
NR 29
TC 7
Z9 7
U1 0
U2 5
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 JUN
PY 2013
VL 113
IS 2
BP 229
EP 238
DI 10.1007/s11060-013-1122-6
PG 10
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA 162CD
UT WOS:000320241100008
PM 23525950
ER
PT J
AU Shonka, NA
Theeler, B
Cahill, D
Yung, A
Smith, L
Lei, XD
Gilbert, MR
AF Shonka, Nicole A.
Theeler, Brett
Cahill, Daniel
Yung, Alfred
Smith, Lynette
Lei, Xiudong
Gilbert, Mark R.
TI Outcomes for patients with anaplastic astrocytoma treated with
chemoradiation, radiation therapy alone or radiation therapy followed by
chemotherapy: a retrospective review within the era of temozolomide
SO JOURNAL OF NEURO-ONCOLOGY
LA English
DT Article
DE Anaplastic astrocytoma; Radiation therapy; Chemotherapy; Treatment
ID MALIGNANT GLIOMAS; PHASE-III; GLIOBLASTOMA; RADIOTHERAPY; NECROSIS;
BRAIN; DIBROMODULCITOL; SURVIVAL; TRIAL
AB Treatment for anaplastic astrocytoma (AA) is controversial. To assess three primary treatment approaches, patients from a single institution were retrospectively evaluated. To represent modern treatment selection, patients diagnosed with AA from December 2003 to December 2009 were selected. Those with insufficient data, incomplete pathology, and transformation or reclassification to glioblastoma in fewer than 6 months were excluded. A total of 163 patients were included in the final analyses. Median follow-up time was 4.2 years (range 0.5-7.8 years). Median age and Karnofsky performance status at diagnosis were 39.2 years and 90, respectively. 23.6 % of patients underwent biopsy, and 72.2 % underwent resection. Approximately 31 % received concurrent chemoradiation (CRT), 26.1 % had radiation therapy alone (RT), 38.2 % had radiation therapy followed by chemotherapy (RT-C), and 3 % were treated only with chemotherapy. Temozolomide was used almost exclusively during CRT (94.2 %) and adjuvantly. A median of 9.5 cycles of adjuvant chemotherapy was given. The combination of radiation and chemotherapy, either concurrent or sequential trended toward a higher rate of radiation necrosis. Median progression free survival (PFS) favored RT (not reached) over CRT (1.5 years) and RT-C (3.6 years) adjusted for pairwise comparison (p = 0.033, p = 0.050). Median overall survival (OS) was 5.7 years, and did not differ significantly by treatment group. OS for patients with AA did not vary by initial treatment selection. Although the longer PFS in those receiving RT versus CRT may be confounded by pseudoprogression, the equivalent OS among groups supports RT.
C1 [Shonka, Nicole A.; Smith, Lynette] Univ Nebraska Med Ctr, Nebraska Med Ctr 987680, Omaha, NE 68198 USA.
[Theeler, Brett] Walter Reed Natl Mil Med Ctr, Bethesda, MD 20889 USA.
[Cahill, Daniel] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Yung, Alfred; Lei, Xiudong; Gilbert, Mark R.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
RP Shonka, NA (reprint author), Univ Nebraska Med Ctr, Nebraska Med Ctr 987680, Omaha, NE 68198 USA.
EM nshonka@unmc.edu
RI Gilbert, Mark/J-7494-2016;
OI Gilbert, Mark/0000-0003-2556-9722; Cahill, Daniel/0000-0003-2552-6546
FU NCI NIH HHS [P30 CA016672]
NR 21
TC 12
Z9 13
U1 0
U2 5
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 JUN
PY 2013
VL 113
IS 2
BP 305
EP 311
DI 10.1007/s11060-013-1116-4
PG 7
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA 162CD
UT WOS:000320241100016
PM 23526410
ER
PT J
AU Prabhakar, AM
Harvey, HB
Hirsch, JA
Wicky, S
Oklu, R
AF Prabhakar, Anand M.
Harvey, H. Benjamin
Hirsch, Joshua A.
Wicky, Stephan
Oklu, Rahmi
TI Medical Device Excise Tax: Implications for Interventional Radiologists
SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY
LA English
DT Editorial Material
ID HEALTH REFORM
C1 [Prabhakar, Anand M.; Harvey, H. Benjamin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Imaging, Boston, MA 02114 USA.
[Wicky, Stephan; Oklu, Rahmi] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc Imaging & Intervent, Boston, MA 02114 USA.
[Hirsch, Joshua A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Neurointervent Radiol, Boston, MA 02114 USA.
RP Oklu, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc Imaging & Intervent, 55 Fruit St,GRB 290A, Boston, MA 02114 USA.
EM rahmioklu@gmail.com
NR 13
TC 1
Z9 1
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1051-0443
J9 J VASC INTERV RADIOL
JI J. Vasc. Interv. Radiol.
PD JUN
PY 2013
VL 24
IS 6
BP 795
EP 796
DI 10.1016/j.jvir.2013.02.027
PG 2
WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular
Disease
SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System &
Cardiology
GA 158FY
UT WOS:000319956100006
PM 23707088
ER
PT J
AU Grady, CD
Schwarz, EB
Emeremni, CA
Yabes, J
Akers, A
Zite, N
Borrero, S
AF Grady, Cynthia D.
Schwarz, Eleanor Bimla
Emeremni, Chetachi A.
Yabes, Jonathan
Akers, Aletha
Zite, Nikki
Borrero, Sonya
TI Does a History of Unintended Pregnancy Lessen the Likelihood of Desire
for Sterilization Reversal?
SO JOURNAL OF WOMENS HEALTH
LA English
DT Article
ID TUBAL-STERILIZATION; UNITED-STATES; FEMALE STERILIZATION; REGRET
AB Background: Unintended pregnancy has been significantly associated with subsequent female sterilization. Whether women who are sterilized after experiencing an unintended pregnancy are less likely to express desire for sterilization reversal is unknown.
Methods: This study used national, cross-sectional data collected by the 2006-2010 National Survey of Family Growth. The study sample included women ages 15-44 who were surgically sterile from a tubal sterilization at the time of interview. Multivariable logistic regression was used to examine the relationship between a history of unintended pregnancy and desire for sterilization reversal while controlling for potential confounders.
Results: In this nationally representative sample of 1,418 women who were sterile from a tubal sterilization, 78% had a history of at least one unintended pregnancy and 28% expressed a desire to have their sterilization reversed. In unadjusted analysis, having a prior unintended pregnancy was associated with higher odds of expressing desire for sterilization reversal (odds ratio [OR]: 1.80; 95% confidence interval [CI]: 1.15-2.79). In adjusted analysis controlling for sociodemographic factors, unintended pregnancy was no longer significantly associated with desire for reversal (OR: 1.46; 95% CI: 0.91-2.34).
Conclusion: Among women who had undergone tubal sterilization, a prior history of unintended pregnancy did not decrease desire for sterilization reversal.
C1 [Grady, Cynthia D.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15213 USA.
[Schwarz, Eleanor Bimla; Yabes, Jonathan; Borrero, Sonya] Univ Pittsburgh, Sch Med, Div Gen Internal Med, Pittsburgh, PA 15213 USA.
[Schwarz, Eleanor Bimla] Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA 15213 USA.
[Emeremni, Chetachi A.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15213 USA.
[Yabes, Jonathan; Akers, Aletha] Univ Pittsburgh, Res Ctr, Hlth Care Data Ctr, Pittsburgh, PA 15213 USA.
[Zite, Nikki] Univ Tennessee, Grad Sch Med, Dept Obstet & Gynecol, Knoxville, TN USA.
[Borrero, Sonya] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA.
RP Borrero, S (reprint author), Univ Pittsburgh, Div Gen Internal Med, 230 McKee Pl,Suite 600, Pittsburgh, PA 15213 USA.
EM borrerosp@upmc.edu
OI Schwarz, Eleanor Bimla/0000-0002-9912-8236
FU National Center for Research Resources; National Center For Advancing
Translational Sciences of the National Institutes of Health [2KL2
RR024154-06]
FX Dr. Borrero's effort on this project was supported by the National
Center for Research Resources and the National Center For Advancing
Translational Sciences of the National Institutes of Health through
Grant Number 2KL2 RR024154-06.
NR 20
TC 3
Z9 3
U1 0
U2 2
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1540-9996
J9 J WOMENS HEALTH
JI J. Womens Health
PD JUN
PY 2013
VL 22
IS 6
BP 501
EP 506
DI 10.1089/jwh.2012.3885
PG 6
WC Public, Environmental & Occupational Health; Medicine, General &
Internal; Obstetrics & Gynecology; Women's Studies
SC Public, Environmental & Occupational Health; General & Internal
Medicine; Obstetrics & Gynecology; Women's Studies
GA 161BE
UT WOS:000320164600006
PM 23621776
ER
PT J
AU Mauguen, A
Pignon, JP
Burdett, S
Domerg, C
Fisher, D
Paulus, R
Mandrekar, SJ
Belani, CP
Shepherd, FA
Eisen, T
Pang, H
Collette, L
Sause, WT
Dahlberg, SE
Crawford, J
O'Brien, M
Schild, SE
Parmar, M
Tierney, JF
Le Pechoux, C
Michiels, S
AF Mauguen, Audrey
Pignon, Jean-Pierre
Burdett, Sarah
Domerg, Caroline
Fisher, David
Paulus, Rebecca
Mandrekar, Samithra J.
Belani, Chandra P.
Shepherd, Frances A.
Eisen, Tim
Pang, Herbert
Collette, Laurence
Sause, William T.
Dahlberg, Suzanne E.
Crawford, Jeffrey
O'Brien, Mary
Schild, Steven E.
Parmar, Mahesh
Tierney, Jayne F.
Le Pechoux, Cecile
Michiels, Stefan
CA Surrogate Lung Project Collaborati
TI Surrogate endpoints for overall survival in chemotherapy and
radiotherapy trials in operable and locally advanced lung cancer: a
re-analysis of meta-analyses of individual patients' data
SO LANCET ONCOLOGY
LA English
DT Article
ID PROGRESSION-FREE SURVIVAL; COLORECTAL-CANCER; CLINICAL-TRIALS; TUMOR
RESPONSE; VALIDATION; TIME
AB Background The gold standard endpoint in clinical trials of chemotherapy and radiotherapy for lung cancer is overall survival. Although reliable and simple to measure, this endpoint takes years to observe. Surrogate endpoints that would enable earlier assessments of treatment effects would be useful. We assessed the correlations between potential surrogate endpoints and overall survival at individual and trial levels.
Methods We analysed individual patients' data from 15071 patients involved in 60 randomised clinical trials that were assessed in six meta-analyses. Two meta-analyses were of adjuvant chemotherapy in non-small-cell lung cancer, three were of sequential or concurrent chemotherapy, and one was of modified radiotherapy in locally advanced lung cancer. We investigated disease-free survival (DFS) or progression-free survival (PFS), defined as the time from randomisation to local or distant relapse or death, and locoregional control, defined as the time to the first local event, as potential surrogate endpoints. At the individual level we calculated the squared correlations between distributions of these three endpoints and overall survival, and at the trial level we calculated the squared correlation between treatment effects for endpoints.
Findings In trials of adjuvant chemotherapy, correlations between DFS and overall survival were very good at the individual level (square(2)=0.83, 95% CI 0.83-0.83 in trials without radiotherapy, and 0.87, 0.87-0.87 in trials with radiotherapy) and excellent at trial level (R-2=0.92, 95% CI 0.88-0.95 in trials without radiotherapy and 0.99, 0.98-1.00 in trials with radiotherapy). In studies of locally advanced disease, correlations between PFS and overall survival were very good at the individual level (square(2) range 0.77-0.85, dependent on the regimen being assessed) and trial level (R-2 range 0.89-0.97). In studies with data on locoregional control, individual-level correlations were good (square(2)=0.71, 95% CI 0.71-0.71 for concurrent chemotherapy and square(2)=0.61, 0.61-0.61 for modified vs standard radiotherapy) and trial-level correlations very good (R-2=0.85, 95% CI 0.77-0.92 for concurrent chemotherapy and R-2=0.95, 0.91-0.98 for modified vs standard radiotherapy).
Interpretation We found a high level of evidence that DFS is a valid surrogate endpoint for overall survival in studies of adjuvant chemotherapy involving patients with non-small-cell lung cancers, and PFS in those of chemotherapy and radiotherapy for patients with locally advanced lung cancers. Extrapolation to targeted agents, however, is not automatically warranted.
C1 [Mauguen, Audrey; Pignon, Jean-Pierre; Domerg, Caroline; Michiels, Stefan] Inst Gustave Roussy, Metaanal Unit, Dept Biostat & Epidemiol, F-94805 Villejuif, France.
[Le Pechoux, Cecile] Inst Gustave Roussy, Dept Radiotherapy, F-94805 Villejuif, France.
[Burdett, Sarah; Fisher, David; Parmar, Mahesh; Tierney, Jayne F.] MRC Clin Trials Unit, London, England.
[Paulus, Rebecca] RTOG Stat Ctr, Philadelphia, PA USA.
[Mandrekar, Samithra J.; Schild, Steven E.] Mayo Clin, Rochester, MN USA.
[Mandrekar, Samithra J.; Schild, Steven E.] North Cent Canc Treatment Grp, Rochester, MN USA.
[Belani, Chandra P.] Penn State Hershey Canc Inst, Hershey, PA USA.
[Shepherd, Frances A.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada.
[Shepherd, Frances A.] NCIC Clin Trials Grp, Toronto, ON, Canada.
[Eisen, Tim] Cambridge Biomed Res Ctr, Cambridge, England.
[Pang, Herbert; Crawford, Jeffrey] Duke Univ, Canc & Leukemia Grp B, Ctr Stat, Durham, NC USA.
[Collette, Laurence] EORTC Headquarters, Brussels, Belgium.
[Sause, William T.] Intermt Med Ctr, Murray, UT USA.
[Dahlberg, Suzanne E.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Dahlberg, Suzanne E.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[O'Brien, Mary] Royal Marsden Hosp, London SW3 6JJ, England.
[Michiels, Stefan] Univ Libre Bruxelles, Inst Jules Bordet, Brussels, Belgium.
[Michiels, Stefan] Univ Paris 11, Paris, France.
RP Pignon, JP (reprint author), Inst Gustave Roussy, Metaanal Unit, Dept Biostat & Epidemiol, 114 Rue Edoudard Vaillant, F-94805 Villejuif, France.
EM jppignon@igr.fr
RI koning, caro/A-5339-2008; Michiels, Stefan/L-1516-2013; Higgins,
Julian/H-4008-2011;
OI Michiels, Stefan/0000-0002-6963-2968; Higgins,
Julian/0000-0002-8323-2514; Belani, Chandra/0000-0001-5049-5329; schild,
steven/0000-0002-2850-4126; Mauguen, Audrey/0000-0003-3236-6093;
DAUTZENBERG, Bertrand/0000-0001-6937-8907
FU Programme Hospitalier de Recherche Clinique; Ligue Nationale Contre le
Cancer; British Medical Research Council; Sanofi Aventis; Sanofi-Aventis
FX Programme Hospitalier de Recherche Clinique, Ligue Nationale Contre le
Cancer, British Medical Research Council, Sanofi Aventis.; This study
was sponsored by Programme Hospitalier de Recherche Clinique, Ligue
Nationale Contre le Cancer, British Medical Research Council, and
Sanofi-Aventis. We thank the participating collaborative groups: Study
Group of Adjuvant Chemotherapy for Lung Cancer, Arbeitsgemeinschaft
Radioonkologie der Deutschen Krebsgesellschaft, Groupe d'Etude et de
Traitement des Cancers Bronchiques, Cancer and Leukemia Group B, Eastern
Cooperative Oncology Group, European Organization for Research and
Treatment of Cancer, Groupe d'Oncologie Thoracique
Lyon-Saint-Etienne-Groupe Francais de Pneumo-Cancerologie, Japan
Clinical Oncology Group, Japan Lung Cancer Research Group, Medical
Research Council, North Central Cancer Treatment Group, National Cancer
Institute of Canada Clinical Trial Group, Radiation Therapy Oncology
Group, and West Japan Study Group for Lung Cancer Surgery, and the
clinical investigators of the trials and the patients.
NR 28
TC 41
Z9 41
U1 0
U2 10
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1470-2045
EI 1474-5488
J9 LANCET ONCOL
JI Lancet Oncol.
PD JUN
PY 2013
VL 14
IS 7
BP 619
EP 626
DI 10.1016/S1470-2045(13)70158-X
PG 8
WC Oncology
SC Oncology
GA 163XH
UT WOS:000320371100048
PM 23680111
ER
PT J
AU Marak, CP
Dorokhova, O
Guddati, AK
AF Marak, Creticus P.
Dorokhova, Olena
Guddati, Achuta K.
TI Solitary fibrous tumor of the pleura
SO MEDICAL ONCOLOGY
LA English
DT Article
DE Solitary; Fibrous tumor; Pleura; Hemangiopericytoma
ID DOEGE-POTTER-SYNDROME; SURGICAL-TREATMENT; LOCALIZED BENIGN;
MESOTHELIOMA; HYPOGLYCEMIA; EXPRESSION; DIAGNOSIS; RESECTION; GIANT
AB Solitary fibrous tumor of the pleura (SFTP) is a rare tumor of mesenchymal origin which can grow to a large size and present with symptoms of cough and pleuritic chest pain. No specific etiological factors for SFTPs are known and they may grow undetected for several years. These tumors are usually benign and may mimic a variety of malignancies. SFTPs are often detected as peripheral opacities on chest X-ray. Unfortunately, fine needle aspiration rarely provides adequate information for a definitive diagnosis. Imaging with computed tomography provides details about the size and extent of any invasion into adjacent tissues. Surgical resection is the mainstay of treatment, and immunohistochemistry of the resected tumor often provides confirmation of the diagnosis. Some SFTPs have been observed to be malignant, and surgical intervention is often lifesaving. There is no adequate data to support the usage of radiotherapy and chemotherapy in the treatment of SFTPs. This tumor exemplifies malignancies which require surgical resection to preempt worse outcomes. Awareness of their presentation and clinical course may help the clinician provide a prompt referral to the thoracic surgeon for resection.
C1 [Marak, Creticus P.] Yeshiva Univ, Albert Einstein Coll Med, Montefiore Hosp, Div Pulm & Crit Care Med, New York, NY 10033 USA.
[Dorokhova, Olena] Yeshiva Univ, Albert Einstein Coll Med, Montefiore Hosp, Dept Pathol, New York, NY 10033 USA.
[Guddati, Achuta K.] Harvard Univ, Massachusetts Gen Hosp, Harvard Med Sch, Dept Internal Med, Boston, MA 02115 USA.
RP Guddati, AK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Harvard Med Sch, Dept Internal Med, 50 Fruit St, Boston, MA 02115 USA.
EM aguddati@partners.org
NR 42
TC 3
Z9 5
U1 0
U2 1
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 1357-0560
J9 MED ONCOL
JI Med. Oncol.
PD JUN
PY 2013
VL 30
IS 2
AR UNSP 573
DI 10.1007/s12032-013-0573-0
PG 6
WC Oncology
SC Oncology
GA 151HD
UT WOS:000319450400080
PM 23576139
ER
PT J
AU Shaheen, S
Guddati, AK
AF Shaheen, Shagufta
Guddati, Achuta K.
TI Secondary mucosa-associated lymphoid tissue (MALT) lymphoma of the colon
SO MEDICAL ONCOLOGY
LA English
DT Article
DE MALT; Secondary; Colon; Adenocarcinoma; Lymphoma
ID HELICOBACTER-PYLORI ERADICATION; OF-THE-LITERATURE; GASTRIC LYMPHOMA;
RECTUM; RADIOTHERAPY; REGRESSION; PROGNOSIS; FEATURES
AB Mucosa-associated lymphoid tissue (MALT)type lymphomas most commonly occur in the stomach and have been associated with Helicobacter pylori infection. However, MALT-type lymphoma of the colon is a rare entity. It commonly manifests with symptoms of weight loss, low-grade fever, constipation, melena, and hematochezia. Unlike gastric lymphoma, it is difficult to detect MALT-type lymphoma of the colon by imaging. Colonoscopy may reveal lesions whose biopsy most commonly shows abundant B lymphocytes. There is no universal immunohistochemistry profile for MALT-type lymphoma but CD 20 staining is commonly seen. Trisomies and translocations have been described and their presence has been correlated with treatment response. Due to the rarity of colonic MALT-type lymphoma, no standard guidelines are available for its management. It often occurs individually and rarely occurs simultaneously with concurrent colon adenocarcinoma. This case report describes the presentation and clinical course of a secondary MALT-type lymphoma in a patient who underwent colectomy for a prior colon adenocarcinoma.
C1 [Shaheen, Shagufta; Guddati, Achuta K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Internal Med, Boston, MA 02115 USA.
RP Guddati, AK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Internal Med, 50 Fruit St, Boston, MA 02115 USA.
EM aguddati@partners.org
NR 24
TC 2
Z9 2
U1 0
U2 11
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 1357-0560
J9 MED ONCOL
JI Med. Oncol.
PD JUN
PY 2013
VL 30
IS 2
AR UNSP 502
DI 10.1007/s12032-013-0502-2
PG 4
WC Oncology
SC Oncology
GA 151HD
UT WOS:000319450400011
PM 23423787
ER
PT J
AU Li, XH
Zhang, D
Liu, B
AF Li, Xinhua
Zhang, Da
Liu, Bob
TI Workload and transmission data for the installation of a digital breast
tomosynthesis system
SO MEDICAL PHYSICS
LA English
DT Article
DE radiation protection; x rays; shielding; workload; transmission; breast
tomosynthesis
ID MAMMOGRAPHY; FACILITIES; SCATTER; KVP
AB Purpose: Digital breast tomosynthesis (DBT) differs from conventional mammography in target/filter, kVp range, and imaging geometry. The aim of this study was to assess the breast input exposure of a DBT system by completing a workload survey of DBT installations, and to determine the parameters alpha, beta, and gamma in the Archer equation for the primary radiation generated by the clinical workload distributions.
Methods: The authors conducted a retrospective survey of the x-ray breast imaging performed between September 2011 and September 2012 in three clinical DBT rooms equipped with Selenia Dimensions systems (Hologic Inc., Bedford, MA). A total of 343 examinations were analyzed to calculate the workload (mA-minute) and the primary air kerma at 1 m from the source (K-1). Transmission curves were calculated for the primary radiation generated by the workload distributions of the DBT rooms, and were fitted to the Archer equation.
Results: There were large variations in patient volume and workload in the three examination rooms. In all these rooms, the average tube voltage (kVp) was about 31, the average K-1 per patient was 16-21 mGy, and the average mA-minute per patient was 1.4-2.2 times higher than that of the mammography room described in NCRP Report No. 147. Most DBT screening examinations consisted of four two-dimensional mammographic views plus four tomosynthesis scans; the numbers of views acquired in diagnostic examinations varied widely. Tomosynthesis scans contributed about 30% of total mA-minute and about 50% of K-1. For the primary radiation generated by the clinical workload distributions, a was similar to that of 40-45 kVp W/Al (target/filter), and alpha + beta was similar to that of 30 kVp W/Al.
Conclusions: The workload (mA-minute and K1) distributions of mammographic examinations with DBT differ from conventional mammography. A field survey of patient volume and x-ray tube usage is important for the shielding design of DBT facilities. The clinical workloads and transmission data presented in this paper may be useful for clinical medical physicists. (C) 2013 American Association of Physicists in Medicine.
C1 [Liu, Bob] Massachusetts Gen Hosp, Div Diagnost Imaging Phys, Boston, MA 02114 USA.
Massachusetts Gen Hosp, Webster Ctr Adv Res & Educ Radiat, Dept Radiol, Boston, MA 02114 USA.
RP Liu, B (reprint author), Massachusetts Gen Hosp, Div Diagnost Imaging Phys, Boston, MA 02114 USA.
EM bliu7@bics.bwh.harvard.edu
NR 10
TC 3
Z9 3
U1 0
U2 12
PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS
PI MELVILLE
PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA
SN 0094-2405
J9 MED PHYS
JI Med. Phys.
PD JUN
PY 2013
VL 40
IS 6
AR 063901
DI 10.1118/1.4803470
PG 8
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 157IF
UT WOS:000319889100040
PM 23718617
ER
PT J
AU Chang, I
Majid, S
Saini, S
Zaman, MS
Yamamura, S
Chiyomaru, T
Shahryari, V
Fukuhara, S
Deng, GR
Dahiya, R
Tanaka, Y
AF Chang, Inik
Majid, Shahana
Saini, Sharanjot
Zaman, Mohd S.
Yamamura, Soichiro
Chiyomaru, Takeshi
Shahryari, Varahram
Fukuhara, Shinichiro
Deng, Guoren
Dahiya, Rajvir
Tanaka, Yuichiro
TI Hrk Mediates 2-Methoxyestradiol- Induced Mitochondrial Apoptotic
Signaling in Prostate Cancer Cells
SO MOLECULAR CANCER THERAPEUTICS
LA English
DT Article
ID BH3-ONLY PROTEINS; MEMBRANE PERMEABILIZATION; PROMOTER METHYLATION;
BCL-2 PROTEINS; GENE; BAX; INACTIVATION; EXPRESSION; TARGET;
IDENTIFICATION
AB Prostate cancer is one of the most prevalent cancers in males and ranks as the second most common cause of cancer-related deaths. 2-methoxyestradiol (2-ME), an endogenous estrogen metabolite, is a promising anticancer agent for various types of cancers. Although 2-ME has been shown to activate c-Jun-NH2-kinase (JNK) and mitochondrial-dependent apoptotic signaling pathways, the underlying mechanisms, including downstream effectors, remain unclear. Here, we report that the human Bcl-2 homology 3 (BH3)-only protein harakiri (Hrk) is a critical effector of 2-ME-induced JNK/mitochondria-dependent apoptosis in prostate cancer cells. Hrk mRNA and protein are preferentially upregulated by 2-ME, and Hrk induction is dependent on the JNK activation of c-Jun. Hrk knockdown prevents 2-ME-mediated apoptosis by attenuating the decrease in mitochondrial membrane potential, subsequent cytochrome c (cyt c) release, and caspase activation. Involvement of the proapoptotic protein Bak in this process suggested the possible interaction between Hrk and Bak. Thus, Hrk activation by 2-ME or its overexpression displaced Bak from the complex with antiapoptotic protein Bcl-xL, whereas deletion of the Hrk BH3 domain abolished its interaction with Bcl-xL, reducing the proapoptotic function of Hrk. Finally, Hrk is also involved in the 2-ME-mediated reduction of X-linked inhibitor of apoptosis through Bak activation in prostate cancer cells. Together, our findings suggest that induction of the BH3-only protein Hrk is a critical step in 2-ME activation of the JNK-induced apoptotic pathway, targeting mitochondria by liberating proapoptotic protein Bak. (C) 2013 AACR.
C1 [Tanaka, Yuichiro] San Francisco VA Med Ctr, Dept Urol, San Francisco, CA 94121 USA.
[Tanaka, Yuichiro] Univ Calif San Francisco, San Francisco, CA 94121 USA.
RP Tanaka, Y (reprint author), San Francisco VA Med Ctr, Dept Urol, 4150 Clement St, San Francisco, CA 94121 USA.
EM yuichiro.tanaka@ucsf.edu
FU Veterans Affairs Merit Review grant; Research Enhancement Award Program
FX This study was supported by the Veterans Affairs Merit Review grant and
Research Enhancement Award Program (Y. Tanaka).
NR 39
TC 6
Z9 7
U1 1
U2 6
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 JUN
PY 2013
VL 12
IS 6
BP 1049
EP 1059
DI 10.1158/1535-7163.MCT-12-1187
PG 11
WC Oncology
SC Oncology
GA 160HT
UT WOS:000320110500020
PM 23580416
ER
PT J
AU Hu, J
Locasale, JW
Bielas, JH
O'Sullivan, J
Sheahan, K
Cantley, LC
Vander Heiden, MG
Vitkup, D
AF Hu, Jie
Locasale, Jason W.
Bielas, Jason H.
O'Sullivan, Jacintha
Sheahan, Kieran
Cantley, Lewis C.
Vander Heiden, Matthew G.
Vitkup, Dennis
TI Heterogeneity of tumor-induced gene expression changes in the human
metabolic network
SO NATURE BIOTECHNOLOGY
LA English
DT Article
ID ACUTE MYELOID-LEUKEMIA; GLUTAMINE-METABOLISM; CANCER METABOLISM;
PYRUVATE-KINASE; CELL-METABOLISM; HYPOXIA; GROWTH; HYDROXYLASES;
LIPOGENESIS; INHIBITION
AB Reprogramming of cellular metabolism is an emerging hallmark of neoplastic transformation. However, it is not known how the expression of metabolic genes in tumors differs from that in normal tissues, or whether different tumor types exhibit similar metabolic changes. Here we compare expression patterns of metabolic genes across 22 diverse types of human tumors. Overall, the metabolic gene expression program in tumors is similar to that in the corresponding normal tissues. Although expression changes of some metabolic pathways (e.g., upregulation of nucleotide biosynthesis and glycolysis) are frequently observed across tumors, expression changes of other pathways (e.g., oxidative phosphorylation) are very heterogeneous. Our analysis also suggests that the expression changes of some metabolic genes (e.g., isocitrate dehydrogenase and fumarate hydratase) may enhance or mimic the effects of recurrent mutations in tumors. On the level of individual biochemical reactions, many hundreds of metabolic isoenzymes show significant and tumor-specific expression changes. These isoenzymes are potential targets for anticancer therapy.
C1 [Hu, Jie; Vitkup, Dennis] Columbia Univ, Ctr Computat Biol & Bioinformat, New York, NY 10027 USA.
[Hu, Jie; Vitkup, Dennis] Columbia Univ, Initiat Syst Biol, New York, NY USA.
[Locasale, Jason W.] Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA.
[Bielas, Jason H.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Translat Res Program, Seattle, WA 98104 USA.
[Bielas, Jason H.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA.
[O'Sullivan, Jacintha; Sheahan, Kieran] St Vincents Univ Hosp, Dublin 4, Ireland.
[Cantley, Lewis C.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA.
[Cantley, Lewis C.] Harvard Univ, Beth Israel Deaconess Med Ctr, Div Signal Transduct, Sch Med, Boston, MA 02215 USA.
[Cantley, Lewis C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Vander Heiden, Matthew G.] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA.
[Vander Heiden, Matthew G.] MIT, Dept Biol, Cambridge, MA USA.
[Vander Heiden, Matthew G.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Vitkup, Dennis] Columbia Univ, Dept Biomed Informat, New York, NY USA.
RP Vitkup, D (reprint author), Columbia Univ, Ctr Computat Biol & Bioinformat, New York, NY 10027 USA.
EM dv2121@columbia.edu
RI Cantley, Lewis/D-1800-2014; Hu, Jie/J-5075-2012;
OI Cantley, Lewis/0000-0002-1298-7653; O'Sullivan,
Jacintha/0000-0001-8622-9858; Locasale, Jason/0000-0002-7766-3502
FU US National Institutes of Health [GM079759]; US National Centers for
Biomedical Computing [U54CA121852]; NIH Pathway to Independence Award
[R00CA168997]; Ellison Medical Foundation New Scholar [AG-NS-0577-09];
National Institute of Environmental Health Sciences [R01ES019319]; New
Development Funds from the Fred Hutchinson Cancer Research Center;
Burroughs Wellcome Fund; Damon Runyon Cancer Research Foundation;
National Cancer Institute
FX We would like to sincerely thank the members of the Vitkup laboratory
for discussions. This work was supported by US National Institutes of
Health grant GM079759 to D.V. and US National Centers for Biomedical
Computing grant U54CA121852 to Columbia University. J.W.L. is supported
by an NIH Pathway to Independence Award R00CA168997. J.H.B. is supported
by an Ellison Medical Foundation New Scholar award AG-NS-0577-09, a
National Institute of Environmental Health Sciences grant R01ES019319,
and New Development Funds from the Fred Hutchinson Cancer Research
Center. M.G.V.H. acknowledges support from the Burroughs Wellcome Fund,
the Damon Runyon Cancer Research Foundation, the Smith Family and the
National Cancer Institute.
NR 50
TC 84
Z9 86
U1 0
U2 24
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1087-0156
J9 NAT BIOTECHNOL
JI Nat. Biotechnol.
PD JUN
PY 2013
VL 31
IS 6
BP 522
EP U11
DI 10.1038/nbt.2530
PG 10
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA 160IO
UT WOS:000320113200023
PM 23604282
ER
PT J
AU Allareddy, V
Karimbux, NY
Dodson, TB
Lee, MK
AF Allareddy, Veerasathpurush
Karimbux, Nadeem Y.
Dodson, Thomas B.
Lee, Min Kyeong
TI Predictors of never events in patients undergoing radical dissection of
cervical lymph nodes
SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY
LA English
DT Article
ID SMALL-AREA VARIATIONS; RISK ADJUSTMENT; ADVERSE EVENTS; HEALTH-CARE;
COMPLICATIONS; HOSPITALIZATION; MORTALITY; QUALITY; RATES
AB Objective. The aim of this study was to identify variables associated with infection-related never events in patients undergoing radical neck dissections for head and neck cancer.
Study Design. All hospitalizations with head and neck cancer that underwent radical dissection of cervical lymph nodes were selected from the Nationwide Inpatient Sample. Predictor variables included patient and hospital-level factors. Outcome variable was occurrence of >= 1 never events. Association between predictor and outcome variables was examined by using bivariate and multivariable logistic regression models.
Results. There were 10,660 hospitalizations. At least 1 never event occurred in 7.8% of hospitalizations. Teaching hospitals were associated with higher odds of having >= 1 never event compared with nonteaching hospitals (odds ratio 1.92; P = .02). Presence of comorbid conditions and race were other significant predictors of never events.
Conclusions. Teaching hospitals and presence of comorbid conditions were associated with higher odds of experiencing a never event.
C1 [Allareddy, Veerasathpurush; Lee, Min Kyeong] Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA.
[Karimbux, Nadeem Y.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA.
[Dodson, Thomas B.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Ctr Appl Clin Outcomes, Boston, MA 02114 USA.
[Dodson, Thomas B.] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA.
RP Lee, MK (reprint author), Harvard Univ, Sch Dent Med, Dept Dev Biol, 188 Longwood Ave, Boston, MA 02115 USA.
EM minkyeong_lee@hsdm.harvard.edu
NR 21
TC 7
Z9 7
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 2212-4403
J9 OR SURG OR MED OR PA
JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol.
PD JUN
PY 2013
VL 115
IS 6
BP 710
EP 716
DI 10.1016/j.oooo.2012.09.004
PG 7
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 163WN
UT WOS:000320368600012
PM 23246228
ER
PT J
AU Festa, F
Rollins, SM
Vattem, K
Hathaway, M
Lorenz, P
Mendoza, EA
Yu, XB
Qiu, J
Kilmer, G
Jensen, P
Webb, B
Ryan, ET
LaBaer, J
AF Festa, Fernanda
Rollins, Sean M.
Vattem, Krishna
Hathaway, Margarita
Lorenz, Phillip
Mendoza, Eliseo A.
Yu, Xiaobo
Qiu, Ji
Kilmer, Greg
Jensen, Penny
Webb, Brian
Ryan, Ed T.
LaBaer, Joshua
TI Robust microarray production of freshly expressed proteins in a human
milieu
SO PROTEOMICS CLINICAL APPLICATIONS
LA English
DT Article
DE Human Coupled IVT; In vitro transcription and translation; NAPPA;
Protein microarray
ID HUMORAL IMMUNE-RESPONSES; RHEUMATOID-ARTHRITIS; CANCER; AUTOANTIBODIES;
GENERATION; PROTEOME; ARRAYS; DNA
AB Purpose In vitro transcription/translation (IVTT) systems are widely used in proteomics. For clinical applications, mammalian systems are preferred for protein folding and activity; however, the level of protein obtained is low. A new system extracted from human cells (1-Step Human Coupled IVT (HCIVT)) has the potential to overcome this problem and deliver high yields of protein expressed in a human milieu. Experimental design Western blots and self-assembled protein microarrays were used to test the efficiency of protein synthesis by HCIVT compared to rabbit reticulocyte lysate (RRL). The arrays were also used to measure the immune response obtained from serum of patients exposed to pathogens or vaccine. Results HCIVT performed better than RRL in all experiments. The yield of protein synthesized in HCIVT is more than ten times higher than RRL, in both Western blot and protein microarrays. Moreover, HCIVT showed a robust lot-to-lot reproducibility. In immune assays, the signals of many antigens were detected only in HCIVT-expressed arrays, mainly due to the reduction in the background signal and the increased levels of protein on the array. Conclusion and clinical relevance HCIVT is a robust in vitro transcription and translation system that yields high levels of protein produced in a human milieu. It can be used in applications where protein expression in a mammalian system and high yields are needed. The increased immunogenic response of HCIVT-expressed proteins will be critical for biomarker discovery in many diseases, including cancer.
C1 [Festa, Fernanda; Hathaway, Margarita; Lorenz, Phillip; Mendoza, Eliseo A.; Yu, Xiaobo; Qiu, Ji; LaBaer, Joshua] Arizona State Univ, Biodesign Inst, Virginia G Piper Ctr Personalized Diagnost, Tempe, AZ 85287 USA.
[Rollins, Sean M.; Ryan, Ed T.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Rollins, Sean M.] Fitchburg State Univ, Fitchburg, MA USA.
RP LaBaer, J (reprint author), Arizona State Univ, Biodesign Inst, Virginia G Piper Ctr Personalized Diagnost, 1001 S McAllister Ave, Tempe, AZ 85287 USA.
EM jlabaer@asu.edu
RI Yu, Xiaobo/F-5997-2015
OI Rollins, Sean/0000-0002-3724-1989;
FU NIH [U01CA117374, U01AI077883]; Virginia G. Piper Foundation
FX The authors would like to thank Garrick Wallstrom for his help in the
data analysis and Deborah Paterick for the preparation of the NAPPA
schematic figure. This project was supported by the NIH grant
U01CA117374, U01AI077883, and Virginia G. Piper Foundation.
NR 33
TC 16
Z9 16
U1 0
U2 11
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA POSTFACH 101161, 69451 WEINHEIM, GERMANY
SN 1862-8346
EI 1862-8354
J9 PROTEOM CLIN APPL
JI Proteom. Clin. Appl.
PD JUN
PY 2013
VL 7
IS 5-6
SI SI
BP 372
EP 377
DI 10.1002/prca.201200063
PG 6
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 166KZ
UT WOS:000320554800007
PM 23027544
ER
PT J
AU Gu, JW
Xu, XG
Caracappa, PF
Liu, B
AF Gu, Jianwei
Xu, X. George
Caracappa, Peter F.
Liu, Bob
TI Fetal doses to pregnant patients from CT with tube current modulation
calculated using Monte Carlo simulations and realistic phantoms
SO RADIATION PROTECTION DOSIMETRY
LA English
DT Article
ID MULTIDETECTOR CT; REDUCTION; ORGAN; FETUS; MDCT; DOSIMETRY; SCANNER
AB To investigate the radiation dose to the fetus using retrospective tube current modulation (TCM) data selected from archived clinical records. This paper describes the calculation of fetal doses using retrospective TCM data and Monte Carlo (MC) simulations. Three TCM schemes were adopted for use with three pregnant patient phantoms. MC simulations were used to model CT scanners, TCM schemes and pregnant patients. Comparisons between organ doses from TCM schemes and those from non-TCM schemes show that these three TCM schemes reduced fetal doses by 14, 18 and 25 , respectively. These organ doses were also compared with those from ImPACT calculation. It is found that the difference between the calculated fetal dose and the ImPACT reported dose is as high as 46 . This work demonstrates methods to study organ doses from various TCM protocols and potential ways to improve the accuracy of CT dose calculation for pregnant patients.
C1 [Gu, Jianwei; Xu, X. George; Caracappa, Peter F.] Rensselaer Polytech Inst, Program Nucl Engn & Engn Phys, Troy, NY 12180 USA.
[Liu, Bob] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
RP Xu, XG (reprint author), Rensselaer Polytech Inst, Program Nucl Engn & Engn Phys, Troy, NY 12180 USA.
EM xug2@rpi.edu
FU National Cancer Institute [R01CA116743]
FX Dr Xinhua Li from Massachusetts General Hospital provided help in CTDI
measurements. The CT scanner modelling and MC computing resources were
made available from a project funded by the National Cancer Institute
(R01CA116743).
NR 26
TC 7
Z9 8
U1 1
U2 9
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0144-8420
J9 RADIAT PROT DOSIM
JI Radiat. Prot. Dosim.
PD JUN
PY 2013
VL 155
IS 1
BP 64
EP 72
DI 10.1093/rpd/ncs312
PG 9
WC Environmental Sciences; Public, Environmental & Occupational Health;
Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical
Imaging
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Nuclear Science & Technology; Radiology, Nuclear Medicine &
Medical Imaging
GA 162OO
UT WOS:000320274900008
PM 23222824
ER
PT J
AU Davidson, CL
Babson, KA
Bonn-Miller, MO
Souter, T
Vannoy, S
AF Davidson, Collin L.
Babson, Kimberly A.
Bonn-Miller, Marcel O.
Souter, Tasha
Vannoy, Steven
TI The Impact of Exercise on Suicide Risk: Examining Pathways through
Depression, PTSD, and Sleep in an Inpatient Sample of Veterans
SO SUICIDE AND LIFE-THREATENING BEHAVIOR
LA English
DT Article
ID POSTTRAUMATIC-STRESS-DISORDER; RANDOMIZED CONTROLLED-TRIAL; NATIONAL
COMORBIDITY SURVEY; LATE-LIFE DEPRESSION; PHYSICAL-ACTIVITY;
PRIMARY-CARE; MENTAL-HEALTH; MAJOR DEPRESSION; COMMUNITY SAMPLE;
OLDER-ADULTS
AB Suicide has a large public health impact. Although effective interventions exist, the many people at risk for suicide cannot access these interventions. Exercise interventions hold promise in terms of reducing suicide because of their ease of implementation. While exercise reduces depression, and reductions in depressive symptoms are linked to reduced suicidal ideation, no studies have directly linked exercise and suicide risk. The current study examined this association, including potential mediators (i.e., sleep disturbance, posttraumatic stress symptoms, and depression), in a sample of Veterans. SEM analyses revealed that exercise was directly and indirectly associated with suicide risk. Additionally, exercise was associated with fewer depressive symptoms and better sleep patterns, each of which was, in turn, related to lower suicide risk.
C1 [Davidson, Collin L.] Denver VA Med Ctr, VA VISN MIRECC 19, Denver, CO USA.
[Babson, Kimberly A.; Bonn-Miller, Marcel O.] VA Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat, Menlo Pk, CA USA.
[Babson, Kimberly A.; Souter, Tasha] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Palo Alto, CA 94304 USA.
[Bonn-Miller, Marcel O.] VA Palo Alto Hlth Care Syst, Natl Ctr PTSD, Menlo Pk, CA USA.
[Bonn-Miller, Marcel O.] Philadelphia VAMC, Ctr Excellence Subst Abuse Treatment & Educ, Philadelphia, PA USA.
[Souter, Tasha] VA Palo Alto Hlth Care Syst, Menlo Pk, CA USA.
[Vannoy, Steven] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
RP Davidson, CL (reprint author), 1055 Clermont St, Denver, CO 80220 USA.
EM collin.davidson@va.gov
OI Babson, Kimberly/0000-0002-9233-8230; Vannoy, Steven/0000-0003-3029-8306
NR 73
TC 14
Z9 14
U1 8
U2 38
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 JUN
PY 2013
VL 43
IS 3
BP 279
EP 289
DI 10.1111/sltb.12014
PG 11
WC Psychiatry; Psychology, Multidisciplinary
SC Psychiatry; Psychology
GA 161GO
UT WOS:000320180700005
PM 23901428
ER
PT J
AU Dai, HB
Yu, ZY
Fan, X
Liu, N
Yan, M
Chen, Z
Lo, EH
Hajjar, KA
Wang, XY
AF Dai, Haibin
Yu, Zhanyang
Fan, Xiang
Liu, Ning
Yan, Min
Chen, Zhong
Lo, Eng H.
Hajjar, Katherine A.
Wang, Xiaoying
TI Dysfunction of annexin A2 contributes to hyperglycaemia-induced loss of
human endothelial cell surface fibrinolytic activity
SO THROMBOSIS AND HAEMOSTASIS
LA English
DT Article
DE Annexin A2; hyperglycaemia; fibrinolytic activity; advanced glycation
end-product; human brain microvascular endothelial cells
ID TISSUE-PLASMINOGEN-ACTIVATOR; GLYCATION END-PRODUCTS; CAROTID-ARTERY;
POTENTIAL ROLE; IN-VITRO; T-PA; RECEPTOR; ATHEROSCLEROSIS; INHIBITOR-1;
THROMBOSIS
AB Hyperglycaemia impairs fibrinolytic activity on the surface of endothelial cells, but the underlying mechanisms are not fully understood. In this study, we tested the hypothesis that hyperglycaemia causes dysfunction of the endothelial membrane protein annexin A2, thereby leading to an overall reduction of fibrinolytic activity. Hyperglycaemia for 7 days significantly reduced cell surface fibrinolytic activity in human brain microvascular endothelial cells (HBMEC). Hyperglycaemia also decreased tissue type plasminogen activator (t-PA), plasminogen, and annexin A2 mRNA and protein expression, while increasing plasminogen activator inhibitor-1 (PAI-1). No changes in p11 mRNA or protein expression were detected. Hyperglycaemia significantly increased AGE-modified forms of total cellular and membrane annexin A2. The hyperglycemia-associated reduction in fibrinolytic activity was fully restored upon incubation with recombinant annexin A2 (rA2), but not AGE-modified annexin A2 or exogenous t-PA. Hyperglycaemia decreased t-PA, upregulated PAI-1 and induced AGE-related disruption of annexin A2 function, all of which contributed to the overall reduction in endothelial cell surface fibrinolytic activity. Further investigations to elucidate the underlying molecular mechanisms and pathophysiological implications of A2 derivatisation might ultimately lead to a better understanding of mechanisms of impaired vascular fibrinolysis, and to development of new interventional strategies for the thrombotic vascular complications in diabetes.
C1 [Dai, Haibin; Yan, Min; Chen, Zhong] Zhejiang Univ, Sch Med, Affiliated Hosp 2, Hangzhou 310009, Zhejiang, Peoples R China.
[Dai, Haibin; Yu, Zhanyang; Fan, Xiang; Liu, Ning; Lo, Eng H.; Wang, Xiaoying] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroprotect Res Lab,Dept Neurol, Charlestown, MA USA.
[Dai, Haibin; Yu, Zhanyang; Fan, Xiang; Liu, Ning; Lo, Eng H.; Wang, Xiaoying] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA USA.
[Dai, Haibin; Yu, Zhanyang; Fan, Xiang; Liu, Ning; Lo, Eng H.; Wang, Xiaoying] Harvard Univ, Sch Med, Program Neurosci, Charlestown, MA USA.
[Hajjar, Katherine A.] Weill Cornell Med Coll, Dept Cell & Dev Biol, New York, NY USA.
RP Dai, HB (reprint author), Zhejiang Univ, Sch Med, Affiliated Hosp 2, Hangzhou 310009, Zhejiang, Peoples R China.
EM haibindai@zju.edu.cn; wangxi@helix.mgh.harvard.edu
OI Dai, Haibin/0000-0002-5768-2714
FU National Institute of Health [R01-NS065998, UO1-NS072324, P01-NS55104,
R01-HL042493, R01-HL090895]; China National Natural Science Foundation
[81173040]
FX This work was supported in part by the National Institute of Health
grants R01-NS065998 and UO1-NS072324 (to X. Wang), P01-NS55104 (to E.H.
Lo), and R01-HL042493 and R01-HL090895 (to K.A. Hajjar); and the China
National Natural Science Foundation grant 81173040 (to H. Dai).
NR 41
TC 11
Z9 12
U1 1
U2 7
PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN
PI STUTTGART
PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY
SN 0340-6245
J9 THROMB HAEMOSTASIS
JI Thromb. Haemost.
PD JUN
PY 2013
VL 109
IS 6
BP 1070
EP 1078
DI 10.1160/TH12-12-0944
PG 9
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 163RY
UT WOS:000320355800012
PM 23572070
ER
PT J
AU Gao, CY
Xie, R
Li, W
Zhou, J
Liu, SC
Cao, FL
Liu, Y
Ma, RS
Si, Y
Liu, Y
Bi, YY
Gilbert, GE
Shi, JL
AF Gao, Chunyan
Xie, Rui
Li, Wen
Zhou, Jin
Liu, Shuchuan
Cao, Fenglin
Liu, Yue
Ma, Ruishuang
Si, Yu
Liu, Yan
Bi, Yayan
Gilbert, Gary E.
Shi, Jialan
TI Endothelial cell phagocytosis of senescent neutrophils decreases
procoagulant activity
SO THROMBOSIS AND HAEMOSTASIS
LA English
DT Article
DE Phagocytosis; endothelial cell; neutrophil; procoagulant activity;
lactadherin
ID ACUTE PROMYELOCYTIC LEUKEMIA; PHOSPHATIDYL-L-SERINE; APOPTOTIC CELLS;
TISSUE FACTOR; BACTERIAL LIPOPOLYSACCHARIDE; DEPENDENT PHAGOCYTOSIS;
EXTRACELLULAR TRAPS; BLOOD-COAGULATION; KUPFFER CELLS; WHOLE-BLOOD
AB Abundant senescent neutrophils traverse the vascular compartment and may contribute to pathologic conditions. For example, they become procoagulant when undergoing apoptosis and may contribute to thrombosis or inflammation. Our previous studies demonstrated a dominant clearance pathway in which the neutrophils can be phagocytosed by liver macrophages. The aim of this study was to explore an alternate pathway of neutrophil clearance by endothelial cells. Phagocytosis of the neutrophils by endothelial cells was performed using various experimental approaches including flow cytometry, confocal microscopy and electron microscopy assays in vitro and in vivo. Procoagulant activity of cultured neutrophils was evaluated by coagulation time, factor Xase and prothrombinase assays. Lactadherin functioned as a novel probe for the detection of phosphatidylserine on apoptotic cells, an opsonin (bridge) between apoptotic cell and phagocyte for promoting phagocytosis, and an efficient anticoagulant for inhibition of factor Xase and thrombin formation. When cultured, purified human neutrophils spontaneously entered apoptosis and developed, procoagulant activity that was directly related to the degree of phosphatidylserine exposure. Co-culture of aged neutrophils and endothelial cells resulted in phagocytosis of the neutrophils and prolonged coagulation time. Lactadherin diminished the procoagulant activity and increased the rate of neutrophil clearance. In vivo, neutrophils were sequestered by endothelial cells after blockade of Kupffer cells, a process that was dependent upon both phosphatidylserine exposure and P-selectin expression. Thus, the ability of endothelial cells to clear senescent neutrophils may limit the procoagulant and/or inflammatory impact of these cells.
C1 [Gao, Chunyan; Xie, Rui; Li, Wen; Zhou, Jin; Liu, Shuchuan; Cao, Fenglin; Liu, Yue; Ma, Ruishuang; Si, Yu; Liu, Yan; Shi, Jialan] Heilongjiang Inst Hematol & Oncol, Dept Hematol, Harbin, Peoples R China.
[Bi, Yayan] Harbin Med Univ, Affiliated Hosp 1, Dept Cardiol, Harbin 150001, Peoples R China.
[Gilbert, Gary E.; Shi, Jialan] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,VA Boston Healthcare Syst, Boston, MA 02115 USA.
RP Shi, JL (reprint author), Harbin Med Univ, Affiliated Hosp 1, Dept Med, 23 Youzheng St, Harbin 150001, Peoples R China.
EM jialan_shi@hms.harvard.edu
FU National Natural Science Foundation of China [30871227, 81270588];
Science Foundation of Heilongjiang Province [GB08C401-02]
FX This work was supported by grants from the National Natural Science
Foundation of China (30871227 and 81270588), and the Science Foundation
of Heilongjiang Province (GB08C401-02).
NR 49
TC 8
Z9 8
U1 2
U2 10
PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN
PI STUTTGART
PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY
SN 0340-6245
J9 THROMB HAEMOSTASIS
JI Thromb. Haemost.
PD JUN
PY 2013
VL 109
IS 6
BP 1079
EP 1090
DI 10.1160/TH12-12-0894
PG 12
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 163RY
UT WOS:000320355800013
PM 23571768
ER
PT J
AU Dzik, WS
Cserti-Gazdewich, CM
Stowell, C
AF Dzik, Walter Sunny
Cserti-Gazdewich, Christine M.
Stowell, Christopher
TI Tissue hypoxia results in lactic acidosis
SO TRANSFUSION
LA English
DT Article
C1 [Dzik, Walter Sunny; Cserti-Gazdewich, Christine M.; Stowell, Christopher] Massachusetts Gen Hosp, Blood Transfus Serv, Boston, MA 02114 USA.
RP Dzik, WS (reprint author), Massachusetts Gen Hosp, Blood Transfus Serv, 55 Fruit St, Boston, MA 02114 USA.
EM sdzik@partners.org
NR 3
TC 1
Z9 1
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0041-1132
J9 TRANSFUSION
JI Transfusion
PD JUN
PY 2013
VL 53
IS 6
BP 1168
EP 1168
DI 10.1111/j.1537-2995.2012.03926.x
PG 1
WC Hematology
SC Hematology
GA 161HI
UT WOS:000320183000005
PM 23750930
ER
PT J
AU Saxena, R
Welt, CK
AF Saxena, R.
Welt, C. K.
TI Polycystic ovary syndrome is not associated with genetic variants that
mark risk of type 2 diabetes
SO ACTA DIABETOLOGICA
LA English
DT Article
DE Testosterone; FSH; Hyperandrogenism; Triglycerides
ID GENOME-WIDE ASSOCIATION; IMPAIRED GLUCOSE-TOLERANCE; INSULIN-RESISTANCE;
SUSCEPTIBILITY LOCI; SYNDROME PCOS; COMMON VARIANTS; FAMILY-HISTORY;
ADMIXTURE MAP; TCF7L2 GENE; FTO GENE
AB Polycystic ovary syndrome (PCOS) is a disorder of irregular menses, hyperandrogenism and/or polycystic ovary morphology. A large proportion of women with PCOS also exhibit insulin resistance, beta-cell dysfunction, impaired glucose tolerance and/or type 2 diabetes (T2D). We therefore hypothesized that genetic variants that predispose to risk of T2D also result in risk of PCOS. Variants robustly associated with T2D in candidate gene or genome-wide association studies (GWAS; n = 56 SNPs from 33 loci) were genotyped in women of European ancestry with PCOS (n = 525) and controls (n = 472), aged 18-45 years. Metabolic, reproductive and anthropomorphic data were examined as a function of the T2D variants. All genetic association analyses were adjusted for age, BMI and ancestry and were reported after correction for multiple testing. There was a nominal association between variants in KCNJ11 and risk of PCOS. However, a risk score of 33 independent T2D-associated variants from GWAS was not significantly associated with PCOS. T2D variants were associated with PCOS phenotype parameters including those in THADA and WFS1 with testosterone levels, ENPP/PC1 with triglyceride levels, FTO with glucose levels and KCNJ11 with FSH levels. Diabetes risk variants are not important risk variants for PCOS.
C1 [Saxena, R.] Massachusetts Gen Hosp, Dept Anaesthesia, Boston, MA 02114 USA.
[Saxena, R.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Welt, C. K.] Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA.
RP Welt, CK (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, BHX 511,55 Fruit St, Boston, MA 02114 USA.
EM cwelt@partners.org
OI Welt, Corrine/0000-0002-8219-5504
FU National Institutes of Health [U01 HD 4417, 1R01HD065029]; ADA
[1-10-CT-57]; National Center for Research Resources [M01-RR-01066];
Harvard Clinical and Translational Science Center [1 UL1 RR025758]
FX This work was supported by the National Institutes of Health U01 HD 4417
and 1R01HD065029, ADA 1-10-CT-57, and 1 UL1 RR025758 Harvard Clinical
and Translational Science Center and M01-RR-01066 from the National
Center for Research Resources.
NR 46
TC 8
Z9 8
U1 0
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0940-5429
J9 ACTA DIABETOL
JI Acta Diabetol.
PD JUN
PY 2013
VL 50
IS 3
BP 451
EP 457
DI 10.1007/s00592-012-0383-4
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 159SP
UT WOS:000320066500021
PM 22389004
ER
PT J
AU Serrano-Pozo, A
Gomez-Isla, T
Growdon, JH
Frosch, MP
Hyman, BT
AF Serrano-Pozo, Alberto
Gomez-Isla, Teresa
Growdon, John H.
Frosch, Matthew P.
Hyman, Bradley T.
TI A Phenotypic Change But Not Proliferation Underlies Glial Responses in
Alzheimer Disease
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID BLOOD-BRAIN-BARRIER; POSITRON-EMISSION-TOMOGRAPHY; PROTEIN TRANSGENIC
MICE; MICROGLIAL CELLS; MOUSE MODEL; NEUROFIBRILLARY TANGLES; AMYLOID
DEPOSITION; SENILE DEMENTIA; APOE GENOTYPE; NEURON LOSS
AB Classical immunohistochemical studies in the Alzheimer disease (AD) brain reveal prominent glial reactions, but whether this pathological feature is due primarily to cell proliferation or to a phenotypic change of existing resting cells remains controversial. We performed double-fluorescence immunohistochemical studies of astrocytes and microglia, followed by unbiased stereology-based quantitation in temporal cortex of 40 AD patients and 32 age-matched nondemented subjects. Glial fibrillary acidic protein (GFAP) and major histocompatibility complex II (MHC2) were used as markers of astrocytic and microglial activation, respectively. Aldehyde dehydrogenase 1 L1 and glutamine synthetase were used as constitutive astrocytic markers, and ionized calcium-binding adaptor molecule 1 (IBA1) as a constitutive microglial marker. As expected, AD patients had higher numbers of GFAP(+) astrocytes and MHC2(+) microglia than the nondemented subjects. However, both groups had similar numbers of total astrocytes and microglia and, in the AD group, these total numbers remained essentially constant over the clinical course of the disease. The GFAP immunoreactivity of astrocytes, but not the MHC2 immunoreactivity of microglia, increased in parallel with the duration of the clinical illness in the AD group. Cortical atrophy contributed to the perception of increased glia density. We conclude that a phenotypic change of existing glial cells, rather than a marked proliferation of glial precursors, accounts for the majority of the glial responses observed in the AD brain.
C1 [Serrano-Pozo, Alberto; Gomez-Isla, Teresa; Growdon, John H.; Frosch, Matthew P.; Hyman, Bradley T.] Massachusetts Gen Hosp, Massachusetts Alzheimers Dis Res Ctr, Boston, MA 02114 USA.
[Frosch, Matthew P.] Massachusetts Gen Hosp, CS Kubik Lab, Dept Pathol, Boston, MA 02114 USA.
[Serrano-Pozo, Alberto; Gomez-Isla, Teresa; Growdon, John H.; Hyman, Bradley T.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Hyman, BT (reprint author), MassGen Inst Neurodegenerat Dis, Alzheimer Res Unit, 16th St,Bldg 114, Charlestown, MA 02129 USA.
EM bhyman@partners.org
OI SERRANO-POZO, ALBERTO/0000-0003-0899-7530
FU NIH [AG08487, P50-AG05134]; Fundacion Alfonso Martin Escudero (Madrid,
Spain)
FX Supported by NIH grants AG08487 and P50-AG05134 (to B.T.H.). A.S.-P. was
awarded a fellowship from Fundacion Alfonso Martin Escudero (Madrid,
Spain).
NR 64
TC 20
Z9 20
U1 0
U2 12
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9440
J9 AM J PATHOL
JI Am. J. Pathol.
PD JUN
PY 2013
VL 182
IS 6
BP 2332
EP 2344
DI 10.1016/j.ajpath.2013.02.031
PG 13
WC Pathology
SC Pathology
GA 155WT
UT WOS:000319781800036
PM 23602650
ER
PT J
AU He, LZ
Marneros, AG
AF He, Lizhi
Marneros, Alexander G.
TI Macrophages Are Essential for the Early Wound Healing Response and the
Formation of a Fibrovascular Scar
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID RETINAL-PIGMENT EPITHELIUM; ENDOTHELIAL GROWTH-FACTOR; CHOROIDAL
NEOVASCULARIZATION; VASCULAR ENDOTHELIUM; MACULAR DEGENERATION; MICE;
EXPRESSION; CELLS; PROGENITORS; DEPLETION
AB After wounding, multiple cell types interact to form a fibrovascular scar; the formation and cellular origins of these scars are incompletely understood. We used a laser-injury wound model of choroidal neovascularization in the eye to determine the spatiotemporal cellular events that Lead to formation of a fibrovascular scar. After Laser injury, F4/80(+) myeloid cells infiltrate the wound site and induce smooth muscle actin (SMA) expression in adjacent retinal pigment epithelial cells, with subsequent formation of a SMA(+)NG2(+) myofibroblastic scaffold, into which endothelial cells then infiltrate to form a fibrovascular Lesion. Cells of the fibrovascular scaffold express the proangiogenic factor IL-1 beta strongly, whereas retinal pigment epithelial cells are the main source of VEGF-A. Subsequent choroidal neovascularization is limited to the area demarcated by this myofibroblastic scaffold and occurs independently of epithelial- or myeloid-derived VEGF-A. The SMA(+)NG2(+) myofibroblastic cells, F4/80(+) macrophages, and adjacent epithelial cells actively proliferate in the early phase of the wound healing response. Cell-lineage tracing experiments suggest that the SMA(+)NG2(+) myofibroblastic scaffold originates from choroidal pericyte-like cells. Targeted ablation of macrophages inhibits the formation of this fibrovascular scaffold, and expression analysis reveals that these macrophages are Arg1(+)YM1(+)F4/80(+) alternatively activated M2-Like macrophages, which do not require IL-4/STAT6 or IL-10 signaling for their activation. Thus, macrophages are essential for the early wound healing response and the formation of a fibrovascular scar.
C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA.
Harvard Univ, Sch Med, Dept Dermatol, Charlestown, MA 02129 USA.
RP Marneros, AG (reprint author), Harvard Univ, Sch Med, Cutaneous Biol Res Ctr, Bldg 149,13th St Rm 3-216, Charlestown, MA 02129 USA.
EM amarneros@partners.org
FU NIH-NEI [R01-EY019297]
FX Supported by NIH-NEI grant R01-EY019297 (A.G.M.).
NR 32
TC 27
Z9 32
U1 0
U2 10
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9440
J9 AM J PATHOL
JI Am. J. Pathol.
PD JUN
PY 2013
VL 182
IS 6
BP 2407
EP 2417
DI 10.1016/j.ajpath.2013.02.032
PG 11
WC Pathology
SC Pathology
GA 155WT
UT WOS:000319781800042
PM 23602833
ER
PT J
AU Shi, YX
Lo, CS
Chenier, I
Maachi, H
Filep, JG
Ingelfinger, JR
Zhang, SL
Chan, JSD
AF Shi, Yixuan
Lo, Chao-Sheng
Chenier, Isabelle
Maachi, Hasna
Filep, Janos G.
Ingelfinger, Julie R.
Zhang, Shao-Ling
Chan, John S. D.
TI Overexpression of catalase prevents hypertension and tubulointerstitial
fibrosis and normalization of renal angiotensin-converting enzyme-2
expression in Akita mice
SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
LA English
DT Article
DE catalase; hypertension; angiotensin-converting enzyme-2;
tubulointerstitial fibrosis
ID PROXIMAL TUBULAR CELLS; DIABETIC KIDNEY-DISEASE; TRANSGENIC MICE;
OXIDATIVE STRESS; GENE-EXPRESSION; BLOOD-PRESSURE; APOPTOSIS; ACE2;
CARBOXYPEPTIDASE; NEPHROPATHY
AB We investigated the relationship among oxidative stress, hypertension, renal injury, and angiotensin-converting enzyme-2 (ACE2) expression in type 1 diabetic Akita mice. Blood glucose, blood pressure, and albuminuria were monitored for up to 5 mo in adult male Akita and Akita catalase (Cat) transgenic (Tg) mice specifically overexpressing Cat, a key antioxidant enzyme in their renal proximal tubular cells (RPTCs). Same-age non-Akita littermates and Cat-Tg mice served as controls. In separate studies, adult male Akita mice (14 wk) were treated with ANG 1-7 (500 mu g.kg(-1).day(-1) sc) +/- A-779, an antagonist of the Mas receptor (10 mg.kg(-1).day(-1) sc), and euthanized at the age of 18 wk. The left kidneys were processed for histology and apoptosis studies. Renal proximal tubules were isolated from the right kidneys to assess protein and gene expression. Urinary angiotensinogen (AGT), angiotensin II (ANG II), and ANG 1-7 were quantified by specific ELISAs. Overexpression of Cat attenuated renal oxidative stress; prevented hypertension; normalized RPTC ACE2 expression and urinary ANG 1-7 levels (both were low in Akita mice); ameliorated glomerular filtration rate, albuminuria, kidney hypertrophy, tubulointerstitial fibrosis, and tubular apoptosis; and suppressed profibrotic and proapoptotic gene expression in RPTCs of Akita Cat-Tg mice compared with Akita mice. Furthermore, daily administration of ANG 1-7 normalized systemic hypertension in Akita mice, which was reversed by A-779. These data demonstrate that Cat overexpression prevents hypertension and progression of nephropathy and highlight the importance of intrarenal oxidative stress and ACE2 expression contributing to hypertension and renal injury in diabetes.
C1 [Shi, Yixuan; Lo, Chao-Sheng; Chenier, Isabelle; Maachi, Hasna; Zhang, Shao-Ling; Chan, John S. D.] Univ Montreal, Ctr Hosp Univ Montreal CRCHUM, Hotel Dieu Hosp, Ctr Rech, Montreal, PQ H2W 1T8, Canada.
[Filep, Janos G.] Univ Montreal, Maisonneuve Rosemont Hosp, Ctr Rech, Montreal, PQ H2W 1T8, Canada.
[Ingelfinger, Julie R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Nephrol Unit, Boston, MA USA.
RP Chan, JSD (reprint author), Univ Montreal, Ctr Hosp Univ Montreal CRCHUM, Hotel Dieu Hosp, Ctr Rech, Pavillon Masson,3850 St Urbain St, Montreal, PQ H2W 1T8, Canada.
EM john.chan@umontreal.ca
FU Kidney Foundation of Canada; Canadian Institutes of Health Research
[MOP-84363, MOP-93650, MOP-106688, MOP-86450, MOP-12573]; National
Heart, Lung, and Blood Institute Grant [HL-48455]; Foundation of the
CHUM
FX This work was supported in part by grants from the Kidney Foundation of
Canada (to J. S. Chan); Canadian Institutes of Health Research Grants
MOP-84363, MOP-93650, and MOP-106688 (to J. S. Chan), MOP-86450 (to S.
L. Zhang), and MOP-12573 (to J. G. Filep); National Heart, Lung, and
Blood Institute Grant HL-48455 (to J. R. Ingelfinger); and Foundation of
the CHUM.
NR 49
TC 9
Z9 9
U1 2
U2 5
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1931-857X
J9 AM J PHYSIOL-RENAL
JI Am. J. Physiol.-Renal Physiol.
PD JUN
PY 2013
VL 304
IS 11
BP F1335
EP F1346
DI 10.1152/ajprenal.00405.2012
PG 12
WC Physiology; Urology & Nephrology
SC Physiology; Urology & Nephrology
GA 156GQ
UT WOS:000319810300003
PM 23552863
ER
PT J
AU Borzecki, AM
Cevasco, M
Mull, H
Shin, M
Itani, K
Rosen, AK
AF Borzecki, Ann M.
Cevasco, Marisa
Mull, Hillary
Shin, Marlena
Itani, Kamal
Rosen, Amy K.
TI Improving the identification of Postoperative Wound Dehiscence missed by
the Patient Safety Indicator algorithm
SO AMERICAN JOURNAL OF SURGERY
LA English
DT Article
DE Postoperative wound dehiscence; Adverse events; Quality of care; Patient
safety; Quality indicators
AB BACKGROUND: The Patient Safety Indicator (PSI) Postoperative Wound Dehiscence (PWD) is an administrative data-based algorithm that flags cases using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code 54.61 (abdominal wall disruption reclosure). We examined how often PWD missed events and explored ways to improve event identification.
METHODS: We selected 125 high-risk unflagged cases based on predicted probability and the presence of clinically relevant codes. We determined the false-negative proportion and associated reasons through chart review and calculated likelihood ratios of associated codes.
RESULTS: Thirty-two percent of cases were false negatives, 60% of which lacked any abdominal wall repair codes. All individual codes had low likelihood ratios; the combination of diagnosis code 998.3x (operative wound disruption) and particular abdominal wall repair procedure codes occurred exclusively in false-negative cases (representing 24% of false-negative cases).
CONCLUSIONS: Among high-risk cases, the PWD algorithm frequently missed events. Coder training to clarify assignment of abdominal wall repair codes, plus adding specific code combinations to the algorithm, would improve event identification. Published by Elsevier Inc.
C1 [Borzecki, Ann M.] Bedford VA Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA 01730 USA.
[Borzecki, Ann M.; Rosen, Amy K.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA.
[Borzecki, Ann M.] Boston Univ, Sch Med, Dept Med, Gen Internal Med Sect, Boston, MA 02118 USA.
[Cevasco, Marisa; Itani, Kamal] VA Boston Healthcare Syst, Dept Surg, Boston, MA USA.
[Cevasco, Marisa] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA.
[Mull, Hillary; Shin, Marlena; Rosen, Amy K.] VA Boston Healthcare Syst, Ctr Org Leadership & Management Res, Boston, MA USA.
[Mull, Hillary; Itani, Kamal; Rosen, Amy K.] Boston Univ, Sch Med, Dept Surg, Boston, MA 02118 USA.
[Itani, Kamal] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA.
RP Borzecki, AM (reprint author), Bedford VA Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, 200 Springs Rd, Bedford, MA 01730 USA.
EM amb@bu.edu
FU US Department of Veterans Affairs Health Services Research and
Development Service [SDR 07-002]
FX This study was funded by the US Department of Veterans Affairs Health
Services Research and Development Service grant number SDR 07-002. The
funding agency had no involvement in: study design, data collection,
interpretation or analysis, manuscript writing or the decision to submit
this work for publication.
NR 21
TC 1
Z9 1
U1 1
U2 2
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9610
J9 AM J SURG
JI Am. J. Surg.
PD JUN
PY 2013
VL 205
IS 6
BP 674
EP 680
DI 10.1016/j.amjsurg.2012.07.040
PG 7
WC Surgery
SC Surgery
GA 156DY
UT WOS:000319802500009
PM 23395582
ER
PT J
AU Lahtinen, AM
Havulinna, AS
Noseworthy, PA
Jula, A
Karhunen, PJ
Perola, M
Newton-Cheh, C
Salomaa, V
Kontula, K
AF Lahtinen, Annukka M.
Havulinna, Aki S.
Noseworthy, Peter A.
Jula, Antti
Karhunen, Pekka J.
Perola, Markus
Newton-Cheh, Christopher
Salomaa, Veikko
Kontula, Kimmo
TI Prevalence of arrhythmia-associated gene mutations and risk of sudden
cardiac death in the Finnish population
SO ANNALS OF MEDICINE
LA English
DT Article
DE Arrhythmia; genetic epidemiology; genetics; mutation; sudden cardiac
death
ID LONG-QT SYNDROME; POLYMORPHIC VENTRICULAR-TACHYCARDIA; T-WAVE ALTERNANS;
RYANODINE RECEPTOR; FOUNDER MUTATIONS; UNEXPLAINED DEATH; HEART-DISEASE;
PLAKOPHILIN-2 MUTATIONS; CARDIOVASCULAR RISK; INTERVAL DURATION
AB Background. Sudden cardiac death (SCD) remains a major cause of death in Western countries. It has a heritable component, but previous molecular studies have mainly focused on common genetic variants. We studied the prevalence, clinical phenotypes, and risk of SCD presented by ten rare mutations previously associated with arrhythmogenic right ventricular cardiomyopathy, long QT syndrome, or catecholaminergic polymorphic ventricular tachycardia.
Methods. The occurrence of ten arrhythmia-associated mutations was determined in four large prospective population cohorts (FINRISK 1992, 1997, 2002, and Health 2000, n = 28,465) and two series of forensic autopsies (The Helsinki Sudden Death Study and The Tampere Autopsy Study, n = 825). Follow-up data were collected from national registries.
Results. The ten mutations showed a combined prevalence of 79 per 10,000 individuals in Finland, and six of them showed remarkable geographic clustering. Of a total of 715 SCD cases, seven (1.0%) carried one of the ten mutations assayed: three carried KCNH2 R176W, one KCNH2 L552S, two PKP2 Q59L, and one RYR2 R3570W.
Conclusions. Arrhythmia-associated mutations are prevalent in the general Finnish population but do not seem to present a major risk factor for SCD, at least during a mean of 10-year follow-up of a random adult population sample.
C1 [Lahtinen, Annukka M.; Kontula, Kimmo] Univ Helsinki, Res Programs Unit, FIN-00290 Helsinki, Finland.
[Lahtinen, Annukka M.; Kontula, Kimmo] Univ Helsinki, Dept Med, FIN-00290 Helsinki, Finland.
[Havulinna, Aki S.; Perola, Markus; Salomaa, Veikko] Natl Inst Hlth & Welf, Helsinki, Finland.
[Noseworthy, Peter A.; Newton-Cheh, Christopher] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Noseworthy, Peter A.; Newton-Cheh, Christopher] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Noseworthy, Peter A.; Newton-Cheh, Christopher] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
[Jula, Antti] Natl Inst Hlth & Welf, Turku, Finland.
[Karhunen, Pekka J.] Univ Tampere, Sch Med, FIN-33101 Tampere, Finland.
[Karhunen, Pekka J.] Tampere Univ Hosp, Ctr Lab Med, Tampere, Finland.
[Perola, Markus] Univ Helsinki, Inst Mol Med Finland FIMM, FIN-00290 Helsinki, Finland.
RP Kontula, K (reprint author), Univ Helsinki, Dept Med, FIN-00290 Helsinki, Finland.
EM kimmo.kontula@hus.fi
OI Tuiskula, Annukka/0000-0002-6538-635X
FU Finnish Cultural Foundation; Max Schaldach Fellowship in Cardiac Pacing
and Electrophysiology; Burroughs Wellcome Fund travel grant; Finnish
Academy SALVE program 'Pubgensense ' [10404]; Wellcome Trust; Academy of
Finland [129494, 139635]; Finnish Foundation for Cardiovascular
Research; Sigrid Juselius Foundation; National Institutes of Health
[HL080025, HL098283]; Doris Duke Charitable Foundation; Burroughs
Wellcome Fund
FX The authors report no conflicts of interest. This study was supported by
the Finnish Cultural Foundation (to A. M. L.); the Max Schaldach
Fellowship in Cardiac Pacing and Electrophysiology (to P.A.N.); a
Burroughs Wellcome Fund travel grant (to P.A.N.); Finnish Academy SALVE
program 'Pubgensense ' (#10404 to M. P.); the Wellcome Trust, the
Academy of Finland (to K. K. and #129494 and #139635 to V. S.); the
Finnish Foundation for Cardiovascular Research (to K. K. and V. S.); the
Sigrid Juselius Foundation (to K. K. and V. S.); the National Institutes
of Health (HL080025, HL098283 to C. N.-C.); the Doris Duke Charitable
Foundation (to C. N.-C.); and the Burroughs Wellcome Fund (to C.N.-C.).
NR 56
TC 9
Z9 9
U1 0
U2 7
PU INFORMA HEALTHCARE
PI NEW YORK
PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA
SN 0785-3890
J9 ANN MED
JI Ann. Med.
PD JUN
PY 2013
VL 45
IS 4
BP 328
EP 335
DI 10.3109/07853890.2013.783995
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 156RZ
UT WOS:000319841400004
PM 23651034
ER
PT J
AU Navarro-Millan, I
Charles-Schoeman, C
Yang, S
Bathon, JM
Bridges, SL
Chen, L
Cofield, SS
Dell'Italia, LJ
Moreland, LW
O'Dell, JR
Paulus, HE
Curtis, JR
AF Navarro-Millan, Iris
Charles-Schoeman, Christina
Yang, Shuo
Bathon, Joan M.
Bridges, S. Louis, Jr.
Chen, Lang
Cofield, Stacey S.
Dell'Italia, Louis J.
Moreland, Larry W.
O'Dell, James R.
Paulus, Harold E.
Curtis, Jeffrey R.
TI Changes in Lipoproteins Associated With Methotrexate or Combination
Therapy in Early Rheumatoid Arthritis: Results From the Treatment of
Early Rheumatoid Arthritis Trial
SO ARTHRITIS AND RHEUMATISM
LA English
DT Article
ID CARDIOVASCULAR RISK-FACTORS; HIGH-DENSITY-LIPOPROTEIN;
MYOCARDIAL-INFARCTION; LIPID PROFILES; RECEPTOR INHIBITION;
DOUBLE-BLIND; ATHEROSCLEROSIS; CHOLESTEROL; TOCILIZUMAB; DISEASE
AB Objective To study changes in lipid profiles at 24 weeks among patients with early rheumatoid arthritis (RA) participating in the Treatment of Early RA (TEAR) trial and randomized to receive methotrexate (MTX) plus etanercept, triple therapy (MTX plus sulfasalazine plus hydroxychloroquine), or aggressively titrated MTX monotherapy. Methods This TEAR substudy included 459 participants with biologic specimens. Serum levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol were measured at 0 and 24 weeks. Results At 24 weeks, there were statistically significant increases in mean cholesterol levels in the MTX plus etanercept, triple therapy, and MTX monotherapy arms. The observed increases were 31.4 mg/dl, 28.7 mg/dl, and 30 mg/dl in LDL cholesterol, 19.3 mg/dl, 22.3 mg/dl, and 20.6 mg/dl in HDL cholesterol, and 56.8 mg/dl, 53 mg/dl, and 57.3 mg/dl in total cholesterol (P < 0.0001 versus baseline for each comparison). There was a statistically significant decrease in the ratio of total cholesterol to HDL cholesterol at 24 weeks in all 3 treatment groups versus baseline. There was no difference in any lipid changes between the 3 treatment arms. After multivariable adjustment, change in C-reactive protein, but not the Disease Activity Score in 28 joints, was associated with change in LDL cholesterol (P = 0.03) and total cholesterol (P = 0.01). Baseline glucocorticoid use was associated with changes in HDL cholesterol (P = 0.03) and total cholesterol (P = 0.02). Conclusion Levels of total cholesterol, LDL cholesterol, and HDL cholesterol increased comparably shortly after initiation of MTX plus etanercept, triple therapy, and MTX monotherapy among patients with early RA with active disease participating in a clinical trial. The clinical relevance of short-term changes in traditional lipids on cardiovascular outcomes remains to be determined.
C1 [Navarro-Millan, Iris; Yang, Shuo; Bridges, S. Louis, Jr.; Chen, Lang; Cofield, Stacey S.; Dell'Italia, Louis J.; Curtis, Jeffrey R.] Univ Alabama Birmingham, Birmingham, AL 35294 USA.
[Charles-Schoeman, Christina; Paulus, Harold E.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Bathon, Joan M.] Columbia Univ, New York, NY USA.
[Dell'Italia, Louis J.] Birmingham VA Med Ctr, Birmingham, AL USA.
[Moreland, Larry W.] Univ Pittsburgh, Pittsburgh, PA USA.
[O'Dell, James R.] Univ Nebraska Med Ctr, Omaha, NE USA.
RP Curtis, JR (reprint author), Univ Alabama Birmingham, 510 20th St South,FOT 802D, Birmingham, AL 35294 USA.
EM jcurtis@uab.edu
FU Arthritis Foundation; NIH (National Heart, Lung, and Blood Institute)
[5K23-HL-094834]; NIH (National Institute of Arthritis and
Musculoskeletal and Skin Diseases) [R21-AR-057913-01A1]; Margaret J.
Miller Endowed Professor of Arthritis Research Chair at the University
of Pittsburgh; NIH [AR-053351, R01-AR-052658]; Agency for Healthcare
Research and Quality [R01-HS-018517]; Amgen
FX Supported by the Arthritis Foundation (grant to Dr. Curtis). Dr.
Charles-Schoeman's work was supported by the NIH (National Heart, Lung,
and Blood Institute grant 5K23-HL-094834 and National Institute of
Arthritis and Musculoskeletal and Skin Diseases grant
R21-AR-057913-01A1). Dr. Moreland's work was supported by the Margaret
J. Miller Endowed Professor of Arthritis Research Chair at the
University of Pittsburgh. Dr. Curtis' work was supported by the NIH
(grant AR-053351) and the Agency for Healthcare Research and Quality
(grant R01-HS-018517). The Treatment of Early Rheumatoid Arthritis
(TEAR) biorepository was funded by the NIH (grant R01-AR-052658 to Dr.
Bridges). The TEAR trial was supported by Amgen.
NR 39
TC 38
Z9 40
U1 0
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD JUN
PY 2013
VL 65
IS 6
BP 1430
EP 1438
DI 10.1002/art.37916
PG 9
WC Rheumatology
SC Rheumatology
GA 155IG
UT WOS:000319740600004
PM 23460074
ER
PT J
AU Wofsy, D
Hillson, JL
Diamond, B
AF Wofsy, David
Hillson, Jan L.
Diamond, Betty
TI Comparison of Alternative Primary Outcome Measures for Use in Lupus
Nephritis Clinical Trials
SO ARTHRITIS AND RHEUMATISM
LA English
DT Article
ID CYCLOPHOSPHAMIDE; THERAPY
AB Objective Clinical trials of therapies for lupus nephritis have used many different primary outcome measures, ranging from complete response to time to end-stage renal disease. The objective of this study was to compare several possible outcome measures, using data from a large, multicenter trial of abatacept in lupus nephritis, to gain insight into which outcome measure, if any, was best able to discern differences among treatment groups. Methods Study patients received either abatacept or placebo, on a background of mycophenolate mofetil and glucocorticoids. Using data from this trial, the following primary outcome measures at 24 and 52 weeks were compared: complete response rate, major clinical response rate, total response rate (complete plus partial response), improvement in proteinuria, improvement in estimated glomerular filtration rate, and frequency of treatment failure. Time to complete response was also evaluated. Results Complete response rate, major clinical response rate, and time to complete response were the measures that best discriminated between the abatacept groups and placebo, and the sensitivities of these 3 measures were comparable. For these measures, sample sizes of 50 patients would have been sufficient to demonstrate a statistically significant difference between treatment and control at 52 weeks. Each of the other measures also discriminated between treatment and control, but much larger group sizes would have been required to determine statistical significance. Conclusion The choice of primary outcome measure can substantially influence the ability to detect therapeutic benefit in lupus nephritis trials. This study suggests that complete response rate, major clinical response rate at 52 weeks, and time to complete response may be the most sensitive outcome measures for detecting differences among therapeutic regimens.
C1 [Wofsy, David] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Hillson, Jan L.] Bristol Myers Squibb Co, Princeton, NJ USA.
[Diamond, Betty] Feinstein Inst Med Res, Manhasset, NY USA.
RP Wofsy, D (reprint author), San Francisco VA Med Ctr, Arthrit Immunol Unit 111R, 4150 Clement St, San Francisco, CA 94121 USA.
EM wofsyd@medsch.ucsf.edu
FU Rosalind Russell Medical Research Center for Arthritis at the University
of California, San Francisco
FX Supported by the Rosalind Russell Medical Research Center for Arthritis
at the University of California, San Francisco.
NR 8
TC 31
Z9 31
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD JUN
PY 2013
VL 65
IS 6
BP 1586
EP 1591
DI 10.1002/art.37940
PG 6
WC Rheumatology
SC Rheumatology
GA 155IG
UT WOS:000319740600021
PM 23529285
ER
PT J
AU Vudattu, NK
Strle, K
Steere, AC
Drouin, EE
AF Vudattu, Nalini K.
Strle, Klemen
Steere, Allen C.
Drouin, Elise E.
TI Dysregulation of CD4+CD25high T Cells in the Synovial Fluid of Patients
With Antibiotic-Refractory Lyme Arthritis
SO ARTHRITIS AND RHEUMATISM
LA English
DT Article
ID INDUCED TNF RECEPTOR; BORRELIA-BURGDORFERI; AUTOIMMUNE-DISEASES; CUTTING
EDGE; JOINT FLUID; SUPPRESSION; RESPONSES; LIGAND; INFLAMMATION;
MOLECULES
AB Objective To examine the role of immune dysregulation in antibiotic-refractory Lyme arthritis by comparing the phenotype, frequency, and function of CD4+ Teff cells and Treg cells in patients with antibiotic- responsive arthritis and patients with antibiotic-refractory arthritis. Methods Matched peripheral blood and synovial fluid samples from 15 patients with antibiotic-responsive arthritis were compared with those from 16 patients with antibiotic-refractory arthritis, using flow cytometry, suppression assays, and cytokine assays. Results Critical differences between the 2 patient groups were observed in the synovial fluid CD4+CD25high population, a cell subset usually composed of FoxP3-positive Treg cells. In patients with antibiotic-refractory arthritis, this cell population often had fewer FoxP3-positive cells and a greater frequency of FoxP3-negative (Teff) cells compared with patients with antibiotic-responsive arthritis. Moreover, the expression of glucocorticoid-induced tumor necrosis factor receptor and OX40 on CD4+CD25high cells was significantly higher in the antibody-refractory group. Suppression assays showed that CD4+CD25high cells in patients with antibiotic-refractory arthritis did not effectively suppress proliferation of CD4+CD25- cells or secretion of interferon- and tumor necrosis factor , whereas those cells in patients with antibiotic-responsive arthritis did suppress proliferation of CD4+CD25- cells and secretion of interferon- and tumor necrosis factor . Finally, in the antibiotic-refractory group, higher ratios of CD25high FoxP3-negative cells to CD25high FoxP3-positive cells correlated directly with a longer duration of arthritis after antibiotic treatment. Conclusion Patients with antibiotic-refractory Lyme arthritis often have lower frequencies of Treg cells, higher expression of activation coreceptors, and less effective inhibition of proinflammatory cytokines. This suggests that immune responses in these patients are excessively amplified, leading to immune dysregulation and antibiotic-refractory arthritis.
C1 [Vudattu, Nalini K.; Strle, Klemen; Steere, Allen C.; Drouin, Elise E.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Vudattu, Nalini K.; Strle, Klemen; Steere, Allen C.; Drouin, Elise E.] Harvard Univ, Sch Med, Boston, MA USA.
RP Drouin, EE (reprint author), Massachusetts Gen Hosp, 55 Fruit St,CNY 149-8301, Boston, MA 02114 USA.
EM edrouin@partners.org
RI Vudattu, Nalini/L-1779-2014
OI Vudattu, Nalini/0000-0001-6705-3332
FU NIH [AI-101175, AR-20358]; Mathers Foundation; English, Bonter; Mitchell
Foundation; Eshe Fund; Lyme/Arthritis Research Fund at Massachusetts
General Hospital; Massachusetts General Hospital; Walter J. and Lille A.
Berbecker Foundation; Arthritis Foundation
FX Supported by the NIH (grants AI-101175 and AR-20358), the Mathers
Foundation, the English, Bonter, Mitchell Foundation, the Eshe Fund, and
the Lyme/Arthritis Research Fund at Massachusetts General Hospital. Dr.
Vudattu is recipient of a Postdoctoral Fellowship from the Walter J. and
Lille A. Berbecker Foundation. Dr. Strle is recipient of Postdoctoral
Fellowships from the Walter J. and Lille A. Berbecker Foundation and the
Arthritis Foundation.
NR 46
TC 13
Z9 14
U1 0
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD JUN
PY 2013
VL 65
IS 6
BP 1643
EP 1653
DI 10.1002/art.37910
PG 11
WC Rheumatology
SC Rheumatology
GA 155IG
UT WOS:000319740600027
PM 23450683
ER
PT J
AU Giralt, S
McCarthy, PL
Anderson, KC
Carter, SL
Richardson, PG
Rajkumar, SV
Laport, GG
Stadtmauer, EA
Pasquini, MC
Horowitz, MM
AF Giralt, Sergio
McCarthy, Philip L.
Anderson, Kenneth C.
Carter, Shelly L.
Richardson, Paul G.
Rajkumar, S. Vincent
Laport, Ginna G.
Stadtmauer, Edward A.
Pasquini, Marcelo C.
Horowitz, Mary M.
TI Anatomy of a Successful Practice-Changing Study: A Blood and Marrow
Transplantation Clinical Trials Network-National Cancer Institute
Cooperative Group Collaboration
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Editorial Material
ID STEM-CELL TRANSPLANTATION; MULTIPLE-MYELOMA; LENALIDOMIDE
C1 [Giralt, Sergio] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA.
[McCarthy, Philip L.] Roswell Pk Canc Inst, Blood & Marrow Transplant Program, Buffalo, NY 14263 USA.
[Anderson, Kenneth C.; Richardson, Paul G.] Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Dept Med Oncol, Boston, MA USA.
[Carter, Shelly L.] EMMES Corp, Rockville, MD USA.
[Rajkumar, S. Vincent] Mayo Clin, Coll Med, Div Hematol, Rochester, MN USA.
[Laport, Ginna G.] Stanford Univ, Ctr Med, Div Blood & Marrow Transplantat, Stanford, CA 94305 USA.
[Stadtmauer, Edward A.] Univ Penn, Abramson Canc Ctr, Myeloma Program, Philadelphia, PA 19104 USA.
[Pasquini, Marcelo C.; Horowitz, Mary M.] Med Coll Wisconsin, Div Hematol & Oncol, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA.
RP Horowitz, MM (reprint author), Med Coll Wisconsin, Div Hematol & Oncol, Ctr Int Blood & Marrow Transplant Res, 9200 W Wisconsin Ave,Suite C5500, Milwaukee, WI 53226 USA.
EM marymh@mcw.edu
OI Rajkumar, S. Vincent/0000-0002-5862-1833
FU NCI NIH HHS [U10 CA021115, U24 CA076518, CA33601, CA31946, U10 CA031946,
CA21115, U10 CA033601]; NHLBI NIH HHS [U01 HL069294, U10 HL069294, U10
HL069315, U10 HL069348, U10 HL069286, U10 HL069291, HL069294]
NR 5
TC 1
Z9 1
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD JUN
PY 2013
VL 19
IS 6
BP 858
EP 859
DI 10.1016/j.bbmt.2013.03.015
PG 2
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA 156TX
UT WOS:000319847900005
PM 23545332
ER
PT J
AU Kim, HT
Armand, P
AF Kim, Haesook T.
Armand, Philippe
TI Clinical Endpoints in Allogeneic Hematopoietic Stem Cell Transplantation
Studies: The Cost of Freedom
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Review
DE Allogeneic transplantation; Clinical endpoints; Competing risks data
ID BONE-MARROW-TRANSPLANTATION; GRAFT-VERSUS-LEUKEMIA; UMBILICAL-CORD
BLOOD; CONSENSUS DEVELOPMENT PROJECT; TREATMENT-RELATED MORTALITY; ACUTE
MYELOID-LEUKEMIA; COMPETING RISKS DATA; WORKING GROUP-REPORT; CUMULATIVE
INCIDENCE; UNRELATED DONORS
AB When designing a study for allogeneic hematopoietic stem cell transplantation (HSCT), many choices must be made, including conditioning regimen, stem cell source, and graft-versus-host disease (GVHD) prevention method. For each of these, there are a growing number of options, which can be combined into a bewildering number of possible HSCT protocols. To properly interpret the results of a given strategy and compare them with others, it is essential that there be agreement on the definitions and estimation methods of HSCT endpoints. We report a survey of the recent HSCT literature that confirms the heterogeneity of endpoint definitions and estimation methods used. Unfortunately, this heterogeneity may lead to significant biases in the estimates of key endpoints, including nonrelapse mortality, relapse, GVHD, or engraftment. This can preclude adequate comparisons among studies, even though such comparisons are the major tool with which to improve HSCT outcome. In the context of our survey, we discuss some of the statistical issues that arise when dealing with HSCT endpoints and the ramifications of the choice of endpoint definition, when the endpoint occurs in the context of competing risks. Our hope is to generate discussion and motivate a search for consensus among those who perform transplantations and statisticians. (C) 2013 American Society for Blood and Marrow Transplantation.
C1 [Kim, Haesook T.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA.
[Armand, Philippe] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
RP Kim, HT (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, 450 Brookline Ave, Boston, MA 02215 USA.
EM Kim.haesook@jimmy.harvard.edu
FU NIAID [U19 AI29530]; NCI [PO1 CA142106]; American Society of Hematology;
ASCO/Conquer Cancer Foundation
FX Supported by NIAID U19 AI29530, and NCI PO1 CA142106. P.A. is a
recipient of an American Society of Hematology Scholar Award and an
ASCO/Conquer Cancer Foundation Career Development Award.
NR 32
TC 2
Z9 2
U1 0
U2 6
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 JUN
PY 2013
VL 19
IS 6
BP 860
EP 866
DI 10.1016/j.bbmt.2013.01.003
PG 7
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA 156TX
UT WOS:000319847900006
PM 23305679
ER
PT J
AU Hitzler, JK
He, WS
Doyle, J
Cairo, M
Camitta, BM
Chan, KW
Perez, MAD
Fraser, C
Gross, TG
Horan, JT
Kennedy-Nasser, AA
Kitko, C
Kurtzberg, J
Lehmann, L
O'Brien, T
Pulsipher, MA
Smith, FO
Zhang, MJ
Eapen, M
Carpenter, PA
AF Hitzler, Johann K.
He, Wensheng
Doyle, John
Cairo, Mitchell
Camitta, Bruce M.
Chan, Ka Wah
Perez, Miguel A. Diaz
Fraser, Christopher
Gross, Thomas G.
Horan, John T.
Kennedy-Nasser, Alana A.
Kitko, Carrie
Kurtzberg, Joanne
Lehmann, Leslie
O'Brien, Tracey
Pulsipher, Michael A.
Smith, Franklin O.
Zhang, Mei-Jie
Eapen, Mary
Carpenter, Paul A.
CA CIBMTR Pediat Canc Working Comm
TI Outcome of Transplantation for Acute Myelogenous Leukemia in Children
with Down Syndrome
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Article
DE Hematopoietic stem cell transplantation; Down syndrome; Trisomy 21; AML;
ALL; Relapse; Pediatric
ID ACUTE MYELOID-LEUKEMIA; BONE-MARROW-TRANSPLANTATION; ONCOLOGY GROUP;
THERAPY; TOXICITY; DISEASE; REGIMEN; TRIAL; RISK
AB Data on outcomes of allogeneic transplantation in children with Down syndrome and acute myelogenous leukemia (DS-AML) are scarce and conflicting. Early reports stress treatment-related mortality as the main barrier; a recent case series points to posttransplantation relapse. We reviewed outcome data for 28 patients with DS-AML reported to the Center for International Blood and Marrow Transplant Research between 2000 and 2009 and performed a first matched-pair analysis of 21 patients with DS-AML and 80 non-DS AML controls. The median age at transplantation for DS-AML was 3 years, and almost half of the cohort was in second remission. The 3-year probability of overall survival was only 19%. In multivariate analysis, adjusting for interval from diagnosis to transplantation, risks of relapse (hazard ratio [HR], 2.84; P<.001; 62% versus 37%) and transplant-related mortality (HR, 2.52; P=.04; 24% versus 15%) were significantly higher for DS-AML compared to non-DS AML Overall mortality risk (HR, 2.86; P<.001; 21% versus 52%) was significantly higher for DS-AML. Both transplant-related mortality and relapse contribute to higher mortality. Excess mortality in DS-AML patients can only effectively be addressed through an international multicenter effort to pilot strategies aimed at lowering both transplant-related mortality and relapse risks. (C) 2013 American Society for Blood and Marrow Transplantation.
C1 [Hitzler, Johann K.; Doyle, John] Univ Toronto, Hosp Sick Children, Toronto, ON M5G 1X8, Canada.
[He, Wensheng; Zhang, Mei-Jie; Eapen, Mary] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Dept Med, Milwaukee, WI 53226 USA.
[Cairo, Mitchell] New York Med Coll, Valhalla, NY 10595 USA.
[Camitta, Bruce M.] Med Coll Wisconsin, Midwest Ctr Canc & Blood Disorders, Milwaukee, WI 53226 USA.
[Chan, Ka Wah] Texas Transplant Inst, San Antonio, TX USA.
[Perez, Miguel A. Diaz] Hosp Nino Jesus, Madrid, Spain.
[Fraser, Christopher] Royal Childrens Hosp, Herston, Qld, Australia.
[Gross, Thomas G.] Nationwide Childrens Hosp, Columbus, OH USA.
[Horan, John T.] Childrens Healthcare Atlanta Egleston, Atlanta, GA USA.
[Kennedy-Nasser, Alana A.] Texas Childrens Hosp, Baylor Coll Med, Houston, TX 77030 USA.
[Kitko, Carrie] Univ Michigan, Ann Arbor, MI 48109 USA.
[Kurtzberg, Joanne] Duke Univ, Durham, NC USA.
[Lehmann, Leslie] Dana Farber Canc Inst, Boston, MA USA.
[O'Brien, Tracey] Sydney Childrens Hosp, Sydney, NSW, Australia.
[Pulsipher, Michael A.] Primary Childrens Med Ctr, Salt Lake City, UT 84103 USA.
[Smith, Franklin O.] Univ Cincinnati, Inst Canc, Cincinnati, OH USA.
[Carpenter, Paul A.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
RP Carpenter, PA (reprint author), Fred Hutchinson Canc Res Ctr, D5-290,1024 Fairview Ave N, Seattle, WA 98109 USA.
EM pcarpent@fhcrc.org
FU Public Health Service from the National Cancer Institute, the National
Heart, Lung and Blood Institute, and the National Institute of Allergy
and Infectious Diseases [U24-CA76518]; Health Resources and Services
Administration [HHSH234200637015C]
FX Supported by Public Health Service Grant/Cooperative Agreement
U24-CA76518 from the National Cancer Institute, the National Heart, Lung
and Blood Institute, and the National Institute of Allergy and
Infectious Diseases and HHSH234200637015C, from the Health Resources and
Services Administration. The views expressed in this article do not
reflect the official policy or position of the National Institute of
Health, the Department of the Navy, the Department of Defense, or any
other agency of the US Government.
NR 24
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U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD JUN
PY 2013
VL 19
IS 6
BP 893
EP 897
DI 10.1016/j.bbmt.2013.02.017
PG 5
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA 156TX
UT WOS:000319847900010
PM 23467128
ER
PT J
AU Bar, M
Sandmaier, BM
Inamoto, Y
Bruno, B
Hari, P
Chauncey, T
Martin, PJ
Storb, R
Maloney, DG
Storer, B
Flowers, MED
AF Bar, Merav
Sandmaier, Brenda M.
Inamoto, Yoshihiro
Bruno, Benedetto
Hari, Parameswaran
Chauncey, Thomas
Martin, Paul J.
Storb, Rainer
Maloney, David G.
Storer, Barry
Flowers, Mary E. D.
TI Donor Lymphocyte Infusion for Relapsed Hematological Malignancies after
Allogeneic Hematopoietic Cell Transplantation: Prognostic Relevance of
the Initial CD3(+) T Cell Dose
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Article
DE Donor lymphocyte infusion (DLI); Hematopoietic cell transplantation
(HCT); CD3(+) T cells; Graft-versus-host disease (GVHD); Adoptive
immunotherapy for relapse after HCT
ID VERSUS-HOST-DISEASE; BONE-MARROW-TRANSPLANTATION; CHRONIC
MYELOID-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; LEUKOCYTE INFUSIONS;
ADOPTIVE IMMUNOTHERAPY; CHRONIC GRAFT; MULTIPLE-MYELOMA; WORKING PARTY;
CHEMOTHERAPY
AB The impact of donor lymphocyte infusion (DLI) initial cell dose on its outcome is known in patients with chronic myeloid leukemia but limited in patients with other hematological malignancies. In this retrospective study, we evaluated the effect of initial DLI CD3(+) cell dose on graft-versus-host disease (GVHD) and overall survival after DLI given for relapse of any hematological malignancies after allogeneic hematopoietic cell transplantation (HCT) with high- or reduced-intensity conditioning. The cohort included 225 patients. Initial DLI CD3(+) cell dose per kilogram of recipient body weight was <= 1 x 10(7) (n = 84; group A), >1.0 to <10 x 10(7) (n = 58; group B), and >= 10 x 10(7) (n = 66; group C). The initial cell dose was unknown for the remaining 17 patients. Cumulative incidence rates of GVHD at 12 months after DLI were 21%, 45%, and 55% for groups A, B, and C, respectively. Multivariate analysis showed that initial DLI CD3(+) cell >= 10 x 10(7) dose per kilogram is associated with an increased risk of GVHD after DLI (P = .03). Moreover, an initial DLI CD3(+) cell dose of 10 x 10(7) or higher did not decrease the risk of relapse and did not improve overall survival. Thus, these results support the use of less than 10 x 10(7) CD3(+) cell per kilogram as the initial cell dose of DLI for treatment of persistent or recurrent hematological malignancy after HCT. (C) 2013 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
C1 [Bar, Merav; Sandmaier, Brenda M.; Inamoto, Yoshihiro; Chauncey, Thomas; Martin, Paul J.; Storb, Rainer; Maloney, David G.; Storer, Barry; Flowers, Mary E. D.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA.
[Bar, Merav; Sandmaier, Brenda M.; Chauncey, Thomas; Martin, Paul J.; Storb, Rainer; Maloney, David G.; Flowers, Mary E. D.] Univ Washington, Dept Med, Seattle, WA USA.
[Bruno, Benedetto; Storer, Barry] Univ Turin, Turin, Italy.
[Hari, Parameswaran] Med Coll Wisconsin, Milwaukee, WI 53226 USA.
[Chauncey, Thomas] VA Puget Sound Hlth Care Syst, Seattle, WA USA.
[Storer, Barry] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
RP Bar, M (reprint author), Fred Hutchinson Canc Res Ctr, POB 19024, Seattle, WA 98109 USA.
EM mbar@u.washington.edu
OI Hari, Parameswaran/0000-0002-8800-297X
FU National Institutes of Health [CA78902, CA018029]
FX This study was supported in part by grants CA78902 and CA018029 from the
National Institutes of Health.
NR 36
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U2 4
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 JUN
PY 2013
VL 19
IS 6
BP 949
EP 957
DI 10.1016/j.bbmt.2013.03.001
PG 9
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA 156TX
UT WOS:000319847900018
PM 23523892
ER
PT J
AU Pidala, J
Chai, XY
Martin, P
Inamoto, Y
Cutler, C
Palmer, J
Weisdorf, D
Pavletic, S
Arora, M
Jagasia, M
Jacobsohn, D
Lee, SJ
AF Pidala, Joseph
Chai, Xiaoyu
Martin, Paul
Inamoto, Yoshihiro
Cutler, Corey
Palmer, Jeanne
Weisdorf, Daniel
Pavletic, Steven
Arora, Mukta
Jagasia, Madan
Jacobsohn, David
Lee, Stephanie J.
TI Hand Grip Strength and 2-Minute Walk Test in Chronic Graft-versus-Host
Disease Assessment: Analysis from the Chronic GVHD Consortium
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Article
DE Hand grip strength; Two minute walk test; Chronic graft vs. host disease
ID CONSENSUS DEVELOPMENT PROJECT; WORKING GROUP-REPORT; QUALITY-OF-LIFE;
BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; HUMAN ACTIVITY
PROFILE; CLINICAL-TRIALS; PROGNOSTIC VALUE; PINCH STRENGTH; CRITERIA
AB Hand grip strength (HGS) and the 2-minute walk test (2MWT) have been proposed as elements of chronic graft-versus-host disease (GVHD) assessment in clinical trials. Using all available data (n = 584 enrollment visits, 1689 follow-up visits, total of 2273 visits) from a prospective observational cohort study, we explored the relationship between HGS and 2MWT and patient-reported measures (Lee symptom scale, MOS 36-Item Short-Form Health Survey [SF-36], and Functional Assessment of Cancer Therapy [FACT]-Bone Marrow Transplantation quality of life instruments and Human Activity Profile [HAP]), chronic GVHD global severity (National Institutes of Health global score, clinician global score; and patient-reported global score), calculated and clinician-reported chronic GVHD response, and mortality (overall survival, nonrelapse mortality, and failure-free survival) in multivariable analyses adjusted for significant covariates. 2MWT was significantly associated with intuitive domains of the Lee Symptom Scale (overall, skin, lung, energy), SF-36 domain and summary scores, FACT summary and domain scores, and HAP scores (all P < .001). Fewer associations were detected with the HGS. The 2MWT and HGS both had significant association with global chronic GVHD severity. In multivariable analysis, 2MWT was significantly associated with overall survival, nonrelapse mortality, and failure-free survival, whereas no association was found for HGS. 2MWT and HGS were not sensitive to National Institutes of Health or clinician-reported response. Based on independent association with mortality, these data support the importance of the 2MWT for identification of high-risk chronic GVHD patients. However, change in 2MWT is not sensitive to chronic GVHD response, limiting its usefulness in clinical trials. (C) 2013 American Society for Blood and Marrow Transplantation.
C1 [Pidala, Joseph] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA.
[Chai, Xiaoyu; Martin, Paul; Inamoto, Yoshihiro; Lee, Stephanie J.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Cutler, Corey] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Palmer, Jeanne] Med Coll Wisconsin, Milwaukee, WI 53226 USA.
[Weisdorf, Daniel; Arora, Mukta] Univ Minnesota, Med Ctr, Minneapolis, MN 55455 USA.
[Pavletic, Steven] NCI, Bethesda, MD 20892 USA.
[Jagasia, Madan] Vanderbilt Univ, Med Ctr, Nashville, TN USA.
[Jacobsohn, David] Childrens Natl Med Ctr, Washington, DC 20010 USA.
RP Pidala, J (reprint author), Univ S Florida, H Lee Moffitt Canc Ctr, 12902 Magnolia Dr, Tampa, FL 33612 USA.
EM Joseph.pidala@moffitt.org
FU NIAID [U54 AI 083028]; [CA 118953]
FX Supported by grant CA 118953 (principle investigator, S.J.L.) and NIAID
U54 AI 083028 (principle investigator, S.J.L.).
NR 38
TC 12
Z9 12
U1 0
U2 7
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 JUN
PY 2013
VL 19
IS 6
BP 967
EP 972
DI 10.1016/j.bbmt.2013.03.014
PG 6
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA 156TX
UT WOS:000319847900020
PM 23542686
ER
PT J
AU Chen, YB
Coughlin, E
Kennedy, KF
Alyea, EP
Armand, P
Attar, EC
Ballen, KK
Cutler, C
Dey, BR
Koreth, J
McAfee, SL
Spitzer, TR
Antin, JH
Soiffer, RJ
Ho, VT
AF Chen, Yi-Bin
Coughlin, Erin
Kennedy, Kevin F.
Alyea, Edwin P.
Armand, Philippe
Attar, Eyal C.
Ballen, Karen K.
Cutler, Corey
Dey, Bimalangshu R.
Koreth, John
McAfee, Steven L.
Spitzer, Thomas R.
Antin, Joseph H.
Soiffer, Robert J.
Ho, Vincent T.
TI Busulfan Dose Intensity and Outcomes in Reduced-Intensity Allogeneic
Peripheral Blood Stem Cell Transplantation for Myelodysplastic Syndrome
or Acute Myeloid Leukemia
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Article
DE Busulfan; Reduced intensity transplant; Conditioning regimen
ID ACUTE MYELOGENOUS LEUKEMIA; CONDITIONING REGIMEN; COMPLETE REMISSION;
PATIENTS OLDER; AGE; CYTOGENETICS; STANDARD; IMPACT; GVHD; MDS
AB Comparisons of myeloablative conditioning versus reduced-intensity conditioning (RIC) have demonstrated a tradeoff between relapse and toxicity. Dose intensity across RIC regimens vary and may affect treatment outcomes. In this retrospective analysis, we investigated the effect of i.v. busulfan dosing (total dose 3.2 mg/kg versus 6.4 mg/kg) in RIC regimens that combined fludarabine and busulfan on outcomes in patients who were undergoing hematopoietic stem cell transplantation (HSCT) for myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). A total of 217 consecutive patients with MDS or AML underwent first busulfan and fludarabine RIC peripheral blood stem cell transplantation from well-matched related or unrelated donors at our institutions between 2004 and 2009. Of the 217 patients, 135 patients received Bu1 (3.2 mg/kg of busulfan) and 82 patients received Bu2 (6.4 mg/kg of busulfan), both with daily fludarabine (30 mg/m(2)/day for 4 days). The choice of RIC regimen was based on temporal institutional standard, enrollment on protocols, and physician choice. Patients had similar characteristics with a few notable differences: Patients who received Bu1 were younger (median age 61 versus 64 years, P <. 001), received more single-antigen mismatched unrelated grafts (14.1% versus 1.2%, P <. 001), received more sirolimus-based graft-versus-host disease (GVHD) prophylaxis regimens (63% versus 45%, P < .0001), received less antithymocyte globulin for GVHD prophylaxis (0% versus 22%, P < .001), and had less enrollment on a clinical trial that used prophylactic rituximab for the prevention of chronic GVHD (2.2% versus 11.0%, P = .011). Clinical disease status was similar between the groups. Median follow-up for survivors was 4.4 years for Bu1 and 3.2 years for Bu2. Because of the differences in characteristics, the 2 groups were compared with the adjustment of a propensity score that predicted Bu2 to account for measured differences. The day +200 cumulative incidence rates of grades II to IV acute GVHD (Bu1, 17%, versus Bu2, 8.5%; hazard ratio [HR], .56; 95% confidence interval [CI], .22 to 1.41; P = .22) or grades III to IV acute GVHD (Bu1, 6.7%, versus Bu2, 4.9%) were not different. The 2-year cumulative incidence of chronic GVHD was not significantly different between Bu1 and Bu2 (41.5% versus 28%, respectively; HR, .70; CI, .42 to 1.17; P = .09). Two-year nonrelapse mortality rates were similar for Bu1 and Bu2 (8.9% versus 9.8%, respectively; HR, .80; CI, .29 to 2.21; P = .67). Two-year progression-free survival and overall survival were also similar between Bu1 and Bu2 (progression-free survival: 40.6% versus 39.3%, respectively; HR, .82; CI, .57 to 1.30; P = .33; and overall survival: 47.4% versus 48.8%, respectively; HR, .96; CI, .64 to 1.44; P = .85). Subset analysis defined by clinical disease and cytogenetic risk with the propensity risk score applied suggest that in patients with high clinical disease risk and nonadverse cytogenetics, the higher dose busulfan RIC regimen may be of marginal benefit (2-year progression-free survival: HR, .54; CI, .29 to 1.03; P = .062). For the majority of patients with MDS or AML undergoing busulfan and fludarabine RIC peripheral blood stem cell transplantation, however, the dose of busulfan (3.2 mg/kg versus 6.4 mg/kg) is not associated with significant differences in overall outcomes. (C) 2013 American Society for Blood and Marrow Transplantation.
C1 [Chen, Yi-Bin; Coughlin, Erin; Attar, Eyal C.; Ballen, Karen K.; Dey, Bimalangshu R.; McAfee, Steven L.; Spitzer, Thomas R.] Massachusetts Gen Hosp, Bone Marrow Transplant Unit, Boston, MA 02114 USA.
[Alyea, Edwin P.; Armand, Philippe; Cutler, Corey; Koreth, John; Antin, Joseph H.; Soiffer, Robert J.; Ho, Vincent T.] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA.
RP Chen, YB (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Bone Marrow Transplant Unit,Canc Ctr, Cox 106,55 Fruit St, Boston, MA 02114 USA.
EM ychen6@partners.org
FU MGH Mary "Nan" DiPiero Leukemia Research Fund; MGH Clinical Research
Scholar Award; Otsuka Pharmaceuticals, Inc.
FX This research was supported by the MGH Mary "Nan" DiPiero Leukemia
Research Fund. Y.C. is supported by an MGH Clinical Research Scholar
Award.; Y.C. reports receiving consulting fees and funding to conduct
clinical trials from Otsuka Pharmaceuticals, Inc. The remaining authors
have no relevant conflicts of interest to disclose.
NR 21
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U1 0
U2 4
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 JUN
PY 2013
VL 19
IS 6
BP 981
EP 987
DI 10.1016/j.bbmt.2013.03.016
PG 7
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA 156TX
UT WOS:000319847900022
PM 23562738
ER
PT J
AU Chen, YB
Cutler, CS
AF Chen, Y-B
Cutler, C. S.
TI Biomarkers for acute GVHD: can we predict the unpredictable?
SO BONE MARROW TRANSPLANTATION
LA English
DT Review
DE GVHD; biomarkers; transplant
ID VERSUS-HOST-DISEASE; BONE-MARROW-TRANSPLANTATION; STEM-CELL
TRANSPLANTATION; SERUM CYTOKINE LEVELS; CLINICAL-TRIALS NETWORK;
NECROSIS-FACTOR-ALPHA; BLOOD UREA NITROGEN; SOLUBLE
INTERLEUKIN-2-RECEPTOR; COMPLICATIONS; MIGRATION
AB Acute GVHD remains an important complication after allogeneic hematopoietic cell transplantation (HCT). Many efforts have been devoted to identifying potential noninvasive peripheral blood biomarkers to help improve the diagnosis or management of acute GVHD while avoiding invasive tissue biopsies. Early attempts to identify biomarkers focused on inflammatory cytokines, especially IL-2 or TNF-alpha, however, both of these and others were not specific for GVHD, often being elevated in the setting of generalized inflammation, accompanying other major complications of HCT as well. More recent efforts have focused on additional cytokines and other cell-surface molecules, which function in leukocyte trafficking and activation with the hope that these can also serve as targets for novel therapeutic approaches. Modern proteomic methods have allowed the screening of large numbers of patient samples and yielded several novel candidate biomarkers, including elafin and reg3 alpha, which may not be directly involved in the immunological pathogenesis of GVHD, but may be unique biomarkers for end-organ injury. Combining these new molecules with traditionally identified cytokines to form an acute GVHD biomarker panel has recently shown the ability to predict outcomes in patients who develop acute GVHD. The ultimate goals of identifying a specific biomarker are to refine diagnosis, guide therapy and develop risk-adapted approaches in order to better treat patients and improve outcomes after allogeneic HCT. These approaches include differential treatment for patients who develop acute GVHD with a high-risk biomarker profile as well as pre-emptive therapy in patients after HCT prior to the development of symptoms. With the recent progress summarized below, these goals may soon be realized.
C1 [Chen, Y-B] Massachusetts Gen Hosp, Bone Marrow Transplant Unit, Div Hematol Oncol, Boston, MA 02114 USA.
[Cutler, C. S.] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA.
RP Chen, YB (reprint author), Massachusetts Gen Hosp, Bone Marrow Transplant Unit, Div Hematol Oncol, Cox 106, Boston, MA 02114 USA.
EM ychen6@partners.org
FU Millennium Pharmaceuticals, Inc.; Seattle Genetics
FX Dr Y-B Chen has received funding for clinical trials from Millennium
Pharmaceuticals, Inc. and has served as a consultant for and received
funding for clinical trials from Seattle Genetics.
NR 53
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U1 0
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0268-3369
J9 BONE MARROW TRANSPL
JI Bone Marrow Transplant.
PD JUN
PY 2013
VL 48
IS 6
BP 755
EP 760
DI 10.1038/bmt.2012.143
PG 6
WC Biophysics; Oncology; Hematology; Immunology; Transplantation
SC Biophysics; Oncology; Hematology; Immunology; Transplantation
GA 158JW
UT WOS:000319967200002
PM 22863728
ER
PT J
AU Shaughnessy, P
Uberti, J
Devine, S
Maziarz, RT
Vose, J
Micallef, I
Jacobsen, E
McCarty, J
Stiff, P
Artz, A
Ball, ED
Berryman, R
Dugan, M
Joyce, R
Hsu, FJ
Johns, D
McSweeney, P
AF Shaughnessy, P.
Uberti, J.
Devine, S.
Maziarz, R. T.
Vose, J.
Micallef, I.
Jacobsen, E.
McCarty, J.
Stiff, P.
Artz, A.
Ball, E. D.
Berryman, R.
Dugan, M.
Joyce, R.
Hsu, F. J.
Johns, D.
McSweeney, P.
TI Plerixafor and G-CSF for autologous stem cell mobilization in patients
with NHL, Hodgkin's lymphoma and multiple myeloma: results from the
expanded access program
SO BONE MARROW TRANSPLANTATION
LA English
DT Article
DE plerixafor; mobilization; autologous transplant
ID BONE-MARROW TRANSPLANTATION; RANDOMIZED TRIAL; CHEMOTHERAPY; ALGORITHM;
KINETICS
AB Before US regulatory approval, an expanded access program provided plerixafor to patients with non-Hodgkin's lymphoma (NHL), Hodgkin's lymphoma (HD) or multiple myeloma (MM) who had not previously failed mobilization and were otherwise candidates for auto-SCT. Patients received granulocyte-CSF (G-CSF) 10 mcg/kg daily and plerixafor 0.24 mg/kg starting on day 4 with apheresis on day 5; all repeated daily until collection was complete. Overall, 104 patients received >= 1 dose of plerixafor. The addition of plerixafor to G-CSF resulted in a median threefold increase in peripheral blood CD34+ cell count between days 4 and 5. Among 43 NHL patients, 74% met the target of >= 5 x 10(6) CD34+ cells/kg (median, 1 day apheresis, range 1-5 days); among 7 HD patients, 57% met the target of >= 5 x 10(6) CD34+ cells/kg (median, 2 days apheresis, range 1-3); and among 54 MM patients, 89% met the target of >= 6 x 10(6) CD34+ cells/kg (median, 1 day apheresis, range 1-4). Overall, 93% of patients had >= 2 x 10(6) CD34+ cells/kg collected within 1-3 days. Plerixafor-related toxicities were minimal. Engraftment kinetics, graft durability and transplant outcomes demonstrated no unexpected outcomes. Efficacy and safety results were similar to results in phase II and III clinical trials.
C1 [Shaughnessy, P.] Texas Transplant Inst, San Antonio, TX 78229 USA.
[Uberti, J.] Karmanos Canc Inst, Detroit, MI USA.
[Devine, S.] Ohio State Univ, Dept Internal Med Hematol Oncol, Columbus, OH 43210 USA.
[Maziarz, R. T.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA.
[Vose, J.] Univ Nebraska Med Ctr, Omaha, NE USA.
[Micallef, I.] Mayo Clin, Rochester, MN USA.
[Jacobsen, E.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[McCarty, J.] Virginia Commonwealth Univ, Richmond, VA USA.
[Stiff, P.] Loyola Univ, Med Ctr, Maywood, IL 60153 USA.
[Artz, A.] Univ Chicago, Chicago, IL 60637 USA.
[Ball, E. D.] Univ Calif San Diego, La Jolla, CA 92093 USA.
[Berryman, R.] Baylor Blood & Marrow Transplant Ctr, Dallas, TX USA.
[Dugan, M.] Indiana Blood & Marrow Transplantat, Beech Grove, IN USA.
[Joyce, R.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Hsu, F. J.; Johns, D.] Sanofi Oncol, Cambridge, MA USA.
[McSweeney, P.] Rocky Mt Canc Ctr, Denver, CO USA.
RP Shaughnessy, P (reprint author), Texas Transplant Inst, 4410 Med Dr Suite 410, San Antonio, TX 78229 USA.
EM paul.shaughnessy@mhshealth.com; paul.shaughnessy@mhshealth.com
FU Sanofi Oncology; Genzyme; Sanofi/Genzyme
FX This study was sponsored by Sanofi Oncology (previously Genzyme
Corporation). PS, RTM, JMC, SD, MD and PMS received honoraria and
research funding from Genzyme. IM, JV and PS received research funding
from Sanofi/Genzyme. FJH is a former Genzyme employee and is now an
employee of Zyngenia, Inc. DJ is an employee of Sanofi Oncology
(formerly Genzyme). All the other author declare no conflicts of
interest.
NR 16
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U1 0
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0268-3369
J9 BONE MARROW TRANSPL
JI Bone Marrow Transplant.
PD JUN
PY 2013
VL 48
IS 6
BP 777
EP 781
DI 10.1038/bmt.2012.219
PG 5
WC Biophysics; Oncology; Hematology; Immunology; Transplantation
SC Biophysics; Oncology; Hematology; Immunology; Transplantation
GA 158JW
UT WOS:000319967200005
PM 23178544
ER
PT J
AU Akpek, G
Pasquini, MC
Logan, B
Agovi, MA
Lazarus, HM
Marks, DI
Bornhaeuser, M
Ringden, O
Maziarz, RT
Gupta, V
Popat, U
Maharaj, D
Bolwell, BJ
Rizzo, JD
Ballen, KK
Cooke, KR
McCarthy, PL
Ho, VT
AF Akpek, G.
Pasquini, M. C.
Logan, B.
Agovi, M-A
Lazarus, H. M.
Marks, D. I.
Bornhaeueser, M.
Ringden, O.
Maziarz, R. T.
Gupta, V.
Popat, U.
Maharaj, D.
Bolwell, B. J.
Rizzo, J. D.
Ballen, K. K.
Cooke, K. R.
McCarthy, P. L.
Ho, V. T.
CA CIBMTR
TI Effects of spleen status on early outcomes after hematopoietic cell
transplantation
SO BONE MARROW TRANSPLANTATION
LA English
DT Article
DE engraftment; splenectomy; spleen; SCT; myeloproliferative disease
ID BONE-MARROW-TRANSPLANTATION; CHRONIC GRANULOCYTIC-LEUKEMIA; CHRONIC
MYELOID-LEUKEMIA; VERSUS-HOST DISEASE; PRIMARY MYELOFIBROSIS; RADIATION
INJURY; HLA MISMATCH; SPLENECTOMY; STEM; GRAFT
AB To assess the impact of spleen status on engraftment, and early morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT), we analyzed 9,683 myeloablative allograft recipients from 1990 to 2006; 472 had prior splenectomy (SP), 300 splenic irradiation (SI), 1,471 with splenomegaly (SM), and 7,440 with normal spleen (NS). Median times to neutrophil engraftment (NE) and platelet engraftment (PE) were 15 vs 18 days and 22 vs 24 days for the SP and NS groups, respectively (P < 0.001). Hematopoietic recovery at day +100 was not different across all groups, however the odds ratio of days +14 and +21 NE and day +28 PE were 3.26, 2.25 and 1.28 for SP, and 0.56, 0.55, and 0.82 for SM groups compared to NS (P < 0.001), respectively. Among patients with SM, use of peripheral blood grafts improved NE at day +21, and CD34+ cell dose >5.7 x 10(6)/kg improved PE at day +28. After adjusting variables by Cox regression, the incidence of GVHD and OS were not different among groups. SM is associated with delayed engraftment, whereas SP prior to HCT facilitates early engraftment without having an impact on survival.
C1 [Akpek, G.] Univ Maryland, Marlene & Stewart Greenbaum Canc Ctr, Baltimore, MD 21201 USA.
[Pasquini, M. C.; Logan, B.; Agovi, M-A; Rizzo, J. D.] Med Coll Wisconsin, CIBMTR, Milwaukee, WI 53226 USA.
[Lazarus, H. M.; Cooke, K. R.] Univ Hosp Case Med Ctr, Cleveland, OH USA.
[Marks, D. I.] Bristol Childrens Hosp, Bristol, Avon, England.
[Bornhaeueser, M.] Univ Klinikum Carl Gustav Carus, Dresden, Germany.
[Ringden, O.] Karolinska Univ Hosp, Ctr Allogene Stem Cell Transplantat, Stockholm, Sweden.
[Maziarz, R. T.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Gupta, V.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada.
[Popat, U.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Maharaj, D.] Bethesda Hlth City, Boynton Beach, FL USA.
[Bolwell, B. J.] Cleveland Clin Fdn, Cleveland, OH 44195 USA.
[Ballen, K. K.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[McCarthy, P. L.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA.
[Ho, V. T.] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Akpek, G (reprint author), Banner MD Anderson Canc Ctr, Stem Cell Transplantat & Cellular Therapy Program, 2940 E Banner Gateway Dr, Gilbert, AZ 85234 USA.
EM GAkpek@mdanderson.org
FU Public Health Service from the National Cancer Institute [U24-CA76518];
National Heart, Lung and Blood Institute (NHLBI); National Institute of
Allergy and Infectious Diseases (NIAID); NHLBI [5U01HL069294]; NCI;
Health Resources and Services Administration (HRSA/DHHS)
[HHSH234200637015C]; Office of Naval Research [N00014-06-1-0704,
N00014-08-1-0058]; Allos, Inc.; Amgen, Inc.; Angioblast
FX The CIBMTR is supported by Public Health Service Grant/Cooperative
Agreement U24-CA76518 from the National Cancer Institute, 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; Kiadis Pharma; The Leukemia and Lymphoma Society; the
Medical College of Wisconsin; Millennium Pharmaceuticals, Inc.; Milliman
USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; Optum
Healthcare Solutions, Inc.; Otsuka America Pharmaceutical, Inc.; Seattle
Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; Swedish Orphan
Biovitrum; THERAKOS, Inc.; and Wellpoint, Inc. The views expressed in
this article do not reflect the official policy or position of the
National Institute of Health, the Department of the Navy, the Department
of Defense or any other agency of the U.S. Government.
NR 30
TC 17
Z9 17
U1 1
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0268-3369
J9 BONE MARROW TRANSPL
JI Bone Marrow Transplant.
PD JUN
PY 2013
VL 48
IS 6
BP 825
EP 831
DI 10.1038/bmt.2012.249
PG 7
WC Biophysics; Oncology; Hematology; Immunology; Transplantation
SC Biophysics; Oncology; Hematology; Immunology; Transplantation
GA 158JW
UT WOS:000319967200014
PM 23222382
ER
PT J
AU Culley, DJ
Cotran, EK
Karlsson, E
Palanisamy, A
Boyd, JD
Xie, Z
Crosby, G
AF Culley, D. J.
Cotran, E. K.
Karlsson, E.
Palanisamy, A.
Boyd, J. D.
Xie, Z.
Crosby, G.
TI Isoflurane affects the cytoskeleton but not survival, proliferation, or
synaptogenic properties of rat astrocytes in vitro
SO BRITISH JOURNAL OF ANAESTHESIA
LA English
DT Article
DE astrocytes; isoflurane
ID VOLATILE ANESTHETICS; NERVOUS-SYSTEM; CELLS; BRAIN; GLIA; ACTIVATION;
MEMORY; NEUROGENESIS; PERSPECTIVE; IMPAIRMENT
AB More than half of the cells in the brain are glia and yet the impact of general anaesthetics on these cells is largely unexamined. We hypothesized that astroglia, which are strongly implicated in neuronal well-being and synapse formation and function, are vulnerable to adverse effects of isoflurane.
Cultured rat astrocytes were treated with 1.4 isoflurane in air or air alone for 4 h. Viability, proliferation, and cytoskeleton were assessed by colorimetric assay, immunocytochemistry, or a migration assay at the end of treatment or 2 days later. Also, primary rat cortical neurones were treated for 4 days with conditioned medium from control [astrocyte-conditioned media (ACM)], or isoflurane-exposed astrocytes (Iso-ACM) and synaptic puncta were assessed by synapsin 1 and PSD-95 immunostaining.
By several measures, isoflurane did not kill astrocytes. Nor, based on incorporation of a thymidine analogue, did it inhibit proliferation. Isoflurane had no effect on F-actin but reduced expression of -tubulin and glial fibrillary acidic protein both during exposure (P0.05 and P0.001, respectively) and 2 days later (P0.01), but did not impair astrocyte motility. ACM increased formation of PSD-95 but not synapsin 1 positive puncta in neuronal cultures, and Iso-ACM was equally effective.
Isoflurane decreased expression of microtubule and intermediate filament proteins in astrocytes in vitro, but did not affect their viability, proliferation, motility, and ability to support synapses.
C1 [Culley, D. J.; Cotran, E. K.; Karlsson, E.; Palanisamy, A.; Crosby, G.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA.
[Boyd, J. D.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Harvard NeuroDiscovery Ctr,LDDN, Cambridge, MA 02139 USA.
[Xie, Z.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
RP Culley, DJ (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA.
EM dculley@zeus.bwh.harvard.edu
FU National Institutes of Health [K08 GM077057, R01 GM088817]; Milton Fund
of Harvard University; Department of Anesthesiology, Perioperative and
Pain Medicine, Brigham and Women's Hospital, Boston, MA, USA
FX This study was supported by National Institutes of Health grants K08
GM077057 (D.J.C.), R01 GM088817 (G.C.), the Milton Fund of Harvard
University (D.J.C.), and the Department of Anesthesiology, Perioperative
and Pain Medicine, Brigham and Women's Hospital, Boston, MA, USA.
NR 38
TC 19
Z9 20
U1 0
U2 7
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0007-0912
J9 BRIT J ANAESTH
JI Br. J. Anaesth.
PD JUN
PY 2013
VL 110
SU 1
SI SI
BP 19
EP 28
DI 10.1093/bja/aet169
PG 10
WC Anesthesiology
SC Anesthesiology
GA 156JK
UT WOS:000319817700004
ER
PT J
AU Zhang, L
Zhang, J
Yang, L
Dong, Y
Zhang, Y
Xie, Z
AF Zhang, L.
Zhang, J.
Yang, L.
Dong, Y.
Zhang, Y.
Xie, Z.
TI Isoflurane and sevoflurane increase interleukin-6 levels through the
nuclear factor-kappa B pathway in neuroglioma cells
SO BRITISH JOURNAL OF ANAESTHESIA
LA English
DT Article
DE anaesthetic; interleukin-6; NF-kappa B
ID AMYLOID PROTEIN-LEVELS; PYRROLIDINE DITHIOCARBAMATE; COGNITIVE
DYSFUNCTION; CYTOKINE EXPRESSION; INDUCED APOPTOSIS; AGED RATS;
ACTIVATION; ANESTHETICS; BEHAVIOR; BRAIN
AB Isoflurane can increase pro-inflammatory cytokine interleukin (IL)-6 levels. However, the up-stream mechanism remains unknown. Nuclear factor-kappa B (NF-B) promotes the generation of pro-inflammatory cytokines. We examined the effects of isoflurane and sevoflurane on the NF-B signalling pathway and its association with IL-6 levels in cultured cells.
H4 human neuroglioma cells (H4 cells), and mouse primary neurones and microglia were treated with 2 isoflurane or 4.1 sevoflurane for 6 h, for analysis of IL-6 and NF-B. Pyrrolidine dithiocarbamate (an NF-B inhibitor) or 2-deoxy-d-glucose (2-DG) (an inhibitor of glucose glycolysis) was applied 1 h before anaesthetic treatment.
Isoflurane or sevoflurane treatment increased the levels of IL-6 [isoflurane: 410 (54); sevoflurane: 290 (24)], the nuclear levels of NF-B [isoflurane: 170 (36); sevoflurane: 320 (30)], and the transcription activity of NF-B in H4 cells. Moreover, isoflurane enhanced the transcription activity of NF-B in mouse microglia, but not primary neurones. Finally, pyrrolidine dithiocarbamate and 2-DG attenuated isoflurane-induced increases in IL-6 and NF-B, and the transcription activity of NF-B.
These studies in H4 cells suggest that the NF-B signalling pathway could contribute to isoflurane or sevoflurane-induced neuroinflammation. This could lead to the targeted intervention of anaesthetic-induced neuroinflammation.
C1 [Zhang, L.; Zhang, J.; Yang, L.; Dong, Y.; Zhang, Y.; Xie, Z.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Geriatr Anesthesia Res Unit, Charlestown, MA 02129 USA.
[Zhang, L.; Zhang, J.; Yang, L.; Dong, Y.; Zhang, Y.; Xie, Z.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
[Zhang, L.] Shanghai Jiao Tong Univ, Sch Med, Peoples Hosp 9, Dept Anesthesiol, Shanghai 200011, Peoples R China.
[Zhang, J.] Huazhong Univ Sci & Technol, Tongji Hosp, Dept Anesthesiol, Tongji Med Coll, Wuhan 430030, Peoples R China.
RP Xie, Z (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Geriatr Anesthesia Res Unit, Charlestown, MA 02129 USA.
EM zxie@partners.org
FU National Institutes of Health, Bethesda, MD, USA [R21AG038994, R01
GM088801, R01 AG041274]; Alzheimer's Association, Chicago, IL, USA; Cure
Alzheimer's Fund, Wellesley, MA, USA
FX This research was supported by R21AG038994, R01 GM088801 and R01
AG041274 from National Institutes of Health, Bethesda, MD, USA;
investigator-initiated research grant from Alzheimer's Association,
Chicago, IL, USA; and Cure Alzheimer's Fund, Wellesley, MA, USA to Z.X.
Isoflurane and sevoflurane were generously provided by the Department of
Anaesthesia, Critical Care and Pain Medicine, Massachusetts General
Hospital and Harvard Medical School, Boston, MA, USA. These studies are
attributed to the Department of Anaesthesia, Critical Care and Pain
Medicine, Massachusetts General Hospital and Harvard Medical School.
NR 41
TC 33
Z9 35
U1 2
U2 10
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0007-0912
J9 BRIT J ANAESTH
JI Br. J. Anaesth.
PD JUN
PY 2013
VL 110
SU 1
SI SI
BP 82
EP 91
DI 10.1093/bja/aet115
PG 10
WC Anesthesiology
SC Anesthesiology
GA 156JK
UT WOS:000319817700010
ER
PT J
AU Wu, B
Hur, S
AF Wu, Bin
Hur, Sun
TI Viral counterattack against the host innate immune system
SO CELL RESEARCH
LA English
DT Editorial Material
ID PARAMYXOVIRUS V PROTEINS; DSRNA RECOGNITION; MDA5 FILAMENTS; RIG-I; RNA
C1 [Wu, Bin; Hur, Sun] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Wu, Bin; Hur, Sun] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA.
RP Hur, S (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
EM hur@idi.harvard.edu
RI Wu, Bin/C-4715-2015
NR 10
TC 2
Z9 2
U1 0
U2 3
PU INST BIOCHEMISTRY & CELL BIOLOGY
PI SHANGHAI
PA SIBS, CAS, 319 YUEYANG ROAD, SHANGHAI, 200031, PEOPLES R CHINA
SN 1001-0602
J9 CELL RES
JI Cell Res.
PD JUN
PY 2013
VL 23
IS 6
BP 735
EP 736
DI 10.1038/cr.2013.32
PG 2
WC Cell Biology
SC Cell Biology
GA 156FL
UT WOS:000319807100002
PM 23478300
ER
PT J
AU Gupta, H
Ramanan, B
Gupta, PK
Fang, X
Polich, A
Modrykamien, A
Schuller, D
Morrow, LE
AF Gupta, Himani
Ramanan, Bala
Gupta, Prateek K.
Fang, Xiang
Polich, Ann
Modrykamien, Ariel
Schuller, Dan
Morrow, Lee E.
TI Impact of COPD on Postoperative Outcomes Results From a National
Database
SO CHEST
LA English
DT Article
ID OBSTRUCTIVE PULMONARY-DISEASE; ABDOMINAL WOUND DEHISCENCE; AFFAIRS
SURGICAL RISK; NUTRITIONAL-STATUS; NONCARDIAC SURGERY; PROGNOSTIC VALUE;
RENAL-FAILURE; OLDER-ADULTS; MORTALITY; CARE
AB Background: Although COPD affects large sections of the population, its effects on postoperative outcomes have not been rigorously studied. The objectives of this study were to describe the prevalence of COPD in patients undergoing surgery and to analyze the associations between COPD and postoperative morbidity, mortality, and hospital length of stay.
Methods: Patients with COPD who underwent surgery were identified from the National Surgical Quality Improvement Program database (2007-2008). Univariate and multivariate analyses were performed on this multicenter, prospective data set (N = 468,795).
Results: COPD was present in 22,576 patients (4.82%). These patients were more likely to be older, men, white, smokers, and taking corticosteroids and had a lower BMI (P <.0001 for each). Median length of stay was 4 days for patients with COPD vs 1 day in those without COPD (P <.0001). Thirty-day morbidity rates were 25.8% and 10.2% for patients with and without COPD, respectively (P <.0001). Thirty-day death rates were 6.7% and 1.4% for patients with and without COPD, respectively (P <.0001). After controlling for >50 comorbidities through logistic regression modeling, COPD was independently associated with higher postoperative morbidity (OR, 1.35; 95% CI, 1.30-1.40; P <.0001) and mortality (OR, 1.29; 95% CI, 1.19-1.39; P <.0001). Multivariate analyses with each individual postoperative complication as the outcome of interest showed that COPD was associated with increased risk for postoperative pneumonia, respiratory failure, myocardial infarction, cardiac arrest, sepsis, return to the operating room, and renal insufficiency or failure (P <.05 for each).
Conclusions: COPD is common among patients undergoing surgery and is associated with increased morbidity, mortality, and length of stay.
C1 [Gupta, Himani] William S Middleton Mem Vet Adm Med Ctr, Dept Med, Madison, WI USA.
[Ramanan, Bala] Creighton Univ, Dept Surg, Omaha, NE 68178 USA.
[Fang, Xiang] Creighton Univ, Biostat Core, Omaha, NE 68178 USA.
[Polich, Ann] Creighton Univ, Dept Med, Omaha, NE 68178 USA.
[Modrykamien, Ariel; Schuller, Dan; Morrow, Lee E.] Creighton Univ, Div Pulm Crit Care & Sleep Med, Omaha, NE 68178 USA.
[Gupta, Prateek K.] Univ Wisconsin Hosp & Clin, Dept Surg, Madison, WI 53792 USA.
RP Gupta, PK (reprint author), Univ Wisconsin Hosp & Clin, Dept Surg, 600 Highland Ave, Madison, WI 53792 USA.
EM pgupta@uwhealth.org
NR 42
TC 21
Z9 23
U1 1
U2 3
PU AMER COLL CHEST PHYSICIANS
PI NORTHBROOK
PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA
SN 0012-3692
J9 CHEST
JI Chest
PD JUN
PY 2013
VL 143
IS 6
BP 1599
EP 1606
DI 10.1378/chest.12-1499
PG 8
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 159UN
UT WOS:000320072900018
PM 23287892
ER
PT J
AU Kinsey, CM
Folch, E
Majid, A
Channick, CL
AF Kinsey, C. Matthew
Folch, Erik
Majid, Adnan
Channick, Colleen L.
TI Evaluation and Management of Pill Aspiration Case Discussion and Review
of the Literature
SO CHEST
LA English
DT Editorial Material
ID IRON TABLET; BRONCHIAL NECROSIS; FERROUS SULFATE; FOREIGN-BODY;
INHALATION; LUNG
AB Pill aspiration represents a unique type of foreign body aspiration requiring a distinct diagnostic and therapeutic approach. In many cases, the "foreign body" itself may no longer be present, whereas the airway manifestations may persist for months to years. Limited data exist to guide management decisions. We report two cases of severe airway injury secondary to pill aspiration and provide a review of the literature. Endobronchial surveillance may be important to identify impending airway obstruction via secretions, edema, granulation tissue, or fibrotic stricture. In many cases, the airway sequelae of pill aspiration can be effectively managed with bronchoscopy.
C1 [Kinsey, C. Matthew; Channick, Colleen L.] Massachusetts Gen Hosp, Pulm Special Procedures Unit, Boston, MA 02114 USA.
[Folch, Erik; Majid, Adnan] Beth Israel Deaconess Med Ctr, Div Thorac Surg & Intervent Pulmonol, Boston, MA 02215 USA.
[Kinsey, C. Matthew; Folch, Erik; Majid, Adnan; Channick, Colleen L.] Harvard Univ, Sch Med, Boston, MA USA.
RP Channick, CL (reprint author), Massachusetts Gen Hosp, Pulm Special Procedures Unit, 55 Fruit St,Bigelow 952, Boston, MA 02114 USA.
EM cchannick@partners.org
OI Folch, Erik/0000-0001-7076-7328
NR 16
TC 7
Z9 7
U1 0
U2 2
PU AMER COLL CHEST PHYSICIANS
PI GLENVIEW
PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA
SN 0012-3692
J9 CHEST
JI Chest
PD JUN
PY 2013
VL 143
IS 6
BP 1791
EP 1795
DI 10.1378/chest.12-1571
PG 5
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 159UN
UT WOS:000320072900043
PM 23732590
ER
PT J
AU Levsky, JM
Moy, MP
Haramati, LB
AF Levsky, Jeffrey M.
Moy, Matthew P.
Haramati, Linda B.
TI Basis of Estimating Pleural Effusion Size on CT Scan Reasonable Grouping
of Volume Percentage Response
SO CHEST
LA English
DT Letter
C1 [Levsky, Jeffrey M.; Haramati, Linda B.] Albert Einstein Coll Med, Bronx, NY 10467 USA.
[Levsky, Jeffrey M.; Haramati, Linda B.] Montefiore Med Ctr, Bronx, NY 10467 USA.
[Moy, Matthew P.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Levsky, JM (reprint author), Montefiore Med Ctr, Albert Einstein Coll Med, 111 E 210 St, Bronx, NY 10467 USA.
EM jlevsky@montefiore.org
NR 3
TC 0
Z9 0
U1 0
U2 0
PU AMER COLL CHEST PHYSICIANS
PI NORTHBROOK
PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA
SN 0012-3692
J9 CHEST
JI Chest
PD JUN
PY 2013
VL 143
IS 6
BP 1839
EP 1840
DI 10.1378/chest.13-0569
PG 2
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 159UN
UT WOS:000320072900060
PM 23732611
ER
PT J
AU Oberg, K
Casanovas, O
Castano, JP
Chung, D
Delle Fave, G
Denefle, P
Harris, P
Khan, MS
Kulke, MH
Scarpa, A
Tang, LH
Wiedenmann, B
AF Oberg, Kjell
Casanovas, Oriol
Castano, Justo P.
Chung, Daniel
Delle Fave, Gianfranco
Denefle, Patrice
Harris, Philip
Khan, Mohid S.
Kulke, Matthew H.
Scarpa, Aldo
Tang, Laura H.
Wiedenmann, Bertram
TI Molecular Pathogenesis of Neuroendocrine Tumors: Implications for
Current and Future Therapeutic Approaches
SO CLINICAL CANCER RESEARCH
LA English
DT Review
ID PANCREATIC ENDOCRINE TUMORS; SOMATOSTATIN RECEPTORS; REVEALS
ALTERATIONS; MESSENGER-RNA; BREAST-CANCER; MTOR PATHWAY; CELLS;
EXPRESSION; RESISTANCE; INHIBITION
AB The treatment landscape and biologic understanding of neuroendocrine tumors ( NET) has shifted dramatically in recent years. Recent studies have shown that somatostatin analogues have the potential not only to control symptoms of hormone hypersecretion but also have the ability to slow tumor growth in patients with advanced carcinoid. The results of clinical trials have further shown that the VEGF pathway inhibitor sunitinib and the mTOR inhibitor everolimus have efficacy in patients with advanced pancreatic NETs. The efficacy of these targeted therapies in NET suggests that the molecular characterization of NETs may provide an avenue to predict both which patients may benefit most from the treatment and to overcome potential drug resistance. Recent genomic studies of NETs have further suggested that pathways regulating chromatin remodeling and epigenetic modification may play a key role in regulating NET growth. These observations offer the potential for new therapeutic and diagnostic advances for patients with NET. (C) 2013 AACR.
C1 [Oberg, Kjell] Univ Uppsala Hosp, Dept Endocrine Oncol, S-75185 Uppsala, Sweden.
[Casanovas, Oriol] Catalan Inst Oncol IDIBELL, Translat Res Lab, Tumor Angiogenesis Grp, Barcelona, Spain.
[Castano, Justo P.] Univ Cordoba, Hosp Univ Reina Sofia, IMIBIC, Dept Cell Biol Physiol & Immunol, Cordoba, Spain.
[Castano, Justo P.] CIBERobn, Cordoba, Spain.
[Chung, Daniel] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
[Chung, Daniel] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
[Kulke, Matthew H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Delle Fave, Gianfranco] Univ Roma La Sapienza, Sch Med, Dept Translat Med, Rome, Italy.
[Scarpa, Aldo] Univ & Hosp Trust Verona, Dept Pathol & Diagnost, Verona, Italy.
[Scarpa, Aldo] Univ & Hosp Trust Verona, ARC NET Ctr Appl Res Canc, Verona, Italy.
[Denefle, Patrice] Ipsen Ltd, Translat Sci, Les Ulis, France.
[Harris, Philip] Ipsen Ltd, Sci Affairs, Slough, Berks, England.
[Khan, Mohid S.] Univ Coll London Hosp, Div Gastrointestinal Serv, London, England.
[Tang, Laura H.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA.
[Wiedenmann, Bertram] Charite, Dept Internal Med, Div Gastroenterol Hepatol & Metab, Berlin, Germany.
RP Oberg, K (reprint author), Univ Uppsala Hosp, Dept Endocrine Oncol, S-75185 Uppsala, Sweden.
EM kjell.oberg@medsci.uu.se
RI Castano, Justo P/A-7124-2010; scarpa, aldo/K-6832-2016;
OI Castano, Justo P/0000-0002-3145-7287; scarpa, aldo/0000-0003-1678-739X;
Casanovas, Oriol/0000-0002-4298-3995
FU Ipsen; Novartis
FX K. Oberg has received honoraria from the speakers' bureau and is a
consultant/advisory board member of USD, EUR. O. Casanovas has received
honoraria from the speakers' bureaus of Ipsen and Pfizer and is a
consultant/advisory board member of TEVA and Ipsen. J.P. Castano has a
commercial research grant from Ipsen and has received honoraria from the
speakers' bureaus of Ipsen and Novartis. D. Chung is a
consultant/advisory board member of Ipsen. M.S. Khan has received
honoraria from the speakers' bureaus of Ipsen and Novartis. M.H. Kulke
has commercial research grants from Novartis and Ipsen and is a
consultant/advisory board member of Ipsen, Novartis, Pfizer, and
Lexicon. B. Wiedenmann has received honoraria from the speakers' bureaus
of Pfizer, Novartis, and IOSEN Biotech and is a consultant/advisory
board member of Pfizer, Novartis, and Ipsen. No potential conflicts of
interest were disclosed by the other authors.
NR 67
TC 28
Z9 29
U1 0
U2 7
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD JUN 1
PY 2013
VL 19
IS 11
BP 2842
EP 2849
DI 10.1158/1078-0432.CCR-12-3458
PG 8
WC Oncology
SC Oncology
GA 155FF
UT WOS:000319732000010
PM 23459719
ER
PT J
AU Ouillette, P
Saiya-Cork, K
Seymour, E
Li, C
Shedden, K
Malek, SN
AF Ouillette, Peter
Saiya-Cork, Kamlai
Seymour, Erlene
Li, Cheng
Shedden, Kerby
Malek, Sami N.
TI Clonal Evolution, Genomic Drivers, and Effects of Therapy in Chronic
Lymphocytic Leukemia
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID ACUTE MYELOGENOUS LEUKEMIA; SHORT SURVIVAL; COPY NUMBER; MDM2
INHIBITORS; MUTATION STATUS; P53 MUTATIONS; GENE MUTATION; WIDE
ANALYSIS; ABERRATIONS; RESISTANCE
AB Purpose: The identification of gene mutations and structural genomic aberrations that are critically involved in chronic lymphocytic leukemia (CLL) pathogenesis is still evolving. One may postulate that genomic driver lesions with effects on CLL cell proliferation, apoptosis thresholds, or chemotherapy resistance should increase in frequency over time when measured sequentially in a large CLL cohort.
Experimental Design: We sequentially sampled a large well-characterized CLL cohort at a mean of 4 years between samplings and measured acquired copy number aberrations (aCNA) and LOH using single-nucleotide polymorphism (SNP) 6.0 array profiling and the mutational state of TP53, NOTCH1, and SF3B1 using Sanger sequencing. The paired analysis included 156 patients, of whom 114 remained untreated and 42 received intercurrent therapies, predominantly potent chemoimmunotherapy, during the sampling interval.
Results: We identify a strong effect of intercurrent therapies on the frequency of acquisition of aCNAs in CLL. Importantly, the spectrum of acquired genomic changes was largely similar in patients who did or did not receive intercurrent therapies; therefore, various genomic changes that become part of the dominant clones are often already present in CLL cell populations before therapy. Furthermore, we provide evidence that therapy of CLL with preexisting TP53 mutations results in outgrowth of genomically very complex clones, which dominate at relapse.
Conclusions: Using complementary technologies directed at the detection of genomic events that are present in substantial proportions of the clinically relevant CLL disease bulk, we capture aspects of genomic evolution in CLL over time, including increases in the frequency of genomic complexity, specific recurrent aCNAs, and TP53 mutations. (c) 2013 AACR.
C1 [Ouillette, Peter; Saiya-Cork, Kamlai; Seymour, Erlene; Malek, Sami N.] Univ Michigan, Div Hematol & Oncol, Dept Internal Med, Ann Arbor, MI 48109 USA.
[Shedden, Kerby] Univ Michigan, Dept Stat, Ann Arbor, MI 48109 USA.
[Li, Cheng] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Li, Cheng] Harvard Univ, Sch Publ Hlth, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Li, Cheng] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Malek, SN (reprint author), Univ Michigan, Div Hematol & Oncol, Dept Internal Med, 1500 E,Med Ctr Dr, Ann Arbor, MI 48109 USA.
EM smalek@med.umich.edu
FU NIH [CA136537]; Clinical Scholars Award of the Leukemia and Lymphoma
Society of America; Translational Research Program of the Leukemia and
Lymphoma Society of America; collaborative research grant by the
Lymphoma Research Foundation; NIH through the University of Michigan's
Cancer Center Support Grant [5 P30 CA46592]
FX This work was supported by the NIH through CA136537 (to S.N. Malek), a
Clinical Scholars Award of the Leukemia and Lymphoma Society of America
(to S.N. Malek), the Translational Research Program of the Leukemia and
Lymphoma Society of America (to S.N. Malek), and a collaborative
research grant by the Lymphoma Research Foundation. This research is
supported (in part) by the NIH through the University of Michigan's
Cancer Center Support Grant (5 P30 CA46592).
NR 41
TC 30
Z9 30
U1 0
U2 4
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD JUN 1
PY 2013
VL 19
IS 11
BP 2893
EP 2904
DI 10.1158/1078-0432.CCR-13-0138
PG 12
WC Oncology
SC Oncology
GA 155FF
UT WOS:000319732000015
PM 23620403
ER
PT J
AU Martin, ES
Belmont, PJ
Sinnamon, MJ
Richard, LG
Yuan, J
Coffee, EM
Roper, J
Lee, L
Heidari, P
Lunt, SY
Goel, G
Ji, XD
Xie, Z
Xie, T
Lamb, J
Weinrich, SL
VanArsdale, T
Bronson, RT
Xavier, RJ
Vander Heiden, MG
Kan, JLC
Mahmood, U
Hung, KE
AF Martin, Eric S.
Belmont, Peter J.
Sinnamon, Mark J.
Richard, Larissa Georgeon
Yuan, Jing
Coffee, Erin M.
Roper, Jatin
Lee, Lydia
Heidari, Pedram
Lunt, Sophia Y.
Goel, Gautam
Ji, Xiadong
Xie, Zhi
Xie, Tao
Lamb, John
Weinrich, Scott L.
VanArsdale, Todd
Bronson, Roderick T.
Xavier, Ramnik J.
Vander Heiden, Matthew G.
Kan, Julie L. C.
Mahmood, Umar
Hung, Kenneth E.
TI Development of a Colon Cancer GEMM-Derived Orthotopic Transplant Model
for Drug Discovery and Validation
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID METASTATIC COLORECTAL-CANCER; SYNTHETIC LETHAL INTERACTIONS; TARGETED
THERAPIES; ONCOGENIC KRAS; MOUSE MODEL; CELLS; RAS; TUMORS; MUTATIONS;
PIK3CA
AB Purpose: Effective therapies for KRAS-mutant colorectal cancer (CRC) are a critical unmet clinical need. Previously, we described genetically engineered mouse models (GEMM) for sporadic Kras-mutant and non-mutant CRC suitable for preclinical evaluation of experimental therapeutics. To accelerate drug discovery and validation, we sought to derive low-passage cell lines from GEMM Kras-mutant and wild-type tumors for in vitro screening and transplantation into the native colonic environment of immunocompetent mice for in vivo validation.
Experimental Design: Cell lines were derived from Kras-mutant and non-mutant GEMM tumors under defined media conditions. Growth kinetics, phosphoproteomes, transcriptomes, drug sensitivity, and metabolism were examined. Cell lines were implanted in mice and monitored for in vivo tumor analysis.
Results: Kras-mutant cell lines displayed increased proliferation, mitogen-activated protein kinase signaling, and phosphoinositide-3 kinase signaling. Microarray analysis identified significant overlap with human CRC-related gene signatures, including KRAS-mutant and metastatic CRC. Further analyses revealed enrichment for numerous disease-relevant biologic pathways, including glucose metabolism. Functional assessment in vitro and in vivo validated this finding and highlighted the dependence of Kras-mutant CRC on oncogenic signaling and on aerobic glycolysis.
Conclusions: We have successfully characterized a novel GEMM-derived orthotopic transplant model of human KRAS-mutant CRC. This approach combines in vitro screening capability using low-passage cell lines that recapitulate human CRC and potential for rapid in vivo validation using cell line-derived tumors that develop in the colonic microenvironment of immunocompetent animals. Taken together, this platform is a clear advancement in preclinical CRC models for comprehensive drug discovery and validation efforts. (c) 2013 AACR.
C1 [Martin, Eric S.; Bronson, Roderick T.] Dana Farber Canc Inst, San Diego, CA USA.
[Belmont, Peter J.; Yuan, Jing; Ji, Xiadong; Xie, Zhi; Xie, Tao; Lamb, John; Weinrich, Scott L.; VanArsdale, Todd; Kan, Julie L. C.] Pfizer Global Res & Dev, Oncol Res Unit, San Diego, CA 92121 USA.
[Sinnamon, Mark J.; Richard, Larissa Georgeon; Coffee, Erin M.; Roper, Jatin; Lee, Lydia; Hung, Kenneth E.] Tufts Med Ctr, Div Gastroenterol, Boston, MA USA.
[Lunt, Sophia Y.; Vander Heiden, Matthew G.] MIT, Koch Inst Integrat Canc Res, Boston, MA USA.
[Heidari, Pedram; Mahmood, Umar] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Goel, Gautam; Xavier, Ramnik J.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
RP Martin, ES (reprint author), Pfizer Global Res & Dev, 10724 Sci Ctr Dr CB3-2227, San Diego, CA 92121 USA.
EM Eric.Martin@pfizer.com; kenneth.hung@tufts.edu
OI Lunt, Sophia/0000-0003-4522-6065; Roper, Jatin/0000-0002-8851-1352
FU NCI NIH HHS [U01 CA084301]; NIDDK NIH HHS [K08 DK078033, P30 DK043351,
R03 DK088014]
NR 46
TC 13
Z9 13
U1 0
U2 6
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD JUN 1
PY 2013
VL 19
IS 11
BP 2929
EP 2940
DI 10.1158/1078-0432.CCR-12-2307
PG 12
WC Oncology
SC Oncology
GA 155FF
UT WOS:000319732000018
PM 23403635
ER
PT J
AU Chauhan, D
Ray, A
Viktorsson, K
Spira, J
Paba-Prada, C
Munshi, N
Richardson, P
Lewensohn, R
Anderson, KC
AF Chauhan, Dharminder
Ray, Arghya
Viktorsson, Kristina
Spira, Jack
Paba-Prada, Claudia
Munshi, Nikhil
Richardson, Paul
Lewensohn, Rolf
Anderson, Kenneth C.
TI In Vitro and In Vivo Antitumor Activity of a Novel Alkylating Agent,
Melphalan-Flufenamide, against Multiple Myeloma Cells
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID FLUOROPHENYLALANINE ETHYL-ESTER; PRODRUG J1; CLINICAL RESISTANCE;
RANDOMIZED-TRIAL; AMINOPEPTIDASE-N; DRUG-RESISTANCE; APOPTOSIS;
THALIDOMIDE; INHIBITOR; CHEMOTHERAPY
AB Purpose: The alkylating agent melphalan prolongs survival in patients with multiple myeloma; however, it is associated with toxicities and development of drug-resistance. Here, we evaluated the efficacy of melphalan-flufenamide (mel-flufen), a novel dipeptide prodrug of melphalan in multiple myeloma.
Experimental Design: Multiple myeloma cell lines, primary patient cells, and the human multiple myeloma xenograft animal model were used to study the antitumor activity of mel-flufen.
Results: Low doses of mel-flufen trigger more rapid and higher intracellular concentrations of melphalan in multiple myeloma cells than are achievable by free melphalan. Cytotoxicity analysis showed significantly lower IC50 of mel-flufen than melphalan in multiple myeloma cells. Importantly, mel-flufen induces apoptosis even in melphalan-and bortezomib-resistant multiple myeloma cells. Mechanistic studies show that siRNA knockdown of aminopeptidase N, a key enzyme mediating intracellular conversion of mel-flufen to melphalan, attenuates anti-multiple myeloma activity of mel-flufen. Furthermore, mel-flufen-induced apoptosis was associated with: (i) activation of caspases and PARP cleavage; (ii) reactive oxygen species generation; (iii) mitochondrial dysfunction and release of cytochrome c; and (iv) induction of DNA damage. Moreover, mel-flufen inhibits multiple myeloma cell migration and tumor-associated angiogenesis. Human multiple myeloma xenograft studies showed amore potent inhibition of tumor growth in mice treated withmel-flufen than mice receiving equimolar doses of melphalan. Finally, combining mel-flufen with lenalidomide, bortezomib, or dexamethasone triggers synergistic anti-multiple myeloma activity.
Conclusion: Our preclinical study supports clinical evaluation of mel-flufen to enhance therapeutic potential of melphalan, overcome drug-resistance, and improve multiple myeloma patient outcome. (C) 2013 AACR.
C1 [Chauhan, Dharminder; Ray, Arghya; Paba-Prada, Claudia; Munshi, Nikhil; Richardson, Paul; Anderson, Kenneth C.] Harvard Univ, Sch Med, LeBow Inst Myeloma Therapeut, Boston, MA USA.
[Chauhan, Dharminder; Ray, Arghya; Paba-Prada, Claudia; Munshi, Nikhil; Richardson, Paul; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA.
[Viktorsson, Kristina; Lewensohn, Rolf] Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden.
[Viktorsson, Kristina; Lewensohn, Rolf] Karolinska Univ Hosp, Stockholm, Sweden.
[Spira, Jack] Karolinska Inst Sci Pk, Oncopeptides AB, Solna, Sweden.
RP Chauhan, D (reprint author), Dana Farber Canc Inst, M561,450 Brookline Ave, Boston, MA 02215 USA.
EM Dharminder_Chauhan@dfci.harvard.edu; Rolf.lewensohn@ki.se;
Kenneth_Anderson@dfci.harvard.edu
FU NIH [P50100707, CA078378]; Swedish Cancer Society, Swedish Research
Council and Stockholm Cancer Society
FX This investigation was supported by NIH grants P50100707 and CA078378
(to D. Chauhan and K. C. Anderson); Swedish Cancer Society, Swedish
Research Council and Stockholm Cancer Society (to K. Viktorsson and R.
Lewensohn).
NR 47
TC 12
Z9 14
U1 0
U2 6
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD JUN 1
PY 2013
VL 19
IS 11
BP 3019
EP 3031
DI 10.1158/1078-0432.CCR-12-3752
PG 13
WC Oncology
SC Oncology
GA 155FF
UT WOS:000319732000026
PM 23584492
ER
PT J
AU Socinski, MA
Goldman, J
El-Hariry, I
Koczywas, M
Vukovic, V
Horn, L
Paschold, E
Salgia, R
West, H
Sequist, LV
Bonomi, P
Brahmer, J
Chen, LC
Sandler, A
Belani, CP
Webb, T
Harper, H
Huberman, M
Ramalingam, S
Wong, KK
Teofilovici, F
Guo, W
Shapiro, GI
AF Socinski, Mark A.
Goldman, Jonathan
El-Hariry, Iman
Koczywas, Marianna
Vukovic, Vojo
Horn, Leora
Paschold, Eugene
Salgia, Ravi
West, Howard
Sequist, Lecia V.
Bonomi, Philip
Brahmer, Julie
Chen, Lin-Chi
Sandler, Alan
Belani, Chandra P.
Webb, Timothy
Harper, Harry
Huberman, Mark
Ramalingam, Suresh
Wong, Kwok-Kin
Teofilovici, Florentina
Guo, Wei
Shapiro, Geoffrey I.
TI A Multicenter Phase II Study of Ganetespib Monotherapy in Patients with
Genotypically Defined Advanced Non-Small Cell Lung Cancer
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID POTENT ANTITUMOR-ACTIVITY; HSP90 INHIBITOR; B-RAF; ANAPLASTIC LYMPHOMA;
KINASE INHIBITORS; FUSION ONCOGENE; ALK; EML4-ALK; RESISTANCE; CHAPERONE
AB Purpose: Ganetespib is a novel inhibitor of the heat shock protein 90 (Hsp90), a chaperone protein critical to tumor growth and proliferation. In this phase II study, we evaluated the activity and tolerability of ganetespib in previously treated patients with non-small cell lung cancer (NSCLC).
Experimental Design: Patients were enrolled into cohort A (mutant EGFR), B (mutant KRAS), or C (no EGFR or KRAS mutations). Patients were treated with 200 mg/m(2) ganetespib by intravenous infusion once weekly for 3 weeks followed by 1 week of rest, until disease progression. The primary endpoint was progression-free survival (PFS) at 16 weeks. Secondary endpoints included objective response (ORR), duration of treatment, tolerability, median PFS, overall survival (OS), and correlative studies.
Results: Ninety-nine patients with a median of 2 prior systemic therapies were enrolled; 98 were assigned to cohort A (n = 15), B (n = 17), or C (n = 66), with PFS rates at 16 weeks of 13.3%, 5.9%, and 19.7%, respectively. Four patients (4%) achieved partial response (PR); all had disease that harbored anaplastic lymphoma kinase (ALK) gene rearrangement, retrospectively detected by FISH (n 1) or PCR-based assays (n = 3), in crizotinib-naive patients enrolled to cohort C. Eight patients (8.1%) experienced treatment-related serious adverse events (AE); 2 of these (cardiac arrest and renal failure) resulted in death. The most common AEs were diarrhea, fatigue, nausea, and anorexia.
Conclusions: Ganetespib monotherapy showed a manageable side effect profile as well as clinical activity in heavily pretreated patients with advanced NSCLCs, particularly in patients with tumors harboring ALK gene rearrangement.
C1 [Socinski, Mark A.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15232 USA.
[Belani, Chandra P.] Penn State Hershey Canc Inst, Hershey, PA USA.
[Goldman, Jonathan] Premiere Oncol, Santa Monica, CA USA.
[Koczywas, Marianna] City Hope Natl Med Ctr, Duarte, CA USA.
[El-Hariry, Iman; Vukovic, Vojo; Teofilovici, Florentina; Guo, Wei] Synta Pharmaceut Corp, Lexington, KY USA.
[Sequist, Lecia V.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Huberman, Mark] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Wong, Kwok-Kin; Shapiro, Geoffrey I.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Horn, Leora] Vanderbilt Ingram Canc Ctr, Nashville, TN USA.
[Paschold, Eugene] Piedmont Hematol Oncol Associates, Winston Salem, NC USA.
[Salgia, Ravi] Univ Chicago, Med Ctr, Chicago, IL 60637 USA.
[Bonomi, Philip] Rush Univ, Med Ctr, Chicago, IL 60612 USA.
[West, Howard] Swedish Canc Ctr, Seattle, WA USA.
[Brahmer, Julie] Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
[Chen, Lin-Chi] Nevada Canc Inst, Las Vegas, NV USA.
[Sandler, Alan] Knight Canc Inst, OHSU, Portland, OR USA.
[Webb, Timothy] Genesis Canc Ctr, Hot Springs, AR USA.
[Harper, Harry] Hackensack Univ, Med Ctr, Hackensack, NJ USA.
[Ramalingam, Suresh] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA.
RP Socinski, MA (reprint author), Univ Pittsburgh, UPMC Canc Pavil, 5150 Ctr Ave,5th Floor, Pittsburgh, PA 15232 USA.
EM socinskima@upmc.edu; geoffrey_shapiro@dfci.harvard.edu
OI Belani, Chandra/0000-0001-5049-5329; wong, kwok kin/0000-0001-6323-235X
FU Synta Pharmaceuticals; Dana-Farber/Harvard Cancer Center Specialized
Program for Research Excellence (SPORE) in Lung Cancer NIH [P50 CA90578]
FX This study was supported by Synta Pharmaceuticals. K.-K. Wong and G.I.
Shapiro were also supported by the Dana-Farber/Harvard Cancer Center
Specialized Program for Research Excellence (SPORE) in Lung Cancer NIH
grant (P50 CA90578).
NR 49
TC 103
Z9 106
U1 3
U2 17
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD JUN 1
PY 2013
VL 19
IS 11
BP 3068
EP 3077
DI 10.1158/1078-0432.CCR-12-3381
PG 10
WC Oncology
SC Oncology
GA 155FF
UT WOS:000319732000031
PM 23553849
ER
PT J
AU LoRusso, P
Janne, PA
Oliveira, M
Rizvi, N
Malburg, L
Keedy, V
Yee, L
Copigneaux, C
Hettmann, T
Wu, CY
Ang, A
Halim, AB
Beckman, RA
Beaupre, D
Berlin, J
AF LoRusso, Patricia
Jaenne, Pasi A.
Oliveira, Moacyr
Rizvi, Naiyer
Malburg, Lisa
Keedy, Vicki
Yee, Lorrin
Copigneaux, Catherine
Hettmann, Thore
Wu, Chi-Yuan
Ang, Agnes
Halim, Abdel-Baset
Beckman, Robert A.
Beaupre, Darrin
Berlin, Jordan
TI Phase I Study of U3-1287, a Fully Human Anti-HER3 Monoclonal Antibody,
in Patients with Advanced Solid Tumors
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID CELL LUNG-CANCER; EPIDERMAL-GROWTH-FACTOR; TYROSINE KINASE;
BREAST-CANCER; RECEPTOR INTERACTIONS; SIGNALING NETWORK; OVARIAN-CANCER;
MESSENGER-RNA; THERAPY; HER3
AB Purpose: HER3 is a key dimerization partner for other HER family members, and its expression is associated with poor prognosis. This first-in-human study of U3-1287 (NCT00730470), a fully human anti-HER3 monoclonal antibody, evaluated its safety, tolerability, and pharmacokinetics in patients with advanced solid tumor.
Experimental Design: The study was conducted in 2 parts: part 1-sequential cohorts received escalating doses (0.3-20 mg/kg) of U3-1287 every 2 weeks, starting 3 weeks after the first dose; part 2-additional patients received 9, 14, or 20 mg/kg U3-1287 every 2 weeks, based on observed tolerability and pharmacokinetics from part 1. Recommended phase II dose, adverse event rates, pharmacokinetics, and tumor response were determined.
Results: Fifty-seven patients (part 1: 26; part 2: 31) received U3-1287. As no dose-limiting toxicities were reported, the maximum-tolerated dose was not reached. The maximum-administered dose was 20 mg/kg every 2 weeks. The most frequent adverse events related to U3-1287 were fatigue (21.1%), diarrhea (12.3%), nausea (10.5%), decreased appetite (7.0%), and dysgeusia (5.3%). No patient developed anti-U3-1287 antibodies. In these heavily pretreated patients, stable disease was maintained 9 weeks or more in 19.2% in part 1 and 10 weeks or more in 25.8% in part 2.
Conclusion: U3-1287 treatment was well tolerated, and some evidence of disease stabilization was observed. Pharmacokinetic data support U3-1287 dosing of 9 to 20 mg/kg every 2 to 3 weeks. Combination studies of U3-1287 are ongoing.
C1 [LoRusso, Patricia; Malburg, Lisa] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA.
[Jaenne, Pasi A.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Oliveira, Moacyr] Northwest Med Specialties, Tacoma, WA USA.
[Yee, Lorrin] Vista Oncol, Olympia, WA USA.
[Rizvi, Naiyer] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Keedy, Vicki; Berlin, Jordan] Vanderbilt Univ, Med Ctr, Nashville, TN USA.
[Copigneaux, Catherine; Halim, Abdel-Baset; Beckman, Robert A.] Daiichi Sankyo Pharma Dev, Edison, NJ USA.
[Hettmann, Thore] U3 Pharma GmbH, Munich, Germany.
[Wu, Chi-Yuan; Ang, Agnes; Beaupre, Darrin] Amgen Inc, Thousand Oaks, CA 91320 USA.
RP LoRusso, P (reprint author), Karmanos Canc Inst, 4100 John R St, Detroit, MI 48201 USA.
EM lorussop@karmanos.org
FU Daiichi Sankyo Pharmaceutical Development and Amgen, Inc.; U3 Pharma;
Amgen and Daiichi Sankyo Pharmaceutical
FX This study was sponsored by Daiichi Sankyo Pharmaceutical Development
and Amgen, Inc. Funding for medical writing support was provided by
Daiichi Sankyo.; P.M. LoRusso has a commercial research grant from U3
Pharma. P.A. Janne is a consultant/advisory board member of Amgen,
Boehringer Ingelheim, Roche, Pfizer, Astra Zeneca, Clovis Oncology, and
Lab Corp. V.L. Keedy has other commercial research support from Amgen
and Daiichi Sankyo Pharmaceutical. L. Yee is a consultant/advisory board
member of Dendreon, Spectrum Pharmaceutical, and Sanofi Aventis. C.
Copigneaux is employed (other than primary affiliation; e.g.,
consulting) as a director (clinical development) at Daiichi Sankyo. A.
Ang has ownership interest (including patents) in Amgen Inc. R.A.
Beckman is employed (other than primary affiliation; e.g., consulting)
as Chief ScientificOfficer of Onco-Mind, LLC.J. Berlin is a
consultant/advisory board member of Amgen. No potential conflicts of
interest were disclosed by the other authors.
NR 36
TC 45
Z9 46
U1 0
U2 10
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD JUN 1
PY 2013
VL 19
IS 11
BP 3078
EP 3087
DI 10.1158/1078-0432.CCR-12-3051
PG 10
WC Oncology
SC Oncology
GA 155FF
UT WOS:000319732000032
PM 23591447
ER
PT J
AU Lee, RJ
Saylor, PJ
Michaelson, MD
Rothenberg, SM
Smas, ME
Miyamoto, DT
Gurski, CA
Xie, WL
Maheswaran, S
Haber, DA
Goldin, JG
Smith, MR
AF Lee, Richard J.
Saylor, Philip J.
Michaelson, M. Dror
Rothenberg, S. Michael
Smas, Malgorzata E.
Miyamoto, David T.
Gurski, Carol A.
Xie, Wanling
Maheswaran, Shyamala
Haber, Daniel A.
Goldin, Jonathan G.
Smith, Matthew R.
TI A Dose-Ranging Study of Cabozantinib in Men with Castration-Resistant
Prostate Cancer and Bone Metastases
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; PHASE-II; C-MET; CLINICAL-TRIALS; END-POINTS;
EXPRESSION; RECEPTOR; INHIBITION; PREDNISONE; SUNITINIB
AB Background: Cabozantinib is an oral MET/VEGFR2 inhibitor. A recent phase II study of cabozantinib (100 mg daily) showed improved bone scans in subjects with metastatic castration-resistant prostate cancer (mCRPC), but adverse events (AE) caused frequent dose reductions. This study was designed to determine the efficacy and tolerability of cabozantinib at lower starting doses.
Experimental Design: An adaptive design was used to determine the lowest active daily dose among 60, 40, and 20 mg. The primary endpoint was week 6 bone scan response, defined as >= 30% decrease in bone scan lesion area. The secondary endpoint was change in circulating tumor cells (CTC).
Results: Among 11 evaluable subjects enrolled at 40 mg, there were 9 partial responses (PR), 1 complete response, and 1 stable disease (SD). Of 10 subjects subsequently enrolled at 20 mg, there were 1 PR, 5 SDs, and 4 with progressive disease. Among 13 subjects enrolled on the 40mgexpansion cohort, there were 6 PRs and 7 SDs. No subjects required dose reduction or treatment interruption at 6 or 12 weeks; 3 subjects at dose level 0 discontinued due to AEs by 12 weeks. At 40 mg, median treatment duration was 27 weeks. 58% of subjects with >= 5 CTCs/7.5mL at baseline converted to <5.
Conclusions: Cabozantinib 40 mg daily was associated with a high rate of bone scan response. Cabozantinib 40 mg daily was associated with better tolerability than previously reported for cabozantinib 100 mg daily. These observations informed the design of phase III studies of cabozantinib in mCRPC.
C1 [Lee, Richard J.; Saylor, Philip J.; Michaelson, M. Dror; Rothenberg, S. Michael; Smas, Malgorzata E.; Miyamoto, David T.; Gurski, Carol A.; Maheswaran, Shyamala; Haber, Daniel A.; Smith, Matthew R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
[Xie, Wanling] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Goldin, Jonathan G.] Univ Calif Los Angeles, Ctr Comp Vis & Imaging Biomarkers, Los Angeles, CA USA.
RP Lee, RJ (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,Yawkey 7018, Boston, MA 02114 USA.
EM rjlee@partners.org
OI Michaelson, Dror/0000-0001-9249-6338
FU Exelixis, Inc.; South San Francisco, CA; Department of Defense Prostate
Cancer Research Program [W81XWH-09-1-0471]; Conquer Cancer Foundation;
NIH [5K24CA121990]; Prostate Cancer Foundation
FX This study was supported by Exelixis, Inc., South San Francisco, CA; by
the Department of Defense Prostate Cancer Research Program (Award
W81XWH-09-1-0471 to R.J. Lee); the Conquer Cancer Foundation (Career
Development Award to R.J. Lee); the NIH [Midcareer Investigator Award
No. 5K24CA121990 to M.R. Smith]; and competitive research awards from
the Prostate Cancer Foundation.
NR 26
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Z9 42
U1 0
U2 3
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD JUN 1
PY 2013
VL 19
IS 11
BP 3088
EP 3094
DI 10.1158/1078-0432.CCR-13-0319
PG 7
WC Oncology
SC Oncology
GA 155FF
UT WOS:000319732000033
PM 23553848
ER
PT J
AU Young, B
AF Young, Bessie
TI Geography and ESRD Care: What Contributes Most to Hemodialysis
Patient-Provider Visit Variation?
SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Editorial Material
ID CLINICAL-PERFORMANCE TARGETS; STAGE RENAL-DISEASE; REGIONAL-VARIATIONS;
PHYSICIAN CONTACT; OUTCOMES; FREQUENCY; QUALITY
C1 [Young, Bessie] Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Kidney Res Inst, Div Nephrol, Seattle, WA 98195 USA.
RP Young, B (reprint author), Vet Affairs Puget Sound Hlth Care Syst, 111-A RDU,1660 S Columbian Way, Seattle, WA 98108 USA.
EM youngb@u.washington.edu
NR 20
TC 0
Z9 0
U1 0
U2 3
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1555-9041
J9 CLIN J AM SOC NEPHRO
JI Clin. J. Am. Soc. Nephrol.
PD JUN
PY 2013
VL 8
IS 6
BP 898
EP 900
DI 10.2215/CJN.03970413
PG 3
WC Urology & Nephrology
SC Urology & Nephrology
GA 160VZ
UT WOS:000320149900003
PM 23749447
ER
PT J
AU Isakova, T
Barchi-Chung, A
Enfield, G
Smith, K
Vargas, G
Houston, J
Xie, HL
Wahl, P
Schiavenato, E
Dosch, A
Gutierrez, OM
Diego, J
Lenz, O
Contreras, G
Mendez, A
Weiner, RB
Wolf, M
AF Isakova, Tamara
Barchi-Chung, Allison
Enfield, Gwen
Smith, Kelsey
Vargas, Gabriella
Houston, Jessica
Xie, Huiliang
Wahl, Patricia
Schiavenato, Eva
Dosch, Austin
Gutierrez, Orlando M.
Diego, Jorge
Lenz, Oliver
Contreras, Gabriel
Mendez, Armando
Weiner, Rory B.
Wolf, Myles
TI Effects of Dietary Phosphate Restriction and Phosphate Binders on FGF23
Levels in CKD
SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID CHRONIC KIDNEY-DISEASE; GROWTH-FACTOR 23; CARDIOVASCULAR EVENTS;
PARATHYROID-HORMONE; PHOSPHORUS; FGF-23; MEN; INITIATION; DIALYSIS;
CALCIUM
AB Background Elevated levels of fibroblast growth factor 23 (FGF23) are associated with increased risk of adverse outcomes in patients with CKD. Reducing dietary phosphate intake or absorption may decrease FGF23 levels, but data on the combined effects of dietary phosphate restriction and phosphate binders in CKD are limited.
Design, setting, participants, & measurements In this 2 X 2 factorial, single-blinded, placebo-controlled, 3-month study, conducted between July 2009 and March 2012, 39 patients with CKD stages 3 or 4 and normal serum phosphate levels were randomly assigned to one of four groups: ad libitum diet plus lanthanum carbonate (LC) placebo (n=10), 900-mg phosphate diet plus LC placebo (n=10), ad libitum diet plus LC (n=11), or 900-mg phosphate diet plus LC (n=8). The dose of LC was 1000 mg three times daily with meals. Dietary restriction was accomplished with outpatient counseling. The primary end point was change in FGF23 levels from baseline.
Results Compared with ad libitum diet, the 900-mg phosphate diet did not significantly reduce FGF23 levels (diet X time interaction, P=0.05). Compared with placebo, LC alone also did not significantly reduce FGF23 levels (LC X time interaction, P=0.21). However, the dual intervention significantly decreased FGF23 levels throughout the study period (diet X LC X time interaction, P=0.02), resulting in a 35% (95% confidence interval, 8%-62%) reduction by study end.
Conclusion The combination of LC plus counseling for a phosphate-restricted diet decreased FGF23 levels in patients with CKD stages 3-4 and normal serum phosphate levels.
C1 [Isakova, Tamara; Barchi-Chung, Allison; Smith, Kelsey; Vargas, Gabriella; Houston, Jessica; Wahl, Patricia; Schiavenato, Eva; Dosch, Austin; Diego, Jorge; Lenz, Oliver; Contreras, Gabriel; Wolf, Myles] Univ Miami, Miller Sch Med, Div Nephrol & Hypertens, Dept Med, Miami, FL 33136 USA.
[Enfield, Gwen] Univ Miami, Miller Sch Med, Clin Res Ctr, Miami, FL 33136 USA.
[Xie, Huiliang] Univ Miami, Miller Sch Med, Dept Epidemiol & Publ Hlth, Miami, FL 33136 USA.
[Mendez, Armando] Univ Miami, Miller Sch Med, Div Endocrinol Diabet & Metab, Dept Med,Diabet Res Inst, Miami, FL 33136 USA.
[Gutierrez, Orlando M.] Univ Alabama Birmingham, Dept Med, Div Nephrol, Birmingham, AL 35294 USA.
[Weiner, Rory B.] Massachusetts Gen Hosp, Dept Med, Cardiol Unit, Boston, MA 02114 USA.
RP Wolf, M (reprint author), Univ Miami, Miller Sch Med, Div Nephrol & Hypertens, 1120 NW 14th St,CRB 819, Miami, FL 33136 USA.
EM mwolf2@med.miami.edu
RI Lenz, Oliver/M-4672-2016
OI Lenz, Oliver/0000-0003-2997-3976
FU Shire Pharmaceuticals; National Institutes of Health; National Institute
of Diabetes and Digestive and Kidney Diseases [K23DK087858, R01DK076116,
R01DK081374]; University of Miami Clinical and Translational Science
Institute, from the National Center for Advancing Translational Sciences
[1UL1TR000460]; National Institute on Minority Health and Health
Disparities
FX This study was supported by a grant from Shire Pharmaceuticals and by
grants from the National Institutes of Health and the National Institute
of Diabetes and Digestive and Kidney Diseases: K23DK087858 (T.I.),
R01DK076116 (M.W.) and R01DK081374 (M.W.).; The project described was
supported by grant no. 1UL1TR000460, University of Miami Clinical and
Translational Science Institute, from the National Center for Advancing
Translational Sciences and the National Institute on Minority Health and
Health Disparities. Its contents are solely the responsibility of the
authors and do not necessarily represent the official views of the
National Institutes of Health.
NR 19
TC 36
Z9 39
U1 0
U2 32
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1555-9041
J9 CLIN J AM SOC NEPHRO
JI Clin. J. Am. Soc. Nephrol.
PD JUN
PY 2013
VL 8
IS 6
BP 1009
EP 1018
DI 10.2215/CJN.09250912
PG 10
WC Urology & Nephrology
SC Urology & Nephrology
GA 160VZ
UT WOS:000320149900018
PM 23471131
ER
PT J
AU Hoenig, MP
Shapiro, E
Hladik, GA
AF Hoenig, Melanie P.
Shapiro, Evelyn
Hladik, Gerald A.
TI Lessons Learned from the ASN Renal Educator Listserv and Survey
SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID MEDICAL-EDUCATION; CURRICULUM; STUDENTS
AB Nephrology ranks next to last in career choices among US medical school graduates. The American Society of Nephrology established a Workforce Committee to help address this issue. Surveys of US medical students indicate that experiences during kidney pathophysiology courses in the preclerkship years may impact their decision to consider a career in nephrology. In October of 2011, preclinical kidney physiology and pathophysiology course directors at US medical schools were surveyed about teaching methods, curricular content, resources, and institutional support for teaching to identify what worked well and what impairs their teaching efforts. A Listserv of these educators, the American Society of Nephrology Renal Educators Listserv, was used to electronically administer the survey. Course leaders from 62 of 114 (54.4%) surveyed medical schools responded. Most of these educators are nephrologists, but physiologists and other clinicians also lead courses; 60% of course directors noted that lectures are videotaped, resulting in decreased attendance. A range of resources is used: 68% use audience response systems, 16% use the simulation center, and none of the educators indicated use of social media (such as Twitter or Facehook); 50% of respondents receive no remuneration, and 68% receive no full-time equivalent for their efforts. Audience response systems, virtual microscopy, and flash animations were identified as valuable teaching tools. Course directors, during subsequent dialogue on the American Society of Nephrology Renal Educators Listserv, have cited incorporation of case scenarios and integration of clinical exposure during preclinical years as methods that inspired interest. Hopefully, adoption of such approaches will ultimately serve to stimulate interest in nephrology.
C1 [Hoenig, Melanie P.] Joslin Clin, Div Nephrol, Boston, MA 02215 USA.
[Hoenig, Melanie P.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Hoenig, Melanie P.] Harvard Univ, Sch Med, Boston, MA USA.
[Shapiro, Evelyn] Amer Soc Nephrol, Washington, DC USA.
[Hladik, Gerald A.] Univ N Carolina, Sch Med, Div Nephrol, Chapel Hill, NC USA.
[Hladik, Gerald A.] Univ N Carolina, Kidney Ctr, Chapel Hill, NC USA.
RP Hoenig, MP (reprint author), Joslin Clin, Renal Unit, Boston, MA 02215 USA.
EM Melanie.Hoenig@joslin.harvard.edu
NR 36
TC 8
Z9 8
U1 1
U2 6
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1555-9041
J9 CLIN J AM SOC NEPHRO
JI Clin. J. Am. Soc. Nephrol.
PD JUN
PY 2013
VL 8
IS 6
BP 1054
EP 160
DI 10.2215/CJN.07410712
PG 7
WC Urology & Nephrology
SC Urology & Nephrology
GA 160VZ
UT WOS:000320149900024
PM 23293124
ER
PT J
AU Runz, H
AF Runz, Heiko
TI Lipids: new biology and therapeutic targets revealed through human
genetics
SO CLINICAL LIPIDOLOGY
LA English
DT Editorial Material
ID PATHWAYS
AB This year's Deuel Conference on Lipids focused on the seminal contribution of human genetics to lipid biology and disease. Named in honor of Harry J Deuel Jr, famous single author of the three-volume textbook The Lipids (Interscience Publishers Inc., NY, USA) and established in 1955, the Deuel Conference is considered the longest-standing annual meeting on lipid metabolism in the USA. The 2013 meeting took place at the Silverado Resort of Napa Valley (CA, USA) and was characterized by first-rank scientific contributions and discussions in a friendly and informal setting. Four scientific sessions over 2 and a half days, a poster session and generous breaks allowed for stimulating scientific, as well as social interactions of scientists from academia and industry alike.
C1 [Runz, Heiko] Heidelberg Univ, Inst Human Genet, Mol Med Partnership Unit, D-69120 Heidelberg, Germany.
[Runz, Heiko] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
RP Runz, H (reprint author), Heidelberg Univ, Inst Human Genet, Mol Med Partnership Unit, INF 350, D-69120 Heidelberg, Germany.
EM heiko.runz@med.uni-heidelberg.de
NR 15
TC 0
Z9 0
U1 0
U2 2
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 1758-4299
J9 CLIN LIPIDOL
JI Clin. Lipidol.
PD JUN
PY 2013
VL 8
IS 3
BP 295
EP 298
DI 10.2217/CLP.13.22
PG 4
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 158KX
UT WOS:000319970500011
ER
PT J
AU Magidson, JF
Wang, S
Lejuez, CW
Iza, M
Blanco, C
AF Magidson, Jessica F.
Wang, Shuai
Lejuez, C. W.
Iza, Miren
Blanco, Carlos
TI PROSPECTIVE STUDY OF SUBSTANCE-INDUCED AND INDEPENDENT MAJOR DEPRESSIVE
DISORDER AMONG INDIVIDUALS WITH SUBSTANCE USE DISORDERS IN A NATIONALLY
REPRESENTATIVE SAMPLE
SO DEPRESSION AND ANXIETY
LA English
DT Article
DE major depressive disorder; substance-related disorder; classification;
epidemiology; substance use
ID PSYCHIATRIC RESEARCH INTERVIEW; ALCOHOL-USE DISORDER; EPIDEMIOLOGIC
SURVEY; ANXIETY DISORDERS; DEPENDENT PATIENTS; MENTAL-DISORDERS; DSM-IV;
RELIABILITY; MOOD; COMORBIDITY
AB Background Depression and substance use disorders (SUDs) commonly co-occur, which presents diagnostic challenges in classifying independent major depressive disorder (MDD) versus substance-induced depressive disorder (SIDD). It remains unclear if distinct characteristics and/or patterns in temporal course distinguish MDD-SUD and SIDD to guide these decisions. Further, evidence suggests that a significant portion of individuals with SIDD are later reclassified as having independent MDD. Continued research to improve our understanding of differences between these two and changes in reclassification over time is necessary for diagnostic clarification and to guide clinical decisions when treating depression in the context of SUDs. Methods The current study compared individuals with MDD-SUD versus SIDD at baseline and examined reclassification of DSM-IV Axis I diagnoses over a 3-year follow up in a large, nationally representative epidemiological sample (n = 2,121). Results Findings demonstrated that SIDD was extremely rare at both time points. At baseline, individuals with SIDD were more likely to be non-White, have less education, less likely to have insurance, less likely to have dysthymia or alcohol abuse, and more likely to have drug dependence compared to those with independent MDD. Of individuals with SIDD at Wave 1 who had a depressive episode between Waves 1 and 2, the overwhelming majority (>95%) had an independent MDD, not SIDD, episode. There were no significant group differences in the incidence of other mood disorders or SUDs at Wave 2. Conclusions Findings have important etiological and treatment implications for the classification and treatment of depression in the context of SUDs. (C) 2013 Wiley Periodicals, Inc.
C1 [Magidson, Jessica F.; Lejuez, C. W.] Univ Maryland, College Pk, MD 20742 USA.
[Magidson, Jessica F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
[Wang, Shuai; Iza, Miren; Blanco, Carlos] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York State Psychiat Inst, New York, NY USA.
RP Magidson, JF (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 15 Parkman St,ACC 812, Boston, MA 02114 USA.
EM jmagidson@partners.org
RI Blanco, Carlos/I-4906-2013
OI Blanco, Carlos/0000-0001-6187-3057
FU National Institute on Alcohol Abuse and Alcoholism; NIH [DA019606,
DA020783, DA023200, DA023973, MH082773, R36DA034513]; New York State
Psychiatric Institute
FX The National Epidemiologic Survey on alcohol and related conditions was
sponsored by the National Institute on Alcohol Abuse and Alcoholism with
supplemental support from the National Institute on Drug Abuse. Work on
this manuscript was supported by NIH grants DA019606, DA020783,
DA023200, DA023973, and MH082773 (Blanco), R36DA034513 (Magidson), and
the New York State Psychiatric Institute (Blanco).
NR 25
TC 6
Z9 6
U1 0
U2 12
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1091-4269
J9 DEPRESS ANXIETY
JI Depress. Anxiety
PD JUN
PY 2013
VL 30
IS 6
BP 538
EP 545
DI 10.1002/da.22122
PG 8
WC Psychology, Clinical; Psychiatry; Psychology
SC Psychology; Psychiatry
GA 157CC
UT WOS:000319872200005
PM 23649540
ER
PT J
AU Olson, J
Kalina, C
Berg, D
AF Olson, Jonathan
Kalina, Carol
Berg, Daniel
TI Foam Dressing as a Suturing Model
SO DERMATOLOGIC SURGERY
LA English
DT Letter
ID FLAP MECHANICS
C1 [Olson, Jonathan; Berg, Daniel] Univ Washington, Sch Med, Dept Med, Div Dermatol, Seattle, WA 98195 USA.
[Kalina, Carol] Vet Affairs Puget Sound Healthcare Syst, Dermatol Sect, Seattle, WA USA.
RP Olson, J (reprint author), Univ Washington, Sch Med, Dept Med, Div Dermatol, Seattle, WA 98195 USA.
NR 5
TC 2
Z9 2
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1076-0512
J9 DERMATOL SURG
JI Dermatol. Surg.
PD JUN
PY 2013
VL 39
IS 6
BP 952
EP 953
DI 10.1111/dsu.12169
PG 2
WC Dermatology; Surgery
SC Dermatology; Surgery
GA 157ST
UT WOS:000319920100020
PM 23464974
ER
PT J
AU Spiegelman, BM
AF Spiegelman, Bruce M.
TI Banting Lecture 2012 Regulation of Adipogenesis: Toward New Therapeutics
for Metabolic Disease
SO DIABETES
LA English
DT Article
ID BROWN ADIPOSE-TISSUE; COACTIVATOR; MUSCLE; FAT; THERMOGENESIS;
ADIPOCYTES; DISTINCT; PRDM16; DRIVES; BEIGE
AB The Banting Medal for Scientific Achievement Award is the American Diabetes Association's highest scientific award and honors an individual who has made significant, long-term contributions to the understanding of diabetes, its treatment, and/or prevention. The award is named after Nobel Prize winner Sir Frederick Banting, who codiscovered insulin treatment for diabetes.
Bruce M. Spiegelman, PhD, of Harvard Medical School and the Dana-Farber Cancer Institute in Boston, received the American Diabetes Association's Banting Medal for Scientific Achievement at the Association's 72nd Scientific Sessions, 8-12 June 2012, Philadelphia, Pennsylvania. He presented the Banting Lecture, "Transcriptional Control of Adipogenesis Toward a New Generation of Therapeutics for Metabolic Disease," on Sunday, 10 June 2012. In his lecture, Dr. Spiegelman described the discovery of several transcriptional components that control adipose cell development: PPAR-gamma, PGC1-alpha, and PRDM16. He also described the cloning and characterization of beige fat cells, the thermogenic "brown-like" cells that can develop in white fat depots. Lastly, Dr. Spiegelman discussed irisin, a newly discovered regulatory hormone that converts white fat into the more thermogenic beige fat. Dr. Spiegelman's research has found that irisin, which is induced by exercise, appears to activate some of the same health benefits as exercise, including improvement of glycemic control. Understanding the regulation of adipose tissue, white, brown, and beige, can potentially lead to the development of a new generation of therapeutics for diabetes prevention and treatment.
C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, 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 National Institutes of Health (the National Institute of Diabetes and
Digestive and Kidney Diseases specifically); JPB Foundation
FX This work has been funded by the National Institutes of Health (the
National Institute of Diabetes and Digestive and Kidney Diseases
specifically) and by The JPB Foundation.
NR 17
TC 52
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U1 3
U2 30
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0012-1797
J9 DIABETES
JI Diabetes
PD JUN
PY 2013
VL 62
IS 6
BP 1774
EP 1782
DI 10.2337/db12-1665
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 156SU
UT WOS:000319845000001
PM 23704518
ER
PT J
AU Sacks, H
Symonds, ME
AF Sacks, Harold
Symonds, Michael E.
TI Anatomical Locations of Human trovvn Adipose Tissue Functional Relevance
and Implications in Obesity and Type 2 Diabetes
SO DIABETES
LA English
DT Article
ID BROWN ADIPOSE; ADULT HUMANS; SKIN TEMPERATURE; ENERGY-BALANCE;
GLUCOSE-UPTAKE; COLD-EXPOSURE; FAT; THERMOGENESIS; AGE; IDENTIFICATION
AB We will review information about and present hypotheses as to the anatomy of brown adipose tissue (BAT). Why is it located where it is in humans? Its anatomical distribution is likely to confer survival value by protecting critical organs from hypothermia by adaptive thermogenesis. Ultimately, the location and function will be important when considering therapeutic strategies for preventing and treating obesity and type 2 diabetes, in which case successful interventions will need to have a significant effect on BAT function in subjects living in a thermoneutral environment. In view of the diverse locations and potential differences in responsiveness between BAT depots, it is likely that BAT will be shown to have much more subtle and thus previously overlooked functions and regulatory control mechanisms.
C1 [Sacks, Harold] VA Greater Los Angeles Healthcare Syst, Endocrinol & Diabet Div, Los Angeles, CA 90095 USA.
[Symonds, Michael E.] Univ Nottingham, Early Life Nutr Res Unit, Acad Div Child Hlth, Sch Clin Sci,Univ Hosp, Nottingham NG7 2RD, England.
RP Sacks, H (reprint author), VA Greater Los Angeles Healthcare Syst, Endocrinol & Diabet Div, Los Angeles, CA 90095 USA.
EM hsacks@hotmail.com
OI Symonds, Michael/0000-0001-9649-8963
NR 50
TC 45
Z9 46
U1 0
U2 16
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0012-1797
J9 DIABETES
JI Diabetes
PD JUN
PY 2013
VL 62
IS 6
BP 1783
EP 1790
DI 10.2337/db12-1430
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 156SU
UT WOS:000319845000002
PM 23704519
ER
PT J
AU Kelly, JF
Hoeppner, BB
AF Kelly, John F.
Hoeppner, Bettina B.
TI Does Alcoholics Anonymous work differently for men and women? A
moderated multiple-mediation analysis in a large clinical sample
SO DRUG AND ALCOHOL DEPENDENCE
LA English
DT Article
DE Alcoholics Anonymous; Gender; Recovery; Addiction treatment; 12-Step;
Women
ID GENDER-DIFFERENCES; BEHAVIOR-CHANGE; SOCIAL ROLES; INDUSTRIALIZED
COUNTRIES; PROJECT MATCH; MECHANISMS; DEPRESSION; PARTICIPATION;
OUTCOMES; ASSOCIATION
AB Background: Alcoholics Anonymous (AA) began as a male organization, but about one third is now female. Studies have found that women participate at least as much as men and benefit equally from AA, but it is unclear whether women benefit from AA in the same or different ways as men. This study tested whether gender moderated the mechanisms through which AA aids recovery.
Methods: A cohort study of alcohol dependent adults (N = 1726; 24% female; Project MATCH) was assessed on AA attendance during treatment; with mediators at 9 months; outcomes (Percent Days Abstinent [PDA] and Drinks per Drinking Day [DDD]) at 15 months. Multiple mediator models tested whether purported mechanisms (i.e., self-efficacy, depression, social networks, spirituality/religiosity) explained AA's effects differently for men and women controlling for baseline values, mediators, treatment, and other confounders.
Results: For PDA, the proportion of AA's effect accounted for by the mediators was similar for men (53%) and women (49%). Both men and women were found to benefit from changes in social factors but these mechanisms were more important among men. For DDD, the mediators accounted for 70% of the effect of AA for men and 41% for women. Again, men benefitted mostly from social changes. Independent of AA's effects, negative affect self-efficacy was shown to have a strong relationship to outcome for women but not men.
Conclusions: The recovery benefits derived from AA differ in nature and magnitude between men and women and may reflect differing needs based on recovery challenges related to gender-based social roles and drinking contexts. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
C1 [Kelly, John F.] Massachusetts Gen Hosp, Ctr Addict Med, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
RP Kelly, JF (reprint author), Massachusetts Gen Hosp, Ctr Addict Med, 60 Staniford St, Boston, MA 02114 USA.
EM jkelly11@partners.org
FU National Institute of Alcohol Abuse and Alcoholism (NIAAA) [R21
AA016762]; National Institute on Drug Abuse [K01 DA027097]
FX This research was supported by a grant from the National Institute of
Alcohol Abuse and Alcoholism (NIAAA, R21 AA016762; Mechanisms and
Moderators of Behavior Change in Alcoholics Anonymous) and a grant from
the National Institute on Drug Abuse (K01 DA027097). NIAAA and NIDA had
no further role in study design; in the collection, analysis and
interpretation of data; in the writing of the report; or in the decision
to submit the paper for publication.
NR 59
TC 3
Z9 4
U1 2
U2 26
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 JUN 1
PY 2013
VL 130
IS 1-3
BP 186
EP 193
DI 10.1016/j.drugalcdep.2012.11.005
PG 8
WC Substance Abuse; Psychiatry
SC Substance Abuse; Psychiatry
GA 154ZK
UT WOS:000319715000024
PM 23206376
ER
PT J
AU McKenna, JT
Kocsis, B
McCarley, RW
AF McKenna, James T.
Kocsis, Bernat
McCarley, Robert W.
TI Aberrant cortical neuroplasticity in the OSA patient (Commentary on Opie
et al.)
SO EUROPEAN JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID THETA-BURST STIMULATION; OBSTRUCTIVE SLEEP-APNEA; CORTEX
C1 [McKenna, James T.; McCarley, Robert W.] Harvard Univ, Dept Psychiat, VA Boston Healthcare Syst, Sch Med, Brockton, MA 02301 USA.
[Kocsis, Bernat] Harvard Univ, Beth Israel Deaconess Med Ctr, Dept Psychiat, Sch Med, Boston, MA 02215 USA.
RP McKenna, JT (reprint author), Harvard Univ, Dept Psychiat, VA Boston Healthcare Syst, Sch Med, Brockton, MA 02301 USA.
RI McCarley, Robert/N-5562-2014
OI McCarley, Robert/0000-0001-5705-7495
NR 8
TC 0
Z9 0
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0953-816X
J9 EUR J NEUROSCI
JI Eur. J. Neurosci.
PD JUN
PY 2013
VL 37
IS 11
BP 1843
EP 1843
DI 10.1111/ejn.12221
PG 1
WC Neurosciences
SC Neurosciences & Neurology
GA 156PK
UT WOS:000319834600012
PM 23725099
ER
PT J
AU Farhat, MR
Loring, SH
Riskind, P
Weinhouse, G
AF Farhat, Maha R.
Loring, Stephen H.
Riskind, Peter
Weinhouse, Gerald
TI Disturbance of respiratory muscle control in a patient with early-stage
multiple sclerosis
SO EUROPEAN RESPIRATORY JOURNAL
LA English
DT Letter
ID DYSFUNCTION; INVOLVEMENT
C1 [Farhat, Maha R.] Massachusetts Gen Hosp, Div Pulm & Crit Care, Boston, MA 02114 USA.
[Loring, Stephen H.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Anaesthesia & Crit Care, Boston, MA 02215 USA.
[Riskind, Peter] Univ Massachusetts, Mem Hosp, Dept Neurol, Worcester, MA 01605 USA.
[Weinhouse, Gerald] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pulm & Crit Care, Boston, MA USA.
RP Farhat, MR (reprint author), Massachusetts Gen Hosp, Div Pulm & Crit Care, 55 Fruit St,Bulfinch 148, Boston, MA 02114 USA.
EM mrfarhat@partners.org
OI Farhat, Maha/0000-0002-3871-5760
NR 10
TC 1
Z9 1
U1 0
U2 0
PU EUROPEAN RESPIRATORY SOC JOURNALS LTD
PI SHEFFIELD
PA 442 GLOSSOP RD, SHEFFIELD S10 2PX, ENGLAND
SN 0903-1936
J9 EUR RESPIR J
JI Eur. Resp. J.
PD JUN
PY 2013
VL 41
IS 6
BP 1454
EP 1456
DI 10.1183/09031936.00172312
PG 3
WC Respiratory System
SC Respiratory System
GA 161RT
UT WOS:000320211700030
PM 23728406
ER
PT J
AU Rinne, ML
Lee, EQ
Nayak, L
Norden, AD
Beroukhim, R
Wen, PY
Reardon, DA
AF Rinne, Mikael L.
Lee, Eudocia Q.
Nayak, Lakshmi
Norden, Andrew D.
Beroukhim, Rameen
Wen, Patrick Y.
Reardon, David A.
TI Update on bevacizumab and other angiogenesis inhibitors for brain cancer
SO EXPERT OPINION ON EMERGING DRUGS
LA English
DT Review
DE angiogenesis; brain metastases; glioblastoma; malignant glioma; vascular
endothelial growth factor
ID PHASE-II TRIAL; RECURRENT MALIGNANT GLIOMA; HIGH-GRADE GLIOMAS;
NEWLY-DIAGNOSED GLIOBLASTOMA; ENDOTHELIAL GROWTH-FACTOR; NERVOUS-SYSTEM
METASTASES; TYROSINE KINASE INHIBITOR; PROGRESSION-FREE SURVIVAL;
SINGLE-AGENT BEVACIZUMAB; INTEGRATED GENOMIC ANALYSIS
AB Introduction: Primary and metastatic brain tumors remain a major challenge. The most common primary adult malignant brain tumor, glioblastoma (GBM), confers a dismal prognosis as does the development of CNS metastases for most systemic malignancies. Anti-angiogenic therapy has been a major clinical research focus in neuro-oncology over the past 5 years.
Areas covered: Culmination of this work includes US FDA accelerated approval of bevacizumab for recurrent GBM and the completion of two placebo-controlled Phase III studies of bevacizumab for newly diagnosed GBM. A multitude of anti-angiogenics are in evaluation for neurooncology patients but none has thus far surpassed the therapeutic benefit of bevacizumab.
Expert opinion: These agents demonstrate adequate safety and the majority of GBM patients derive benefit. Furthermore, their anti-permeability effect can substantially decrease tumor-associated edema leading to stable or improved neurologic function and quality of life. In particular, anti-angiogenics significantly prolong progression-free survival-a noteworthy achievement in the context of infiltrative and destructive brain tumors like GBM; however, in a manner analogous to other cancers, their impact on overall survival for GBM patients is modest at best. Despite substantial clinical research efforts, many fundamental questions regarding anti-angiogenic agents in brain tumor patients remain unanswered.
C1 [Rinne, Mikael L.; Lee, Eudocia Q.; Nayak, Lakshmi; Norden, Andrew D.; Beroukhim, Rameen; Wen, Patrick Y.; Reardon, David A.] Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA USA.
[Rinne, Mikael L.; Lee, Eudocia Q.; Nayak, Lakshmi; Norden, Andrew D.; Wen, Patrick Y.] Brigham & Womens Hosp, Dept Neurol, Div Neurooncol, Boston, MA 02115 USA.
[Beroukhim, Rameen; Reardon, David A.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Beroukhim, Rameen; Reardon, David A.] Brigham & Womens Hosp, Ctr Neurooncol, Dept Med Oncol, Boston, MA 02215 USA.
RP Reardon, DA (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,SW460F, Boston, MA 02115 USA.
EM david_reardon@dfci.harvard.edu
FU Merck/Schering-Plough; Roche/Genentech; Merck KGaA/EMD Serono (G)
FX DA Reardon has received financial compensation as a consultant for
Merck/Schering-Plough, Roche/Genentech, and Merck KGaA/EMD Serono (G).
He is a member of the speakers' bureau for Merck/Schering-Plough and
Roche/Genentech. R Beroukhim has received financial compensation as a
consultant for Novartis. P Wen has received funds or other from Amgen,
Astra Zeneca, Exelixis, Eisai, Genentech, Merck, Novartis, Medimmune,
Sanofi Aventis, Vascular Biogenics and Stemline. E Lee is a member of
the advisory board to Novartis.
NR 172
TC 17
Z9 18
U1 3
U2 17
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1472-8214
EI 1744-7623
J9 EXPERT OPIN EMERG DR
JI Expert Opin Emerg. Drugs
PD JUN
PY 2013
VL 18
IS 2
BP 137
EP 153
DI 10.1517/14728214.2013.794784
PG 17
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 156QM
UT WOS:000319837500003
PM 23668489
ER
PT J
AU Tecilazich, F
Dinh, TL
Veves, A
AF Tecilazich, Francesco
Dinh, Thanh L.
Veves, Aristidis
TI Emerging drugs for the treatment of diabetic ulcers
SO EXPERT OPINION ON EMERGING DRUGS
LA English
DT Review
DE diabetes; foot ulceration; growth factors; new treatments
ID ENDOTHELIAL PROGENITOR CELLS; PROTEIN-TYROSINE PHOSPHATASES; RANDOMIZED
CLINICAL-TRIAL; FIBROBLAST-GROWTH-FACTOR; PLATELET-RICH PLASMA;
SMOOTH-MUSCLE-CELLS; SHOCK-WAVE THERAPY; FOOT ULCERS; SUBSTANCE-P;
NEUROPEPTIDE-Y
AB Introduction: Diabetic ulcers are chronic nonhealing ulcerations that despite the available medical tools still result in high amputation rates. Growing evidence suggests that alteration of the biochemical milieu of the chronic wound plays a significant role in impaired diabetic wound healing.
Areas covered: The basic pathophysiology and the conventional treatment strategy of diabetic foot ulcers have been reviewed in the first section. In the second part, the most up-to-date bench and translational research in the field are described. The third section focuses on the drugs currently under development and the ongoing clinical trials evaluating their safety and efficacy. Finally, the major drug development issues and the possible scientific approaches to overcome them are analyzed.
Expert opinion: Significant strides in understanding the chronic wound development have led to the development of topical therapies to address aberrant expression of growth factors and overexpression of inflammatory cytokines. Current research in the laboratory suggests that while decreased growth factor expression occurs at the local wound level, increased systemic serum levels of growth factors suggest growth factor resistance.
C1 [Tecilazich, Francesco; Veves, Aristidis] Harvard Univ, Sch Med, Joslin Beth Israel Deaconess Foot Ctr, Boston, MA 02215 USA.
[Tecilazich, Francesco; Veves, Aristidis] Beth Israel Deaconess Foot Ctr, Microcirculat Lab, Boston, MA USA.
[Dinh, Thanh L.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Podiatry, Boston, MA 02215 USA.
RP Veves, A (reprint author), Harvard Univ, Sch Med, Joslin Beth Israel Deaconess Foot Ctr, Boston, MA 02215 USA.
EM aveves@bidmc.harvard.edu
FU National Institutes of Health [R01-NS046710, R01-DK076937, R01 NS066205]
FX This work was supported by National Institutes of Health Grants
R01-NS046710, R01-DK076937 and R01 NS066205 to Aristidis Veves. All
authors state no conflict of interest.
NR 102
TC 3
Z9 5
U1 2
U2 17
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1472-8214
J9 EXPERT OPIN EMERG DR
JI Expert Opin Emerg. Drugs
PD JUN
PY 2013
VL 18
IS 2
BP 207
EP 217
DI 10.1517/14728214.2013.802305
PG 11
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 156QM
UT WOS:000319837500007
PM 23687931
ER
PT J
AU Correll, M
Johnson, CK
Ferrari, G
Brizzio, M
Mak, AWC
Quackenbush, J
Shaw, RE
Zapolanski, A
Grau, JB
AF Correll, Mick
Johnson, Christopher K.
Ferrari, Giovanni
Brizzio, Mariano
Mak, Andrew W. C.
Quackenbush, John
Shaw, Richard E.
Zapolanski, Alex
Grau, Juan B.
TI Mutational analysis clopidogrel resistance and platelet function in
patients scheduled for coronary artery bypass grafting
SO GENOMICS
LA English
DT Article
DE Cardiovascular surgery; Ultra-high throughput sequencing; Gene
polymorphisms; Platelets
ID CARDIOVASCULAR OUTCOMES; ANTIPLATELET THERAPY; HEART-ASSOCIATION;
CYP2C19 GENOTYPE; TASK-FORCE; REACTIVITY; INTERVENTION; RESPONSIVENESS;
POLYMORPHISMS; INHIBITION
AB Clopidogrel is an oral antiplatelet pro-drug prescribed to 40 million patients worldwide who are at risk for thrombotic events or receiving percutaneous coronary intervention (PCI). However about a fifth of patients treated with clopidogrel do not respond adequately to the drug. From a cohort of 105 patients on whom we had functional data on clopidogrel response, we used ultra-high throughput sequencing to assay mutations in CYP2C19 and ABCB1, the two genes genetically linked to respond. Testing for mutations in CYP2C19, as recommended by the FDA, only correctly predicted if a patient would respond to clopidogrel 52.4% of the time. Similarly, testing of the ABCB1 gene only correctly foretold response in 51 (48.6%) patients. These results are clinically relevant and suggest that until additional genetic factors are discovered that predict response more completely, functional assays are more appropriate for clinical use. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Correll, Mick; Quackenbush, John] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA.
[Correll, Mick; Quackenbush, John] Dana Farber Canc Inst, Ctr Canc Computat Biol, Boston, MA 02215 USA.
[Johnson, Christopher K.; Ferrari, Giovanni; Brizzio, Mariano; Mak, Andrew W. C.; Quackenbush, John; Shaw, Richard E.; Zapolanski, Alex; Grau, Juan B.] Columbia Univ Coll Phys & Surg, Valley Columbia Heart Ctr, Ridgewood, NJ 07450 USA.
[Ferrari, Giovanni; Grau, Juan B.] Univ Penn, Sch Med, Glenolden, PA 19036 USA.
RP Grau, JB (reprint author), Valley Columbia Heart Ctr, 223 North Van Dien Ave, Ridgewood, NJ 07450 USA.
EM jbg2136@columbia.edu
OI Ferrari, Giovanni/0000-0002-8863-2496
FU NHLBI NIH HHS [P01 HL083069]; NLM NIH HHS [R01 LM010129]
NR 25
TC 1
Z9 3
U1 0
U2 11
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0888-7543
J9 GENOMICS
JI Genomics
PD JUN
PY 2013
VL 101
IS 6
BP 313
EP 317
DI 10.1016/j.ygeno.2013.01.005
PG 5
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA 156SS
UT WOS:000319844800001
PM 23462555
ER
PT J
AU Bentov, I
Damodarasamy, M
Plymate, S
Reed, MJ
AF Bentov, Itay
Damodarasamy, Mamatha
Plymate, Stephen
Reed, May J.
TI B16/F10 tumors in aged 3D collagen in vitro simulate tumor growth and
gene expression in aged mice in vivo
SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL
LA English
DT Article
DE Aged; Mice; Gene expression; B16/F10 melanoma tumors; 3D collagen
ID HORMONE RECEPTOR; HUMAN-MELANOMA; CANCER; OLD; CELLS; GELS
AB Although the incidence of cancer rises with age, tumor growth is often slowed in older hosts. The B16/F10 melanoma cell line is commonly used in murine models of age-related tumor growth suppression. We wished to determine if the growth pattern and gene expression of B16/10 tumors grown in aged mice could be simulated in 3D collagen matrices derived from aged mice. Outcome measures were tumor size in vitro and gene expression of the key growth regulatory molecules: growth hormone receptor (GHR), IL-10R beta, IL-4R alpha, and IL-6. B16/F10 tumors were grown in 20-25-mo-old C57/BL6 male mice. Tumor sizes ranged from 30 to 4,910 mg in vivo. Tumors from a subset of mice were removed after euthanasia, and equivalent amounts of each tumor were placed in aged 3D collagen and grown for 5 d. Tumor sizes in aged 3D collagen correlated highly with their original tumor size in vivo. Gene expression changes noted in vivo were also maintained during tumor growth in aged 3D collagen in vitro. The relative expression of GHR was increased, IL-10R beta was unchanged, and IL-4R alpha and IL-6 were decreased in the larger tumors relative to the smaller tumors in vitro, in a pattern similar to that noted in vivo. We propose that 3D matrices from aged mice provide an in vitro model of tumor growth that correlates highly with tumor size and expression of key regulatory molecules in vivo.
C1 [Bentov, Itay] Univ Washington, Dept Anesthesiol & Pain Med, Seattle, WA 98104 USA.
[Damodarasamy, Mamatha; Plymate, Stephen; Reed, May J.] Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA 98104 USA.
[Plymate, Stephen] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA.
[Reed, May J.] Univ Washington, Harborview Med Ctr, Dept Med, Seattle, WA 98104 USA.
RP Reed, MJ (reprint author), Univ Washington, Harborview Med Ctr, Dept Med, Box 359625,325 9th Ave, Seattle, WA 98104 USA.
EM mjr@uw.edu
FU [U54 CA126540]; [R01 AG015837]; [R21 AG033391]
FX The authors thank Nathan Karres, Margaret Eugenio, and Matthew NR
Johnson for assistance with the tumor samples. This work was supported
by U54 CA126540, R01 AG015837, and R21 AG033391.
NR 23
TC 3
Z9 3
U1 0
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1071-2690
J9 IN VITRO CELL DEV-AN
JI In Vitro Cell. Dev. Biol.-Anim.
PD JUN
PY 2013
VL 49
IS 6
BP 395
EP 399
DI 10.1007/s11626-013-9623-3
PG 5
WC Cell Biology; Developmental Biology
SC Cell Biology; Developmental Biology
GA 162QG
UT WOS:000320279500001
PM 23661088
ER
PT J
AU Rosenberg, AR
Dussel, V
Kang, T
Geyer, JR
Gerhardt, CA
Feudtner, C
Wolfe, J
AF Rosenberg, Abby R.
Dussel, Veronica
Kang, Tammy
Geyer, J. Russel
Gerhardt, Cynthia A.
Feudtner, Chris
Wolfe, Joanne
TI Psychological Distress in Parents of Children With Advanced Cancer
SO JAMA PEDIATRICS
LA English
DT Article
ID POSTTRAUMATIC STRESS SYMPTOMS; BEREAVED PARENTS; CHILDHOOD-CANCER;
GENERAL-POPULATION; PEDIATRIC CANCER; SCREENING SCALES; MENTAL-HEALTH;
ADJUSTMENT; FAMILY; ILLNESS
AB Importance: Parent psychological distress can impact the well-being of childhood cancer patients and other children in the home. Recognizing and alleviating factors of parent distress may improve overall family survivorship experiences following childhood cancer.
Objectives: To describe the prevalence and factors of psychological distress (PD) among parents of children with advanced cancer.
Design: Cohort study embedded within a randomized clinical trial (Pediatric Quality of Life and Evaluation of Symptoms Technology [PediQUEST] study).
Setting: Multicenter study conducted at 3 children's hospitals (Boston Children's Hospital, Children's Hospital of Philadelphia, and Seattle Children's Hospital).
Participants: Parents of children with advanced (progressive, recurrent, or refractory) cancer.
Main Outcome Measure: Parental PD, as measured by the Kessler-6 Psychological Distress Scale.
Results: Eighty-six of 104 parents completed the Survey About Caring for Children With Cancer (83% par-ticipation); 81 parents had complete Kessler-6 Psychological Distress Scale data. More than 50% of parents reported high PD and 16% met criteria for serious PD (compared with US prevalence of 2%-3%). Parent perceptions of prognosis, goals of therapy, child symptoms/suffering, and financial hardship were associated with PD. In multivariate analyses, average parent Kessler-6 Psychological Distress Scale scores were higher among parents who believed their child was suffering highly and who reported great economic hardship. Conversely, PD was significantly lower among parents whose prognostic understanding was aligned with concrete goals of care.
Conclusions and Relevance: Parenting a child with advanced cancer is strongly associated with high to severe levels of PD. Interventions aimed at aligning prognostic understanding with concrete care goals and easing child suffering and financial hardship may mitigate parental PD.
C1 [Rosenberg, Abby R.; Geyer, J. Russel] Univ Washington, Seattle Childrens Hosp, Div Pediat Hematol Oncol, Seattle, WA 98195 USA.
[Rosenberg, Abby R.; Geyer, J. Russel] Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA.
[Rosenberg, Abby R.; Geyer, J. Russel] Univ Washington, Seattle, WA 98195 USA.
[Dussel, Veronica; Wolfe, Joanne] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA.
[Wolfe, Joanne] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA.
[Wolfe, Joanne] Boston Childrens Hosp, Dept Med, Boston, MA USA.
[Dussel, Veronica] Inst Clin Effectiveness & Hlth Policy, Buenos Aires, DF, Argentina.
[Kang, Tammy; Feudtner, Chris] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Gerhardt, Cynthia A.] Ohio State Univ, Columbus, OH 43210 USA.
[Gerhardt, Cynthia A.] Nationwide Childrens Hosp, Res Inst, Columbus, OH USA.
RP Wolfe, J (reprint author), Dana Farber Canc Inst, Ctr Outcomes & Policy Res, 450 Brookline Ave, Boston, MA 02215 USA.
EM joanne_wolfe@dfci.harvard.edu
RI Gerhardt, Cynthia/E-3109-2011
FU National Institutes of Health/National Cancer Institute [1K07
CA096746-01]; Charles H. Hood Foundation Child Health Research Award;
American Cancer Society Pilot and Exploratory Project Award; Ruth L.
Kirschstein National Research Service Award [T32CA009351]
FX Funding/Support: This project was part of the Pedi-QUEST study and
funded by National Institutes of Health/National Cancer Institute grant
1K07 CA096746-01, a Charles H. Hood Foundation Child Health Research
Award, and an American Cancer Society Pilot and Exploratory Project
Award in Palliative Care of Cancer Patients and Their Families. Dr
Rosenberg was supported by Ruth L. Kirschstein National Research Service
Award T32CA009351.
NR 41
TC 22
Z9 23
U1 1
U2 24
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 2168-6203
J9 JAMA PEDIATR
JI JAMA Pediatr.
PD JUN
PY 2013
VL 167
IS 6
BP 537
EP 543
DI 10.1001/jamapediatrics.2013.628
PG 7
WC Pediatrics
SC Pediatrics
GA 156NR
UT WOS:000319829700008
PM 23545569
ER
PT J
AU Duda, DG
Munn, LL
Jain, RK
AF Duda, Dan G.
Munn, Lance L.
Jain, Rakesh K.
TI Can We Identify Predictive Biomarkers for Antiangiogenic Therapy of
Cancer Using Mathematical Modeling?
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Editorial Material
ID ENDOTHELIAL GROWTH-FACTOR; PHASE-III; BEVACIZUMAB; VEGF; ANGIOGENESIS;
TRIALS; IMPACT; CELLS
C1 [Duda, Dan G.; Munn, Lance L.; Jain, Rakesh K.] Massachusetts Gen Hosp, Dept Radiat Oncol, Steele Lab, Boston, MA 02114 USA.
[Duda, Dan G.; Munn, Lance L.; Jain, Rakesh K.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Jain, RK (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Steele Lab, 100 Blossom St, Boston, MA 02114 USA.
EM jain@steele.mgh.harvard.edu
RI Munn, Lance/L-3950-2016
OI Munn, Lance/0000-0003-0698-7232
FU NCI NIH HHS [R01-CA115767, P01-CA080124, R01-CA085140, R01-CA126642,
R01-CA149285, R01-CA159258, R21-CA139168]
NR 24
TC 7
Z9 7
U1 1
U2 11
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 JNCI-J NATL CANCER I
JI JNCI-. Natl. Cancer Inst.
PD JUN
PY 2013
VL 105
IS 11
BP 762
EP 765
DI 10.1093/jnci/djt114
PG 4
WC Oncology
SC Oncology
GA 160QK
UT WOS:000320134100006
PM 23670727
ER
PT J
AU Soeteman, DI
Stout, NK
Ozanne, EM
Greenberg, C
Hassett, MJ
Schrag, D
Punglia, RS
AF Soeteman, Djra I.
Stout, Natasha K.
Ozanne, Elissa M.
Greenberg, Caprice
Hassett, Michael J.
Schrag, Deborah
Punglia, Rinaa S.
TI Modeling the Effectiveness of Initial Management Strategies for Ductal
Carcinoma In Situ
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID SURGICAL ADJUVANT BREAST; LOCAL RECURRENCE; OLDER WOMEN; CANCER;
RADIOTHERAPY; TAMOXIFEN; TRIAL; SURVIVAL; DIAGNOSIS; OUTCOMES
AB The prevalence of ductal carcinoma in situ (DCIS) and the marked variability in patterns of care highlight the need for comparative effectiveness research. We sought to quantify the tradeoffs among alternative management strategies for DCIS with respect to disease outcomes and breast preservation.
We developed a disease simulation model integrating data from the published literature to simulate the clinical events after six treatments (lumpectomy alone, lumpectomy with radiation, lumpectomy with radiation and tamoxifen, lumpectomy with tamoxifen, and mastectomy with and without breast reconstruction) for women with newly diagnosed DCIS. Outcomes included disease-free, invasive disease-free, and overall survival and breast preservation.
For a cohort of 1 million simulated women aged 45 years at diagnosis, both mastectomy and lumpectomy with radiation and tamoxifen were associated with a 12-month improvement in overall survival relative to lumpectomy alone. Adding radiation therapy to lumpectomy resulted in a 6-month improvement in overall survival but decreased long-term breast-preservation outcomes (likelihood of lifetime breast preservation 0.781 vs 0.843 for lumpectomy alone). This decrement with radiation therapy was mitigated by the addition of tamoxifen (likelihood of lifetime breast preservation 0.846).
Overall survival benefits of the six management strategies for DCIS are within 1 year, suggesting that treatment decisions can be informed by the patients preference for breast preservation and disutility for recurrence. Our delineation of personalized outcomes for each strategy can help patients understand the implications of their treatment choice, so their decisions may reflect their own personal values and help improve the quality of care for patients with DCIS.
C1 [Soeteman, Djra I.] Harvard Univ, Ctr Hlth Decis Sci, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA.
[Stout, Natasha K.] Harvard Univ, Sch Med, Dept Populat Med, Boston, MA USA.
[Stout, Natasha K.] Harvard Pilgrim Hlth Care Inst, Boston, MA USA.
[Ozanne, Elissa M.] Univ Calif San Francisco, Dept Surg, Inst Hlth Policy Studies, San Francisco, CA 94143 USA.
[Greenberg, Caprice] Univ Wisconsin, Dept Surg, Madison, WI USA.
[Hassett, Michael J.; Schrag, Deborah] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02115 USA.
[Punglia, Rinaa S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol,Brigham & Womens Hosp, Boston, MA 02115 USA.
RP Soeteman, DI (reprint author), Harvard Univ, Ctr Hlth Decis Sci, Sch Publ Hlth, 718 Huntington Ave,2nd Fl, Boston, MA 02115 USA.
EM dsoetema@hsph.harvard.edu
FU Agency for Healthcare Research and Quality (AHRQ) [HHSA290200500161]
FX This work was supported by contract HHSA290200500161 from the Agency for
Healthcare Research and Quality (AHRQ). The views expressed in this
article are those of the authors, and no official endorsement by AHRQ or
the US Department of Health and Human Services is intended or should be
inferred.
NR 32
TC 8
Z9 8
U1 0
U2 3
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 JNCI-J NATL CANCER I
JI JNCI-. Natl. Cancer Inst.
PD JUN
PY 2013
VL 105
IS 11
BP 774
EP 781
DI 10.1093/jnci/djt096
PG 8
WC Oncology
SC Oncology
GA 160QK
UT WOS:000320134100008
PM 23644480
ER
PT J
AU Ganz, PA
Kwan, L
Castellon, SA
Oppenheim, A
Bower, JE
Silverman, DHS
Cole, SW
Irwin, MR
Ancoli-Israel, S
Belin, TR
AF Ganz, Patricia A.
Kwan, Lorna
Castellon, Steven A.
Oppenheim, Amy
Bower, Julienne E.
Silverman, Daniel H. S.
Cole, Steve W.
Irwin, Michael R.
Ancoli-Israel, Sonia
Belin, Thomas R.
TI Cognitive Complaints After Breast Cancer Treatments: Examining the
Relationship With Neuropsychological Test Performance
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID STANDARD-DOSE CHEMOTHERAPY; ADJUVANT CHEMOTHERAPY; WORKING-MEMORY;
SYSTEMIC CHEMOTHERAPY; VERBAL MEMORY; SURVIVORS; WOMEN; DYSFUNCTION;
SYMPTOMS; THERAPY
AB Cognitive complaints are reported frequently after breast cancer treatments. Their association with neuropsychological (NP) test performance is not well-established.
Early-stage, posttreatment breast cancer patients were enrolled in a prospective, longitudinal, cohort study prior to starting endocrine therapy. Evaluation included an NP test battery and self-report questionnaires assessing symptoms, including cognitive complaints. Multivariable regression models assessed associations among cognitive complaints, mood, treatment exposures, and NP test performance.
One hundred eighty-nine breast cancer patients, aged 2165 years, completed the evaluation; 23.3% endorsed higher memory complaints and 19.0% reported higher executive function complaints (> 1 SD above the mean for healthy control sample). Regression modeling demonstrated a statistically significant association of higher memory complaints with combined chemotherapy and radiation treatments (P .01), poorer NP verbal memory performance (P .02), and higher depressive symptoms (P < .001), controlling for age and IQ. For executive functioning complaints, multivariable modeling controlling for age, IQ, and other confounds demonstrated statistically significant associations with better NP visual memory performance (P .03) and higher depressive symptoms (P < .001), whereas combined chemotherapy and radiation treatment (P .05) approached statistical significance.
About one in five postadjuvant treatment breast cancer patients had elevated memory and/or executive function complaints that were statistically significantly associated with domain-specific NP test performances and depressive symptoms; combined chemotherapy and radiation treatment was also statistically significantly associated with memory complaints. These results and other emerging studies suggest that subjective cognitive complaints in part reflect objective NP performance, although their etiology and biology appear to be multifactorial, motivating further transdisciplinary research.
C1 [Ganz, Patricia A.] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Hlth Policy & Management, Los Angeles, CA 90095 USA.
[Belin, Thomas R.] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90095 USA.
[Ganz, Patricia A.; Kwan, Lorna; Oppenheim, Amy] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Div Canc Prevent & Control Res, Los Angeles, CA 90095 USA.
[Ganz, Patricia A.; Cole, Steve W.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA.
[Silverman, Daniel H. S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA.
[Bower, Julienne E.; Irwin, Michael R.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA.
[Castellon, Steven A.; Bower, Julienne E.; Irwin, Michael R.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA.
[Bower, Julienne E.; Cole, Steve W.; Irwin, Michael R.] Univ Calif Los Angeles, Semel Inst, Cousins Ctr Psychoneuroimmunol, Los Angeles, CA 90095 USA.
[Castellon, Steven A.] VA Greater Los Angeles Hlth Care Syst, Dept Psychiat & Mental Hlth, Los Angeles, CA USA.
[Ancoli-Israel, Sonia] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA.
[Ancoli-Israel, Sonia] Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA.
RP Ganz, PA (reprint author), Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Div Canc Prevent & Control Res, A2-125 CHS,Box 956900, Los Angeles, CA 90095 USA.
EM pganz@mednet.ucla.edu
RI Irwin, Michael/H-4870-2013
OI Irwin, Michael/0000-0002-1502-8431
FU National Cancer Institute [R01 CA 109650, R01-AG034588, R01-AG026364,
R01-CA119159, R01-HL079955, R01 HL095799, P30-AG028748, UL RR 033176,
R01CA112035]; Breast Cancer Research Foundation; National Institutes of
Health; Cousins Center for Psychoneuroimmunology
FX This research was supported by funding from the National Cancer
Institute R01 CA 109650 and the Breast Cancer Research Foundation (to
PAG); the National Institutes of Health and National Cancer Institute
R01-AG034588; R01-AG026364; R01-CA119159; R01-HL079955; R01 HL095799;
P30-AG028748; UL RR 033176 (to MRI), and the Cousins Center for
Psychoneuroimmunology (to MRI); the National Cancer Institute
R01CA112035 (to SA-I).
NR 51
TC 43
Z9 44
U1 1
U2 31
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 JNCI-J NATL CANCER I
JI JNCI-. Natl. Cancer Inst.
PD JUN
PY 2013
VL 105
IS 11
BP 791
EP 801
DI 10.1093/jnci/djt073
PG 11
WC Oncology
SC Oncology
GA 160QK
UT WOS:000320134100010
PM 23606729
ER
PT J
AU Choi, HR
Kwon, YM
Freiberg, AA
Nelson, SB
Malchau, H
AF Choi, Ho-Rim
Kwon, Young-Min
Freiberg, Andrew A.
Nelson, Sandra B.
Malchau, Henrik
TI Periprosthetic Joint Infection with Negative Culture Results: Clinical
Characteristics and Treatment Outcome
SO JOURNAL OF ARTHROPLASTY
LA English
DT Article
DE periprosthetic joint infection; negative culture result; clinical
characteristics; treatment outcomes
ID TOTAL KNEE ARTHROPLASTY; TOTAL HIP-ARTHROPLASTY; EXCHANGE ARTHROPLASTY;
DIAGNOSIS; FLUID; COUNT
AB Negative culture result is frequently encountered in periprosthetic joint infection, but its clinical feature has not been well studied. In this study, clinical characteristics and treatment outcome were compared in two patient groups: (1) 40 periprosthetic joint infections with negative culture results (culture-negative group) and (2) 135 patients with positive culture results (culture-positive group). In comparison of two groups, the culture-negative group showed significantly higher incidence of prior antibiotic use (p = 0.005), higher incidence of prior resection surgery (p<0.001) and lower ESR (p = 0.02) than the culture-positive group. The success rate of infection control was higher in the culture-negative group (p = 0.006), which suggests that culture negativity may not necessarily be a negative prognostic factor for periprosthetic joint infection. (C) 2013 Published by Elsevier Inc.
C1 [Choi, Ho-Rim; Kwon, Young-Min; Malchau, Henrik] Massachusetts Gen Hosp, Dept Orthoped Surg, Harris Orthoped Lab, Boston, MA 02114 USA.
[Freiberg, Andrew A.] Massachusetts Gen Hosp, Dept Orthoped Surg, Adult Reconstruct Serv, Boston, MA 02114 USA.
[Nelson, Sandra B.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA.
RP Malchau, H (reprint author), Massachusetts Gen Hosp, Dept Orthoped Surg, Harris Orthoped Lab, 55 Fruit St,GRJ 1126, Boston, MA 02114 USA.
OI Malchau, Henrik/0000-0002-4291-2441
NR 22
TC 14
Z9 16
U1 0
U2 2
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 JUN
PY 2013
VL 28
IS 6
BP 899
EP 903
DI 10.1016/j.arth.2012.10.022
PG 5
WC Orthopedics
SC Orthopedics
GA 156TI
UT WOS:000319846400005
PM 23523496
ER
PT J
AU Hess, PL
Grau-Sepulveda, MV
Hernandez, AF
Peterson, ED
Bhatt, DL
Schwamm, LH
Yancy, CW
Fonarow, GC
Al-Khatib, SM
AF Hess, Paul L.
Grau-Sepulveda, Maria V.
Hernandez, Adrian F.
Peterson, Eric D.
Bhatt, Deepak L.
Schwamm, Lee H.
Yancy, Clyde W.
Fonarow, Gregg C.
Al-Khatib, Sana M.
CA Get Guidelines Steering Comm & Hos
TI Age Differences in the Use of Implantable Cardioverter-Defibrillators
Among Older Patients Hospitalized with Heart Failure
SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY
LA English
DT Article
DE age; implantable; defibrillator; heart failure; healthcare disparities;
sex
ID SUDDEN CARDIAC DEATH; PRACTICE SETTING FINDINGS; PRIMARY PREVENTION;
MYOCARDIAL-INFARCTION; IMPROVE HF; OF-LIFE; OUTCOMES; CARE; SEX;
DISPARITIES
AB Age and ICD Use Among Older HF Patients Introduction Practice guidelines recommend the use of ICDs in patients with heart failure (HF) and a left ventricular ejection fraction (LVEF) of 35% in the absence of contraindications. Methods and Results We performed an analysis of ICD use among patients admitted with HF with LVEF of 35% and discharged alive from 251 hospitals participating in the American Heart Association's Get With The Guidelines-HF Program between January 2005 and September 2011. Among 35,772 guideline-eligible patients, 17,639 received an ICD prior to hospitalization (10,886), during hospitalization (4,876), or were discharged with plans to undergo ICD placement after hospitalization (1,877). After adjustment, increasing age was associated with lower ICD use (odds ratio [OR] 0.89, 95% confidence interval [CI] 0.87-0.91 per 5-year increase in age, P < 0.0001). Compared with patient age < 55 years, older age groups 65 years were less likely to receive an ICD (P < 0.003). Compared with men in the same age group, women were significantly less likely to receive an ICD; this difference was more marked with increasing age (P value for interaction = 0.006). There was a temporal increase in ICD use (adjusted OR 1.23, 95% CI 1.15-1.31 of ICD use per year) that was similar in each age group (P value for interaction = 0.665). Conclusions Eligible older HF patients age 65 years were significantly less likely to receive an ICD. With increasing age, women were less likely to receive an ICD than men. ICD use significantly increased over time in all age groups; however, age-related differences in ICD use persisted.
C1 [Hess, Paul L.; Grau-Sepulveda, Maria V.; Hernandez, Adrian F.; Peterson, Eric D.; Al-Khatib, Sana M.] Duke Univ, Duke Clin Res Inst, Sch Med, Durham, NC 27715 USA.
[Hess, Paul L.; Hernandez, Adrian F.; Peterson, Eric D.; Al-Khatib, Sana M.] Duke Univ, Dept Med, Sch Med, Durham, NC 27715 USA.
[Bhatt, Deepak L.] Vet Affairs Boston Hlth Syst, Boston, MA USA.
[Bhatt, Deepak L.; Schwamm, Lee H.] Harvard Univ, Sch Med, Boston, MA USA.
[Bhatt, Deepak L.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Schwamm, Lee H.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Yancy, Clyde W.] Northwestern Univ, Dept Med, Chicago, IL 60611 USA.
[Fonarow, Gregg C.] Ronald Reagan UCLA Med Ctr, Ahmanson UCLA Cardiomyopathy Ctr, Los Angeles, CA USA.
RP Hess, PL (reprint author), Duke Univ, Duke Clin Res Inst, Sch Med, POB 17969, Durham, NC 27715 USA.
EM p.hess@duke.edu
RI Hernandez, Adrian F./A-7818-2016
OI Schwamm, Lee/0000-0003-0592-9145; Hernandez, Adrian
F./0000-0003-3387-9616
FU American Heart Association; Medtronic; Ortho-McNeil; American Heart
Association Pharmaceuticals Roundtable; GlaxoSmithKline; GWTG Young
Investigator Database Research Seed Grant; NIH [HL069749-09]
FX Funding for the GWTG-HF program is provided by the American Heart
Association. The GWTG-HF program is supported in part by Medtronic,
Ortho-McNeil, and the American Heart Association Pharmaceuticals
Roundtable. GWTG-HF was funded in the past by GlaxoSmithKline. This
analysis was funded by the GWTG Young Investigator Database Research
Seed Grant. The sponsors of GWTG-HF had no role in the design or conduct
of the study or the management, analysis, or interpretation of the data.
P.L. Hess was funded by NIH T-32 training grant HL069749-09.
NR 31
TC 4
Z9 4
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1045-3873
J9 J CARDIOVASC ELECTR
JI J. Cardiovasc. Electrophysiol.
PD JUN
PY 2013
VL 24
IS 6
BP 664
EP 671
DI 10.1111/jce.12100
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 157LV
UT WOS:000319898500010
PM 23437793
ER
PT J
AU Lee, J
Radhakrishnan, H
Wu, WC
Daneshmand, A
Climov, M
Ayata, C
Boas, DA
AF Lee, Jonghwan
Radhakrishnan, Harsha
Wu, Weicheng
Daneshmand, Ali
Climov, Mihail
Ayata, Cenk
Boas, David A.
TI Quantitative imaging of cerebral blood flow velocity and intracellular
motility using dynamic light scattering-optical coherence tomography
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Article
DE acute stroke; animal models; cerebral blood flow measurement;
microscopy; optical imaging
ID FLUORESCENCE CORRELATION SPECTROSCOPY; ISCHEMIC-STROKE; IN-VIVO;
NONERGODIC MEDIA; DIFFUSION; RAT; MICROSCOPY; PERFUSION; CORTEX; MRI
AB This paper describes a novel optical method for label-free quantitative imaging of cerebral blood flow (CBF) and intracellular motility (IM) in the rodent cerebral cortex. This method is based on a technique that integrates dynamic light scattering (DLS) and optical coherence tomography (OCT), named DLS-OCT. The technique measures both the axial and transverse velocities of CBF, whereas conventional Doppler OCT measures only the axial one. In addition, the technique produces a three-dimensional map of the diffusion coefficient quantifying nontranslational motions. In the DLS-OCT diffusion map, we observed high-diffusion spots, whose locations highly correspond to neuronal cell bodies and whose diffusion coefficient agreed with that of the motion of intracellular organelles reported in vitro in the literature. Therefore, the present method has enabled, for the first time to our knowledge, label-free imaging of the diffusion-like motion of intracellular organelles in vivo. As an example application, we used the method to monitor CBF and IM during a brief ischemic stroke, where we observed an induced persistent reduction in IM despite the recovery of CBF after stroke. This result supports that the IM measured in this study represent the cellular energy metabolism-related active motion of intracellular organelles rather than free diffusion of intracellular macromolecules.
C1 [Lee, Jonghwan; Wu, Weicheng; Boas, David A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
[Radhakrishnan, Harsha] Penn State Univ, Ctr Neural Engn, University Pk, PA 16802 USA.
[Daneshmand, Ali; Climov, Mihail; Ayata, Cenk] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Stroke & Neurovasc Regulat Lab,Dept Radiol, Charlestown, MA 02129 USA.
RP Lee, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr Biomed Imaging, 149 13th St,Room 2280, Charlestown, MA 02129 USA.
EM jonghwan@nmr.mgh.harvard.edu
OI Climov, Mihail/0000-0001-9150-8608
FU NIH [R01-NS057476, R01-EB000790, P01NS055104]; AFOSR [MFEL
FA9550-07-1-0101]
FX This study was supported by the NIH (R01-NS057476, R01-EB000790,
P01NS055104) and the AFOSR (MFEL FA9550-07-1-0101).
NR 43
TC 19
Z9 19
U1 1
U2 20
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 JUN
PY 2013
VL 33
IS 6
BP 819
EP 825
DI 10.1038/jcbfm.2013.20
PG 7
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA 156KP
UT WOS:000319821100004
PM 23403378
ER
PT J
AU Abrahamson, EE
Foley, LM
DeKosky, ST
Hitchens, TK
Ho, C
Kochanek, PM
Ikonomovic, MD
AF Abrahamson, Eric E.
Foley, Lesley M.
DeKosky, Steven T.
Hitchens, T. Kevin
Ho, Chien
Kochanek, Patrick M.
Ikonomovic, Milos D.
TI Cerebral blood flow changes after brain injury in human amyloid-beta
knock-in mice
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Article
DE Alzheimer's disease; amyloid; arterial spin-labeling MRI; blood flow;
brain injury; statin
ID TRAUMA-INDUCED INCREASES; NITRIC-OXIDE SYNTHASE; ALZHEIMERS-DISEASE;
PRECURSOR PROTEIN; A-BETA; FUNCTIONAL HYPEREMIA; REDUCTASE INHIBITORS;
OXIDATIVE STRESS; SIMVASTATIN; ACTIVATION
AB Traumatic brain injury (TBI) is an environmental risk factor for Alzheimer's disease (AD). Increased brain concentrations of amyloid-beta (A beta) peptides and impaired cerebral blood flow (CBF) are shared pathologic features of TBI and AD and promising therapeutic targets. We used arterial spin-labeling magnetic resonance imaging to examine if CBF changes after TBI are influenced by human A beta and amenable to simvastatin therapy. CBF was measured 3 days and 3 weeks after controlled cortical impact (CCI) injury in transgenic human A beta-expressing APP(NLh/NLh) mice compared to murine A beta-expressing C57Bl/6J wild types. Compared to uninjured littermates, CBF was reduced in the cortex of the injured hemisphere in both A beta transgenics and wild types; deficits were more pronounced in the transgenic group, which exhibited injury-induced increased concentrations of human A beta. In the hemisphere contralateral to CCI, CBF levels were stable in A beta transgenic mice but increased in wild-type mice, both relative to uninjured littermates. Post-injury treatment of A beta transgenic mice with simvastatin lowered brain A beta concentrations, attenuated deficits in CBF ipsilateral to injury, restored hyperemia contralateral to injury, and reduced brain tissue loss. Future studies examining long-term effects of simvastatin therapy on CBF and chronic neurodegenerative changes after TBI are warranted.
C1 [Abrahamson, Eric E.; Ikonomovic, Milos D.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15213 USA.
[Abrahamson, Eric E.; Ikonomovic, Milos D.] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA.
[Foley, Lesley M.; Hitchens, T. Kevin; Ho, Chien] Carnegie Mellon Univ, Dept Biol Sci, VA Pittsburgh Healthcare Syst, Pittsburgh NMR Ctr Biomed Res, Pittsburgh, PA 15213 USA.
[DeKosky, Steven T.] Univ Virginia, Sch Med, Off Dean, Charlottesville, VA 22908 USA.
[DeKosky, Steven T.] Univ Virginia, Sch Med, Dept Neurol, Charlottesville, VA 22908 USA.
[Kochanek, Patrick M.] Univ Pittsburgh, Pittsburgh, PA 15213 USA.
[Kochanek, Patrick M.] Univ Pittsburgh, Safar Ctr Resuscitat Res, Pittsburgh, PA 15213 USA.
[Ikonomovic, Milos D.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15213 USA.
RP Ikonomovic, MD (reprint author), Univ Pittsburgh, Dept Neurol, BSTWR S-521,200 Lothrop St, Pittsburgh, PA 15213 USA.
EM ikonomovicmd@upmc.edu
RI Kochanek, Patrick/D-2371-2015; Ho, Chien/O-6112-2016
OI Kochanek, Patrick/0000-0002-2627-913X; Ho, Chien/0000-0002-4094-9232
FU NIH [P50 NS30318]; National Institutes of Health [P41-EB001977]
FX Supported by NIH P50 NS30318. The Pittsburgh NMR Center for Biomedical
Research is supported by a grant from the National Institutes of Health
(P41-EB001977). We acknowledge expert technical assistance provided by
Mr. William Paljug, Mr. John Melick, and Ms. Lan Shao.
NR 37
TC 5
Z9 5
U1 0
U2 9
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 JUN
PY 2013
VL 33
IS 6
BP 826
EP 833
DI 10.1038/jcbfm.2013.24
PG 8
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA 156KP
UT WOS:000319821100005
PM 23443172
ER
PT J
AU Huang, S
Kim, JK
Atochin, DN
Farrar, CT
Huang, PL
Suh, JY
Kwon, SJ
Shim, WH
Cho, H
Cho, G
Kim, YR
AF Huang, Shuning
Kim, Jeong Kon
Atochin, Dmitriy N.
Farrar, Christian T.
Huang, Paul L.
Suh, Ji Yeon
Kwon, Seon Joo
Shim, Woo Hyun
Cho, Hyungjoon
Cho, Gyunggoo
Kim, Young Ro
TI Cerebral blood volume affects blood-brain barrier integrity in an acute
transient stroke model
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Article
DE blood-brain barrier; cerebral blood volume; stroke; water exchange; MRI
ID ACUTE ISCHEMIC-STROKE; WATER EXCHANGE; HEMORRHAGIC TRANSFORMATION;
MAGNETIC-RESONANCE; MATRIX METALLOPROTEINASES; EDEMA FORMATION;
PERFUSION CT; RAT-BRAIN; GD-DTPA; MRI
AB Insufficient vascular reserve after an ischemic stroke may induce biochemical cascades that subsequently deteriorate the blood-brain barrier (BBB) function. However, the direct relationship between poor cerebral blood volume (CBV) restoration and BBB disruption has not been examined in acute stroke. To quantify BBB integrity at acute stages of transient stroke, in particular for cases in which extravasation of the standard contrast agent (Gd-DTPA) is not observed, we adopted the water exchange index (WEI), a novel magnetic resonance image-derived parameter to estimate the water permeability across the BBB. The apparent diffusion coefficient (ADC) and R-2 relaxation rate constant were also measured for outlining the tissue abnormality, while fractional CBV and WEI were quantified for assessing vascular alterations. The significantly decreased ADC and R-2 in the ischemic cortices did not correlate with the changes in CBV or WEI. In contrast, a strong negative correlation between the ipsilesional WEI and CBV was found, in which stroke mice were clustered into two groups: (1) high WEI and low CBV and (2) normal WEI and CBV. The low CBV observed for mice with a disrupted BBB, characterized by a high WEI, indicates the importance of CBV restoration for maintaining BBB stability in acute stroke.
C1 [Huang, Shuning; Kim, Jeong Kon; Farrar, Christian T.; Suh, Ji Yeon; Kwon, Seon Joo; Shim, Woo Hyun; Kim, Young Ro] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA.
[Kim, Jeong Kon; Cho, Gyunggoo] Korea Basic Sci Inst, Div Magnet Resonance, Ochang, South Korea.
[Kim, Jeong Kon; Suh, Ji Yeon] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Radiol, Seoul, South Korea.
[Atochin, Dmitriy N.; Huang, Paul L.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Dept Med, Charlestown, MA 02129 USA.
[Atochin, Dmitriy N.; Huang, Paul L.] Massachusetts Gen Hosp, Div Cardiol, Charlestown, MA 02129 USA.
[Cho, Hyungjoon; Kim, Young Ro] Ulsan Natl Inst Sci & Technol, Ulsan, South Korea.
RP Kim, YR (reprint author), Massachusetts Gen Hosp, Harvard MIT HST Athinoula A Martinos Ctr Biomed I, Bldg 149,13th St, Charlestown, MA 02129 USA.
EM spmn@nmr.mgh.harvard.edu
RI Cho, HyungJoon/F-1423-2010; Atochin, Dmitriy/Q-3150-2016
FU American Heart Association (SDG) [0835451N]; Basic Science Research
Program [2011-0028826]; Advanced Research Center through the National
Research Foundation of Korea (NRF) [2012-0008999]; Ministry of
Education, Science of Technology; National Institutes of Health
[K25-AG029415]
FX The authors gratefully acknowledge financial support from the American
Heart Association (SDG #0835451N), the Basic Science Research Program
(No. 2011-0028826), and Advanced Research Center (No. 2012-0008999)
through the National Research Foundation of Korea (NRF) funded by the
Ministry of Education, Science of Technology and the National Institutes
of Health (K25-AG029415).
NR 39
TC 5
Z9 7
U1 5
U2 15
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 JUN
PY 2013
VL 33
IS 6
BP 898
EP 905
DI 10.1038/jcbfm.2013.27
PG 8
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA 156KP
UT WOS:000319821100013
PM 23462571
ER
PT J
AU Ayata, C
Shin, HK
Dilekoz, E
Atochin, DN
Kashiwagi, S
Eikermann-Haerter, K
Huang, PL
AF Ayata, Cenk
Shin, Hwa Kyoung
Dilekoez, Ergin
Atochin, Dmitriy N.
Kashiwagi, Satoshi
Eikermann-Haerter, Katharina
Huang, Paul L.
TI Hyperlipidemia disrupts cerebrovascular reflexes and worsens ischemic
perfusion defect
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Article
DE apolipoprotein E knockout mice; autoregulation; hypercapnia;
hypercholesterolemia; middle cerebral artery occlusion; neurovascular
coupling
ID APOLIPOPROTEIN-E-DEFICIENT; CEREBRAL-BLOOD-FLOW; FAMILIAL
HYPERCHOLESTEROLEMIA; DENSITY-LIPOPROTEIN; CO2 REACTIVITY; MICE;
ATHEROSCLEROSIS; DYSFUNCTION; STROKE; BRAIN
AB Hyperlipidemia is a highly prevalent risk factor for coronary and cervical atherosclerosis and stroke. However, even in the absence of overt atherosclerosis, hyperlipidemia disrupts endothelial and smooth muscle function. We investigated the impact of hyperlipidemia on resting-brain perfusion, fundamental cerebrovascular reflexes, and dynamic perfusion defect during acute focal ischemia in hyperlipidemic apolipoprotein E knockout mice before the development of flow-limiting atherosclerotic stenoses. Despite elevated blood pressures, absolute resting cerebral blood flow was reduced by 20% in apolipoprotein E knockout compared with wild type when measured by [C-14]-iodoamphetamine technique. Noninvasive, high spatiotemporal resolution laser speckle flow imaging revealed that the lower autoregulatory limit was elevated in apolipoprotein E knockout mice (60 vs. 40 mm Hg), and cortical hyperemic responses to hypercapnia and functional activation were attenuated by 30% and 64%, respectively. Distal middle cerebral artery occlusion caused significantly larger perfusion defects and infarct volumes in apolipoprotein E knockout compared with wild type. Cerebrovascular dysfunction showed a direct relationship to the duration of high-fat diet. These data suggest that hyperlipidemia disrupts cerebral blood flow regulation and diminishes collateral perfusion in acute stroke in the absence of hemodynamically significant atherosclerosis.
C1 [Ayata, Cenk; Shin, Hwa Kyoung; Dilekoez, Ergin; Eikermann-Haerter, Katharina] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurovasc Res Lab,Dept Radiol, Charlestown, MA 02129 USA.
[Ayata, Cenk] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Stroke Serv & Neurosci Intens Care Un, Charlestown, MA 02129 USA.
[Atochin, Dmitriy N.; Kashiwagi, Satoshi; Huang, Paul L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA.
[Atochin, Dmitriy N.; Kashiwagi, Satoshi; Huang, Paul L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Charlestown, MA 02129 USA.
RP Ayata, C (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurovasc Res Lab, 149 13th St,Room 6403, Charlestown, MA 02129 USA.
EM cayata@partners.org
RI Atochin, Dmitriy/Q-3150-2016
FU National Institutes of Health [NS055104, NS061505, NS33335]; American
Heart Association [SDG0835344N]; National Research Foundation (NRF) of
Korea; Ministry of Education, Science and Technology, Harvard Catalyst
[2010-0007470]; Harvard Clinical and Translational Science Center (NIH)
[UL1RR025758]; Harvard University and its affiliated academic health
care centers; Deane Institute for Integrative Research in Stroke and
Atrial Fibrillation; Andrew David Heitman Foundation
FX This work was supported by the National Institutes of Health (NS055104,
NS061505, NS33335), American Heart Association (SDG0835344N), Basic
Science Research Program through the National Research Foundation (NRF)
of Korea funded by the Ministry of Education, Science and Technology
(Grants 2010-0007470), Harvard Catalyst. The Harvard Clinical and
Translational Science Center (NIH Award #UL1RR025758 and financial
contributions from Harvard University and its affiliated academic health
care centers), the Deane Institute for Integrative Research in Stroke
and Atrial Fibrillation, and Neuroendovascular Research Fund from the
Andrew David Heitman Foundation.
NR 38
TC 11
Z9 13
U1 2
U2 5
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 JUN
PY 2013
VL 33
IS 6
BP 954
EP 962
DI 10.1038/jcbfm.2013.38
PG 9
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA 156KP
UT WOS:000319821100020
PM 23486293
ER
PT J
AU Basile, JN
Bloch, MJ
AF Basile, Jan N.
Bloch, Michael J.
TI Determining the Relative Antihypertensive Potency and Relative
Cardiovascular Risk Reduction Associated With Different Thiazide and
Thiazide-Type Diuretics
SO JOURNAL OF CLINICAL HYPERTENSION
LA English
DT Article
C1 [Basile, Jan N.] Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Div Gen Internal Med Geriatr, Seinsheimer Cardiovasc Hlth Program, Charleston, SC 29425 USA.
[Bloch, Michael J.] Univ Nevada, Sch Med, Dept Internal Med, Reno, NV 89557 USA.
RP Bloch, MJ (reprint author), Univ Hlth Syst, 1500 East 2nd St,Suite 302, Reno, NV 89502 USA.
EM mbloch@aol.com
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1524-6175
J9 J CLIN HYPERTENS
JI J. Clin. Hypertens.
PD JUN
PY 2013
VL 15
IS 6
BP 359
EP 361
DI 10.1111/jch.12079
PG 3
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 157MA
UT WOS:000319899000001
PM 23730981
ER
PT J
AU Sharma, DB
Bondell, HD
Zhang, HH
AF Sharma, Dhruv B.
Bondell, Howard D.
Zhang, Hao Helen
TI Consistent Group Identification and Variable Selection in Regression
With Correlated Predictors
SO JOURNAL OF COMPUTATIONAL AND GRAPHICAL STATISTICS
LA English
DT Article
DE Coefficient shrinkage; Correlation; Oracle properties; Penalization;
Structure identification; Supervised clustering
ID ORACLE PROPERTIES; ADAPTIVE LASSO; ELASTIC-NET; SHRINKAGE; MODEL
AB Statistical procedures for variable selection have become integral elements in any analysis. Successful procedures are characterized by high predictive accuracy, yielding interpretable models while retaining computational efficiency. Penalized methods that perform coefficient shrinkage have been shown to be successful in many cases. Models with correlated predictors are particularly challenging to tackle. We propose a penalization procedure that performs variable selection while clustering groups of predictors automatically. The oracle properties of this procedure, including consistency in group identification, are also studied. The proposed method compares favorably with existing selection approaches in both prediction accuracy and model discovery, while retaining its computational efficiency. Supplementary materials are available online.
C1 [Sharma, Dhruv B.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Sharma, Dhruv B.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Bondell, Howard D.; Zhang, Hao Helen] N Carolina State Univ, Dept Stat, Raleigh, NC 27695 USA.
RP Sharma, DB (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
EM dbsharma@hsph.harvard.edu; howard_bondell@ncsu.edu; helen_zhang@ncsu.edu
FU NIH (National Institutes of Health) [P01-CA-134294, R01-MH-084022,
P01-CA-142538, R01-CA-085848, P01-CA-142538.]; NSF (National Science
Foundation) [DMS-1005612, DMS-0645293]
FX The authors are grateful to the editor, an associate editor, and two
anonymous referees for their valuable comments. Sharma's research was
supported in part by the NIH (National Institutes of Health) grant
P01-CA-134294. Bondell's research was supported in part by the NSF
(National Science Foundation) grant DMS-1005612 and NIH grants
R01-MH-084022 and P01-CA-142538. Zhang's research was supported in part
by the NSF grant DMS-0645293 and NIH grants R01-CA-085848 and
P01-CA-142538.
NR 22
TC 8
Z9 9
U1 0
U2 5
PU AMER STATISTICAL ASSOC
PI ALEXANDRIA
PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA
SN 1061-8600
EI 1537-2715
J9 J COMPUT GRAPH STAT
JI J. Comput. Graph. Stat.
PD JUN
PY 2013
VL 22
IS 2
BP 319
EP 340
DI 10.1080/15533174.2012.707849
PG 22
WC Statistics & Probability
SC Mathematics
GA 158FD
UT WOS:000319954000006
PM 23772171
ER
PT J
AU Reinherz, EL
Kung, PC
Goldstein, G
Schlossman, SF
AF Reinherz, Ellis L.
Kung, Patrick C.
Goldstein, Gideon
Schlossman, Stuart F.
TI Separation of functional subsets of human T cells by a monoclonal
antibody (Reprinted from Proceedings of the National Academy of
Sciences, U.S.A., vol 76, pg 4061-4065, 1979)
SO JOURNAL OF IMMUNOLOGY
LA English
DT Reprint
ID HUMAN LYMPHOCYTE SUBPOPULATIONS; IMMUNOLOGICAL FUNCTIONS; SUPPRESSOR;
SUBCLASSES; DISEASE; BLOOD; TH2+
AB A monoclonal antibody was produced to human peripheral blood T cells. This hybridoma antibody, termed OKT4, was reactive by indirect immunofluorescence with only 55-60% of the peripheral blood T cell population (OKT4(+)) and unreactive with normal B cells, null cells, and macrophages. The OKT4(-) T cell population contained the previously described TH2+ subset that has been shown to contain cytotoxie/suppressor cells. With cell-sorter separation of OKT4(+) and OKT4(-) cells, it was shown that these T cell subsets were functionally discrete. Both gave proliferative responses with concanavalin A, alloantigens, and phytohemagglutinin, although OKT4(+) cells were much more responsive to the latter. OKT4(+) cells alone responded to soluble antigens whereas OKT4(-) cells alone were cytotoxic after alloantigenic sensitization of unfractionated T cells. However, both OKT4(+) and OKT4(-) cells were required during sensitization for optimal development of cytotoxicity. These data suggest that the OKT4(+) subset represents a helper population and that the OKTA4(-) subset contains the cytotoxic effector population. OKT4 could be a valuable reagent for determining alterations of these functional subsets in human diseases.
C1 [Reinherz, Ellis L.; Schlossman, Stuart F.] Harvard Univ, Sch Med, Sidney Farber Canc Inst, Div Tumor Immunol, Boston, MA 02115 USA.
[Kung, Patrick C.; Goldstein, Gideon] Ortho Pharmaceut Corp, Div Immunosci, Raritan, NJ 08869 USA.
RP Reinherz, EL (reprint author), Sidney Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA.
NR 25
TC 0
Z9 0
U1 2
U2 7
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD JUN 1
PY 2013
VL 190
IS 11
BP 5346
EP 5350
PG 5
WC Immunology
SC Immunology
GA 147XY
UT WOS:000319205900004
PM 23687191
ER
PT J
AU Kung, PC
Goldstein, G
Reinherz, EL
Schlossman, SF
AF Kung, Patrick C.
Goldstein, Gideon
Reinherz, Ellis L.
Schlossman, Stuart F.
TI Monoclonal Antibodies Defining Distinctive Human T Cell Surface Antigens
(Reprinted from Science, vol 206, pg 347, 1979)
SO JOURNAL OF IMMUNOLOGY
LA English
DT Reprint
ID GLOBULIN; SUBSET
AB Three novel monoclonal antibodies. (designated OKT1, OKT3 and OKT4) were generated against surface determinants of human peripheral T cells. Both OKT1 and OKT3 reacted with till human peripheral T cells and 5 to 10 percent of thymocytes but differed in their reactivities with T cell lines. By contrast, OKT4 reacted with 55 percent of human peripheral T cells and 80 percent of thymocytes, three antibodies were selective for T cells in the peripheral blood in that they did not react with normal B cells, null cells, monocytes. or granulocytes.
C1 [Kung, Patrick C.; Goldstein, Gideon] Ortho Pharmaceut Corp, Raritan, NJ 08869 USA.
[Reinherz, Ellis L.; Schlossman, Stuart F.] Harvard Univ, Sch Med, Sidney Farber Canc Inst, Div Tumor Immunol, Boston, MA 02115 USA.
RP Kung, PC (reprint author), Ortho Pharmaceut Corp, Raritan, NJ 08869 USA.
NR 21
TC 0
Z9 0
U1 0
U2 1
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD JUN 1
PY 2013
VL 190
IS 11
BP 5351
EP 5353
PG 3
WC Immunology
SC Immunology
GA 147XY
UT WOS:000319205900005
PM 23687192
ER
PT J
AU Giallourakis, CC
Benita, Y
Molinie, B
Cao, ZF
Despo, O
Pratt, HE
Zukerberg, LR
Daly, MJ
Rioux, JD
Xavier, RJ
AF Giallourakis, Cosmas C.
Benita, Yair
Molinie, Benoit
Cao, Zhifang
Despo, Orion
Pratt, Henry E.
Zukerberg, Lawrence R.
Daly, Mark J.
Rioux, John D.
Xavier, Ramnik J.
TI Genome-wide Analysis of Immune System Genes by Expressed Sequence Tag
Profiling
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID NONCODING RNAS; FRUCTOSE 1,6-BISPHOSPHATASE; IMMUNOLOGICAL GENOME;
DATABASE; CELLS; IDENTIFICATION; TRANSCRIPTOME; INFORMATION; ANNOTATION;
MECHANISMS
AB Profiling studies of mRNA and microRNA, particularly microarray-based studies, have been extensively used to create compendia of genes that are preferentially expressed in the immune system. In some instances, functional studies have been subsequently pursued. Recent efforts such as the Encyclopedia of DNA Elements have demonstrated the benefit of coupling RNA sequencing analysis with information from expressed sequence tags (ESTs) for transcriptomic analysis. However, the full characterization and identification of transcripts that function as modulators of human immune responses remains incomplete. In this study, we demonstrate that an integrated analysis of human ESTs provides a robust platform to identify the immune transcriptome. Beyond recovering a reference set of immune-enriched genes and providing large-scale cross-validation of previous microarray studies, we discovered hundreds of novel genes preferentially expressed in the immune system, including noncoding RNAs. As a result, we have established the Immunogene database, representing an integrated EST road map of gene expression in human immune cells, which can be used to further investigate the function of coding and noncoding genes in the immune system. Using this approach, we have uncovered a unique metabolic gene signature of human macrophages and identified PRDM15 as a novel overexpressed gene in human lymphomas. Thus, we demonstrate the utility of EST profiling as a basis for further deconstruction of physiologic and pathologic immune processes.
C1 [Giallourakis, Cosmas C.; Benita, Yair; Molinie, Benoit; Cao, Zhifang; Despo, Orion; Pratt, Henry E.; Xavier, Ramnik J.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
[Giallourakis, Cosmas C.; Benita, Yair; Molinie, Benoit; Cao, Zhifang; Despo, Orion; Pratt, Henry E.; Zukerberg, Lawrence R.; Daly, Mark J.; Xavier, Ramnik J.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Giallourakis, Cosmas C.; Benita, Yair; Molinie, Benoit; Cao, Zhifang; Despo, Orion; Pratt, Henry E.; Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA.
[Benita, Yair; Cao, Zhifang; Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA.
[Zukerberg, Lawrence R.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Daly, Mark J.; Xavier, Ramnik J.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Dept Med, Boston, MA 02114 USA.
[Daly, Mark J.; Xavier, Ramnik J.] Broad Inst Massachusetts Inst Technol & Harvard U, Cambridge, MA 02142 USA.
[Rioux, John D.] Univ Montreal, Lab Genet & Genom Med Inflammat, Montreal, PQ H1T 1C8, Canada.
RP Xavier, RJ (reprint author), Massachusetts Gen Hosp, Richard B Simches Res Ctr, Ctr Computat & Integrat Biol, 185 Cambridge St, Boston, MA 02114 USA.
EM xavier@molbio.mgh.harvard.edu
RI Rioux, John/A-9599-2015
OI Rioux, John/0000-0001-7560-8326
FU National Institutes of Health [DK083756, DK086502, HL088297, DK043351]
FX This work was supported by Grants DK083756, DK086502, HL088297, and
DK043351 from the National Institutes of Health (to R.J.X.).
NR 37
TC 5
Z9 5
U1 1
U2 19
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD JUN 1
PY 2013
VL 190
IS 11
BP 5578
EP 5587
DI 10.4049/jimmunol.1203471
PG 10
WC Immunology
SC Immunology
GA 147XY
UT WOS:000319205900028
PM 23616578
ER
PT J
AU Eisenberg, G
Uzana, R
Pato, A
Frankenburg, S
Merims, S
Yefenof, E
Ferrone, S
Peretz, T
Machenkin, A
Lotem, M
AF Eisenberg, Galit
Uzana, Ronny
Pato, Aviad
Frankenburg, Shoshana
Merims, Sharon
Yefenof, Eitan
Ferrone, Soldano
Peretz, Tamar
Machenkin, Arthur
Lotem, Michal
TI Imprinting of Lymphocytes with Melanoma Antigens Acquired by
Trogocytosis Facilitates Identification of Tumor-Reactive T Cells
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID ADOPTIVE TRANSFER THERAPY; FLOW-CYTOMETRY; INFILTRATING LYMPHOCYTES;
MEMBRANE-FRAGMENTS; TARGET-CELLS; NK CELLS; B-CELL; CAPTURE; ACTIVATION;
GENERATION
AB Trogocytosis is a contact-dependent intercellular transfer of membrane fragments and associated molecules from APCs to effector lymphocytes. We previously demonstrated that trogocytosis also occurs between tumor target and cognate melanoma Ag-specific cytotoxic T cells (CTL). In this study, we show that, following trogocytosis, immune effector cells acquire molecular components of the tumor, including surface Ags, which are detectable by specific mAbs. We demonstrate that CD8(+) and CD4(+) T cells from melanoma patients' PBMC and tumor-infiltrating lymphocytes (TIL) capture melanoma Ags, enabling identification of trogocytosing lymphocytes by staining with Ag-specific Abs. This finding circumvents the necessity of tumor prelabeling, which in the past was mandatory to detect membrane-capturing T cells. Through the detection of melanoma Ags on TIL, we sorted trogocytosing T cells and verified their preferential reactivity and cytotoxicity. Furthermore, tumor Ag imprinted T cells were detected at low frequency in fresh TIL cultures shortly after extraction from the tumor. Thus, T cell imprinting by tumor Ags may allow the enrichment of melanoma Ag-specific T cells for research and potentially even for the adoptive immunotherapy of patients with cancer. The Journal of Immunology, 2013, 190: 5856-5865.
C1 [Eisenberg, Galit; Uzana, Ronny; Pato, Aviad; Frankenburg, Shoshana; Merims, Sharon; Peretz, Tamar; Machenkin, Arthur; Lotem, Michal] Hadassah Med Org, Sharett Inst Oncol, IL-91120 Jerusalem, Israel.
[Yefenof, Eitan] Hebrew Univ Jerusalem, Lautenberg Ctr Gen & Tumor Immunol, IL-91120 Jerusalem, Israel.
[Ferrone, Soldano] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
RP Machenkin, A (reprint author), Hadassah Med Org, Sharett Inst Oncol, POB 12000, IL-91120 Jerusalem, Israel.
EM arthurm@hadassah.org.il; mlotem@hadassah.org.il
FU Dr. Miriam and Sheldon G. Adelson Medical Research Foundation; United
States-Israel Binational Science Foundation; Israel Cancer Association
FX This work was supported by the Dr. Miriam and Sheldon G. Adelson Medical
Research Foundation, the United States-Israel Binational Science
Foundation, the Israel Cancer Association, the Chief Scientist of the
Israel Ministry of Health (Grant 4886), and a Perlstein Family donation.
This work was also supported by Public Health Service Grants RO1
CA110249 and RO1 CA138188 awarded by the National Cancer Institute.
NR 38
TC 7
Z9 7
U1 0
U2 6
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD JUN 1
PY 2013
VL 190
IS 11
BP 5856
EP 5865
DI 10.4049/jimmunol.1202879
PG 10
WC Immunology
SC Immunology
GA 147XY
UT WOS:000319205900057
PM 23626012
ER
PT J
AU Cai, CS
Twyford, P
Fried, S
AF Cai, Changsi
Twyford, Perry
Fried, Shelley
TI The response of retinal neurons to high-frequency stimulation
SO JOURNAL OF NEURAL ENGINEERING
LA English
DT Article
ID ACTION-POTENTIAL INITIATION; ISOLATED CHICKEN RETINA; GANGLION-CELLS;
ELECTRICAL-STIMULATION; VISUAL-PERCEPTION; CONDUCTION BLOCK; NATURAL
SCENES; PULSE TRAINS; MAMMALIAN RETINA; IN-VITRO
AB Objective. High-rate pulse trains have proven to be effective in cochlear prosthetics and, more recently, have been shown to elicit a wide range of interesting response properties in axons of the peripheral nervous system. Surprisingly, the effectiveness of such trains for use in retinal prostheses has not been explored. Approach. Using cell-attached patch clamp methods, we measured the in vitro response of two rabbit retinal ganglion cell types, OFF-brisk transient (OFF-BT) and ON-OFF directionally selective (DS), to trains of biphasic pulses delivered at 2000 pulses per second (PPS). Main Results. For OFF-BT cells, response onset occurred at similar to 20 mu A, and maximum response occurred at similar to 40 mu A. Interestingly, spiking levels decreased for further increases in amplitude. In contrast, DS cells had a spiking onset at similar to 25 mu A and maintained strong spiking as stimulus amplitude was increased, even at the highest levels tested. Thus, a low-amplitude stimulus train at 2000 PPS (similar to 25 mu A) will activate OFF-BT cells strongly, while simultaneously activating DS cells only weakly. In contrast, a high amplitude train (similar to 75 mu A) will activate DS cells strongly while suppressing responses in OFF-BT cells. Significance. The response differences between cell types suggest some forms of preferential activation may be possible, and further testing is warranted. Further, the scope of the response differences found here suggests activation mechanisms that are more complex than those described in previous studies.
C1 [Cai, Changsi; Twyford, Perry; Fried, Shelley] VA Boston Healthcare Syst, Boston, MA USA.
[Cai, Changsi] Shanghai Jiao Tong Univ, Sch Biomed Engn, Shanghai 200030, Peoples R China.
[Cai, Changsi; Twyford, Perry; Fried, Shelley] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA.
[Cai, Changsi; Twyford, Perry; Fried, Shelley] Harvard Univ, Sch Med, Boston, MA USA.
[Cai, Changsi] Aarhus Univ, CFIN, Aarhus, Denmark.
RP Fried, S (reprint author), VA Boston Healthcare Syst, Boston, MA USA.
EM fried.shelley@mgh.harvard.edu
FU VA Boston Healthcare System [1 I01RX000350]; NIH [1 R01EY019967-01]
FX This work was funded in part by the VA Boston Healthcare System (1
I01RX000350) and the NIH (1 R01EY019967-01).
NR 62
TC 9
Z9 9
U1 2
U2 9
PU IOP PUBLISHING LTD
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 1741-2560
J9 J NEURAL ENG
JI J. Neural Eng.
PD JUN
PY 2013
VL 10
IS 3
AR UNSP 036009
DI 10.1088/1741-2560/10/3/036009
PG 14
WC Engineering, Biomedical; Neurosciences
SC Engineering; Neurosciences & Neurology
GA 152DM
UT WOS:000319510800012
PM 23594620
ER
PT J
AU Perge, JA
Homer, ML
Malik, WQ
Cash, S
Eskandar, E
Friehs, G
Donoghue, JP
Hochberg, LR
AF Perge, Janos A.
Homer, Mark L.
Malik, Wasim Q.
Cash, Sydney
Eskandar, Emad
Friehs, Gerhard
Donoghue, John P.
Hochberg, Leigh R.
TI Intra-day signal instabilities affect decoding performance in an
intracortical neural interface system
SO JOURNAL OF NEURAL ENGINEERING
LA English
DT Article
ID HIPPOCAMPAL PYRAMIDAL CELLS; BRAIN-MACHINE INTERFACE; LOCAL-FIELD
POTENTIALS; FALSE DISCOVERY RATE; PRIMARY MOTOR CORTEX; CORTICAL
CONTROL; SPIKING ACTIVITY; MUSCLE-ACTIVITY; TETRAPLEGIA; ENSEMBLE
AB Objective. Motor neural interface systems (NIS) aim to convert neural signals into motor prosthetic or assistive device control, allowing people with paralysis to regain movement or control over their immediate environment. Effector or prosthetic control can degrade if the relationship between recorded neural signals and intended motor behavior changes. Therefore, characterizing both biological and technological sources of signal variability is important for a reliable NIS. Approach. To address the frequency and causes of neural signal variability in a spike-based NIS, we analyzed within-day fluctuations in spiking activity and action potential amplitude recorded with silicon microelectrode arrays implanted in the motor cortex of three people with tetraplegia (BrainGate pilot clinical trial, IDE). Main results. 84% of the recorded units showed a statistically significant change in apparent firing rate (3.8 +/- 8.71 Hz or 49% of the mean rate) across several-minute epochs of tasks performed on a single session, and 74% of the units showed a significant change in spike amplitude (3.7 +/- 6.5 mu V or 5.5% of mean spike amplitude). 40% of the recording sessions showed a significant correlation in the occurrence of amplitude changes across electrodes, suggesting array micro-movement. Despite the relatively frequent amplitude changes, only 15% of the observed within-day rate changes originated from recording artifacts such as spike amplitude change or electrical noise, while 85% of the rate changes most likely emerged from physiological mechanisms. Computer simulations confirmed that systematic rate changes of individual neurons could produce a directional 'bias' in the decoded neural cursor movements. Instability in apparent neuronal spike rates indeed yielded a directional bias in 56% of all performance assessments in participant cursor control (n = 2 participants, 108 and 20 assessments over two years), resulting in suboptimal performance in these sessions. Significance. We anticipate that signal acquisition and decoding methods that can adapt to the reported instabilities will further improve the performance of intracortically-based NISs.
C1 [Perge, Janos A.; Malik, Wasim Q.; Donoghue, John P.; Hochberg, Leigh R.] Brown Univ, Sch Engn, Providence, RI 02912 USA.
[Perge, Janos A.; Homer, Mark L.; Malik, Wasim Q.; Donoghue, John P.; Hochberg, Leigh R.] Brown Univ, Inst Brain Sci, Providence, RI 02912 USA.
[Perge, Janos A.; Malik, Wasim Q.; Donoghue, John P.; Hochberg, Leigh R.] Rehabil R&D Serv, Dept Vet Affairs Med Ctr, Ctr Neurorestorat & Neurotechnol, Providence, RI USA.
[Homer, Mark L.] Brown Univ, Providence, RI 02912 USA.
[Malik, Wasim Q.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
[Cash, Sydney; Eskandar, Emad; Hochberg, Leigh R.] Harvard Univ, Sch Med, Boston, MA USA.
[Cash, Sydney; Hochberg, Leigh R.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Eskandar, Emad] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA.
[Friehs, Gerhard] Rhode Isl Hosp, Dept Neurosurg, Providence, RI USA.
[Donoghue, John P.] Brown Univ, Dept Neurosci, Providence, RI 02912 USA.
RP Perge, JA (reprint author), Brown Univ, Sch Engn, Providence, RI 02912 USA.
EM janos_perge@brown.edu
OI Hochberg, Leigh/0000-0003-0261-2273
FU NIH: NIDCD [R01DC009899]; NIH: NICHD-NCMRR [N01HD53403, N01HD10018];
Rehabilitation Research and Development Service, Office of Research and
Development, Department of Veterans Affairs [B6310N, B6453R, B6459L];
DARPA REPAIR [N66001-10-C-2010]; Department of Defense (CIMIT USAMRAA);
Doris Duke Charitable Foundation; MGH-Deane Institute; Katie Samson
Foundation; Cyberkinetics Neurotechnology Systems, Inc.; Massachusetts
General Hospital; Spaulding Rehabilitation Hospital
FX We are grateful to participants S3, A1, and T1 for their dedication to
this research, to the caregiver staff at The Boston Home, to Cindy
Chestek for valuable comments on the manuscript, and to John Simeral for
contributing analysis software. The contents do not represent the views
of the Department of Veterans Affairs or the United States Government.
This work was supported by NIH: NIDCD (R01DC009899) and NICHD-NCMRR
(N01HD53403, N01HD10018); Rehabilitation Research and Development
Service, Office of Research and Development, Department of Veterans
Affairs (B6310N, B6453R, and B6459L); DARPA REPAIR (N66001-10-C-2010);
Department of Defense (CIMIT USAMRAA); Doris Duke Charitable Foundation,
MGH-Deane Institute, and Katie Samson Foundation. The pilot clinical
trial from which these data are derived was sponsored in part by
Cyberkinetics Neurotechnology Systems, Inc. JPD is a former Chief
Scientific Officer and director of Cyberkinetics Neurotechnology
Systems, Inc. (CKI); he held stocks and received compensation. LRH
received research support from Massachusetts General and Spaulding
Rehabilitation Hospitals, which in turn received clinical trial support
from CKI. CKI ceased operations in 2009. The BrainGate pilot clinical
trial is now directed by Massachusetts General Hospital. CAUTION:
Investigational Device. Limited by Federal Law to Investigational Use.
NR 67
TC 29
Z9 29
U1 0
U2 7
PU IOP PUBLISHING LTD
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 1741-2560
J9 J NEURAL ENG
JI J. Neural Eng.
PD JUN
PY 2013
VL 10
IS 3
AR 036004
DI 10.1088/1741-2560/10/3/036004
PG 14
WC Engineering, Biomedical; Neurosciences
SC Engineering; Neurosciences & Neurology
GA 152DM
UT WOS:000319510800007
PM 23574741
ER
PT J
AU Naab, F
Brown, R
Heidrich, S
AF Naab, Florence
Brown, Roger
Heidrich, Susan
TI Psychosocial Health of Infertile Ghanaian Women and Their Infertility
Beliefs
SO JOURNAL OF NURSING SCHOLARSHIP
LA English
DT Article
DE Beliefs; infertility; psychosocial; women
ID REPRESENTATIONAL APPROACH; PATIENT EDUCATION; TREATMENT-SEEKING;
SOUTH-AFRICA; RESPONSES; PREVALENCE; VALIDATION; CHILDREN; STRESS; TRIAL
AB Purpose The purpose of this study was to describe infertile women's psychosocial health problems and their infertility-related beliefs and examine the relationships between their beliefs about infertility and psychosocial health problems. Design The study was a descriptive correlational cross-sectional survey. Women (N = 203) who were receiving treatment for fertility problems in two public hospitals in Ghana were recruited. Methods Participants completed a Fertility Belief Questionnaire; measures of infertility-related stress, anxiety, social isolation, perceived stigma, and depressive symptoms; and sociodemographic and infertility-related health questions. Descriptive statistics, Pearson's correlations, and hierarchical regression analyses were performed. Findings The women reported high levels of infertility-related stress, low levels of anxiety, some social isolation, low levels of perceived stigma, and high levels of depressive symptoms. Beliefs that infertility has negative consequences and that one has a poor understanding of infertility were significantly related to infertility-related stress, social isolation, and depressive symptoms. Belief that infertility could be managed by personal control was significantly related to lower levels of anxiety and perceived stigma. Beliefs about consequences, illness coherence, and personal control explained significant proportions of the variances in anxiety, stress, social isolation, perceived stigma, and depressive symptoms. Conclusions Infertile women in Ghana have psychosocial health problems that are associated with their beliefs about infertility. Clinical Relevance Findings have implications for nursing care of infertile women in Ghana.
C1 [Naab, Florence] Univ Ghana, Dept Maternal & Child Hlth, Sch Nursing, Coll Hlth Sci, Legon, Accra, Ghana.
[Brown, Roger] Univ Wisconsin, Sch Nursing, Madison, WI USA.
[Brown, Roger] Univ Wisconsin, Sch Med, Madison, WI USA.
[Brown, Roger] Univ Wisconsin, Sch Publ Hlth, Madison, WI USA.
[Heidrich, Susan] Univ Wisconsin, Madison, WI USA.
[Heidrich, Susan] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA.
RP Naab, F (reprint author), Univ Ghana, Dept Maternal & Child Hlth, Sch Nursing, Coll Hlth Sci, POB LG 43, Legon Boundary, Accra, Ghana.
EM florencenaab@yahoo.com
NR 41
TC 4
Z9 4
U1 1
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1527-6546
J9 J NURS SCHOLARSHIP
JI J. Nurs. Scholarsh.
PD JUN
PY 2013
VL 45
IS 2
BP 132
EP 140
DI 10.1111/jnu.12013
PG 9
WC Nursing
SC Nursing
GA 157OA
UT WOS:000319906400005
PM 23731032
ER
PT J
AU Sherry, D
Fennessy, MM
Benavente, VG
Ruppar, TM
Collins, EG
AF Sherry, Daisy
Fennessy, Michelle M.
Benavente, Viola G.
Ruppar, Todd M.
Collins, Eileen G.
TI Important Considerations When Applying for a Postdoctoral Fellowship
SO JOURNAL OF NURSING SCHOLARSHIP
LA English
DT Article
DE Postdoctoral nurse fellowship; graduate training; nurse education
ID OPPORTUNITIES; GRANTS; NINR
AB Purpose To examine important decision points that graduates should consider before applying for a postdoctoral fellowship. Methods A literature review was performed. Findings and Conclusions A synthesis of the present data on the postdoctoral fellowship, eligibility criteria, application process, and important considerations was provided. Experiential knowledge from four present postdoctoral fellows was included. The goals, advantages, and disadvantages of the fellowship were discussed. In conclusion, the postdoctoral fellowship was examined to offer important considerations in the decision to pursue this opportunity. Clinical Relevance The clinical relevance of this article is related to the training and education of nurses to become the next generation of independent, successful scholars and scientists. Postdoctoral training adds valuable contributions and quality to the field of nursing.
C1 [Sherry, Daisy] US Dept Vet Affairs, Edward Hines Jr VA Hosp, Hines, IL 60141 USA.
[Fennessy, Michelle M.] Univ Calif Davis Hlth Syst, Betty Irene Moore Sch Nursing, Sacramento, CA USA.
[Benavente, Viola G.] Boston Coll, William F Connell Sch Nursing, Chestnut Hill, MA 02167 USA.
[Ruppar, Todd M.] Univ Missouri, Sinclair Sch Nursing, Columbia, MO USA.
[Collins, Eileen G.] US Dept Vet Affairs, Dept Rehabil, Hines, IL 60141 USA.
RP Sherry, D (reprint author), US Dept Vet Affairs, Edward Hines Jr VA Hosp, 5000 S 5th Ave 151H, Hines, IL 60141 USA.
EM daisyc6@juno.com
RI Ruppar, Todd/B-8091-2015
OI Ruppar, Todd/0000-0003-0794-5544
FU U.S. Department of Veterans Affairs; Gordon & Betty Moore Foundation;
Ruth L. Kirschstein National Research Institutional Training Program;
National Institutes of Health, National Institute of Nursing Research
[T32NR007106]; John A. Hartford Foundation; Atlantic Philanthropies
Claire M. Fagin Fellowship
FX Dr. Sherry is funded by the U.S. Department of Veterans Affairs
Postdoctoral Fellowship. Dr. Fennessy is funded by a fellowship through
the Gordon & Betty Moore Foundation. Dr. Benavente is funded by a Ruth
L. Kirschstein National Research Institutional Training Program funded
by the National Institutes of Health, National Institute of Nursing
Research, T32NR007106 Biobehavioral Nursing Research Training Program
(principal investigator Dr. Carol Landis). Dr. Ruppar is funded by a
John A. Hartford Foundation and Atlantic Philanthropies Claire M. Fagin
Fellowship.
NR 21
TC 0
Z9 0
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1527-6546
J9 J NURS SCHOLARSHIP
JI J. Nurs. Scholarsh.
PD JUN
PY 2013
VL 45
IS 2
BP 210
EP 218
DI 10.1111/jnu.12012
PG 9
WC Nursing
SC Nursing
GA 157OA
UT WOS:000319906400014
PM 23452068
ER
PT J
AU Epstein, AS
Volandes, AE
Chen, LY
Gary, KA
Li, YL
Agre, P
Levin, TT
Reidy, DL
Meng, RD
Segal, NH
Yu, KH
Abou-Alfa, GK
Janjigian, YY
Kelsen, DP
O'Reilly, EM
AF Epstein, Andrew S.
Volandes, Angelo E.
Chen, Ling Y.
Gary, Kristen A.
Li, Yuelin
Agre, Patricia
Levin, Tomer T.
Reidy, Diane L.
Meng, Raymond D.
Segal, Neil H.
Yu, Kenneth H.
Abou-Alfa, Ghassan K.
Janjigian, Yelena Y.
Kelsen, David P.
O'Reilly, Eileen M.
TI A Randomized Controlled Trial of a Cardiopulmonary Resuscitation Video
in Advance Care Planning for Progressive Pancreas and Hepatobiliary
Cancer Patients
SO JOURNAL OF PALLIATIVE MEDICINE
LA English
DT Article; Proceedings Paper
CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY JUN 01-06, 2012
CL Chicago, IL
SP Amer Soc Clin Oncol (ASCO)
ID OF-LIFE DISCUSSIONS; HOSPITALIZED-PATIENTS; ILL PATIENTS; DIRECTIVES;
DETERMINANTS; PREFERENCES; PHYSICIANS; PROGNOSES; SUPPORT; COHORT
AB Background: Cardiopulmonary resuscitation (CPR) is an important advance directive (AD) topic in patients with progressive cancer; however such discussions are challenging.
Objective: This study investigates whether video educational information about CPR engenders broader advance care planning (ACP) discourse.
Methods: Patients with progressive pancreas or hepatobiliary cancer were randomized to an educational CPR video or a similar CPR narrative. The primary end-point was the difference in ACP documentation one month posttest between arms. Secondary end-points included study impressions; pre- and post-intervention knowledge of and preferences for CPR and mechanical ventilation; and longitudinal patient outcomes.
Results: Fifty-six subjects were consented and analyzed. Rates of ACP documentation (either formal ADs or documented discussions) were 40% in the video arm (12/30) compared to 15% in the narrative arm (4/26), OR=3.6 [95% CI: 0.9-18.0], p = 0.07. Post-intervention knowledge was higher in both arms. Posttest, preferences for CPR had changed in the video arm but not in the narrative arm. Preferences regarding mechanical ventilation did not change in either arm. The majority of subjects in both arms reported the information as helpful and comfortable to discuss, and they recommended it to others. More deaths occurred in the video arm compared to the narrative arm, and more subjects died in hospice settings in the video arm.
Conclusions: This pilot randomized trial addressing downstream ACP effects of video versus narrative decision tools demonstrated a trend towards more ACP documentation in video subjects. This trend, as well as other video effects, is the subject of ongoing study.
C1 [Epstein, Andrew S.; Chen, Ling Y.; Gary, Kristen A.; Li, Yuelin; Agre, Patricia; Levin, Tomer T.; Reidy, Diane L.; Meng, Raymond D.; Segal, Neil H.; Yu, Kenneth H.; Abou-Alfa, Ghassan K.; Janjigian, Yelena Y.; Kelsen, David P.; O'Reilly, Eileen M.] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA.
[Volandes, Angelo E.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Epstein, AS (reprint author), Mem Sloan Kettering Canc Ctr, Div Gastrointestinal Med Oncol, 300 E 66th St,Room 1013, New York, NY 10065 USA.
EM epsteina@mskcc.org
RI Levin, Tomer/D-2997-2016
OI Levin, Tomer/0000-0001-5054-5103
FU NCI NIH HHS [P30 CA008748]
NR 34
TC 23
Z9 23
U1 5
U2 14
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 JUN
PY 2013
VL 16
IS 6
BP 623
EP 631
DI 10.1089/jpm.2012.0524
PG 9
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA 155GW
UT WOS:000319736900010
PM 23725233
ER
PT J
AU Rosenberg, AR
Baker, KS
Syrjala, KL
Back, AL
Wolfe, J
AF Rosenberg, Abby R.
Baker, K. Scott
Syrjala, Karen L.
Back, Anthony L.
Wolfe, Joanne
TI Promoting Resilience among Parents and Caregivers of Children with
Cancer
SO JOURNAL OF PALLIATIVE MEDICINE
LA English
DT Article
ID QUALITY-OF-LIFE; POSTTRAUMATIC-STRESS-DISORDER;
BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION;
CHILDHOOD-CANCER; PEDIATRIC ONCOLOGY; PSYCHOSOCIAL CARE; PSYCHOLOGICAL
DISTRESS; INDIVIDUAL-DIFFERENCES; FAMILY RESILIENCE
AB Background: Promoting resilience is an aspect of psychosocial care that affects patient and whole-family wellbeing. There is little consensus about how to define or promote resilience during and after pediatric cancer.
Objectives: The aims of this study were (1) to review the resilience literature in pediatric cancer settings; (2) to qualitatively ascertain caregiver-reported perceptions of resilience; and (3) to develop an integrative model of fixed and mutable factors of resilience among family members of children with cancer, with the goal of enabling better study and promotion of resilience among pediatric cancer families.
Methods: The study entailed qualitative analysis of small group interviews with eighteen bereaved parents and family members of children with cancer treated at Seattle Children's Hospital. Small-group interviews were conducted with members of each bereaved family. Participant statements were coded for thematic analysis. An integrative, comprehensive framework was then developed.
Results: Caregivers' personal appraisals of the cancer experience and their child's legacy shape their definitions of resilience. Described factors of resilience include baseline characteristics (i.e., inherent traits, prior expectations of cancer), processes that evolve over time (i.e., coping strategies, social support, provider interactions), and psychosocial outcomes (i.e., post-traumatic growth and lack of psychological distress). These elements were used to develop a testable model of resilience among family members of children with cancer.
Conclusions: Resilience is a complex construct that may be modifiable. Once validated, the proposed framework will not only serve as a model for clinicians, but may also facilitate the development of interventions aimed at promoting resilience in family members of children with cancer.
C1 [Rosenberg, Abby R.; Baker, K. Scott] Seattle Childrens Hosp, Seattle, WA 98105 USA.
[Rosenberg, Abby R.; Baker, K. Scott; Syrjala, Karen L.; Back, Anthony L.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Rosenberg, Abby R.; Baker, K. Scott; Syrjala, Karen L.; Back, Anthony L.] Univ Washington, Seattle, WA 98195 USA.
[Wolfe, Joanne] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Wolfe, Joanne] Childrens Hosp, Boston, MA 02115 USA.
[Wolfe, Joanne] Harvard Univ, Sch Med, Boston, MA USA.
RP Rosenberg, AR (reprint author), Seattle Childrens Hosp, Div Pediat Hematol Oncol, M-S MB 8-501,POB 5371, Seattle, WA 98105 USA.
EM abby.rosenberg@seattlechildrens.org
FU Ruth L. Kirschstein National Research Service Award [T32CA009351];
Conquer Cancer Foundation of ASCO Jane C. Wright Young Investigator
Award; ASCO; Conquer Cancer Foundation Board of Directors
FX Abby R. Rosenberg is a St. Baldrick's Foundation Fellow and was
supported by the Ruth L. Kirschstein National Research Service Award
T32CA009351 and a Conquer Cancer Foundation of ASCO Jane C. Wright Young
Investigator Award, supported by the ASCO and the Conquer Cancer
Foundation Board of Directors. Any opinions, findings, and conclusions
expressed in this material are those of the authors and do not
necessarily reflect those of the American Society of Clinical Oncology,
the Conquer Cancer Foundation, or the ASCO and the Conquer Cancer
Foundation Board of Directors.
NR 53
TC 22
Z9 23
U1 6
U2 42
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 JUN
PY 2013
VL 16
IS 6
BP 645
EP 652
DI 10.1089/jpm.2012.0494
PG 8
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA 155GW
UT WOS:000319736900013
PM 23646887
ER
PT J
AU Smith, AK
Thai, JN
Bakitas, MA
Meier, DE
Spragens, LH
Temel, JS
Weissman, DE
Rabow, MW
AF Smith, Alexander K.
Thai, Julie N.
Bakitas, Marie A.
Meier, Diane E.
Spragens, Lynn H.
Temel, Jennifer S.
Weissman, David E.
Rabow, Michael W.
TI The Diverse Landscape of Palliative Care Clinics
SO JOURNAL OF PALLIATIVE MEDICINE
LA English
DT Article
ID OUTPATIENT; CANCER; ONCOLOGY; CENTERS
AB Background: Many health care organizations are interested in instituting a palliative care clinic. However, there are insufficient published data regarding existing practices to inform the development of new programs.
Objective: Our objective was to obtain in-depth information about palliative care clinics.
Methods: We conducted a cross-sectional survey of 20 outpatient palliative care practices in diverse care settings. The survey included both closed-and open-ended questions regarding practice size, utilization of services, staffing, referrals, services offered, funding, impetus for starting, and challenges.
Results: Twenty of 21 (95%) practices responded. Practices self-identified as: hospital-based (n = 7), within an oncology division/cancer center (n = 5), part of an integrated health system (n = 6), and hospice-based (n = 2). The majority of referred patients had a cancer diagnosis. Additional common diagnoses included chronic obstructive pulmonary disease, neurologic disorders, and congestive heart failure. All practices ranked "pain management" and "determining goals of care" as the most common reasons for referrals. Twelve practices staffed fewer than 5 half-days of clinic per week, with 7 operating only one half-day per week. Practices were staffed by a mixture of physicians, advanced practice nurses or nurse practitioners, nurses, or social workers. Eighteen practices expected their practice to grow within the next year. Eleven practices noted a staffing shortage and 8 had a wait time of a week or more for a new patient appointment. Only 12 practices provide 24/7 coverage. Billing and institutional support were the most common funding sources. Most practices described starting because inpatient palliative providers perceived poor quality outpatient care in the outpatient setting. The most common challenges included: funding for staffing (11) and being overwhelmed with referrals (8).
Conclusions: Once established, outpatient palliative care practices anticipate rapid growth. In this context, outpatient practices must plan for increased staffing and develop a sustainable financial model.
C1 [Smith, Alexander K.; Thai, Julie N.] Univ Calif San Francisco, Dept Med, Div Geriatr, San Francisco, CA 94941 USA.
[Rabow, Michael W.] Univ Calif San Francisco, Dept Med, Div Gen Internal Med, San Francisco, CA 94941 USA.
[Smith, Alexander K.; Thai, Julie N.] San Francisco VA Med Ctr, San Francisco, CA USA.
[Bakitas, Marie A.] Dartmouth Hitchcock Med Ctr, Dartmouth Med Sch, Sect Palliat Med, Dept Anesthesiol, Lebanon, NH 03766 USA.
[Meier, Diane E.] Mt Sinai Med Ctr, Dept Geriatr & Palliat Med, New York, NY 10029 USA.
[Spragens, Lynn H.] Spragens & Associates LLC, Durham, NC USA.
[Temel, Jennifer S.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Weissman, David E.] Med Coll Wisconsin, Palliat Care Ctr, Dept Internal Med, Milwaukee, WI 53226 USA.
RP Smith, AK (reprint author), Univ Calif San Francisco, 4150 Clement St 181G, San Francisco, CA 94941 USA.
EM aksmith@ucsf.edu
OI Bakitas, Marie/0000-0002-2913-2053
FU National Center for Research Resources UCSF-CTSI [UL1 RR024131]; NINR
[1R01NR011871-01]
FX Dr. Smith was supported by the National Center for Research Resources
UCSF-CTSI (UL1 RR024131). Marie A. Bakitas, APRN, DnSc, was support by
NINR grant number 1R01NR011871-01.
NR 9
TC 16
Z9 16
U1 1
U2 8
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 JUN
PY 2013
VL 16
IS 6
BP 661
EP 668
DI 10.1089/jpm.2012.0469
PG 8
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA 155GW
UT WOS:000319736900015
PM 23662953
ER
PT J
AU Qiu, JY
Chen, WJ
Gao, XF
Xu, Y
Tong, HQ
Yang, M
Xiao, ZP
Yang, M
AF Qiu, Jianyin
Chen, Weijun
Gao, Xiufei
Xu, Yong
Tong, Huiqi
Yang, Min
Xiao, Zeping
Yang, Min
TI A randomized controlled trial of group cognitive behavioral therapy for
Chinese breast cancer patients with major depression
SO JOURNAL OF PSYCHOSOMATIC OBSTETRICS AND GYNECOLOGY
LA English
DT Article
DE Breast cancer; group cognitive behavioral therapy; major depression
ID WOMEN; PREVALENCE; DISORDERS; SURVIVORS; INTERVENTION; SYMPTOMS;
EFFICACY; ANXIETY
AB Background: This study aims to evaluate the effects of Group Cognitive Behavioral Therapy (GCBT) in treating major depression in Chinese women with breast cancer.
Methods: Sixty-two breast cancer patients diagnosed with major depression were randomly assigned to GCBT group (N=31) or a waiting list control group provided with an educational booklet (N=31). The primary outcome measure was the 17-Item Hamilton Depression Rating Scale (17-HAMD). The second outcome measures were Self-Rating Anxiety Scale, Functional Assessment of Cancer Therapy - Breast and Self-Esteem Scale (SES). Assessments were carried out at completion of the study and six-month afterwards.
Results: Patients in the GCBT group had a significant reduction in the 17-HAMD mean score by 9 points (p<0.001), more than any reduction among patients in the control group from baseline to the end of therapy and a significant 7 points (p<0.001) more reduction from baseline to six-month follow-up. GCBT also yielded significantly greater improvement than the control group with regard to quality of life (QoL; p<0.01) and self-esteem (p<0.05). No significant differences were found between groups on improving anxiety (p>0.05).
Conclusion: The results of this trial suggest that GCBT is effective for treating major depression, as well as for improving QoL and self-esteem in breast cancer patients.
C1 [Qiu, Jianyin; Chen, Weijun; Xu, Yong; Xiao, Zeping] Shanghai Jiao Tong Univ, Dept Clin Psychol, Shanghai Mental Hlth Ctr, Sch Med, Shanghai 200030, Peoples R China.
[Gao, Xiufei] Shanghai Univ TCM, Longhua Hosp, Dept Breast Care, Shanghai, Peoples R China.
[Tong, Huiqi] San Francisco VA Med Ctr, Womens Clin, San Francisco, CA USA.
[Yang, Min; Yang, Min] Univ Nottingham, Dept Psychiat, Nottingham NG7 2RD, England.
RP Yang, M (reprint author), Univ Nottingham, Dept Psychiat, Univ Pk, Nottingham NG7 2RD, England.
EM Min.Yang@nottingham.ac.uk
FU WHO [WP/2006/CHN/MNH/2.4/001]
FX This study was funded by grant number WP/2006/CHN/MNH/2.4/001 from WHO.
NR 42
TC 8
Z9 10
U1 3
U2 26
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 0167-482X
J9 J PSYCHOSOM OBST GYN
JI J. Psychosomat. Obstet. Gynecol.
PD JUN
PY 2013
VL 34
IS 2
BP 60
EP 67
DI 10.3109/0167482X.2013.766791
PG 8
WC Psychology, Clinical; Obstetrics & Gynecology; Psychiatry
SC Psychology; Obstetrics & Gynecology; Psychiatry
GA 155LB
UT WOS:000319748300002
PM 23646866
ER
PT J
AU Appleton, KM
Luttrell, LM
AF Appleton, Kathryn M.
Luttrell, Louis M.
TI Emergent biological properties of arrestin pathway-selective biased
agonism
SO JOURNAL OF RECEPTORS AND SIGNAL TRANSDUCTION
LA English
DT Article
DE Arrestin; functional genomics; functional selectivity; G protein-coupled
receptor; heterotrimeric G protein; pharmacology
ID PROTEIN-COUPLED RECEPTOR; PARATHYROID-HORMONE; BETA(2)-ADRENERGIC
RECEPTOR; CRYSTAL-STRUCTURE; CARDIAC MYOCYTES; LIGAND EFFICACY; IN-VIVO;
ACTIVATION; REVEALS; ALLOSTERISM
AB Our growing appreciation of the pluridimensionality of G protein-coupled receptor ( GPCR) signaling, combined with the phenomenon of orthosteric ligand "bias'', has created the possibility of drugs that selectively modulate different aspects of GPCR function for therapeutic benefit. When viewed from the short-term perspective, e.g. changes in receptor conformation, effector coupling or second messenger generation, biased ligands appear to activate a subset of the response profile produced by a conventional agonist. Yet when examined in vivo, the limited data available suggest that biased ligand effects can diverge from their conventional counterparts in ways that cannot be predicted from their in vitro efficacy profile. What is currently missing, at least with respect to G protein and arrestin pathway-selective ligands, is a rational framework for relating the in vitro efficacy of a "biased'' agonist to its in vivo actions that will enable drug screening programs to identify ligands with the desired biological effects.
C1 [Appleton, Kathryn M.] Med Univ S Carolina, Coll Pharm, Dept Pharmaceut & Biomed Sci, Charleston, SC 29425 USA.
[Luttrell, Louis M.] Med Univ S Carolina, Coll Med, Dept Med, Charleston, SC 29425 USA.
[Luttrell, Louis M.] Med Univ S Carolina, Coll Med, Dept Biochem & Mol Biol, Charleston, SC 29425 USA.
[Luttrell, Louis M.] Ralph H Johnson Vet Affairs Med Ctr, Res Serv, Charleston, SC USA.
RP Luttrell, LM (reprint author), Div Endocrinol Diabet & Med Genet, 96 Jonathan Lucas St,Suite 816 CSB,MSC624, Charleston, SC 29425 USA.
EM luttrell@musc.edu
FU NIDDK NIH HHS [DK55524, DK64353]
NR 34
TC 5
Z9 5
U1 0
U2 12
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1079-9893
J9 J RECEPT SIG TRANSD
JI J. Recept. Signal Transduct.
PD JUN
PY 2013
VL 33
IS 3
BP 153
EP 161
DI 10.3109/10799893.2013.769004
PG 9
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 155LI
UT WOS:000319749200005
PM 23448506
ER
PT J
AU Appleton, KM
Lee, MH
Alele, C
Luttrell, DK
Peterson, YK
Luttrell, LM
AF Appleton, Kathryn M.
Lee, Mi-Hye
Alele, Christine
Luttrell, Deirdre K.
Peterson, Yuri K.
Luttrell, Louis M.
TI DISSOCIATION OF ARRESTIN-DEPENDENT SIGNALING FROM RECEPTOR
DESENSITIZATION USING FUNCTIONALLY-SELECTIVE PARATHYROID HORMONE
RECEPTOR LIGANDS
SO JOURNAL OF RECEPTORS AND SIGNAL TRANSDUCTION
LA English
DT Meeting Abstract
C1 [Appleton, Kathryn M.; Peterson, Yuri K.] Med Univ S Carolina, Coll Pharm, Dept Pharmaceut & Biomed Sci, Charleston, SC 29425 USA.
[Lee, Mi-Hye; Alele, Christine; Luttrell, Louis M.] Med Univ S Carolina, Dept Med & Biochem & Mol Biol, Charleston, SC 29425 USA.
[Luttrell, Deirdre K.] Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA.
[Luttrell, Louis M.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1079-9893
J9 J RECEPT SIG TRANSD
JI J. Recept. Signal Transduct.
PD JUN
PY 2013
VL 33
IS 3
BP 184
EP 184
PG 1
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 155LI
UT WOS:000319749200011
ER
PT J
AU Leonard, A
Appleton, KM
Luttrell, LM
Peterson, YK
AF Leonard, Anthony
Appleton, Kathryn M.
Luttrell, Louis M.
Peterson, Yuri K.
TI A HIGH-CONTENT, LIVE-CELL, AND REAL-TIME APPROACH TO THE QUANTITATION OF
LIGAND INDUCED B-ARRESTIN2 AND CLASS A/CLASS B GPCR MOBILIZATION
SO JOURNAL OF RECEPTORS AND SIGNAL TRANSDUCTION
LA English
DT Meeting Abstract
C1 [Leonard, Anthony; Appleton, Kathryn M.; Peterson, Yuri K.] Med Univ S Carolina, Coll Pharm, Dept Pharmaceut & Biomed Sci, Charleston, SC 29425 USA.
[Luttrell, Louis M.] Med Univ S Carolina, Dept Med & Biochem & Mol Biol, Charleston, SC 29425 USA.
[Luttrell, Louis M.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1079-9893
J9 J RECEPT SIG TRANSD
JI J. Recept. Signal Transduct.
PD JUN
PY 2013
VL 33
IS 3
BP 199
EP 199
PG 1
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 155LI
UT WOS:000319749200057
ER
PT J
AU McDougle, CJ
AF McDougle, Christopher J.
TI Sounding a Wake-Up Call: Improving the Lives of Adults With Autism
SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY
LA English
DT Editorial Material
C1 [McDougle, Christopher J.] Massachusetts Gen Hosp, Lexington, MA 02421 USA.
RP McDougle, CJ (reprint author), Massachusetts Gen Hosp, Dept Psychiat & Pediat, 1 Maguire Rd, Lexington, MA 02421 USA.
EM cmcdougle@partners.org
NR 9
TC 4
Z9 4
U1 0
U2 12
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0890-8567
J9 J AM ACAD CHILD PSY
JI J. Am. Acad. Child Adolesc. Psychiatr.
PD JUN
PY 2013
VL 52
IS 6
BP 566
EP 568
DI 10.1016/j.jaac.2013.03.013
PG 3
WC Psychology, Developmental; Pediatrics; Psychiatry
SC Psychology; Pediatrics; Psychiatry
GA 160UZ
UT WOS:000320147300003
PM 23702444
ER
PT J
AU Burstein, HJ
AF Burstein, Harold J.
TI Lou Gehrig, Angelina Jolie, and Cancer Genetics
SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK
LA English
DT Editorial Material
C1 [Burstein, Harold J.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[Burstein, Harold J.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Burstein, Harold J.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Burstein, Harold J.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Burstein, HJ (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
NR 1
TC 2
Z9 2
U1 0
U2 4
PU HARBORSIDE PRESS
PI COLD SPRING HARBOR
PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA
SN 1540-1405
J9 J NATL COMPR CANC NE
JI J. Natl. Compr. Cancer Netw.
PD JUN
PY 2013
VL 11
IS 6
BP 631
EP 632
PG 2
WC Oncology
SC Oncology
GA 158MJ
UT WOS:000319975400001
PM 23744861
ER
PT J
AU Kumar, P
Moy, B
AF Kumar, Pallavi
Moy, Beverly
TI Cancer Health Disparities and the Cost of Cancer Care: Payment Model
Issues
SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK
LA English
DT Editorial Material
ID AMERICAN SOCIETY; INSURANCE; MEDICAID; ASSOCIATION
C1 [Moy, Beverly] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
NR 13
TC 3
Z9 3
U1 0
U2 1
PU HARBORSIDE PRESS
PI COLD SPRING HARBOR
PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA
SN 1540-1405
J9 J NATL COMPR CANC NE
JI J. Natl. Compr. Cancer Netw.
PD JUN
PY 2013
VL 11
IS 6
BP 633
EP 636
PG 4
WC Oncology
SC Oncology
GA 158MJ
UT WOS:000319975400002
PM 23744862
ER
PT J
AU Ettinger, DS
Akerley, W
Borghaei, H
Chang, AC
Cheney, RT
Chirieac, LR
D'Amico, TA
Demmy, TL
Govindan, R
Grannis, FW
Grant, SC
Horn, L
Jahan, TM
Komaki, R
Kong, FM
Kris, MG
Krug, LM
Lackner, RP
Lennes, IT
Loo, BW
Martins, R
Otterson, GA
Patel, JD
Pinder-Schenck, MC
Pisters, KM
Reckamp, K
Riely, GJ
Rohren, E
Shapiro, TA
Swanson, SJ
Tauer, K
Wood, DE
Yang, SC
Gregory, K
Hughes, M
AF Ettinger, David S.
Akerley, Wallace
Borghaei, Hossein
Chang, Andrew C.
Cheney, Richard T.
Chirieac, Lucian R.
D'Amico, Thomas A.
Demmy, Todd L.
Govindan, Ramaswamy
Grannis, Frederic W., Jr.
Grant, Stefan C.
Horn, Leora
Jahan, Thierry M.
Komaki, Ritsuko
Kong, Feng-Ming (Spring)
Kris, Mark G.
Krug, Lee M.
Lackner, Rudy P.
Lennes, Inga T.
Loo, Billy W., Jr.
Martins, Renato
Otterson, Gregory A.
Patel, Jyoti D.
Pinder-Schenck, Mary C.
Pisters, Katherine M.
Reckamp, Karen
Riely, Gregory J.
Rohren, Eric
Shapiro, Theresa A.
Swanson, Scott J.
Tauer, Kurt
Wood, Douglas E.
Yang, Stephen C.
Gregory, Kristina
Hughes, Miranda
TI Non-Small Cell Lung Cancer, Version 2.2013 Featured Updates to the NCCN
Guidelines
SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK
LA English
DT Article
ID SUBSOLID PULMONARY NODULES; NEEDLE ASPIRATION; COMPUTED-TOMOGRAPHY;
TOBACCO DEPENDENCE; FLEISCHNER-SOCIETY; UNITED-STATES; CT SCANS;
EPIDEMIOLOGY; MANAGEMENT; MORTALITY
AB These NCCN Guidelines Insights focus on the diagnostic evaluation of suspected lung cancer. This topic was the subject of a major update in the 2013 NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer. The NCCN Guidelines Insights focus on the major updates in the NCCN Guidelines and discuss the new updates in greater detail.
C1 [Ettinger, David S.] Sidney Kimmel Comprehens Canc Ctr Johns Hop, Sidney, BC, Canada.
[Akerley, Wallace] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA.
[Borghaei, Hossein] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
[Chang, Andrew C.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA.
[Cheney, Richard T.; Demmy, Todd L.] Roswell Pk Canc Inst, Buffalo, NY USA.
[Chirieac, Lucian R.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA.
[Grannis, Frederic W., Jr.] Washington Univ, Sch Med, St Louis, MO 63130 USA.
[Grant, Stefan C.] City Hope Comprehens Canc Ctr, Duarte, CA USA.
[Horn, Leora] Univ Alabama, Comprehens Canc Ctr, Tuscaloosa, AL 35487 USA.
[Jahan, Thierry M.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA.
[Jahan, Thierry M.] UCSF Helen Diller Family, Comprehens Canc Ctr, San Francisco, CA USA.
[Komaki, Ritsuko] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Kong, Feng-Ming (Spring); Kris, Mark G.; Krug, Lee M.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Lackner, Rudy P.] Nebraska Med Ctr, UNMC Eppley Canc Ctr, Omaha, NE USA.
[Lennes, Inga T.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
[Loo, Billy W., Jr.] Stanford Canc Inst, Stanford, CA USA.
[Martins, Renato] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA.
[Otterson, Gregory A.] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA.
[Patel, Jyoti D.] Solove Res Inst, Columbus, OH USA.
[Pinder-Schenck, Mary C.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA.
[Pinder-Schenck, Mary C.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA.
[Gregory, Kristina; Hughes, Miranda] Univ Tennessee, Inst Canc, Knoxville, TN 37996 USA.
RP Ettinger, DS (reprint author), Sidney Kimmel Comprehens Canc Ctr Johns Hop, Sidney, BC, Canada.
OI Chang, Andrew/0000-0001-9506-0425; Reckamp, Karen/0000-0002-9213-0325
FU Exelixis Inc.; Abraxis Oncology; Boehringer Ingelheim GmbH; Celgene
Corporation; Genentech, Inc.; GlaxoSmithKline; Pfizer Inc;
Pharmacyclics; Eli Lilly and Company; Eisai, Inc.; Millennium; Takeda
Oncology Company; Teva Pharmaceuticals; Bayer HealthCare Pharmaceuticals
Inc.; Endo Pharmaceuticals and HealthTronics; Genentech; ARIAD
Pharmaceuticals, Inc.
FX Dr. Martins: PI for Bayer HealthCare; Eisai Inc.; Genentech, Inc.;
Novartis Pharmaceuticals Corporation; and Pfizer Inc. Receives research
funding from Exelixis Inc.; Dr. Otterson: Receives research funding from
Abraxis Oncology; Boehringer Ingelheim GmbH; Celgene Corporation;
Genentech, Inc.; GlaxoSmithKline; Pfizer Inc; and Pharmacyclics.
Consultant for Abraxis Bioscience, Inc. Advisory board member for
Genentech, Inc.; Dr. Patel: Receives research funding from Eli Lilly and
Company. Advisory board member for Genentech, Inc.; Supported by
educational grants from Eisai, Inc.; Millennium: The Takeda Oncology
Company; Teva Pharmaceuticals; Bayer HealthCare Pharmaceuticals Inc.;
Celgene Corporation; Endo Pharmaceuticals and HealthTronics; Genentech;
and ARIAD Pharmaceuticals, Inc.
NR 36
TC 105
Z9 122
U1 3
U2 11
PU HARBORSIDE PRESS
PI COLD SPRING HARBOR
PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA
SN 1540-1405
J9 J NATL COMPR CANC NE
JI J. Natl. Compr. Cancer Netw.
PD JUN
PY 2013
VL 11
IS 6
BP 645
EP 653
PG 9
WC Oncology
SC Oncology
GA 158MJ
UT WOS:000319975400004
PM 23744864
ER
PT J
AU Biermann, JS
Adkins, DR
Agulnik, M
Benjamin, RS
Brigman, B
Butrynski, JE
Cheong, D
Chow, W
Curry, WT
Frassica, DA
Frassica, FJ
Hande, KR
Hornicek, FJ
Jones, RL
Mayerson, J
McGarry, SV
McGrath, B
Morris, CD
O'Donnell, RJ
Randall, RL
Santana, VM
Satcher, RL
Siegel, HJ
von Mehren, M
Bergman, MA
Sundar, H
AF Biermann, J. Sybil
Adkins, Douglas R.
Agulnik, Mark
Benjamin, Robert S.
Brigman, Brian
Butrynski, James E.
Cheong, David
Chow, Warren
Curry, William T.
Frassica, Deborah A.
Frassica, Frank J.
Hande, Kenneth R.
Hornicek, Francis J.
Jones, Robin L.
Mayerson, Joel
McGarry, Sean V.
McGrath, Brian
Morris, Carol D.
O'Donnell, Richard J.
Randall, R. Lor
Santana, Victor M.
Satcher, Robert L.
Siegel, Herrick J.
von Mehren, Margaret
Bergman, Mary Anne
Sundar, Hema
TI Bone Cancer Clinical Practice Guidelines in Oncology
SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK
LA English
DT Review
ID GIANT-CELL TUMOR; SCANDINAVIAN-SARCOMA-GROUP; HIGH-GRADE OSTEOSARCOMA;
TERM-FOLLOW-UP; POSITRON-EMISSION-TOMOGRAPHY; CORE NEEDLE-BIOPSY; CARBON
ION RADIOTHERAPY; DEDIFFERENTIATED PAROSTEAL OSTEOSARCOMA;
INTENSITY-MODULATED RADIOTHERAPY; SELECTIVE ARTERIAL EMBOLIZATION
AB Primary bone cancers are extremely rare neoplasms, accounting for fewer than 0.2% of all cancers. The evaluation and treatment of patients with bone cancers requires a multidisciplinary team of physicians, including musculoskeletal, medical, and radiation oncologists, and surgeons and radiologists with demonstrated expertise in the management of these tumors. Long-term surveillance and follow-up are necessary for the management of treatment late effects related to surgery, radiation therapy, and chemotherapy. These guidelines discuss the management of chordoma, giant cell tumor of the bone, and osteosarcoma.
C1 [Biermann, J. Sybil] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA.
[Adkins, Douglas R.] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA.
[Adkins, Douglas R.] Washington Univ, Sch Med, St Louis, MO 63130 USA.
[Agulnik, Mark] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA.
[Benjamin, Robert S.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Butrynski, James E.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA.
[Cheong, David] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA.
[Chow, Warren] City Hope Comprehens Canc Ctr, Duarte, CA USA.
[Curry, William T.; Hornicek, Francis J.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
[Frassica, Deborah A.; Frassica, Frank J.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Sidney, BC, Canada.
[Hande, Kenneth R.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA.
[Jones, Robin L.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA.
[Mayerson, Joel] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA.
[Mayerson, Joel] Solove Res Inst, Columbus, OH USA.
[McGarry, Sean V.] Nebraska Med Ctr, UNMC Eppley Canc Ctr, Omaha, NE USA.
[McGrath, Brian] Roswell Pk Canc Inst, Buffalo, NY USA.
[Morris, Carol D.] Mem Sloan Kettering Canc Ctr, New York, NY USA.
[Randall, R. Lor] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA.
[Santana, Victor M.] Univ Tennessee, Hlth Sci Ctr, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA.
[Siegel, Herrick J.] Univ Alabama, Ctr Comprehens Canc, Tuscaloosa, AL 35487 USA.
[Bergman, Mary Anne] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
RP Biermann, JS (reprint author), Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA.
NR 236
TC 23
Z9 23
U1 0
U2 12
PU HARBORSIDE PRESS
PI COLD SPRING HARBOR
PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA
SN 1540-1405
J9 J NATL COMPR CANC NE
JI J. Natl. Compr. Cancer Netw.
PD JUN
PY 2013
VL 11
IS 6
BP 688
EP 723
PG 36
WC Oncology
SC Oncology
GA 158MJ
UT WOS:000319975400008
PM 23744868
ER
PT J
AU Wachen, JS
Shipherd, JC
Suvak, M
Vogt, D
King, LA
King, DW
AF Wachen, Jennifer Schuster
Shipherd, Jillian C.
Suvak, Michael
Vogt, Dawne
King, Lynda A.
King, Daniel W.
TI Posttraumatic Stress Symptomatology as a Mediator of the Relationship
Between Warzone Exposure and Physical Health Symptoms in Men and Women
SO JOURNAL OF TRAUMATIC STRESS
LA English
DT Article
ID GULF-WAR VETERANS; SEXUAL-HARASSMENT; PERCEIVED HEALTH; MILITARY
PERSONNEL; COMBAT EXPOSURE; CHRONIC PAIN; DISORDER; ILLNESS; TRAUMA;
SAMPLE
AB The mediating role of posttraumatic stress symptomatology (PSS) on the association between warzone exposure and physical health symptoms in 7 bodily systems (cardiovascular, dermatological, gastrointestinal, genitourinary, musculoskeletal, neurological, and pulmonary) was examined. We also examined if mediation effects varied as a function of sex. A sample of 317 U. S. Gulf war veterans was assessed for warzone exposure, PSS, and physical health symptoms 10 years after deployment. PSS was significantly associated with postdeployment physical health in all symptom categories when accounting for predeployment health (with effect sizes ranging from a 1.27-1.64 increase in the likelihood of postdeployment physical health symptoms with a 1 standard deviation increase in the PSS symptoms). PSS severity mediated the relationship between warzone exposure and postdeployment symptoms in all physical health domains (with percent mediation ranging 44%-75%). A significant Warzone Exposure x PSS interaction emerged for 5 outcomes such that the effect of PSS on physical health was stronger for veterans reporting lower warzone exposure. No significant interactions with sex emerged. These findings suggest the important influence of PSS on physical health symptoms for both men and women.
C1 [Wachen, Jennifer Schuster; Shipherd, Jillian C.; Suvak, Michael; Vogt, Dawne; King, Lynda A.] VA Boston Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA 02130 USA.
[Wachen, Jennifer Schuster; Shipherd, Jillian C.; Vogt, Dawne; King, Lynda A.; King, Daniel W.] Boston Univ, Sch Med, Boston, MA 02118 USA.
[King, Daniel W.] VA Boston Healthcare Syst, Natl Ctr PTSD, Behav Sci Div, Boston, MA 02130 USA.
RP Wachen, JS (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div, 150 South Huntington Ave 116B-3, Boston, MA 02130 USA.
EM Jennifer.Wachen@va.gov
NR 48
TC 4
Z9 4
U1 6
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0894-9867
J9 J TRAUMA STRESS
JI J. Trauma Stress
PD JUN
PY 2013
VL 26
IS 3
BP 319
EP 328
DI 10.1002/jts.21818
PG 10
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA 157GA
UT WOS:000319882800003
PM 23695839
ER
PT J
AU Wolf, EJ
Harrington, KM
Reardon, AF
Castillo, D
Taft, CT
Miller, MW
AF Wolf, Erika J.
Harrington, Kelly M.
Reardon, Annemarie F.
Castillo, Diane
Taft, Casey T.
Miller, Mark W.
TI A Dyadic Analysis of the Influence of Trauma Exposure and Posttraumatic
Stress Disorder Severity on Intimate Partner Aggression
SO JOURNAL OF TRAUMATIC STRESS
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; MALE VIETNAM VETERANS; INTERDEPENDENCE
MODEL; RELATIONSHIP ABUSE; SYMPTOMS; PERPETRATION; SCALE; PTSD;
ASSOCIATIONS; DISTRESS
AB This study used structural equation modeling to evaluate a mediation model of the relationship between trauma exposure, posttraumatic stress disorder (PTSD) symptoms, and perpetration of intimate partner physical and psychological aggression in trauma-exposed veterans and their cohabitating spouses (n = 286 couples; 88% male veteran and female spouse, 80.8% White, non-Hispanic). Dyadic data analyses were used to simultaneously evaluate actor and partner effects using the actor-partner interdependence model (Kashy & Kenny, 2000). The primary hypothesis was that PTSD would mediate the association between trauma exposure and intimate partner physical and psychological aggression with these effects evident both within and across members of a couple (i.e., actor and partner effects). The best-fitting model included (a) equivalent actor and partner direct effects of trauma on veterans' acts of psychological aggression (beta = .17 to .20, p = .001), and (b) equivalent actor and partner indirect effects via PTSD on veterans' acts of physical aggression (beta = .08 to .10, p < .001). There were no direct or indirect effects predicting the spouses' aggression. Results suggest it is important to consider the trauma histories and possible presence of PTSD in both partners as this may be a point of intervention when treating distressed couples.
C1 [Wolf, Erika J.; Reardon, Annemarie F.; Taft, Casey T.; Miller, Mark W.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA.
[Wolf, Erika J.; Taft, Casey T.; Miller, Mark W.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA.
[Harrington, Kelly M.] VA Boston Healthcare Syst, MAVERIC, Boston, MA 02130 USA.
[Castillo, Diane] VA New Mexico Healthcare Syst, Albuquerque, NM USA.
RP Miller, MW (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD 116B 2, 150 South Huntington Ave, Boston, MA 02130 USA.
EM mark.miller5@va.gov
RI Miller, Mark/G-7322-2011;
OI Miller, Mark/0000-0001-6393-8563; Wolf, Erika/0000-0003-2666-2435
FU Intramural VA [CDA-2-067-10S]; NIMH NIH HHS [R01 MH079806]
NR 47
TC 6
Z9 6
U1 0
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0894-9867
J9 J TRAUMA STRESS
JI J. Trauma Stress
PD JUN
PY 2013
VL 26
IS 3
BP 329
EP 337
DI 10.1002/jts.21805
PG 9
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA 157GA
UT WOS:000319882800004
PM 23636815
ER
PT J
AU Sripada, RK
Rauch, SAM
Tuerk, PW
Smith, E
Defever, AM
Mayer, RA
Messina, M
Venners, M
AF Sripada, Rebecca K.
Rauch, Sheila A. M.
Tuerk, Peter W.
Smith, Erin
Defever, Andrew M.
Mayer, Rebecca A.
Messina, Michael
Venners, Margaret
TI Mild Traumatic Brain Injury and Treatment Response in Prolonged Exposure
for PTSD
SO JOURNAL OF TRAUMATIC STRESS
LA English
DT Article
ID POSTTRAUMATIC-STRESS-DISORDER; PERSISTENT POSTCONCUSSIVE SYMPTOMS;
RANDOMIZED CONTROLLED-TRIAL; THERAPY; VETERANS; IRAQ; METAANALYSIS;
AFGHANISTAN; MECHANISMS; CLINICIAN
AB A proportion of U.S. veterans returning from Iraq and Afghanistan have experienced mild traumatic brain injury (mTBI), which is associated with increased risk for developing posttraumatic stress disorder (PTSD). Prolonged Exposure (PE) has proven effectiveness in the treatment of PTSD; however, some clinicians have reservations about using PE with individuals with a history of mTBI. We examined the impact of PE for veterans with PTSD and with or without a history of mTBI in a naturalistic sample of 51 veterans who received PE at a Veterans Health Administration PTSD clinic. We also analyzed previously collected data from a controlled trial of 22 veterans randomly assigned to PE or present centered therapy. For both sets of data, we found that PE reduced symptom levels and we also did not detect an effect for mTBI, suggesting that PE may be helpful for individuals with PTSD and a history of mTBI.
C1 [Sripada, Rebecca K.; Rauch, Sheila A. M.; Smith, Erin; Defever, Andrew M.; Mayer, Rebecca A.; Messina, Michael; Venners, Margaret] Univ Michigan, Sch Med, VA Ann Arbor Hlth Care Syst, Ann Arbor, MI USA.
[Tuerk, Peter W.] Med Univ S Carolina, Ralph H Johnson VAMC, Charleston, SC 29425 USA.
RP Sripada, RK (reprint author), VA Serious Mental Illness Treatment Resource & Ev, Ann Arbor, MI USA.
EM rekaufma@umich.edu
RI Rauch, Sheila/K-4450-2015;
OI Rauch, Sheila/0000-0001-9686-4011; Sripada, Rebecca/0000-0002-2844-3458
NR 48
TC 14
Z9 14
U1 1
U2 13
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0894-9867
J9 J TRAUMA STRESS
JI J. Trauma Stress
PD JUN
PY 2013
VL 26
IS 3
BP 369
EP 375
DI 10.1002/jts.21813
PG 7
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA 157GA
UT WOS:000319882800009
PM 23696427
ER
PT J
AU Steenkamp, MM
Litz, BT
Dickstein, BD
Salters-Pedneault, K
Hofmann, SG
AF Steenkamp, Maria M.
Litz, Brett T.
Dickstein, Benjamin D.
Salters-Pedneault, Kristalyn
Hofmann, Stefan G.
TI What Is the Typical Response to Sexual Assault? Reply to Bonanno (2013)
SO JOURNAL OF TRAUMATIC STRESS
LA English
DT Editorial Material
ID POSTTRAUMATIC-STRESS-DISORDER; RESILIENCE; TRAJECTORIES; TRAUMA;
SYMPTOMS; INJURY; SURVIVORS; EVENTS; US
AB We respond to Bonanno's (2013) comment on our longitudinal evaluation of sexual assault survivors. Bonanno posits that minor disruption in functioning is the modal response to any stressor or trauma, yet most women we studied had marked initial symptoms in the immediate months following assault, which gradually improved over time. We argue that sexual violence is one example of intentional and malicious victimization, which differs from other experiences studied by Bonanno, such as spinal cord injury. Our study also differed from most previous studies in that it specifically examined the acute reactions period, which is the only period that can distinguish between resilience and recovery: Both trajectories ultimately involve good adaptation, but are distinguished by the degree of initial postevent disruption. We address Bonanno's contention that our results should be dismissed on methodological and statistical grounds. Our findings suggest that prior research about the frequency of resilience may in part be confounded by the degree and type of stress exposure.
C1 [Steenkamp, Maria M.; Litz, Brett T.; Hofmann, Stefan G.] Boston Univ, Dept Psychol, Boston, MA 02215 USA.
[Steenkamp, Maria M.; Litz, Brett T.] VA Boston Healthcare Syst, Boston, MA USA.
[Dickstein, Benjamin D.] VA Cincinnati Healthcare Syst, Cincinnati, OH USA.
[Salters-Pedneault, Kristalyn] Eastern Connecticut State Univ, Dept Psychol, Willimantic, CT 06226 USA.
RP Steenkamp, MM (reprint author), Boston Vet Affairs Med Ctr, 150 South Huntington Ave 13B-73, Boston, MA 02130 USA.
EM maria.steenkamp2@va.gov
RI Hofmann, Stefan/B-8769-2014
OI Hofmann, Stefan/0000-0002-3548-9681
NR 18
TC 1
Z9 1
U1 1
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0894-9867
J9 J TRAUMA STRESS
JI J. Trauma Stress
PD JUN
PY 2013
VL 26
IS 3
BP 394
EP 396
DI 10.1002/jts.21804
PG 3
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA 157GA
UT WOS:000319882800013
PM 23737299
ER
PT J
AU Hoban, R
Bucher, S
Neuman, I
Chen, MH
Tesfaye, N
Spector, JM
AF Hoban, Rebecca
Bucher, Sherri
Neuman, Ida
Chen, Minghua
Tesfaye, Neghist
Spector, Jonathan M.
TI 'Helping Babies Breathe' Training in Sub-Saharan Africa: Educational
Impact and Learner Impressions
SO JOURNAL OF TROPICAL PEDIATRICS
LA English
DT Article
DE neonatal resuscitation; international child health; developing
countries; educational intervention; neonatal mortality
ID NEONATAL RESUSCITATION; SETTINGS
AB Background: Poor resuscitation contributes significantly to neonatal deaths globally. Helping Babies Breathe (HBB) is a new evidence-based neonatal resuscitation curriculum for low-resource settings. Objective: We sought to characterize knowledge changes after national-level HBB training in Ethiopia, factors correlated with successful training, resuscitation skills and trainees' perceptions. Methods: Trainees completed multiple-choice questionnaires (MCQ) before and after a 2-day course. After training, bag-mask ventilation (BMV) skills were assessed and feedback questionnaires completed. Results: Resuscitation knowledge improved from 8.7/10 (SD 1.4) to 9.4/10 (SD 1.1; p = 0.003). Correct MCQ responses relating to essential aspects of resuscitation increased 68-79%. Pre-training knowledge differences between physicians and non-physicians disappeared. MCQ scores increased as trainer:trainee ratio decreased (p = 0.004). Mean post-HBB BMV scores [5.7/7 (SD 1.6)] were not impacted by trainer:trainee ratio. Conclusions: Ethiopian HBB training improved neonatal resuscitation knowledge and was well received. Lower trainer:trainee ratio was associated with increased MCQ scores. HBB eliminated baseline knowledge differences between Ethiopian healthworker cadres.
C1 [Hoban, Rebecca] Rush Univ, Med Ctr, Dept Pediat, Div Neonatol, Chicago, IL 60612 USA.
[Bucher, Sherri] Indiana Univ Sch Med, Dept Pediat, Indianapolis, IN USA.
[Bucher, Sherri] Indiana Univ Sch Med, IU Kenya Program, Indianapolis, IN USA.
[Chen, Minghua] Tufts Med Ctr, Div Newborn Med, Boston, MA USA.
[Spector, Jonathan M.] Massachusetts Gen Hosp, Dept Neonatol, Boston, MA 02114 USA.
[Spector, Jonathan M.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
RP Hoban, R (reprint author), Rush Univ, Med Ctr, Dept Pediat, Div Neonatol, 1653 W Congress Pkwy,622 Murdock Bldg, Chicago, IL 60612 USA.
EM Rebecca.hoban@gmail.com
FU Laerdal Foundation
FX We thank the Ethiopian MoH and all who contributed to HBB Ethiopia
including Laerdal Foundation, UNICEF, Nalini Singhal, Jonathan Davis,
Eileen Schoen and the AAP for permission to publish the HBB BMV test and
modified MCQ test. The funding sponsors of HBB Ethiopia did not
contribute to the study design, analysis or interpretation of the data.
HBB trainers, some from funding partners, did assist in data collection
during the training. Ida Neuman of UNICEF assisted with the writing of
the manuscript. S.B.'s travel expenses to Ethiopia were supported by the
Laerdal Foundation. All authors have made substantial contributions to
(i) the conception and design of the study, or acquisition of data, or
analysis and interpretation of data, (ii) drafting the article or
revising it critically for important intellectual content and (3) final
approval of the version to be submitted. Specifically, R. H., S. B. and
J.S. contributed to the design of the study. R. H. performed the
literature review. All authors except M. C. made significant
contributions to data collection. M. C. performed the statistical
analysis. R. H. wrote the bulk of the manuscript, with all authors
contributing to editing of the manuscript. All authors approved the
final manuscript.
NR 12
TC 12
Z9 12
U1 0
U2 5
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0142-6338
J9 J TROP PEDIATRICS
JI J. Trop. Pediatr.
PD JUN
PY 2013
VL 59
IS 3
BP 180
EP 186
DI 10.1093/tropej/fms077
PG 7
WC Pediatrics; Tropical Medicine
SC Pediatrics; Tropical Medicine
GA 156IE
UT WOS:000319814500004
PM 23335632
ER
PT J
AU White, JM
Mimiaga, MJ
Reisner, SL
Mayer, KH
AF White, Jaclyn M.
Mimiaga, Matthew J.
Reisner, Sari L.
Mayer, Kenneth H.
TI HIV Sexual Risk Behavior among Black Men Who Meet Other Men on the
Internet for Sex
SO JOURNAL OF URBAN HEALTH-BULLETIN OF THE NEW YORK ACADEMY OF MEDICINE
LA English
DT Article
DE MSM; Internet; African American/Black; HIV; Sexual risk
ID AFRICAN-AMERICAN MEN; CAGE QUESTIONNAIRE; EVOLUTIONARY TREES;
MAXIMUM-LIKELIHOOD; HIDDEN POPULATIONS; UNITED-STATES; CONDOM USE; MSM;
PREVENTION; PARTNERS
AB Using the Internet to meet sexual partners is associated with increased HIV risk behavior, including substance use, sex with multiple or anonymous partners, and unprotected anal sex (UAS), among diverse samples of MSM, yet little is known about Internet use and HIV risk among Black MSM specifically. In 2008, a sample of 197 Black MSM completed an interviewer-administered assessment and voluntary HIV counseling and testing. One fifth of the sample (20 %) reported meeting a sexual partner via the Internet in the past 12 months. Men who met sexual partners over the Internet had significantly more male sex partners (M = 13.44, SD = 20.01) than men who did not meet partners in this manner (M = 4.11, SD = 4.14, p < 0.001) and reported significantly higher rates of UAS (p < 0.05). Adjusting for sociodemographic and other HIV-related covariates, factors significantly associated with the increased odds of engaging in at least one episode of UAS with a male partner in the past 12 months included: meeting sexual partners on the Internet, identifying as gay, and lower knowledge about HIV transmission. These findings highlight the unique HIV risk behaviors among Black MSM meeting sexual partners via the Internet and warrant tailoring of prevention activities to address the specific behaviors and social influences that may contribute to increased HIV spread among this population.
C1 [White, Jaclyn M.; Mimiaga, Matthew J.; Reisner, Sari L.; Mayer, Kenneth H.] Fenway Hlth, Fenway Inst, Boston, MA USA.
[Mimiaga, Matthew J.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Mimiaga, Matthew J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Reisner, Sari L.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA.
[Mayer, Kenneth H.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA.
RP Mimiaga, MJ (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA.
EM mmimiaga@partners.org
FU HIV/AIDS Bureau, Massachusetts Department of Public Health
FX This work was funded by the HIV/AIDS Bureau, Massachusetts Department of
Public Health.
NR 53
TC 12
Z9 12
U1 0
U2 11
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1099-3460
J9 J URBAN HEALTH
JI J. Urban Health
PD JUN
PY 2013
VL 90
IS 3
BP 464
EP 481
DI 10.1007/s11524-012-9701-y
PG 18
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 154NQ
UT WOS:000319683100008
PM 22689294
ER
PT J
AU Kim, SP
Karnes, RJ
Nguyen, PL
Ziegenfuss, JY
Han, LC
Thompson, RH
Trinh, QD
Sun, M
Boorjian, SA
Beebe, TJ
Tilburt, JC
AF Kim, Simon P.
Karnes, R. Jeffrey
Nguyen, Paul L.
Ziegenfuss, Jeanette Y.
Han, Leona C.
Thompson, R. Houston
Quoc-Dien Trinh
Sun, Maxine
Boorjian, Stephen A.
Beebe, Timothy J.
Tilburt, Jon C.
TI Clinical Implementation of Quality of Life Instruments and Prediction
Tools for Localized Prostate Cancer: Results from a National Survey of
Radiation Oncologists and Urologists
SO JOURNAL OF UROLOGY
LA English
DT Article
DE prostate; prostatic neoplasms; nomograms; urology; radiation oncology
ID RADICAL PROSTATECTOMY; RESPONSE RATES; INDEX; MEN; VALIDATION;
CARCINOMA; SURVIVORS; UPDATE; STAGE; CARE
AB Purpose: Although clinical guidelines recommend assessing quality of life, cancer aggressiveness and life expectancy for making localized prostate cancer treatment decisions, it is unknown whether instruments that objectively measure such outcomes have disseminated into clinical practice. In this context we determined whether quality of life and prediction instruments for prostate cancer have been adopted by radiation oncologists and urologists in the United States.
Materials and Methods: Using a nationally representative mail survey of 1,422 prostate cancer specialists in the United States, we queried about self-reported clinical implementation of quality of life instruments, prostate cancer nomograms and life expectancy prediction tools in late 2011. The Pearson chi-square test and multivariate logistic regression were used to determine differences in the use of each instrument by physician characteristics.
Results: A total of 313 radiation oncologists and 328 urologists completed the survey for a 45% response rate. Although 55% of respondents reported using prostate cancer nomograms, only 27% and 23% reported using quality of life and life expectancy prediction instruments, respectively. On multivariate analysis urologists were less likely to use quality of life instruments than radiation oncologists (OR 0.40, p < 0.001). Physicians who spent 30 minutes or more counseling patients were consistently more likely to use quality of life instruments (OR 2.57, p < 0.001), prostate cancer nomograms (OR 1.83, p = 0.009) and life expectancy prediction tools (OR 1.85, p = 0.02) than those who spent less than 15 minutes.
Conclusions: Although prostate cancer nomograms have been implemented into clinical practice to some degree, the use of quality of life and life expectancy tools has been more limited. Increased attention to implementing validated instruments into clinical practice may facilitate shared decision making for patients with prostate cancer.
C1 [Kim, Simon P.; Karnes, R. Jeffrey; Thompson, R. Houston; Boorjian, Stephen A.] Mayo Clin, Dept Urol, Rochester, MN 55905 USA.
[Han, Leona C.; Beebe, Timothy J.] Mayo Clin, Div Hlth Care Policy & Res, Rochester, MN 55905 USA.
[Tilburt, Jon C.] Mayo Clin, Knowledge & Evaluat Unit, Rochester, MN 55905 USA.
[Han, Leona C.; Tilburt, Jon C.] Mayo Clin, Biomed Eth Res Unit, Rochester, MN 55905 USA.
[Ziegenfuss, Jeanette Y.] HealthPartners Inst Educ & Res, Minneapolis, MN USA.
[Nguyen, Paul L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA.
[Quoc-Dien Trinh] Henry Ford Hlth Syst, Vattikuti Urol Inst, Detroit, MI USA.
[Quoc-Dien Trinh; Sun, Maxine] Univ Montreal, Ctr Hlth, Canc Prognost & Hlth Outcomes Unit, Montreal, PQ, Canada.
[Sun, Maxine] Univ Montreal, Ctr Hlth, Fac Med, Dept Publ Hlth, Montreal, PQ, Canada.
RP Tilburt, JC (reprint author), Mayo Clin, Dept Internal Med, 200 1st St Southwest, Rochester, MN 55905 USA.
EM tilburt.jon@mayo.edu
FU Informed Medical Decisions Foundation Robert Derzon Award; Mayo Clinic
Healthcare Delivery Research Scholars Program; Heritage Medical Research
Institute-Prostate Cancer Foundation Young Investigator Award
FX Supported by the Informed Medical Decisions Foundation Robert Derzon
Award, Mayo Clinic Healthcare Delivery Research Scholars Program and
Heritage Medical Research Institute-Prostate Cancer Foundation Young
Investigator Award.
NR 29
TC 12
Z9 12
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5347
J9 J UROLOGY
JI J. Urol.
PD JUN
PY 2013
VL 189
IS 6
BP 2092
EP 2098
DI 10.1016/j.juro.2012.11.174
PG 7
WC Urology & Nephrology
SC Urology & Nephrology
GA 158PY
UT WOS:000319985900022
PM 23219546
ER
PT J
AU Chuang, PY
Fu, J
He, JC
AF Chuang, Peter Y.
Fu, Jia
He, John C.
TI Capturing the in vivo molecular signature of the podocyte
SO KIDNEY INTERNATIONAL
LA English
DT Editorial Material
ID GLOMERULI
AB The podocyte has an essential role in glomerular function. When cultured ex vivo, podocytes do not recapitulate their in vivo phenotype. Several technical barriers have prevented isolation of podocytes from animals with sufficient yield and purity to allow genome-wide assessment of their molecular fingerprint. Boerries et al. overcame some of these barriers and characterized the transcriptome and proteome of freshly isolated podocytes. These data sets and isolation protocol are valuable resources for the podocyte research community.
C1 [Chuang, Peter Y.; He, John C.] Mt Sinai Sch Med, Dept Med, Div Nephrol, New York, NY 10029 USA.
[Fu, Jia] Nanjing Univ, Sch Med, Jinling Hosp, Res Inst Nephrol, Nanjing 210008, Jiangsu, Peoples R China.
[He, John C.] James J Peters Vet Affairs Med Ctr, Dept Med, Bronx, NY USA.
RP Chuang, PY (reprint author), Mt Sinai Sch Med, Dept Med, 1 Gustave L Levy Pl,Box 1243, New York, NY 10029 USA.
EM cijiang.he@mssm.edu
FU NIDDK NIH HHS [P01-DK56492, R01 DK088541, 5K08-DK082760, K08 DK082760,
1R01-DK088541, R01 DK078897, P01 DK056492]
NR 9
TC 0
Z9 0
U1 1
U2 4
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 JUN
PY 2013
VL 83
IS 6
BP 986
EP 988
DI 10.1038/ki.2013.65
PG 4
WC Urology & Nephrology
SC Urology & Nephrology
GA 155ID
UT WOS:000319740300003
PM 23727999
ER
PT J
AU Friedman, AN
Yu, ZS
Tabbey, R
Denski, C
Tamez, H
Wenger, J
Thadhani, R
Li, Y
Watkins, BA
AF Friedman, Allon N.
Yu, Zhangsheng
Tabbey, Rebeka
Denski, Cheryl
Tamez, Hector
Wenger, Julia
Thadhani, Ravi
Li, Yong
Watkins, Bruce A.
TI Inverse relationship between long-chain n-3 fatty acids and risk of
sudden cardiac death in patients starting hemodialysis
SO KIDNEY INTERNATIONAL
LA English
DT Article
DE fatty acids; hemodialysis; n-3; omega-3; sudden cardiac death
ID IMPLANTABLE CARDIOVERTER-DEFIBRILLATORS; FISH-OIL SUPPLEMENTATION;
UNITED-STATES; CARDIOVASCULAR EVENTS; TERM HEMODIALYSIS; DIALYSIS
PATIENTS; CONTROLLED-TRIAL; DISEASE; BLOOD; OMEGA-3-FATTY-ACIDS
AB Experimental and clinical evidence suggests that long-chain n-3 fatty acids may protect against sudden cardiac death, the leading cause of mortality in hemodialysis patients. Here we investigated whether long-chain n-3 fatty acids have a protective relationship with sudden cardiac death in 100 patients who died of sudden cardiac death during the first year of starting hemodialysis and 300 patients who survived. Individuals were selected from a nationally representative cohort of over 1000 US hemodialysis units in 2004-2005. The odds of sudden cardiac death were calculated by quartile of long-chain n-3 fatty acid levels over the first year. There was a significant inverse relationship between long-chain n-3 fatty acids and the risk of sudden cardiac death even after adjusting for relevant comorbid conditions, biochemical values, and dietary fats. The odds of sudden cardiac death at 1 year for the second, third, and fourth quartile groups of long-chain n-3 fatty acids were 0.37, 0.22, and 0.20, respectively, compared with the lowest quartile. This significant inverse relationship was maintained even during the highest-risk first few months on hemodialysis. Thus, long-chain n-3 fatty acids are strongly and independently associated with a lower risk of sudden cardiac death in hemodialysis patients throughout the first year of hemodialysis.
C1 [Friedman, Allon N.] Indiana Univ Sch Med, Dept Med, Div Nephrol, Indianapolis, IN 46202 USA.
[Yu, Zhangsheng; Tabbey, Rebeka; Denski, Cheryl] Indiana Univ Sch Med, Dept Biostat, Indianapolis, IN 46202 USA.
[Tamez, Hector; Wenger, Julia; Thadhani, Ravi] Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA.
[Li, Yong; Watkins, Bruce A.] Univ Connecticut, Dept Nutr Sci, Lipid Chem & Mol Biol Lab, Storrs, CT USA.
RP Friedman, AN (reprint author), Indiana Univ Sch Med, Dept Med, Div Nephrol, 535 Barnhill Dr,RT 150R, Indianapolis, IN 46202 USA.
EM allfried@iupui.edu
FU National Institutes of Health [DK084403, DK094872, HL112746]; National
Kidney Foundation
FX ANF was supported by funding from the National Institutes of Health
(DK084403) and the National Kidney Foundation. RT is supported by
funding from the National Institutes of Health (DK094872, HL112746).
NR 41
TC 12
Z9 12
U1 0
U2 6
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 JUN
PY 2013
VL 83
IS 6
BP 1130
EP 1135
DI 10.1038/ki.2013.4
PG 6
WC Urology & Nephrology
SC Urology & Nephrology
GA 155ID
UT WOS:000319740300021
PM 23389417
ER
PT J
AU Bhensdadia, NM
Hunt, KJ
Lopes-Virella, MF
Tucker, JM
Mataria, MR
Alge, JL
Neely, BA
Janech, MG
Arthur, JM
AF Bhensdadia, Nishant M.
Hunt, Kelly J.
Lopes-Virella, Maria F.
Tucker, J. Michael
Mataria, Mohammad R.
Alge, Joseph L.
Neely, Benjamin A.
Janech, Michael G.
Arthur, John M.
CA Vet Affairs Diabet Trial VADT Stud
TI Urine haptoglobin levels predict early renal functional decline in
patients with type 2 diabetes
SO KIDNEY INTERNATIONAL
LA English
DT Article
DE biological markers; chronic kidney disease; diabetes; diabetic
nephropathy; type 2 diabetes; urine
ID GELATINASE-ASSOCIATED LIPOCALIN; CLINICAL PROTEINURIA; GLUCOSE CONTROL;
BLOOD-PRESSURE; RISK-FACTORS; MICROALBUMINURIA; NEPHROPATHY;
COMPLICATIONS; INSUFFICIENCY; ALBUMINURIA
AB Diabetic nephropathy is the leading cause of end-stage renal disease. The urinary albumin to creatinine ratio is used as a predictor for the development of nephropathy but it is neither sensitive nor specific. Here we used liquid chromatography/mass spectrometry on urine of eight normoalbuminuric patients with type 2 diabetes from the VA Diabetes Trial to identify candidate markers for loss of renal function. Initial verification of seven markers (agrin, haptoglobin, mannan-binding lectin serine protease 2, LAMP-2, angiotensinogen, NGAL, and uromodulin) in the urine of an additional 30 patients showed that haptoglobin was the best predictor of early renal functional decline. We then measured this in the urine of 204 patients with type 2 diabetes who did not yet have significant kidney disease (estimated glomerular filtration rate stage 2 or better and an albumin to creatinine ratio < 300mg/g). In comparing the highest to lowest tertiles, the odds ratio for having early renal function decline was 2.70 (CI: 1.15, 6.32) using the haptoglobin to creatinine ratio compared with 2.50 (CI 1.14, 5.48) using the albumin to creatinine ratio after adjusting for treatment group and use of ACE inhibitors. Addition of the haptoglobin to creatinine ratio to a model using the albumin to creatinine ratio to predict early renal function decline resulted in improved predictive performance. Thus, the haptoglobin to creatinine ratio may be useful to predict patients with type 2 diabetes at risk of nephropathy before the development of macroalbuminuria or reduced glomerular filtration rate.
C1 [Bhensdadia, Nishant M.; Hunt, Kelly J.; Lopes-Virella, Maria F.; Tucker, J. Michael; Mataria, Mohammad R.; Alge, Joseph L.; Neely, Benjamin A.; Janech, Michael G.; Arthur, John M.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA.
[Lopes-Virella, Maria F.; Janech, Michael G.; Arthur, John M.] Ralph H Johnson VA Med Ctr, Charleston, SC USA.
RP Arthur, JM (reprint author), Med Univ S Carolina, Dept Med, 829 CSB,96 Jonathan Lucas St, Charleston, SC 29425 USA.
EM arthurj@musc.edu
OI Neely, Benjamin/0000-0001-6120-7695; Alge, Joseph/0000-0002-2491-1066;
Janech, Michael/0000-0002-3202-4811
FU Biomedical Laboratory Research and Development Program of the Department
of Veterans Affairs; NIH [R01 DK080234, UL1 RR029882, ULI RR029882];
Cooperative Studies Program of the Department of Veterans Affairs Office
of Research and Development; VA Merit Review Award
FX This study was supported by a merit review award (JMA) and a career
development 2 award (MGJ) from the Biomedical Laboratory Research and
Development Program of the Department of Veterans Affairs and NIH grants
R01 DK080234 and UL1 RR029882. The VADT study was sponsored by the
Cooperative Studies Program of the Department of Veterans Affairs Office
of Research and Development. The contents do not necessarily represent
the views of the Department of Veterans Affairs or the United States
Government. Portions of the data were presented in abstract form at the
2012 American Society of Nephrology meeting.; Sources of support that
require acknowledgment:; VA Merit Review Award; NIH R01DK080234; ULI
RR029882
NR 41
TC 19
Z9 23
U1 1
U2 9
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 JUN
PY 2013
VL 83
IS 6
BP 1136
EP 1143
DI 10.1038/ki.2013.57
PG 8
WC Urology & Nephrology
SC Urology & Nephrology
GA 155ID
UT WOS:000319740300022
PM 23536133
ER
PT J
AU Merchant, ML
Niewczas, MA
Ficociello, LH
Lukenbill, JA
Wilkey, DW
Li, M
Khundmiri, SJ
Warram, JH
Krolewski, AS
Klein, JB
AF Merchant, Michael L.
Niewczas, Monika A.
Ficociello, Linda H.
Lukenbill, Janice A.
Wilkey, Daniel W.
Li, Ming
Khundmiri, Syed J.
Warram, James H.
Krolewski, Andrzej S.
Klein, Jon B.
TI Plasma kininogen and kininogen fragments are biomarkers of progressive
renal decline in type 1 diabetes
SO KIDNEY INTERNATIONAL
LA English
DT Article
DE ACE inhibitors; diabetic nephropathy; mass spectrometry;
microalbuminuria; proteomic analysis
ID B2 RECEPTORS; BRADYKININ; MICROALBUMINURIA; NEPHROPATHY; MICE;
MECHANISMS; PATHWAYS; INJURY; RISK
AB The ability of microalbuminuria to predict early progressive renal function decline in type 1 diabetic patients has been questioned. To resolve this, we determined the plasma proteome differences between microalbuminuric patients with type 1 diabetes and stable renal function (controls) and patients at risk for early progressive renal function decline (cases) and asked whether these differences have value as surrogate biomarkers. Mass spectrometry was used to analyze small (< 3 kDa) plasma peptides isolated from well-matched case and control plasma obtained at the beginning of an 8-12 year follow-up period. A Spearman analysis of plasma peptide abundance and the rate of renal function decline during follow-up identified seven masses with a significant negative correlation with early progressive renal function decline. Tandem mass spectrometry identified three fragments of high-molecular-weight kininogen. Increased plasma high-molecular-weight kininogen in the cases was confirmed by immunoblot. One peptide, des-Arg9-BK(1-8), induced Erk1/2 phosphorylation when added apically to two proximal tubular cell lines grown on permeable inserts. Thus, we have identified plasma protein fragments, some of which have biological activity with moderate to strong correlation, with early progressive renal function decline in microalbuminuric patients with type 1 diabetes. Other peptides are candidates for validation as candidate biomarkers of diabetes-associated renal dysfunction.
C1 [Merchant, Michael L.; Lukenbill, Janice A.; Wilkey, Daniel W.; Li, Ming; Khundmiri, Syed J.; Klein, Jon B.] Univ Louisville, Kidney Dis Program, Louisville, KY 40292 USA.
[Merchant, Michael L.; Lukenbill, Janice A.; Wilkey, Daniel W.; Li, Ming; Khundmiri, Syed J.; Klein, Jon B.] Univ Louisville, Clin Prote Ctr, Louisville, KY 40292 USA.
[Niewczas, Monika A.; Ficociello, Linda H.; Warram, James H.; Krolewski, Andrzej S.] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA.
[Niewczas, Monika A.; Krolewski, Andrzej S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA.
[Klein, Jon B.] Vet Adm Med Ctr, Louisville, KY 40202 USA.
RP Krolewski, AS (reprint author), Joslin Diabet Ctr, Div Res, Room 368,1 Joslin Pl, Boston, MA 02215 USA.
EM andrzej.krolewski@joslin.harvard.edu; jon.klein@louisville.edu
RI Merchant, Michael/F-7109-2013; Merchant, Michael/N-7444-2013
OI Merchant, Michael/0000-0003-4128-4057
FU National Institutes of Health [R01 DK067638, R01 DK041526]; Office of
Research and Development, Medical Research Service, Department of
Veterans Affairs; ADA [7-03-MN- 28, U01 DK085673-01, R01 DK091584-01A1];
DOE [DE-FG02-05ER6406]
FX We thank Nina Lesousky for Technical Support regarding OK cells. This
work was supported by National Institutes of Health grants R01 DK067638
(A.S.K. and J.B.K.), R01 DK041526 (A.S.K.), ADA Grant 7-03-MN- 28
(M.A.N.), U01 DK085673-01 (M.L.M. and J.B.K.), R01 DK091584-01A1
(M.L.M.), DOE DE-FG02-05ER6406 (J.B.K. and M.L.M.), and the Office of
Research and Development, Medical Research Service, Department of
Veterans Affairs (J.B.K.).
NR 25
TC 11
Z9 11
U1 0
U2 4
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 JUN
PY 2013
VL 83
IS 6
BP 1177
EP 1184
DI 10.1038/ki.2013.8
PG 8
WC Urology & Nephrology
SC Urology & Nephrology
GA 155ID
UT WOS:000319740300027
PM 23466993
ER
PT J
AU Huang, JM
Mckee, M
Huang, HD
Xiang, A
Davidson, AJ
Lu, HAJ
AF Huang, Jianmin
Mckee, Mary
Huang, Hong D.
Xiang, Alice
Davidson, Alan J.
Lu, Hua A. J.
TI A zebrafish model of conditional targeted podocyte ablation and
regeneration
SO KIDNEY INTERNATIONAL
LA English
DT Article
DE ablation; kidney regeneration; nitroreductase; podocyte; zebrafish
ID CHRONIC KIDNEY-DISEASE; TRANSGENIC ZEBRAFISH; IGA NEPHROPATHY; INJURY;
GLOMERULOSCLEROSIS; PROTEINURIA; CELLS; NITROREDUCTASE; EXPRESSION;
PRONEPHROS
AB Podocytes are specialized cells that contribute critically to the normal structure and function of the glomerular filtration barrier. Their depletion plays an important role in the pathogenesis of glomerulosclerosis. Here, we report generation of a genetic model of conditional podocyte ablation and regeneration in zebrafish using a bacterial nitroreductase strategy to convert a prodrug, metronidazole, into a cytotoxic metabolite. A transgenic zebrafish line was generated that expresses green fluorescence protein (GFP) and the nitroreductase fusion protein under the control of the podocin promoter Tg(podocin: nitroreductase-GFP). Treatment of these transgenic zebrafish with metronidazole results in podocyte apoptosis, a loss of nephrin and podocin expression, foot process effacement, and a leaky glomerular filtration barrier. Following metronidazole washout, proliferating cells were detected in the glomeruli of recovering transgenic fish with a restoration of nitroreductase-GFP fluorescence, nephrin and podocin expression, a reestablishment of normal foot process architecture, and glomerular barrier function. Thus, our studies show that zebrafish podocytes are capable of regenerating following depletion, and establish the Tg(podocin: NTR-GFP) fish as a new model to study podocyte injury and repair.
C1 [Huang, Jianmin; Mckee, Mary; Huang, Hong D.; Xiang, Alice; Lu, Hua A. J.] Massachusetts Gen Hosp, Dept Med, Div Nephrol, Ctr Syst Biol,Program Membrane Biol, Boston, MA 02114 USA.
[Huang, Jianmin; Mckee, Mary; Huang, Hong D.; Xiang, Alice; Lu, Hua A. J.] Harvard Univ, Sch Med, Boston, MA USA.
[Davidson, Alan J.] Univ Auckland, Sch Med Sci, Dept Mol Med & Pathol, Auckland 1, New Zealand.
RP Lu, HAJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Membrane Biol,Div Nephrol,Dept Med, CPZN 8150,185 Cambridge St, Boston, MA 02114 USA.
EM Halu@partners.org
FU NIH [DK075940, RO3 DK084295]; American Society of Nephrology (ASN);
Center for Regenerative Medicine; Boston Area Diabetes and Endocrinology
Research Center (NIH) [DK-57521]; Center for the Study of Inflammatory
Bowel Disease (NIH) [DK-43351]
FX We thank Dr Dennis Brown for assistance with electron microscopy
analysis; Dr Yawei Kong for assistance with generating the constructs
and transgenic zebrafish; Drs J Malicki, Lem (Tufts University, Boston),
Tepass, and Silva-Gagliardi (University of Toronto, Canada) for
providing anti-crumbs antibody (panCrb); and Dr Iain Drummond for
assistance with image analysis of zebrafish and providing constructs for
probe generation. We thank Renee Ethier and David Machon in the
zebrafish facility at Massachusetts General Hospital for their dedicated
support and Dr Patricia K Donahoe for providing support for image
acquisition and analysis. Dr AJD is supported by the Rutherford
Foundation, Marsden Fund, and the Auckland Medical Research Foundation.
HJL is supported by NIH KO8 grant DK075940, NIH RO3 DK084295, and a
Gottschalk research grant from the American Society of Nephrology (ASN).
The zebrafish facility is supported by the Center for Regenerative
Medicine (MGH). The Program in Membrane Biology receives additional
support from the Boston Area Diabetes and Endocrinology Research Center
(NIH DK-57521) and from the Center for the Study of Inflammatory Bowel
Disease (NIH DK-43351).
NR 45
TC 13
Z9 16
U1 2
U2 21
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 JUN
PY 2013
VL 83
IS 6
BP 1193
EP 1200
DI 10.1038/ki.2013.6
PG 8
WC Urology & Nephrology
SC Urology & Nephrology
GA 155ID
UT WOS:000319740300029
PM 23466998
ER
PT J
AU Freeman, MP
Hirschberg, AM
Wang, B
Petrillo, LF
Connors, S
Regan, S
Joffe, H
Cohen, LS
AF Freeman, Marlene P.
Hirschberg, April M.
Wang, Betty
Petrillo, Laura F.
Connors, Stephanie
Regan, Susan
Joffe, Hadine
Cohen, Lee S.
TI Duloxetine for major depressive disorder and daytime and nighttime hot
flashes associated with the menopausal transition
SO MATURITAS
LA English
DT Article
DE Depression; Major depressive disorder; Menopause; Vasomotor symptoms;
Hot flashes; Anxiety
ID SEROTONIN REUPTAKE INHIBITORS; RANDOMIZED CONTROLLED-TRIAL;
QUALITY-OF-LIFE; POSTMENOPAUSAL WOMEN; BREAST-CANCER; PERIMENOPAUSAL
WOMEN; VASOMOTOR SYMPTOMS; DOUBLE-BLIND; EFFICACY; MOOD
AB Background: We sought to obtain preliminary data regarding the efficacy of duloxetine for major depressive disorder (MDD) during the menopausal transition. The secondary outcomes were vasomotor symptoms (VMS, or hot flashes), specifically assessed as daytime or nighttime, and anxiety.
Methods: After a single-blind placebo lead-in, peri- and postmenopausal women with MDD (n=19) received eight weeks of open-label treatment with duloxetine (60 mg/day). The Hamilton Rating Scale for Depression (17-item) (HAM-D) was the primary outcome measure. Hot flashes were monitored prospectively using daily diaries, the Greene Climacteric Scale (GCS), and the Hot Flash-Related Daily Interference Scale (HFRDIS). Anxiety was measured with the Generalized Anxiety Disorder scale (GAD-7).
Results: Of 19 participants treated with duloxetine, 16 (84.2%) were evaluable (returned for >= 1 follow up), and 13 (68.4%) completed the study. Three discontinued due to side effects. The pre-treatment and final median HAM-D scores were 15 (interquartile range [IQR] 14-18), and 6.5 (IQR 4-11.5), respectively, reflecting a significant decrease (p=.0006). The response and remission rates were 56.3% (all responders were also remitters, having >= 50% decrease in HAM-D scores and final scores <= 7). Anxiety improved with treatment (p=.012). GCS and HFRDIS scores decreased significantly. Among those who reported hot flashes at baseline, number and severity of hot flashes improved significantly overall (p=.009 and p=.008, respectively). Daytime but not nighttime hot flashes improved significantly.
Conclusions: These data support further study of duloxetine for the treatment of a spectrum of symptoms associated with the menopausal transition. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
C1 [Freeman, Marlene P.; Wang, Betty; Petrillo, Laura F.; Joffe, Hadine; Cohen, Lee S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 USA.
[Hirschberg, April M.; Connors, Stephanie; Regan, Susan] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Freeman, MP (reprint author), Massachusetts Gen Hosp, Perinatal & Reprod Psychiat Program, 185 Cambridge St, Boston, MA 02114 USA.
EM mfreeman@partners.org
OI Regan, Susan/0000-0003-0940-2017
FU Lilly
FX This study was an Investigator Initiated Trial funded by Lilly. The
sponsor had no input in the study design, implementation, or data
analysis.
NR 32
TC 3
Z9 3
U1 2
U2 5
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0378-5122
J9 MATURITAS
JI Maturitas
PD JUN
PY 2013
VL 75
IS 2
BP 170
EP 174
DI 10.1016/j.maturitas.2013.03.007
PG 5
WC Geriatrics & Gerontology; Obstetrics & Gynecology
SC Geriatrics & Gerontology; Obstetrics & Gynecology
GA 160WG
UT WOS:000320150600013
PM 23602542
ER
PT J
AU Courville, EL
Wu, Y
Kourda, J
Roth, CG
Brockmann, J
Muzikansky, A
Fathi, AT
de Leval, L
Orazi, A
Hasserjian, RP
AF Courville, Elizabeth L.
Wu, Yue
Kourda, Jihen
Roth, Christine G.
Brockmann, Jillian
Muzikansky, Alona
Fathi, Amir T.
de Leval, Laurence
Orazi, Attilio
Hasserjian, Robert P.
TI Clinicopathologic analysis of acute myeloid leukemia arising from
chronic myelomonocytic leukemia
SO MODERN PATHOLOGY
LA English
DT Article
DE acute myeloid leukemia; chronic myelomonocytic leukemia; cytogenetics
ID MYELODYSPLASIA-RELATED CHANGES; PROGNOSTIC SCORING SYSTEM; CYTOGENETIC
ABNORMALITIES; MULTILINEAGE DYSPLASIA; RETROSPECTIVE ANALYSIS; NPM1
MUTATIONS; CLASSIFICATION; PROPOSALS; FEATURES; HISTORY
AB Acute myeloid leukemia arising from chronic myelomonocytic leukemia is currently classified as acute myeloid leukemia with myelodysplasia-related changes, a high-risk subtype. However, the specific features of these cases have not been well described. We studied 38 patients with chronic myelomonocytic leukemia who progressed to acute myeloid leukemia. We compared the clinicopathologic and genetic features of these cases with 180 patients with de novo acute myeloid leukemia and 34 patients with acute myeloid leukemia following myelodysplastic syndromes. We also examined features associated with progression from chronic myelomonocytic leukemia to acute myeloid leukemia by comparing the progressed chronic myelomonocytic leukemia cases with a cohort of chronic myelomonocytic leukemia cases that did not transform to acute myeloid leukemia. Higher white blood cell count, marrow cellularity, karyotype risk score, and Revised International Prognostic Scoring System score were associated with more rapid progression from chronic myelomonocytic leukemia to acute myeloid leukemia. Patients with acute myeloid leukemia ex chronic myelomonocytic leukemia were older (P < 0.01) and less likely to receive aggressive treatment (P = 0.02) than de novo acute myeloid leukemia patients. Most cases showed monocytic differentiation and fell into the intermediate acute myeloid leukemia karyotype risk group; 55% had normal karyotype and 17% had NPM1 mutation. Median overall survival was 6 months, which was inferior to de novo acute myeloid leukemia (17 months, P = 0.002) but similar to post myelodysplastic syndrome acute myeloid leukemia. On multivariate analysis of all acute myeloid leukemia patients, only age and karyotype were independent prognostic variables for overall survival. Our findings indicate that acute myeloid leukemia following chronic myelomonocytic leukemia displays aggressive behavior and support placement of these cases within the category of acute myeloid leukemia with myelodysplasia-related changes. The poor prognosis of these patients may be related to an older population and lack of favorable-prognosis karyotypes that characterize many de novo acute myeloid leukemia cases.
C1 [Courville, Elizabeth L.; Brockmann, Jillian; Muzikansky, Alona; Hasserjian, Robert P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Wu, Yue; Orazi, Attilio] Weill Cornell Med Coll, Dept Pathol, New York, NY USA.
[Kourda, Jihen; de Leval, Laurence] Inst Univ Pathol, Lausanne, Switzerland.
[Roth, Christine G.] Univ Pittsburgh, Med Ctr, Dept Pathol, Pittsburgh, PA USA.
[Fathi, Amir T.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
RP Hasserjian, RP (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,WRN 244, Boston, MA 02114 USA.
EM rhasserjian@partners.org
NR 42
TC 6
Z9 6
U1 1
U2 6
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 JUN
PY 2013
VL 26
IS 6
BP 751
EP 761
DI 10.1038/modpathol.2012.218
PG 11
WC Pathology
SC Pathology
GA 156EY
UT WOS:000319805800001
PM 23307061
ER
PT J
AU Krings, G
Ramachandran, R
Jain, D
Wu, TT
Yeh, MM
Torbenson, M
Kakar, S
AF Krings, Gregor
Ramachandran, Rageshree
Jain, Dhanpat
Wu, Tsung-Teh
Yeh, Matthew M.
Torbenson, Michael
Kakar, Sanjay
TI Immunohistochemical pitfalls and the importance of glypican 3 and
arginase in the diagnosis of scirrhous hepatocellular carcinoma
SO MODERN PATHOLOGY
LA English
DT Article
DE arginase; cholangiocarcinoma; glypican 3; scirrhous hepatocellular
carcinoma
ID TISSUE MICROARRAY ANALYSIS; LIVER-TRANSPLANTATION; INTRAHEPATIC
CHOLANGIOCARCINOMA; CYTOKERATIN-19 EXPRESSION; HEPATOCYTE PARAFFIN-1;
METASTATIC CARCINOMA; NEOPLASTIC TISSUES; ONCOFETAL PROTEIN;
NEEDLE-BIOPSY; MARKER
AB Scirrhous hepatocellular carcinoma is a rare ill-defined morphological subtype of hepatocellular carcinoma characterized by marked stromal fibrosis. This variant can be difficult to distinguish from intrahepatic cholangiocarcinoma and metastatic adenocarcinoma, especially on needle biopsies. We performed immunohistochemistry for hepatocellular and adenocarcinoma-associated markers on 20 scirrhous hepatocellular carcinoma cases and compared the results with classical hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Scirrhous hepatocellular carcinomas were significantly less likely to be HepPar-1 positive than classical hepatocellular carcinomas (26% and 74%, respectively; P<0.001) and were significantly more likely to express adenocarcinoma-associated markers such as epithelial cell adhesion molecule (63 vs 11%; P<0.001), cytokeratin 19 (26 vs 2%; P<0.001), and cytokeratin 7 (53 vs 2%; P<0.001). At least one of these adenocarcinoma-related markers was positive in 80% of scirrhous hepatocellular carcinoma cases. Glypican 3 and arginase were positive in 79% and 85% of cases of scirrhous hepatocellular carcinoma, respectively; the combined use of these two markers yielded 100% sensitivity for scirrhous hepatocellular carcinoma. In conclusion, the scirrhous morphology, absence of HepPar-1 staining, and frequent positivity with adenocarcinoma-related markers in scirrhous hepatocellular carcinoma can lead to an erroneous diagnosis of adenocarcinoma. Glypican 3 and arginase are the most reliable markers for identifying hepatocellular differentiation in this setting.
C1 [Krings, Gregor; Ramachandran, Rageshree; Kakar, Sanjay] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94140 USA.
[Jain, Dhanpat] Yale Univ, Dept Pathol, New Haven, CT USA.
[Wu, Tsung-Teh] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA.
[Yeh, Matthew M.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA.
[Torbenson, Michael] Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA.
[Kakar, Sanjay] Vet Affairs Med Ctr, Dept Pathol, San Francisco, CA 94121 USA.
RP Kakar, S (reprint author), San Francisco VA Med Ctr, Dept Anat Pathol, 4150 Clement St, San Francisco, CA 94121 USA.
EM sanjay.kakar@ucsf.edu
FU Department of Pathology, University of California, San Francisco
FX The study was funded by the Department of Pathology, University of
California, San Francisco.
NR 50
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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 JUN
PY 2013
VL 26
IS 6
BP 782
EP 791
DI 10.1038/modpathol.2012.243
PG 10
WC Pathology
SC Pathology
GA 156EY
UT WOS:000319805800004
PM 23348905
ER
PT J
AU Osborn, MJ
Starker, CG
McElroy, AN
Webber, BR
Riddle, MJ
Xia, L
DeFeo, AP
Gabriel, R
Schmidt, M
von Kalle, C
Carlson, DF
Maeder, ML
Joung, JK
Wagner, JE
Voytas, DF
Blazar, BR
Tolar, J
AF Osborn, Mark J.
Starker, Colby G.
McElroy, Amber N.
Webber, Beau R.
Riddle, Megan J.
Xia, Lily
DeFeo, Anthony P.
Gabriel, Richard
Schmidt, Manfred
von Kalle, Christof
Carlson, Daniel F.
Maeder, Morgan L.
Joung, J. Keith
Wagner, John E.
Voytas, Daniel F.
Blazar, Bruce R.
Tolar, Jakub
TI TALEN-based Gene Correction for Epidermolysis Bullosa
SO MOLECULAR THERAPY
LA English
DT Article
ID ZINC-FINGER NUCLEASES; DOUBLE-STRAND BREAKS; MAMMALIAN-CELLS;
STEM-CELLS; THERAPY; TARGET; EFFECTORS; VECTORS; DESIGN; KERATINOCYTES
AB Recessive dystrophic epidermolysis bullosa (RDEB) is characterized by a functional deficit of type VII collagen protein due to gene defects in the type VII collagen gene (COL7A1). Gene augmentation therapies are promising, but run the risk of insertional mutagenesis. To abrogate this risk, we explored the possibility of using engineered transcription activator-like effector nucleases (TALEN) for precise genome editing. We report the ability of TALEN to induce site-specific double-stranded DNA breaks (DSBs) leading to homology-directed repair (HDR) from an exogenous donor template. This process resulted in COL7A1 gene mutation correction in primary fibroblasts that were subsequently reprogrammed into inducible pluripotent stem cells and showed normal protein expression and deposition in a teratoma-based skin model in vivo. Deep sequencing-based genome-wide screening established a safety profile showing on-target activity and three off-target (OT) loci that, importantly, were at least 10 kb from a coding sequence. This study provides proof-of-concept for TALEN-mediated in situ correction of an endogenous patient-specific gene mutation and used an unbiased screen for comprehensive TALEN target mapping that will cooperatively facilitate translational application.
C1 [Osborn, Mark J.; McElroy, Amber N.; Webber, Beau R.; Riddle, Megan J.; Xia, Lily; DeFeo, Anthony P.; Wagner, John E.; Blazar, Bruce R.; Tolar, Jakub] Univ Minnesota, Dept Pediat, Div Blood & Marrow Transplantat, Minneapolis, MN 55455 USA.
[Osborn, Mark J.; Starker, Colby G.; Carlson, Daniel F.; Voytas, Daniel F.] Univ Minnesota, Ctr Genome Engn, Minneapolis, MN 55455 USA.
[Starker, Colby G.; Voytas, Daniel F.] Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN USA.
[Gabriel, Richard; Schmidt, Manfred; von Kalle, Christof] Natl Ctr Tumor Dis, Dept Translat Oncol, Heidelberg, Germany.
[Gabriel, Richard; Schmidt, Manfred; von Kalle, Christof] German Canc Res Ctr, Heidelberg, Germany.
[Maeder, Morgan L.; Joung, J. Keith] Massachusetts Gen Hosp, Mol Pathol Unit, Ctr Computat & Integrat Biol, Charlestown, MA USA.
[Maeder, Morgan L.; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA USA.
[Maeder, Morgan L.; Joung, J. Keith] Harvard Univ, Sch Med, Program Biol & Biomed Sci, Boston, MA USA.
[Maeder, Morgan L.; Joung, J. Keith] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RP Tolar, J (reprint author), Univ Minnesota, Sch Med, MMC 366,420 Delaware St SE, Minneapolis, MN 55455 USA.
EM tolar003@umn.edu
OI Tolar, Jakub/0000-0002-0957-4380
FU Epidermolysis Bullosa Research Fund; Jackson Gabriel Silver Foundation;
DebRA International; University of Minnesota Academic Health Center;
Pioneering Unique Cures for Kids foundation; Children's Cancer Research
Fund; Minneapolis; Minnesota; United States of America Department of
Defense; National Institutes of Health [R01 GM098861]; National
Institutes of Health Director's Pioneer Award [DP1 OD006862]; Jim and
Ann Orr MGH Research Scholar Award; National Science Foundation
FX This study was supported in part by grants from Epidermolysis Bullosa
Research Fund, Jackson Gabriel Silver Foundation, DebRA International,
University of Minnesota Academic Health Center, Pioneering Unique Cures
for Kids foundation, Children's Cancer Research Fund, Minneapolis,
Minnesota, and the United States of America Department of Defense. D. F.
V. was supported by National Institutes of Health (R01 GM098861). J.K.J.
was supported by a National Institutes of Health Director's Pioneer
Award DP1 OD006862, and the Jim and Ann Orr MGH Research Scholar Award.
M. L. M was supported by a National Science Foundation Graduate Research
Fellowship. D. F. V. is a listed inventor on a patent application titled
"TAL effector-mediated DNA modification," which is co-owned by Iowa
State Univ. and the Univ. of Minnesota, and has been licensed to
Cellectis, a European biotechnology company. J.K.J. has a financial
interest in Transposagen Biopharmaceuticals. J.K.J.'s interests were
reviewed and are managed by Massachusetts General Hospital and Partners
HealthCare in accordance with their conflict of interest policies. The
other authors declare no conflict of interest.
NR 49
TC 109
Z9 116
U1 6
U2 49
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD JUN
PY 2013
VL 21
IS 6
BP 1151
EP 1159
DI 10.1038/mt.2013.56
PG 9
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 156YB
UT WOS:000319859000009
PM 23546300
ER
PT J
AU Lee, YK
Cowan, CA
AF Lee, Youn-Kyoung
Cowan, Chad A.
TI White to brite adipocyte transition and back again
SO NATURE CELL BIOLOGY
LA English
DT Editorial Material
ID BROWN ADIPOSE-TISSUE; FAT; OBESITY; ADULTS; CELLS; MICE
AB Identification and characterization of a third type of adipocyte known as brite (brown-in-white) adipocytes has drawn considerable attention, as these cells are thought to regulate energy expenditure and may help combat obesity. Remarkably, white adipocytes can adopt the characteristics of brite adipocytes following cold stimulation, and this process is reversible in vivo.
C1 [Lee, Youn-Kyoung] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA.
RP Lee, YK (reprint author), Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
EM ccowan@fas.harvard.edu
NR 14
TC 9
Z9 9
U1 3
U2 11
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 JUN
PY 2013
VL 15
IS 6
BP 568
EP 569
PG 2
WC Cell Biology
SC Cell Biology
GA 156EM
UT WOS:000319804200005
PM 23728463
ER
PT J
AU Settembre, C
De Cegli, R
Mansueto, G
Saha, PK
Vetrini, F
Visvikis, O
Huynh, T
Carissimo, A
Palmer, D
Klisch, TJ
Wollenberg, AC
Di Bernardo, D
Chan, L
Irazoqui, JE
Ballabio, A
AF Settembre, Carmine
De Cegli, Rossella
Mansueto, Gelsomina
Saha, Pradip K.
Vetrini, Francesco
Visvikis, Orane
Tuong Huynh
Carissimo, Annamaria
Palmer, Donna
Klisch, Tiemo Juergen
Wollenberg, Amanda C.
Di Bernardo, Diego
Chan, Lawrence
Irazoqui, Javier E.
Ballabio, Andrea
TI TFEB controls cellular lipid metabolism through a starvation-induced
autoregulatory loop
SO NATURE CELL BIOLOGY
LA English
DT Article
ID CAENORHABDITIS-ELEGANS; TRANSCRIPTION FACTORS; LYSOSOMAL BIOGENESIS;
NETWORK REVEALS; GENE-EXPRESSION; TRANSGENIC MICE; PPAR-ALPHA;
AUTOPHAGY; COACTIVATORS; FIBROBLAST-GROWTH-FACTOR-21
AB The lysosomal autophagic pathway is activated by starvation and plays an important role in both cellular clearance and lipid catabolism. However, the transcriptional regulation of this pathway in response to metabolic cues is uncharacterized. Here we show that the transcription factor EB (TFEB), a master regulator of lysosomal biogenesis and autophagy, is induced by starvation through an autoregulatory feedback loop and exerts a global transcriptional control on lipid catabolism via Ppargc 1 alpha and Ppar 1 alpha. Thus, during starvation a transcriptional mechanism links the autophagic pathway to cellular energy metabolism. The conservation of this mechanism in Caenorhabditis elegans suggests a fundamental role for TFEB in the evolution of the adaptive response to food deprivation. Viral delivery of TFEB to the liver prevented weight gain and metabolic syndrome in both diet-induced and genetic mouse models of obesity, suggesting a new therapeutic strategy for disorders of lipid metabolism.
C1 [Settembre, Carmine; De Cegli, Rossella; Mansueto, Gelsomina; Carissimo, Annamaria; Di Bernardo, Diego; Ballabio, Andrea] Telethon Inst Genet & Med TIGEM, I-80131 Naples, Italy.
[Settembre, Carmine; Vetrini, Francesco; Tuong Huynh; Palmer, Donna; Klisch, Tiemo Juergen; Ballabio, Andrea] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
[Settembre, Carmine; Vetrini, Francesco; Tuong Huynh; Klisch, Tiemo Juergen; Ballabio, Andrea] Texas Children Hosp, Jan & Dan Duncan Neurol Res Inst, Houston, TX 77030 USA.
[Settembre, Carmine; Ballabio, Andrea] Univ Naples Federico II, Dept Pediat, I-80131 Naples, Italy.
[Saha, Pradip K.; Chan, Lawrence] Baylor Coll Med, Dept Med, Diabet & Endocrinol Res Ctr, Div Diabet,Dept Pediat, Houston, TX 77030 USA.
[Visvikis, Orane; Wollenberg, Amanda C.; Irazoqui, Javier E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Dev Immunol,Dept Pediat, Boston, MA 02115 USA.
[Di Bernardo, Diego] Univ Naples Federico II, Dept Syst & Comp Sci, I-80125 Naples, Italy.
[Chan, Lawrence] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA.
[Chan, Lawrence] Baylor Coll Med, Dept Biochem, Houston, TX 77030 USA.
[Chan, Lawrence] St Lukes Episcopal Hosp, Houston, TX 77030 USA.
RP Settembre, C (reprint author), Telethon Inst Genet & Med TIGEM, Via Pietro Castellino 111, I-80131 Naples, Italy.
EM settembre@tigem.it; ballabio@tigem.it
RI di Ronza, Alberto/H-7674-2016; VISVIKIS, ORANE/N-1818-2016;
OI di Ronza, Alberto/0000-0002-9813-5143; VISVIKIS,
ORANE/0000-0001-7719-5836; Irazoqui, Javier/0000-0001-6553-1329;
SETTEMBRE, Carmine/0000-0002-5829-8589; BALLABIO,
Andrea/0000-0003-1381-4604; di Bernardo, Diego/0000-0002-1911-7407
FU Italian Telethon Foundation [TGM11CB6, TGM11SB1]; Beyond Batten Disease
Foundation; European Research Council [250154]; March of Dimes
[6-FY11-306]; US National Institutes of Health [R01-NS078072,
R01-HL51586]; Diabetes and Endocrinology Research Center [P30-DK079638];
Mouse Metabolism Core at Baylor College of Medicine; Cancer Prevention
and Research Institute of Texas [RP110390]; Fund for Medical Discovery
postdoctoral fellowship from the Massachusetts General Hospital;
National Institute of General Medical Sciences of the National
Institutes of Health [R01GM101056-01]
FX We thank G. Karsenty, D. Moore, H. Zoghbi, S. Colamarino, E. Abrams, D.
Sabatini and R. Zoncu for critical reading of the manuscript. We thank
G. Diez-Roux for critical reading of the manuscript, helpful discussions
and support in manuscript preparation. We are also grateful to D.
Medina, C. Spampanato and F. Annunziata for their contribution. We thank
A. Soukas for help with the oil red O staining of C. elegans. We
acknowledge the support of the Italian Telethon Foundation grant numbers
TGM11CB6 (C.S., R.D.C. and A.B) and TGM11SB1 (A.C. and D.D.B.); the
Beyond Batten Disease Foundation (C.S., F.V., T.H. and A.B.); European
Research Council Advanced Investigator grant no. 250154 (A.B.); March of
Dimes #6-FY11-306 (A.B.); US National Institutes of Health
(R01-NS078072) (A.B.). This work was supported in part by grants from
the US National Institutes of Health (R01-HL51586) to L.C. and the
Diabetes and Endocrinology Research Center (P30-DK079638, L.C.) and the
Mouse Metabolism Core (P.K.S.) at Baylor College of Medicine. T.J.K. is
in part supported by the Cancer Prevention and Research Institute of
Texas (RP110390). O.V. was funded by a Fund for Medical Discovery
postdoctoral fellowship from the Massachusetts General Hospital. This
study was funded in part by the National Institute of General Medical
Sciences of the National Institutes of Health under award number
R01GM101056-01 to J.E.I. The content is solely the responsibility of the
authors and does not necessarily represent the official views of the
National Institutes of Health.
NR 56
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U1 4
U2 47
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 JUN
PY 2013
VL 15
IS 6
BP 647
EP +
DI 10.1038/ncb2718
PG 23
WC Cell Biology
SC Cell Biology
GA 156EM
UT WOS:000319804200015
PM 23604321
ER
PT J
AU O'Rourke, EJ
Ruvkun, G
AF O'Rourke, Eyleen J.
Ruvkun, Gary
TI MXL-3 and HLH-30 transcriptionally link lipolysis and autophagy to
nutrient availability
SO NATURE CELL BIOLOGY
LA English
DT Article
ID PROTEIN SUBCELLULAR-LOCALIZATION; CAENORHABDITIS-ELEGANS; C. ELEGANS;
LIFE-SPAN; LYSOSOMAL BIOGENESIS; LIPID-METABOLISM; GENE-EXPRESSION; FAT;
HOMEOSTASIS; STARVATION
AB Fat is stored or mobilized according to food availability. Malfunction of the mechanisms that ensure this coordination underlie metabolic diseases in humans. In mammals, lysosomal and autophagic function is required for normal fat storage and mobilization in the presence or absence of food. Autophagy is tightly linked to nutrients. However, if and how lysosomal lipolysis is coupled to nutritional status remains to be determined. Here we identify MXL-3 and HLH-30 as transcriptional switches coupling lysosomal lipolysis and autophagy to nutrient availability and controlling fat storage and ageing in Caenorhabditis elegans. Transcriptional coupling of lysosomal lipolysis and autophagy to nutrients is also observed in mammals. Thus, MXL-3 and HLH-30 orchestrate an adaptive and conserved cellular response to nutritional status and regulate lifespan.
C1 [O'Rourke, Eyleen J.; Ruvkun, Gary] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
[O'Rourke, Eyleen J.; Ruvkun, Gary] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA.
RP Ruvkun, G (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
EM eorourke@molbio.mgh.harvard.edu; ruvkun@molbio.mgh.harvard.edu
RI di Ronza, Alberto/H-7674-2016
OI di Ronza, Alberto/0000-0002-9813-5143
FU Human Frontiers Science Program Postdoctoral fellowship; [R01DK070147];
[K99DK087928]
FX We thank members of the Ruvkun, Ausubel and Kaplan laboratories for
helpful comments, especially S. Curran, A. Lee-Conery and M. Wang for
help with longevity experiments, J. Larkins-Ford for carrying out
Biosort analyses, J. Xu for help with qRT-PCR experiments, J. Bai for
acquiring confocal microscopy images, and J. Melo, C. Danna and A. Frand
for helpful reading of the manuscript. We are grateful to R. Niedra, B.
Seed, Y. Namiki and M. Oettinger for sharing expertise and reagents for
mammalian experiments, and thanks H. Y. Mak, A. Soukas, M. Van Gilst, M.
Freeman, A. Saghatelian and A. Tyler for protocols, access to equipment
and discussions on lipid measurements. We are also grateful to A. Mah
and D. Baillie for generating some transgenic strains used early in this
project but not presented here, and thank N. Martinez and M. Walhout for
sharing reagents and expertise on yeast one-hybrid experiments. We would
like to thank the National Bioresource Project, the C. elegans Genetics
Center, C. Bargmann and G. Hermann for strains. E.J.O'R. was a recipient
of a Human Frontiers Science Program Postdoctoral fellowship. This work
was supported by grants R01DK070147 to G.R. and K99DK087928 to E.J.O'R.
NR 33
TC 73
Z9 88
U1 0
U2 7
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 JUN
PY 2013
VL 15
IS 6
BP 668
EP +
DI 10.1038/ncb2741
PG 20
WC Cell Biology
SC Cell Biology
GA 156EM
UT WOS:000319804200017
PM 23604316
ER
PT J
AU Diaz, LA
Polyak, K
AF Diaz, Luis A., Jr.
Polyak, Kornelia
TI Tracking tumor resistance using 'liquid biopsies'
SO NATURE MEDICINE
LA English
DT Editorial Material
ID CANCER; PLASMA; CELLS; DNA
AB Cancers are known to evolve in response to therapy, which may result in drug resistance. However, following this process in patients is challenging, as repeated biopsies of tumor tissue involves invasive procedures and tumor heterogeneity confounds interpretation of analyses. A recent study by Murtaza et al. 1 describes an approach to trace the genomic evolution of tumors in response to therapy by sampling circulating cell-free tumor DNA (ctDNA) from patient plasma at different time points during treatment. This strategy allowed the authors to detect mutations associated with therapy resistance. We asked three experts to comment on this study and its implications for studying and treating tumors in the clinic.
C1 [Diaz, Luis A., Jr.] Johns Hopkins, Swim Across Amer Lab, Baltimore, MD 21218 USA.
[Polyak, Kornelia] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Diaz, LA (reprint author), Johns Hopkins, Swim Across Amer Lab, Baltimore, MD 21218 USA.
NR 14
TC 1
Z9 1
U1 5
U2 33
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 JUN
PY 2013
VL 19
IS 6
BP 676
EP 677
DI 10.1038/nm.3233
PG 2
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA 158OK
UT WOS:000319981600014
ER
PT J
AU Krop, IE
AF Krop, Ian E.
TI TARGETED THERAPIES HER2-positive breast cancer-sifting through many good
options
SO NATURE REVIEWS CLINICAL ONCOLOGY
LA English
DT Editorial Material
ID TRASTUZUMAB PLUS DOCETAXEL; PHASE-3 TRIAL; LAPATINIB; MULTICENTER
AB The addition of lapatinib to paclitaxel improves survival in patients with newly diagnosed HER2-positive metastatic breast cancer, further validating the importance of HER2 signalling as a target in this cancer subtype. However, the availability of other more-effective and less-toxic HER2-targeted therapies limits the clinical usefulness of the regimen.
C1 Harvard Univ, Sch Med, Breast Oncol Ctr, Dana Farber Canc Inst, Boston, MA 02215 USA.
RP Krop, IE (reprint author), Harvard Univ, Sch Med, Breast Oncol Ctr, Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA.
EM ikrop@partners.org
NR 10
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 1759-4774
J9 NAT REV CLIN ONCOL
JI Nat. Rev. Clin. Oncol.
PD JUN
PY 2013
VL 10
IS 6
BP 312
EP 313
DI 10.1038/nrclinonc.2013.72
PG 3
WC Oncology
SC Oncology
GA 152VU
UT WOS:000319560300004
PM 23629473
ER
PT J
AU Ning, MM
Lopez, M
Sarracino, D
Cao, J
Karchin, M
McMullin, D
Wang, X
Buonanno, FS
Lo, EH
AF Ning, M. M.
Lopez, M.
Sarracino, D.
Cao, J.
Karchin, M.
McMullin, D.
Wang, X.
Buonanno, F. S.
Lo, E. H.
TI Pharmaco-proteomics opportunities for individualizing neurovascular
treatment
SO NEUROLOGICAL RESEARCH
LA English
DT Review
DE Patent foramen ovale (PFO)-related stroke; Proteomics; Cardiac arrest;
Therapeutic hypothermia; Thrombolysis
ID PATENT FORAMEN OVALE; ACUTE ISCHEMIC-STROKE; HOSPITAL CARDIAC-ARREST;
FOCAL CEREBRAL-ISCHEMIA; TISSUE-PLASMINOGEN ACTIVATOR;
BLOOD-BRAIN-BARRIER; INTERNATIONAL LIAISON COMMITTEE;
AMERICAN-HEART-ASSOCIATION; EVALUATION TRIAL EPITHET; THERAPEUTIC
HYPOTHERMIA
AB Neurovascular disease often involves multi-organ system injury. For example, patent foramen ovale (PFO) related ischemic strokes involve not just the brain, but also the heart, the lung, and the peripheral vascular circulation. For higher-risk but high-reward systemic therapy (e.g., thrombolytics, therapeutic hypothermia (TH), PFO closure) to be implemented safely, very careful patient selection and close monitoring of disease progression and therapeutic efficacy are imperative. For example, more than a decade after the approval of therapeutic hypothermic and intravenous thrombolysis treatments, they both remain extremely underutilized, in part due to lack of clinical tools for patient selection or to follow therapeutic efficacy. Therefore, in understanding the complexity of the global effects of clinical neurovascular diseases and their therapies, a systemic approach may offer a unique perspective and provide tools with clinical utility. Clinical proteomic approaches may be promising to monitor systemic changes in complex multi-organ diseases - especially where the disease process can be 'sampled' in clinically accessible fluids such as blood, urine, and CSF. Here, we describe a 'pharmaco-proteomic' approach to three major challenges in translational neurovascular research directly at bedside - in order to better stratify risk, widen therapeutic windows, and explore novel targets to be validated at the bench - (i) thrombolytic treatment for ischemic stroke, (ii) therapeutic hypothermia for post-cardiac arrest syndrome, and (iii) treatment for PFO related paradoxical embolic stroke. In the future, this clinical proteomics approach may help to improve patient selection, ensure more precise clinical phenotyping for clinical trials, and individualize patient treatment.
C1 [Ning, M. M.; Lopez, M.; Sarracino, D.; Cao, J.; Karchin, M.; McMullin, D.; Buonanno, F. S.; Lo, E. H.] Massachusetts Gen Hosp, Dept Neurol, Clin Prote Res Ctr, Boston, MA 02114 USA.
[Ning, M. M.; Lopez, M.; Sarracino, D.; Cao, J.; Karchin, M.; McMullin, D.; Wang, X.; Buonanno, F. S.; Lo, E. H.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Ning, M. M.; Wang, X.; Buonanno, F. S.; Lo, E. H.] Massachusetts Gen Hosp, Dept Neurol & Radiol, Neuroprotect Res Lab, Boston, MA 02114 USA.
[Lopez, M.; Sarracino, D.] Thermo Fisher BRIMS, Cambridge, MA USA.
RP Ning, MM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, 15 Parkman St,ACC-739C, Boston, MA 02114 USA.
EM ning@hms.harvard.edu; lo@helix.mgh.harvard.edu
RI Wang, Xiangdong/F-2913-2014
FU NIH/NINDS [R01 NS067139, P01-NS55104]
FX This work was supported by the NIH/NINDS: R01 NS067139 (Ning) and
P01-NS55104 (Lo).
NR 138
TC 10
Z9 10
U1 0
U2 9
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 0161-6412
EI 1743-1328
J9 NEUROL RES
JI Neurol. Res.
PD JUN
PY 2013
VL 35
IS 5
BP 448
EP 456
DI 10.1179/1743132813Y.0000000213
PG 9
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 156IY
UT WOS:000319816500003
PM 23711324
ER
PT J
AU Duong, TQ
AF Duong, Timothy Q.
TI Magnetic resonance imaging of perfusion-diffusion mismatch in rodent and
non-human primate stroke models
SO NEUROLOGICAL RESEARCH
LA English
DT Review
DE Magnetic resonance imaging; Perfusion-diffusion mismatch; Apparent
diffusion coefficient; Cerebral blood flow; Diffusion-weighted imaging;
Perfusion-weighted imaging; Experimental stroke model; Rodents; Oxygen
challenge; Predictive mode; Rats; Hyperperfusion; Functional magnetic
resonance imaging
ID ISCHEMIC TISSUE FATE; CEREBRAL-BLOOD-FLOW; QUANTITATIVE PREDICTION;
PLASMINOGEN ACTIVATOR; FOCAL ISCHEMIA; FUNCTIONAL MRI; BRAIN-INJURY;
RAT-BRAIN; BASE-LINE; BOLD
AB Stroke is a leading cause of death and long-term disability. Non-invasive magnetic resonance imaging (MRI) has been widely used for the early detection of ischemic stroke and the longitudinal monitoring of novel treatment strategies. Recent advances in MRI techniques have enabled improved sensitivity and specificity to detecting ischemic brain injury and monitoring functional recovery. This review describes recent progresses in the development and application of multimodal MRI and image analysis techniques to study experimental stroke in rats and non-human primates.
C1 [Duong, Timothy Q.] South Texas Vet Hlth Care Syst, Dept Vet Affairs, San Antonio, TX USA.
[Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, Dept Ophthalmol, San Antonio, TX 78229 USA.
[Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, Dept Radiol, San Antonio, TX 78229 USA.
[Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, Dept Physiol, San Antonio, TX 78229 USA.
RP Duong, TQ (reprint author), Res Imaging Inst, 8403 Floyd Curl Dr, San Antonio, TX 78229 USA.
EM duongt@uthscsa.edu
RI Duong, Timothy/B-8525-2008
FU NIH [R01-NS45879]; American Heart Association [EIA 0940104N, SDG
0830293N]
FX This work was supported by the NIH (R01-NS45879) and the American Heart
Association (EIA 0940104N and SDG 0830293N).
NR 46
TC 2
Z9 2
U1 0
U2 4
PU MANEY PUBLISHING
PI LEEDS
PA STE 1C, JOSEPHS WELL, HANOVER WALK, LEEDS LS3 1AB, W YORKS, ENGLAND
SN 0161-6412
J9 NEUROL RES
JI Neurol. Res.
PD JUN
PY 2013
VL 35
IS 5
BP 465
EP 469
DI 10.1179/1743132813Y.0000000211
PG 5
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 156IY
UT WOS:000319816500005
PM 23594679
ER
PT J
AU Beacham, BL
Deatrick, JA
AF Beacham, Barbara L.
Deatrick, Janet A.
TI Health Care Autonomy in Children with Chronic Conditions Implications
for Self-Care and Family Management
SO NURSING CLINICS OF NORTH AMERICA
LA English
DT Article
DE Child; Development; Chronic health conditions; Family management;
Self-care; Autonomy
ID CHRONIC ILLNESS; ADOLESCENT AUTONOMY; CHILDHOOD; PERSPECTIVES;
PERCEPTIONS; ADHERENCE; SUPPORT; IMPACT; STYLE
AB Health care autonomy typically occurs during late adolescence but health care providers and families often expect children with chronic health conditions to master self-care earlier. Few studies have examined the development of health care autonomy as it pertains to self-care and family management. This review links the 3 concepts and discusses the implications for families and health care providers. Case studies are provided as exemplars to highlight areas where intervention and research is needed.
C1 [Beacham, Barbara L.; Deatrick, Janet A.] Univ Penn, Sch Nursing, Ctr Hlth Equ Res, Philadelphia, PA 19104 USA.
RP Beacham, BL (reprint author), Univ Penn, Sch Nursing, Ctr Hlth Equ Res, Room 243 2Lower Claire M Fagin Hall,418 Curie Blv, Philadelphia, PA 19104 USA.
EM blynne@nursing.upenn.edu
FU National Institutes of Health, National Institute of Nursing Research
[F31NR11524, T32NR007100]; Sigma Theta Tau Xi Chapter, University of
Pennsylvania
FX This work was supported by grant nos. F31NR11524 and T32NR007100 from
the National Institutes of Health, National Institute of Nursing
Research and by a grant from the Sigma Theta Tau Xi Chapter, University
of Pennsylvania.
NR 27
TC 4
Z9 6
U1 2
U2 22
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0029-6465
J9 NURS CLIN N AM
JI Nurs. Clin. North Am.
PD JUN
PY 2013
VL 48
IS 2
BP 305
EP +
DI 10.1016/j.cnur.2013.01.010
PG 14
WC Nursing
SC Nursing
GA 158FJ
UT WOS:000319954600010
PM 23659815
ER
PT J
AU Hebert, PL
McBean, AM
O'Connor, H
Frank, B
Good, C
Maciejewski, ML
AF Hebert, Paul L.
McBean, Alexander Marshall
O'Connor, Heidi
Frank, Barbara
Good, Charles
Maciejewski, Matthew L.
TI Time until incident dementia among Medicare beneficiaries using
centrally acting or non-centrally acting ACE inhibitors
SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY
LA English
DT Article
DE dementia; hypertension; centrally active; ACE inhibitor; Alzheimer's;
Medicare; pharmacoepidemiology
ID CONVERTING ENZYME-INHIBITORS; ALZHEIMERS-DISEASE; INSTRUMENTAL
VARIABLES; PRESCRIBING PREFERENCE; COGNITIVE IMPAIRMENT; PROSPECTIVE
COHORT; PROPENSITY-SCORE; ANGIOTENSIN; PERINDOPRIL; PERFORMANCE
AB Background Centrally active (CA) angiotensin-converting enzyme inhibitors (ACEIs) are able to cross the blood-brain barrier. Small observational studies and mouse models suggest that use of CA versus non-CA ACEIs is associated with a reduced incidence of Alzheimer's disease and related dementias (ADRD). Objective The aim of this research was to assess the effect of CA versus non-CA ACEI use on incident ADRD. Design This is a retrospective cohort study with a non-equivalent control group. Setting and patients This study used a national random sample of Medicare beneficiaries enrolled in Part D with an ACEI prescription. A prevalent ACEI user cohort included beneficiaries (n=107179) with an ACEI prescription prior to 30 April 2007; beneficiaries without an ACEI prescription before this date were defined as incident ACEI users (n=9840). Measurements The main outcome was time until first diagnosis of ADRD in Medicare claims. Results The unadjusted, propensity-matched and instrumental variable analyses of both the prevalent and incident ACEI user cohorts consistently showed similar time until incident ADRD in those taking CA ACEIs compared with those who took non-CA ACEIs. Limitations The limitations of this study include the use of observational data, relatively short follow-up time and claims-based measure of cognitive decline. Conclusions In this analysis of Medicare beneficiaries who were prevalent or incident users of ACEIs in 2007-2009, the use of CA ACEIs was unrelated to cognitive decline within 3years of index prescription. Continued follow-up of these patients and more sensitive measures of cognitive decline are necessary to determine whether a cognitive benefit of CA ACEIs is realized in the long term. Copyright (c) 2013 John Wiley & Sons, Ltd.
C1 [Hebert, Paul L.] VA Puget Sound Hlth Care Syst, Northwest Ctr Outcomes Res Older Adults, Seattle, WA USA.
[Hebert, Paul L.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
[McBean, Alexander Marshall; O'Connor, Heidi; Frank, Barbara; Good, Charles] Univ Minnesota, Sch Publ Hlth, Div Hlth Policy & Management, Minneapolis, MN USA.
[Maciejewski, Matthew L.] Durham VA Med Ctr, Ctr Hlth Serv Res Primary Care, Durham, NC USA.
[Maciejewski, Matthew L.] Duke Univ, Div Gen Internal Med, Dept Med, Durham, NC 27705 USA.
RP Maciejewski, ML (reprint author), Duke Univ, Med Ctr, Dept Med, Div Gen Internal Med, Durham, NC 27705 USA.
EM mlm34@duke.edu
FU Centers for Medicare and Medicaid Services (CMS) [HHSM-500-2005-00271];
VA Health Services Research and Development Service (HSR&D) Research
Career Scientist Award [RCS-10-391]
FX This project was supported by the Centers for Medicare and Medicaid
Services (CMS) contract HHSM-500-2005-00271. Dr. Maciejewski is
supported by a VA Health Services Research and Development Service
(HSR&D) Research Career Scientist Award (RCS-10-391).
NR 29
TC 6
Z9 7
U1 0
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1053-8569
J9 PHARMACOEPIDEM DR S
JI Pharmacoepidemiol. Drug Saf.
PD JUN
PY 2013
VL 22
IS 6
BP 641
EP 648
DI 10.1002/pds.3449
PG 8
WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
GA 157DG
UT WOS:000319875400010
PM 23620414
ER
PT J
AU Chan, ED
Chan, MM
Chan, MM
AF Chan, Edward D.
Chan, Michael M.
Chan, Mallory M.
TI Pulse oximetry: Understanding its basic principles facilitates
appreciation of its limitations
SO RESPIRATORY MEDICINE
LA English
DT Review
DE Pulse oximetry; Oxygen saturation; Co-oximetry; Carboxyhemoglobin;
Methemoglobin
ID DECREASED OXYGEN-SATURATION; SICKLE-CELL-DISEASE; NAIL POLISH;
HEMOGLOBIN KOLN; ANEMIA; SULFHEMOGLOBINEMIA; DESATURATION; ACCURACY;
READINGS; BLOOD
AB Pulse oximetry has revolutionized the ability to monitor oxygenation in a continuous, accurate, and non-invasive fashion. Despite its ubiquitous use, it is our impression and supported by studies that many providers do not know the basic principles behind its mechanism of function. This knowledge is important because it provides the conceptual basis of appreciating its Limitations and recognizing when pulse oximeter readings may be erroneous. In this review, we discuss how pulse oximeters are able to distinguish oxygenated hemoglobin from deoxygenated hemoglobin and how they are able to recognize oxygen saturation only from the arterial compartment of blood. Based on these principles, we discuss the various conditions that can cause spurious readings and the mechanisms underlying them. Published by Elsevier Ltd.
C1 [Chan, Edward D.] Denver Vet Affairs Med Ctr, Denver, CO USA.
[Chan, Edward D.] Natl Jewish Hlth, Dept Med, Denver, CO 80206 USA.
[Chan, Edward D.] Natl Jewish Hlth, Dept Acad Affairs, Denver, CO 80206 USA.
[Chan, Edward D.] Univ Colorado, Div Pulm Sci & Crit Care Med, Aurora, CO USA.
[Chan, Michael M.] Univ Colorado, Skaggs Sch Pharm & Pharmaceut Sci, Aurora, CO USA.
[Chan, Mallory M.] Univ Colorado, Denver Sch Med, Aurora, CO USA.
RP Chan, ED (reprint author), Natl Jewish Hlth, D509,Neustadt Bldg,1400 Jackson St, Denver, CO 80206 USA.
EM chane@njhealth.org
NR 55
TC 24
Z9 26
U1 8
U2 50
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 JUN
PY 2013
VL 107
IS 6
BP 789
EP 799
DI 10.1016/j.rmed.2013.02.004
PG 11
WC Cardiac & Cardiovascular Systems; Respiratory System
SC Cardiovascular System & Cardiology; Respiratory System
GA 155ZO
UT WOS:000319789700001
PM 23490227
ER
PT J
AU Chervin, RD
Chesson, AL
Benca, RM
Greenough, GP
O'Hearn, DJ
Auckley, DH
Littner, M
Mullington, JM
Malhotra, A
Berry, RB
Malhotra, RK
Schulman, DA
AF Chervin, Ronald D.
Chesson, Andrew L., Jr.
Benca, Ruth M.
Greenough, Glen P.
O'Hearn, Daniel J.
Auckley, Dennis H.
Littner, Michael
Mullington, Janet M.
Malhotra, Atul
Berry, Richard B.
Malhotra, Raman K.
Schulman, David A.
TI Organization and Structure for Sleep Medicine Programs at Academic
Institutions: Part 1-Current Challenges
SO SLEEP
LA English
DT Editorial Material
ID DISORDERS; CENTERS
C1 [Chervin, Ronald D.] Univ Michigan, Dept Neurol, Sleep Disorders Ctr, Ann Arbor, MI 48109 USA.
[Chesson, Andrew L., Jr.] Louisiana State Univ, Sch Med, Dept Neurol, Div Sleep Med, Shreveport, LA USA.
[Benca, Ruth M.] Univ Wisconsin, Dept Psychiat, Madison, WI 53706 USA.
[Greenough, Glen P.] Dartmouth Hitchcock Med Ctr, Sleep Disorders Ctr, Lebanon, NH 03766 USA.
[O'Hearn, Daniel J.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Auckley, Dennis H.] MetroHlth Med Ctr, Div Pulm Crit Care & Sleep Med, Cleveland, OH USA.
[Auckley, Dennis H.] Case Western Reserve Univ, Sch Med, Cleveland, OH USA.
[Littner, Michael] VA Greater Los Angeles Healthcare Syst, Sepulveda, CA USA.
[Mullington, Janet M.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Malhotra, Atul] Brigham & Womens Hosp, Sleep Disorders Res Program, Boston, MA 02115 USA.
[Malhotra, Atul] Harvard Univ, Sch Med, Boston, MA USA.
[Berry, Richard B.] Univ Florida, Gainesville, FL USA.
[Malhotra, Raman K.] SLUcare Sleep Disorders Ctr, St Louis, MO USA.
[Schulman, David A.] Emory Univ, Sch Med, Div Pulm Allergy & Crit Care Med, Atlanta, GA USA.
RP Chervin, RD (reprint author), Univ Michigan, Sleep Disorders Ctr, Michael S Aldrich Sleep Disorders Lab, C728 Med Inn Bldg,1500 East Med Ctr Dr, Ann Arbor, MI 48109 USA.
FU NHLBI NIH HHS [R01 HL085188, R01 HL090897, K24 HL093218]
NR 10
TC 0
Z9 0
U1 1
U2 5
PU AMER ACAD SLEEP MEDICINE
PI WESTCHESTER
PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA
SN 0161-8105
J9 SLEEP
JI Sleep
PD JUN 1
PY 2013
VL 36
IS 6
BP 795
EP 801
DI 10.5665/sleep.2690
PG 7
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 155HX
UT WOS:000319739700001
PM 23729918
ER
PT J
AU Chesson, AL
Chervin, RD
Benca, RM
Greenough, GP
O'Hearn, DJ
Auckley, DH
Littner, M
Mullington, JM
Malhotra, A
Berry, RB
Malhotra, RK
Schulman, DA
AF Chesson, Andrew L., Jr.
Chervin, Ronald D.
Benca, Ruth M.
Greenough, Glen P.
O'Hearn, Daniel J.
Auckley, Dennis H.
Littner, Michael
Mullington, Janet M.
Malhotra, Atul
Berry, Richard B.
Malhotra, Raman K.
Schulman, David A.
TI Organization and Structure for Sleep Medicine Programs at Academic
Institutions: Part 2-Goals and Strategies to Optimize Patient Care,
Education, and Discovery
SO SLEEP
LA English
DT Editorial Material
C1 [Chesson, Andrew L., Jr.] Louisiana State Univ, Sch Med, Dept Neurol, Div Sleep Med, Shreveport, LA USA.
[Chervin, Ronald D.] Univ Michigan, Dept Neurol, Sleep Disorders Ctr, Ann Arbor, MI USA.
[Benca, Ruth M.] Univ Wisconsin, Dept Psychiat, Madison, WI 53706 USA.
[Greenough, Glen P.] Dartmouth Hitchcock Med Ctr, Sleep Disorders Ctr, Lebanon, NH 03766 USA.
[O'Hearn, Daniel J.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Auckley, Dennis H.] MetroHlth Med Ctr, Div Pulm Crit Care & Sleep Med, Cleveland, OH USA.
[Auckley, Dennis H.] Case Western Reserve Univ, Sch Med, Cleveland, OH USA.
[Littner, Michael] VA Greater Los Angeles Healthcare Syst, Sepulveda, CA USA.
[Mullington, Janet M.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Malhotra, Atul] Brigham & Womens Hosp, Sleep Disorders Res Program, Boston, MA 02115 USA.
[Malhotra, Atul] Harvard Univ, Sch Med, Boston, MA USA.
[Berry, Richard B.] Univ Florida, Gainesville, FL USA.
[Malhotra, Raman K.] SLUcare Sleep Disorders Ctr, St Louis, MO USA.
[Schulman, David A.] Emory Univ, Sch Med, Div Pulm Allergy & Crit Care Med, Atlanta, GA USA.
RP Chesson, AL (reprint author), LSUHSC, Sch Med, 1501 Kings Highway,POB 33932, Shreveport, LA 71130 USA.
FU NHLBI NIH HHS [K24 HL093218, R01 HL085188, R01 HL090897]
NR 3
TC 0
Z9 0
U1 0
U2 4
PU AMER ACAD SLEEP MEDICINE
PI WESTCHESTER
PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA
SN 0161-8105
J9 SLEEP
JI Sleep
PD JUN 1
PY 2013
VL 36
IS 6
BP 803
EP 811
DI 10.5665/sleep.2692
PG 9
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 155HX
UT WOS:000319739700002
PM 23729919
ER
PT J
AU Hyder, O
Hatzaras, I
Sotiropoulos, GC
Paul, A
Alexandrescu, S
Marques, H
Pulitano, C
Barroso, E
Clary, BM
Aldrighetti, L
Ferrone, CR
Zhu, AX
Bauer, TW
Walters, DM
Groeschl, R
Gamblin, TC
Marsh, JW
Nguyen, KT
Turley, R
Popescu, I
Hubert, C
Meyer, S
Choti, MA
Gigot, JF
Mentha, G
Pawlik, TM
AF Hyder, Omar
Hatzaras, Ioannis
Sotiropoulos, Georgios C.
Paul, Andreas
Alexandrescu, Sorin
Marques, Hugo
Pulitano, Carlo
Barroso, Eduardo
Clary, Bryan M.
Aldrighetti, Luca
Ferrone, Cristina R.
Zhu, Andrew X.
Bauer, Todd W.
Walters, Dustin M.
Groeschl, Ryan
Gamblin, T. Clark
Marsh, J. Wallis
Nguyen, Kevin T.
Turley, Ryan
Popescu, Irinel
Hubert, Catherine
Meyer, Stephanie
Choti, Michael A.
Gigot, Jean-Francois
Mentha, Gilles
Pawlik, Timothy M.
TI Recurrence after operative management of intrahepatic cholangiocarcinoma
SO SURGERY
LA English
DT Article; Proceedings Paper
CT 65th Annual Cancer Symposium of the Society-of-Surgical-Oncology (SSO)
CY MAR 21-24, 2012
CL Orlando, FL
SP Soc Surg Oncol (SSO)
ID PROGNOSTIC-FACTORS; SURGICAL RESECTION; PREDICTIVE FACTORS; SURGERY;
SURVIVAL; RADIOTHERAPY
AB Introduction. Data on recurrence after operation for intrahepatic cholarigiocarcinoma (ICC) are limited. We sought to investigate rates and patterns of recurrence in patients after operative intervention for ICC.
Methods. We identified 301 patients who underwent operation for ICC between 1990 and 2011 from an international, multi-institutional database. Clinicopathologic data, recurrence patterns, and recurrencefree survival (RFS) were analyzed.
Results. During the median follow up duration of 31 months (range 1-208), 53.5% developed a recurrence. Median RFS was 20.2 months and 5-year actuarial disease-free survival, 32.1%. The most common site for initial recurrence after operation of ICC was intrahepatic (n = 98; 60.9%), followed by simultaneous intra- and extrahepdtic disease (n = 30; 18.6%); 33 (21.0%) patients developed extrahepatic recurrence only as the first site of recurrence. Macrovascular invasion (hazard ratio [HR], 2.08; 95% confidence interval [CI], 1.34-3.21; P < .001), nodal metastasis (HR, 1.55; 95% CI, 1.01-2.45; P = .04), unknown nodal status (HR, 1.57; 95% CI, 1.10-2.25; P = .04), and tumor size cm (H.R., 1.84; 95% CI, 1.28-2.65; P < .001) were independently associated with increased risk of recurrence. Patients were assigned a clinical score from 0 to 3 according to the presence of these risk factors. The 5-year RFS for patients with scores of 0, 1, 2, and 3 was 61.8%, 36.2%, 19.5%, and 9.6%, respectively.
Conclusion. Recurrence after operative intervention for ICC was common. Disease recurred both at intraand extrahepatic sites with roughly the same frequency. Factors such as lymph node metastasis, tumor size, and vascular invasion predict highest risk of recurrence.
C1 [Hyder, Omar; Hatzaras, Ioannis; Choti, Michael A.; Pawlik, Timothy M.] Johns Hopkins Univ, Sch Med, Dept Surg, Baltimore, MD 21205 USA.
[Sotiropoulos, Georgios C.; Paul, Andreas] Univ Hosp Essen, Dept Surg, Essen, Germany.
[Alexandrescu, Sorin; Popescu, Irinel] Inst Digest Dis & Liver Transplantat Fundeni, Bucharest, Romania.
[Marques, Hugo; Barroso, Eduardo] Curry Cabral Hosp, Dept Surg, Lisbon, Portugal.
[Pulitano, Carlo; Aldrighetti, Luca] Univ Milan, Osped San Raffaele, Dept Surg, I-20127 Milan, Italy.
[Clary, Bryan M.; Turley, Ryan] Duke Med Ctr, Dept Surg, Durham, NC USA.
[Ferrone, Cristina R.; Zhu, Andrew X.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Bauer, Todd W.] Univ Virginia, Dept Surg, Charlottesville, VA USA.
[Walters, Dustin M.] Med Coll Wisconsin, Dept Surg, Milwaukee, WI 53226 USA.
[Groeschl, Ryan; Gamblin, T. Clark] Univ Pittsburgh, Dept Surg, Pittsburgh, PA USA.
[Marsh, J. Wallis; Nguyen, Kevin T.; Hubert, Catherine; Gigot, Jean-Francois] Clin Univ St Luc, Dept Surg, B-1200 Brussels, Belgium.
[Meyer, Stephanie; Mentha, Gilles] Hop Univ Geneve, Dept Surg, Geneva, Switzerland.
RP Pawlik, TM (reprint author), Dept Surg, Div Surg Oncol, Blalock 688,600 N Wolfe St, Baltimore, MD 21287 USA.
EM tpawlik1@jhmi.edu
RI Hyder, Omar/D-1441-2013; POPESCU, IRINEL/B-3048-2008
OI Hyder, Omar/0000-0002-0965-5543;
FU NCI NIH HHS [P30 CA006973]
NR 31
TC 42
Z9 45
U1 0
U2 16
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0039-6060
J9 SURGERY
JI Surgery
PD JUN
PY 2013
VL 153
IS 6
BP 811
EP 818
PG 8
WC Surgery
SC Surgery
GA 157JC
UT WOS:000319891400009
PM 23499016
ER
PT J
AU Upadhyaya, P
Smith, R
Swift, UM
Warshaw, AL
Harken, AH
AF Upadhyaya, Pooja
Smith, Randi
Swift, Upasna Mini
Warshaw, Andrew L.
Harken, Alden H.
TI Mentoring for global health missions
SO SURGERY
LA English
DT Editorial Material
C1 [Upadhyaya, Pooja] Mobilizing Hlth, San Francisco, CA USA.
[Smith, Randi] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Swift, Upasna Mini] Alameda Cty Med Ctr, Dept Med, Oakland, CA USA.
[Warshaw, Andrew L.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Harken, Alden H.] Univ Calif, Dept Surg, Oakland, CA 94602 USA.
RP Harken, AH (reprint author), Univ Calif, Dept Surg, 1411 E 31st St, Oakland, CA 94602 USA.
EM aharken@acmedctr.org
NR 5
TC 0
Z9 0
U1 0
U2 3
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0039-6060
J9 SURGERY
JI Surgery
PD JUN
PY 2013
VL 153
IS 6
BP 866
EP 870
DI 10.1016/j.surg.2013.01.002
PG 5
WC Surgery
SC Surgery
GA 157JC
UT WOS:000319891400016
PM 23489941
ER
PT J
AU Shonka, N
Piao, Y
Gilbert, M
Yung, A
Chang, S
DeAngelis, LM
Lassman, AB
Liu, J
Cloughesy, T
Robins, HI
Lloyd, R
Chen, A
Prados, M
Wen, PY
Heymach, J
de Groot, J
AF Shonka, Nicole
Piao, Yuji
Gilbert, Mark
Yung, Alfred
Chang, Susan
DeAngelis, Lisa M.
Lassman, Andrew B.
Liu, Jun
Cloughesy, Timothy
Robins, H. Ian
Lloyd, Rita
Chen, Alice
Prados, Michael
Wen, Patrick Y.
Heymach, John
de Groot, John
TI Cytokines associated with toxicity in the treatment of recurrent
glioblastoma with aflibercept
SO TARGETED ONCOLOGY
LA English
DT Article
DE Glioblastoma; Aflibercept; VEGF; Cytokines; Toxicity
ID ADVANCED SOLID TUMORS; GROWTH-FACTOR TRAP; CELL LUNG-CANCER; PHASE-II;
RADIOTHERAPY; BIOMARKERS; INHIBITOR; SUNITINIB; AXITINIB; PROSTATE
AB Plasma profiling of patients treated with antiangiogenic agents may identify markers that correlate with toxicity. Objectives were to correlate changes in cytokine and angiogenic factors as potential markers of toxicity to aflibercept. Circulating cytokine and angiogenic factors were measured in 28 patients with recurrent glioblastoma in a single-arm phase II study of aflibercept. Plasma samples were analyzed at baseline, 24 h, and 28 days using multiplex assays or ELISA. We evaluated log-transformed baseline biomarker expressions with Cox proportional hazard regression models to assess the effect of markers on any grade II-IV (Gr II-IV) toxicity, on-target toxicity (hypertension, proteinuria, thromboembolism), and fatigue. All tests were two sided with a statistical significance level of p = 0.05. Among 28 pts, there were 116 Gr II-IV events. Changes in IL-13 from baseline to 24 h predicted on-target toxicities. Increases in IL-1b, IL-6, and IL-10 at 24 h were significantly associated with fatigue. Progression-free survival was 14.9 months for patients in the all-toxicity group and 9.0 months for patients in the on-target toxicity group compared to 4.3 months for those who did not develop any Gr II-IV toxicity (p = 0.002 and p = 0.045, respectively). Toxicity from antiangiogenic therapy remains an important cause of antiangiogenic treatment discontinuation and patient morbidity. Changes in IL6, IL10, and IL13 were repeatedly correlated with toxicity. Profiling of IL-13 as a surrogate for endothelial dysfunction could individualize patients at risk during antiangiogenic therapy, as could identifying those at higher risk for fatigue using IL-6 and IL-10.
C1 [Shonka, Nicole] Univ Nebraska Med Ctr, Div Oncol & Hematol, Omaha, NE 68198 USA.
[Piao, Yuji; Gilbert, Mark; Yung, Alfred; Liu, Jun; Heymach, John; de Groot, John] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Chang, Susan; Prados, Michael] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[DeAngelis, Lisa M.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Lassman, Andrew B.] New York Presbyterian Columbia Univ, Dept Neurol, New York, NY 10032 USA.
[Lassman, Andrew B.] New York Presbyterian Columbia Univ, Herbert Irving Comprehens Canc Ctr, New York, NY 10032 USA.
[Cloughesy, Timothy] Univ Calif Los Angeles, Los Angeles, CA 90095 USA.
[Robins, H. Ian; Lloyd, Rita] Univ Wisconsin, Sch Med, Madison, WI 53792 USA.
[Chen, Alice] NCI, NIH, Bethesda, MD 20892 USA.
[Chen, Alice] CTEP, Bethesda, MD USA.
[Wen, Patrick Y.] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Shonka, N (reprint author), Univ Nebraska Med Ctr, Div Oncol & Hematol, Omaha, NE 68198 USA.
EM nshonka@unmc.edu
FU National Institutes of Health [U01-CA62399, 1R21A126127]; ASCO
FX Funding was received from the National Institutes of Health [U01-CA62399
to NABTC, 1R21A126127 to J. de G.] and the ASCO Career Development Award
[to J. de G.].
NR 34
TC 4
Z9 4
U1 0
U2 3
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1776-2596
EI 1776-260X
J9 TARGET ONCOL
JI Target. Oncol.
PD JUN
PY 2013
VL 8
IS 2
BP 117
EP 125
DI 10.1007/s11523-013-0254-0
PG 9
WC Oncology
SC Oncology
GA 155VN
UT WOS:000319776600005
PM 23345034
ER
PT J
AU Sujoy, V
Pinto, A
Nose, V
AF Sujoy, Victoria
Pinto, Andre
Nose, Vania
TI Columnar Cell Variant of Papillary Thyroid Carcinoma: A Study of 10
Cases with Emphasis on CDX2 Expression
SO THYROID
LA English
DT Article
ID AGGRESSIVE VARIANT; MARKER; CANCER; TUMORS; BRAF
AB Background: Columnar cell variant is a recognized rare variant of papillary thyroid carcinoma (PTC) that has an uncertain clinical course. This variant has two subvariants, and one is regarded as a more aggressive form in comparison to the more common classical and follicular variants. These tumors have morphological resemblance with endometrial or colonic adenocarcinoma. CDX2, a transcription factor of the caudal homeobox family, plays a key role in intestinal development and differentiation, and it is widely used as a marker to detect adenocarcinomas of intestinal and colonic origin. CDX2 has been rarely reported in PTC.
Methods: We studied 10 cases of columnar cell variant of PTC (CCV-PTC). The histological, architectural, and cytological features fulfilled the diagnostic criteria of the CCV-PTC, as defined by the current World Health Organization classification. Ten patients (six men and four women) ranging in age from 32 to 90 years (mean, 58.3 years) presented with tumors classified as indolent (four cases) or aggressive (six cases); three harbored a BRAF(V600E) mutation. All cases were beta-catenin negative. The Ki-67 proliferative index was up to 50%. All cases were thyroid transcription factor-1-positive. Using paraffin-embedded blocks, immunohistochemistry for CDX2 was performed to evaluate the reactivity of this antibody to this variant of PTC.
Results: Nuclear positivity for CDX2 was detected in one out of the 10 cases studied (10%); the other nine cases did not express CDX2.
Conclusion: Only one of our cases showed nuclear positivity for CDX2. Therefore, our study failed to confirm it as a marker for CCV-PTC. The absence of CDX2 in the majority of the cases does not support the theory of CDX2 playing a role in the intestinal phenotype of these tumors.
C1 [Sujoy, Victoria; Pinto, Andre] Univ Miami, Dept Pathol, Miami, FL USA.
[Nose, Vania] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
RP Nose, V (reprint author), Massachusetts Gen Hosp, Warren 214 55 Fruit St, Boston, MA 02114 USA.
EM vnose@partners.org
NR 23
TC 4
Z9 8
U1 0
U2 0
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1050-7256
J9 THYROID
JI Thyroid
PD JUN
PY 2013
VL 23
IS 6
BP 714
EP 719
DI 10.1089/thy.2012.0455
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 159GB
UT WOS:000320032500011
PM 23488912
ER
PT J
AU Pretorius, E
Vermeulen, N
Bester, J
Lipinski, B
Kell, DB
AF Pretorius, Etheresia
Vermeulen, Natasha
Bester, Janette
Lipinski, Boguslaw
Kell, Douglas B.
TI A novel method for assessing the role of iron and its functional
chelation in fibrin fibril formation: the use of scanning electron
microscopy
SO TOXICOLOGY MECHANISMS AND METHODS
LA English
DT Article
DE Ferric iron; iron chelation; platelet rich plasma; purified fibrinogen;
scanning electron microscopy
ID LABILE PLASMA IRON; PERIPHERAL ARTERIAL-DISEASE; NONTRANSFERRIN-BOUND
IRON; INDUCED OXIDATIVE STRESS; ALZHEIMERS-DISEASE; AORTIC INTIMA;
CARDIOVASCULAR-DISEASES; MAGNETIC-RESONANCE; PARKINSONS-DISEASE;
DIABETES-MELLITUS
AB Aims: Inflammatory diseases associated with iron overload are characterized by a changed coagulation profile, where there is a persistent presence of fibrin-like material of dense-matted deposits (DMDs). It is believed that one source of such material is a result of the activation of blood coagulation without the generation of thrombin, causing clots to become resistant to fibrinolytic dissolution. The aim of the current manuscript therefore is to apply a novel scanning electron microscopy method for assessing the role of functional chelation in the prevention or reversal of iron-induced fibrin formation.
Methods and results: Purified fibrinogen and platelet-rich plasma were exposed to chelating agents followed by iron, to determine the chelating effects. We show that there is another, pathological pathway of fibrin formation initiated by free iron (initially as Fe (III)), leading to the formation of highly reactive oxygen species such as the hydroxyl radical that can oxidize and insolubilize proteins, a process that might be inhibited by iron-chelating compounds. The final product of such a pathway is a fibrin-like material, termed DMDs that are remarkably resistant to proteolytic degradation.
Conclusions: Scanning electron microscopy shows that iron-chelating agents are effective inhibitors of DMD formation. The most active inhibitors of DMD formation proved to be Desferal, Clioquinol and Curcumin, whereas Epigallocatechin gallate and Deferiprone were less effective. The functional model we describe may point the clinical utility of various substances in iron-mediated degenerative diseases.
C1 [Pretorius, Etheresia; Vermeulen, Natasha; Bester, Janette] Univ Pretoria, Fac Hlth Sci, Dept Physiol, ZA-0007 Arcadia, South Africa.
[Lipinski, Boguslaw] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA.
[Kell, Douglas B.] Univ Manchester, Sch Chem, Manchester, Lancs, England.
[Kell, Douglas B.] Univ Manchester, Manchester Inst Biotechnol, Manchester, Lancs, England.
RP Pretorius, E (reprint author), Univ Pretoria, Fac Hlth Sci, Dept Physiol, Private Bag X323, ZA-0007 Arcadia, South Africa.
EM resia.pretorius@up.ac.za
OI Kell, Douglas/0000-0001-5838-7963
NR 76
TC 19
Z9 19
U1 1
U2 14
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1537-6516
J9 TOXICOL MECH METHOD
JI Toxicol. Mech. Methods
PD JUN
PY 2013
VL 23
IS 5
BP 352
EP 359
DI 10.3109/15376516.2012.762082
PG 8
WC Toxicology
SC Toxicology
GA 155KC
UT WOS:000319745600009
PM 23278212
ER
PT J
AU Venkataramani, AS
Maughan-Brown, B
AF Venkataramani, Atheendar S.
Maughan-Brown, Brendan
TI Effects of Household Shocks and Poverty on the Timing of Traditional
Male Circumcision and HIV Risk in South Africa
SO AIDS AND BEHAVIOR
LA English
DT Article
DE Economic shocks; Poverty; Male circumcision; HIV; South Africa
ID SEXUAL-BEHAVIOR; INFECTION; PREVENTION; HEALTH; ACCEPTABILITY;
COMPLICATIONS; INTERVENTION; PREVALENCE; WEALTH; MALAWI
AB Poverty may influence HIV risk by increasing vulnerability to economic shocks and thereby preventing key health investments. We explored this possibility by examining the relationship between household shocks and the timing of traditional male circumcision, a practice associated with considerable expense and whose HIV-prevention benefits are larger when done earlier, even within young adulthood. Using unique data on a sample of Xhosa men, a group that almost universally practices traditional circumcision, we found that respondents in the poorest households delayed circumcision by 2 years if a household member experienced loss of income or death and/or illness. The impact of these shocks declined with increasing household income. Our findings suggest that interventions that work to mitigate the impact of shocks among the poor may be useful in HIV prevention efforts. More generally, they illustrate that the relationship between HIV and wealth may be more nuanced than assumed in previous work.
C1 [Venkataramani, Atheendar S.] Harvard Univ, Massachusetts Gen Hosp, Dept Med, Cambridge, MA 02138 USA.
[Maughan-Brown, Brendan] Univ Cape Town, SALDRU, ZA-7701 Cape Town, South Africa.
RP Maughan-Brown, B (reprint author), Univ Cape Town, SALDRU, ZA-7701 Cape Town, South Africa.
EM brendan.maughanbrown@gmail.com
NR 27
TC 0
Z9 0
U1 1
U2 11
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 JUN
PY 2013
VL 17
IS 5
BP 1668
EP 1674
DI 10.1007/s10461-013-0459-3
PG 7
WC Public, Environmental & Occupational Health; Social Sciences, Biomedical
SC Public, Environmental & Occupational Health; Biomedical Social Sciences
GA 150SZ
UT WOS:000319412800009
PM 23536141
ER
PT J
AU Vogenthaler, NS
Kushel, MB
Hadley, C
Frongillo, EA
Riley, ED
Bangsberg, DR
Weiser, SD
AF Vogenthaler, Nicholas S.
Kushel, Margot B.
Hadley, Craig
Frongillo, Ed A., Jr.
Riley, Elise D.
Bangsberg, David R.
Weiser, Sheri D.
TI Food Insecurity and Risky Sexual Behaviors Among Homeless and Marginally
Housed HIV-Infected Individuals in San Francisco
SO AIDS AND BEHAVIOR
LA English
DT Article
DE Food insecurity; HIV/AIDS; Sexual risk
ID INJECTION-DRUG USERS; INSUFFICIENCY; HIV/AIDS; ATLANTA; HAART;
VULNERABILITY; PREVALENCE; SYMPTOMS; POVERTY; AFRICA
AB Food insecurity is common among HIV-infected populations in resource-rich and resource-poor countries. We hypothesized that food insecurity would be associated with risky sexual behaviors. We examined this hypothesis among all sexually active participants (n = 154) in the Research on Access to Care in the Homeless (REACH) cohort in San Francisco. The outcomes were unprotected vaginal or anal sex and multiple sexual partners during the prior 90 days. Associations were examined using repeated measures multivariable logistic regression analyses. Food insecurity was independently associated with unprotected sexual activity (AOR = 2.01 for each five point increase in HFIAS scale, 95 % CI 1.31-3.10) and multiple sexual partners (AOR = 1.54 for each five-point increase in HFIAS scale, 95 % CI 1.05-2.29). Food insecurity is a risk factor for unprotected sexual activity and multiple sexual partners among homeless and marginally housed HIV-infected individuals in San Francisco. Measures to alleviate food insecurity may play a role in decreasing secondary HIV transmission.
C1 [Vogenthaler, Nicholas S.] Hennepin Cty Med Ctr, Div Infect Dis, Minneapolis, MN 55415 USA.
[Kushel, Margot B.] Univ Calif San Francisco, Div Gen Internal Med, San Francisco Gen Hosp, San Francisco, CA 94143 USA.
[Hadley, Craig] Emory Univ, Dept Anthropol, Atlanta, GA 30322 USA.
[Frongillo, Ed A., Jr.] Univ S Carolina, Arnold Sch Publ Hlth, Dept Hlth Promot Educ & Behav, Columbia, SC 29208 USA.
[Riley, Elise D.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Bangsberg, David R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Harvard Initiat Global Hlth, Boston, MA USA.
[Weiser, Sheri D.] Univ Calif San Francisco, Ctr AIDS Prevent Studies, San Francisco, CA 94143 USA.
RP Vogenthaler, NS (reprint author), Hennepin Cty Med Ctr, Div Infect Dis, 701 Pk Ave,O1, Minneapolis, MN 55415 USA.
EM nicholas.vogenthaler@hcmed.org
RI Nguyen, Giang/D-9027-2016
FU NCRR NIH HHS [UL1 RR024131]; NIAID NIH HHS [P30 AI060354]; NIMH NIH HHS
[K-24 MH 87227, K23 MH079713, K23 MH079713-01, K24 MH087227, R01
MH054907]; PHS HHS [R0-1 54907]
NR 35
TC 12
Z9 13
U1 0
U2 11
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 JUN
PY 2013
VL 17
IS 5
BP 1688
EP 1693
DI 10.1007/s10461-012-0355-2
PG 6
WC Public, Environmental & Occupational Health; Social Sciences, Biomedical
SC Public, Environmental & Occupational Health; Biomedical Social Sciences
GA 150SZ
UT WOS:000319412800012
PM 23086429
ER
PT J
AU O'Cleirigh, C
Newcomb, ME
Mayer, KH
Skeer, M
Traeger, L
Safren, SA
AF O'Cleirigh, Conall
Newcomb, Michael E.
Mayer, Kenneth H.
Skeer, Margie
Traeger, Lara
Safren, Steven A.
TI Moderate Levels of Depression Predict Sexual Transmission Risk in
HIV-Infected MSM: A Longitudinal Analysis of Data From Six Sites
Involved in a "Prevention for Positives" Study
SO AIDS AND BEHAVIOR
LA English
DT Article
DE HIV prevention with positives; Men who have sex with men; Sexual risk;
Depression
ID HUMAN-IMMUNODEFICIENCY-VIRUS; CONTROLLED-TRIAL; YOUNG MEN; WOMEN;
THERAPY; SCALE
AB Depression is highly comorbid with HIV and may contribute to increased sexual transmission risk behavior (TRB) amongst HIV-infected MSM, the largest risk group for HIV in the U.S. However, examinations of this effect are inconsistent. The present longitudinal analyses of 746 HIV-infected MSM is from a multi-site "prevention for positives" study. A non-linear association between depression and TRB emerged. Moderate levels of depression (compared to either low or high levels) were associated with a more modest decline in the odds of sexual risk behavior over 12-month follow-up. Assessing depression in HIV primary care settings may help to identify those at risk and integrating the treatment of depression into secondary prevention and treatment initiatives may decrease the likelihood of sexual risk and help to contain the epidemic among MSM.
C1 [O'Cleirigh, Conall; Newcomb, Michael E.; Traeger, Lara; Safren, Steven A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[O'Cleirigh, Conall; Newcomb, Michael E.; Mayer, Kenneth H.; Traeger, Lara; Safren, Steven A.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[O'Cleirigh, Conall; Newcomb, Michael E.; Mayer, Kenneth H.; Skeer, Margie; Safren, Steven A.] Fenway Hlth, Fenway Inst, Boston, MA USA.
[Mayer, Kenneth H.] Beth Israel Hosp, Boston, MA USA.
RP O'Cleirigh, C (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA.
EM cocleirigh@partners.org
FU NIDA NIH HHS [R34 DA031038]; NIMH NIH HHS [R01 MH095624, K24 MH094214,
K24MH094214]; PHS HHS [H97HA01293-01-00]
NR 24
TC 24
Z9 24
U1 1
U2 5
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 JUN
PY 2013
VL 17
IS 5
BP 1764
EP 1769
DI 10.1007/s10461-013-0462-8
PG 6
WC Public, Environmental & Occupational Health; Social Sciences, Biomedical
SC Public, Environmental & Occupational Health; Biomedical Social Sciences
GA 150SZ
UT WOS:000319412800020
PM 23605154
ER
PT J
AU Simon, HB
AF Simon, Harvey B.
TI The Write Stuff: How Good Writing Can Enhance Patient Care and
Professional Growth
SO AMERICAN JOURNAL OF MEDICINE
LA English
DT Editorial Material
ID SHARED DECISION-MAKING; HEALTH LITERACY; COHORT; RECORD
C1 [Simon, Harvey B.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
[Simon, Harvey B.] MIT, Hlth Sci Technol Fac, Cambridge, MA 02139 USA.
[Simon, Harvey B.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Simon, HB (reprint author), Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
NR 13
TC 1
Z9 1
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9343
J9 AM J MED
JI Am. J. Med.
PD JUN
PY 2013
VL 126
IS 6
BP 467
EP 471
DI 10.1016/j.amjmed.2012.11.020
PG 5
WC Medicine, General & Internal
SC General & Internal Medicine
GA 146TY
UT WOS:000319116400018
PM 23561628
ER
PT J
AU Clair, C
Meigs, JB
Rigotti, NA
AF Clair, Carole
Meigs, James B.
Rigotti, Nancy A.
TI Smoking Behavior among US Adults with Diabetes or Impaired Fasting
Glucose
SO AMERICAN JOURNAL OF MEDICINE
LA English
DT Article
DE Diabetes; Impaired fasting glucose; Smoking
ID CIGARETTE-SMOKING; NATIONAL-HEALTH; BODY-FAT; RISK; INDIVIDUALS;
POPULATION; DISEASE; TRENDS
AB BACKGROUND: Cigarette smoking is a well-known cardiovascular risk factor and its impact on cardiovascular disease is even greater among people with diabetes. The aim of this study is to compare the prevalence and determinants of smoking among US adults with diabetes or impaired fasting glucose, and those without diabetes or impaired fasting glucose.
METHODS: Weanalyzed data from the National Health and Nutrition Examination Surveys (1999-2008). Age-adjusted prevalence of smoking was calculated, and we used logistic regression models to identify the correlates of smoking among people with diabetes, impaired fasting glucose, and normal glucose metabolism.
RESULTS: Among 24,649 participants >= 20 years old, age-adjusted smoking prevalence was 25.7% in 3111 individuals with diabetes, 24.2% in 3557 individuals with impaired fasting glucose, and 24.1% in 17,981 individuals without diabetes. Smoking prevalence did not differ across groups or change over time (1999-2008) in any group. Younger age, less education, more alcohol consumption, less physical activity, and major depression symptoms were associated with smoking in people with diabetes, impaired fasting glucose, and normal glucose metabolism.
CONCLUSIONS: In the US, smoking prevalence among people with diabetes and impaired fasting glucose has not changed and is comparable with the nondiabetic population. Tobacco control efforts should be intensified among this population at high risk for complications and mortality. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Clair, Carole; Rigotti, Nancy A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Tobacco Res & Treatment Ctr, Boston, MA USA.
[Meigs, James B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Med, Boston, MA USA.
RP Clair, C (reprint author), Dept Ambulatory Care & Community Med, 44 Bugnon Ave, CH-1011 Lausanne, Switzerland.
EM carole.willi@gmail.com
RI Clair, Carole/D-9786-2014
OI Clair, Carole/0000-0001-5281-0943
FU Swiss National Science Foundation [PBLAP3-127728/1]; SICPA foundation;
National Heart Lung and Blood Institute [K24-HL04440]; National
Institute of Diabetes and Digestive Kidney Disease [K24 DK080140];
Pfizer; Nabi Biopharmaceuticals
FX CC was supported by a grant from the Swiss National Science Foundation,
PBLAP3-127728/1, and by a grant from the SICPA foundation. NAR's effort
was supported by a grant from the National Heart Lung and Blood
Institute (K24-HL04440). JBM was supported by National Institute of
Diabetes and Digestive Kidney Disease grant K24 DK080140.; Conflict of
Interest: CC does not report any conflict of interest. NAR has consulted
without pay for Pfizer and Free and Clear, Inc. about smoking cessation
and has conducted research projects sponsored by Pfizer and Nabi
Biopharmaceuticals. JBM does not report any conflicts of interest.
NR 14
TC 4
Z9 4
U1 0
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9343
J9 AM J MED
JI Am. J. Med.
PD JUN
PY 2013
VL 126
IS 6
BP 541
EP U117
DI 10.1016/j.amjmed.2012.11.029
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA 146TY
UT WOS:000319116400031
ER
PT J
AU Willett, LL
Estrada, CA
Adams, M
Arora, V
Call, S
Chacko, K
Chaudhry, S
Halvorsen, AJ
Hopkins, R
McDonald, FS
AF Willett, Lisa L.
Estrada, Carlos A.
Adams, Michael
Arora, Vineet
Call, Stephanie
Chacko, Karen
Chaudhry, Saima
Halvorsen, Andrew J.
Hopkins, Robert
McDonald, Furman S.
TI Challenges with Continuity Clinic and Core Faculty Accreditation
Requirements
SO AMERICAN JOURNAL OF MEDICINE
LA English
DT Editorial Material
ID INTERNAL-MEDICINE; PROGRAM-DIRECTORS; EDUCATION
C1 [Willett, Lisa L.] Univ Alabama Birmingham, Dept Med, Div Gen Internal Med, Birmingham, AL 35294 USA.
[Estrada, Carlos A.] Birmingham Vet Affairs Med Ctr, Vet Affairs Natl Qual Scholars Program, Birmingham, AL USA.
[Estrada, Carlos A.] Univ Alabama Birmingham, Div Gen Internal Med, Birmingham, AL 35294 USA.
[Adams, Michael] Medstar Georgetown Univ Hosp, Washington, DC USA.
[Arora, Vineet] Univ Chicago, Dept Med, Chicago, IL 60637 USA.
[Call, Stephanie] Virginia Commonwealth Univ, Dept Internal Med, Richmond, VA 23284 USA.
[Chacko, Karen] Univ Colorado, Primary Care Internal Med Residency Program, Denver, CO 80202 USA.
[Chacko, Karen] Univ Colorado, Internal Med Residency Program, Denver, CO 80202 USA.
[Chaudhry, Saima] Hofstra North Shore LIJ Sch Med, Dept Med, Internal Med Residency Program, Hempstead, NY USA.
[Halvorsen, Andrew J.] Mayo Clin, Dept Med, Internal Med Residency Off Educ Innovat, Rochester, MI USA.
[Hopkins, Robert] Univ Arkansas Med Sci, Little Rock, AR 72205 USA.
[Hopkins, Robert] Univ Arkansas Med Sci, Div Gen Internal Med, Little Rock, AR 72205 USA.
[McDonald, Furman S.] Mayo Clin, Dept Med, Rochester, MI USA.
[McDonald, Furman S.] Mayo Clin, Div Gen, Rochester, MI USA.
[McDonald, Furman S.] Mayo Clin, Hosp Internal Med, Rochester, MI USA.
RP Willett, LL (reprint author), Univ Alabama Birmingham, Dept Med, Div Gen Internal Med, BDB 341,1720 2nd Ave S, Birmingham, AL 35294 USA.
EM lwillett@uab.edu
OI Arora, Vineet/0000-0002-4745-7599
NR 16
TC 4
Z9 4
U1 0
U2 2
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 JUN
PY 2013
VL 126
IS 6
BP 550
EP 556
DI 10.1016/j.amjmed.2013.02.008
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 146TY
UT WOS:000319116400033
PM 23684398
ER
PT J
AU Wasserman, MS
Rose, AJ
AF Wasserman, Michael S.
Rose, Adam J.
TI An Unusual Presenting Complaint for Herpes Zoster
SO AMERICAN JOURNAL OF MEDICINE
LA English
DT Letter
C1 [Wasserman, Michael S.; Rose, Adam J.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.
[Wasserman, Michael S.; Rose, Adam J.] VA Boston Healthcare Syst, Boston, MA USA.
[Rose, Adam J.] Bedford VA Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA.
RP Wasserman, MS (reprint author), 72 East Concord St,A-208, Boston, MA 02118 USA.
EM michaelswasserman@gmail.com
NR 2
TC 0
Z9 0
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9343
J9 AM J MED
JI Am. J. Med.
PD JUN
PY 2013
VL 126
IS 6
BP E3
EP E4
DI 10.1016/j.amjmed.2013.01.015
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 146TY
UT WOS:000319116400002
PM 23541377
ER
PT J
AU Kerr, DA
Lopez, HU
Deshpande, V
Hornicek, FJ
Duan, ZF
Zhang, YX
Rosenberg, AE
Borger, DR
Nielsen, GP
AF Kerr, Darcy A.
Lopez, Hector U.
Deshpande, Vikram
Hornicek, Francis J.
Duan, Zhenfeng
Zhang, Yaxia
Rosenberg, Andrew E.
Borger, Darrel R.
Nielsen, G. Petur
TI Molecular Distinction of Chondrosarcoma From Chondroblastic Osteosarcoma
Through IDH1/2 Mutations
SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY
LA English
DT Article
DE IDH1; IDH2; chondrosarcoma; dedifferentiation; osteosarcoma
ID ISOCITRATE DEHYDROGENASE 1; IDH2 MUTATIONS; MYELOPROLIFERATIVE
NEOPLASMS; MAFFUCCI SYNDROME; OLLIER DISEASE; CANCER; TUMORS;
2-HYDROXYGLUTARATE; DIFFERENTIATION; LEUKEMIA
AB Distinguishing chondrosarcoma from chondroblastic osteosarcoma can be difficult and highly subjective, especially on a small biopsy specimen. This distinction is critical in determining the most accurate prognosis and appropriate treatment modality, as adjuvant chemotherapy with surgery is standard treatment for osteosarcoma, whereas chondrosarcoma is generally treated by surgical excision alone. Cartilaginous neoplasms have recently been shown to frequently (56%) harbor gene mutations in the metabolic enzymes isocitrate dehydrogenase 1 (IDH1) and IDH2 (IDH1 > IDH2), whereas other mesenchymal tumors lack these genetic aberrations. We investigated whether the presence of IDH1/2 mutations can be used to distinguish chondrosarcoma from chondroblastic osteosarcoma. Tumors including 25 predominantly high-grade chondrosarcomas and 65 osteosarcomas (44 chondroblastic osteosarcomas and 21 mixed osteosarcomas with a chondroblastic component) were evaluated, and a total of 59 cases (66%) were suitable for genotyping. Mutational analysis was performed using a multiplexed polymerase chain reaction genotyping platform to query for hotspot mutations in the genes IDH1 at codon R132. IDH1-negative cases underwent Sanger sequencing of IDH2 exon 4. No osteosarcomas (0/36) and 61% of chondrosarcomas (14/23) harbored a somatic mutation in IDH1/2, with the majority (86%) of mutations found in the IDH1 gene. IDH1/2 mutation analysis appears to be a promising biomarker for the distinction of chondrosarcoma from chondroblastic osteosarcoma. A positive result strongly favors the diagnosis of chondrosarcoma over chondroblastic osteosarcoma. The presence of IDH1/2 mutations can also help confirm the diagnosis of dedifferentiated chondrosarcoma when the tumor displays osteosarcomatous differentiation.
C1 [Kerr, Darcy A.; Deshpande, Vikram; Nielsen, G. Petur] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Lopez, Hector U.; Borger, Darrel R.] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA.
[Hornicek, Francis J.; Duan, Zhenfeng] Massachusetts Gen Hosp, Ctr Sarcoma & Connect Tissue Oncol, Boston, MA 02114 USA.
[Kerr, Darcy A.; Deshpande, Vikram; Hornicek, Francis J.; Duan, Zhenfeng; Borger, Darrel R.; Nielsen, G. Petur] Harvard Univ, Sch Med, Boston, MA USA.
[Zhang, Yaxia; Rosenberg, Andrew E.] Univ Miami, Dept Pathol, Miami, FL USA.
[Zhang, Yaxia; Rosenberg, Andrew E.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA.
RP Nielsen, GP (reprint author), Massachusetts Gen Hosp, MGH Pathol Serv, Warren Bldg 225,55 Fruit St, Boston, MA 02114 USA.
EM gnielsen@partners.org
FU Vickery Grant, MGH Pathology Department
FX Supported by a Vickery Grant, MGH Pathology Department. D.R.B. is a paid
consultant for Bio-Reference Laboratories Inc. (licensee of SNaPshot).
For the remaining authors none were declared.
NR 28
TC 21
Z9 21
U1 0
U2 7
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 JUN
PY 2013
VL 37
IS 6
BP 787
EP 795
DI 10.1097/PAS.0b013e31827ab703
PG 9
WC Pathology; Surgery
SC Pathology; Surgery
GA 145WE
UT WOS:000319049000001
PM 23598960
ER
PT J
AU Gilks, CB
Oliva, E
Soslow, RA
AF Gilks, C. Blake
Oliva, Esther
Soslow, Robert A.
TI Poor Interobserver Reproducibility in the Diagnosis of High-grade
Endometrial Carcinoma
SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY
LA English
DT Article
DE endometrial carcinoma; subtype diagnosis; reproducibility; serous;
endometrioid
ID GYNECOLOGIC-ONCOLOGY-GROUP; CLEAR-CELL; CLINICOPATHOLOGICAL ANALYSIS;
SEROUS CARCINOMAS; OVARIAN-CARCINOMA; BREAST-CANCER; TRIAL;
DIFFERENTIATION; RADIOTHERAPY; MULTICENTER
AB Patients with high-grade subtypes of endometrial carcinoma (grade 3 endometrioid, serous, clear cell, or carcinosarcoma) have a relatively poor prognosis. The specific subtype may be used to guide patient management, but there is little information on the reproducibility of subtype diagnosis in cases of high-grade endometrial carcinoma. Fifty-six cases diagnosed as a high-grade subtype of endometrial carcinoma were identified from the pathology archives of Vancouver General Hospital. All slides for each case were reviewed independently by 3 pathologists, who diagnosed the specific tumor subtype(s) and assigned the percentage of each subtype for mixed tumors. Agreement between observers was categorized as follows: major disagreement: (A) no consensus for low-grade endometrioid versus high- grade carcinoma (any subtype), or (B) no consensus with respect to the predominant high- grade subtype present; minor disagreement: consensus was reached about the cell type of the predominant component of a mixed tumor, but there was disagreement about the subtype of the minor component. A tissue microarray was constructed from these cases and immunostained for p16, ER, PR, PTEN, and p53. In 35 of 56 (62.5%) cases, there was agreement between all 3 reviewers regarding the subtype diagnosis of the exclusive (in pure tumors) or predominant (in mixed tumors) high- grade component. Of these cases, there was a minor disagreement (ie, disagreement about the minor high- grade component subtype in a mixed tumor) in 4 cases (4/56, 7.1%). In 20 of 56 (35.8%) cases there was a major disagreement; in 17 (30.4%) of these cases there was no consensus about the major subtype diagnosis, whereas in 3 (5.4%) cases there was disagreement about whether a component of high- grade endometrial carcinoma was present. In the final case, all 3 reviewers diagnosed the case as low-grade endometrioid carcinoma, disagreeing with the original diagnosis of high- grade carcinoma. The most frequent areas of disagreement were serous versus clear cell (7 cases) and serous versus grade 3 endometrioid (6 cases). Immunostaining results using the 5-marker immunopanel were then used to adjudicate in the 6 cases in which there was disagreement between reviewers with respect to serous versus endometrioid carcinoma, and these supported a diagnosis of serous carcinoma in 4 of 6 cases and endometrioid carcinoma in 2 of 6 cases. Pairwise comparison between the reviewers for the 20 cases classified as showing major disagreement was as follows: reviewer 1 and reviewer 2 agreed in 5/20 cases, reviewer 1 and reviewer 3 agreed in 7/20 cases, and reviewer 2 and reviewer 3 agreed in 8/20 cases, indicating that disagreements were not because of a single reviewer holding outlier opinions. Diagnostic consensus among 3 reviewers about the exclusive or major subtype of high- grade endometrial carcinoma was reached in only 35/56 (62.5%) cases, and in 4 of these cases there was disagreement about the minor component present. This poor reproducibility did not reflect systematic bias on the part of any 1 reviewer. There is a need for molecular tools to aid in the accurate and reproducible diagnosis of high- grade endometrial carcinoma subtype.
C1 [Gilks, C. Blake] Vancouver Gen Hosp, Dept Pathol & Lab Med, Vancouver, BC V5Z 1M9, Canada.
[Gilks, C. Blake] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada.
[Oliva, Esther] Massachusetts Gen Hosp, Dept Pathol & Lab Med, Boston, MA 02114 USA.
[Soslow, Robert A.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA.
RP Gilks, CB (reprint author), Vancouver Gen Hosp, Dept Pathol & Lab Med, Rm 1503,1st Floor JPPN,855 West 12th Ave, Vancouver, BC V5Z 1M9, Canada.
EM blake.gilks@vch.ca
OI Soslow, Robert/0000-0002-7269-5898
NR 34
TC 53
Z9 53
U1 2
U2 7
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 JUN
PY 2013
VL 37
IS 6
BP 874
EP 881
DI 10.1097/PAS.0b013e31827f576a
PG 8
WC Pathology; Surgery
SC Pathology; Surgery
GA 145WE
UT WOS:000319049000011
PM 23629444
ER
PT J
AU Shanmugasundararaj, S
Zhou, XJ
Neunzig, J
Bernhardt, R
Cotten, JF
Ge, R
Miller, KW
Raines, DE
AF Shanmugasundararaj, Sivananthaperumal
Zhou, Xiaojuan
Neunzig, Jens
Bernhardt, Rita
Cotten, Joseph F.
Ge, Rile
Miller, Keith W.
Raines, Douglas E.
TI . Carboetomidate: An Analog of Etomidate That Interacts Weakly with 11
beta-Hydroxylase
SO ANESTHESIA AND ANALGESIA
LA English
DT Article
ID ADRENOCORTICAL-FUNCTION; CYTOCHROME P4502B4; ANESTHETIC ETOMIDATE;
ANGSTROM RESOLUTION; BINDING; COORDINATION; INHIBITION; IMIDAZOLE;
INSIGHT
AB BACKGROUND: Carboetomidate is a pyrrole etomidate analog that is 3 orders of magnitude less potent an inhibitor of in vitro cortisol synthesis than etomidate (an imidazole) and does not inhibit in vivo steroid production. Although carboetomidate's reduced functional effect on steroid synthesis is thought to reflect lower binding affinity to 11 beta-hydroxylase, differential binding to this enzyme has never been experimentally demonstrated. In the current study, we tested the hypothesis that carboetomidate and etomidate bind with differential affinity to 11 beta-hydroxylase by comparing their abilities to inhibit photoaffinity labeling of purified enzyme by a photoactivatable etomidate analog and to modify the enzyme's absorption spectrum in a way that is indicative of ligand binding. In addition, we made a preliminary exploration of the manner in which etomidate and carboetomidate might differentially interact with this site using spectroscopic methods as well as molecular modeling techniques to better understand the structural basis for their selectivity.
METHODS: The ability of azi-etomidate to inhibit cortisol synthesis was tested by assessing its ability to inhibit cortisol synthesis by H295R cells. The binding affinities of etomidate and carboetomidate to 11 beta-hydroxylase were compared by assessing their abilities to (1) inhibit photoincorporation of the photolabile etomidate analog [H-3]azi-etomidate into the enzyme and (2) modify the absorption spectrum of the enzyme's heme group. In silico docking studies of etomidate, carboetomidate, and azi-etomidate binding to 11 beta-hydroxylase were performed using the computer software GOLD.
RESULTS: Similar to etomidate, azi-etomidate potently inhibits in vitro cortisol synthesis. Etomidate inhibited [H-3]azi-etomidate photolabeling of 11 beta-hydroxylase in a concentration-dependent manner. At a concentration of 40 mu M, etomidate reduced photoincorporation of [H-3] azi-etomidate by 96% +/- 1% whereas carboetomidate had no experimentally detectable effect. On addition of etomidate to 11 beta-hydroxylase, a type 2 difference spectrum was produced indicative of etomidate complexation with the enzyme's heme iron; carboetomidate had no effect whereas azi-etomidate produced a reverse type 1 spectrum. Computer modeling studies predicted that etomidate, carboetomidate, and azi-etomidate can fit into the heme-containing pocket that forms 11 beta-hydroxylase's active site and pose with their carbonyl oxygens interacting with the heme iron and their phenyl rings stacking with phenylalanine-80. However, additional unique poses were identified for etomidate and azi-etomidate that likely account for their higher affinities.
CONCLUSIONS: Carboetomidate's reduced ability to suppress in vitro and in vivo steroid synthesis as compared with etomidate reflects its lower binding affinity to 11 beta-hydroxylase and may be attributed to carboetomidate's inability to form a coordination bond with the heme iron located at the enzyme's active site.
C1 [Shanmugasundararaj, Sivananthaperumal; Zhou, Xiaojuan; Cotten, Joseph F.; Ge, Rile; Miller, Keith W.; Raines, Douglas E.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
[Neunzig, Jens; Bernhardt, Rita] Univ Saarland, Inst Biochem, Saarbrucken, Germany.
RP Raines, DE (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA.
EM draines@partners.org
FU National Institutes of Health, Bethesda, MD [R01-GM087316,
R21-DA029253]; Deutsche Forschungsgemeinschaft [FOR 13698]; Department
of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General
Hospital; National Institutes of Health [P41 RR-01081]; [K08-GM083216]
FX This research was supported by grants to D.E.R. (R01-GM087316 and
R21-DA029253 from the National Institutes of Health, Bethesda, MD), R.B.
(FOR 13698 from the Deutsche Forschungsgemeinschaft), J.F.C.
(K08-GM083216), and by the Department of Anesthesia, Critical Care, and
Pain Medicine, Massachusetts General Hospital.; The authors thank Prof.
Hermans (Department of Pharmacology and Toxicology, Cardiovascular
Research Institute, University Maastricht, the Netherlands) for
providing them with the published homology model and Wolfgang Reinle for
preparation of the protein. Molecular graphics images were produced
using the University of California, San Francisco Chimera package from
the Resource for Biocomputing, Visualization, and Informatics at the
University of California, San Francisco (supported by National
Institutes of Health P41 RR-01081).
NR 26
TC 3
Z9 4
U1 0
U2 10
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0003-2999
J9 ANESTH ANALG
JI Anesth. Analg.
PD JUN
PY 2013
VL 116
IS 6
BP 1249
EP 1256
DI 10.1213/ANE.0b013e31828b3637
PG 8
WC Anesthesiology
SC Anesthesiology
GA 154XU
UT WOS:000319710800011
PM 23492967
ER
PT J
AU Bateman, BT
Mhyre, JM
Ehrenfeld, J
Kheterpal, S
Abbey, KR
Argalious, M
Berman, MF
St Jacques, P
Levy, W
Loeb, RG
Paganelli, W
Smith, KW
Wethington, KL
Wax, D
Pace, NL
Tremper, K
Sandberg, WS
AF Bateman, Brian T.
Mhyre, Jill M.
Ehrenfeld, Jesse
Kheterpal, Sachin
Abbey, Kenneth R.
Argalious, Maged
Berman, Mitchell F.
St Jacques, Paul
Levy, Warren
Loeb, Robert G.
Paganelli, William
Smith, Kelly W.
Wethington, Kevin L.
Wax, David
Pace, Nathan L.
Tremper, Kevin
Sandberg, Warren S.
TI The Risk and Outcomes of Epidural Hematomas After Perioperative and
Obstetric Epidural Catheterization: A Report from the Multicenter
Perioperative Outcomes Group Research Consortium
SO ANESTHESIA AND ANALGESIA
LA English
DT Article
ID REGIONAL-ANESTHESIA; COMPLICATIONS; THERAPY
AB BACKGROUND: In this study, we sought to determine the frequency and outcomes of epidural hematomas after epidural catheterization.
METHODS: Eleven centers participating in the Multicenter Perioperative Outcomes Group used electronic anesthesia information systems and quality assurance databases to identify patients who had epidural catheters inserted for either obstetrical or surgical indications. From this cohort, patients undergoing laminectomy for the evacuation of hematoma within 6 weeks of epidural placement were identified.
RESULTS: Seven of 62,450 patients undergoing perioperative epidural catheterizations developed hematoma requiring surgical evacuation. The event rate was 11.2 x 10(-5)(95% confidence interval [CI], 4.5 x 10(-5) to 23.1 x 10(-5)). Four of the 7 had anticoagulation/antiplatelet therapy that deviated from American Society of Regional Anesthesia guidelines. None of 79,837 obstetric patients with epidural catheterizations developed hematoma (upper limit of the 95% CI, 4.6 x 10(-5)). The hematoma rate in obstetric epidural catheterizations was significantly lower than in perioperative epidural catheterizations (P = 0.003).
CONCLUSIONS: In this series, the 95% CI for the frequency of epidural hematoma requiring laminectomy after epidural catheter placement for perioperative anesthesia/analgesia was 1 event per 22,189 placements to 1 event per 4330 placements. Risk was significantly lower in obstetric epidurals.
C1 [Bateman, Brian T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
[Bateman, Brian T.] Harvard Univ, Div Pharmacoepidemiol & Pharmacoecon, Sch Med, Brigham & Womens Hosp, Boston, MA 02114 USA.
[Mhyre, Jill M.; Kheterpal, Sachin; Tremper, Kevin] Univ Michigan Hlth Syst, Dept Anesthesiol, Ann Arbor, MI USA.
[Ehrenfeld, Jesse] Vanderbilt Univ, Dept Anesthesiol & Biomed Informat, Nashville, TN USA.
[Abbey, Kenneth R.] Oregon Hlth & Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR 97201 USA.
[Argalious, Maged] Cleveland Clin, Cleveland, OH 44106 USA.
[Berman, Mitchell F.] Columbia Univ, Dept Anesthesiol, New York, NY USA.
[St Jacques, Paul; Sandberg, Warren S.] Vanderbilt Univ, Sch Med, Dept Anesthesiol, Nashville, TN 37212 USA.
[St Jacques, Paul; Sandberg, Warren S.] Vanderbilt Univ, Sch Med, Dept Biomed Informat, Nashville, TN 37212 USA.
[St Jacques, Paul; Sandberg, Warren S.] Vanderbilt Univ, Sch Med, Dept Surg, Nashville, TN 37212 USA.
[Levy, Warren] Univ Penn, Dept Anesthesia, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Loeb, Robert G.] Univ Arizona, Dept Anesthesiol, Tucson, AZ USA.
[Paganelli, William] Univ Vermont, Fletcher Allen Hlth Care, Burlington, VT USA.
[Smith, Kelly W.; Wethington, Kevin L.; Pace, Nathan L.] Univ Utah, Dept Anesthesiol, Salt Lake City, UT USA.
[Argalious, Maged] Mt Sinai Sch Med, Dept Anesthesiol, New York, NY USA.
RP Bateman, BT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA.
EM BBateman@partners.org
OI Ehrenfeld, Jesse/0000-0003-3427-0140
NR 10
TC 35
Z9 37
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0003-2999
J9 ANESTH ANALG
JI Anesth. Analg.
PD JUN
PY 2013
VL 116
IS 6
BP 1380
EP 1385
DI 10.1213/ANE.0b013e318251daed
PG 6
WC Anesthesiology
SC Anesthesiology
GA 154XU
UT WOS:000319710800029
PM 22504213
ER
PT J
AU Crane, C
Cornejo, A
Lyons, R
Alter, GJ
AF Crane, Curtis
Cornejo, Agustin
Lyons, Robert
Alter, Gary J.
TI Urethral Reconstruction Using a Prefabricated Pedicled Gracilis Flap
SO ANNALS OF PLASTIC SURGERY
LA English
DT Article
DE urethral injury; urethral disruption; urethral reconstruction; pedicled
gracilis flap; Fournier reconstruction
AB This case study describes a patient who experienced an iatrogenic urethral injury because of a Fournier gangrene debridement. Because of the extent of the debridement, which resected all penile and scrotal dartos tissue, no local flaps that would typically be used to reconstruct a urethral disruption were possible. The authors chose to use a prefabricated pedicled gracilis flap to restore urethral continuity.
C1 [Crane, Curtis; Alter, Gary J.] Univ Texas Hlth Sci Ctr San Antonio, Dept Plast Surg, San Antonio, TX 78229 USA.
[Cornejo, Agustin] Univ Texas Hlth Sci Ctr San Antonio, Dept Gen Surg, San Antonio, TX 78229 USA.
[Lyons, Robert] South Texas Vet Hlth Care Syst, Audie L Murphy Surg Serv, San Antonio, TX USA.
[Alter, Gary J.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA.
RP Crane, C (reprint author), Dept Plast Surg, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA.
EM cnd51924@yahoo.com
NR 5
TC 0
Z9 0
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0148-7043
J9 ANN PLAS SURG
JI Ann. Plast. Surg.
PD JUN
PY 2013
VL 70
IS 6
BP 691
EP 693
DI 10.1097/SAP.0b013e3182414843
PG 3
WC Surgery
SC Surgery
GA 146DA
UT WOS:000319068200020
PM 22791063
ER
PT J
AU Zhao, GF
Yu, YM
Kaneki, M
Tompkins, RG
Fischman, AJ
AF Zhao, Gaofeng
Yu, Yong-Ming
Kaneki, Masao
Tompkins, Ronald G.
Fischman, Alan J.
TI Simvastatin Protects Hepatocytes From Apoptosis by Suppressing the
TNF-alpha/Caspase-3 Signaling Pathway in Mice With Burn Injury
SO ANNALS OF SURGERY
LA English
DT Article
DE Apoptosis; Caspase-3; Hepatocyte; Simvastatin; tumor necrosis factor
alpha
ID INDUCED OXIDATIVE INJURY; INDUCED LIVER-INJURY; THERMAL-INJURY; REMOTE
ORGANS; STRESS; CANCER; TNF; ROSUVASTATIN; INFECTION; RATS
AB Objective: To investigate the liver cellular apoptosis in response to burn injury and find out if statin treatment can ameliorate this process. The hypothesis is that statin may modulate apoptosis-related gene expression and thereby reduce hepatocytic apoptosis after burn injury.
Methods: Mice were subjected to 30% full-thickness burn injury and then treated either with or without simvastatin. The livers were harvested for histological assessment and determinations of gene expression. To investigate the mechanism involved, tumor necrosis factor (TNF)-alpha and caspase-3 knockout (KO) mice were also used to evaluate the effects of burn injury and simvastatin treatment on burn-induced liver injury. The effects of simvastatin on TNF-alpha and caspase-3 expressions were also evaluated in cultured mouse hepatocytes.
Results: Burn injury induced significant liver damage, which was indicated by striking levels of apoptosis. Simvastatin reduced the apoptotic index in the livers of mice with burn injury and this effect could be abrogated by TNF-alpha or caspase-3 inhibitors. Simvastatin also decreased burn-induced TNF-alpha and caspase-3 expression in the liver. TNF-alpha and caspase-3 KO mice demonstrated lower levels of apoptotic hepatocytes in response to burn, and simvastatin did not further decrease hepatocyte apoptosis in either strain of KO mice. An in vitro study demonstrated that simvastatin suppresses TNF-alpha and caspase-3 expression in primary cultures of mouse hepatocytes.
Conclusions: Simvastatin reduces mouse hepatocyte apoptosis by suppressing expression of the TNF-alpha/caspase-3 pathway.
C1 [Zhao, Gaofeng] Massachusetts Gen Hosp, Shriners Hosp Children, Surg Serv, Boston, MA 02114 USA.
[Zhao, Gaofeng] Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Zhao, GF (reprint author), Massachusetts Gen Hosp, Shriners Hosp Children, Surg Serv, 55 Fruit St, Boston, MA 02114 USA.
EM jingxizh@yahoo.com
FU Shriners Hospitals for Children [87100]; National Institutes of Health
[P50 21700]
FX This study was supported in part by grants from Shriners Hospitals for
Children (Shriners grant 87100) and the National Institutes of Health
(P50 21700). The authors declare no conflicts of interest.
NR 27
TC 1
Z9 4
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0003-4932
J9 ANN SURG
JI Ann. Surg.
PD JUN
PY 2013
VL 257
IS 6
BP 1129
EP 1136
DI 10.1097/SLA.0b013e318273fdca
PG 8
WC Surgery
SC Surgery
GA 145VP
UT WOS:000319047300031
PM 23275311
ER
PT J
AU Joehanes, R
Ying, SX
Huan, TX
Johnson, AD
Raghavachari, N
Wang, R
Liu, PC
Woodhouse, KA
Sen, SK
Tanriverdi, K
Courchesne, P
Freedman, JE
O'Donnell, CJ
Levy, D
Munson, PJ
AF Joehanes, Roby
Ying, Saixia
Huan, Tianxiao
Johnson, Andrew D.
Raghavachari, Nalini
Wang, Richard
Liu, Poching
Woodhouse, Kimberly A.
Sen, Shurjo K.
Tanriverdi, Kahraman
Courchesne, Paul
Freedman, Jane E.
O'Donnell, Christopher J.
Levy, Daniel
Munson, Peter J.
TI Gene Expression Signatures of Coronary Heart Disease
SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
LA English
DT Article
DE biomarkers; coronary artery disease; coronary heart disease; gene
expression; myocardial infarction; transcriptomics
ID GENOME-WIDE ASSOCIATION; UBIQUITIN-PROTEASOME SYSTEM; BLOOD
MONONUCLEAR-CELLS; ARTERY-DISEASE; CARDIOVASCULAR-DISEASE; GRANZYME-B;
NONDIABETIC PATIENTS; WHOLE-BLOOD; APOPTOSIS; PROTEIN
AB Objective-To identify transcriptomic biomarkers of coronary heart disease (CHD) in 188 cases with CHD and 188 age-and sex-matched controls who were participants in the Framingham Heart Study.
Approach and Results-A total of 35 genes were differentially expressed in cases with CHD versus controls at false discovery rate< 0.5, including GZMB, TMEM56, and GUK1. Cluster analysis revealed 3 gene clusters associated with CHD, 2 linked to increased erythrocyte production and a third to reduced natural killer and T cell activity in cases with CHD. Exon-level results corroborated and extended the gene-level results. Alternative splicing analysis suggested that GUK1 and 38 other genes were differentially spliced in cases with CHD versus controls. Gene Ontology analysis linked ubiquitination and T-cell-related pathways with CHD.
Conclusions-Two bioinformatically defined groups of genes show consistent associations with CHD. Our findings are consistent with the hypotheses that hematopoesis is upregulated in CHD, possibly reflecting a compensatory mechanism, and that innate immune activity is disrupted in CHD or altered by its treatment. Transcriptomic signatures may be useful in identifying pathways associated with CHD and point toward novel therapeutic targets for its treatment and prevention.
C1 [Joehanes, Roby; Huan, Tianxiao; Johnson, Andrew D.; Courchesne, Paul; O'Donnell, Christopher J.; Levy, Daniel] NHLBI Framingham Heart Study, Framingham, MA USA.
[Joehanes, Roby; Huan, Tianxiao; Johnson, Andrew D.; Courchesne, Paul; O'Donnell, Christopher J.; Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA.
[Joehanes, Roby; Ying, Saixia; Munson, Peter J.] NIH, Math & Stat Comp Lab, Ctr Informat Technol, Bethesda, MD 20892 USA.
[Raghavachari, Nalini; Wang, Richard; Liu, Poching; Woodhouse, Kimberly A.] NHLBI, DNA Sequencing & Genom Core, Genet & Dev Biol Ctr, NIH, Bethesda, MD 20892 USA.
[Sen, Shurjo K.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Tanriverdi, Kahraman; Freedman, Jane E.] Univ Massachusetts, Sch Med, High Throughput Gene Express Biomarker Core, Worcester, MA USA.
[O'Donnell, Christopher J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA.
RP Munson, PJ (reprint author), Ctr Informat Technol, Math & Stat Comp Lab, NIH Bldg 12A,Room 2039, Bethesda, MD 20892 USA.
EM Levyd@NIH.Gov; Munson@helix.nih.gov
RI Huan, Tianxiao/D-6020-2014; Johnson, Andrew/G-6520-2013
FU Center for Population Studies; Boston University School of Medicine;
National Heart, Lung, and Blood Institute [N01-HC-25195]; Intramural
Research Programs of the National Heart, Lung, and Blood Institute, the
Center for Information Technology of the National Institutes of Health
FX This work was supported by funds from the Center for Population Studies
and the Intramural Research Programs of the National Heart, Lung, and
Blood Institute, the Center for Information Technology of the National
Institutes of Health, and from Boston University School of Medicine. The
Framingham Heart Study is supported by National Heart, Lung, and Blood
Institute contract N01-HC-25195.
NR 47
TC 29
Z9 29
U1 0
U2 14
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 JUN
PY 2013
VL 33
IS 6
BP 1418
EP +
DI 10.1161/ATVBAHA.112.301169
PG 37
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 146UR
UT WOS:000319119500044
PM 23539218
ER
PT J
AU van Eijsden, RGE
Stassen, C
Daenen, L
Van Mulders, SE
Bapat, PM
Siewers, V
Goossens, KVY
Nielsen, J
Delvaux, FR
Van Hummelen, P
Devreese, B
Willaert, RG
AF van Eijsden, Rudy G. E.
Stassen, Catherine
Daenen, Luk
Van Mulders, Sebastiaan E.
Bapat, Prashant M.
Siewers, Verena
Goossens, Katty V. Y.
Nielsen, Jens
Delvaux, Freddy R.
Van Hummelen, Paul
Devreese, Bart
Willaert, Ronnie G.
TI A universal fixation method based on quaternary ammonium salts
(RNAlater) for omics-technologies: Saccharomyces cerevisiae as a case
study
SO BIOTECHNOLOGY LETTERS
LA English
DT Article
DE Fluxomics; Genomics; Omics; RNAlater; Saccharomyces cerevisiae;
Transcriptomics
ID TISSUE STORAGE METHODS; MESSENGER-RNA; PRESERVATION; METABOLISM; NUMBER;
FROZEN; YEAST; PCR; DNA
AB Genomics, transcriptomics, proteomics and fluxomics are powerful omics-technologies that play a major role in today's research. For each of these techniques good sample quality is crucial. Major factors contributing to the quality of a sample is the actual sampling procedure itself and the way the sample is stored directly after sampling. It has already been described that RNAlater can be used to store tissues and cells in a way that the RNA quality and quantity are preserved. In this paper, we demonstrate that quaternary ammonium salts (RNAlater) are also suitable to preserve and store samples from Saccharomyces cerevisiae for later use with the four major omics-technologies. Moreover, it is shown that RNAlater also preserves the cell morphology and the potential to recover growth, permitting microscopic analysis and yeast cell culturing at a later stage.
C1 [van Eijsden, Rudy G. E.] VIB, VIB Nucle Core, Louvain, Belgium.
[Stassen, Catherine; Devreese, Bart] Univ Ghent, Dept Biochem & Microbiol, Lab Prot Biochem & Biomol Engn, B-9000 Ghent, Belgium.
[Daenen, Luk; Van Mulders, Sebastiaan E.; Delvaux, Freddy R.] Katholieke Univ Leuven, Ctr Malting & Brewing Sci, Dept Microbial & Mol Syst, Louvain, Belgium.
[Bapat, Prashant M.] Tech Univ Denmark, Ctr Microbial Biotechnol, Dept Syst Biol, DK-2800 Lyngby, Denmark.
[Siewers, Verena; Nielsen, Jens] Chalmers, Dept Chem & Biol Engn, S-41296 Gothenburg, Sweden.
[Goossens, Katty V. Y.; Willaert, Ronnie G.] Vrije Univ Brussel, Dept Bioengn Sci, Res Grp Struct Biol, B-1050 Brussels, Belgium.
[Van Hummelen, Paul] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
RP Goossens, KVY (reprint author), Vrije Univ Brussel, Dept Bioengn Sci, Res Grp Struct Biol, Pl Laan 2, B-1050 Brussels, Belgium.
EM rudy.vaneijsden@vib.be; catherine.stassen@vub.ac.be;
prashant.bapat@gmail.com; siewers@chalmers.se; katty.goossens@vub.ac.be;
nielsenj@chalmers.se; freddy.delvaux@biw.kuleuven.be;
paul_vanhummelen@dfci.harvard.edu; bart.devreese@ugent.be;
ronnie.willaert@vub.ac.be
RI Devreese, Bart/B-2011-2009;
OI Devreese, Bart/0000-0002-9764-2581; Nielsen, Jens/0000-0002-9955-6003
FU Belgian Federal Science Policy Office; Danish Agency for Space and
Technology; European Space Agency (ESA) PRODEX program
FX The Belgian Federal Science Policy Office, the Danish Agency for Space
and Technology, and the European Space Agency (ESA) PRODEX program
supported this work.
NR 28
TC 4
Z9 5
U1 1
U2 23
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0141-5492
EI 1573-6776
J9 BIOTECHNOL LETT
JI Biotechnol. Lett.
PD JUN
PY 2013
VL 35
IS 6
BP 891
EP 900
DI 10.1007/s10529-013-1163-0
PG 10
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA 150YK
UT WOS:000319427500008
PM 23417260
ER
PT J
AU Kaplan, JR
Kowalczyk, KJ
Borza, T
Gu, XM
Lipsitz, SR
Nguyen, PL
Friedlander, DF
Trinh, QD
Hu, JC
AF Kaplan, Joshua R.
Kowalczyk, Keith J.
Borza, Tudor
Gu, Xiangmei
Lipsitz, Stuart R.
Nguyen, Paul L.
Friedlander, David F.
Quoc-Dien Trinh
Hu, Jim C.
TI Patterns of care and outcomes of radiotherapy for lymph node positivity
after radical prostatectomy
SO BJU INTERNATIONAL
LA English
DT Article
DE prostate cancer; radical prostatectomy; radiation therapy; outcomes
ID ANDROGEN-DEPRIVATION THERAPY; RANDOMIZED CLINICAL-TRIAL; TERM-FOLLOW-UP;
RADIATION-THERAPY; ADJUVANT RADIOTHERAPY; PELVIC LYMPHADENECTOMY;
HORMONAL-THERAPY; ANTIGEN LEVEL; CANCER; RISK
AB Objective To evaluate the use and outcomes of adjuvant radiation therapy (ART) for men with lymph node (LN)-positive disease after radical prostatectomy (RP) using a population-based approach.
Patients and Methods Surveillance, Epidemiology, and End Results (SEER)-Medicare linked data from 1995 to 2007 was used to identify 577 men with LN metastases discovered during RP and absence of distant metastases, of which 177 underwent ART 1 year of RP.
Propensity score models were used to compare overall mortality and prostate cancer-specific mortality (PCSM) for men that did and those that did not receive ART.
Results Men in both groups received adjuvant androgen-deprivation therapy at similar rates after propensity weighting adjustments (33.6% vs 33.7%, P=0.977).
ART was not associated with differences in overall (5.09 vs 3.77 events per 100 person-years, P=0.153) or PCSM (2.89 vs 1.31, P=0.090) relative to men who did not receive ART.
Conclusions ART after RP in men with LN-positive prostate cancer was not associated with improved overall or disease-specific survival, in contrast to previous single-centre studies.
Prospective randomised studies are needed to assess the effectiveness of ART in this patient population.
C1 [Kaplan, Joshua R.; Borza, Tudor] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Urol Surg, Boston, MA 02115 USA.
[Kowalczyk, Keith J.] Georgetown Univ Hosp, Dept Urol, Washington, DC 20007 USA.
[Gu, Xiangmei; Lipsitz, Stuart R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Surg & Publ Hlth, Boston, MA 02115 USA.
[Nguyen, Paul L.] Dana Farber Canc Inst, Dept Radiat Oncol, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA.
[Friedlander, David F.] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA.
[Quoc-Dien Trinh] Henry Ford Hlth Syst, Vattikuti Urol Inst, Detroit, MI USA.
[Hu, Jim C.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA 90095 USA.
RP Kaplan, JR (reprint author), 45 Francis St,ASB 2-3, Boston, MA 02115 USA.
EM jrkaplan@partners.org
OI Kaplan, Joshua/0000-0001-6153-3829
FU Department of Defense Prostate Cancer Physician Training Award
[W81XWH-08-1-0283]
FX This work was supported by a Department of Defense Prostate Cancer
Physician Training Award (W81XWH-08-1-0283) presented to Dr Hu. This
study used the linked SEER-Medicare database. The interpretation and
reporting of these data are the sole responsibility of the authors.
NR 34
TC 15
Z9 15
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1464-4096
J9 BJU INT
JI BJU Int.
PD JUN
PY 2013
VL 111
IS 8
BP 1208
EP 1214
DI 10.1111/bju.12079
PG 7
WC Urology & Nephrology
SC Urology & Nephrology
GA 152GW
UT WOS:000319520800020
PM 23551838
ER
PT J
AU Schiavina, R
Borghesi, M
Brunocilla, E
Manferrari, F
Fiorentino, M
Vagnoni, V
Baccos, A
Pultrone, CV
Rocca, GC
Rizzi, S
Martorana, G
AF Schiavina, Riccardo
Borghesi, Marco
Brunocilla, Eugenio
Manferrari, Fabio
Fiorentino, Michelangelo
Vagnoni, Valerio
Baccos, Alessandro
Pultrone, Cristian Vincenzo
Rocca, Giovanni Christian
Rizzi, Simona
Martorana, Giuseppe
TI Differing risk of cancer death among patients with lymph node metastasis
after radical prostatectomy and pelvic lymph node dissection:
identification of risk categories according to number of positive nodes
and Gleason score
SO BJU INTERNATIONAL
LA English
DT Article
DE radical prostatectomy; pelvic lymph node dissection; Gleason score;
lymph node metastasis; survival
ID STAGE D1 T1-3; ANDROGEN DEPRIVATION; EXTRANODAL EXTENSION; DISEASE
PROGRESSION; PROGNOSTIC-FACTORS; SURVIVAL; RECURRENCE; IMPACT; THERAPY
AB What's known on the subject? and What does the study add? Lymph node (LN) status is one of the most important prognostic variables in patients undergoing radical prostatectomy, but not all patients with node-positive PCa are at the same risk of recurrence and cancer-specific death. In this study we evaluated the role of pathological variables in stratifying the risk of cancer death in patients with prostate cancer. Patients with 1-3 positive LNs and Gleason score (GS) 7 experienced better CSS and OS than those with >3 metastatic LNs and/or GS >7. This evidence could allow urologists to better predict oncological outcomes of patients and select more appropriate therapeutic management.
Objectives To evaluate the outcomes in patients with node-positive prostate cancer (PCa) after radical prostatectomy (RP) and pelvic lymph node dissection (PLND) according to the number of positive lymph nodes (LNs).
To identify different risk groups among patients with node-positive PCa.
Patients and Methods We evaluated 98 consecutive patients with pN1M0 PCa who underwent RP between November 1995 and May 2011.
Kaplan-Meier and Cox proportional univariable and multivariable regression models were used to analyse the survival rates.
Patients were divided into two groups according to number of positive LNs using the most informative positive LN theshold for predicting survival, then into three different risk groups according to number of positive LNs and pathological Gleason score (GS).
Results Mean (range) follow-up was 68.4 (10-192) months.
Patients with 1-3 positive LNs (n = 75; 76.5%) had significantly better cancer-specific survival (CSS) and overall survival (OS) compared with those with >3 positive nodes (n = 23; 23.4%; P < 0.01).
Patients with 1-3 positive LNs and pathological GS 7 (Group 1) had significantly better CSS than those with >3 positive LNs or GS 8-10 (Group 2 [P = 0.015]). Group 2 patients, moreover, had significantly better CSS (P = 0.019) and OS (P = 0.021) than those with >3 positive LNs and GS 8-10 (Group 3).
Conclusions Patients with 1-3 positive LNs have higher CSS and OS rates than those with >3 metastatic LNs.
Taking into account the pathological GS, as well as the number of positive nodes, three risk group categories with considerable differences in terms of survival can be found. Patients with LN-positive PCa should be stratified into different groups according to these two measures, to obtain a better prediction of oncological outcomes.
C1 [Schiavina, Riccardo; Borghesi, Marco; Brunocilla, Eugenio; Manferrari, Fabio; Vagnoni, Valerio; Baccos, Alessandro; Pultrone, Cristian Vincenzo; Rocca, Giovanni Christian; Rizzi, Simona; Martorana, Giuseppe] Univ Bologna, S Orsola M Malpighi Hosp, Dept Urol, I-40138 Bologna, Italy.
[Fiorentino, Michelangelo] Univ Bologna, S Orsola M Malpighi Hosp, Dept Pathol & Mol Oncol, I-40138 Bologna, Italy.
[Fiorentino, Michelangelo] Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Schiavina, R (reprint author), Univ Bologna, S Orsola M Malpighi Hosp, Dept Urol, Palogi 9 St, I-40138 Bologna, Italy.
EM rschiavina@yahoo.it
OI Borghesi, Marco/0000-0001-6021-6805
NR 31
TC 11
Z9 11
U1 2
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1464-4096
J9 BJU INT
JI BJU Int.
PD JUN
PY 2013
VL 111
IS 8
BP 1237
EP 1244
DI 10.1111/j.1464-410X.2012.11602.x
PG 8
WC Urology & Nephrology
SC Urology & Nephrology
GA 152GW
UT WOS:000319520800024
PM 23331345
ER
PT J
AU Bianchi, M
Becker, A
Hansen, J
Trinh, QD
Tian, Z
Abdollah, F
Briganti, A
Shariat, SF
Perrotte, P
Montorsi, F
Karakiewicz, PI
Sun, M
AF Bianchi, Marco
Becker, Andreas
Hansen, Jens
Quoc-Dien Trinh
Tian, Zhe
Abdollah, Firas
Briganti, Alberto
Shariat, Shahrokh F.
Perrotte, Paul
Montorsi, Francesco
Karakiewicz, Pierre I.
Sun, Maxine
TI Conditional survival after nephrectomy for renal cell carcinoma (RCC):
changes in future survival probability over time
SO BJU INTERNATIONAL
LA English
DT Article
DE renal cell carcinoma; RCC; conditional survival; nephrectomy
ID CANCER; DEATH
AB Objective To examine the impact of length of survival on future survival probability, otherwise known as the effect of conditional survival (CS), after nephrectomy (NT) in patients diagnosed with renal cell carcinoma (RCC).
Patients and Methods Overall, 42090 patients with RCC who underwent NT were abstracted from the Surveillance, Epidemiology, and End Results database (1988-2008).
Based on cumulative survival estimates, CS rates were derived according to patient and disease characteristics.
Separate multivariable Cox regression analyses were performed for the prediction of cancer-specific mortality (CSM), according to 1-, 2-, 3-, 4- and 5-year survival postoperatively.
Results Immediately after surgery, the 5-year cancer-specific survival rate was 83.5%. Amongst patients who survived 1, 2, 3, 4, and 5 years after NT, the probability rates for surviving an additional 5 years were 87.0, 89.6, 90.9, 92.0 and 92.3%, respectively. Provided that patients survived 1 and 2 years after NT, the probability of being CSM-free for another 5 years increased by +4.1 and 4.3% for stage III and +12.9 and 10.3% for stage IV disease, respectively.
Similar observations were recorded for patient age, grade, nodal stage and tumour size, and were confirmed upon multivariable analyses.
Conclusion Survival probabilities vary according to length of survival after NT. Specifically, even amongst patients with more advanced disease at surgery, a more favourable prognosis can be achieved after surviving for 1-2 years.
C1 [Bianchi, Marco; Becker, Andreas; Quoc-Dien Trinh; Tian, Zhe; Karakiewicz, Pierre I.; Sun, Maxine] Univ Montreal, Ctr Hlth, Canc Prognost & Hlth Outcomes Unit, Montreal, PQ H2X 3J4, Canada.
[Bianchi, Marco; Abdollah, Firas; Briganti, Alberto; Montorsi, Francesco] Univ Vita Salute San Raffaele, Dept Urol, Milan, Italy.
[Becker, Andreas; Hansen, Jens] Prostate Canc Ctr Hamburg Eppendorf, Martini Clin, Hamburg, Germany.
[Quoc-Dien Trinh] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Surg,Div Urol,Med Sch, Boston, MA 02115 USA.
[Shariat, Shahrokh F.] Cornell Univ, Weill Med Coll, Dept Urol, New York, NY 10021 USA.
[Perrotte, Paul; Karakiewicz, Pierre I.] Univ Montreal, Ctr Hlth, Dept Urol, Montreal, PQ H2X 3J4, Canada.
RP Becker, A (reprint author), Univ Montreal, Ctr Hlth, 1058 Rue St Denis, Montreal, PQ H2X 3J4, Canada.
EM a.becker@uke.de
FU University of Montreal Health Centre Urology Specialists; Fonds de la
Recherche en Sante du Qubec; University of Montreal Department of
Surgery; University of Montreal Health Centre (CHUM) Foundation
FX P. I. K. is partially supported by the University of Montreal Health
Centre Urology Specialists, Fonds de la Recherche en Sante du Qubec, the
University of Montreal Department of Surgery and the University of
Montreal Health Centre (CHUM) Foundation. All authors made substantial
contribution to the preparation of the current manuscript and consented
to its final format prior to submission.
NR 16
TC 6
Z9 6
U1 0
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1464-4096
J9 BJU INT
JI BJU Int.
PD JUN
PY 2013
VL 111
IS 8
BP E283
EP E289
DI 10.1111/bju.12115
PG 7
WC Urology & Nephrology
SC Urology & Nephrology
GA 152GW
UT WOS:000319520800002
PM 23714646
ER
PT J
AU Wu, CW
Aronson, WJ
Terris, MK
Presti, JC
Kane, CJ
Amling, CL
Freedland, SJ
AF Wu, Chenwei
Aronson, William J.
Terris, Martha K.
Presti, Joseph C., Jr.
Kane, Christopher J.
Amling, Christopher L.
Freedland, Stephen J.
TI Diabetes predicts metastasis after radical prostatectomy in obese men:
results from the SEARCH database
SO BJU INTERNATIONAL
LA English
DT Article
DE diabetes; obesity; race; prostate cancer; metastasis
ID CANCER-SPECIFIC MORTALITY; SERUM TESTOSTERONE LEVEL; BODY-MASS INDEX;
GROWTH-FACTOR-I; PATHOLOGICAL STAGE; UNITED-STATES; SEX-HORMONES; RISK;
MELLITUS; INSULIN
AB What's known on the subject? and What does the study add? Diabetes is known to be associated with a slightly lower risk of prostate cancer. Only a limited number of studies have examined the impact of diabetes on prostate cancer outcomes, with mixed results. This study builds on our prior work showing that on the whole, diabetes is not a risk factor for progression to metastases after surgery. However, intriguingly we found a significant interaction with obesity for modifying the relationship between diabetes and progression. If confirmed in future studies, this suggests the mechanisms by which diabetes alters prostate cancer aggressiveness may differ in obese and non-obese men.
Objective To examine the association between diabetes and metastasis risk after radical prostatectomy (RP) and to determine if race or obesity modifies this relationship.
Patients and Methods Patients comprised 2058 US veterans with prostate cancer (PCa) enrolled in the Shared Equal-Access Regional Cancer Hospital (SEARCH) database and treated with RP between 1988 and 2010.
The association of diabetes with metastasis risk or secondary treatment rates was examined using Cox proportional hazards, adjusting for preoperative and, separately, clinical and postoperative findings.
The effect modification by race (black vs white) and obesity (body mass index [BMI] 30 vs <30kg/m2) was tested via interaction terms.
Results Men with diabetes had higher BMIs and were more likely to be non-white (all P 0.001).
On multivariable analysis, diabetes was not associated with metastasis risk (P 0.45), but, among men with diabetes, longer diabetes duration was associated with higher metastasis risk (P 0.035).
When stratified by obesity, diabetes was linked with higher metastasis risk in obese but not in non-obese men (P-interaction 0.037), but there was no significant interaction with race (P-interaction 0.56).
Diabetes also predicted more aggressive secondary treatment among obese men but less aggressive treatment among non-obese men (hazard ratio 1.39 vs 0.63, P-interaction = 0.006).
Where applicable, results were similar for both pre- and postoperative models.
Conclusions Diabetes was not associated with metastasis risk overall.
Stratification by obesity yielded significant differences, with diabetes linked to a fourfold higher metastasis risk in obese men, despite predicting more aggressive secondary treatment. Longer diabetes duration was also associated with increased metastasis risk.
C1 [Wu, Chenwei; Freedland, Stephen J.] Duke Univ, Sch Med, Durham, NC USA.
[Wu, Chenwei; Freedland, Stephen J.] Duke Univ, Med Ctr, Durham VA Med Ctr, Urol Sect, Durham, NC USA.
[Freedland, Stephen J.] Duke Univ, Med Ctr, Dept Surg, Div Urol Surg, Durham, NC 27710 USA.
[Freedland, Stephen J.] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA.
[Freedland, Stephen J.] Duke Univ, Med Ctr, Duke Prostate Ctr, Durham, NC USA.
[Aronson, William J.] UCLA Hlth Syst, Dept Urol, Los Angeles, CA USA.
[Aronson, William J.] VA Greater Los Angeles Healthcare Syst, Urol Sect, Los Angeles, CA USA.
[Presti, Joseph C., Jr.] Stanford Sch Med, Dept Urol, Palo Alto, CA USA.
[Presti, Joseph C., Jr.] VA Palo Alto Healthcare Syst, Urol Sect, Palo Alto, CA USA.
[Kane, Christopher J.] UC San Diego Hlth Syst, Dept Surg, Div Urol, San Diego, CA USA.
[Terris, Martha K.] Med Coll Georgia, Dept Surg, Urol Sect, Augusta, GA 30912 USA.
[Terris, Martha K.] Charlie Norwood VA Med Ctr, Urol Sect, Augusta, GA USA.
[Amling, Christopher L.] Oregon Hlth & Sci Univ, Div Urol, Portland, OR 97201 USA.
RP Freedland, SJ (reprint author), DUMC 2626 Suite 475, Durham, NC 27710 USA.
EM steve.freedland@duke.edu
OI Terris, Martha/0000-0002-3843-7270
FU American Urological Association Foundation/Astellas Rising Star in
Urology Award (S.J.F.); Howard Hughes Medical Institute Medical Research
Fellows scholarship (C. W.)
FX This work was supported by the American Urological Association
Foundation/Astellas Rising Star in Urology Award (S.J.F.) and a Howard
Hughes Medical Institute Medical Research Fellows scholarship (C.W.)
NR 39
TC 7
Z9 7
U1 2
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1464-4096
J9 BJU INT
JI BJU Int.
PD JUN
PY 2013
VL 111
IS 8
BP E310
EP E318
DI 10.1111/j.1464-410X.2012.11687.x
PG 9
WC Urology & Nephrology
SC Urology & Nephrology
GA 152GW
UT WOS:000319520800006
PM 23305170
ER
PT J
AU Lin, NU
Thomssen, C
Cardoso, F
Cameron, D
Cufer, T
Fallowfield, L
Francis, PA
Kyriakides, S
Pagani, O
Senkus, E
Costa, A
Winer, EP
AF Lin, Nancy U.
Thomssen, Christoph
Cardoso, Fatima
Cameron, David
Cufer, Tanja
Fallowfield, Lesley
Francis, Prudence A.
Kyriakides, Stella
Pagani, Olivia
Senkus, Elzbieta
Costa, Alberto
Winer, Eric P.
CA ESO-MBC Task Force
TI International guidelines for management of metastatic breast cancer
(MBC) from the European School of Oncology (ESO)-MBC Task Force:
Surveillance, staging, and evaluation of patients with early-stage and
metastatic breast cancer
SO BREAST
LA English
DT Review
DE Breast cancer; Guidelines; ABC; Surveillance; Staging; Evaluation;
Follow-up
ID CIRCULATING TUMOR-CELLS; POSITRON-EMISSION-TOMOGRAPHY; DIAGNOSTIC
FOLLOW-UP; CLINICAL-ONCOLOGY; AMERICAN-SOCIETY; RANDOMIZED-TRIAL; BONE
METASTASES; ECONOMIC-EVALUATION; SURVIVAL; WOMEN
AB In clinical practice, the surveillance and follow-up of patients with breast cancer (BC) is quite variable. At the 7th European Breast Cancer Conference, the ESO-MBC Task Force convened a series of lectures, followed by open debate, on the use of physical examination, imaging, and laboratory tests in patients with early-stage BC, and for restaging evaluations and follow-up among patients with MBC. Based on the available data, the Task Force recommends against intensive, routine radiologic or blood-based surveillance (with the exception of mammography) in patients with early-stage BC. As systemic therapies for MBC continue to improve, this question might be re-visited in the context of a carefully controlled clinical trial in specific BC subtypes. For patients with MBC, response to therapy should generally be assessed 2-3 months after initiation of treatment, and thereafter every 2-4 months for endocrine therapy or every 2-4 cycles for chemotherapy, depending on the dynamics of the disease, the location and extent of metastatic involvement, and type of treatment. Additional testing should be performed irrespective of the planned intervals if progression of disease is suspected (e.g. in the case of specific symptoms). Use of tumor markers is not recommended for surveillance of early-stage patients, but may be helpful in monitoring response to therapy in patients with metastatic disease. However, change in tumor markers alone should not be used for decision-making. Moving forward, enhanced efforts to document quality of life over time should be made in order to more fully evaluate the risk/benefit ratio of available options. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Lin, Nancy U.; Winer, Eric P.] Dana Farber Brigham & Womens Canc Ctr, Dept Med Oncol, Boston, MA 02215 USA.
[Thomssen, Christoph] Univ Halle Wittenberg, Dept Gynecol, D-06097 Halle, Saale, Germany.
[Cardoso, Fatima] Champalimaud Canc Ctr, Breast Canc Unit, P-1400048 Lisbon, Portugal.
[Cameron, David] Univ Edinburgh, Edinburgh Canc Res Ctr, Edinburgh EH4 2XU, Midlothian, Scotland.
[Cufer, Tanja] Univ Clin Golnik, Golnik 4204, Slovenia.
[Fallowfield, Lesley] Univ Sussex, Brighton & Sussex Med Sch, Sussex Hlth Outcomes Res & Educ Canc SHORE C, Falmer BN1 9RX, England.
[Francis, Prudence A.] Peter MacCallum Canc Ctr, Div Canc Med, Melbourne, Vic 8006, Australia.
[Kyriakides, Stella] Europa Donna Cyprus, CY-1101 Nicosia, Cyprus.
[Pagani, Olivia] Osped San Giovanni Bellinzona, Inst Oncol Southern Switzerland, CH-6500 Bellinzona, Switzerland.
[Senkus, Elzbieta] Med Univ Gdansk, Dept Oncol & Radiotherapy, PL-80211 Gdansk, Poland.
[Costa, Alberto] European Sch Oncol, Milan, Italy.
[Costa, Alberto] Maugeri Fdn Breast Unit, Pavia, Italy.
RP Cardoso, F (reprint author), Champalimaud Canc Ctr, Breast Canc Unit, Av Brasilia Doca Pedroucos, P-1400048 Lisbon, Portugal.
EM nlin@partners.org; christoph.thomssen@medizin.uni-halle.de;
fatimacardoso@fundacaochampalimaud.pt; d.cameron@ed.ac.uk;
tanja.cufer@klinika-golnik.si; LJ.Fallowfield@Sussex.ac.uk;
prue.francis@petermac.org; cysky@cytanet.com.cy; olivia.pagani@eoc.ch;
elsenkus@gumed.edu.pl; acosta@eso.net; ewiner@partners.org
RI Francis, Prudence/J-4003-2012;
OI Fallowfield, Lesley/0000-0002-3328-4447; Senkus,
Elzbieta/0000-0001-6855-397X; Gligorov, Joseph/0000-0002-9900-6386;
Fallowfield, Lesley/0000-0003-0577-4518; Cardoso,
Fatima/0000-0002-6692-2249
FU European School of Oncology
FX This work was supported by the European School of Oncology.
NR 71
TC 26
Z9 27
U1 0
U2 25
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 0960-9776
J9 BREAST
JI Breast
PD JUN
PY 2013
VL 22
IS 3
BP 203
EP 210
DI 10.1016/j.breast.2013.03.006
PG 8
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 151XE
UT WOS:000319492900001
PM 23601761
ER
PT J
AU Nahleh, ZA
Lin, NU
Wolff, AC
Cardoso, F
AF Nahleh, Zeina A.
Lin, Nancy U.
Wolff, Antonio C.
Cardoso, Fatima
CA BIG-NABCG Collaboration
TI Perceptions and needs of women with metastatic breast cancer: A focus on
clinical trials
SO BREAST
LA English
DT Article
DE Perceptions; Metastatic; Breast; Cancer; BIG-NABCG
ID SURVIVAL
AB Many patients are living longer with Metastatic Breast Cancer (MBC) than ever before. However, complete responses remain uncommon, and progression of disease is often inevitable. The experience of living with MBC exposes patients to a wide variety of clinical, psychological, social and spiritual issues. Although much research effort has focused on decision-making and coping strategies among women with early breast cancer, relatively little attention has been given to the needs, experiences, and perceptions of women living with MBC. Furthermore, there are major research gaps in understanding and prioritizing the types of psycho-social interventions that would make the most difference in the lives of these patients. Fortunately, the tide is turning. This communication represents a joint effort of the Breast International Group and the National Cancer Institute (NCI)-sponsored North American Breast Cancer Group (BIG-NABCG) to highlight perceptions and needs of patients living with MBC and current obstacles facing them, and recommends strategies for better addressing some of these unmet needs. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Nahleh, Zeina A.] Texas Tech Univ, Hlth Sci Ctr, Paul L Foster Sch Med, El Paso, TX 79905 USA.
[Lin, Nancy U.] Dana Farber Canc Inst, Boston, MA 02215 USA.
[Wolff, Antonio C.] Johns Hopkins Kimmel Comprehens Canc Ctr, Breast Canc Program, Baltimore, MD 21287 USA.
[Cardoso, Fatima] Champalimaud Canc Ctr, P-1400048 Lisbon, Portugal.
RP Nahleh, ZA (reprint author), Texas Tech Univ, Hlth Sci Ctr, Paul L Foster Sch Med, 4800 Alberta Ave, El Paso, TX 79905 USA.
EM Zeina.nahleh@ttuhsc.edu; Nancy_Lin@dfci.harvard.edu; awolff@jhmi.edu;
fatimacardoso@fundacaochampalimaud.pt
OI Wolff, Antonio/0000-0003-3734-1063; Cardoso, Fatima/0000-0002-6692-2249
FU NCI NIH HHS [P30 CA006973]
NR 22
TC 2
Z9 2
U1 0
U2 6
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 0960-9776
J9 BREAST
JI Breast
PD JUN
PY 2013
VL 22
IS 3
BP 370
EP 373
DI 10.1016/j.breast.2013.02.017
PG 4
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 151XE
UT WOS:000319492900027
PM 23535510
ER
PT J
AU Picaud, S
Da Costa, D
Thanasopoulou, A
Filippakopoulos, P
Fish, PV
Philpott, M
Fedorov, O
Brennan, P
Bunnage, ME
Owen, DR
Bradner, JE
Taniere, P
O'Sullivan, B
Muller, S
Schwaller, J
Stankovic, T
Knapp, S
AF Picaud, Sarah
Da Costa, David
Thanasopoulou, Angeliki
Filippakopoulos, Panagis
Fish, Paul V.
Philpott, Martin
Fedorov, Oleg
Brennan, Paul
Bunnage, Mark E.
Owen, Dafydd R.
Bradner, James E.
Taniere, Philippe
O'Sullivan, Brendan
Mueller, Susanne
Schwaller, Juerg
Stankovic, Tatjana
Knapp, Stefan
TI PFI-1, a Highly Selective Protein Interaction Inhibitor, Targeting BET
Bromodomains
SO CANCER RESEARCH
LA English
DT Article
ID BONE-MARROW-CELLS; C-MYC; AURORA-B; KINASE INHIBITORS; STRUCTURAL BASIS;
EXPRESSION; CANCER; BRD4; RECOGNITION; LEUKEMIA
AB Bromo and extra terminal (BET) proteins (BRD2, BRD3, BRD4, and BRDT) are transcriptional regulators required for efficient expression of several growth promoting and antiapoptotic genes as well as for cell-cycle progression. BET proteins are recruited on transcriptionally active chromatin via their two N-terminal bromodomains (BRD), a protein interaction module that specifically recognizes acetylated lysine residues in histones H3 and H4. Inhibition of the BET-histone interaction results in transcriptional downregulation of a number of oncogenes, providing a novel pharmacologic strategy for the treatment of cancer. Here, we present a potent and highly selective dihydroquinazoline-2-one inhibitor, PFI-1, which efficiently blocks the interaction of BET BRDs with acetylated histone tails. Cocrystal structures showed that PFI-1 acts as an acetyl-lysine (K-ac) mimetic inhibitor efficiently occupying the K-ac binding site in BRD4 and BRD2. PFI-1 has antiproliferative effects on leukemic cell lines and efficiently abrogates their clonogenic growth. Exposure of sensitive cell lines with PFI-1 results in G(1) cell-cycle arrest, downregulation of MYC expression, as well as induction of apoptosis and induces differentiation of primary leukemic blasts. Intriguingly, cells exposed to PFI-1 showed significant downregulation of Aurora B kinase, thus attenuating phosphorylation of the Aurora substrate H3S10, providing an alternative strategy for the specific inhibition of this well-established oncology target. (C) 2013 AACR.
C1 [Picaud, Sarah; Filippakopoulos, Panagis; Philpott, Martin; Fedorov, Oleg; Brennan, Paul; Mueller, Susanne; Knapp, Stefan] Univ Oxford, Struct Genom Consortium, Oxford OX3 7DQ, Oxon, England.
[Knapp, Stefan] Univ Oxford, Nuffield Dept Clin Med, Target Discovery Inst, Oxford OX3 7DQ, Oxon, England.
[Da Costa, David; Stankovic, Tatjana] Univ Birmingham, Sch Canc Sci, Birmingham B15 2TT, W Midlands, England.
[Taniere, Philippe; O'Sullivan, Brendan] Queen Elizabeth Med Ctr, Dept Cellular Pathol, Birmingham, W Midlands, England.
[Fish, Paul V.; Bunnage, Mark E.; Owen, Dafydd R.] Pfizer Worldwide R&D, Pfizer Worldwide Med Chem, Sandwich, Kent, England.
[Thanasopoulou, Angeliki; Schwaller, Juerg] Univ Basel, Dept Biomed, Lab Childhood Leukemia, CH-4031 Basel, Switzerland.
[Thanasopoulou, Angeliki; Schwaller, Juerg] Univ Basel, Childrens Hosp, CH-4031 Basel, Switzerland.
[Knapp, Stefan] George Washington Univ, Sch Med & Hlth Sci, Dept Biochem & Mol Biol, Washington, DC 20037 USA.
[Bradner, James E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Bradner, James E.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
RP Knapp, S (reprint author), Univ Oxford, Struct Genom Consortium, Oxford OX3 7DQ, Oxon, England.
EM j.schwaller@unibas.ch; t.stankovic@bham.ac.uk; stefan.knapp@sgc.ox.ac.uk
RI Fedorov, Oleg/B-6412-2014; schwaller, juerg/A-3044-2016;
OI Fedorov, Oleg/0000-0001-9004-1815; Filippakopoulos,
Panagis/0000-0002-1515-1317; Knapp, Stefan/0000-0001-5995-6494;
Muller-Knapp, Susanne/0000-0003-2402-4157
FU Wellcome Trust Career-Development Fellowship [095751/Z/11/Z]; Gertrude
von Meissner Foundation; Swiss National Research Foundation (SNF)
[31003A-130661]; Swiss Cancer League [OCS02357-2009]; Swiss Bridge Award
FX S. Picaud, M. Philpott, O. Fedorov, P. Brennan, S. Muller, and S. Knapp
are supported by the SGC, a registered charity (number 1097737) that
receives funds from the Canadian Institutes for Health Research, the
Canada Foundation for Innovation, Genome Canada, GlaxoSmithKline,
Pfizer, Eli Lilly, Takeda, AbbVie, the Novartis Research Foundation, the
Ontario Ministry of Research and Innovation, and the Wellcome Trust. P.
Filippakopoulos is supported by a Wellcome Trust Career-Development
Fellowship (095751/Z/11/Z). J. Schwaller was supported by the Gertrude
von Meissner Foundation, the Swiss National Research Foundation (SNF,
31003A-130661), the Swiss Cancer League (OCS02357-2009), and the Swiss
Bridge Award.
NR 46
TC 87
Z9 88
U1 5
U2 45
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD JUN 1
PY 2013
VL 73
IS 11
BP 3336
EP 3346
DI 10.1158/0008-5472.CAN-12-3292
PG 11
WC Oncology
SC Oncology
GA 155GV
UT WOS:000319736800015
PM 23576556
ER
PT J
AU Price, RL
Song, J
Bingmer, K
Kim, TH
Yi, JY
Nowicki, MO
Mo, XK
Hollon, T
Murnan, E
Alvarez-Breckenridge, C
Fernandez, S
Kaur, B
Rivera, A
Oglesbee, M
Cook, C
Chiocca, EA
Kwon, CH
AF Price, Richard L.
Song, Jieun
Bingmer, Katherine
Kim, Tae Hyong
Yi, Ji-Yeun
Nowicki, Michal O.
Mo, Xiaokui
Hollon, Todd
Murnan, Eric
Alvarez-Breckenridge, Christopher
Fernandez, Soledad
Kaur, Balveen
Rivera, Andreana
Oglesbee, Michael
Cook, Charles
Chiocca, E. Antonio
Kwon, Chang-Hyuk
TI Cytomegalovirus Contributes to Glioblastoma in the Context of Tumor
Suppressor Mutations
SO CANCER RESEARCH
LA English
DT Article
ID NEURAL STEM/PROGENITOR CELLS; MURINE CYTOMEGALOVIRUS; BRAIN-TUMORS;
DNA-SEQUENCE; IN-VIVO; INFECTION; ASTROCYTOMAS; ASSOCIATION; PATHWAYS;
GLIOMAS
AB To study the controversial role of cytomegalovirus (CMV) in glioblastoma, we assessed the effects of murine CMV (MCMV) perinatal infection in a GFAP-cre; Nf1(loxP/+); Trp53(-/+) genetic mouse model of glioma (Mut3 mice). Early on after infection, MCMV antigen was predominantly localized in CD45+ lymphocytes in the brain with active viral replication and local areas of inflammation, but, by 7 weeks, there was a generalized loss of MCMV in brain, confirmed by bioluminescent imaging. MCMV-infected Mut3 mice exhibited a shorter survival time from their gliomas than control Mut3 mice perinatally infected with mock or with a different neurotropic virus. Animal survival was also significantly shortened when orthotopic gliomas were implanted in mice perinatally infected with MCMV versus controls. MCMV infection increased phosphorylated STAT3 (p-STAT3) levels in neural stem cells (NSC) harvested from Mut3 mice subventricular zone, and, in vivo, there was increased p-STAT3 in NSCs in MCMV-infected compared with control mice. Of relevance, human CMV (HCMV) also increased p-STAT3 and proliferation of patient-derived glioblastoma neurospheres, whereas a STAT3 inhibitor reversed this effect in vitro and in vivo. These findings thus associate CMV infection to a STAT3-dependent modulatory role in glioma formation/progression in the context of tumor suppressor mutations in mice and possibly in humans. (C) 2013 AACR.
C1 [Price, Richard L.; Song, Jieun; Bingmer, Katherine; Kim, Tae Hyong; Yi, Ji-Yeun; Hollon, Todd; Murnan, Eric; Alvarez-Breckenridge, Christopher; Kaur, Balveen; Chiocca, E. Antonio; Kwon, Chang-Hyuk] Ohio State Univ, Med Ctr, Dept Neurol Surg, Dardinger Neurooncol Ctr, Columbus, OH 43210 USA.
[Song, Jieun; Kim, Tae Hyong; Yi, Ji-Yeun; Murnan, Eric; Kwon, Chang-Hyuk] Ohio State Univ, Med Ctr, Solid Tumor Program, James Comprehens Canc Ctr, Columbus, OH 43210 USA.
[Mo, Xiaokui; Fernandez, Soledad] Ohio State Univ, Med Ctr, Ctr Biostat, Columbus, OH 43210 USA.
[Rivera, Andreana] Ohio State Univ, Med Ctr, Dept Pathol, Columbus, OH 43210 USA.
[Oglesbee, Michael] Ohio State Univ, Med Ctr, Dept Vet Biosci, Columbus, OH 43210 USA.
[Cook, Charles] Ohio State Univ, Med Ctr, Dept Surg, Columbus, OH 43210 USA.
[Nowicki, Michal O.; Chiocca, E. Antonio] Brigham & Womens Hosp, Dept Neurol Surg, Boston, MA 02115 USA.
[Nowicki, Michal O.; Chiocca, E. Antonio] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA.
RP Chiocca, EA (reprint author), Brigham & Womens Faulkner Hosp, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA.
EM EAChiocca@partners.org; Chang-Hyuk.Kwon@osumc.edu
RI Cook, Charles/D-5574-2009; Kwon, Chang-hyuk/E-3450-2011; kaur,
Balveen/E-3355-2011;
OI Cook, Charles/0000-0003-4446-3616; SONG, JIEUN/0000-0001-7886-1765
FU NIH [P30NS045758-06, R01NS064607]; Viral Oncology Program Grant;
Dardinger Neuro-oncology Fund; Jeffrey Thomas Hayden Foundation; OSU
MBCG Program grant; OSU CCC Start-up Fund
FX This study was funded by NIH P30NS045758-06, R01NS064607 (B. Kaur), a
Viral Oncology Program Grant, the Dardinger Neuro-oncology Fund, the
Jeffrey Thomas Hayden Foundation (E.A. Chiocca), OSU MBCG Program grant
(E.A. Chiocca and C.-H. Kwon), and OSU CCC Start-up Fund (C.-H. Kwon)
NR 40
TC 22
Z9 22
U1 0
U2 9
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD JUN 1
PY 2013
VL 73
IS 11
BP 3441
EP 3450
DI 10.1158/0008-5472.CAN-12-3846
PG 10
WC Oncology
SC Oncology
GA 155GV
UT WOS:000319736800024
PM 23729642
ER
PT J
AU Pender-Cudlip, MC
Krag, KJ
Martini, D
Yu, J
Guidi, A
Skinner, SS
Zhang, Y
Qu, XY
He, CW
Xu, Y
Qian, SY
Kang, JX
AF Pender-Cudlip, Marilla C.
Krag, Karen J.
Martini, David
Yu, Jeanne
Guidi, Anthony
Skinner, Sandy S.
Zhang, Yu
Qu, Xiying
He, Chengwei
Xu, Yi
Qian, Steven Y.
Kang, Jing X.
TI Delta-6-desaturase activity and arachidonic acid synthesis are increased
in human breast cancer tissue
SO CANCER SCIENCE
LA English
DT Article
ID FATTY-ACIDS; EICOSAPENTAENOIC ACID; DELTA-6 DESATURASE;
GENETIC-VARIANTS; DIETARY N-3; RAT-LIVER; METABOLISM; DISEASE; RISK;
MICE
AB Omega-6 (n-6) arachidonic acid (AA) and its pro-inflammatory metabolites, including prostaglandin E2 (PGE2), are known to promote tumorigenesis. Delta-6 desaturase (D6D) is the rate-limiting enzyme for converting n-6 linoleic acid (LA) to AA. Our objective was to determine if AA synthesis, specifically D6D activity, and PGE2 levels are increased in cancerous breast tissue, and whether these variables differ between estrogen receptor positive (ER+) and negative (ER) breast cancers. Gas chromatography was performed on surgical breast tissue samples collected from 69 women with breast cancer. Fifty-four had ER+ breast cancer, and 15 had ER breast cancer. Liquid chromatography-mass spectrometry was used to determine PGE2 levels. Lipid analysis revealed higher levels of LA metabolites (C18:3 n-6, C20:3 n-6, and AA) in cancerous tissue than in adjacent noncancerous tissue (P<0.01). The ratio of LA metabolites to LA, a measure of D6D activity, was increased in cancerous tissue, suggesting greater conversion of LA to AA (P<0.001), and was higher in ER than in ER+ patients, indicating genotype-related trends. Similarly, PGE2 levels were increased in cancerous tissue, particularly in ER patients. The results showed that the endogenous AA synthetic pathway, D6D activity, and PGE2 levels are increased in breast tumors, particularly those of the ER genotype. These findings suggest that the AA synthetic pathway and the D6D enzyme in particular may be involved in the pathogenesis of breast cancer. The development of drugs and nutritional interventions to alter this pathway may provide new strategies for breast cancer prevention and treatment.
C1 [Pender-Cudlip, Marilla C.; Zhang, Yu; Qu, Xiying; He, Chengwei; Kang, Jing X.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lab Lipid Med & Technol,Dept Med, Boston, MA 02115 USA.
[Krag, Karen J.; Martini, David; Yu, Jeanne] Mass Gen North Shore Canc Ctr, Danvers, MA USA.
[Guidi, Anthony; Skinner, Sandy S.] North Shore Med Ctr, Salem, MA USA.
[Xu, Yi; Qian, Steven Y.] N Dakota State Univ, Fargo, ND 58105 USA.
RP Kang, JX (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lab Lipid Med & Technol,Dept Med, Boston, MA 02115 USA.
EM kang.jing@mgh.harvard.edu
FU READ Charitable Trust (Salem, MA, USA)
FX We thank the READ Charitable Trust (Salem, MA, USA) for their generous
financial support of this study and Erin D. Gleason for manuscript edits
and preparation.
NR 40
TC 15
Z9 16
U1 2
U2 27
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1347-9032
J9 CANCER SCI
JI Cancer Sci.
PD JUN
PY 2013
VL 104
IS 6
BP 760
EP 764
DI 10.1111/cas.12129
PG 5
WC Oncology
SC Oncology
GA 150PZ
UT WOS:000319404600015
PM 23414387
ER
PT J
AU Todoran, TM
Zile, MR
AF Todoran, Thomas M.
Zile, Michael R.
TI Neuromodulation Device Therapy for Treatment of Hypertensive Heart
Disease
SO CIRCULATION JOURNAL
LA English
DT Review
DE Baroreflex activation therapy; Hypertension; Spinal cord stimulation;
Sympathetic renal denervation; Vagal nerve stimulation
ID RENAL SYMPATHETIC DENERVATION; BAROREFLEX ACTIVATION THERAPY;
LEFT-VENTRICULAR HYPERTROPHY; DRUG-RESISTANT HYPERTENSION; LOWERS
BLOOD-PRESSURE; RHEOS PIVOTAL TRIAL; LEFT ATRIAL VOLUME; BARORECEPTOR
STIMULATION; MULTICENTER FEASIBILITY; DIASTOLIC DYSFUNCTION
AB Hypertensive heart disease (HHD) is the leading cause of mortality and morbidity in the United States. Despite the availability of medical therapy it remains a challenge to treat. Autonomic nervous system imbalance resulting in overactivity of the sympathetic nervous system and under activity of the parasympathetic nervous system is integral in the development of hypertension and ultimately the development of HHD. Emerging data suggest that neuromodulation device therapy for treatment of HHD is promising.
C1 Med Univ S Carolina, Div Cardiol, Charleston, SC 29425 USA.
Vet Affairs Med Ctr, Ralph H Johnson Dept, Charleston, SC 29403 USA.
RP Todoran, TM (reprint author), 25 Courtenay Dr,MSC 592, Charleston, SC 29425 USA.
EM todoran@musc.edu
FU CVRx; Medtronic
FX T.M.T. has nothing to disclose. M.R.Z. is a consultant for and receives
research funds from CVRx and Medtronic.
NR 47
TC 3
Z9 4
U1 1
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 JUN
PY 2013
VL 77
IS 6
BP 1351
EP 1363
DI 10.1253/circj.CJ-13-0390
PG 13
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 154CG
UT WOS:000319648500001
PM 23657125
ER
PT J
AU Warren, SR
Raisch, DW
Campbell, HM
Guarino, PD
Kaufman, JS
Petrokaitis, E
Goldfarb, DS
Gaziano, JM
Jamison, RL
AF Warren, Stuart R.
Raisch, Dennis W.
Campbell, Heather M.
Guarino, Peter D.
Kaufman, James S.
Petrokaitis, Elizabeth
Goldfarb, David S.
Gaziano, J. Michael
Jamison, Rex L.
CA Vet Affairs Site Investigators
TI Medication adherence assessment in a clinical trial with centralized
follow-up and direct-to-patient drug shipments
SO CLINICAL TRIALS
LA English
DT Article
ID SELF-REPORT; THERAPY; AGREEMENT
AB Background Assessment of adherence to study medications is a common challenge in clinical research. Counting unused study medication is the predominant method by which adherence is assessed in outpatient clinical trials but it has limitations that include questionable validity and burdens on research personnel.
Purpose To compare capsule counts, patient questionnaire responses, and plasma drug levels as methods of determining adherence in a clinical trial that had 2056 participants and used centralized drug distribution and patient follow-up.
Methods Capsule counts from study medication bottles returned by participants and responses to questions regarding adherence during quarterly telephone interviews were averaged and compared. Both measures were compared to plasma drug levels obtained at the 3-month study visit of patients in the treatment group. Counts and questionnaire responses were converted to adherence rates (doses taken divided by days elapsed) and were categorized by stringent (>= 85.7%) and liberal (>= 71.4%) definitions. We calculated the prevalence-adjusted bias-adjusted kappa to assess agreement between the two measures.
Results Using a pre-paid mailer, participants returned 76.0% of study medication bottles to the central pharmacy. Both capsule counts and questionnaire responses were available for 65.8% of participants and were used to assess adherence. Capsule counts identified more patients who were under-adherent (18.8% by the stringent definition and 7.5% by the liberal definition) than self-reports did (10.4% by the stringent definition and 2.1% by the liberal definition). The prevalence-adjusted bias-adjusted kappa was 0.58 (stringent) and 0.83 (liberal), indicating fair and very good agreement, respectively. Both measures were also in agreement with plasma drug levels determined at the 3-month visit (capsule counts: p = 0.005 for the stringent and p = 0.003 for the liberal definition; questionnaire: p = 0.002 for both adherence definitions).
Limitations Inconsistent bottle returns and incomplete notations of medication start and stop dates resulted in missing data but exploratory missing data analyses showed no reason to believe that the missing data resulted in systematic bias.
Conclusions Depending upon the definition of adherence, there was fair to very good agreement between questionnaire results and capsule counts among returned study bottles, confirmed by plasma drug levels. We conclude that a self-report of medication adherence is potentially comparable to capsule counts as a method of assessing adherence in a clinical trial, if a relatively low adherence threshold is acceptable, but adherence should be confirmed by other measures if a high adherence threshold is required.
C1 [Warren, Stuart R.; Raisch, Dennis W.; Campbell, Heather M.] VA Cooperat Studies Program, Clin Res Pharm Coordinating Ctr, Albuquerque, NM 87106 USA.
[Warren, Stuart R.; Raisch, Dennis W.; Campbell, Heather M.] Univ New Mexico, Coll Pharm, Albuquerque, NM 87131 USA.
[Guarino, Peter D.; Petrokaitis, Elizabeth] VA Connecticut Healthcare Syst, VA Cooperat Studies Program Coordinating Ctr, West Haven, CT USA.
[Kaufman, James S.] VA Boston Healthcare Syst, Renal Sect, Boston, MA USA.
[Kaufman, James S.] Boston Univ, Sch Med, Renal Sect, Boston, MA 02118 USA.
[Goldfarb, David S.] New York Harbor Healthcare Syst, Nephrol Sect, New York, NY USA.
[Goldfarb, David S.] NYU, Sch Med, Nephrol Sect, New York, NY USA.
[Gaziano, J. Michael] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat MAVERI, Boston, MA USA.
[Gaziano, J. Michael] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA.
[Jamison, Rex L.] Vet Affairs VA Palo Alto Hlth Care Syst, Palo Alto, CA USA.
[Jamison, Rex L.] Stanford Univ, Dept Med, Sch Med, Div Nephrol, Stanford, CA 94305 USA.
RP Warren, SR (reprint author), VA Cooperat Studies Program, Clin Res Pharm Coordinating Ctr, 2401 Ctr Ave SE, Albuquerque, NM 87106 USA.
EM stuart.warren@va.gov
OI Goldfarb, David/0000-0002-9215-1273
FU Cooperative Studies Program, Department of Veterans Affairs Office of
Research and Development; PamLab LLC; Abbott Laboratories
FX This study was sponsored by the Cooperative Studies Program, Department
of Veterans Affairs Office of Research and Development, and was
supported in part by PamLab LLC and Abbott Laboratories.
NR 29
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Z9 2
U1 0
U2 9
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 JUN
PY 2013
VL 10
IS 3
BP 441
EP 448
DI 10.1177/1740774511410331
PG 8
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 148FI
UT WOS:000319228200010
PM 21813583
ER
PT J
AU Kuruvilla, MS
Green, JR
Ayaz, H
Murman, DL
AF Kuruvilla, Mili S.
Green, Jordan R.
Ayaz, Hasan
Murman, Daniel L.
TI Neural correlates of cognitive decline in ALS: An fNIRS study of the
prefrontal cortex
SO COGNITIVE NEUROSCIENCE
LA English
DT Article
DE ALS; Cognition; fNIRS; Functional near infrared spectroscopy; N-back
ID AMYOTROPHIC-LATERAL-SCLEROSIS; WORKING-MEMORY; AUDITORY-CORTEX; VERBAL
FLUENCY; BRAIN; RETRIEVAL; WORKLOAD; MRI; PET
AB Functional near infrared spectroscopy (fNIRS) is a clinically feasible functional neuroimaging modality for detecting early cortical changes due to neurodegenerative diseases that affect cognition. The objective of this preliminary investigation was to test for reduced prefrontal activity in persons with cognitive impairments due to amyotrophic lateral sclerosis (ALS). Participants were required to complete two N-back working memory tasks of increasing complexity during fNIRS recordings. Five participants with ALS and age- and gender-matched healthy participants comprised the experimental and control groups, respectively. Significant reductions in prefrontal oxygenation levels were observed for the left and right hemispheres in the ALS group compared to the control group. Reduced prefrontal activation despite intact behavioral performance for a working memory task may suggest early neuroanatomical, neurophysiological and/or compensatory mechanisms in affected individuals. The fNIRS-derived oxygenation measure shows promise as a sensitive neural marker to identify early neuropsychological impairments due to ALS.
C1 [Kuruvilla, Mili S.] Univ Nebraska Med Ctr, Munroe Meyer Inst Genet & Rehabil, Omaha, NE 68198 USA.
[Green, Jordan R.] Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA.
[Ayaz, Hasan] Drexel Univ, Sch Biomed Engn Sci & Hlth Syst, Philadelphia, PA 19104 USA.
[Murman, Daniel L.] Univ Nebraska Med Ctr, Dept Neurol Sci, Omaha, NE 68198 USA.
RP Kuruvilla, MS (reprint author), Univ Nebraska Med Ctr, Munroe Meyer Inst Genet & Rehabil, 985450 Nebraska Med Ctr, Omaha, NE 68198 USA.
EM mili.kuruvilla@unmc.edu
OI Kuruvilla-Dugdale, Mili/0000-0001-7900-2364; Ayaz,
Hasan/0000-0001-5514-2741
FU Barkley Trust; NIH-NIDCD [R01 DC009890]; Munroe Meyer Institute of
Genetics and Rehabilitation
FX This research was funded by the Barkley Trust, an NIH-NIDCD grant R01
DC009890, and a seed grant from the Munroe Meyer Institute of Genetics
and Rehabilitation. The authors would like to thank Cynthia Didion, Lori
Synhorst, Jun Wang, and Suyash Joshi for their help with data collection
and analysis.
NR 37
TC 1
Z9 1
U1 2
U2 12
PU PSYCHOLOGY PRESS
PI HOVE
PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND
SN 1758-8928
J9 COGN NEUROSCI-UK
JI Cogn. Neurosci
PD JUN 1
PY 2013
VL 4
IS 2
BP 115
EP 121
DI 10.1080/17588928.2013.797889
PG 7
WC Neurosciences
SC Neurosciences & Neurology
GA 151YA
UT WOS:000319495100008
PM 24073736
ER
PT J
AU Fonseca, R
Pitman, MB
AF Fonseca, R.
Pitman, M. B.
TI Lymphangioma of the pancreas: a multimodal approach to pre-operative
diagnosis
SO CYTOPATHOLOGY
LA English
DT Article
DE EUS-FNA; endoscopic ultrasound-guided FNA; lymphangioma; pancreas;
multimodal diagnosis; cytology
ID CYST-FLUID ANALYSIS; FINE-NEEDLE-ASPIRATION; PAPILLARY MUCINOUS
NEOPLASMS; EUS-GUIDED FNA; DIFFERENTIAL-DIAGNOSIS; LESIONS; MANAGEMENT;
CYSTADENOMA; CYTOLOGY
AB Background: Lymphangioma of the pancreas is an extremely rare benign tumour of lymphatic origin, with only four cases diagnosed by EUS-FNA reported to date. Methods and materials: Five cases of either cytologically or histologically diagnosed pancreatic lymphangioma with pre-operative cytological analysis by EUS-FNAC were reviewed. Results: All patients were female, with a mean age of 56.4years. By imaging, the cystic lesions ranged in size from 2 to 7cm (mean 4.5cm) and were mainly located in the head of the pancreas. All cysts had thin walls and no cyst demonstrated a mural nodule. Diagnosis based on imaging features was benign in all cases due to the absence of high-risk features. Four samples were sent for biochemical analysis, which showed low CEA levels (range, <0.519.4ng/ml; mean, 5.45ng/ml) and CA 19.9 and CA 72.4 levels within normal range. All cyst fluids showed numerous small lymphocytes with no atypia; no epithelial cells were present, including no gastrointestinal contamination. Flow cytometry in two cases showed T lymphocytes with a mature phenotype. Surgical resection in two patients confirmed the cytological diagnosis. Benign clinical follow-up was available in three patients at 2, 3 and 3.5years. Conclusion: A multimodal approach to cytological diagnosis (combining clinical, radiological and cyst fluid gross, biochemical and cytological characteristics) can lead to the diagnosis of this cystic neoplasm and distinguish it from other more common cysts in the pancreas, potentially avoiding the need for unnecessary surgery.
C1 [Fonseca, R.] Inst Portugues Oncol Francisco Gentil, Dept Pathol, P-1099023 Lisbon, Portugal.
[Pitman, M. B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Labs, Boston, MA USA.
RP Fonseca, R (reprint author), Inst Portugues Oncol Francisco Gentil, Dept Pathol, R Prof Lima Basto, P-1099023 Lisbon, Portugal.
EM ricardo.fonseca@netcabo.pt
NR 26
TC 3
Z9 3
U1 1
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0956-5507
J9 CYTOPATHOLOGY
JI Cytopathology
PD JUN
PY 2013
VL 24
IS 3
BP 172
EP 176
DI 10.1111/j.1365-2303.2011.00897.x
PG 5
WC Cell Biology; Pathology
SC Cell Biology; Pathology
GA 151OM
UT WOS:000319469900004
PM 21810124
ER
PT J
AU Zhang, Y
Harrison, JM
Nateras, OS
Chalfin, S
Duong, TQ
AF Zhang, Yi
Harrison, Joseph M.
Nateras, Oscar San Emeterio
Chalfin, Steven
Duong, Timothy Q.
TI Decreased retinal-choroidal blood flow in retinitis pigmentosa as
measured by MRI
SO DOCUMENTA OPHTHALMOLOGICA
LA English
DT Article
DE Retinal diseases; Magnetic resonance imaging; Electroretinography;
Retinal degeneration
ID MANGANESE-ENHANCED MRI; RAT RETINA; FUNCTIONAL MRI; MOUSE MODEL;
MORPHOLOGICAL-CHANGES; ABYSSINIAN CATS; VASCULAR LAYERS; ANATOMICAL MRI;
IN-VIVO; DEGENERATION
AB To evaluate retinal and choroidal blood flow (BF) using high-resolution magnetic resonance imaging (MRI) as well as visual function measured by the electroretinogram (ERG) in patients with retinitis pigmentosa (RP).
MRI studies were performed in 6 RP patients (29-67 years) and 5 healthy volunteers (29-64 years) on a 3-Tesla scanner with a custom-made surface coil. Quantitative BF was measured using the pseudo-continuous arterial spin-labeling technique at 0.5 x 0.8 x 6.0 mm. Full-field ERGs of all patients were recorded. Amplitudes and implicit times of standard ERGs were analyzed.
Basal BF in the posterior retinal-choroid was 142 +/- A 16 ml/100ml/min (or 1.14 +/- A 0.13 mu l/mm(2)/min) in the control group and was 70 +/- 19 ml/100ml/min (or 0.56 +/- A 0.15 mu l/mm(2)/min) in the RP group. Retinal-choroidal BF was significantly reduced by 52 +/- A 8 % in RP patients compared to controls (P < 0.05). ERG a- and b-wave amplitudes of RP patients were reduced, and b-wave implicit times were delayed. There were statistically significant correlations between a-wave amplitude and BF value (r=0.9, P < 0.05) but not between b-wave amplitude and BF value (r =0.7, P=0.2).
This study demonstrates a novel non-invasive MRI approach to measure quantitative retinal and choroidal BF in RP patients. We found that retinal-choroidal BF was markedly reduced and significantly correlated with reduced amplitudes of the a-wave of the standard combined ERG.
C1 [Zhang, Yi; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA.
[Zhang, Yi; Nateras, Oscar San Emeterio; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, San Antonio, TX 78229 USA.
[Harrison, Joseph M.; Chalfin, Steven; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Ophthalmol, San Antonio, TX 78229 USA.
[Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA.
[Duong, Timothy Q.] South Texas Vet Hlth Care Syst, San Antonio, TX USA.
RP Duong, TQ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, 8403 Floyd Curl Dr, San Antonio, TX 78229 USA.
EM duongt@uthscsa.edu
RI Duong, Timothy/B-8525-2008
FU Clinical Translational Science Award Pilot Grant; Translational
Technology Resource grant [UL1TR000149]; NIH/NEI [R01 EY014211,
EY018855]; Department of Veterans Affairs MERIT awards; Translational
Science Training award through the University of Texas System Graduate
Program Initiative
FX This work was supported by a Clinical Translational Science Award Pilot
Grant and a Translational Technology Resource grant (parent grant
UL1TR000149), NIH/NEI (R01 EY014211 and EY018855), and Department of
Veterans Affairs MERIT awards to TQD. YZ was supported by a
Translational Science Training award through the University of Texas
System Graduate Program Initiative.
NR 65
TC 14
Z9 15
U1 0
U2 11
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0012-4486
J9 DOC OPHTHALMOL
JI Doc. Ophthalmol.
PD JUN
PY 2013
VL 126
IS 3
BP 187
EP 197
DI 10.1007/s10633-013-9374-1
PG 11
WC Ophthalmology
SC Ophthalmology
GA 151QX
UT WOS:000319476400002
PM 23408312
ER
PT J
AU Moon, HS
Dalamaga, M
Kim, SY
Polyzos, SA
Hamnvik, OP
Magkos, F
Paruthi, J
Mantzoros, CS
AF Moon, Hyun-Seuk
Dalamaga, Maria
Kim, Sang-Yong
Polyzos, Stergios A.
Hamnvik, Ole-Petter
Magkos, Faidon
Paruthi, Jason
Mantzoros, Christos S.
TI Leptin's Role in Lipodystrophic and Nonlipodystrophic Insulin-Resistant
and Diabetic Individuals
SO ENDOCRINE REVIEWS
LA English
DT Review
ID FATTY LIVER-DISEASE; ACTIVE ANTIRETROVIRAL THERAPY; HEPATIC STELLATE
CELLS; DIET-INDUCED OBESITY; RECOMBINANT HUMAN LEPTIN;
TYROSINE-PHOSPHATASE SHP-2; VIRUS-INFECTED PATIENTS; METHIONYL HUMAN
LEPTIN; EMERGING CLINICAL-APPLICATIONS; TERM METRELEPTIN TREATMENT
AB Leptin is an adipocyte-secreted hormone that has been proposed to regulate energy homeostasis as well as metabolic, reproductive, neuroendocrine, and immune functions. In the context of open-label uncontrolled studies, leptin administration has demonstrated insulin-sensitizing effects in patients with congenital lipodystrophy associated with relative leptin deficiency. Leptin administration has also been shown to decrease central fat mass and improve insulin sensitivity and fasting insulin and glucose levels in HIV-infected patients with highly active antiretroviral therapy (HAART)-induced lipodystrophy, insulin resistance, and leptin deficiency. On the contrary, the effects of leptin treatment in leptin-replete or hyperleptinemic obese individuals with glucose intolerance and diabetes mellitus have been minimal or null, presumably due to leptin tolerance or resistance that impairs leptin action. Similarly, experimental evidence suggests a null or a possibly adverse role of leptin treatment in nonlipodystrophic patients with nonalcoholic fatty liver disease. In this review, we present a description of leptin biology and signaling; we summarize leptin's contribution to glucose metabolism in animals and humans in vitro, ex vivo, and in vivo; and we provide insights into the emerging clinical applications and therapeutic uses of leptin in humans with lipodystrophy and/or diabetes.
C1 [Moon, Hyun-Seuk; Kim, Sang-Yong; Hamnvik, Ole-Petter; Magkos, Faidon; Paruthi, Jason; Mantzoros, Christos S.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA.
[Dalamaga, Maria] Univ Athens, Sch Med, Attikon Gen Univ Hosp, Dept Clin Biochem, Athens 15784, Greece.
[Kim, Sang-Yong] Chosun Univ, Sch Med, Div Endocrinol & Metab, Kwangju 501717, South Korea.
[Polyzos, Stergios A.] Aristotle Univ Thessaloniki, Ippokrat Hosp, Med Clin 2, Thessaloniki 11527, Greece.
[Hamnvik, Ole-Petter] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA.
[Mantzoros, Christos S.] Harvard Univ, Boston VA Healthcare Syst, Sch Med, Endocrinol Sect, Boston, MA 02118 USA.
RP Mantzoros, CS (reprint author), Harvard Univ, Sch Med, JP9B52A,150 South Huntington Ave, Boston, MA 02130 USA.
EM cmantzor@bidmc.harvard.edu
RI Hamnvik, Ole-Petter/D-1719-2011; Moon, Hyun-Seuk/G-8576-2015;
OI Moon, Hyun-Seuk/0000-0002-5216-2090; Polyzos,
Stergios/0000-0001-9232-4042; Dalamaga, Maria/0000-0002-7008-388X
FU National Institute of Diabetes and Digestive and Kidney Diseases [58785,
79929, 81913, AG032030]; VA Merit award [10684957]; Beth Israel
Deaconess Medical Center
FX The Mantzoros laboratory is supported by National Institute of Diabetes
and Digestive and Kidney Diseases Grants 58785, 79929, 81913, and
AG032030 and a VA Merit award (Grant 10684957). The Mantzoros Laboratory
is also supported by a discretionary grant from Beth Israel Deaconess
Medical Center.
NR 321
TC 74
Z9 80
U1 0
U2 14
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0163-769X
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2013
VL 34
IS 3
BP 377
EP 412
DI 10.1210/er.2012-1053
PG 36
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 154KN
UT WOS:000319674300003
PM 23475416
ER
PT J
AU Olivry, T
Bizikova, P
Paps, JS
Dunston, S
Lerner, EA
Yosipovitch, G
AF Olivry, Thierry
Bizikova, Petra
Paps, Judy S.
Dunston, Stan
Lerner, Ethan A.
Yosipovitch, Gil
TI Cowhage can induce itch in the atopic dog
SO EXPERIMENTAL DERMATOLOGY
LA English
DT Article
DE canine; dog; itch; model; pruritus
ID PROTEINASE-ACTIVATED RECEPTOR-2; DERMATITIS; SKIN; HISTAMINE; AGENTS;
MODEL
AB Itch is a cardinal symptom of atopic dermatitis in humans and dogs. Until now, experimental induction of itch in dogs has proven difficult. The objectives of this study were to determine whether protease-rich spicules, protein extracts and the protease mucunain of the tropical legume cowhage provoked itch and inflammation when rubbed onto canine skin. Native spicules variably induced itch manifestations in about half of the dogs, while challenges with protease-deactivated spicules remained negative. The epicutaneous application of cowhage extract and mucunain after microneedle roller usage also induced pruritus and inflammation. Importantly, there was an interindividual inconsistency in pruritus and inflammation induction and also marked differences in pruritus intensity after challenge. In conclusion, cowhage spicules, protein-rich extracts and mucunain can all induce pruritus and inflammation in dogs as in other species, but the inconsistency of provocation is currently a limitation of this challenge type for future studies of pruritus in dogs.
C1 [Olivry, Thierry; Bizikova, Petra; Paps, Judy S.; Dunston, Stan] NC State Univ, Coll Vet Med, Dept Clin Sci, Raleigh, NC USA.
[Olivry, Thierry; Bizikova, Petra] NC State Univ, Ctr Comparat Med & Translat Res, Raleigh, NC USA.
[Lerner, Ethan A.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA.
[Yosipovitch, Gil] Wake Forest Univ, Med Ctr, Dept Dermatol, Winston Salem, NC 27109 USA.
RP Olivry, T (reprint author), N Carolina State Univ, Coll Vet Med, Dept Clin Sci, 1060 Williams Moore Dr, Raleigh, NC 27607 USA.
EM tolivry@ncsu.edu
FU Novartis Animal Health
FX This study was funded by Novartis Animal Health. The authors thank Dr.
Kristine Rossbach for her help during pilot challenges. The author also
thanks GY and EL who designed the study; JS, PB and SD who performed the
research and analysed the data; and PB, GY and EL who wrote the
manuscript.
NR 15
TC 4
Z9 4
U1 1
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0906-6705
J9 EXP DERMATOL
JI Exp. Dermatol.
PD JUN
PY 2013
VL 22
IS 6
BP 435
EP 437
DI 10.1111/exd.12158
PG 3
WC Dermatology
SC Dermatology
GA 151PE
UT WOS:000319471800017
PM 23711071
ER
PT J
AU Sawyer, TK
Wu, JC
Sawyer, JR
English, JM
AF Sawyer, Tomi K.
Wu, Joe C.
Sawyer, Jonathon R.
English, Jessie M.
TI Protein kinase inhibitors: breakthrough medicines and the next
generation
SO EXPERT OPINION ON INVESTIGATIONAL DRUGS
LA English
DT Editorial Material
DE kinase inhibitor; protein kinase; proteins; small-molecule
ID DRUG
AB In this issue of Expert Opinion on Investigational Drugs, several protein kinases families and pathways underlying cancer and other diseases are reviewed and several small molecule inhibitors that are in clinical trials are further described. Highlights of these reviews and drug evaluations are summarized in this editorial.
C1 [Sawyer, Tomi K.] Aileron Therapeut, Cambridge, MA 02139 USA.
[Wu, Joe C.] GlaxoSmithKline PLC, Cambridge, MA 02139 USA.
[Sawyer, Jonathon R.] Providence Coll, Providence, RI 02908 USA.
[English, Jessie M.] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02115 USA.
RP Sawyer, TK (reprint author), Aileron Therapeut, Cambridge, MA 02139 USA.
EM sawyerkrt@aol.com
NR 14
TC 6
Z9 8
U1 0
U2 5
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 JUN
PY 2013
VL 22
IS 6
BP 675
EP 678
DI 10.1517/13543784.2013.804509
PG 4
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 150TP
UT WOS:000319414400001
PM 23705633
ER
PT J
AU Kurihara, T
Jones, CN
Yu, YM
Fischman, AJ
Watada, S
Tompkins, RG
Fagan, SP
Irimia, D
AF Kurihara, Tomohiro
Jones, Caroline N.
Yu, Yong-Ming
Fischman, Alan J.
Watada, Susumu
Tompkins, Ronald G.
Fagan, Shawn P.
Irimia, Daniel
TI Resolvin D2 restores neutrophil directionality and improves survival
after burns
SO FASEB JOURNAL
LA English
DT Article
DE chemotaxis; microfluidics; inflammation; innate immunity; lipid
mediators
ID THERMAL-INJURY; D1; SEPSIS; INFECTION; MEDIATORS; TRAUMA; INFLAMMATION;
MICE; RESOLUTION; MORTALITY
AB Following severe burns and trauma injuries, the changes of neutrophil migratory phenotype are a double-edged sword. Activated neutrophils migrate into injured tissues and help contain microbial infections, but they can also enter normal tissues and damage vital organs. Depleting the neutrophils from circulation protects vital organs against neutrophil-induced damage but leaves the body exposed to infectious complications. Here we show that restoring normal neutrophil migratory phenotype in rats with burn injuries correlates with improved survival in a classical double-injury model of sequential burn and septic insults. We uncovered that the directionality of neutrophils from burned rats can be restored both in vitro by 1 nM resolvin D2 (RvD2) and in vivo by RvD2 for 7 d, 25 ng/kg body mass (8-10 ng/rat). Restoring neutrophil directionality dramatically increases survival after a second septic insult at d 9 postburn. Survival of RvD2-treated animals increases from 0 to 100% after lipopolysaccharide injection and is extended by 1 wk after cecal ligation. Survival does not significantly increase when the restoration of neutrophil directionality is incomplete, following shorter regimens of RvD2. We conclude that restoring neutrophil directionality using RvD2 could have prophylactic value and delay lethal complications after burn injuries.-Kurihara T., Jones, C. N., Yu, Y.-M., Fischman, A. J., Watada, S., Tompkins, R. G., Fagan, S. P., Irimia, D. Resolvin D2 restores neutrophil directionality and improves survival after burns.
C1 [Kurihara, Tomohiro; Jones, Caroline N.; Yu, Yong-Ming; Fischman, Alan J.; Watada, Susumu; Tompkins, Ronald G.; Fagan, Shawn P.; Irimia, Daniel] Shriners Hosp Children, Boston, MA USA.
[Kurihara, Tomohiro; Jones, Caroline N.; Yu, Yong-Ming; Watada, Susumu; Tompkins, Ronald G.; Fagan, Shawn P.; Irimia, Daniel] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Jones, Caroline N.; Irimia, Daniel] Harvard Univ, Massachusetts Gen Hosp, Sch Med, BioMEMS Resource Ctr, Boston, MA USA.
[Fischman, Alan J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Nucl Med, Boston, MA USA.
RP Irimia, D (reprint author), MGH CNY, 114 16th St,1404, Boston, MA 02129 USA.
EM dirimia@hms.harvard.edu
OI Irimia, Daniel/0000-0001-7347-2082
FU Shriners Burns Hospital; U.S. National Institutes of Health [GM-092804,
GM-007035, DE-019938]
FX This work was supported in part by funds from Shriners Burns Hospital
and U.S. National Institutes of Health grants GM-092804, GM-007035, and
DE-019938.
NR 44
TC 30
Z9 30
U1 0
U2 11
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 JUN
PY 2013
VL 27
IS 6
BP 2270
EP 2281
DI 10.1096/fj.12-219519
PG 12
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 154II
UT WOS:000319667600017
PM 23430978
ER
PT J
AU Sachse, CC
Kim, YH
Agsten, M
Huth, T
Alzheimer, C
Kovacs, DM
Kim, DY
AF Sachse, Carolyn C.
Kim, Young Hye
Agsten, Marianne
Huth, Tobias
Alzheimer, Christian
Kovacs, Dora M.
Kim, Doo Yeon
TI BACE1 and presenilin/gamma-secretase regulate proteolytic processing of
KCNE1 and 2, auxiliary subunits of voltage-gated potassium channels
SO FASEB JOURNAL
LA English
DT Article
DE MinK; MiRP; Alzheimer's disease; KCNQ1
ID LONG QT SYNDROME; ALZHEIMERS-DISEASE; BETA-SECRETASE; I-KS;
SODIUM-CHANNELS; TARGETED DISRUPTION; MEDIATED CLEAVAGE;
NEURONAL-ACTIVITY; ALPHA-SECRETASE; GAMMA-SECRETASE
AB BACE1 and presenilin (PS)/gamma-secretase play a major role in Alzheimer's disease pathogenesis by regulating amyloid-beta peptide generation. We recently showed that these secretases also regulate the processing of voltage-gated sodium channel auxiliary beta-subunits and thereby modulate membrane excitability. Here, we report that KCNE1 and KCNE2, auxiliary subunits of voltage-gated potassium channels, undergo sequential cleavage mediated by either alpha-secretase and PS/gamma-secretase or BACE1 and PS/gamma-secretase in cells. Elevated alpha-secretase or BACE1 activities increased C-terminal fragment (CTF) levels of KCNE1 and 2 in human embryonic kidney (HEK293T) and rat neuroblastoma (B104) cells. KCNE-CTFs were then further processed by PS/gamma-secretase to KCNE intracellular domains. These KCNE cleavages were specifically blocked by chemical inhibitors of the secretases in the same cell models. We also verified our results in mouse cardiomyocytes and cultured primary neurons. Endogenous KCNE1- and KCNE2-CTF levels increased by 2- to 4-fold on PS/gamma-secretase inhibition or BACE1 overexpression in these cells. Furthermore, the elevated BACE1 activity increased KCNE1 processing and shifted KCNE1/KCNQ1 channel activation curve to more positive potentials in HEK cells. KCNE1/KCNQ1 channel is a cardiac potassium channel complex, and the positive shift would lead to a decrease in membrane repolarization during cardiac action potential. Together, these results clearly showed that KCNE1 and KCNE2 cleavages are regulated by BACE1 and PS/gamma-secretase activities under physiological conditions. Our results also suggest a functional role of KCNE cleavage in regulating voltage-gated potassium channels.-Sachse, C. C., Kim, Y. H., Agsten, M., Huth, T., Alzheimer, C., Kovacs, D. M., and Kim, D. Y. BACE1 and presenilin/gamma-secretase regulate proteolytic processing of KCNE1 and 2, auxiliary subunits of voltage-gated potassium channels.
C1 [Sachse, Carolyn C.; Kim, Young Hye; Kovacs, Dora M.; Kim, Doo Yeon] Harvard Univ, MassGen Inst Neurodegenerat Dis, Massachusetts Gen Hosp, Neurobiol Dis Lab,Genet & Aging Res Unit,Med Sch, Charlestown, MA USA.
[Kim, Young Hye] Korea Basic Sci Inst, Div Mass Spectrometry Res, Ochang, South Korea.
[Agsten, Marianne; Huth, Tobias; Alzheimer, Christian] Univ Erlangen Nurnberg, Inst Physiol & Pathophysiol, D-91054 Erlangen, Germany.
RP Kim, DY (reprint author), Massachusetts Gen Hosp, Genet & Aging Res Unit, 114 16th St, Charlestown, MA 02129 USA.
EM dkim@helix.mgh.harvard.edu
OI Huth, Tobias/0000-0002-6414-8923
FU Cure Alzheimer's fund; U.S. National Institutes of Health/National
Institute on Aging; Dr. Ernst und Anita Bauer-Stiftung; Johannes und
Frieda Marohn-Stiftung
FX The authors thank Stephanie Hartmann (University of Erlangen-Nurnberg)
for her contribution in revising this manuscript and Dr. Jordan Tang
(University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA)
for BACE1 inhibitor DR9. This work is supported by grants
from the Cure Alzheimer's fund to D.Y.K, the U.S. National Institutes of
Health/National Institute on Aging to D.M.K and D.Y.K., the Dr. Ernst
und Anita Bauer-Stiftung to S.H., and the Johannes und Frieda
Marohn-Stiftung to T.H. and C.A.
NR 48
TC 11
Z9 11
U1 0
U2 12
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 JUN
PY 2013
VL 27
IS 6
BP 2458
EP 2467
DI 10.1096/fj.12-214056
PG 10
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 154II
UT WOS:000319667600033
PM 23504710
ER
PT J
AU Righi, V
Constantinou, C
Mintzopoulos, D
Khan, N
Mupparaju, SP
Rahme, LG
Swartz, HM
Szeto, HH
Tompkins, RG
Tzika, AA
AF Righi, Valeria
Constantinou, Caterina
Mintzopoulos, Dionyssios
Khan, Nadeem
Mupparaju, S. P.
Rahme, Laurence G.
Swartz, Harold M.
Szeto, Hazel H.
Tompkins, Ronald G.
Tzika, A. Aria
TI Mitochondria-targeted antioxidant promotes recovery of skeletal muscle
mitochondrial function after burn trauma assessed by in vivo P-31
nuclear magnetic resonance and electron paramagnetic resonance
spectroscopy
SO FASEB JOURNAL
LA English
DT Article
DE physiology; molecular medicine; mice; mitochondria; oxidative stress
ID INSULIN-RESISTANCE; INDUCED APOPTOSIS; NMR-SPECTROSCOPY;
DOWN-REGULATION; PEPTIDE; INJURY; ACONITASE; METABOLISM; MODULATION;
DYSFUNCTION
AB Burn injury causes a major systemic catabolic response that is associated with mitochondrial dysfunction in skeletal muscle. We investigated the effects of the mitochondria-targeted peptide antioxidant Szeto-Schiller 31 (SS-31) on skeletal muscle in a mouse burn model using in vivo phosphorus-31 nuclear magnetic resonance (P-31 NMR) spectroscopy to noninvasively measure high-energy phosphate levels; mitochondrial aconitase activity measurements that directly correlate with TCA cycle flux, as measured by gas chromatography mass spectrometry (GC-MS); and electron paramagnetic resonance (EPR) to assess oxidative stress. At 6 h postburn, the oxidative ATP synthesis rate was increased 5-fold in burned mice given a single dose of SS-31 relative to untreated burned mice (P=0.002). Furthermore, SS-31 administration in burned animals decreased mitochondrial aconitase activity back to control levels. EPR revealed a recovery in redox status of the SS-31-treated burn group compared to the untreated burn group (P<0.05). Our multidisciplinary convergent results suggest that SS-31 promotes recovery of mitochondrial function after burn injury by increasing ATP synthesis rate, improving mitochondrial redox status, and restoring mitochondrial coupling. These findings suggest use of noninvasive in vivo NMR and complementary EPR offers an approach to monitor the effectiveness of mitochondrial protective agents in alleviating burn injury symptoms.
C1 [Righi, Valeria; Constantinou, Caterina; Mintzopoulos, Dionyssios; Tzika, A. Aria] Harvard Univ, Sch Med, Massachusetts Gen Hosp, NMR Surg Lab,Dept Surg, Boston, MA 02114 USA.
[Constantinou, Caterina; Rahme, Laurence G.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Surg Lab,Dept Surg, Boston, MA 02114 USA.
[Righi, Valeria; Constantinou, Caterina; Mintzopoulos, Dionyssios; Rahme, Laurence G.; Tompkins, Ronald G.; Tzika, A. Aria] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Div Burns, Boston, MA 02114 USA.
[Righi, Valeria; Mintzopoulos, Dionyssios; Tzika, A. Aria] Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol,Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Righi, Valeria; Mintzopoulos, Dionyssios; Tzika, A. Aria] Harvard Univ, Sch Med, Shriners Burns Inst, Boston, MA 02114 USA.
[Khan, Nadeem; Mupparaju, S. P.; Swartz, Harold M.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch,Dept Diagnost Radiol, Electron Paramagnet Resonance EPR Ctr Viable Syst, Hanover, NH 03756 USA.
[Szeto, Hazel H.] Cornell Univ, Joan & Sanford I Weill Med Coll, Dept Pharmacol, New York, NY 10021 USA.
RP Tzika, AA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, NMR Surg Lab,Dept Surg, 51 Blossom St,Rm 261, Boston, MA 02114 USA.
EM atzika@hms.harvard.edu
OI Righi, Valeria/0000-0003-2394-8462; Constantinou,
Caterina/0000-0003-3589-0739
FU U.S. National Institute Institutes of Health (NIH) [P50GM021700];
Shriner's Hospital for Children [8893, 8892]; U.S. Defense Medical
Research and Development Program (DMRDP) [DM103014]
FX This work was supported in part by a U.S. National Institute Institutes
of Health (NIH) center grant (P50GM021700) to R. G. T. (A. A. T.,
director of the NMR core), Shriner's Hospital for Children research
grants to A. A. T. (8893) and L. G. R. (8892), and a research support
grant (DM103014) from the U.S. Defense Medical Research and Development
Program (DMRDP). The authors thank Dr. Alan J. Fischman for his advice.
The authors also thank Dr. Ann Power Smith (Write Science Right, Las
Vegas, NV, USA) for editorial assistance. Disclosure: the SS peptides
technology has been licensed for commercial development to Stealth
Peptides Inc. (Newton Centre, MA, USA) by the Cornell Research
Foundation (CRF), and both CRF and H. H. S. have financial interests.
NR 45
TC 6
Z9 6
U1 2
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 JUN
PY 2013
VL 27
IS 6
BP 2521
EP 2530
DI 10.1096/fj.12-220764
PG 10
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 154II
UT WOS:000319667600040
PM 23482635
ER
PT J
AU Avior, Y
Bomze, D
Ramon, O
Nahmias, Y
AF Avior, Yishai
Bomze, David
Ramon, Ory
Nahmias, Yaakov
TI Flavonoids as dietary regulators of nuclear receptor activity
SO FOOD & FUNCTION
LA English
DT Review
ID PROLIFERATOR-ACTIVATED RECEPTOR; PREGNANE X-RECEPTOR; OBESE ZUCKER RATS;
CITRUS POLYMETHOXYLATED FLAVONES; ALPHA-INDEPENDENT MECHANISMS;
APOLIPOPROTEIN-B SECRETION; CYP3A4 GENE-EXPRESSION; ESTROGEN-LIKE
ACTIVITY; NITRIC-OXIDE SYNTHASE; BONE-MINERAL DENSITY
AB Metabolic diseases such as obesity, type II diabetes, and dyslipidemia are a rising cause of mortality worldwide. The progression of many metabolic diseases is fundamentally regulated on the transcriptional level by a family of ligand-activated transcription factors, called nuclear receptors, which detect and respond to metabolic changes. Their role in maintaining metabolic homeostasis makes nuclear receptors an important pharmaceutical and dietary target. This review will present the growing evidence that flavonoids, natural secondary plant metabolites, are important regulators of nuclear receptor activity. Structural similarities between flavonoids and cholesterol derivatives combined with the promiscuous nature of most nuclear receptors provide a wealth of possibilities for pharmaceutical and dietary modulation of metabolism. While the challenges of bringing flavonoid-derived therapeutics to the market are significant, we consider this rapidly growing field to be an essential aspect of the functional food initiative and an important mine for pharmaceutical compounds.
C1 [Avior, Yishai; Ramon, Ory; Nahmias, Yaakov] Hebrew Univ Jerusalem, Ctr Bioengn, Sch Engn & Comp Sci, IL-91904 Jerusalem, Israel.
[Bomze, David; Nahmias, Yaakov] Hebrew Univ Jerusalem, Inst Life Sci, Dept Cell & Dev Biol, IL-91904 Jerusalem, Israel.
[Nahmias, Yaakov] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
RP Avior, Y (reprint author), Hebrew Univ Jerusalem, Ctr Bioengn, Sch Engn & Comp Sci, Edmond J Safra Campus Givat Ram,Silberman 3-512, IL-91904 Jerusalem, Israel.
EM ynahmias@cs.huji.ac.il
RI Nahmias, Yaakov/H-4725-2013;
OI Nahmias, Yaakov/0000-0002-6051-616X
FU European Research Council Starting Grant [TMIHCV 242699]
FX This work was supported by the European Research Council Starting Grant
(TMIHCV 242699). Resources were provided by National Institute of
Diabetes and Digestive and Kidney Diseases (K01DK080241) and the Harvard
Clinical Nutrition Research Center (P30-DK040561). The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 209
TC 15
Z9 15
U1 2
U2 36
PU ROYAL SOC CHEMISTRY
PI CAMBRIDGE
PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS,
ENGLAND
SN 2042-6496
EI 2042-650X
J9 FOOD FUNCT
JI Food Funct.
PD JUN
PY 2013
VL 4
IS 6
BP 831
EP 844
DI 10.1039/c3fo60063g
PG 14
WC Biochemistry & Molecular Biology; Food Science & Technology
SC Biochemistry & Molecular Biology; Food Science & Technology
GA 152GE
UT WOS:000319518700001
PM 23598551
ER
PT J
AU Chan, BK
Abedon, ST
Loc-Carrillo, C
AF Chan, Benjamin K.
Abedon, Stephen T.
Loc-Carrillo, Catherine
TI Phage cocktails and the future of phage therapy
SO FUTURE MICROBIOLOGY
LA English
DT Review
DE antibacterial; antibiotic resistance; bacteriophage; diversity of
bacterial; pathogen; phage cocktail; polyphage
ID ESCHERICHIA-COLI O157H7; IN-VIVO; PSEUDOMONAS-AERUGINOSA; BACTERIOPHAGE
THERAPY; PERSONALIZED MEDICINE; CAMPYLOBACTER-JEJUNI; INFLUENZA
VACCINES; BROILER-CHICKENS; HOST-RANGE; RESISTANCE
AB Viruses of bacteria, known as bacteriophages or phages, were discovered nearly 100 years ago. Their potential as antibacterial agents was appreciated almost immediately, with the first 'phage therapy' trials predating Fleming's discovery of penicillin by approximately a decade. In this review, we consider phage therapy that can be used for treating bacterial infections in humans, domestic animals and even biocontrol in foods. Following an overview of the topic, we explore the common practice - both experimental and, in certain regions of the world, clinical - of mixing therapeutic phages into cocktails consisting of multiple virus types. We conclude with a discussion of the commercial and medical context of phage cocktails as therapeutic agents. In comparing off-the-shelf versus custom approaches, we consider the merits of a middle ground, which we deem 'modifiable'. Finally, we explore a regulatory framework for such an approach based on an influenza vaccine model.
C1 [Chan, Benjamin K.] Univ Utah, Dept Internal Med, Salt Lake City, UT 84112 USA.
[Abedon, Stephen T.] Ohio State Univ, Dept Microbiol, Mansfield, OH USA.
[Loc-Carrillo, Catherine] Univ Utah, Dept Orthoped, Salt Lake City, UT 84112 USA.
[Loc-Carrillo, Catherine] US Dept Vet Affairs, Hlth Care Syst, Salt Lake City, UT USA.
RP Loc-Carrillo, C (reprint author), Univ Utah, Dept Orthoped, Salt Lake City, UT 84112 USA.
EM c.loc.carrillo@hsc.utah.edu
RI Loc Carrillo, Catherine/B-5461-2014
OI Loc Carrillo, Catherine/0000-0002-7265-1203
NR 103
TC 101
Z9 104
U1 29
U2 165
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 1746-0913
EI 1746-0921
J9 FUTURE MICROBIOL
JI Future Microbiol.
PD JUN
PY 2013
VL 8
IS 6
BP 769
EP 783
DI 10.2217/FMB.13.47
PG 15
WC Microbiology
SC Microbiology
GA 151EH
UT WOS:000319443000014
PM 23701332
ER
PT J
AU Schmeler, KM
Ramirez, PT
Reyes-Martinez, CA
Chernofsky, MR
del Carmen, MG
Diaz-Montes, TP
Padilla, L
Tejada-Berges, T
Tarraza, H
Bermudez, A
Trimble, EL
AF Schmeler, Kathleen M.
Ramirez, Pedro T.
Reyes-Martinez, Cesar A.
Chernofsky, Mildred R.
del Carmen, Marcela G.
Diaz-Montes, Teresa P.
Padilla, Luis
Tejada-Berges, Trevor
Tarraza, Hector
Bermudez, Adriana
Trimble, Edward L.
TI The Central America Gynecologic Oncology Education Program (CONEP):
Improving gynecologic oncology education and training on a global scale
SO GYNECOLOGIC ONCOLOGY
LA English
DT Editorial Material
ID VISUAL INSPECTION; ACETIC-ACID
C1 [Schmeler, Kathleen M.; Ramirez, Pedro T.] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol & Reprod Med, Houston, TX 77230 USA.
[Reyes-Martinez, Cesar A.] Hosp Gen San Juan, Dept Obstet & Ginecol, De Dios, Guatemala.
[Chernofsky, Mildred R.] Sibley Mem Hosp, Sibley Ctr Gynecol Oncol & Adv Pelv Surg, Washington, DC USA.
[del Carmen, Marcela G.] Massachusetts Gen Hosp, Dept Gynecol Oncol, Boston, MA 02114 USA.
[Diaz-Montes, Teresa P.] Johns Hopkins Med Inst, Dept Gynecol Oncol, Baltimore, MD USA.
[Padilla, Luis] Univ New Mexico, Dept Gynecol Oncol, Albuquerque, NM 87131 USA.
[Tejada-Berges, Trevor] Women & Infants Hosp Rhode Isl, Dept Gynecol Oncol, Providence, RI USA.
[Tarraza, Hector] Maine Med Ctr, Dept Gynecol Oncol, Portland, ME USA.
[Bermudez, Adriana] Buenos Aires Univ Hosp, Gynecol Oncol Unit, Buenos Aires, DF, Argentina.
[Trimble, Edward L.] NCI, Ctr Global Hlth, Bethesda, MD 20892 USA.
RP Schmeler, KM (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, POB 301439, Houston, TX 77230 USA.
EM kschmele@mdanderson.org
NR 10
TC 6
Z9 6
U1 1
U2 3
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
EI 1095-6859
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD JUN
PY 2013
VL 129
IS 3
BP 445
EP 447
DI 10.1016/j.ygyno.2013.03.013
PG 3
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 151SK
UT WOS:000319480300002
PM 23528927
ER
PT J
AU Taylor, WC
King, KE
Shegog, R
Paxton, RJ
Evans-Hudnall, GL
Rempel, DM
Chen, V
Yancey, AK
AF Taylor, Wendell C.
King, Kathryn E.
Shegog, Ross
Paxton, Raheem J.
Evans-Hudnall, Gina L.
Rempel, David M.
Chen, Vincent
Yancey, Antronette K.
TI Booster Breaks in the workplace: participants' perspectives on
health-promoting work breaks
SO HEALTH EDUCATION RESEARCH
LA English
DT Article
ID PHYSICAL-ACTIVITY INTERVENTIONS; SEDENTARY BEHAVIOR; AFRICAN-AMERICAN;
TIME; DETERMINANTS; MORTALITY; BELIEFS; OBESITY; LIFE
AB Increasing sedentary work has been associated with greater cardiovascular and metabolic risk, as well as premature mortality. Interrupting the sedentary workday with health-promoting work breaks can counter these negative health effects. To examine the potential sustainability of work-break programs, we assessed the acceptance of these breaks among participants in a Booster Break program. We analyzed qualitative responses from 35 participants across five worksites where one 15-min physical activity break was taken each workday. Two worksites completed a 1-year intervention and three worksites completed a 6-month intervention. Responses to two open-ended questions about the acceptance and feasibility of Booster Breaks were obtained from a survey administered after the intervention. Three themes for benefits and two themes for barriers were identified. The benefit themes were (i) reduced stress and promoted enjoyment, (ii) increased health awareness and facilitated behavior change, and (iii) enhanced workplace social interaction. The barrier themes were the need for (iv) greater variety in Booster Break routines and (v) greater management support. This study provides empirical support for the acceptance and feasibility of Booster Breaks during the workday. Emphasizing the benefits and minimizing the barriers are strategies that can be used to implement Booster Breaks in other workplaces.
C1 [Taylor, Wendell C.; King, Kathryn E.; Chen, Vincent] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Div Hlth Promot & Behav Sci, Houston, TX 77030 USA.
[Shegog, Ross] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Div Hlth Promot & Behav Sci, Houston, TX 77030 USA.
[Paxton, Raheem J.] Univ Texas MD Anderson Canc Ctr, Dorothy I Height Ctr Hlth Equ & Evaluat Res D CHE, Div OVP Canc Prevent & Populat Sci, Houston, TX 77030 USA.
[Evans-Hudnall, Gina L.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Hlth Serv Res & Dev Ctr Excellence, Houston, TX 77030 USA.
[Rempel, David M.] Univ Calif San Francisco, Div Occupat & Environm Med, San Francisco, CA 94143 USA.
[Rempel, David M.] Univ Calif Berkeley, Ergon Program, Dept Bioengn, Richmond, CA 94804 USA.
[Yancey, Antronette K.] UCLA Fielding Sch Publ Hlth, UCLA Kaiser Permanente Ctr Hlth Equ, Dept Hlth Serv, Los Angeles, CA 90095 USA.
RP Taylor, WC (reprint author), Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Div Hlth Promot & Behav Sci, 7000 Fannin St,Suite 2670, Houston, TX 77030 USA.
EM Wendell.C.Taylor@uth.tmc.edu
OI Paxton, Raheem/0000-0001-9430-7051
FU NCI NIH HHS [K01 CA158000]; NINR NIH HHS [R03NR10291]
NR 40
TC 8
Z9 8
U1 2
U2 28
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 JUN
PY 2013
VL 28
IS 3
BP 414
EP 425
DI 10.1093/her/cyt001
PG 12
WC Education & Educational Research; Public, Environmental & Occupational
Health
SC Education & Educational Research; Public, Environmental & Occupational
Health
GA 153YP
UT WOS:000319639000005
PM 23466367
ER
PT J
AU Schliamser, JE
Kadish, AH
Subacius, H
Shalaby, A
Schaechter, A
Levine, J
Goldberger, JJ
AF Schliamser, Jorge E.
Kadish, Alan H.
Subacius, Haris
Shalaby, Alaa
Schaechter, Andi
Levine, Joseph
Goldberger, Jeffrey J.
CA DEFINITE Investigators
TI Significance of follow-up left ventricular ejection fraction
measurements in the Defibrillators in Non-Ischemic Cardiomyopathy
Treatment Evaluation trial (DEFINITE)
SO HEART RHYTHM
LA English
DT Article
DE Nonischemic cardiomyopathy; Implantable cardioverter-defibrillator;
Sudden cardiac death
ID IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR; SUDDEN CARDIAC DEATH; DILATED
CARDIOMYOPATHY; HEART-FAILURE; RISK STRATIFICATION; VARIABILITY;
OUTCOMES
AB BACKGROUND As left ventricular ejection fraction (LVEF) may improve, worsen, or remain the same over time, patients' prognosis may also be expected to change because of the change in LVEF, among other factors. OBJECTIVE To evaluate the effect of LVEF change on outcome in the Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE) trial. METHODS Patients with nonischemic cardiomyopathy with LVEF<36%, history of symptomatic heart failure, and the presence of significant ventricular ectopic activity were enrolled in the DEFINITE trial. Follow-up LVEF measurements were obtained annually in only a minority (17%) of trial participants. This study therefore evaluated survival and arrhythmic end points in patients whose LVEF was reassessed between 90 and 730 days after enrollment. RESULTS During the 90-730-day postrandomization period, 187 of 449 (42%) enrolled patients who survived at least 90 days had at least 1 follow-up LVEF measurement; these patients were younger and white; had diabetes, better 6-minute walk test results, and higher BMI; were more likely to have appropriate shocks; and had fewer deaths compared to those without follow-up LVEF measurements. Patients whose LVEF improved had reduced mortality compared to patients whose LVEF decreased (hazard ratio 0.09; 95% confidence interval 0.02-0.39; P = .001). Survival free of appropriate shocks was not significantly related to LVEF improvement during follow-up. CONCLUSIONS LVEF improvement was associated with improved survival, but not with a significant decrease in appropriate shocks. These data highlight that appropriate caution should be exercised not to extrapolate the positive effect of improved LVEF to the elimination of arrhythmic events.
C1 [Schliamser, Jorge E.; Kadish, Alan H.; Subacius, Haris; Schaechter, Andi; Goldberger, Jeffrey J.] Northwestern Univ, Ctr Cardiovasc Innovat, Chicago, IL 60611 USA.
[Schliamser, Jorge E.; Kadish, Alan H.; Subacius, Haris; Schaechter, Andi; Goldberger, Jeffrey J.] Northwestern Univ, Feinberg Sch Med, Div Cardiol, Chicago, IL 60611 USA.
[Kadish, Alan H.] Touro Coll, Brooklyn, NY USA.
[Kadish, Alan H.] New York Med Coll, Valhalla, NY 10595 USA.
[Shalaby, Alaa] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA.
[Levine, Joseph] St Francis Hosp, Ctr Heart, Roslyn, NY USA.
RP Goldberger, JJ (reprint author), Northwestern Univ, Feinberg Sch Med, Div Cardiol, 251 E Huron St,Feinberg 8-503, Chicago, IL 60611 USA.
EM j-goldberger@northwestern.edu
OI Subacius, Haris/0000-0003-4061-1220
FU St Jude Medical; Sylmar; Medtronic; Boston Scientific; Biotronik
FX DEFINITE was funded by St Jude Medical, Sylmar, CA. Dr Kadish is a
consultant for Impulse Dynamics and Backbeat Medical AK. Dr Shalaby has
received significant research support from St Jude Medical. Dr Levine is
an ad hoc consultant for St Jude Medical and Medtronic. Dr Goldberger is
Director of the Path to Improved Risk Stratification, NFP, a
not-for-profit think tank on the risk stratification for the prevention
of sudden cardiac death, which has received unrestricted educational
grants from Medtronic, Boston Scientific, and St Jude Medical. He has
received grant support and/or honoraria from Medtronic, Biotronik, and
St Jude Medical.
NR 19
TC 25
Z9 27
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1547-5271
J9 HEART RHYTHM
JI Heart Rhythm
PD JUN
PY 2013
VL 10
IS 6
BP 838
EP 846
DI 10.1016/j.hrthm.2013.02.017
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 152BJ
UT WOS:000319504200017
PM 23422221
ER
PT J
AU Chan, AC
Lam, EY
Srinivasan, VJ
AF Chan, Aaron C.
Lam, Edmund Y.
Srinivasan, Vivek J.
TI Comparison of Kasai Autocorrelation and Maximum Likelihood Estimators
for Doppler Optical Coherence Tomography
SO IEEE TRANSACTIONS ON MEDICAL IMAGING
LA English
DT Article
DE Cramer-Rao bound (CRB); Doppler optical coherence tomography; Doppler
ultrasound; frequency estimation; maximum likelihood estimation (MLE)
ID BLOOD-FLOW; FREQUENCY ESTIMATOR; MEAN FREQUENCY; HIGH-SPEED; VELOCITY;
ULTRASOUND; RESOLUTION; FILTER
AB In optical coherence tomography (OCT) and ultrasound, unbiased Doppler frequency estimators with low variance are desirable for blood velocity estimation. Hardware improvements in OCT mean that ever higher acquisition rates are possible, which should also, in principle, improve estimation performance. Paradoxically, however, the widely used Kasai autocorrelation estimator's performance worsens with increasing acquisition rate. We propose that parametric estimators based on accurate models of noise statistics can offer better performance. We derive a maximum likelihood estimator (MLE) based on a simple additive white Gaussian noise model, and show that it can outperform the Kasai autocorrelation estimator. In addition, we also derive the Cramer Rao lower bound (CRLB), and show that the variance of the MLE approaches the CRLB for moderate data lengths and noise levels. We note that the MLE performance improves with longer acquisition time, and remains constant or improves with higher acquisition rates. These qualities may make it a preferred technique as OCT imaging speed continues to improve. Finally, our work motivates the development of more general parametric estimators based on statistical models of decorrelation noise.
C1 [Chan, Aaron C.; Lam, Edmund Y.] Univ Hong Kong, Dept Elect & Elect Engn, Pokfulam, Hong Kong, Peoples R China.
[Srinivasan, Vivek J.] Univ Calif Davis, Dept Biomed Engn, Davis, CA 95616 USA.
[Srinivasan, Vivek J.] Harvard Univ, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Massachusetts Gen Hosp, Sch Med, Charlestown, MA 02129 USA.
RP Lam, EY (reprint author), Univ Hong Kong, Dept Elect & Elect Engn, Pokfulam, Pokfulam, Hong Kong, Peoples R China.
EM cwachan@eee.hku.hk; elam@eee.hku.hk; vjsriniv@ucdavis.edu
FU University Research Committee of the University of Hong Kong [10401797];
National Institutes of Health [R00NS067050, EB001954 R01]; American
Heart Association [11IRG5440002]; Glaucoma Research Foundation Catalyst
for a Cure
FX This work was supported in part by the University Research Committee of
the University of Hong Kong under Project 10401797, in part by in part
by the National Institutes of Health (R00NS067050, EB001954 R01), in
part by the American Heart Association (11IRG5440002), and in part by
the Glaucoma Research Foundation Catalyst for a Cure.
NR 36
TC 8
Z9 8
U1 0
U2 5
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 0278-0062
J9 IEEE T MED IMAGING
JI IEEE Trans. Med. Imaging
PD JUN
PY 2013
VL 32
IS 6
BP 1033
EP 1042
DI 10.1109/TMI.2013.2248163
PG 10
WC Computer Science, Interdisciplinary Applications; Engineering,
Biomedical; Engineering, Electrical & Electronic; Imaging Science &
Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging
SC Computer Science; Engineering; Imaging Science & Photographic
Technology; Radiology, Nuclear Medicine & Medical Imaging
GA 154UQ
UT WOS:000319701800006
PM 23446044
ER
PT J
AU Valenza, G
Citi, L
Scilingo, EP
Barbieri, R
AF Valenza, Gaetano
Citi, Luca
Scilingo, Enzo Pasquale
Barbieri, Riccardo
TI Point-Process Nonlinear Models With Laguerre and Volterra Expansions:
Instantaneous Assessment of Heartbeat Dynamics
SO IEEE TRANSACTIONS ON SIGNAL PROCESSING
LA English
DT Article
DE Bispectrum; heart rate variability (HRV); high order statistics;
Laguerre expansion; nonlinear analysis; point process; trispectrum;
Wiener-Volterra model
ID HIGHER-ORDER SPECTRA; TIME-SERIES ANALYSIS; RATE-VARIABILITY;
SYSTEM-IDENTIFICATION; CARDIOVASCULAR VARIABILITY; AUTONOMIC MODULATION;
APPROXIMATE ENTROPY; STATISTICAL-METHODS; PERIOD VARIABILITY; GAUSSIAN
INPUTS
AB In the last decades, mathematical modeling and signal processing techniques have played an important role in the study of cardiovascular control physiology and heartbeat nonlinear dynamics. In particular, nonlinear models have been devised for the assessment of the cardiovascular system by accounting for short-memory second-order nonlinearities. In this paper, we introduce a novel inverse Gaussian point process model with Laguerre expansion of the nonlinear Volterra kernels. Within the model, the second-order nonlinearities also account for the long-term information given by the past events of the nonstationary non-Gaussian time series. In addition, the mathematical link to an equivalent cubic input-output Wiener-Volterra model allows for a novel instantaneous estimation of the dynamic spectrum, bispectrum and trispectrum of the considered inter-event intervals. The proposed framework is tested with synthetic simulations and two experimental heartbeat interval datasets. Applications on further heterogeneous datasets such as milling inserts, neural spikes, gait from short walks, and geyser geologic events are also reported. Results show that our model improves on previously developed models and, at the same time, it is able to provide a novel instantaneous characterization and tracking of the inherent nonlinearity of heartbeat dynamics.
C1 [Valenza, Gaetano; Citi, Luca; Barbieri, Riccardo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosci Stat Res Lab, Boston, MA 02114 USA.
[Valenza, Gaetano; Citi, Luca; Barbieri, Riccardo] MIT, Cambridge, MA 02139 USA.
[Valenza, Gaetano; Scilingo, Enzo Pasquale] Univ Pisa, Dept Informat Engn, I-56126 Pisa, Italy.
[Valenza, Gaetano; Scilingo, Enzo Pasquale] Univ Pisa, Res Ctr E Piaggio, I-56126 Pisa, Italy.
RP Valenza, G (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosci Stat Res Lab, Boston, MA 02114 USA.
EM g.valenza@ieee.org; lciti@ieee.org; e.scilingo@centropiaggio.unipi.it;
barbieri@neurostat.mit.edu
RI Citi, Luca/G-2270-2011;
OI Citi, Luca/0000-0001-8702-5654; Barbieri, Riccardo/0000-0001-9381-3833;
Scilingo, Enzo Pasquale/0000-0003-2588-4917; Valenza,
Gaetano/0000-0001-6574-1879
FU NIH [R01-HL0845 02]; EU Commission [ICT-247777 Psyche]
FX This work was supported in part by the NIH Grant R01-HL0845 02 and by
the EU Commission under contract ICT-247777 Psyche.
NR 89
TC 25
Z9 25
U1 0
U2 16
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 1053-587X
EI 1941-0476
J9 IEEE T SIGNAL PROCES
JI IEEE Trans. Signal Process.
PD JUN
PY 2013
VL 61
IS 11
BP 2914
EP 2926
DI 10.1109/TSP.2013.2253775
PG 13
WC Engineering, Electrical & Electronic
SC Engineering
GA 153HQ
UT WOS:000319592700015
ER
PT J
AU Brody, AL
Mukhin, AG
La Charite, J
Ta, K
Farahi, J
Sugar, CA
Mamoun, MS
Vellios, E
Archie, M
Kozman, M
Phuong, J
Arlorio, F
Mandelkern, MA
AF Brody, Arthur L.
Mukhin, Alexey G.
La Charite, Jaime
Ta, Karen
Farahi, Judah
Sugar, Catherine A.
Mamoun, Michael S.
Vellios, Evan
Archie, Meena
Kozman, Maggie
Phuong, Jonathan
Arlorio, Franca
Mandelkern, Mark A.
TI Up-regulation of nicotinic acetylcholine receptors in menthol cigarette
smokers
SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE Age; nicotine dependence; nicotinic acetylcholine receptor; positron
emission tomography; tobacco
ID SMOKING-CESSATION; TOBACCO SMOKING; HUMAN-BRAIN; AFRICAN-AMERICAN;
UNITED-STATES; YOUNG-ADULTS; BINDING; ABSTINENCE; OCCUPANCY; PET
AB One-third of smokers primarily use menthol cigarettes and usage of these cigarettes leads to elevated serum nicotine levels and more difficulty quitting in standard treatment programmes. Previous brain imaging studies demonstrate that smoking (without regard to cigarette type) leads to up-regulation of beta*(2)-containing nicotinic acetylcholine receptors (nAChRs). We sought to determine if menthol cigarette usage results in greater nAChR up-regulation than non-menthol cigarette usage. Altogether, 114 participants (22 menthol cigarette smokers, 41 non-menthol cigarette smokers and 51 non-smokers) underwent positron emission tomography scanning using the alpha(4)beta*(2) nAChR radioligand 2-[F-18]fluoro-A-85380 (2-FA). In comparing menthol to non-menthol cigarette smokers, an overall test of 2-FA total volume of distribution values revealed a significant between-group difference, resulting from menthol smokers having 9-28% higher alpha(4)beta*(2) nAChR densities than non-menthol smokers across regions. In comparing the entire group of smokers to non-smokers, an overall test revealed a significant between-group difference, resulting from smokers having higher alpha(4)beta*(2) nAChR levels in all regions studied (36-42%) other than thalamus (3%). Study results demonstrate that menthol smokers have greater up-regulation of nAChRs than non-menthol smokers. This difference is presumably related to higher nicotine exposure in menthol smokers, although other mechanisms for menthol influencing receptor density are possible. These results provide additional information about the severity of menthol cigarette use and may help explain why these smokers have more trouble quitting in standard treatment programmes.
C1 [Brody, Arthur L.; Sugar, Catherine A.] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA 90095 USA.
[Brody, Arthur L.; La Charite, Jaime; Ta, Karen; Mamoun, Michael S.; Vellios, Evan; Archie, Meena; Kozman, Maggie; Phuong, Jonathan; Arlorio, Franca; Mandelkern, Mark A.] VA Greater Los Angeles Healthcare Syst, Dept Res, Los Angeles, CA USA.
[Mukhin, Alexey G.] Duke Univ, Dept Psychiat, Durham, NC 27706 USA.
[Farahi, Judah] VA Greater Los Angeles Healthcare Syst, Dept Radiochem, Los Angeles, CA USA.
[Sugar, Catherine A.] Univ Calif Los Angeles, Dept Biostat, Los Angeles, CA 90095 USA.
[Mandelkern, Mark A.] Univ Calif Irvine, Dept Phys, Irvine, CA 92717 USA.
RP Brody, AL (reprint author), Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, 300 UCLA Med Plaza,Suite 2200, Los Angeles, CA 90095 USA.
EM abrody@ucla.edu
FU Tobacco-Related Disease Research Program [19XT-0135]; National Institute
on Drug Abuse [R01 DA20872]; Veterans Affairs Type I Merit Review Award;
Richard Metzner Chair in Clinical Neuropharmacology; Pfizer, Inc.;
Phillip Morris, Inc.
FX This study was supported by the Tobacco-Related Disease Research Program
[A.L.B. (19XT-0135)], the National Institute on Drug Abuse [A.L.B. (R01
DA20872)] and a Veterans Affairs Type I Merit Review Award (A.L.B.), as
well as by an endowment from the Richard Metzner Chair in Clinical
Neuropharmacology (A.L.B.). The sponsors had no role in the design and
conduct of the study, collection, management, analysis and
interpretation of the data or preparation, review or approval of the
manuscript.; Drs Brody and Mandelkern were previously co-investigators
on a grant funded by Pfizer, Inc., which was unrelated to this study. Dr
Mukhin is a co-investigator on a grant from Phillip Morris, Inc., for
research unrelated to this study.
NR 57
TC 18
Z9 19
U1 0
U2 12
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 1461-1457
J9 INT J NEUROPSYCHOPH
JI Int. J. Neuropsychopharmacol.
PD JUN
PY 2013
VL 16
IS 5
BP 957
EP 966
DI 10.1017/S1461145712001022
PG 10
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 146WW
UT WOS:000319127100003
PM 23171716
ER
PT J
AU Zietman, AL
AF Zietman, Anthony L.
TI The Red Journal's Most Downloaded Articles of 2012
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Editorial Material
ID CLINICAL TARGET VOLUME; MODULATED PELVIC RADIOTHERAPY; ADVANCED
PANCREATIC-CANCER; TERM-FOLLOW-UP; RADIATION-THERAPY; BRACHIAL-PLEXUS;
BREAST-CANCER; POSTMASTECTOMY RADIATION; POSTOPERATIVE TREATMENT;
CONSENSUS GUIDELINES
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Zietman, AL (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 35
TC 5
Z9 5
U1 1
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0360-3016
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD JUN 1
PY 2013
VL 86
IS 2
BP 218
EP 221
DI 10.1016/j.ijrobp.2013.03.011
PG 4
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 151ZZ
UT WOS:000319500200009
PM 23643376
ER
PT J
AU Bahig, H
Roberge, D
Bosch, W
Levin, W
Petersen, I
Haddock, M
Freeman, C
DeLaney, TF
Abrams, RA
Indelicato, DJ
Baldini, EH
Hitchcock, Y
Kirsch, DG
Kozak, KR
Wolfson, A
Wang, D
AF Bahig, Houda
Roberge, David
Bosch, Walter
Levin, William
Petersen, Ivy
Haddock, Michael
Freeman, Carolyn
DeLaney, Thomas F.
Abrams, Ross A.
Indelicato, Danny J.
Baldini, Elizabeth H.
Hitchcock, Ying
Kirsch, David G.
Kozak, Kevin R.
Wolfson, Aaron
Wang, Dian
TI Agreement Among RTOG Sarcoma Radiation Oncologists in Contouring
Suspicious Peritumoral Edema for Preoperative Radiation Therapy of Soft
Tissue Sarcoma of the Extremity
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Article
ID POSTOPERATIVE RADIOTHERAPY; TUMORS; CONSENSUS; IMAGES
AB Purpose: Peritumoral edema may harbor sarcoma cells. The extent of suspicious edema (SE) included in the treatment volume is subject to clinical judgment, balancing the risk of missing tumor cells with excess toxicity. Our goal was to determine variability in SE delineation by sarcoma radiation oncologists (RO).
Methods and Materials: Twelve expert ROs were provided with T1 gadolinium and T2-weighted MR images of 10 patients with high-grade extremity soft-tissue sarcoma. Gross tumor volume, clinical target volume (CTV) 3cm (3 cm longitudinal and 1.5 cm radial margin), and CTV2cm (2 cm longitudinal and 1 cm radial margin) were contoured by a single observer. Suspicious peritumoral edema, defined as abnormal signal on T2 images, was independently delineated by all 12 ROs. Contouring agreement was analyzed using the simultaneous truth and performance level estimation (STAPLE) algorithm and kappa statistics.
Results: The mean volumes of GTV, CTV2cm, and CTV3cm were, respectively, 130 cm 3 (7413 cm(3)), 280 cm(3) and 360 cm(3). The mean consensus volume computed using the STAPLE algorithm at 95% confidence interval was 188 cm 3 (24-565 cm(3)) with a substantial overall agreement corrected for chance (mean kappa Z 0.71; range: 0.32-0.87). The minimum, maximum, and mean volume of SE (excluding the GTV) were 4, 182, and 58 cm(3) (representing a median of 29% of the GTV volume). The median volume of SE not included in the CTV2cm and in the CTV3cm was 5 and 0.3 cm(3), respectively. There were 3 large tumors with >30 cm(3) of SE not included in the CTV3cm volume.
Conclusion: Despite the fact that SE would empirically seem to be a more subjective volume, a substantial or near-perfect interobserver agreement was observed in SE delineation in most cases with high-grade soft-tissue sarcomas of the extremity. A median of 97% of the consensus SE is within the CTV2cm (99.8% within the CTV3cm). In a minority of cases, however, significant expansion of the CTVs is required to cover SE. (C) 2013 Elsevier Inc.
C1 [Bahig, Houda; Roberge, David; Indelicato, Danny J.] Ctr Hosp Univ Montreal, Dept Radiat Oncol, Montreal, PQ, Canada.
[Bosch, Walter] Washington Univ, Dept Radiat Oncol, St Louis, MO USA.
[Levin, William] Univ Penn, Dept Radiat Oncol, Philadelphia, PA 19104 USA.
[Petersen, Ivy; Haddock, Michael] Mayo Clin, Dept Radiat Oncol, Rochester, MN USA.
[Freeman, Carolyn] McGill Univ, Ctr Hlth, Div Radiat Oncol, Montreal, PQ, Canada.
[DeLaney, Thomas F.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Abrams, Ross A.] Rush Univ, Dept Radiat Oncol, Med Ctr, Chicago, IL 60612 USA.
[Indelicato, Danny J.] Univ Florida, Med Ctr, Dept Radiat Oncol, Jacksonville, FL 32209 USA.
[Baldini, Elizabeth H.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA.
[Baldini, Elizabeth H.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Hitchcock, Ying] Univ Utah, Med Ctr, Dept Radiat Oncol, Salt Lake City, UT USA.
[Kirsch, David G.] Duke Univ, Med Ctr, Dept Radiat Oncol, Durham, NC USA.
[Kozak, Kevin R.] Univ Wisconsin, Dept Human Oncol, Sch Med & Publ Hlth, Madison, WI USA.
[Wolfson, Aaron] Univ Miami, Miller Sch Med, Dept Radiat Oncol, Miami, FL 33136 USA.
[Wang, Dian] Med Coll Wisconsin, Dept Radiat Oncol, Milwaukee, WI 53226 USA.
RP Roberge, D (reprint author), Hop Notre Came, Radiat Oncol, TS-3366,1560 Sherbrooke Est, Montreal, PQ H2L 4M1, Canada.
EM david.roberge.chum@ssss.gouv.qc.ca
OI Indelicato, Daniel/0000-0001-5765-1873
FU National Cancer Institute (NCI) [U10 CA37422]
FX Community Clinical Oncology Program (CCOP) grant U10 CA37422 from the
National Cancer Institute (NCI). The contents of this article are solely
the responsibility of the authors and do not necessarily represent the
official views of the NCI.
NR 16
TC 10
Z9 10
U1 1
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0360-3016
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD JUN 1
PY 2013
VL 86
IS 2
BP 298
EP 303
DI 10.1016/j.ijrobp.2013.01.032
PG 6
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 151ZZ
UT WOS:000319500200021
PM 23474110
ER
PT J
AU Coen, JJ
Paly, JJ
Niemierko, A
Kaufman, DS
Heney, NM
Spiegel, DY
Efstathiou, JA
Zietman, AL
Shipley, WU
AF Coen, John J.
Paly, Jonathan J.
Niemierko, Andrzej
Kaufman, Donald S.
Heney, Niall M.
Spiegel, Daphne Y.
Efstathiou, Jason A.
Zietman, Anthony L.
Shipley, William U.
TI Nomograms Predicting Response to Therapy and Outcomes After
Bladder-Preserving Trimodality Therapy for Muscle-Invasive Bladder
Cancer
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Article
ID PROSTATE-CANCER; RADICAL CYSTECTOMY; SELECTIVE BLADDER; RECURRENCE;
RADIATION; RISK; PRESERVATION; CHEMOTHERAPY; RADIOTHERAPY; PROBABILITY
AB Purpose: Selective bladder preservation by use of trimodality therapy is an established management strategy for muscle-invasive bladder cancer. Individual disease features have been associated with response to therapy, likelihood of bladder preservation, and disease-free survival. We developed prognostic nomograms to predict the complete response rate, disease-specific survival, and likelihood of remaining free of recurrent bladder cancer or cystectomy.
Methods and Materials: From 1986 to 2009, 325 patients were managed with selective bladder preservation at Massachusetts General Hospital (MGH) and had complete data adequate for nomogram development. Treatment consisted of a transurethral resection of bladder tumor followed by split-course chemoradiation. Patients with a complete response at midtreatment cystoscopic assessment completed radiation, whereas those with a lesser response underwent a prompt cystectomy. Prognostic nomograms were constructed predicting complete response (CR), disease-specific survival (DSS), and bladder-intact disease-free survival (BI-DFS). BIDFS was defined as the absence of local invasive or regional recurrence, distant metastasis, bladder cancer-related death, or radical cystectomy.
Results: The final nomograms included information on clinical T stage, presence of hydronephrosis, whether a visibly complete transurethral resection of bladder tumor was performed, age, sex, and tumor grade. The predictive accuracy of these nomograms was assessed. For complete response, the area under the receiving operating characteristic curve was 0.69. The Harrell concordance index was 0.61 for both DSS and BI-DFS.
Conclusions: Our nomograms allow individualized estimates of complete response, DSS, and BI-DFS. They may assist patients and clinicians making important treatment decisions. (C) 2013 Elsevier Inc.
C1 [Coen, John J.; Paly, Jonathan J.; Niemierko, Andrzej; Spiegel, Daphne Y.; Efstathiou, Jason A.; Zietman, Anthony L.; Shipley, William U.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Kaufman, Donald S.] Massachusetts Gen Hosp, Dept Med Oncol, Boston, MA 02114 USA.
[Heney, Niall M.] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA.
RP Coen, JJ (reprint author), Hartford Hosp, Helen & Harry Gray Canc Ctr, Dept Radiat Oncol, 80 Seymour St, Hartford, CT 06102 USA.
EM jcoen@harthosp.org
NR 21
TC 10
Z9 10
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0360-3016
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD JUN 1
PY 2013
VL 86
IS 2
BP 311
EP 316
DI 10.1016/j.ijrobp.2013.01.020
PG 6
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 151ZZ
UT WOS:000319500200023
PM 23474117
ER
PT J
AU Grassberger, C
Dowdell, S
Lomax, A
Sharp, G
Shackleford, J
Choi, N
Willers, H
Paganetti, H
AF Grassberger, Clemens
Dowdell, Stephen
Lomax, Antony
Sharp, Greg
Shackleford, James
Choi, Noah
Willers, Henning
Paganetti, Harald
TI Motion Interplay as a Function of Patient Parameters and Spot Size in
Spot Scanning Proton Therapy for Lung Cancer
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Article
ID RADIOTHERAPY; TARGETS; VOLUME; BEAM
AB Purpose: To quantify the impact of respiratory motion on the treatment of lung tumors with spot scanning proton therapy.
Methods and Materials: Four-dimensional Monte Carlo simulations were used to assess the interplay effect, which results from relative motion of the tumor and the proton beam, on the dose distribution in the patient. Ten patients with varying tumor sizes (2.6-82.3 cc) and motion amplitudes (3-30 mm) were included in the study. We investigated the impact of the spot size, which varies between proton facilities, and studied single fractions and conventionally fractionated treatments. The following metrics were used in the analysis: minimum/maximum/mean dose, target dose homogeneity, and 2-year local control rate (2y-LC).
Results: Respiratory motion reduces the target dose homogeneity, with the largest effects observed for the highest motion amplitudes. Smaller spot sizes (sigma approximate to 3 mm) are inherently more sensitive to motion, decreasing target dose homogeneity on average by a factor 2.8 compared with a larger spot size (sigma approximate to 13 mm). Using a smaller spot size to treat a tumor with 30-mm motion amplitude reduces the minimum dose to 44.7% of the prescribed dose, decreasing modeled 2y-LC from 87.0% to 2.7%, assuming a single fraction. Conventional fractionation partly mitigates this reduction, yielding a 2y-LC of 71.6%. For the large spot size, conventional fractionation increases target dose homogeneity and prevents a deterioration of 2y-LC for all patients. No correlation with tumor volume is observed. The effect on the normal lung dose distribution is minimal: observed changes in mean lung dose and lung V-20 are <0.6 Gy(RBE) and <1.7%, respectively.
Conclusions: For the patients in this study, 2y-LC could be preserved in the presence of interplay using a large spot size and conventional fractionation. For treatments using smaller spot sizes and/or in the delivery of single fractions, interplay effects can lead to significant deterioration of the dose distribution and lower 2y-LC. (C) 2013 Elsevier Inc.
C1 [Grassberger, Clemens; Dowdell, Stephen; Sharp, Greg; Shackleford, James; Choi, Noah; Willers, Henning; Paganetti, Harald] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Grassberger, Clemens; Dowdell, Stephen; Sharp, Greg; Shackleford, James; Choi, Noah; Willers, Henning; Paganetti, Harald] Harvard Univ, Sch Med, Boston, MA USA.
[Grassberger, Clemens; Lomax, Antony] Paul Scherrer Inst, Ctr Proton Radiotherapy, Villigen, Switzerland.
RP Grassberger, C (reprint author), Massachusetts Gen Hosp, Francis H Burr Proton Therapy Ctr, 30 Fruit St, Boston, MA 02114 USA.
EM Grassberger.Clemens@mgh.harvard.edu
OI Shackleford, James/0000-0002-7987-651X
FU National Cancer Institute [R01 CA111590]
FX This project was supported by the National Cancer Institute Grant No.
R01 CA111590. We thank Ben Clasie, Antje Knopf, and Joost Verburg for
their assistance.
NR 15
TC 35
Z9 35
U1 0
U2 18
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0360-3016
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD JUN 1
PY 2013
VL 86
IS 2
BP 380
EP 386
DI 10.1016/j.ijrobp.2013.01.024
PG 7
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 151ZZ
UT WOS:000319500200033
PM 23462423
ER
PT J
AU Geng, EH
Bwana, MB
Muyindike, W
Glidden, DV
Bangsberg, DR
Neilands, TB
Bernheimer, I
Musinguzi, N
Yiannoutsos, CT
Martin, JN
AF Geng, Elvin H.
Bwana, Mwebesa B.
Muyindike, Winnie
Glidden, David V.
Bangsberg, David R.
Neilands, Torsten B.
Bernheimer, Ingrid
Musinguzi, Nicolas
Yiannoutsos, Constantin T.
Martin, Jeffrey N.
TI Failure to Initiate Antiretroviral Therapy, Loss to Follow-up and
Mortality Among HIV-Infected Patients During the Pre-ART Period in
Uganda
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE antiretroviral therapy; Africa; loss to follow-up; mortality
ID SAMPLING-BASED APPROACH; FOOD INSECURITY; COMPETING RISKS; SOUTH-AFRICA;
TUBERCULOSIS; PROGRAMS; OUTCOMES; CARE; ACCEPTANCE; COUNTRIES
AB Background: Delays and failures in initiation of antiretroviral therapy (ART) among treatment eligible patients may compromise the effectiveness of HIV care in Africa. An accurate understanding, however, of the pace and completeness of ART initiation and mortality during the waiting period is obscured by frequent losses to follow-up.
Methods: We evaluated newly ART-eligible HIV-infected adults from 2007 to 2011 in a prototypical clinic in Mbarara, Uganda. A random sample of patients lost to follow-up was tracked in the community to determine vital status and ART initiation after leaving the original clinic. Outcomes among the tracked patients were incorporated using probability weights, and a competing risks approach was used in analyses.
Results: Among 2633 ART-eligible patients, 490 were lost to follow-up, of whom a random sample of 132 was tracked and 111 (84.0%) had outcomes ascertained. After incorporating the outcomes among the lost, the cumulative incidence of ART initiation at 30, 90, and 365 days after eligibility was 16.0% [ 95% confidence interval (CI): 14.2 to 17.7], 64.5% (95% CI: 60.9 to 68.1), and 81.7% (95% CI: 77.7 to 85.6). Death before ART was 7.7% at 1 year. Male sex, higher CD4 count, and no education were associated with delayed ART initiation. Lower CD4 level, malnourishment, and travel time to clinic were associated with mortality.
Conclusions: Using a sampling-based approach to account for losses to follow-up revealed that both the speed and the completeness of ART initiation were suboptimal in a prototypical large clinic in Uganda. Improving the kinetics of ART initiation in Africa is needed to make ART more in real-world populations.
C1 [Geng, Elvin H.] Univ Calif San Francisco, San Francisco Gen Hosp, Dept Med, Div HIV AIDS, San Francisco, CA 94110 USA.
[Geng, Elvin H.; Bwana, Mwebesa B.; Muyindike, Winnie; Glidden, David V.; Bangsberg, David R.; Musinguzi, Nicolas; Yiannoutsos, Constantin T.; Martin, Jeffrey N.] East Africa Int Epidemiol Databases Evaluate AIDS, Indianapolis, IN USA.
[Bwana, Mwebesa B.; Muyindike, Winnie; Bangsberg, David R.; Musinguzi, Nicolas] Mbarara Univ Sci & Technol, Mbarara, Uganda.
[Glidden, David V.; Bernheimer, Ingrid; Martin, Jeffrey N.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94110 USA.
[Bangsberg, David R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
[Neilands, Torsten B.] Univ Calif San Francisco, Ctr AIDS Prevent Studies, Dept Med, San Francisco, CA 94110 USA.
[Yiannoutsos, Constantin T.] Indiana Univ, Dept Biostat, Indianapolis, IN 46204 USA.
RP Geng, EH (reprint author), Univ Calif San Francisco, San Francisco Gen Hosp, Posit Hlth Program, 995 Potrero Ave,Bldg 80, San Francisco, CA 94110 USA.
EM genge@php.ucsf.edu
FU National Institutes of Health [K23 AI084544, U01 AI069911, P30
AI027763]; United States President's Emergency Plan for AIDS Relief
FX Supported by the National Institutes of Health Grants K23 AI084544, U01
AI069911, and P30 AI027763; the United States President's Emergency Plan
for AIDS Relief.
NR 32
TC 34
Z9 34
U1 1
U2 2
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 JUN 1
PY 2013
VL 63
IS 2
BP E64
EP E71
DI 10.1097/QAI.0b013e31828af5a6
PG 8
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 146SY
UT WOS:000319112500004
PM 23429504
ER
PT J
AU Joshi, G
Wozniak, J
Petty, C
Martelon, MK
Fried, R
Bolfek, A
Kotte, A
Stevens, J
Furtak, SL
Bourgeois, M
Caruso, J
Caron, A
Biederman, J
AF Joshi, Gagan
Wozniak, Janet
Petty, Carter
Martelon, Mary Kate
Fried, Ronna
Bolfek, Anela
Kotte, Amelia
Stevens, Jonathan
Furtak, Stephannie L.
Bourgeois, Michelle
Caruso, Janet
Caron, Ashley
Biederman, Joseph
TI Psychiatric Comorbidity and Functioning in a Clinically Referred
Population of Adults with Autism Spectrum Disorders: A Comparative Study
SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS
LA English
DT Article
DE Autism spectrum disorders; Psychiatric comorbidity; Adults
ID PERVASIVE DEVELOPMENTAL DISORDERS; DEFICIT HYPERACTIVITY DISORDER;
OBSESSIVE-COMPULSIVE DISORDER; ASPERGER-SYNDROME; YOUNG-ADULTS;
INTELLECTUAL DISABILITY; RESONANCE SPECTROSCOPY; BIPOLAR DISORDER;
ANXIETY SYMPTOMS; AMYGDALA VOLUME
AB To systematically examine the patterns of psychiatric comorbidity and functioning in clinically referred adults with autism spectrum disorders (ASD). Psychiatrically referred adults with and without ASD were compared on measures assessing for psychiatric comorbidity and psychosocial functioning. Sixty-three adults with ASD participated in the study (mean age: 29 +/- A 11 years). Adults with ASD in their lifetime suffered from a higher burden of psychiatric disorders (6 +/- A 3.4 vs. 3.5 +/- A 2.7; p < 0.001) including major depressive disorder and multiple anxiety disorders, and were functionally more impaired with a significant proportion having received both counseling and pharmacotherapy. Adults with ASD have high levels of psychiatric comorbidity and dysfunction comparable to a clinically referred population of adults without ASD.
C1 [Joshi, Gagan; Wozniak, Janet; Petty, Carter; Martelon, Mary Kate; Fried, Ronna; Bolfek, Anela; Kotte, Amelia; Stevens, Jonathan; Furtak, Stephannie L.; Bourgeois, Michelle; Caruso, Janet; Caron, Ashley; Biederman, Joseph] Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA.
[Joshi, Gagan; Wozniak, Janet; Fried, Ronna; Bolfek, Anela; Kotte, Amelia; Stevens, Jonathan; Biederman, Joseph] Harvard Univ, Sch Med, Boston, MA USA.
RP Joshi, G (reprint author), Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, YAW 6900,55 Fruit St, Boston, MA 02114 USA.
EM joshi.gagan@mgh.harvard.edu
OI Kotte, Amelia/0000-0002-0198-7914
NR 65
TC 47
Z9 47
U1 8
U2 38
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0162-3257
J9 J AUTISM DEV DISORD
JI J. Autism Dev. Disord.
PD JUN
PY 2013
VL 43
IS 6
BP 1314
EP 1325
DI 10.1007/s10803-012-1679-5
PG 12
WC Psychology, Developmental
SC Psychology
GA 154NJ
UT WOS:000319682400007
PM 23076506
ER
PT J
AU Waslawski, S
Lo, ES
Ewing, SA
Young, VB
Aronoff, DM
Sharp, SE
Novak-Weekley, SM
Crist, AE
Dunne, WM
Hoppe-Bauer, J
Johnson, M
Brecher, SM
Newton, DW
Walk, ST
AF Waslawski, Sheila
Lo, Eugene S.
Ewing, Sarah A.
Young, Vincent B.
Aronoff, David M.
Sharp, Susan E.
Novak-Weekley, Susan M.
Crist, Arthur E., Jr.
Dunne, W. Michael
Hoppe-Bauer, Joan
Johnson, Michelle
Brecher, Stephen M.
Newton, Duane W.
Walk, Seth T.
TI Clostridium difficile Ribotype Diversity at Six Health Care Institutions
in the United States
SO JOURNAL OF CLINICAL MICROBIOLOGY
LA English
DT Article
ID EPIDEMIOLOGY; INFECTION
AB Capillary-based PCR ribotyping was used to quantify the presence/absence and relative abundance of 98 Clostridium difficile ribotypes from clinical cases of disease at health care institutions in six states of the United States. Regionally important ribotypes were identified, and institutions in close proximity did not necessarily share more ribotype diversity than institutions that were farther apart.
C1 [Waslawski, Sheila; Lo, Eugene S.; Ewing, Sarah A.; Young, Vincent B.; Aronoff, David M.; Walk, Seth T.] Univ Michigan Hosp & Hlth Syst, Div Infect Dis, Dept Internal Med, Ann Arbor, MI USA.
[Young, Vincent B.; Aronoff, David M.] Univ Michigan, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA.
[Sharp, Susan E.] Kaiser Permanente NW, Portland, OR USA.
[Novak-Weekley, Susan M.] So Calif Permanente Med Grp, Reg Reference Labs, North Hollywood, CA USA.
[Crist, Arthur E., Jr.] York Hosp, Dept Lab Serv, Div Clin Microbiol, York, PA USA.
[Dunne, W. Michael] BioMerieux, Durham, NC USA.
[Dunne, W. Michael; Hoppe-Bauer, Joan; Johnson, Michelle] Barnes Jewish Hosp, Dept Microbiol, St Louis, MO 63110 USA.
[Brecher, Stephen M.] VA Boston Healthcare Syst, Boston, MA USA.
[Newton, Duane W.] Univ Michigan Hosp & Hlth Syst, Dept Pathol, Clin Microbiol Labs, Ann Arbor, MI USA.
[Walk, Seth T.] Montana State Univ, Dept Microbiol, Bozeman, MT 59717 USA.
RP Walk, ST (reprint author), Univ Michigan Hosp & Hlth Syst, Div Infect Dis, Dept Internal Med, Ann Arbor, MI USA.
EM seth.walk@montana.edu
FU Department of Pathology at the University of Michigan; National
Institutes of Health [1U19AI090871-01, 1K01AI09728101A1]
FX This work was supported by institutional funds from the Department of
Pathology at the University of Michigan. Additional support came from
the National Institutes of Health grants 1U19AI090871-01 (to V.B.Y. and
D.M.A.) and 1K01AI09728101A1 (to S.T.W.).
NR 15
TC 13
Z9 14
U1 0
U2 4
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 JUN
PY 2013
VL 51
IS 6
BP 1938
EP 1941
DI 10.1128/JCM.00056-13
PG 4
WC Microbiology
SC Microbiology
GA 147VV
UT WOS:000319197800047
PM 23554188
ER
PT J
AU Nair, BG
Horibe, M
Newman, SF
Wu, WY
Schwid, HA
AF Nair, Bala G.
Horibe, Mayumi
Newman, Shu-Fang
Wu, Wei-Ying
Schwid, Howard A.
TI Near real-time notification of gaps in cuff blood pressure recordings
for improved patient monitoring
SO JOURNAL OF CLINICAL MONITORING AND COMPUTING
LA English
DT Article
DE Decision support; Anesthesia information management system; Patient
monitoring; Blood pressure monitoring; Real-time reminders
ID DOCUMENTATION; PERFORMANCE; QUALITY
AB Blood pressure monitoring during anesthesia is an American Society of Anesthesiology standard. However, the anesthesia provider sometimes fails to engage the patient monitor to make periodic (generally every 3-5 min) measurements of Non-Invasive Blood Pressure (NIBP), which can lead to extended periods (> 5 min) when blood pressure is not monitored. We describe a system to automatically detect such gaps in NIBP measurement and notify clinicians in real-time to initiate measurement. We applied a decision support system called the Smart Anesthesia Messenger (SAM) to notify the anesthesia provider if NIBP measurements have not been made in the last 7 min. Notification messages were generated only if direct arterial blood pressure was not being monitored. NIBP gaps were analyzed for 9 months before and after SAM notification was initiated (12,000 cases for each period). SAM notification was able to reduce the occurrence of extended NIBP gaps > 15 min from 15.7 +/- A 4.5 to 6.7 +/- A 2.0 instances per 1,000 cases (p < 0.001). In addition, for extended gaps (> 15 min) the mean gap duration declined from 23.1 +/- A 2.0 to 18.6 +/- A 1.1 min after SAM notification was initiated (p < 0.001). However, for 7-15 min gaps, SAM notification was not effective in reducing the occurrence. The maximum gap encountered before SAM was 64 min, while it was 27 min with SAM notification. Real-time notification using SAM is an effective way to reduce both the number of instances and the duration of inadvertent, extended (> 15 min) gaps in blood pressure measurements in the operating room. However, the frequency of gaps < 15 min could not be reduced using the current configuration of SAM.
C1 [Nair, Bala G.; Schwid, Howard A.] Univ Washington, Dept Anesthesiol & Pain Med, Seattle, WA 98195 USA.
[Horibe, Mayumi] VA Puget Sound Hlth Care Syst, Dept Anesthesiol, Seattle, WA USA.
[Newman, Shu-Fang] Univ Washington, Patient Care Serv, Seattle, WA 98195 USA.
[Wu, Wei-Ying] Natl Dong Hwa Univ, Dept Appl Math, Hualien, Taiwan.
RP Nair, BG (reprint author), Univ Washington, Dept Anesthesiol & Pain Med, BB-1469 Hlth Sci Bldg,1959 NE Pacific St,Mail Box, Seattle, WA 98195 USA.
EM nairbg@uw.edu
FU Laura Cheney Patient Safety grant by the University of Washington
FX This research was supported by Laura Cheney Patient Safety grant
provided by the University of Washington. We would also like to thank
Rafael Vergara for his daily support of the SAM system.
NR 15
TC 7
Z9 7
U1 0
U2 2
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 1387-1307
J9 J CLIN MONIT COMPUT
JI J. Clin. Monitor. Comp.
PD JUN
PY 2013
VL 27
IS 3
BP 265
EP 271
DI 10.1007/s10877-012-9425-2
PG 7
WC Anesthesiology
SC Anesthesiology
GA 146DW
UT WOS:000319070600009
PM 23283561
ER
PT J
AU Pirl, WF
Jacobsen, PB
Deshields, TL
AF Pirl, William F.
Jacobsen, Paul B.
Deshields, Teresa L.
TI Opportunities for Improving Psychosocial Care for Cancer Survivors
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Editorial Material
ID RANDOMIZED-TRIAL; BREAST-CANCER; DEPRESSION; MANAGEMENT; ONCOLOGISTS;
NEEDS
C1 [Pirl, William F.] Massachusetts Gen Hosp, Ctr Canc, Ctr Psychiat Oncol & Behav Sci, Boston, MA 02114 USA.
[Jacobsen, Paul B.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA.
[Deshields, Teresa L.] Siteman Canc Ctr, Siteman Counseling Serv, St Louis, MO USA.
RP Pirl, WF (reprint author), Massachusetts Gen Hosp, Ctr Canc, Ctr Psychiat Oncol & Behav Sci, Boston, MA 02114 USA.
NR 17
TC 4
Z9 4
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 JUN 1
PY 2013
VL 31
IS 16
BP 1920
EP 1921
DI 10.1200/JCO.2012.48.0566
PG 2
WC Oncology
SC Oncology
GA 154FP
UT WOS:000319657600009
PM 23610106
ER
PT J
AU Metzger, O
Procter, M
de Azambuja, E
Leyland-Jones, B
Gelber, RD
Dowsett, M
Loi, S
Saini, KS
Cameron, D
Untch, M
Smith, I
Gianni, L
Baselga, J
Jackisch, C
Bell, R
Sotiriou, C
Viale, G
Piccart-Gebhart, M
AF Metzger-Filho, Otto
Procter, Marion
de Azambuja, Evandro
Leyland-Jones, Brian
Gelber, Richard D.
Dowsett, Mitchell
Loi, Sherene
Saini, Kamal S.
Cameron, David
Untch, Michael
Smith, Ian
Gianni, Luca
Baselga, Jose
Jackisch, Christian
Bell, Richard
Sotiriou, Christos
Viale, Giuseppe
Piccart-Gebhart, Martine
TI Magnitude of Trastuzumab Benefit in Patients With HER2-Positive,
Invasive Lobular Breast Carcinoma: Results From the HERA Trial
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID ADJUVANT CHEMOTHERAPY; PROGNOSTIC VALUE; CANCER; AMPLIFICATION;
EXPRESSION; IMMUNOHISTOCHEMISTRY; OVEREXPRESSION; ASSOCIATION;
RECEPTORS; ESTROGEN
AB Purpose
To evaluate the benefit of adjuvant trastuzumab in patients diagnosed with human epidermal growth factor receptor 2 (HER2) -positive invasive lobular carcinoma (ILC) enrolled onto the Herceptin Adjuvant (HERA) trial.
Patients and Methods
Patients randomly assigned to receive one year of trastuzumab and one year of observation in the HERA trial were included (n = 3,401). Centrally reviewed estrogen receptor (ER), progesterone receptor (PgR), and HER2 copy numbers were used. First site-specific relapse pattern was evaluated for ILC and invasive ductal carcinoma (IDC). The magnitude of trastuzumab benefit was assessed using the Cox proportional hazards model for disease-free survival (DFS) and overall survival (OS).
Results
Median follow-up time was 4 years. A total of 187 ILC and 3,213 IDC patients were included. High Allred scores (6 to 8) were more common in patients with ILC than IDC for both ER (36.9% v 22.7%) and PgR (44.1% v 28.5%). A trend toward decreased HER2 copy number was observed in the ILC group. The ILC and IDC subgroups had similar patterns of first site of disease relapse. DFS hazard ratios (HRs) comparing 1 year of trastuzumab versus observation were 0.63 for ILC (95% CI, 0.34 to 1.15) and 0.77 for IDC (95% CI, 0.67 to 0.89; P for interaction = .49). The OS HRs comparing 1 year of trastuzumab versus observation were 0.60 for ILC (95% CI, 0.27 to 1.31) and 0.86 for IDC (95% CI, 0.71 to 1.06; P for interaction = .29).
Conclusion
In this retrospective analysis, there was no suggestion that patients in the ILC cohort experienced a different magnitude of benefit from adjuvant trastuzumab than those in the IDC cohort. (c) 2013 by American Society of Clinical Oncology
C1 [Metzger-Filho, Otto] Harvard Univ, Sch Med, Dana Farber Canc Inst, Sch Publ Hlth, Boston, MA 02115 USA.
[Metzger-Filho, Otto; de Azambuja, Evandro; Saini, Kamal S.; Sotiriou, Christos; Piccart-Gebhart, Martine] Inst Jules Bordet, B-1000 Brussels, Belgium.
[Metzger-Filho, Otto; de Azambuja, Evandro; Saini, Kamal S.; Sotiriou, Christos; Piccart-Gebhart, Martine] Univ Libre Brussels, Brussels, Belgium.
[Procter, Marion] Frontier Sci Scotland, Kincraig, Scotland.
[Dowsett, Mitchell; Smith, Ian] Royal Marsden Hosp, London, England.
[Smith, Ian] Inst Canc Res, London, England.
[Cameron, David] Univ Edinburgh, Edinburgh, Midlothian, Scotland.
[Leyland-Jones, Brian] Edith Sanford Breast Res, Sioux Falls, SD USA.
[Loi, Sherene] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia.
[Bell, Richard] Andrew Love Canc Ctr, Geelong, Vic, Australia.
[Untch, Michael] HELIOS Klin, Berlin, Germany.
[Jackisch, Christian] Klinikum Offenbach, Offenbach, Germany.
[Gianni, Luca] San Raffaele Inst, Milan, Italy.
[Viale, Giuseppe] European Inst Oncol, Milan, Italy.
[Viale, Giuseppe] Univ Milan, Milan, Italy.
[Baselga, Jose] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
RP Piccart-Gebhart, M (reprint author), Inst Jules Bordet, Blvd Waterloo 121, B-1000 Brussels, Belgium.
EM martine.piccart@bordet.be
RI Loi, Sherene/H-1979-2016;
OI Loi, Sherene/0000-0001-6137-9171
FU Roche
FX Marion Procter, Roche; Richard D. Gelber, Roche; Mitchell Dowsett,
Roche; David Cameron, Roche
NR 27
TC 9
Z9 11
U1 0
U2 5
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JUN 1
PY 2013
VL 31
IS 16
BP 1954
EP U254
DI 10.1200/JCO.2012.46.2440
PG 8
WC Oncology
SC Oncology
GA 154FP
UT WOS:000319657600015
PM 23589556
ER
PT J
AU Warren, JL
Harlan, LC
Stevens, J
Little, RF
Abel, GA
AF Warren, Joan L.
Harlan, Linda C.
Stevens, Jennifer
Little, Richard F.
Abel, Gregory A.
TI Multiple Myeloma Treatment Transformed: A Population-Based Study of
Changes in Initial Management Approaches in the United States
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID STEM-CELL TRANSPLANTATION; HIGH-DOSE THERAPY; STANDARD CHEMOTHERAPY;
PLUS THALIDOMIDE; ELDERLY-PATIENTS; SURVIVAL; TRIAL; PREDNISONE;
MELPHALAN; DEXAMETHASONE
AB Purpose
Despite improved outcomes for multiple myeloma, little is known about changes in initial treatment at the population level for US patients. We report trends in treatment practices.
Patients and Methods
Patients (n = 1,976) with newly diagnosed myeloma in 1999, 2003, and 2007 were examined by using the National Cancer Institute's Patterns of Care Studies. We assessed use of common chemotherapies (melphalan, vincristine, and doxorubicin), novel agents (thalidomide, bortezomib, or lenalidomide), or hematopoietic stem-cell transplantation (HSCT) during the first year after diagnosis. By using logistic regression, we evaluated the association of race and insurance status with receipt of high-cost treatments-transplantation or novel agents.
Results
From 1999 to 2007, use of melphalan alone dropped from 32.0% to 4.1%, and vincristine and doxorubicin use declined from 18.2% to 0.4%. The percentage of patients receiving any novel agent rose from 3.9% in 1999 to 75.5% in 2007. HSCT increased from 11.1% in 1999 to 21.7% in 2007. For white patients, use of novel agents was lower for those with Medicare only (42.6%) than for those with private insurance (50.2%). For patients of other races, those with Medicare only or Medicaid were less likely to receive novel agents or transplantation compared with those with private insurance.
Conclusion
Initial treatment for multiple myeloma has changed markedly. Most patients now receive novel agents, with a decline in the use of traditional chemotherapy. Use of transplantation and novel agents varies with race and insurance. These findings document rapid changes in patterns of care and highlight addressable disparities in myeloma care. (c) 2013 by American Society of Clinical Oncology
C1 [Warren, Joan L.; Harlan, Linda C.; Little, Richard F.] NCI, Bethesda, MD 20892 USA.
[Stevens, Jennifer] Informat Management Serv Inc, Silver Spring, MD USA.
[Abel, Gregory A.] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Warren, JL (reprint author), NCI, 6130 Execut Blvd,Room 4005,MSC 7344, Bethesda, MD 20892 USA.
EM joan_warren@nih.gov
NR 26
TC 19
Z9 19
U1 2
U2 5
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JUN 1
PY 2013
VL 31
IS 16
BP 1984
EP +
DI 10.1200/JCO.2012.46.3323
PG 7
WC Oncology
SC Oncology
GA 154FP
UT WOS:000319657600019
PM 23569317
ER
PT J
AU Diamond, JR
Salgia, R
Varella-Garcia, M
Kanteti, R
LoRusso, PM
Clark, JW
Xu, LG
Wilner, K
Eckhardt, SG
Ching, KA
Lira, ME
Schoenmakers, EFPM
Christensen, JG
Camidge, DR
AF Diamond, Jennifer R.
Salgia, Ravi
Varella-Garcia, Marileila
Kanteti, Rajani
LoRusso, Patricia M.
Clark, Jeffrey W.
Xu, Ling-Guo
Wilner, Keith
Eckhardt, S. Gail
Ching, Keith A.
Lira, Maruja E.
Schoenmakers, Eric F. P. M.
Christensen, James G.
Camidge, D. Ross
TI Initial Clinical Sensitivity and Acquired Resistance to MET Inhibition
in MET-Mutated Papillary Renal Cell Carcinoma
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID HEPATOCYTE GROWTH-FACTOR; ADVANCED SOLID TUMORS; C-MET; SIGNALING
PATHWAY; AMG 102; CANCER; MUTATIONS; RECEPTOR; CRIZOTINIB; SURVIVAL
C1 [Diamond, Jennifer R.; Varella-Garcia, Marileila; Xu, Ling-Guo; Eckhardt, S. Gail; Camidge, D. Ross] Univ Colorado, Ctr Canc, Aurora, CO USA.
[Salgia, Ravi; Kanteti, Rajani] Univ Chicago, Chicago, IL 60637 USA.
[LoRusso, Patricia M.] Karmanos Canc Inst, Detroit, MI USA.
[Clark, Jeffrey W.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Wilner, Keith; Ching, Keith A.; Lira, Maruja E.; Schoenmakers, Eric F. P. M.; Christensen, James G.] Pfizer, San Diego, CA USA.
RP Diamond, JR (reprint author), Univ Colorado, Ctr Canc, Aurora, CO USA.
FU National Institutes of Health (NIH)/National Cancer Institute (NCI)
[5R01CA100750-06, 5R01CA125541-05, 5K12CA086913-10]; Pfizer
FX Supported in part by National Institutes of Health (NIH)/National Cancer
Institute (NCI) Grants No. 5R01CA100750-06 (R.S.) and 5R01CA125541-05,
and by NIH/NCI Grant No. 5K12CA086913-10 (J.R.D.). We thank Pamela
Vizcarra for preparing the tumor slides for analysis.; Patricia M.
LoRusso, Pfizer; Jeffrey W. Clark, Pfizer; S. Gail Eckhardt, Pfizer
NR 25
TC 7
Z9 7
U1 1
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 JUN 1
PY 2013
VL 31
IS 16
BP E254
EP E258
DI 10.1200/JCO.2012.46.4289
PG 5
WC Oncology
SC Oncology
GA 154FP
UT WOS:000319657600004
PM 23610116
ER
PT J
AU Meir, JU
Milsom, WK
AF Meir, Jessica U.
Milsom, William K.
TI High thermal sensitivity of blood enhances oxygen delivery in the
high-flying bar-headed goose
SO JOURNAL OF EXPERIMENTAL BIOLOGY
LA English
DT Article
DE blood-oxygen affinity; oxygen-hemoglobin equilibrium curve; temperature
effect; CO2 Bohr effect; Anser indicus; high altitude
ID HIGH-ALTITUDE; DISSOCIATION CURVE; BIRD BLOOD; RESPIRATORY PROPERTIES;
BODY-TEMPERATURE; HEMOGLOBIN; AFFINITY; EQUILIBRIUM; EXERCISE; HYPOXIA
AB The bar-headed goose (Anser indicus) crosses the Himalaya twice a year at altitudes where oxygen (O-2) levels are less than half those at sea level and temperatures are below -20 degrees C. Although it has been known for over three decades that the major hemoglobin (Hb) component of bar-headed geese has an increased affinity for O-2, enhancing O-2 uptake, the effects of temperature and interactions between temperature and pH on bar-headed goose Hb-O-2 affinity have not previously been determined. An increase in breathing of the hypoxic and extremely cold air experienced by a bar-headed goose at altitude (due to the enhanced hypoxic ventilatory response in this species) could result in both reduced temperature and reduced levels of CO2 at the blood-gas interface in the lungs, enhancing O-2 loading. In addition, given the strenuous nature of flapping flight, particularly in thin air, blood leaving the exercising muscle should be warm and acidotic, facilitating O-2 unloading. To explore the possibility that features of blood biochemistry in this species could further enhance O-2 delivery, we determined the P-50 (the partial pressure of O-2 at which Hb is 50% saturated) of whole blood from bar-headed geese under conditions of varying temperature and [CO2]. We found that blood-O-2 affinity was highly temperature sensitive in bar-headed geese compared with other birds and mammals. Based on our analysis, temperature and pH effects acting on blood-O-2 affinity (cold alkalotic lungs and warm acidotic muscle) could increase O-2 delivery by twofold during sustained flapping flight at high altitudes compared with what would be delivered by blood at constant temperature and pH.
C1 [Meir, Jessica U.; Milsom, William K.] Univ British Columbia, Dept Zool, Vancouver, BC V6T 1Z4, Canada.
RP Meir, JU (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
EM jmeir@partners.org
FU National Science Foundation International Research Fellowship Program
(IRFP) [OISE-0855669]; National Science Foundation RAPID Grant
[OISE-1154099]; Natural Sciences and Engineering Research Council of
Canada grant
FX This work was funded by a National Science Foundation International
Research Fellowship Program (IRFP) post-doctoral fellowship
(OISE-0855669 to J.U.M.) and National Science Foundation RAPID Grant
(OISE-1154099 to J.U.M.), and a Natural Sciences and Engineering
Research Council of Canada grant (to W.K.M.).
NR 34
TC 9
Z9 10
U1 12
U2 99
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 0022-0949
J9 J EXP BIOL
JI J. Exp. Biol.
PD JUN
PY 2013
VL 216
IS 12
BP 2172
EP 2175
DI 10.1242/jeb.085282
PG 4
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA 154GG
UT WOS:000319659900010
PM 23470665
ER
PT J
AU Chang, A
Bowen, JL
Buranosky, RA
Frankel, RM
Ghosh, N
Rosenblum, MJ
Thompson, S
Green, ML
AF Chang, Anna
Bowen, Judith L.
Buranosky, Raquel A.
Frankel, Richard M.
Ghosh, Nivedita
Rosenblum, Michael J.
Thompson, Sara
Green, Michael L.
TI Transforming Primary Care Training-Patient-Centered Medical Home
Entrustable Professional Activities for Internal Medicine Residents
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Article
DE patient-centered medical home; entrustable professional activities;
graduate medical education; internal medicine; primary care
ID TASK-FORCE; EDUCATION; ORGANIZATION; DIRECTORS; REFORM
AB The U.S. faces a critical gap between residency training and clinical practice that affects the recruitment and preparation of internal medicine residents for primary care careers. The patient-centered medical home (PCMH) represents a new clinical microsystem that is being widely promoted and implemented to improve access, quality, and sustainability in primary care practice.
We address two key questions regarding the training of internal medicine residents for practice in PCMHs. First, what are the educational implications of practice transformations to primary care home models? Second, what must we do differently to prepare internal medicine residents for their futures in PCMHs?
The 2011 Society of General Internal Medicine (SGIM) PCMH Education Summit established seven work groups to address the following topics: resident workplace competencies, teamwork, continuity of care, assessment, faculty development, 'medical home builder' tools, and policy. The output from the competency work group was foundational for the work of other groups. The work group considered several educational frameworks, including developmental milestones, competencies, and entrustable professional activities (EPAs).
The competency work group defined 25 internal medicine resident PCMH EPAs. The 2011 National Committee for Quality Assurance (NCQA) PCMH standards served as an organizing framework for EPAs.
The list of PCMH EPAs has the potential to begin to transform the education of internal medicine residents for practice and leadership in the PCMH. It will guide curriculum development, learner assessment, and clinical practice redesign for academic health centers.
C1 [Chang, Anna] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94118 USA.
[Bowen, Judith L.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Bowen, Judith L.] Vet Hlth Adm Off Acad Affiliat, Washington, DC USA.
[Buranosky, Raquel A.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA.
[Frankel, Richard M.] Indiana Univ Sch Med, Richard L Roudebush Vet Affairs Med Ctr, Indianapolis, IN USA.
[Ghosh, Nivedita] Harvard Univ, Sch Med, Brigham & Womens Adv Primary Care Associates, Boston, MA USA.
[Rosenblum, Michael J.] Tufts Univ, Sch Med, Baystate Med Ctr, Springfield, MA 01199 USA.
[Thompson, Sara] Univ Washington, Sch Med, Grp Hlth Family Med Residency, Seattle, WA USA.
[Green, Michael L.] Yale Univ, Sch Med, New Haven, CT USA.
RP Chang, A (reprint author), Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, 3333 Calif St,Suite 380, San Francisco, CA 94118 USA.
EM anna.chang@ucsf.edu
FU Josiah Macy Jr. Foundation; United Health Foundation
FX Josiah Macy Jr. Foundation supported the Education Summit. Additional
financial support for the Summit was provided by the United Health
Foundation. The American College of Physicians, Primary Care Progress,
and the Veterans Health Administration office of Academic Affiliations
provided in-kind support.
NR 39
TC 27
Z9 28
U1 3
U2 18
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 JUN
PY 2013
VL 28
IS 6
BP 801
EP 809
DI 10.1007/s11606-012-2193-3
PG 9
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA 151OB
UT WOS:000319468800013
PM 22997002
ER
PT J
AU Kohler, MJ
Amezaga, M
Drozd, J
Crowley, ST
Gulanski, B
Anderson, DR
Fraenkel, L
AF Kohler, Minna J.
Amezaga, Matxalen
Drozd, James
Crowley, Susan T.
Gulanski, Barbara
Anderson, Daren R.
Fraenkel, Liana
TI Use of a Computerized Order Set to Increase Prescription of Calcium and
Vitamin D Supplementation in Patients Receiving Glucocorticoids
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Article
DE glucocorticoid-induced osteoporosis; adherence; calcium; vitamin D;
prednisone
ID DECISION-SUPPORT-SYSTEMS; CORTICOSTEROID-INDUCED OSTEOPOROSIS;
RHEUMATOID-ARTHRITIS; CONTROLLED-TRIAL; BONE LOSS; MANAGEMENT;
PREVENTION; CARE; MEDICATION; FRACTURE
AB American College of Rheumatology guidelines recommend that patients taking glucocorticoids also take calcium and vitamin D supplements, regardless of the dose or intended duration of glucocorticoid use, to decrease their risk of glucocorticoid-induced osteopenia or osteoporosis (GIOP).
To increase the number of prescriptions made for calcium and vitamin D in patients who receive a prescription for glucocorticoids using an automated, computerized order set.
Pre-post test design.
A total of 1,041 outpatients receiving care at a single VA medical center.
We developed an automated order set in which calcium and vitamin D were automatically co-ordered with glucocorticoid prescriptions of at least 2-week duration. We tested the impact of the order set by comparing the number of calcium and vitamin D prescriptions in patients taking glucocorticoids during a 12-month period before (T1) and after (T2) implementation. The automated order set could be modified by the treating physician, and it was not generated for patients with hypercalcemia.
A total of 535 patients during T1 and 506 patients during T2 had a glucocorticoid prescription of at least 2-week duration. The percent of co-prescriptions for calcium increased from 37 to 49 % and vitamin D from 38 to 53 % (both p < 0.0001) after the new automated order set was implemented.
Implementation of an automatic prescription for calcium and vitamin D supplementation modestly increases the number of patients on glucocorticoids who are prescribed calcium and vitamin D supplementation.
C1 [Kohler, Minna J.] Harvard Univ, Sch Med, Div Rheumatol, Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Amezaga, Matxalen] Baylor Coll Med, Sect Rheumatol Allergy & Immunol, Houston, TX 77030 USA.
[Drozd, James; Crowley, Susan T.; Gulanski, Barbara; Fraenkel, Liana] Vet Affairs VA Connecticut Healthcare Syst, West Haven, CT USA.
[Crowley, Susan T.; Gulanski, Barbara; Fraenkel, Liana] Yale Univ, Sch Med, New Haven, CT USA.
[Anderson, Daren R.] Community Hlth Ctr Inc, Middletown, CT USA.
RP Kohler, MJ (reprint author), Harvard Univ, Sch Med, Div Rheumatol, Massachusetts Gen Hosp, 55 Fruit St,Yawkey 2C, Boston, MA 02114 USA.
EM mkohler@partners.org
FU National Institute of Arthritis and Musculoskeletal and Skin Diseases
(NIAMS) [5 T32 AR007107]; NIAMS [K24 AR060231-01]
FX Dr. Kohler's work was supported by the National Institute of Arthritis
and Musculoskeletal and Skin Diseases (NIAMS) 5 T32 AR007107 Training
Program for Investigative Rheumatology. Dr. Fraenkel is supported by the
NIAMS K24 AR060231-01.
NR 21
TC 4
Z9 4
U1 0
U2 1
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 JUN
PY 2013
VL 28
IS 6
BP 825
EP 829
DI 10.1007/s11606-013-2360-1
PG 5
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA 151OB
UT WOS:000319468800016
PM 23404201
ER
PT J
AU Arakaki, R
Woo, E
Kroshinsky, D
AF Arakaki, R.
Woo, E.
Kroshinsky, D.
TI The impact of dermatology consultations on antibiotic usage for
suspected cases of cellulitis presenting to outpatient internal medicine
offices
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the Medical-Dermatology-Society
CY FEB 28, 2013
CL Miami Beach, FL
SP Med Dermatol Soc
C1 [Arakaki, R.] Harvard Univ, Sch Med, Boston, MA USA.
[Woo, E.; Kroshinsky, D.] 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 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD JUN
PY 2013
VL 133
IS 6
MA 1
BP 1694
EP 1694
PG 1
WC Dermatology
SC Dermatology
GA 146VE
UT WOS:000319121500047
ER
PT J
AU Dolfi, DV
Mansfield, KD
Polley, AM
Doyle, SA
Freeman, GJ
Pircher, H
Schmader, KE
Wherry, EJ
AF Dolfi, Douglas V.
Mansfield, Kathleen D.
Polley, Antonio M.
Doyle, Susan A.
Freeman, Gordon J.
Pircher, Hanspeter
Schmader, Kenneth E.
Wherry, E. John
TI Increased T-bet is associated with senescence of influenza
virus-specific CD8 T cells in aged humans
SO JOURNAL OF LEUKOCYTE BIOLOGY
LA English
DT Article
DE CD57; PD-1; KLRG-1; Eomes; CD107; exhaustion
ID CHRONIC VIRAL-INFECTION; IFN-GAMMA PRODUCTION; TRANSCRIPTION FACTOR;
HUMAN EFFECTOR; OLDER-ADULTS; MEMORY; EXPRESSION; EXHAUSTION;
DIFFERENTIATION; PROTECTION
AB Aged individuals have increased morbidity and mortality following influenza and other viral infections, despite previous exposure or vaccination. Mouse and human studies suggest increased senescence and/or exhaustion of influenza virus-specific CD8 T cells with advanced age. However, neither the relationship between senescence and exhaustion nor the underlying transcriptional pathways leading to decreased function of influenza virus-specific cellular immunity in elderly humans are well-defined. Here, we demonstrate that increased percentages of CD8 T cells from aged individuals express CD57 and KLRG1, along with PD-1 and other inhibitory receptors, markers of senescence, or exhaustion, respectively. Expression of T-box transcription factors, T-bet and Eomes, were also increased in CD8 T cells from aged subjects and correlated closely with expression of CD57 and KLRG1. Influenza virus-specific CD8 T cells from aged individuals exhibited decreased functionality with corresponding increases in CD57, KLRG1, and T-bet, a molecular regulator of terminal differentiation. However, in contrast to total CD8 T cells, influenza virus-specific CD8 T cells had altered expression of inhibitory receptors, including lower PD-1, in aged compared with young subjects. Thus, our data suggest a prominent role for senescence and/or terminal differentiation for influenza virus-specific CD8 T cells in elderly subjects.
C1 [Dolfi, Douglas V.; Mansfield, Kathleen D.; Polley, Antonio M.; Wherry, E. John] Univ Penn, Perelman Sch Med, Dept Microbiol, Inst Immunol, Philadelphia, PA 19104 USA.
[Doyle, Susan A.; Schmader, Kenneth E.] Duke Univ, Med Ctr, Dept Med, Div Geriatr, Durham, NC 27710 USA.
[Doyle, Susan A.; Schmader, Kenneth E.] Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Durham, NC 27705 USA.
[Freeman, Gordon J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Dept Med, Boston, MA 02115 USA.
[Pircher, Hanspeter] Univ Freiburg, Dept Immunol, D-79106 Freiburg, Germany.
RP Wherry, EJ (reprint author), Univ Penn, PerelmanSch Med, Dept Microbiol, 421 Curie Blvd,Room 312, Philadelphia, PA 19104 USA.
EM wherry@mail.med.upenn.edu
FU U.S. National Institutes of Health [P01-A1078897, U19-AI082630]; U.S.
grant [BAA 266200500030C]
FX This work was funded by U.S. National Institutes of Health grants
P01-A1078897 and U19-AI082630 to G.J.F. and E.J.W. and U.S. grant BAA
266200500030C to G.J.F., K. E. S., and E.J.W. The authors thank the
members of the Wherry lab for discussions and critical reading of the
manuscript and Sarah J. Ratcliffe for statistical analysis.
NR 60
TC 21
Z9 21
U1 0
U2 5
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0741-5400
J9 J LEUKOCYTE BIOL
JI J. Leukoc. Biol.
PD JUN
PY 2013
VL 93
IS 6
BP 825
EP 836
DI 10.1189/jlb.0912438
PG 12
WC Cell Biology; Hematology; Immunology
SC Cell Biology; Hematology; Immunology
GA 155DZ
UT WOS:000319727700003
PM 23440501
ER
PT J
AU Ponte, PR
AF Ponte, Patricia Reid
TI Structure, Process, and Empirical Outcomes-the Magnet (R) Journey of
Continuous Improvement
SO JOURNAL OF NURSING ADMINISTRATION
LA English
DT Editorial Material
AB The chairperson of the Commission on Magnet (R) Recognition provides an overview of current and future initiatives supporting cultures of excellence. The article examines the evolving focus on outcomes data and evidence, as well as the commitment of the commission to advancing nursing education at all levels.
C1 [Ponte, Patricia Reid] Patient Care Serv, Boston, MA USA.
[Ponte, Patricia Reid] Dana Farber Canc Inst, Boston, MA 02215 USA.
[Ponte, Patricia Reid] Brigham & Womens Hosp, Nursing Serv, Boston, MA 02115 USA.
[Ponte, Patricia Reid] Brigham & Womens Hosp, Clin Serv, Boston, MA 02115 USA.
RP Ponte, PR (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,Dana 1632, Boston, MA 02215 USA.
EM pat_reid_ponte@dfci.harvard.edu
NR 5
TC 1
Z9 1
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 JUN
PY 2013
VL 43
IS 6
BP 309
EP 310
DI 10.1097/NNA.0b013e3182942b49
PG 2
WC Nursing
SC Nursing
GA 152VS
UT WOS:000319560100001
ER
PT J
AU Ponte, PR
O'Neill, K
AF Ponte, Patricia Reid
O'Neill, Kathleen
TI Hiring Into Advanced Practice Positions The Nurse Practitioner Versus
Physician Assistants Debate
SO JOURNAL OF NURSING ADMINISTRATION
LA English
DT Article
ID PRIMARY-CARE OUTCOMES; DOCTORS; TRIAL
AB Nurse practitioners (NPs) and physician assistants (PAs) have long been part of the care model at our institution. Over the years, however, we have demonstrated a preference for NPs based on the belief that they can better meet our patients' needs. A recent evaluation of our care model led us to question these preferential hiring practices. After carefully examining NP and PA education and licensure requirements, scope of practice, and roles at our institution, we concluded that similarities between the roles far outweighed the differences and that our preferential hiring practices should be replaced by an individualized approach, in which advanced practice positions are filled by whichever candidate best meets the role requirements. This inclusive and analytic approach may be a useful model for other nurse leaders considering the NP/PA question.
C1 [Ponte, Patricia Reid] Dana Farber Canc Inst, Patient Care Serv, Boston, MA 02215 USA.
[Ponte, Patricia Reid] Dana Farber Canc Inst, Boston, MA 02215 USA.
[Ponte, Patricia Reid] Brigham & Womens Hosp, Oncol Nursing Serv, Boston, MA 02115 USA.
[Ponte, Patricia Reid] Brigham & Womens Hosp, Clin Serv, Boston, MA 02115 USA.
[O'Neill, Kathleen] Simmons Sch Nursing & Hlth Sci Boston, Boston, MA USA.
RP Ponte, PR (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,Dana 1632, Boston, MA 02215 USA.
EM pat_reid_ponte@dfci.harvard.edu
NR 26
TC 1
Z9 1
U1 5
U2 15
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 JUN
PY 2013
VL 43
IS 6
BP 329
EP 335
DI 10.1097/NNA.0b013e3182942c73
PG 7
WC Nursing
SC Nursing
GA 152VS
UT WOS:000319560100008
ER
PT J
AU Gordon, PE
Faquin, WC
Lahey, E
Kaban, LB
AF Gordon, Paul E.
Faquin, William C.
Lahey, Edward
Kaban, Leonard B.
TI Floor-of-Mouth Dermoid Cysts: Report of 3 Variants and a Suggested
Change in Terminology
SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY
LA English
DT Article
ID GASTROINTESTINAL CYST
AB Purpose: Dermoid cyst is a frequently used descriptive term, but its definition changes according to the clinician (eg, dermatologists, neurologists, gynecologists, oral and maxillofacial surgeons, and plastic surgeons). It is sometimes used synonymously with teratoma. In oral and maxillofacial surgery, it is applied to describe congenital floor-of-mouth cysts of 3 histologic types: epidermoid, dermoid, and teratoid. This terminology is confusing and has led to some ambiguity in the literature. The purpose of this report is to document 3 cases illustrating the utility of a more specific term, congenital germline fusion cyst of the floor of the mouth.
Patients and Methods: Patients who presented with floor-of-mouth swelling were evaluated by history, clinical examination, and imaging studies (magnetic resonance imaging and computed tomography).
Results: Three cases (1 epidermoid variant, 1 dermoid variant, and 1 teratoid variant) are documented to illustrate the new terminology.
Conclusion: Congenital germline fusion cyst is more reflective of the embryologic origins of the lesion than dermoid cyst and is inclusive of all 3 histologic variants. (C) 2013 American Association of Oral and Maxillofacial Surgeons
C1 Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg,Med Sch, Boston, MA 02115 USA.
Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Dept Pathol,Med Sch, Boston, MA 02115 USA.
RP Gordon, PE (reprint author), 55 Fruit St,Wang ACC Suite 230, Boston, MA 02114 USA.
EM pgordon4@partners.org
FU Massachusetts General Hospital Department of Oral and Maxillofacial
Education and Research Fund
FX This work was funded by the Massachusetts General Hospital Department of
Oral and Maxillofacial Education and Research Fund.
NR 19
TC 4
Z9 5
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 0278-2391
J9 J ORAL MAXIL SURG
JI J. Oral Maxillofac. Surg.
PD JUN
PY 2013
VL 71
IS 6
BP 1034
EP 1041
DI 10.1016/j.joms.2012.12.008
PG 8
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 150IU
UT WOS:000319384600009
PM 23434158
ER
PT J
AU Peacock, ZS
Tricomi, BJ
Murphy, BA
Magill, JC
Kaban, LB
Troulis, MJ
AF Peacock, Zachary S.
Tricomi, Brad J.
Murphy, Brian A.
Magill, John C.
Kaban, Leonard B.
Troulis, Maria J.
TI Automated Continuous Distraction Osteogenesis May Allow Faster
Distraction Rates: A Preliminary Study
SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY
LA English
DT Article
ID CLINICAL-APPLICATION; BONE-FORMATION; ANIMAL-MODEL; DEVICE; FREQUENCY;
MINIPIGS; CONDYLE; TISSUES; DISC; REGENERATION
AB Purpose: To determine if automated continuous distraction osteogenesis (DO) at rates faster than 1 mm/day results in bone formation by clinical and radiographic criteria, in a minipig model.
Materials and Methods: An automated, continuous, curvilinear distraction device was placed across a mandibular osteotomy in 10 minipigs. After 12 mm of distraction and 24 days of fixation, the animals were sacrificed and bone healing was evaluated. The continuous distraction rates were 1.5 mm/day (n = 5) and 3 mm/day (n = 5). A semiquantitative scale was used to assess the ex vivo clinical appearance of the distraction gap (3 = osteotomy not visible; 2 = <50% visible; 1 = >50% visible; 0 = 100% visible), stability (3 = no mobility; 2 and 1 = mobility in 1 plane or 2 planes, respectively; 0 = mobility in 3 planes), and radiographic density (4 = 100% of gap opaque; 3 = >75%; 2 = 50% to 75%; 1 = <50%; 0 = radiolucent). Groups of 4 minipigs distracted discontinuously at 1, 2, and 4 mm/day served as controls.
Results: Automated, continuous DO at 1.5-mm/day and 3-mm/day had similar bone formation compared to discontinuous DO at 1-mm/day. The continuous DO 1.5-mm/day group had significantly higher scores for appearance and radiographic density compared with the discontinuous 4-mm/day group. The continuous DO 3-mm/day group had significantly higher scores for appearance and radiographic density compared with the discontinuous 4-mm/day group and greater stability compared with the discontinuous 2- and 4-mm/day groups.
Conclusions: Results of this preliminary study indicate that continuous DO at rates of 1.5 and 3.0 mm/day produces better bone formation compared with discontinuous DO at rates faster than 1 mm/day. (C) 2013 American Association of Oral and Maxillofacial Surgeons
C1 [Peacock, Zachary S.; Tricomi, Brad J.; Murphy, Brian A.; Magill, John C.; Kaban, Leonard B.; Troulis, Maria J.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA.
RP Peacock, ZS (reprint author), Massachusetts Gen Hosp, Warren 1201,55 Fruit St, Boston, MA 02114 USA.
EM zpeacock@partners.org
FU NIH/NIDCR SBIR [5R44DE014803-03]; Massachusetts General Hospital
Department of Oral and Maxillofacial Surgery Education and Research
Fund; Hanson Foundation (Boston, MA)
FX This work was funded by NIH/NIDCR SBIR grant 5R44DE014803-03; the
Massachusetts General Hospital Department of Oral and Maxillofacial
Surgery Education and Research Fund; and the Hanson Foundation (Boston,
MA).
NR 43
TC 4
Z9 4
U1 0
U2 0
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0278-2391
J9 J ORAL MAXIL SURG
JI J. Oral Maxillofac. Surg.
PD JUN
PY 2013
VL 71
IS 6
BP 1073
EP 1084
DI 10.1016/j.joms.2012.11.015
PG 12
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 150IU
UT WOS:000319384600014
PM 23499159
ER
PT J
AU Mull, HJ
Borzecki, AM
Hickson, K
Itani, KMF
Rosen, AK
AF Mull, Hillary J.
Borzecki, Ann M.
Hickson, Kathleen
Itani, Kamal M. F.
Rosen, Amy K.
TI Development and Testing of Tools to Detect Ambulatory Surgical Adverse
Events
SO JOURNAL OF PATIENT SAFETY
LA English
DT Article
DE surgical adverse event; trigger tool; ambulatory surgery; NSQIP
ID QUALITY IMPROVEMENT PROGRAM; RETURN HOSPITAL VISITS;
OF-VETERANS-AFFAIRS; POSTDISCHARGE SYMPTOMS; OUTPATIENT SURGERY;
AMERICAN-COLLEGE; CARE; READMISSIONS
AB Objectives: Numerous health-care systems in the United States, including the Veterans Health Administration (VA), use the National Surgical Quality Improvement Program (NSQIP) to detect surgical adverse events (AEs). VASQIP sampling methodology excludes many routine ambulatory surgeries from review. Triggers, algorithms derived from clinical logic to flag cases where AEs have most likely occurred, could complement VASQIP by detecting a higher yield of ambulatory surgeries with a true surgical AE.
Methods: We developed and tested a set of ambulatory surgical AE trigger algorithms using a sample of fiscal year 2008 ambulatory surgeries from the VA Boston Healthcare System. We used VA Boston VASQIP-assessed cases to refine triggers and VASQIP-excluded cases to test how many trigger-flagged surgeries had a nurse chart reviewdetected surgical AE. Chart review was performed using the VA electronic medical record. We calculated the ratio of cases with a true surgical AE over flagged cases (i.e., the positive predictive value [PPV]), and the 95% confidence interval for each trigger.
Results: Compared with the VASQIP rate (9 AEs, or 2.8%, of the 322 charts assessed), nurse chart review of the 198 trigger-flagged surgeries yielded more cases with at least 1 AE (47 surgeries with an AE, or 6.0%, of the 782 VASQIP-excluded ambulatory surgeries). Individual trigger PPVs ranged from 12.4% to 58.3%.
Conclusions: In comparison with VASQIP, our set of triggers identified a higher rate of surgeries with AEs in fewer chart-reviewed cases. Because our results are based on a relatively small sample, further research is necessary to confirm these findings.
C1 [Mull, Hillary J.; Rosen, Amy K.] VA Boston Healthcare Syst, Ctr Org Leadership & Management Res, Boston, MA 02130 USA.
[Mull, Hillary J.; Borzecki, Ann M.; Rosen, Amy K.] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Borzecki, Ann M.; Hickson, Kathleen] Bedford VAMC, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA.
[Hickson, Kathleen] VA Boston Healthcare Syst, West Roxbury, MA USA.
[Itani, Kamal M. F.] VA Boston Healthcare Syst, Dept Surg, West Roxbury, MA USA.
[Borzecki, Ann M.; Itani, Kamal M. F.] Boston Univ, Sch Med, Dept Surg, Boston, MA 02118 USA.
[Itani, Kamal M. F.] Harvard Univ, Sch Med, Boston, MA USA.
RP Mull, HJ (reprint author), VA Boston Healthcare Syst, Ctr Org Leadership & Management Res, 150 S Huntington Ave 152M, Boston, MA 02130 USA.
EM hjmull@bu.edu
FU VA Boston Healthcare System Department of Surgery
FX This research was funded through the VA Boston Healthcare System
Department of Surgery.
NR 39
TC 2
Z9 2
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1549-8417
J9 J PATIENT SAF
JI J. Patient Saf.
PD JUN
PY 2013
VL 9
IS 2
BP 96
EP 102
DI 10.1097/PTS.0b013e31827d1a88
PG 7
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA 151FI
UT WOS:000319445700007
PM 23370221
ER
PT J
AU Green, AD
Belkind-Gerson, J
Surjanhata, BC
Mousa, H
Kuo, B
Di Lorenzo, C
AF Green, Alex D.
Belkind-Gerson, Jaime
Surjanhata, Brian C.
Mousa, Hayat
Kuo, Braden
Di Lorenzo, Carlo
TI Wireless Motility Capsule Test in Children with Upper Gastrointestinal
Symptoms
SO JOURNAL OF PEDIATRICS
LA English
DT Article
ID HEALTHY; TRANSIT; GASTROPARESIS
AB Objective To compare scintigraphic gastric emptying and antroduodenal manometry (ADM) studies with the wireless motility capsule test in symptomatic pediatric patients.
Study design Patients aged 8-17 years with severe upper gastrointestinal symptoms (ie, nausea, vomiting, retching, abdominal pain) referred for ADM were recruited. A standardized protocol for ADM was used. On a different day, participants were given a standardized meal and then swallowed the wireless motility capsule. A wireless receiver unit worn during the study recorded transmitted data. If not performed previously, a 2-hour scintigraphic gastric emptying study was completed at the time of ADM testing.
Results A total of 22 patients were recruited, of whom 21 had complete scintigraphic gastric emptying study data and 20 had complete ADM data. The wireless motility capsule test had 100% sensitivity and 50% specificity in detecting gastroparesis compared with the 2-hour scintigraphic gastric emptying study. The wireless motility capsule test detected motor abnormalities in 17 patients, compared with 10 detected by ADM. Dichotomous comparison yielded a diagnostic difference between ADM and the wireless motility capsule test (P<.01). Migrating motor complexes were recognized in all patients by both ADM and the wireless motility capsule test. The wireless motility capsule test was well tolerated in all patients, and there were no side effects.
Conclusion In symptomatic pediatric patients, the wireless motility capsule test is highly sensitive compared with scintigraphic gastric emptying studies in detecting gastroparesis, and seems to be more sensitive than ADM in detecting motor abnormalities.
C1 [Green, Alex D.; Mousa, Hayat; Di Lorenzo, Carlo] Ohio State Univ, Nationwide Childrens Hosp, Dept Gastroenterol Hepatol & Nutr, Columbus, OH 43210 USA.
[Belkind-Gerson, Jaime] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Pediat Gastroenterol, Boston, MA USA.
[Surjanhata, Brian C.; Kuo, Braden] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gastroenterol, Boston, MA USA.
RP Green, AD (reprint author), 500 Parnassus Ave, San Francisco, CA 94143 USA.
EM alex.green@ucsf.edu
NR 14
TC 8
Z9 8
U1 0
U2 6
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-3476
J9 J PEDIATR-US
JI J. Pediatr.
PD JUN
PY 2013
VL 162
IS 6
BP 1181
EP 1187
DI 10.1016/j.jpeds.2012.11.040
PG 7
WC Pediatrics
SC Pediatrics
GA 152AV
UT WOS:000319502700021
PM 23290514
ER
PT J
AU Smith, VC
Hwang, SS
Dukhovny, D
Young, S
Pursley, DM
AF Smith, V. C.
Hwang, S. S.
Dukhovny, D.
Young, S.
Pursley, D. M.
TI Neonatal intensive care unit discharge preparation, family readiness and
infant outcomes: connecting the dots
SO JOURNAL OF PERINATOLOGY
LA English
DT Article
DE intensive care units neonatal; intensive care neonatal; infant preterm;
newborn readiness; patient discharge; education
ID BIRTH-WEIGHT INFANTS; HIGH-RISK NEONATE; HOSPITAL DISCHARGE; PRETERM
INFANTS; RANDOMIZED-TRIAL; CENTERED CARE; BRONCHOPULMONARY DYSPLASIA;
POSTPARTUM DISCHARGE; MOTHERS; INTERVENTION
AB Neonatal intensive care unit (NICU) discharge readiness is defined as the masterful attainment of technical skills and knowledge, emotional comfort, and confidence with infant care by the primary caregivers at the time of discharge. NICU discharge preparation is the process of facilitating comfort and confidence as well as the acquisition of knowledge and skills to successfully make the transition from the NICU to home. In this paper, we first review the literature about discharge readiness as it relates to the NICU population. Understanding that discharge readiness is achieved, in part, through successful discharge preparation, we then outline an approach to NICU discharge preparation.
C1 [Smith, V. C.; Dukhovny, D.; Pursley, D. M.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Neonatol, Boston, MA 02215 USA.
[Hwang, S. S.] Boston Childrens Hosp, Div Newborn Med, Boston, MA USA.
[Young, S.] Beth Israel Deaconess Med Ctr, Dept Nursing, Boston, MA 02215 USA.
RP Smith, VC (reprint author), Harvard Univ, BIDMC, Sch Med, Dept Neonatol, 330 Brookline Ave,Rose 318, Boston, MA 02215 USA.
EM vsmith1@bidmc.harvard.edu
NR 52
TC 13
Z9 15
U1 3
U2 19
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0743-8346
J9 J PERINATOL
JI J. Perinatol.
PD JUN
PY 2013
VL 33
IS 6
BP 415
EP 421
DI 10.1038/jp.2013.23
PG 7
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA 154FM
UT WOS:000319657300001
PM 23492936
ER
PT J
AU Lubelski, D
Abdullah, KG
Steinmetz, MP
Masters, F
Benzel, EC
Mroz, TE
Shin, JH
AF Lubelski, Daniel
Abdullah, Kalil G.
Steinmetz, Michael P.
Masters, Frank
Benzel, Edward C.
Mroz, Thomas E.
Shin, John H.
TI Lateral Extracavitary, Costotransversectomy, and Transthoracic
Thoracotomy Approaches to the Thoracic Spine Review of Techniques and
Complications
SO JOURNAL OF SPINAL DISORDERS & TECHNIQUES
LA English
DT Review
DE lateral extracavitary; costotransversectomy; thoracotomy; thoracic
spine; spine complications
ID SUBARACHNOID-PLEURAL FISTULA; LUMBAR SPINE; SURGICAL-TREATMENT;
THORACOLUMBAR SPINE; DISC HERNIATIONS; POSTEROLATERAL APPROACH; CORD
DECOMPRESSION; POSTERIOR APPROACH; ANTERIOR EXPOSURE; MANAGEMENT
AB Study Design: Systematic review.
Objective: The authors review complications, as reported in the literature, associated with ventral and posterolateral approaches to the thoracic spine.
Summary of Background: The lateral extracavitary, costotransversectomy, and transthoracic thoracotomy techniques allow surgeons to access the ventral thoracic spine for a wide range of spinal disorders including tumor, degeneration, trauma, and infection. Although the transthoracic thoracotomy has been used traditionally to reach the ventral thoracic spine when access to the vertebral body is required, modifications to the various dorsal approaches have enabled surgeons to achieve goals of decompression, reconstruction, and stabilization through a single approach.
Methods: A systematic Medline search from 1991 to 2011 was performed to identify series reporting clinical data related to these surgical approaches. The morbidity associated with each approach is reviewed and strategies for complications avoidance are discussed. Results: Four thousand six hundred seventy-seven articles that assessed outcomes of the approaches to the thoracic spine were identified; of these 31 studies that consisted of 774 patients were selected for inclusion. A mean complication rate of 39%, 17%, and 15% for thoracotomy, lateral extracavitary, and costotransversectomy, respectively, was determined. The thoracotomy approach had the highest reoperation (3.5%) and mortality rates (1.5%). The specific complications and neurological outcomes were categorized.
Conclusions: Outcomes of the surgical approaches to the thoracic spine have been reported with great detail in the literature. There are limited studies comparing the respective advantages and disadvantages and the differences in technique and outcome between these approaches. The present review suggests that in contrast to the historical experience of the laminectomy for thoracic spine disorders, these alternative approaches are safe and rarely associated with neurological deterioration. The differences between these approaches are based on their complication profiles. A thorough understanding of the regional anatomy will help avoid approach-related complications.
C1 [Lubelski, Daniel; Abdullah, Kalil G.] Cleveland Clin, Lerner Coll Med, Cleveland, OH 44106 USA.
[Lubelski, Daniel; Abdullah, Kalil G.; Steinmetz, Michael P.; Masters, Frank] Case Western Reserve Univ, Sch Med, Cleveland, OH USA.
[Steinmetz, Michael P.] Metrohlth Med Ctr, Cleveland, OH USA.
[Benzel, Edward C.; Mroz, Thomas E.] Ctr Spine Hlth, Dept Neurosurg, Neurol Inst, Cleveland, OH USA.
[Mroz, Thomas E.] Cleveland Clin, Dept Orthoped Surg, Cleveland, OH 44106 USA.
[Shin, John H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA USA.
RP Shin, JH (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, 55 Fruit St,WAC 745, Boston, MA 02114 USA.
EM shin.john@mgh.harvard.edu
NR 76
TC 9
Z9 12
U1 2
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 JUN
PY 2013
VL 26
IS 4
BP 222
EP 232
DI 10.1097/BSD.0b013e31823f3139
PG 11
WC Clinical Neurology; Orthopedics
SC Neurosciences & Neurology; Orthopedics
GA 151IX
UT WOS:000319455000015
PM 22143047
ER
PT J
AU Niess, H
Conrad, C
Kleespies, A
Haas, F
Bao, Q
Jauch, KW
Graeb, C
Bruns, CJ
AF Niess, Hanno
Conrad, Claudius
Kleespies, Axel
Haas, Florian
Bao, Qi
Jauch, Karl-Walter
Graeb, Christian
Bruns, Christiane J.
TI Surgery for Metastasis to the Pancreas: Is it Safe and Effective?
SO JOURNAL OF SURGICAL ONCOLOGY
LA English
DT Article
DE pancreatic metastasis; metastasectomy; renal cell carcinoma; pancreatic
surgery
ID RENAL-CELL CARCINOMA; OF-THE-LITERATURE; PULMONARY RESECTION;
SURGICAL-TREATMENT; TUMORS; SURVIVAL; COMPLICATIONS
AB Background Pancreatic metastases are rare and only sparse data exists on treatment options. After recent advances in pancreatic surgery, metastasectomies have become promising treatment alternatives. Methods Twenty-six patients underwent pancreatic metastasectomy between 1991 and 2010 at our institution. Data was evaluated retrospectively. Results Renal cell carcinoma was the most common origin of pancreatic metastases (n=16; 62%). Other primaries include gall bladder carcinoma, leiomyosarcoma, colon cancer (all n=2), and others. The median time interval between primary tumor and pancreatic resection was 5.3 years [024]. Eleven pancreatic head resections (42%), fourteen distal pancreatectomies (54%), and one total pancreatectomy were performed (4%). The estimated 3- and 5-year survival rates were 73.2% and 52.3%, respectively. The estimated median overall survival was 63 months (CI: 37.888.1 months). There' was no perioperative death. The complication rate and relaparotomy rate was 31% and 19%, respectively. Patients suffering from synchronous metastases at the time of pancreatic surgery had a statistically significant shorter median overall survival time (11 months vs. 64 months). Conclusions Despite the operative risk involved, we believe that pancreatic resection should be considered in selected patients with good performance status, stable disease and isolated pancreatic metastases. J. Surg. Oncol. 2013;107:859864. (c) 2013 Wiley Periodicals, Inc.
C1 [Niess, Hanno; Kleespies, Axel; Haas, Florian; Bao, Qi; Jauch, Karl-Walter; Bruns, Christiane J.] Univ Munich, Dept Surg, Munich, Germany.
[Conrad, Claudius] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Graeb, Christian] Klinikum Hof, Dept Surg, Hof, Germany.
RP Conrad, C (reprint author), Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, 55 Fruit St,Yawkey 7B, Boston, MA 02114 USA.
EM cconrad@partners.org
NR 24
TC 13
Z9 13
U1 1
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-4790
J9 J SURG ONCOL
JI J. Surg. Oncol.
PD JUN
PY 2013
VL 107
IS 8
BP 859
EP 864
DI 10.1002/jso.23333
PG 6
WC Oncology; Surgery
SC Oncology; Surgery
GA 150WH
UT WOS:000319421700012
PM 23637007
ER
PT J
AU Akins, CW
AF Akins, Cary W.
TI The Impact of Aortic Valve Replacement for Aortic Stenosis on Mitral
Valve Dynamics: A Surgeon's View
SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY
LA English
DT Editorial Material
ID HEART-VALVE
C1 [Akins, Cary W.] Massachusetts Gen Hosp, Inst Heart Vasc & Stroke Care, Boston, MA 02114 USA.
[Akins, Cary W.] Harvard Univ, Sch Med, Boston, MA USA.
RP Akins, CW (reprint author), Massachusetts Gen Hosp, Inst Heart Vasc & Stroke Care, 55 Fruit St, Boston, MA 02114 USA.
EM caryakins@comcast.net
NR 9
TC 0
Z9 0
U1 0
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0894-7317
J9 J AM SOC ECHOCARDIOG
JI J. Am. Soc. Echocardiogr.
PD JUN
PY 2013
VL 26
IS 6
BP 615
EP 617
DI 10.1016/j.echo.2013.04.006
PG 3
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 151YL
UT WOS:000319496200008
PM 23711343
ER
PT J
AU Wright, CD
AF Wright, Cameron D.
TI Historical perspectives of The American Association for Thoracic
Surgery: Herbert Sloan
SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
LA English
DT Editorial Material
C1 Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA.
RP Wright, CD (reprint author), Massachusetts Gen Hosp, Div Thorac Surg, Blake 1570,55 Fruit St, Boston, MA 02114 USA.
EM wright.cameron@mgh.harvard.edu
NR 7
TC 0
Z9 0
U1 0
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5223
J9 J THORAC CARDIOV SUR
JI J. Thorac. Cardiovasc. Surg.
PD JUN
PY 2013
VL 145
IS 6
BP 1428
EP 1430
DI 10.1016/j.jtcvs.2013.04.001
PG 3
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA 146CK
UT WOS:000319066300015
PM 23583173
ER
PT J
AU Yechoor, P
Blaustein, AS
Bakaeen, FG
Cornwell, LD
Coselli, JS
LeMaire, SA
Chu, D
AF Yechoor, Poornima
Blaustein, Alvin S.
Bakaeen, Faisal G.
Cornwell, Lorraine D.
Coselli, Joseph S.
LeMaire, Scott A.
Chu, Danny
TI The natural history of moderate aortic stenosis in a veteran population
SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
LA English
DT Article
ID CARDIOVASCULAR MORTALITY; VALVE DISEASE; PROGRESSION; MANAGEMENT; MILD
AB Objective: Our objective was to evaluate the natural history of moderate aortic stenosis in veterans-a unique patient population with significant comorbidities.
Methods: We retrospectively reviewed the records of all patients who underwent echocardiography at a single veterans affairs hospital during 2006. We identified consecutive patients who had moderate aortic stenosis as indicated by a mean transaortic gradient of 25 to 40 mm Hg, peak aortic jet velocity of 3 to 4 m/s, or aortic valve area of 1.0 to 1.5 cm(2). The primary end point was defined as survival without aortic valve replacement.
Results: Of the 104 patients (mean age, 74 +/- 10 years), 49% had diabetes, 21% had peripheral vascular disease, 21% were current smokers, 18% had chronic obstructive pulmonary disease, 60% had coronary artery disease, 89% had hypertension, and 31% had a body mass index of 30 kg/m(2) or more. Mean ejection fraction was 49% +/- 12%. During the mean follow-up period of 22 months (range, 1-67 months), 30% of patients underwent aortic valve replacement-26% for symptomatic severe aortic stenosis and 4% concomitantly with coronary artery bypass grafting as the primary indicated operation-and 61% died. Event-free survivals were 48%, 24%, and 15% at 1, 3, and 5 years, respectively.
Conclusions: Our cohort of military veteran patients had significant comorbidities. Event-free survival for such patients who have moderate aortic stenosis is significantly lower than previously reported data suggest. Within this unique group of patients, identifying factors that accelerate the progression of moderate aortic stenosis would help surgeons select patients who may benefit from early aortic valve replacement for moderate aortic stenosis.
C1 St Lukes Episcopal Hosp, Texas Heart Inst, Michael E DeBakey Vet Affairs Med Ctr, Baylor Coll Med,Div Cardiothorac Surg, Houston, TX 77030 USA.
St Lukes Episcopal Hosp, Texas Heart Inst, Michael E DeBakey Vet Affairs Med Ctr, Baylor Coll Med,Div Cardiol, Houston, TX 77030 USA.
RP Chu, D (reprint author), St Lukes Episcopal Hosp, Texas Heart Inst, Baylor Coll Med, Div Cardiothorac Surg, 1 Baylor Plaza, Houston, TX 77030 USA.
EM dchumd@gmail.com
FU Michael E. DeBakey Veterans Affairs Health Services Research &
Development Center of Excellence [HFP90-020]; Baylor College of Medicine
FX Funded by the Michael E. DeBakey Veterans Affairs Health Services
Research & Development Center of Excellence (HFP90-020); internal
funding from Baylor College of Medicine.
NR 25
TC 4
Z9 4
U1 0
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5223
J9 J THORAC CARDIOV SUR
JI J. Thorac. Cardiovasc. Surg.
PD JUN
PY 2013
VL 145
IS 6
BP 1550
EP 1553
DI 10.1016/j.jtcvs.2012.05.013
PG 4
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA 146CK
UT WOS:000319066300038
PM 22664178
ER
PT J
AU Barshes, NR
Ozaki, CK
Kougias, P
Belkin, M
AF Barshes, Neal R.
Ozaki, C. Keith
Kougias, Panos
Belkin, Michael
TI A cost-effectiveness analysis of infrainguinal bypass in the absence of
great saphenous vein conduit
SO JOURNAL OF VASCULAR SURGERY
LA English
DT Article
ID CRITICAL LIMB ISCHEMIA; INFRAPOPLITEAL ARTERIES; POLYTETRAFLUOROETHYLENE
BYPASS; TIBIAL BYPASS; SALVAGE; GRAFTS; METAANALYSIS; MULTICENTER;
MANAGEMENT; PATCH
AB Background: Good-quality great saphenous vein (GSV) is the preferred conduit for infrainguinal surgical revascularizations, but it is not available in all patients. We sought to identify the alternative conduit that would maximize cost-effectiveness in the context of infrapopliteal bypass for critical limb ischemia and nonhealing foot wounds.
Methods: A Markov model was used to create a detailed simulation of 10-year outcomes in a hypothetical Edifoligide for the Prevention of Infrainguinal Vein Graft Failure (PREVENT) III-type patient cohort undergoing infrainguinal bypass for nonhealing foot wounds. The following management options were evaluated: (1) conservative therapy (local wound care, amputation as needed); (2) primary amputation; (3) bypass with autologous alternative vein (AAV), including arm or lesser saphenous vein; (4) bypass with GSV <3 mm in diameter; (5) bypass with polytetrafluoroethylene (PTFE); (6) cryopreserved venous allograft; and (7) cryopreserved arterial allograft. Estimates of 10-year total costs were incorporated into the model. Cost-effectiveness was measured in terms of incremental United States dollars per additional year of ambulation.
Results: Bypass with AAV had the highest effectiveness as measured in median years of ambulation. After primary amputation, bypass with PTFE had the lowest total costs. With incremental cost-effectiveness ratios of $5325 and $21,228, bypass with PTFE or AAV appeared to be cost-effective alternatives to conservative therapy for nonhealing ischemic wounds. Primary amputation, GSV <3 mm, and allograft options were dominated (ie, more costly and less effective). Primary amputation was weakly dominated.
Conclusions: Bypass with PTFE or AAV appears to be a cost-effective option for the management of critical limb ischemia and nonhealing foot wounds when good-quality GSV is not available.
C1 [Barshes, Neal R.; Kougias, Panos] Baylor Coll Med, Div Vasc & Endovasc Surg, Michael E DeBakey Dept Surg, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA.
[Ozaki, C. Keith; Belkin, Michael] Brigham & Womens Hosp, Dept Surg, Div Vasc & Endovasc Surg, Boston, MA 02115 USA.
RP Barshes, NR (reprint author), Baylor Coll Med, Div Vasc & Endovasc Surg, Michael E DeBakey Dept Surg, Michael E DeBakey Vet Affairs Med Ctr, 2002 Holcombe Blvd OCL 112, Houston, TX 77030 USA.
EM nbarshes@bcm.tmc.edu
NR 25
TC 6
Z9 6
U1 0
U2 7
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 JUN
PY 2013
VL 57
IS 6
BP 1466
EP 1470
DI 10.1016/j.jvs.2012.11.115
PG 5
WC Surgery; Peripheral Vascular Disease
SC Surgery; Cardiovascular System & Cardiology
GA 150KN
UT WOS:000319389400003
PM 23395205
ER
PT J
AU Gasper, WJ
Reilly, LM
Rapp, JH
Grenon, SM
Hiramoto, JS
Sobel, JD
Chuter, TAM
AF Gasper, Warren J.
Reilly, Linda M.
Rapp, Joseph H.
Grenon, S. Marlene
Hiramoto, Jade S.
Sobel, Julia D.
Chuter, Timothy A. M.
TI Assessing the anatomic applicability of the multibranched endovascular
repair of thoracoabdominal aortic aneurysm technique
SO JOURNAL OF VASCULAR SURGERY
LA English
DT Article; Proceedings Paper
CT 27th Annual Meeting of the Western-Vascular-Society
CY SEP 22-25, 2012
CL Park City, UT
SP Western Vasc Soc
ID UNITED-STATES; STENT GRAFTS; EXPERIENCE
AB Background: Multibranched endovascular aneurysm repair (MBEVAR) has the potential to lower the morbidity and mortality rates of thoracoabdominal aneurysm repair, but the applicability of the technique is unknown. Our aim was to estimate the prevalence of anatomic suitability for MBEVAR.
Methods: Retrospective review of patients referred for a prospective trial of MBEVAR between November 2005 and July 2012. Anatomic suitability was assessed on three-dimensional computed tomography scan reconstructions according to the current criteria for a custom-made stent graft or a fixed, off-the-shelf stent graft in both standard (22F) and low-profile (18F) delivery systems.
Results: A total of 250 contrast-enhanced computed tomography scans were reviewed, 49 of which were excluded due to inadequate aneurysm size. Of 201 candidates for repair, 149 (74%) were men and 86 (43%) had Crawford classification type IV/paravisceral aneurysms; 109 (58%) were anatomically suitable for a single-stage repair with a custom-made, low-profile stent graft. Another 58 (29%) could have been made suitable for MBEVAR with an adjunct procedure, including angiogram with visceral or renal artery stenting (n = 23), carotid-subclavian bypass (n = 5), or iliac bypass for device insertion (n = 17), or to preserve internal iliac artery flow because of an iliac aneurysm (n = 9), or dissection (n = 8). There was no association between suitability and gender, aneurysm diameter, or type. However, women were significantly more likely to need a conduit or low-profile device (P = .003). Patients with type B aortic dissections were significantly less likely to have anatomy suitable for repair (P = .035) and more likely to require a multistage repair. Thirty-four patients would have been unsuitable for repair because of renal artery anatomy (n = 14), visceral artery anatomy (n = 4), lack of a proximal landing zone due to an arch aneurysm (n = 7), or inadequate access arteries (n = 9). The low-profile device increased the number of patients who would have been suitable for a single-stage repair by 16. The off-the-shelf graft has the advantage of a faster assessment-to-treatment time, but only 64 patients would have been suitable for a single-stage repair and another 30 could have been made suitable with an adjunct procedure.
Conclusions: Most patients would have been suitable or could have been made suitable for a thoracoabdominal stent graft using current anatomic criteria. The applicability of MBEVAR will continue to change as the experience with the technique grows and devices evolve, as evidenced by the potential reduction in iliac bypasses after the introduction of a low-profile device and the ability to treat symptomatic or urgent patients with the off-the-shelf device.
C1 [Gasper, Warren J.; Reilly, Linda M.; Hiramoto, Jade S.; Sobel, Julia D.; Chuter, Timothy A. M.] Univ Calif San Francisco, Div Vasc & Endovasc Surg, San Francisco, CA 94143 USA.
[Rapp, Joseph H.; Grenon, S. Marlene] San Francisco VA Med Ctr, Vasc Surg Sect, San Francisco, CA USA.
RP Gasper, WJ (reprint author), Univ Calif San Francisco, Div Vasc & Endovasc Surg, 400 Parnassus Ave,Box 0222, San Francisco, CA 94143 USA.
EM Warren.Gasper@ucsf.edu
NR 23
TC 17
Z9 17
U1 0
U2 4
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 JUN
PY 2013
VL 57
IS 6
BP 1553
EP 1558
DI 10.1016/j.jvs.2012.12.021
PG 6
WC Surgery; Peripheral Vascular Disease
SC Surgery; Cardiovascular System & Cardiology
GA 150KN
UT WOS:000319389400017
PM 23395201
ER
PT J
AU Berry, K
Ioannou, GN
AF Berry, Kristin
Ioannou, George N.
TI Serum alpha-fetoprotein level independently predicts posttransplant
survival in patients with hepatocellular carcinoma
SO LIVER TRANSPLANTATION
LA English
DT Article
ID LIVER-TRANSPLANTATION; CIRRHOSIS; VALIDATION; ALLOCATION
AB We aimed to determine whether combining serum alpha-fetoprotein (AFP) level with hepatocellular carcinoma (HCC) tumor burden would allow better stratification of posttransplant survival for patients with HCC undergoing liver transplantation. Adjusting for donor and recipient characteristics, we calculated the risk of posttransplant mortality associated with serum AFP level or HCC tumor burden for all first-time adult liver transplants performed in the United States between 2002 and 2011 (n=45,267). Serum AFP level, rather than tumor burden, was the tumor characteristic most strongly associated with posttransplant survival. Although recipients with HCC and a serum AFP level15 ng/mL at the time of transplantation had no excess posttransplant mortality [adjusted hazard ratio (AHR)=1.02, 95% confidence interval (CI)=0.93-1.12], patients with a serum AFP level of 16 to 65 ng/mL (AHR=1.38, 95% CI=1.23-1.54), patients with a serum AFP level of 66 to 320 ng/mL (AHR=1.65, 95% CI=1.45-1.88), and patients with a serum AFP level>320 ng/mL (AHR=2.37, 95% CI=2.06-2.73) had progressively worse posttransplant mortality in comparison with recipients without HCC. Patients with a tumor burden exceeding the Milan criteria (who are usually excluded from transplantation) had excellent posttransplant survival if their serum AFP level was 0 to 15 ng/mL (AHR=0.97, 95% CI=0.66-1.43). In contrast, patients within the Milan criteria (who are routinely considered to be transplant candidates) had poor survival if their serum AFP level was substantially elevated (for a serum AFP level66 ng/mL, AHR=1.93, 95% CI=1.74-2.15). Changes in serum AFP level while patients were on the waiting list corresponded closely to changes in posttransplant mortality. In conclusion, the absolute serum AFP level and changes in the serum AFP level strongly predict posttransplant survival independently of the tumor burden. We hope that these data, in combination with other factors, can be used to inform future studies and ongoing discussions aimed at improving the eligibility criteria for liver transplantation for patients with HCC. Liver Transpl 19:634-645, 2013. (c) 2013 AASLD.
C1 [Berry, Kristin; Ioannou, George N.] Vet Affairs Puget Sound Hlth Care Syst, Res & Dev, Seattle, WA 98108 USA.
[Ioannou, George N.] Vet Affairs Puget Sound Hlth Care Syst, Div Gastroenterol, Dept Med, Seattle, WA 98108 USA.
[Ioannou, George N.] Univ Washington, Seattle, WA 98195 USA.
RP Ioannou, GN (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Div Gastroenterol, Dept Med, 1660 South Columbian Way,S-111 Gastro, Seattle, WA 98108 USA.
EM georgei@medicine.washington.edu
FU Veterans Affairs Office of Research and Development; Health Resources
and Services Administration [231-00-0115]
FX This study was supported by the Research Enhancement Award Program of
the Veterans Affairs Office of Research and Development.; This research
is based on data derived from the United Network for Organ Sharing in
October 2011. This work was supported in part by Health Resources and
Services Administration contract 231-00-0115. The content is the
responsibility of the authors alone and does not necessarily reflect the
views or policies of the Department of Health and Human Services.
NR 16
TC 37
Z9 37
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1527-6465
J9 LIVER TRANSPLANT
JI Liver Transplant.
PD JUN
PY 2013
VL 19
IS 6
BP 634
EP 645
DI 10.1002/lt.23652
PG 12
WC Gastroenterology & Hepatology; Surgery; Transplantation
SC Gastroenterology & Hepatology; Surgery; Transplantation
GA 152FZ
UT WOS:000319518000010
PM 23536495
ER
PT J
AU Tewarie, NMSB
Burgers, IAV
Dawood, Y
den Boon, HC
den Brok, MGHE
Klunder, JH
Koopmans, KB
Rademaker, E
van den Broek, HB
van den Bersselaar, SM
Witjes, JJ
Van Noorden, CJF
Atai, NA
AF Tewarie, Nishita M. S. Baldewpersad
Burgers, Ilsa A. V.
Dawood, Yousif
den Boon, Hannah C.
den Brok, Melina G. H. E.
Klunder, Jet H.
Koopmans, Kristijn B.
Rademaker, Emma
van den Broek, Hans B.
van den Bersselaar, Sil M.
Witjes, Julia J.
Van Noorden, Cornelis J. F.
Atai, Nadia A.
TI NADP(+)-dependent IDH1(R132) mutation and its relevance for glioma
patient survival
SO MEDICAL HYPOTHESES
LA English
DT Article
ID ISOCITRATE DEHYDROGENASE 1; MGMT PROMOTER METHYLATION; HIGH-GRADE
GLIOMAS; IDH2 MUTATIONS; ONCOMETABOLITE 2-HYDROXYGLUTARATE; GENETIC
ALTERATIONS; MUTANT IDH1; IN-VIVO; GLIOBLASTOMA; CANCER
AB The isocitrate dehydrogenase 1 (IDH1) mutation occurs in high frequency in glioma and secondary glioblastoma (GBM). Mutated IDH1 produces the oncometabolite 2-hydroxyglutarate rather than a-ketoglutarate or isocitrate. The oncometabolite is considered to be the major cause of the association between the IDH1 mutation and gliomagenesis. On the other hand, the IDH1 mutation in GBM is associated with prolonged patient survival. This association is not well understood yet but IDH1 involvement in epigenetic silencing of O-6-methylguanine-DNA methyltransferase (MGMT), a DNA repair enzyme is considered to be an important mechanism. However, it was shown recently that the IDH1 mutation and MGMT silencing are independent prognostic factors. Here, we hypothesize that the IDH1 mutation reduces the capacity to produce NADPH and thus reduces the capacity to scavenge reactive oxygen species that are generated during irradiation and chemotherapy. IDH1 activity is responsible for two-thirds of the NADPH production capacity in normal brain, whereas the IDH1 mutation reduces this capacity by almost 40%. Therefore, we hypothesize that the reduced NADPH production capacity due to the IDH1 mutation renders GBM cells more vulnerable to irradiation and chemotherapy thus prolonging survival of the patients. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Tewarie, Nishita M. S. Baldewpersad; Burgers, Ilsa A. V.; Dawood, Yousif; den Boon, Hannah C.; den Brok, Melina G. H. E.; Klunder, Jet H.; Koopmans, Kristijn B.; Rademaker, Emma; van den Broek, Hans B.; van den Bersselaar, Sil M.; Witjes, Julia J.; Van Noorden, Cornelis J. F.; Atai, Nadia A.] Univ Amsterdam, Acad Med Ctr, Dept Cell Biol & Histol, NL-1105 AZ Amsterdam, Netherlands.
[Atai, Nadia A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Neurosci,Dept Neurol, Boston, MA 02129 USA.
RP Van Noorden, CJF (reprint author), Univ Amsterdam, Acad Med Ctr, Dept Cell Biol & Histol, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands.
FU Academic Medical Center (AMC)
FX For the preparation of the manuscript the authors wish to thank M.
Arendse. This study was supported by an Academic Medical Center (AMC)
scholarship (NAA).
NR 52
TC 8
Z9 8
U1 0
U2 18
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 JUN
PY 2013
VL 80
IS 6
BP 728
EP 731
DI 10.1016/j.mehy.2013.02.022
PG 4
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 153WZ
UT WOS:000319634800012
ER
PT J
AU Carbonell, CF
Chitnis, T
AF Carbonell, C. Fernandez
Chitnis, T.
TI Inflammatory demyelinating diseases in children: an update
SO MINERVA PEDIATRICA
LA English
DT Article
DE Child; Multiple sclerosis; Neuromyelitis optica; Encephalomyelitis
ID ACUTE DISSEMINATED ENCEPHALOMYELITIS; PEDIATRIC MULTIPLE-SCLEROSIS;
ACUTE TRANSVERSE MYELITIS; NEUROMYELITIS-OPTICA-IGG; TERM-FOLLOW-UP;
PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; CLINICALLY ISOLATED
SYNDROMES; EPSTEIN-BARR-VIRUS; B-CELL FOLLICLES; EARLY-ONSET
AB Inflammatory demyelinating diseases (DD) affecting the central nervous system (CNS) are increasingly recognized in children. During the past decade significant advances have been made in this field. Pediatric DD are important not just because 3-5% of MS cases are diagnosed in childhood, but also because their pathogenesis may provide unique insights into the earliest events and triggers of acquired CNS DD. The purpose of this article is to offer an update into pediatric DD for the general pediatrician and child neurologist. Current evidence on epidemiology, pathology, diagnosis, management and prognosis are reviewed for both monophasic (ADEM and CIS) and polyphasic/chronic DD (MS and NMO). We also review new research advances including novel biomarkers and treatments from the latest literature.
C1 [Carbonell, C. Fernandez; Chitnis, T.] Massachusetts Gen Hosp, Partners Pediat Multiple Sclerosis Ctr, Dept Child Neurol, Boston, MA 02114 USA.
[Carbonell, C. Fernandez; Chitnis, T.] Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA.
RP Chitnis, T (reprint author), 75 Fruit St,ACC708, Boston, MA 02114 USA.
EM tchitnis@partners.org
NR 199
TC 1
Z9 1
U1 2
U2 14
PU EDIZIONI MINERVA MEDICA
PI TURIN
PA CORSO BRAMANTE 83-85 INT JOURNALS DEPT., 10126 TURIN, ITALY
SN 0026-4946
EI 1827-1715
J9 MINERVA PEDIATR
JI Minerva Pediat.
PD JUN
PY 2013
VL 65
IS 3
BP 307
EP 323
PG 17
WC Pediatrics
SC Pediatrics
GA 152JS
UT WOS:000319528600007
ER
PT J
AU Abels, ER
van der Vos, KE
Skog, J
Hickman, SE
El Khoury, J
Breakefield, XO
AF Abels, Erik R.
van der Vos, Kristan E.
Skog, Johan
Hickman, Suzanne E.
El Khoury, Joseph
Breakefield, Xandra O.
TI Glioblastoma Transfer miRNAs into Microglial Cells through Extracellular
Vesicles
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 16th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 15-18, 2013
CL Salt Lake City, UT
SP Amer Soc Gene & Cell Therapy (ASGCT)
C1 [Abels, Erik R.; van der Vos, Kristan E.; Skog, Johan; Hickman, Suzanne E.; El Khoury, Joseph; Breakefield, Xandra O.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Skog, Johan] Columbia Univ, Med Ctr, Exosome Diagnost Inc, New York, NY 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 1525-0016
J9 MOL THER
JI Mol. Ther.
PD JUN
PY 2013
VL 21
SU 1
MA 304
BP S116
EP S117
PG 2
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 156XY
UT WOS:000319858400303
ER
PT J
AU Badr, CE
Amante, R
Van Hoppe, S
Tannous, BA
AF Badr, Christian E.
Amante, Romain
Van Hoppe, Stephanie
Tannous, Bakhos A.
TI An RNAi Screening Platform To Identify Modulators of Glioma Stem Cells
Viability and Differentiation
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 16th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 15-18, 2013
CL Salt Lake City, UT
SP Amer Soc Gene & Cell Therapy (ASGCT)
C1 [Badr, Christian E.; Amante, Romain; Van Hoppe, Stephanie; Tannous, Bakhos A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Badr, Christian E.; Tannous, Bakhos A.] Harvard Univ, Sch Med, Boston, MA 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 1525-0016
J9 MOL THER
JI Mol. Ther.
PD JUN
PY 2013
VL 21
SU 1
MA 458
BP S176
EP S176
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 156XY
UT WOS:000319858400457
ER
PT J
AU Golebiowski, D
van der Bom, IMJ
Kwon, CS
Maitland, S
Kuhn, AL
Bishop, N
Curren, E
Silva, N
Miller, A
Westmoreland, S
Gounis, M
Martin, DR
Asaad, W
Sena-Esteves, M
AF Golebiowski, Diane
van der Bom, Imramsjah M. J.
Kwon, Churl-Su
Maitland, Stacy
Kuehn, Anna Luisa
Bishop, Nina
Curren, Elizabeth
Silva, Nilsa
Miller, Andrew
Westmoreland, Susan
Gounis, Matthew
Martin, Douglas R.
Asaad, Wael
Sena-Esteves, Miguel
TI Safety Study of Intracranial AAVrh8-Mediated Gene Transfer of
beta-Hexosaminidase in Non-Human Primates
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 16th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 15-18, 2013
CL Salt Lake City, UT
SP Amer Soc Gene & Cell Therapy (ASGCT)
C1 [Golebiowski, Diane; van der Bom, Imramsjah M. J.; Maitland, Stacy; Kuehn, Anna Luisa; Bishop, Nina; Gounis, Matthew; Sena-Esteves, Miguel] Univ Massachusetts, Sch Med, Worcester, MA USA.
[Kwon, Churl-Su] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Curren, Elizabeth; Silva, Nilsa; Miller, Andrew; Westmoreland, Susan] Harvard Univ, Sch Med, New England Primate Res Ctr, Southborough, MA 01772 USA.
[Martin, Douglas R.] Auburn Univ, Scott Ritchey Res Ctr, Auburn, AL 36849 USA.
[Asaad, Wael] Rhode Isl Hosp, Providence, RI USA.
[Asaad, Wael] Brown Univ, Alpert Med Sch, Providence, RI 02912 USA.
RI Asaad, Wael/I-8485-2012
OI Asaad, Wael/0000-0003-4406-9096
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 1525-0016
J9 MOL THER
JI Mol. Ther.
PD JUN
PY 2013
VL 21
SU 1
MA 387
BP S149
EP S149
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 156XY
UT WOS:000319858400386
ER
PT J
AU Hudry, E
Dashkoff, J
Lee, A
Takeda, S
Koffie, RM
Hashimoto, T
Scheel, M
Spires-Jones, T
Arbel-Ornath, M
Betensky, RA
Davidson, BL
Hyman, BT
AF Hudry, Eloise
Dashkoff, Jonathan
Lee, Allyson
Takeda, Shuko
Koffie, Robert M.
Hashimoto, Tadafumi
Scheel, Maria
Spires-Jones, Tara
Arbel-Ornath, Michal
Betensky, Rebecca A.
Davidson, Beverly L.
Hyman, Bradley T.
TI Gene Transfer of Human Apoe epsilon 2 Alleviate the Progression of
Amyloid Deposition In Vivo
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 16th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 15-18, 2013
CL Salt Lake City, UT
SP Amer Soc Gene & Cell Therapy (ASGCT)
C1 [Hudry, Eloise; Dashkoff, Jonathan; Lee, Allyson; Takeda, Shuko; Koffie, Robert M.; Hashimoto, Tadafumi; Spires-Jones, Tara; Arbel-Ornath, Michal; Hyman, Bradley T.] Massachusetts Gen Hosp, Dept Neurol, MassGen Inst Neurodegenerat Dis, Charlestown, MA USA.
[Hudry, Eloise; Dashkoff, Jonathan; Lee, Allyson; Takeda, Shuko; Koffie, Robert M.; Hashimoto, Tadafumi; Spires-Jones, Tara; Arbel-Ornath, Michal; Hyman, Bradley T.] Harvard Univ, Sch Med, Charlestown, MA USA.
[Scheel, Maria; Davidson, Beverly L.] Univ Iowa, Dept Internal Med, Iowa City, IA 52242 USA.
[Scheel, Maria; Davidson, Beverly L.] Univ Iowa, Dept Neurol, Iowa City, IA 52242 USA.
[Scheel, Maria; Davidson, Beverly L.] Univ Iowa, Dept Physiol & Mol Biophys, Iowa City, IA USA.
[Betensky, Rebecca A.] Harvard Univ, Harvard Sch Publ Hlth, Boston, MA 02115 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 1525-0016
J9 MOL THER
JI Mol. Ther.
PD JUN
PY 2013
VL 21
SU 1
MA 283
BP S108
EP S108
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 156XY
UT WOS:000319858400282
ER
PT J
AU Lai, CP
Mardini, O
Maguire, CA
Tannous, BA
Breakefield, XO
AF Lai, Charles P.
Mardini, Osama
Maguire, Casey A.
Tannous, Bakhos A.
Breakefield, Xandra O.
TI Non-Invasive In Vivo Imaging, Biodistribution and Clearance Analyses of
Intravenously Administered Extracellular Vesicles
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 16th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 15-18, 2013
CL Salt Lake City, UT
SP Amer Soc Gene & Cell Therapy (ASGCT)
C1 [Lai, Charles P.; Mardini, Osama; Maguire, Casey A.; Tannous, Bakhos A.; Breakefield, Xandra O.] Massachusetts Gen Hosp, Charlestown, MA USA.
[Lai, Charles P.; Mardini, Osama; Maguire, Casey A.; Tannous, Bakhos A.; Breakefield, Xandra O.] Harvard Univ, Neurosci Program, Sch Med, Charlestown, MA 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 1525-0016
J9 MOL THER
JI Mol. Ther.
PD JUN
PY 2013
VL 21
SU 1
MA 103
BP S42
EP S43
PG 2
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 156XY
UT WOS:000319858400104
ER
PT J
AU Maguire, CA
Crommentuijn, MHW
Mu, DK
Hudry, E
Serrano-Pozo, A
Hyman, B
Tannous, BA
AF Maguire, Casey A.
Crommentuijn, Matheus H. W.
Mu, Dakai
Hudry, Eloise
Serrano-Pozo, Alberto
Hyman, Bradley
Tannous, Bakhos A.
TI Mouse Gender Influences Brain Expression of a Reporter Gene by
Intravascularly-Administered AAV9
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 16th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 15-18, 2013
CL Salt Lake City, UT
SP Amer Soc Gene & Cell Therapy (ASGCT)
C1 [Maguire, Casey A.; Crommentuijn, Matheus H. W.; Tannous, Bakhos A.] Massachusetts Gen Hosp, Dept Neurol, Expt Therapeut & Mol Imaging Lab, Charlestown, MA USA.
[Maguire, Casey A.; Mu, Dakai; Hudry, Eloise; Serrano-Pozo, Alberto; Hyman, Bradley; Tannous, Bakhos A.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA.
[Crommentuijn, Matheus H. W.] Vrije Univ Amsterdam, Med Ctr, Canc Ctr Amsterdam, Neurooncol Res Grp,Dept Neurosurg, Amterstam, Netherlands.
[Mu, Dakai; Hudry, Eloise; Serrano-Pozo, Alberto; Hyman, Bradley] Massachusetts Gen Hosp, Charlestown, MA USA.
[Tannous, Bakhos A.] Massachusetts Gen Hosp, Dept Radiol, Ctr Mol Imaging Res, 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 1525-0016
J9 MOL THER
JI Mol. Ther.
PD JUN
PY 2013
VL 21
SU 1
MA 540
BP S208
EP S208
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 156XY
UT WOS:000319858400539
ER
PT J
AU Taherian, M
Prabhakar, S
Fulci, G
Sena-Esteves, M
Breakefield, XO
Brenner, GJ
AF Taherian, Mehran
Prabhakar, Shilpa
Fulci, Giulia
Sena-Esteves, Miguel
Breakefield, Xandra O.
Brenner, Gary J.
TI Mechanisms of Caspase-1 Mediated Schwannoma Regression
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 16th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 15-18, 2013
CL Salt Lake City, UT
SP Amer Soc Gene & Cell Therapy (ASGCT)
C1 [Taherian, Mehran; Prabhakar, Shilpa; Fulci, Giulia; Breakefield, Xandra O.; Brenner, Gary J.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Sena-Esteves, Miguel] U Mass Med Sch, Worcester, MA USA.
[Prabhakar, Shilpa; Breakefield, Xandra O.] Harvard Univ, Sch Med, Program Neurosci, 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 1525-0016
J9 MOL THER
JI Mol. Ther.
PD JUN
PY 2013
VL 21
SU 1
MA 286
BP S109
EP S109
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 156XY
UT WOS:000319858400285
ER
PT J
AU Tsai, SQ
Reyon, D
Khayter, C
Joung, JK
AF Tsai, Shengdar Q.
Reyon, Deepak
Khayter, Cyd
Joung, J. Keith
TI Precise Modification of Human Genes Directed by Single-Stranded DNA
Oligonucleotides and TALENs
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 16th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 15-18, 2013
CL Salt Lake City, UT
SP Amer Soc Gene & Cell Therapy (ASGCT)
C1 [Tsai, Shengdar Q.; Reyon, Deepak; Khayter, Cyd; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Mol Pathol Unit, Charlestown, MA USA.
[Tsai, Shengdar Q.; Reyon, Deepak; Khayter, Cyd; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA USA.
[Tsai, Shengdar Q.; Reyon, Deepak; Joung, J. Keith] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 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 1525-0016
J9 MOL THER
JI Mol. Ther.
PD JUN
PY 2013
VL 21
SU 1
MA 490
BP S189
EP S189
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 156XY
UT WOS:000319858400489
ER
PT J
AU Turunen, HT
Velez, MVL
Shelke, R
Xiao, R
Bennett, J
Vandenberghe, LH
AF Turunen, Heikki T.
Velez, Maria Victoria Luna
Shelke, Rajani
Xiao, Ru
Bennett, Jean
Vandenberghe, Luk H.
TI Comparing Dual AAV Vector Strategy Efficiencies for Gene Therapy In
Vitro and In Vivo
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 16th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 15-18, 2013
CL Salt Lake City, UT
SP Amer Soc Gene & Cell Therapy (ASGCT)
C1 [Turunen, Heikki T.; Shelke, Rajani; Xiao, Ru; Vandenberghe, Luk H.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst, Boston, MA USA.
[Velez, Maria Victoria Luna] Radboud Univ Nijmegen, NL-6525 ED Nijmegen, Netherlands.
[Velez, Maria Victoria Luna; Bennett, Jean] Univ Penn, Sch Med, Scheie Eye Inst, FM Kirby Ctr Mol Ophthalmol, Philadelphia, PA 19104 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 1525-0016
J9 MOL THER
JI Mol. Ther.
PD JUN
PY 2013
VL 21
SU 1
MA 330
BP S127
EP S127
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 156XY
UT WOS:000319858400329
ER
PT J
AU van Rijn, S
Nilsson, J
Noske, DP
Vandertop, WP
Tannous, BA
Wurdinger, T
AF van Rijn, Sjoerd
Nilsson, Jonas
Noske, David P.
Vandertop, W. Peter
Tannous, Bakhos A.
Wuerdinger, Thomas
TI Transcription Factor Activity Analysis Using a Functional Multiplex
Gaussia Luciferase-Based Reporter Assay
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 16th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 15-18, 2013
CL Salt Lake City, UT
SP Amer Soc Gene & Cell Therapy (ASGCT)
C1 [van Rijn, Sjoerd; Nilsson, Jonas; Noske, David P.; Vandertop, W. Peter; Wuerdinger, Thomas] Vrije Univ Amsterdam, Med Ctr, Neurooncol Res Grp, Amsterdam, Netherlands.
[Nilsson, Jonas] Umea Univ, Dept Radiat Sci, Umea, Sweden.
[Tannous, Bakhos A.; Wuerdinger, Thomas] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 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 1525-0016
J9 MOL THER
JI Mol. Ther.
PD JUN
PY 2013
VL 21
SU 1
MA 321
BP S123
EP S124
PG 2
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 156XY
UT WOS:000319858400320
ER
PT J
AU Charvet, L
Serafin, D
Vazquez, K
Ackerson, J
Braaten, E
Brown, T
O'Donnell, E
Parrish, J
Preston, T
Zaccariello, M
Belman, A
Casper, C
Chitnis, T
Gorman, M
Julian, L
Ness, J
Patterson, M
Rodriguez, M
Waubant, E
Weinstock-Guttman, B
Yeh, A
Benedict, R
Krupp, L
AF Charvet, L.
Serafin, D.
Vazquez, K.
Ackerson, J.
Braaten, E.
Brown, T.
O'Donnell, E.
Parrish, J.
Preston, T.
Zaccariello, M.
Belman, A.
Casper, C.
Chitnis, T.
Gorman, M.
Julian, L.
Ness, J.
Patterson, M.
Rodriguez, M.
Waubant, E.
Weinstock-Guttman, B.
Yeh, A.
Benedict, R.
Krupp, L.
TI Longitudinal Evaluation of Cognitive Impairment in Pediatric MS
SO MULTIPLE SCLEROSIS JOURNAL
LA English
DT Meeting Abstract
CT 2nd Conference of the International-MS-Cognition-Society (IMSCOGS )
CY JUN 28-29, 2013
CL Zurich, SWITZERLAND
SP Int MS Cognit Soc
C1 [Charvet, L.; Serafin, D.; Vazquez, K.; Preston, T.; Belman, A.; Krupp, L.] SUNY Stony Brook, Stony Brook, NY 11794 USA.
[Ackerson, J.; Ness, J.] Univ Alabama, Tuscaloosa, AL USA.
[Parrish, J.; Weinstock-Guttman, B.; Benedict, R.] SUNY Buffalo, Buffalo, NY 14260 USA.
[Braaten, E.; O'Donnell, E.; Chitnis, T.; Gorman, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Brown, T.; Zaccariello, M.; Patterson, M.; Rodriguez, M.] Mayo Clin, Rochester, MN USA.
[Casper, C.] Univ Utah, Salt Lake City, UT USA.
[Julian, L.; Waubant, E.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Yeh, A.] Hosp Sick Children, Toronto, ON M5G 1X8, Canada.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1352-4585
J9 MULT SCLER J
JI Mult. Scler. J.
PD JUN
PY 2013
VL 19
IS 7
MA 8
BP 972
EP 972
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 152YK
UT WOS:000319567900033
ER
PT J
AU Adamala, K
Szostak, JW
AF Adamala, Katarzyna
Szostak, Jack W.
TI Competition between model protocells driven by an encapsulated catalyst
SO NATURE CHEMISTRY
LA English
DT Article
ID SELF-REPRODUCTION; VESICLES; LIFE; MEMBRANES; CELL; CHEMISTRY;
LIPOSOMES; ORIGIN
AB The advent of Darwinian evolution required the emergence of molecular mechanisms for the heritable variation of fitness. One model for such a system involves competing protocell populations, each consisting of a replicating genetic polymer within a replicating vesicle. In this model, each genetic polymer imparts a selective advantage to its protocell by, for example, coding for a catalyst that generates a useful metabolite. Here, we report a partial model of such nascent evolutionary traits in a system that consists of fatty-acid vesicles containing a dipeptide catalyst, which catalyses the formation of a second dipeptide. The newly formed dipeptide binds to vesicle membranes, which imparts enhanced affinity for fatty acids and thus promotes vesicle growth. The catalysed dipeptide synthesis proceeds with higher efficiency in vesicles than in free solution, which further enhances fitness. Our observations suggest that, in a replicating protocell with an RNA genome, ribozyme-catalysed peptide synthesis might have been sufficient to initiate Darwinian evolution.
C1 [Adamala, Katarzyna; Szostak, Jack W.] Massachusetts Gen Hosp, Dept Mol Biol, Howard Hughes Med Inst, Boston, MA 02114 USA.
[Adamala, Katarzyna; Szostak, Jack W.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA.
[Adamala, Katarzyna] Univ Roma Tre, Dipartimento Biol, Rome, Italy.
RP Szostak, JW (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Howard Hughes Med Inst, Boston, MA 02114 USA.
EM szostak@molbio.mgh.harvard.edu
OI Adamala, Kate/0000-0003-1066-7207
FU National Aeronautics and Space Administration Exobiology [NNX07AJ09G]
FX J.W.S. is an Investigator of the Howard Hughes Medical Institute. This
work was supported in part by National Aeronautics and Space
Administration Exobiology grant NNX07AJ09G. We thank A. Engelhart, C.
Hentrich, I. Budin and R. Wieczorek for discussions and help with
manuscript preparation.
NR 24
TC 52
Z9 58
U1 8
U2 101
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1755-4330
J9 NAT CHEM
JI Nat. Chem.
PD JUN
PY 2013
VL 5
IS 6
BP 495
EP 501
DI 10.1038/NCHEM.1650
PG 7
WC Chemistry, Multidisciplinary
SC Chemistry
GA 150QC
UT WOS:000319404900012
PM 23695631
ER
PT J
AU Lonsdale, J
Thomas, J
Salvatore, M
Phillips, R
Lo, E
Shad, S
Hasz, R
Walters, G
Garcia, F
Young, N
Foster, B
Moser, M
Karasik, E
Gillard, B
Ramsey, K
Sullivan, S
Bridge, J
Magazine, H
Syron, J
Fleming, J
Siminoff, L
Traino, H
Mosavel, M
Barker, L
Jewell, S
Rohrer, D
Maxim, D
Filkins, D
Harbach, P
Cortadillo, E
Berghuis, B
Turner, L
Hudson, E
Feenstra, K
Sobin, L
Robb, J
Branton, P
Korzeniewski, G
Shive, C
Tabor, D
Qi, LQ
Groch, K
Nampally, S
Buia, S
Zimmerman, A
Smith, A
Burges, R
Robinson, K
Valentino, K
Bradbury, D
Cosentino, M
Diaz-Mayoral, N
Kennedy, M
Engel, T
Williams, P
Erickson, K
Ardlie, K
Winckler, W
Getz, G
DeLuca, D
MacArthur, D
Kellis, M
Thomson, A
Young, T
Gelfand, E
Donovan, M
Meng, Y
Grant, G
Mash, D
Marcus, Y
Basile, M
Liu, J
Zhu, J
Tu, ZD
Cox, NJ
Nicolae, DL
Gamazon, ER
Im, HK
Konkashbaev, A
Pritchard, J
Stevens, M
Flutre, T
Wen, XQ
Dermitzakis, ET
Lappalainen, T
Guigo, R
Monlong, J
Sammeth, M
Koller, D
Battle, A
Mostafavi, S
McCarthy, M
Rivas, M
Maller, J
Rusyn, I
Nobel, A
Wright, F
Shabalin, A
Feolo, M
Sharopova, N
Sturcke, A
Paschal, J
Anderson, JM
Wilder, EL
Derr, LK
Green, ED
Struewing, JP
Temple, G
Volpi, S
Boyer, JT
Thomson, EJ
Guyer, MS
Ng, C
Abdallah, A
Colantuoni, D
Insel, TR
Koester, SE
Little, AR
Bender, PK
Lehner, T
Yao, Y
Compton, CC
Vaught, JB
Sawyer, S
Lockhart, NC
Demchok, J
Moore, HF
AF Lonsdale, John
Thomas, Jeffrey
Salvatore, Mike
Phillips, Rebecca
Lo, Edmund
Shad, Saboor
Hasz, Richard
Walters, Gary
Garcia, Fernando
Young, Nancy
Foster, Barbara
Moser, Mike
Karasik, Ellen
Gillard, Bryan
Ramsey, Kimberley
Sullivan, Susan
Bridge, Jason
Magazine, Harold
Syron, John
Fleming, Johnelle
Siminoff, Laura
Traino, Heather
Mosavel, Maghboeba
Barker, Laura
Jewell, Scott
Rohrer, Dan
Maxim, Dan
Filkins, Dana
Harbach, Philip
Cortadillo, Eddie
Berghuis, Bree
Turner, Lisa
Hudson, Eric
Feenstra, Kristin
Sobin, Leslie
Robb, James
Branton, Phillip
Korzeniewski, Greg
Shive, Charles
Tabor, David
Qi, Liqun
Groch, Kevin
Nampally, Sreenath
Buia, Steve
Zimmerman, Angela
Smith, Anna
Burges, Robin
Robinson, Karna
Valentino, Kim
Bradbury, Deborah
Cosentino, Mark
Diaz-Mayoral, Norma
Kennedy, Mary
Engel, Theresa
Williams, Penelope
Erickson, Kenyon
Ardlie, Kristin
Winckler, Wendy
Getz, Gad
DeLuca, David
MacArthur, Daniel
Kellis, Manolis
Thomson, Alexander
Young, Taylor
Gelfand, Ellen
Donovan, Molly
Meng, Yan
Grant, George
Mash, Deborah
Marcus, Yvonne
Basile, Margaret
Liu, Jun
Zhu, Jun
Tu, Zhidong
Cox, Nancy J.
Nicolae, Dan L.
Gamazon, Eric R.
Im, Hae Kyung
Konkashbaev, Anuar
Pritchard, Jonathan
Stevens, Matthew
Flutre, Timothee
Wen, Xiaoquan
Dermitzakis, Emmanouil T.
Lappalainen, Tuuli
Guigo, Roderic
Monlong, Jean
Sammeth, Michael
Koller, Daphne
Battle, Alexis
Mostafavi, Sara
McCarthy, Mark
Rivas, Manual
Maller, Julian
Rusyn, Ivan
Nobel, Andrew
Wright, Fred
Shabalin, Andrey
Feolo, Mike
Sharopova, Nataliya
Sturcke, Anne
Paschal, Justin
Anderson, James M.
Wilder, Elizabeth L.
Derr, Leslie K.
Green, Eric D.
Struewing, Jeffery P.
Temple, Gary
Volpi, Simona
Boyer, Joy T.
Thomson, Elizabeth J.
Guyer, Mark S.
Cathy Ng
Abdallah, Assya
Colantuoni, Deborah
Insel, Thomas R.
Koester, Susan E.
Little, A. Roger
Bender, Patrick K.
Lehner, Thomas
Yao, Yin
Compton, Carolyn C.
Vaught, Jimmie B.
Sawyer, Sherilyn
Lockhart, Nicole C.
Demchok, Joanne
Moore, Helen F.
TI The Genotype-Tissue Expression (GTEx) project
SO NATURE GENETICS
LA English
DT Editorial Material
ID GENOME-WIDE ASSOCIATION; HUMAN GENE-EXPRESSION; DISEASE
AB Genome-wide association studies have identified thousands of loci for common diseases, but, for the majority of these, the mechanisms underlying disease susceptibility remain unknown. Most associated variants are not correlated with protein-coding changes, suggesting that polymorphisms in regulatory regions probably contribute to many disease phenotypes. Here we describe the Genotype-Tissue Expression (GTEx) project, which will establish a resource database and associated tissue bank for the scientific community to study the relationship between genetic variation and gene expression in human tissues.
C1 [Lonsdale, John; Thomas, Jeffrey; Salvatore, Mike; Phillips, Rebecca; Lo, Edmund; Shad, Saboor] Natl Dis Res Interchange, Philadelphia, PA USA.
[Hasz, Richard] Gift Life Donor Program, Philadelphia, PA USA.
[Walters, Gary] LifeNet Hlth, Virginia Beach, VA USA.
[Garcia, Fernando] Drexel Univ, Coll Med, Philadelphia, PA 19104 USA.
[Young, Nancy] Albert Einstein Med Ctr, Philadelphia, PA 19141 USA.
[Foster, Barbara; Moser, Mike; Karasik, Ellen; Gillard, Bryan; Ramsey, Kimberley] Roswell Pk Canc Inst, Buffalo, NY 14263 USA.
[Sullivan, Susan; Bridge, Jason] Upstate New York Transplant Serv, Buffalo, NY USA.
[Magazine, Harold; Syron, John; Fleming, Johnelle] Sci Care Inc, Phoenix, AZ USA.
[Siminoff, Laura; Traino, Heather; Mosavel, Maghboeba; Barker, Laura] Virginia Commonwealth Univ, Richmond, VA USA.
[Jewell, Scott; Rohrer, Dan; Maxim, Dan; Filkins, Dana; Harbach, Philip; Cortadillo, Eddie; Berghuis, Bree; Turner, Lisa; Hudson, Eric; Feenstra, Kristin] Van Andel Inst, Grand Rapids, MI USA.
[Sobin, Leslie; Robb, James; Branton, Phillip; Korzeniewski, Greg; Shive, Charles; Tabor, David; Qi, Liqun; Groch, Kevin; Nampally, Sreenath; Buia, Steve; Zimmerman, Angela; Smith, Anna; Burges, Robin; Robinson, Karna; Valentino, Kim; Bradbury, Deborah; Cosentino, Mark; Diaz-Mayoral, Norma; Kennedy, Mary; Engel, Theresa; Williams, Penelope] SAIC Frederick Inc, Frederick, MD USA.
[Erickson, Kenyon] Sapient Govt Serv, Arlington, VA USA.
[Ardlie, Kristin; Winckler, Wendy; Getz, Gad; DeLuca, David; MacArthur, Daniel; Kellis, Manolis; Thomson, Alexander; Young, Taylor; Gelfand, Ellen; Donovan, Molly; Meng, Yan; Grant, George] Broad Inst Harvard & MIT, Cambridge, MA USA.
[Getz, Gad; MacArthur, Daniel] Massachusetts Gen Hosp, Res Ctr, Boston, MA 02114 USA.
[Kellis, Manolis] MIT, Cambridge, MA 02139 USA.
[Mash, Deborah; Marcus, Yvonne; Basile, Margaret] Univ Miami, Sch Med, Miami, FL USA.
[Liu, Jun] Harvard Univ, Boston, MA 02115 USA.
[Zhu, Jun; Tu, Zhidong] Mt Sinai Sch Med, New York, NY USA.
[Cox, Nancy J.; Nicolae, Dan L.; Gamazon, Eric R.; Im, Hae Kyung; Konkashbaev, Anuar; Pritchard, Jonathan; Stevens, Matthew; Flutre, Timothee; Wen, Xiaoquan] Univ Chicago, Chicago, IL 60637 USA.
[Pritchard, Jonathan] Univ Chicago, Howard Hughes Med Inst, Chicago, IL 60637 USA.
[Dermitzakis, Emmanouil T.; Lappalainen, Tuuli] Univ Geneva, Geneva, Switzerland.
[Guigo, Roderic; Monlong, Jean; Sammeth, Michael] Ctr Genom Regulat, Barcelona, Spain.
[Koller, Daphne; Battle, Alexis; Mostafavi, Sara] Stanford Univ, Palo Alto, CA 94304 USA.
[McCarthy, Mark; Rivas, Manual; Maller, Julian] Univ Oxford, Oxford, England.
[Rusyn, Ivan; Nobel, Andrew; Wright, Fred; Shabalin, Andrey] Univ N Carolina, Chapel Hill, NC USA.
[Feolo, Mike; Sharopova, Nataliya; Sturcke, Anne; Paschal, Justin; Anderson, James M.; Wilder, Elizabeth L.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
[Derr, Leslie K.] NIH, Div Program Coordinat Planning & Strateg Initiat, Off Strateg Coordinat Common Fund, Off Director, Bethesda, MD 20892 USA.
[Green, Eric D.; Struewing, Jeffery P.; Temple, Gary; Volpi, Simona; Boyer, Joy T.; Thomson, Elizabeth J.; Guyer, Mark S.; Cathy Ng; Abdallah, Assya; Colantuoni, Deborah] NHGRI, Bethesda, MD 20892 USA.
[Insel, Thomas R.; Koester, Susan E.; Little, A. Roger; Bender, Patrick K.; Lehner, Thomas; Yao, Yin] NIMH, Bethesda, MD 20892 USA.
[Compton, Carolyn C.; Vaught, Jimmie B.; Sawyer, Sherilyn; Lockhart, Nicole C.; Demchok, Joanne; Moore, Helen F.] NCI, Bethesda, MD 20892 USA.
RP Getz, G (reprint author), Broad Inst Harvard & MIT, Cambridge, MA USA.
EM winckler@broadinstitute.org; gadgetz@broadinstitute.org;
struewij@mail.nih.gov
RI Sammeth, Michael/C-1157-2014; Little, A/O-6191-2014; Guigo,
Roderic/D-1303-2010; Rusyn, Ivan/S-2426-2016; Struewing,
Jeffery/I-7502-2013;
OI Sammeth, Michael/0000-0002-6528-9883; Little, A/0000-0001-6831-0177;
Guigo, Roderic/0000-0002-5738-4477; Maller, Julian/0000-0002-1565-9559;
Gamazon, Eric/0000-0003-4204-8734; Struewing,
Jeffery/0000-0002-4848-3334; Shabalin, Andrey/0000-0003-0309-6821;
Lappalainen, Tuuli/0000-0002-7746-8109; Monlong,
Jean/0000-0002-9737-5516; Wen, Xiaoquan/0000-0001-8990-2737
NR 18
TC 420
Z9 421
U1 8
U2 44
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 JUN
PY 2013
VL 45
IS 6
BP 580
EP 585
DI 10.1038/ng.2653
PG 6
WC Genetics & Heredity
SC Genetics & Heredity
GA 152XA
UT WOS:000319563900002
ER
PT J
AU den Hoed, M
Eijgelsheim, M
Esko, T
Brundel, BJJM
Peal, DS
Evans, DM
Nolte, IM
Segre, AV
Holm, H
Handsaker, RE
Westra, HJ
Johnson, T
Isaacs, A
Yang, J
Lundby, A
Zhao, JH
Kim, YJ
Go, MJ
Almgren, P
Bochud, M
Boucher, G
Cornelis, MC
Gudbjartsson, D
Hadley, D
van der Harst, P
Hayward, C
den Heijer, M
Igl, W
Jackson, AU
Kutalik, Z
Luan, J
Kemp, JP
Kristiansson, K
Ladenvall, C
Lorentzon, M
Montasser, ME
Njajou, OT
O'Reilly, PF
Padmanabhan, S
Pourcain, BS
Rankinen, T
Salo, P
Tanaka, T
Timpson, NJ
Vitart, V
Waite, L
Wheeler, W
Zhang, WH
Draisma, HHM
Feitosa, MF
Kerr, KF
Lind, PA
Mihailov, E
Onland-Moret, NC
Song, C
Weedon, MN
Xie, WJ
Yengo, L
Absher, D
Albert, CM
Alonso, A
Arking, DE
de Bakker, PIW
Balkau, B
Barlassina, C
Benaglio, P
Bis, JC
Bouatia-Naji, N
Brage, S
Chanock, SJ
Chines, PS
Chung, M
Darbar, D
Dina, C
Dorr, M
Elliott, P
Felix, SB
Fischer, K
Fuchsberger, C
de Geus, EJC
Goyette, P
Gudnason, V
Harris, TB
Hartikainen, AL
Havulinna, AS
Heckbert, SR
Hicks, AA
Hofman, A
Holewijn, S
Hoogstra-Berends, F
Hottenga, JJ
Jensen, MK
Johansson, A
Junttila, J
Kaab, S
Kanon, B
Ketkar, S
Khaw, KT
Knowles, JW
Kooner, AS
Kors, JA
Kumari, M
Milani, L
Laiho, P
Lakatta, EG
Langenberg, C
Leusink, M
Liu, YM
Luben, RN
Lunetta, KL
Lynch, SN
Markus, MRP
Marques-Vidal, P
Leach, IM
McArdle, WL
McCarroll, SA
Medland, SE
Miller, KA
Montgomery, GW
Morrison, AC
Muller-Nurasyid, M
Navarro, P
Nelis, M
O'Connell, JR
O'Donnell, CJ
Ong, KK
Newman, AB
Peters, A
Polasek, O
Pouta, A
Pramstaller, PP
Psaty, BM
Rao, DC
Ring, SM
Rossin, EJ
Rudan, D
Sanna, S
Scott, RA
Sehmi, JS
Sharp, S
Shin, JT
Singleton, AB
Smith, AV
Soranzo, N
Spector, TD
Stewart, C
Stringham, HM
Tarasov, KV
Uitterlinden, AG
Vandenput, L
Hwang, SJ
Whitfield, JB
Wijmenga, C
Wild, SH
Willemsen, G
Wilson, JF
Witteman, JCM
Wong, A
Wong, QN
Jamshidi, Y
Zitting, P
Boer, JMA
Boomsma, DI
Borecki, IB
van Duijn, CM
Ekelund, U
Forouhi, NG
Froguel, P
Hingorani, A
Ingelsson, E
Kivimaki, M
Kronmal, RA
Kuh, D
Lind, L
Martin, NG
Oostra, BA
Pedersen, NL
Quertermous, T
Rotter, JI
van der Schouw, YT
Verschuren, WMM
Walker, M
Albanes, D
Arnar, DO
Assimes, TL
Bandinelli, S
Boehnke, M
de Boer, RA
Bouchard, C
Caulfield, WLM
Chambers, JC
Curhan, G
Cusi, D
Eriksson, J
Ferrucci, L
van Gilst, WH
Glorioso, N
de Graaf, J
Groop, L
Gyllensten, U
Hsueh, WC
Hu, FB
Huikuri, HV
Hunter, DJ
Iribarren, C
Isomaa, B
Jarvelin, MR
Jula, A
Kahonen, M
Kiemeney, LA
van der Klauw, MM
Kooner, JS
Kraft, P
Iacoviello, L
Lehtimaki, T
Lokki, MLL
Mitchell, BD
Navis, G
Nieminen, MS
Ohlsson, C
Poulter, NR
Qi, L
Raitakari, OT
Rimm, EB
Rioux, JD
Rizzi, F
Rudan, I
Salomaa, V
Sever, PS
Shields, DC
Shuldiner, AR
Sinisalo, J
Stanton, AV
Stolk, RP
Strachan, DP
Tardif, JC
Thorsteinsdottir, U
Tuomilehto, J
van Veldhuisen, DJ
Virtamo, J
Viikari, J
Vollenweider, P
Waeber, G
Widen, E
Cho, YS
Olsen, JV
Visscher, PM
Willer, C
Franke, L
Erdmann, J
Thompson, JR
Pfeufer, A
Sotoodehnia, N
Newton-Cheh, C
Ellinor, PT
Stricker, BHC
Metspalu, A
Perola, M
Beckmann, JS
Smith, GD
Stefansson, K
Wareham, NJ
Munroe, PB
Sibon, OCM
Milan, DJ
Snieder, H
Samani, NJ
Loos, RJF
AF den Hoed, Marcel
Eijgelsheim, Mark
Esko, Tonu
Brundel, Bianca J. J. M.
Peal, David S.
Evans, David M.
Nolte, Ilja M.
Segre, Ayellet V.
Holm, Hilma
Handsaker, Robert E.
Westra, Harm-Jan
Johnson, Toby
Isaacs, Aaron
Yang, Jian
Lundby, Alicia
Zhao, Jing Hua
Kim, Young Jin
Go, Min Jin
Almgren, Peter
Bochud, Murielle
Boucher, Gabrielle
Cornelis, Marilyn C.
Gudbjartsson, Daniel
Hadley, David
van der Harst, Pim
Hayward, Caroline
den Heijer, Martin
Igl, Wilmar
Jackson, Anne U.
Kutalik, Zoltan
Luan, Jian'an
Kemp, John P.
Kristiansson, Kati
Ladenvall, Claes
Lorentzon, Mattias
Montasser, May E.
Njajou, Omer T.
O'Reilly, Paul F.
Padmanabhan, Sandosh
Pourcain, Beate St.
Rankinen, Tuomo
Salo, Perttu
Tanaka, Toshiko
Timpson, Nicholas J.
Vitart, Veronique
Waite, Lindsay
Wheeler, William
Zhang, Weihua
Draisma, Harmen H. M.
Feitosa, Mary F.
Kerr, Kathleen F.
Lind, Penelope A.
Mihailov, Evelin
Onland-Moret, N. Charlotte
Song, Ci
Weedon, Michael N.
Xie, Weijia
Yengo, Loic
Absher, Devin
Albert, Christine M.
Alonso, Alvaro
Arking, Dan E.
de Bakker, Paul I. W.
Balkau, Beverley
Barlassina, Cristina
Benaglio, Paola
Bis, Joshua C.
Bouatia-Naji, Nabila
Brage, Soren
Chanock, Stephen J.
Chines, Peter S.
Chung, Mina
Darbar, Dawood
Dina, Christian
Doerr, Marcus
Elliott, Paul
Felix, Stephan B.
Fischer, Krista
Fuchsberger, Christian
de Geus, Eco J. C.
Goyette, Philippe
Gudnason, Vilmundur
Harris, Tamara B.
Hartikainen, Anna-Liisa
Havulinna, Aki S.
Heckbert, Susan R.
Hicks, Andrew A.
Hofman, Albert
Holewijn, Suzanne
Hoogstra-Berends, Femke
Hottenga, Jouke-Jan
Jensen, Majken K.
Johansson, Asa
Junttila, Juhani
Kaeaeb, Stefan
Kanon, Bart
Ketkar, Shamika
Khaw, Kay-Tee
Knowles, Joshua W.
Kooner, Angrad S.
Kors, Jan A.
Kumari, Meena
Milani, Lili
Laiho, Paeivi
Lakatta, Edward G.
Langenberg, Claudia
Leusink, Maarten
Liu, Yongmei
Luben, Robert N.
Lunetta, Kathryn L.
Lynch, Stacey N.
Markus, Marcello R. P.
Marques-Vidal, Pedro
Leach, Irene Mateo
McArdle, Wendy L.
McCarroll, Steven A.
Medland, Sarah E.
Miller, Kathryn A.
Montgomery, Grant W.
Morrison, Alanna C.
Mueller-Nurasyid, Martina
Navarro, Pau
Nelis, Mari
O'Connell, Jeffrey R.
O'Donnell, Christopher J.
Ong, Ken K.
Newman, Anne B.
Peters, Annette
Polasek, Ozren
Pouta, Anneli
Pramstaller, Peter P.
Psaty, Bruce M.
Rao, Dabeeru C.
Ring, Susan M.
Rossin, Elizabeth J.
Rudan, Diana
Sanna, Serena
Scott, Robert A.
Sehmi, Jaban S.
Sharp, Stephen
Shin, Jordan T.
Singleton, Andrew B.
Smith, Albert V.
Soranzo, Nicole
Spector, Tim D.
Stewart, Chip
Stringham, Heather M.
Tarasov, Kirill V.
Uitterlinden, Andre G.
Vandenput, Liesbeth
Hwang, Shih-Jen
Whitfield, John B.
Wijmenga, Cisca
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Willemsen, Gonneke
Wilson, James F.
Witteman, Jacqueline C. M.
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Wong, Quenna
Jamshidi, Yalda
Zitting, Paavo
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Boomsma, Dorret I.
Borecki, Ingrid B.
van Duijn, Cornelia M.
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Hingorani, Aroon
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Kivimaki, Mika
Kronmal, Richard A.
Kuh, Diana
Lind, Lars
Martin, Nicholas G.
Oostra, Ben A.
Pedersen, Nancy L.
Quertermous, Thomas
Rotter, Jerome I.
van der Schouw, Yvonne T.
Verschuren, W. M. Monique
Walker, Mark
Albanes, Demetrius
Arnar, David O.
Assimes, Themistocles L.
Bandinelli, Stefania
Boehnke, Michael
de Boer, Rudolf A.
Bouchard, Claude
Caulfield, W. L. Mark
Chambers, John C.
Curhan, Gary
Cusi, Daniele
Eriksson, Johan
Ferrucci, Luigi
van Gilst, Wiek H.
Glorioso, Nicola
de Graaf, Jacqueline
Groop, Leif
Gyllensten, Ulf
Hsueh, Wen-Chi
Hu, Frank B.
Huikuri, Heikki V.
Hunter, David J.
Iribarren, Carlos
Isomaa, Bo
Jarvelin, Marjo-Riitta
Jula, Antti
Kahonen, Mika
Kiemeney, Lambertus A.
van der Klauw, Melanie M.
Kooner, Jaspal S.
Kraft, Peter
Iacoviello, Licia
Lehtimaki, Terho
Lokki, Marja-Liisa L.
Mitchell, Braxton D.
Navis, Gerjan
Nieminen, Markku S.
Ohlsson, Claes
Poulter, Neil R.
Qi, Lu
Raitakari, Olli T.
Rimm, Eric B.
Rioux, John D.
Rizzi, Federica
Rudan, Igor
Salomaa, Veikko
Sever, Peter S.
Shields, Denis C.
Shuldiner, Alan R.
Sinisalo, Juha
Stanton, Alice V.
Stolk, Ronald P.
Strachan, David P.
Tardif, Jean-Claude
Thorsteinsdottir, Unnur
Tuomilehto, Jaako
van Veldhuisen, Dirk J.
Virtamo, Jarmo
Viikari, Jorma
Vollenweider, Peter
Waeber, Gerard
Widen, Elisabeth
Cho, Yoon Shin
Olsen, Jesper V.
Visscher, Peter M.
Willer, Cristen
Franke, Lude
Erdmann, Jeanette
Thompson, John R.
Pfeufer, Arne
Sotoodehnia, Nona
Newton-Cheh, Christopher
Ellinor, Patrick T.
Stricker, Bruno H. Ch
Metspalu, Andres
Perola, Markus
Beckmann, Jacques S.
Smith, George Davey
Stefansson, Kari
Wareham, Nicholas J.
Munroe, Patricia B.
Sibon, Ody C. M.
Milan, David J.
Snieder, Harold
Samani, Nilesh J.
Loos, Ruth J. F.
CA Global BPgen Consortium
CARDIoGRAM Consortium
PR GWGWAS Consortium
QRS GWGWAS Consortium
QT-IGCGC Consortium
CHARGE-AF Consortium
TI Identification of heart rate-associated loci and their effects on
cardiac conduction and rhythm disorders
SO NATURE GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; COMMON VARIANTS; SUSCEPTIBILITY LOCI;
ATRIAL-FIBRILLATION; QRS DURATION; QT INTERVAL; PR INTERVAL; DISEASE;
DROSOPHILA; LIBRARY
AB Elevated resting heart rate is associated with greater risk of cardiovascular disease and mortality. In a 2-stage meta-analysis of genome-wide association studies in up to 181,171 individuals, we identified 14 new loci associated with heart rate and confirmed associations with all 7 previously established loci. Experimental downregulation of gene expression in Drosophila melanogaster and Danio rerio identified 20 genes at 11 loci that are relevant for heart rate regulation and highlight a role for genes involved in signal transmission, embryonic cardiac development and the pathophysiology of dilated cardiomyopathy, congenital heart failure and/or sudden cardiac death. In addition, genetic susceptibility to increased heart rate is associated with altered cardiac conduction and reduced risk of sick sinus syndrome, and both heart rate-increasing and heart rate-decreasing variants associate with risk of atrial fibrillation. Our findings provide fresh insights into the mechanisms regulating heart rate and identify new therapeutic targets.
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[Jarvelin, Marjo-Riitta] Univ Oulu, Inst Hlth Sci, Oulu, Finland.
[Jula, Antti] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Turku, Finland.
[Kahonen, Mika; Lehtimaki, Terho] Univ Tampere, Dept Clin Chem, FIN-33101 Tampere, Finland.
[Kahonen, Mika; Lehtimaki, Terho] Tampere Univ Hosp, Tampere, Finland.
[Kiemeney, Lambertus A.] Radboud Univ Nijmegen, Med Ctr, Dept Hlth Evidence, NL-6525 ED Nijmegen, Netherlands.
[Kiemeney, Lambertus A.] Radboud Univ Nijmegen, Med Ctr, Dept Urol, NL-6525 ED Nijmegen, Netherlands.
[van der Klauw, Melanie M.] Univ Groningen, Univ Med Ctr Groningen, Dept Endocrinol, Groningen, Netherlands.
[Iacoviello, Licia] Catholic Univ, Fdn Ric Cura Giovanni Paolo 2, Campobasso, Italy.
[Lokki, Marja-Liisa L.] Univ Helsinki, Haartman Inst, Transplantat Lab, Helsinki, Finland.
[Navis, Gerjan] Univ Groningen, Univ Med Ctr Groningen, Dept Internal Med, Groningen, Netherlands.
[Nieminen, Markku S.; Sinisalo, Juha] Univ Helsinki, Cent Hosp, Div Cardiol, Dept Med, Helsinki, Finland.
[Poulter, Neil R.; Sever, Peter S.] Univ London Imperial Coll Sci Technol & Med, ICCH, London, England.
[Raitakari, Olli T.] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland.
[Raitakari, Olli T.] Univ Turku, Dept Clin Physiol & Nucl Med, Turku, Finland.
[Raitakari, Olli T.; Viikari, Jorma] Turku Univ Hosp, Turku, Finland.
[Rizzi, Federica] Kos Genet, Milan, Italy.
[Shields, Denis C.] Univ Coll Dublin, Complex & Adapt Syst Lab, Dublin 2, Ireland.
[Shields, Denis C.] Univ Coll Dublin, Conway Inst Biomol & Biomed Res, Dublin 2, Ireland.
[Shields, Denis C.] Univ Coll Dublin, Sch Med & Med Sci, Dublin 2, Ireland.
[Shuldiner, Alan R.] Vet Adm Med Ctr, Geriatr Res & Educ Clin Ctr, Baltimore, MD 21218 USA.
[Stanton, Alice V.] Royal Coll Surgeons Ireland, Dublin 2, Ireland.
[Tuomilehto, Jaako] Natl Inst Hlth & Welf, Diabet Unit, Helsinki, Finland.
Danube Univ Krems, Ctr Vasc Prevent, Krems, Austria.
Hosp Univ La Paz, Grp RD06 0014 0015, Red RECAVA, Madrid, Spain.
[Tuomilehto, Jaako] King Abdulaziz Univ, Jeddah 21413, Saudi Arabia.
[Viikari, Jorma] Univ Turku, Dept Med, Turku, Finland.
[Vollenweider, Peter; Waeber, Gerard] Univ Lausanne Hosp, Dept Internal Med, Lausanne, Switzerland.
[Widen, Elisabeth] Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland.
[Cho, Yoon Shin] Hallym Univ, Dept Biomed Sci, Chunchon, South Korea.
[Visscher, Peter M.] Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia.
[Willer, Cristen] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA.
[Franke, Lude] Queen Mary Univ London, Barts & London Sch Med & Dent, Blizard Inst Cell & Mol Sci, London, England.
[Erdmann, Jeanette] Med Univ Lubeck, Inst Integrat & Expt Gen, D-23538 Lubeck, Germany.
[Erdmann, Jeanette] DZHK, Lubeck, Germany.
[Thompson, John R.] Univ Leicester, Dept Hlth Sci, Leicester, Leics, England.
[Pfeufer, Arne] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Human Genet, Munich, Germany.
[Pfeufer, Arne] Tech Univ Munich, Klinikum Rechts Isar, Inst Human Genet, D-80290 Munich, Germany.
[Sotoodehnia, Nona] Univ Washington, Sch Med, Div Cardiol, Dept Med, Seattle, WA USA.
[Newton-Cheh, Christopher] Massachusetts Gen Hosp, Cardiovacular Res Ctr, Ctr Human Genet Res, Boston, MA 02114 USA.
[Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA.
[Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA.
[Stricker, Bruno H. Ch] Inspectorate Hlth Care, The Hague, Netherlands.
[Beckmann, Jacques S.] CHUV Univ Hosp, Serv Med Genet, Lausanne, Switzerland.
[Milan, David J.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Samani, Nilesh J.] Univ Leicester, Glenfield Hosp, Dept Cardiovasc Sci, Leicester, Leics, England.
[Samani, Nilesh J.] Glenfield Hosp, NIHR Leicester Biomed Res Unit Cardiovasc, Leicester, Leics, England.
[Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY USA.
[Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY USA.
[Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY USA.
RP Loos, RJF (reprint author), Addenbrookes Hosp, Inst Metab Sci, Epidemiol Unit, MRC, Cambridge, England.
EM ruth.loos@mssm.edu
RI Wijmenga, Cisca/D-2173-2009; Lundby, Alicia/H-3322-2013; Evans,
David/H-6325-2013; Lind, Penelope/B-2553-2009; Colaus,
PsyColaus/K-6607-2013; Stanton, Alice/F-4697-2012; de Bakker,
Paul/B-8730-2009; van der Klauw, Melanie/A-2138-2014; Kiemeney,
Lambertus/D-3357-2009; Singleton, Andrew/C-3010-2009; Pfeufer,
Arne/B-6634-2013; van Veldhuisen, Dirk Jan/E-8967-2014; Erdmann,
Jeanette/P-7513-2014; Marques-Vidal, Pedro/C-9449-2009; Franke,
Lude/P-7036-2016; Fox, Laura /C-6249-2016; Padmanabhan,
Sandosh/S-3963-2016; Wong, Andrew/M-8899-2016; Kerr,
Kathleen/A-2893-2013; Davey Smith, George/A-7407-2013; Beckmann, Jacques
S /A-9772-2008; Yengo, Loic/D-2692-2017; Feitosa, Mary/K-8044-2012;
Hicks, Andrew/E-9518-2017; Graaf, J./H-8038-2014; Wilson, James
F/A-5704-2009; Polasek, Ozren/B-6002-2011; Montgomery,
Grant/B-7148-2008; Alonso, Alvaro/A-4917-2010; Johansson,
Asa/G-5270-2011; Peters, Annette/A-6117-2011; Bouchard,
Claude/A-7637-2009; Rudan, Igor/I-1467-2012; Smith, Albert/K-5150-2015;
Yang, Jian/A-5852-2010; Bochud, Murielle/A-3981-2010; Hayward,
Caroline/M-8818-2016; BOUATIA-NAJI, NABILA/D-5863-2013; van der Schouw,
Yvonne/F-8327-2014; Pramstaller, Peter/C-2357-2008; Newman,
Anne/C-6408-2013; Medland, Sarah/C-7630-2013; Albanes,
Demetrius/B-9749-2015; Darbar, Dawood/C-9079-2015; Dina,
Christian/D-3535-2015; Milani, Lili/C-8759-2011; Rioux,
John/A-9599-2015; Onland-Moret, N. Charlotte/G-9185-2011; Gudnason,
Vilmundur/K-6885-2015
OI de Bakker, Paul/0000-0001-7735-7858; van der Klauw,
Melanie/0000-0001-7178-009X; Kiemeney, Lambertus/0000-0002-2368-1326;
Markus, Marcello Ricardo Paulista/0000-0002-6234-4955; Navarro,
Pau/0000-0001-5576-8584; Iacoviello, Licia/0000-0003-0514-5885;
Visscher, Peter/0000-0002-2143-8760; Eriksson,
Johan/0000-0002-2516-2060; Kemp, John/0000-0002-9105-2249; Evans,
David/0000-0003-0663-4621; Mitchell, Braxton/0000-0003-4920-4744;
Timpson, Nicholas/0000-0002-7141-9189; Sinisalo,
Juha/0000-0002-0169-5137; de Geus, Eco/0000-0001-6022-2666; Martin,
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Olsen, Jesper/0000-0002-4747-4938; Luben, Robert/0000-0002-5088-6343;
Jamshidi, Yalda/0000-0003-0151-6482; Soranzo,
Nicole/0000-0003-1095-3852; Wijmenga, Cisca/0000-0002-5635-1614; St
Pourcain, Beate/0000-0002-4680-3517; Kumari, Meena/0000-0001-9716-1035;
Forouhi, Nita/0000-0002-5041-248X; Jarvelin,
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Johnson, Toby/0000-0002-5998-3270; Fuchsberger,
Christian/0000-0002-5918-8947; Padmanabhan, Sandosh/0000-0003-3869-5808;
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Alice/0000-0002-4961-165X; Esko, Tonu/0000-0003-1982-6569; Kristiansson,
Kati/0000-0003-4688-107X; Bouatia-Naji, Nabila/0000-0001-5424-2134;
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Wong, Andrew/0000-0003-2079-4779; Davey Smith,
George/0000-0002-1407-8314; Beckmann, Jacques S /0000-0002-9741-1900;
Yengo, Loic/0000-0002-4272-9305; Feitosa, Mary/0000-0002-0933-2410;
Hicks, Andrew/0000-0001-6320-0411; Lunetta, Kathryn/0000-0002-9268-810X;
Song, Ci/0000-0002-0947-9068; Kivimaki, Mika/0000-0002-4699-5627;
Wilson, James F/0000-0001-5751-9178; Polasek, Ozren/0000-0002-5765-1862;
Montgomery, Grant/0000-0002-4140-8139; Alonso,
Alvaro/0000-0002-2225-8323; Johansson, Asa/0000-0002-2915-4498; Rudan,
Igor/0000-0001-6993-6884; Smith, Albert/0000-0003-1942-5845; Yang,
Jian/0000-0003-2001-2474; Bochud, Murielle/0000-0002-5727-0218; Hayward,
Caroline/0000-0002-9405-9550; van der Schouw,
Yvonne/0000-0002-4605-435X; Newman, Anne/0000-0002-0106-1150; Medland,
Sarah/0000-0003-1382-380X; Darbar, Dawood/0000-0002-4103-5977; Dina,
Christian/0000-0002-7722-7348; Milani, Lili/0000-0002-5323-3102; Rioux,
John/0000-0001-7560-8326; Gudnason, Vilmundur/0000-0001-5696-0084
FU British Heart Foundation [PG/12/38/29615]; Chief Scientist Office
[CZB/4/710]; Medical Research Council [G0401527, G0600705, G0801056,
G1000143, G1002084, G9815508, MC_PC_15018, MC_PC_U127592696,
MC_U106179471, MC_U106179472, MC_U106179473, MC_U106188470,
MC_U123092720, MC_U127592696, MC_UP_A100_1003, MC_UU_12013/1,
MC_UU_12013/3, MC_UU_12013/4]; NCATS NIH HHS [UL1 TR000124]; NHLBI NIH
HHS [K24 HL105780, R00 HL094535, R01 HL090620, R01 HL092217, R01
HL105756, R01 HL111314, U19 HL065962]; NIDA NIH HHS [R21 DA026982];
NIDDK NIH HHS [P30 DK020572, P30 DK063491]; NIGMS NIH HHS [T32
GM007753]; Wellcome Trust [092731]
NR 47
TC 72
Z9 72
U1 2
U2 67
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 JUN
PY 2013
VL 45
IS 6
BP 621
EP +
DI 10.1038/ng.2610
PG 14
WC Genetics & Heredity
SC Genetics & Heredity
GA 152XA
UT WOS:000319563900009
PM 23583979
ER
PT J
AU Monda, KL
Chen, GK
Taylor, KC
Palmer, C
Edwards, TL
Lange, LA
Ng, MCY
Adeyemo, AA
Allison, MA
Bielak, LF
Chen, GJ
Graff, M
Irvin, MR
Rhie, SK
Li, G
Liu, YM
Liu, YF
Lu, YC
Nalls, MA
Sun, YV
Wojczynski, MK
Yanek, LR
Aldrich, MC
Ademola, A
Amos, CI
Bandera, EV
Bock, CH
Britton, A
Broeckel, U
Cai, QY
Caporaso, NE
Carlson, CS
Carpten, J
Casey, G
Chen, WM
Chen, F
Chen, YDI
Chiang, CWK
Coetzee, GA
Demerath, E
Deming-Halverson, SL
Driver, RW
Dubbert, P
Feitosa, MF
Feng, Y
Freedman, BI
Gillanders, EM
Gottesman, O
Guo, XQ
Haritunians, T
Harris, T
Harris, CC
Hennis, AJM
Hernandez, DG
McNeill, LH
Howard, TD
Howard, BV
Howard, VJ
Johnson, KC
Kang, SJ
Keating, BJ
Kolb, S
Kuller, LH
Kutlar, A
Langefeld, CD
Lettre, G
Lohman, K
Lotay, V
Lyon, H
Manson, JE
Maixner, W
Meng, YA
Monroe, KR
Morhason-Bello, I
Murphy, AB
Mychaleckyj, JC
Nadukuru, R
Nathanson, KL
Nayak, U
N'Diaye, A
Nemesure, B
Wu, SY
Leske, MC
Neslund-Dudas, C
Neuhouser, M
Nyante, S
Ochs-Balcom, H
Ogunniyi, A
Ogundiran, TO
Ojengbede, O
Olopade, OI
Palmer, JR
Ruiz-Narvaez, EA
Palmer, ND
Press, MF
Rampersaud, E
Rasmussen-Torvik, LJ
Rodriguez-Gil, JL
Salako, B
Schadt, EE
Schwartz, AG
Shriner, DA
Siscovick, D
Smith, SB
Wassertheil-Smoller, S
Speliotes, EK
Spitz, MR
Sucheston, L
Taylor, H
Tayo, BO
Tucker, MA
Van Den Berg, DJ
Edwards, DRV
Wang, Z
Wiencke, JK
Winkler, TW
Witte, JS
Wrensch, M
Wu, XF
Yang, JJ
Levin, AM
Young, TR
Zakai, NA
Cushman, M
Zanetti, KA
Zhao, JH
Zhao, W
Zheng, YL
Zhou, J
Ziegler, RG
Zmuda, JM
Fernandes, JK
Gilkeson, GS
Kamen, DL
Hunt, KJ
Spruill, IJ
Ambrosone, CB
Ambs, S
Arnett, DK
Atwood, L
Becker, DM
Berndt, SI
Bernstein, L
Blot, WJ
Borecki, IB
Bottinger, EP
Bowden, DW
Burke, G
Chanock, SJ
Cooper, RS
Ding, JZ
Duggan, D
Evans, MK
Fox, C
Garvey, WT
Bradfield, JP
Hakonarson, H
Grant, SFA
Hsing, A
Chu, L
Hu, JJ
Huo, DZ
Ingles, SA
John, EM
Jordan, JM
Kabagambe, EK
Kardia, SLR
Kittles, RA
Goodman, PJ
Klein, EA
Kolonel, LN
Le Marchand, L
Liu, SM
McKnight, B
Millikan, RC
Mosley, TH
Padhukasahasram, B
Williams, LK
Patel, SR
Peters, U
Pettaway, CA
Peyser, PA
Psaty, BM
Redline, S
Rotimi, CN
Rybicki, BA
Sale, MM
Schreiner, PJ
Signorello, LB
Singleton, AB
Stanford, JL
Strom, SS
Thun, MJ
Vitolins, M
Zheng, W
Moore, JH
Williams, SM
Ketkar, S
Zhu, XF
Zonderman, AB
Kooperberg, C
Papanicolaou, GJ
Henderson, BE
Reiner, AP
Hirschhorn, JN
Loos, RJF
North, KE
Haiman, CA
AF Monda, Keri L.
Chen, Gary K.
Taylor, Kira C.
Palmer, Cameron
Edwards, Todd L.
Lange, Leslie A.
Ng, Maggie C. Y.
Adeyemo, Adebowale A.
Allison, Matthew A.
Bielak, Lawrence F.
Chen, Guanjie
Graff, Mariaelisa
Irvin, Marguerite R.
Rhie, Suhn K.
Li, Guo
Liu, Yongmei
Liu, Youfang
Lu, Yingchang
Nalls, Michael A.
Sun, Yan V.
Wojczynski, Mary K.
Yanek, Lisa R.
Aldrich, Melinda C.
Ademola, Adeyinka
Amos, Christopher I.
Bandera, Elisa V.
Bock, Cathryn H.
Britton, Angela
Broeckel, Ulrich
Cai, Quiyin
Caporaso, Neil E.
Carlson, Chris S.
Carpten, John
Casey, Graham
Chen, Wei-Min
Chen, Fang
Chen, Yii-Der I.
Chiang, Charleston W. K.
Coetzee, Gerhard A.
Demerath, Ellen
Deming-Halverson, Sandra L.
Driver, Ryan W.
Dubbert, Patricia
Feitosa, Mary F.
Feng, Ye
Freedman, Barry I.
Gillanders, Elizabeth M.
Gottesman, Omri
Guo, Xiuqing
Haritunians, Talin
Harris, Tamara
Harris, Curtis C.
Hennis, Anselm J. M.
Hernandez, Dena G.
McNeill, Lorna H.
Howard, Timothy D.
Howard, Barbara V.
Howard, Virginia J.
Johnson, Karen C.
Kang, Sun J.
Keating, Brendan J.
Kolb, Suzanne
Kuller, Lewis H.
Kutlar, Abdullah
Langefeld, Carl D.
Lettre, Guillaume
Lohman, Kurt
Lotay, Vaneet
Lyon, Helen
Manson, Joann E.
Maixner, William
Meng, Yan A.
Monroe, Kristine R.
Morhason-Bello, Imran
Murphy, Adam B.
Mychaleckyj, Josyf C.
Nadukuru, Rajiv
Nathanson, Katherine L.
Nayak, Uma
N'Diaye, Amidou
Nemesure, Barbara
Wu, Suh-Yuh
Leske, M. Cristina
Neslund-Dudas, Christine
Neuhouser, Marian
Nyante, Sarah
Ochs-Balcom, Heather
Ogunniyi, Adesola
Ogundiran, Temidayo O.
Ojengbede, Oladosu
Olopade, Olufunmilayo I.
Palmer, Julie R.
Ruiz-Narvaez, Edward A.
Palmer, Nicholette D.
Press, Michael F.
Rampersaud, Evandine
Rasmussen-Torvik, Laura J.
Rodriguez-Gil, Jorge L.
Salako, Babatunde
Schadt, Eric E.
Schwartz, Ann G.
Shriner, Daniel A.
Siscovick, David
Smith, Shad B.
Wassertheil-Smoller, Sylvia
Speliotes, Elizabeth K.
Spitz, Margaret R.
Sucheston, Lara
Taylor, Herman
Tayo, Bamidele O.
Tucker, Margaret A.
Van Den Berg, David J.
Edwards, Digna R. Velez
Wang, Zhaoming
Wiencke, John K.
Winkler, Thomas W.
Witte, John S.
Wrensch, Margaret
Wu, Xifeng
Yang, James J.
Levin, Albert M.
Young, Taylor R.
Zakai, Neil A.
Cushman, Mary
Zanetti, Krista A.
Zhao, Jing Hua
Zhao, Wei
Zheng, Yonglan
Zhou, Jie
Ziegler, Regina G.
Zmuda, Joseph M.
Fernandes, Jyotika K.
Gilkeson, Gary S.
Kamen, Diane L.
Hunt, Kelly J.
Spruill, Ida J.
Ambrosone, Christine B.
Ambs, Stefan
Arnett, Donna K.
Atwood, Larry
Becker, Diane M.
Berndt, Sonja I.
Bernstein, Leslie
Blot, William J.
Borecki, Ingrid B.
Bottinger, Erwin P.
Bowden, Donald W.
Burke, Gregory
Chanock, Stephen J.
Cooper, Richard S.
Ding, Jingzhong
Duggan, David
Evans, Michele K.
Fox, Caroline
Garvey, W. Timothy
Bradfield, Jonathan P.
Hakonarson, Hakon
Grant, Struan F. A.
Hsing, Ann
Chu, Lisa
Hu, Jennifer J.
Huo, Dezheng
Ingles, Sue A.
John, Esther M.
Jordan, Joanne M.
Kabagambe, Edmond K.
Kardia, Sharon L. R.
Kittles, Rick A.
Goodman, Phyllis J.
Klein, Eric A.
Kolonel, Laurence N.
Le Marchand, Loic
Liu, Simin
McKnight, Barbara
Millikan, Robert C.
Mosley, Thomas H.
Padhukasahasram, Badri
Williams, L. Keoki
Patel, Sanjay R.
Peters, Ulrike
Pettaway, Curtis A.
Peyser, Patricia A.
Psaty, Bruce M.
Redline, Susan
Rotimi, Charles N.
Rybicki, Benjamin A.
Sale, Michele M.
Schreiner, Pamela J.
Signorello, Lisa B.
Singleton, Andrew B.
Stanford, Janet L.
Strom, Sara S.
Thun, Michael J.
Vitolins, Mara
Zheng, Wei
Moore, Jason H.
Williams, Scott M.
Ketkar, Shamika
Zhu, Xiaofeng
Zonderman, Alan B.
Kooperberg, Charles
Papanicolaou, George J.
Henderson, Brian E.
Reiner, Alex P.
Hirschhorn, Joel N.
Loos, Ruth J. F.
North, Kari E.
Haiman, Christopher A.
CA NABEC Consortium
UKBECEC Consortium
BioBank Japan Project
AGEN Consortium
TI A meta-analysis identifies new loci associated with body mass index in
individuals of African ancestry
SO NATURE GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; MULTILOCUS GENOTYPE DATA; COMMON VARIANTS;
POSITIVE SELECTION; SEQUENCE VARIANTS; HUMAN-POPULATIONS;
GENETIC-VARIATION; ADULT OBESITY; FTO GENE; RISK
AB Genome-wide association studies (GWAS) have identified 36 loci associated with body mass index (BMI), predominantly in populations of European ancestry. We conducted a meta-analysis to examine the association of >3.2 million SNPs with BMI in 39,144 men and women of African ancestry and followed up the most significant associations in an additional 32,268 individuals of African ancestry. We identified one new locus at 5q33 (GALNT10, rs7708584, P = 3.4 x 10(-11)) and another at 7p15 when we included data from the GIANT consortium (MIR148A-NFE2L3, rs10261878, P = 1.2 x 10(-10)). We also found suggestive evidence of an association at a third locus at 6q16 in the African-ancestry sample (KLHL32, rs974417, P = 6.9 x 10(-8)). Thirty-two of the 36 previously established BMI variants showed directionally consistent effect estimates in our GWAS (binomial P = 9.7 x 10(-7)), five of which reached genome-wide significance. These findings provide strong support for shared BMI loci across populations, as well as for the utility of studying ancestrally diverse populations.
C1 [Monda, Keri L.] Amgen Inc, Ctr Observat Res, Thousand Oaks, CA 91320 USA.
[Taylor, Kira C.; Graff, Mariaelisa; North, Kari E.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27515 USA.
[Chen, Gary K.; Rhie, Suhn K.; Casey, Graham; Coetzee, Gerhard A.; Feng, Ye; Monroe, Kristine R.; Van Den Berg, David J.; Ingles, Sue A.; Henderson, Brian E.; Haiman, Christopher A.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Taylor, Kira C.] Univ Louisville, Dept Epidemiol & Populat Hlth, Louisville, KY 40292 USA.
[Palmer, Cameron; Hirschhorn, Joel N.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA.
[Palmer, Cameron; Hirschhorn, Joel N.] Childrens Hosp, Div Genet, Boston, MA 02115 USA.
[Palmer, Cameron; Hirschhorn, Joel N.] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.
[Edwards, Todd L.] Vanderbilt Univ, Dept Med, Vanderbilt Epidemiol Ctr, Ctr Human Genet Res, Nashville, TN USA.
[Lange, Leslie A.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
[Ng, Maggie C. Y.; Palmer, Nicholette D.; Shriner, Daniel A.; Zhou, Jie; Bowden, Donald W.] Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC USA.
[Ng, Maggie C. Y.; Howard, Timothy D.; Palmer, Nicholette D.; Bowden, Donald W.] Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC USA.
[Adeyemo, Adebowale A.; Chen, Guanjie; Rotimi, Charles N.] NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA.
[Allison, Matthew A.] Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA.
[Bielak, Lawrence F.] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
[Howard, Virginia J.; Arnett, Donna K.] Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA.
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[Liu, Yongmei] Wake Forest Sch Med, Div Publ Hlth Sci, Dept Epidemiol & Prevent, Winston Salem, NC USA.
[Liu, Youfang; Jordan, Joanne M.] Univ N Carolina, Thurston Arthrit Res Ctr, Chapel Hill, NC USA.
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[Hennis, Anselm J. M.] Univ W Indies, Chron Dis Res Ctr, Bridgetown, Barbados.
[Hennis, Anselm J. M.] Univ W Indies, Fac Med Sci, Bridgetown, Barbados.
[Hennis, Anselm J. M.] Minist Hlth, Bridgetown, Barbados.
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[Neuhouser, Marian] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98104 USA.
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[Ochs-Balcom, Heather] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA.
[Ogunniyi, Adesola; Salako, Babatunde] Univ Ibadan, Dept Med, Ibadan, Nigeria.
[Olopade, Olufunmilayo I.; Zheng, Yonglan] Univ Chicago, Dept Med, Chicago, IL 60637 USA.
[Palmer, Julie R.; Ruiz-Narvaez, Edward A.] Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA.
[Press, Michael F.] Univ So Calif, Keck Sch Med, Dept Pathol, Los Angeles, CA 90033 USA.
[Rampersaud, Evandine] Univ Miami, Miller Sch Med, Dept Human Genet, Miami, FL 33136 USA.
[Rasmussen-Torvik, Laura J.] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA.
[Rodriguez-Gil, Jorge L.; Hu, Jennifer J.] Univ Miami, Miller Sch Med, Dept Epidemiol & Publ Hlth, Miami, FL 33136 USA.
[Rodriguez-Gil, Jorge L.; Hu, Jennifer J.] Univ Miami, Miller Sch Med, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA.
[Schadt, Eric E.] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY USA.
[Schadt, Eric E.] Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, New York, NY USA.
[Siscovick, David] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Wassertheil-Smoller, Sylvia] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA.
[Speliotes, Elizabeth K.] Univ Michigan, Div Gastroenterol, Dept Internal Med, Ann Arbor, MI 48109 USA.
[Speliotes, Elizabeth K.] Univ Michigan, Ctr Computat Med & Bioinformat, Ann Arbor, MI 48109 USA.
[Speliotes, Elizabeth K.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA.
[Speliotes, Elizabeth K.; Young, Taylor R.] Broad Inst, Cambridge, MA USA.
[Spitz, Margaret R.] Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA.
[Sucheston, Lara; Ambrosone, Christine B.] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA.
[Taylor, Herman; Mosley, Thomas H.] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA.
[Tayo, Bamidele O.; Cooper, Richard S.] Loyola Univ, Chicago Stritch Sch Med, Dept Prevent Med & Epidemiol, Maywood, IL 60153 USA.
[Edwards, Digna R. Velez] Vanderbilt Univ, Vanderbilt Epidemiol Ctr, Ctr Human Genet Res, Nashville, TN USA.
[Edwards, Digna R. Velez] Vanderbilt Univ, Vanderbilt Epidemiol Ctr, Dept Obstet & Gynecol, Nashville, TN USA.
[Wang, Zhaoming] NCI, Core Genotype Facil, SAIC Frederick, Frederick, MD 21701 USA.
[Wiencke, John K.; Wrensch, Margaret] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA.
[Wiencke, John K.; Wrensch, Margaret] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA USA.
[Winkler, Thomas W.] Univ Regensburg, Inst Epidemiol & Prevent Med, Dept Genet Epidemiol, D-93053 Regensburg, Germany.
[Witte, John S.] Univ Calif San Francisco, Inst Human Genet, Dept Epidemiol & Biostatist, San Francisco, CA 94143 USA.
[Zakai, Neil A.; Cushman, Mary] Univ Vermont, Coll Med, Dept Med, Burlington, VT 05405 USA.
[Zhao, Jing Hua; Loos, Ruth J. F.] Addenbrookes Hosp, Med Res Council Epidemiol Unit, Cambridge, England.
[Zhao, Wei; Kardia, Sharon L. R.; Peyser, Patricia A.] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
[Fernandes, Jyotika K.; Gilkeson, Gary S.; Kamen, Diane L.; Hunt, Kelly J.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA.
[Spruill, Ida J.] Med Univ S Carolina, Coll Nursing, Charleston, SC 29425 USA.
[Atwood, Larry] Boston Univ, Sch Med, Framingham Heart Study, Boston, MA 02118 USA.
[Bernstein, Leslie] City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Divis Canc Etiol, Duarte, CA USA.
[Blot, William J.] Int Epidemiol Inst, Rockville, MD USA.
[Burke, Gregory; Vitolins, Mara] Wake Forest Univ, Bowman Gray Sch Med, Div Publ Hlth Sci, Winston Salem, NC USA.
[Ding, Jingzhong] Wake Forest Sch Med, Dept Internal Med, Sect Gerontol & Geriatr Med, Winston Salem, NC USA.
[Evans, Michele K.] NIA, Hlth Dispar Res Sect, Lab Populat Sci, NIH, Baltimore, MD 21224 USA.
[Fox, Caroline] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Fox, Caroline] NHLBI, Ctr Populat Studies, Framingham, MA USA.
[Fox, Caroline] Brigham & Womens Hosp, Div Endocrinol, Boston, MA 02115 USA.
[Fox, Caroline] Harvard Univ, Sch Med, Boston, MA USA.
[Garvey, W. Timothy] Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA.
[Garvey, W. Timothy] Birmingham VA Med Ctr, Birmingham, MA USA.
[Bradfield, Jonathan P.; Hakonarson, Hakon; Grant, Struan F. A.] Childrens Hosp Philadelphia, Ctr Appl Genom, Res Inst, Philadelphia, PA 19104 USA.
[Bradfield, Jonathan P.; Hakonarson, Hakon; Grant, Struan F. A.] Childrens Hosp Philadelphia, Res Inst, Div Human Genet, Philadelphia, PA 19104 USA.
[Hakonarson, Hakon; Grant, Struan F. A.] Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Hakonarson, Hakon; Grant, Struan F. A.] Univ Penn, Inst Diabet Obes & Metab, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Hsing, Ann; John, Esther M.] Canc Prevent Inst Calif, Fremont, CA USA.
[Hsing, Ann; John, Esther M.] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Div Epidemiol, Stanford, CA USA.
[Hsing, Ann; Chu, Lisa; John, Esther M.] Stanford Univ, Sch Med, Stanford Canc Inst, Stanford, CA USA.
[Huo, Dezheng] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA.
[Kittles, Rick A.] Univ Chicago, Dept Med, Chicago, IL 60637 USA.
[Goodman, Phyllis J.] SWOG Stat Ctr, Southwest Oncol Grp, Seattle, WA USA.
[Klein, Eric A.] Cleveland Clin, Glickman Urol & Kidney Inst, Cleveland, OH 44106 USA.
[Kolonel, Laurence N.; Le Marchand, Loic] Univ Hawaii, Ctr Canc, Epidemiol Program, Honolulu, HI 96822 USA.
[Liu, Simin] Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90024 USA.
[McKnight, Barbara] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Padhukasahasram, Badri; Williams, L. Keoki] Henry Ford Hlth Syst, Ctr Hlth Policy & Hlth Serv Res, Detroit, MI USA.
[Williams, L. Keoki] Henry Ford Hlth Syst, Dept Internal Med, Detroit, MI USA.
[Patel, Sanjay R.] Brigham & Womens Hosp, Div Sleep Med, Boston, MA 02115 USA.
[Pettaway, Curtis A.] Univ Texas MD Anderson Canc Ctr, Dept Urol, Houston, TX 77030 USA.
[Psaty, Bruce M.] Univ Washington, Dept Epidemiol & Hlth Serv, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Grp Hlth Res Inst, Grp Hlth Cooperat, Seattle, WA USA.
[Redline, Susan] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Sale, Michele M.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA.
[Sale, Michele M.] Univ Virginia, Dept Med, Charlottesville, VA USA.
[Sale, Michele M.] Univ Virginia, Dept Biochem & Mol Genet, Charlottesville, VA USA.
[Signorello, Lisa B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Moore, Jason H.; Williams, Scott M.] Dartmouth Coll, Geisel Sch Med, Inst Quantitat Biomed Sci, Lebanon, NH 03756 USA.
[Moore, Jason H.; Williams, Scott M.] Dartmouth Coll, Geisel Sch Med, Dept Genet, Lebanon, NH 03756 USA.
[Moore, Jason H.] Dartmouth Coll, Geisel Sch Med, Dept Community & Family Med, Lebanon, NH 03756 USA.
[Ketkar, Shamika] Washington Univ, Human & Stat Genet Program, Div Biol & Biomed Sci, St Louis, MO USA.
[Zhu, Xiaofeng] Case Western Reserve Univ, Dept Epidemiol & Biostatist, Cleveland, OH 44106 USA.
[Zonderman, Alan B.] NIA, Behav Epidemiol Sect, Lab Populat Sci, NIH, Baltimore, MD USA.
[Papanicolaou, George J.] NHLBI, Div Prevent & Populat Sci, NIH, Bethesda, MD 20892 USA.
[Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY USA.
[Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY USA.
RP North, KE (reprint author), Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27515 USA.
EM kari_north@unc.edu; haiman@usc.edu
RI Singleton, Andrew/C-3010-2009; Liu, Simin/I-3689-2014; Bandera,
Elisa/M-4169-2014; Tucker, Margaret/B-4297-2015; Feitosa,
Mary/K-8044-2012;
OI Zonderman, Alan B/0000-0002-6523-4778; Liu, Simin/0000-0003-2098-3844;
Patel, Sanjay/0000-0002-9142-5172; Chiang,
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Bandera, Elisa/0000-0002-8789-2755; Feitosa, Mary/0000-0002-0933-2410;
Ruiz-Narvaez, Edward/0000-0002-0339-5824; Palmer,
Julie/0000-0002-6534-335X; Nathanson, Katherine/0000-0002-6740-0901;
Adeyemo, Adebowale/0000-0002-3105-3231
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NR 48
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Z9 81
U1 1
U2 43
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 JUN
PY 2013
VL 45
IS 6
BP 690
EP +
DI 10.1038/ng.2608
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA 152XA
UT WOS:000319563900019
PM 23583978
ER
PT J
AU Gunta, SS
Thadhani, RI
Mak, RH
AF Gunta, Sujana S.
Thadhani, Ravi I.
Mak, Robert H.
TI The effect of vitamin D status on risk factors for cardiovascular
disease
SO NATURE REVIEWS NEPHROLOGY
LA English
DT Review
ID CHRONIC KIDNEY-DISEASE; RENIN-ANGIOTENSIN SYSTEM; RANDOMIZED
CONTROLLED-TRIAL; LEFT-VENTRICULAR HYPERTROPHY; NUTRITION EXAMINATION
SURVEY; PLASMA 25-HYDROXYVITAMIN D; IMMATURE DENDRITIC CELLS; CHRONIC
HEART-FAILURE; D-RECEPTOR ACTIVATORS; 3RD NATIONAL-HEALTH
AB Vitamin-D-related pathways are implicated in various endocrine, inflammatory and endothelial functions. An estimated 1 billion people in the world have vitamin D deficiency or insufficiency, and undiagnosed vitamin D deficiency is common. Vitamin D deficiency is associated with substantial increases in the incidence of hypertension, hyperlipidaemia, myocardial infarction and stroke, as well as in diseases such as chronic kidney disease and type 2 diabetes. Low vitamin D levels also upregulate the renin-angiotensin-aldosterone system, increase inflammation and cause endothelial dysfunction. However, the role of vitamin D deficiency in cardiovascular morbidity and mortality is an emerging and hotly debated topic. Epidemiological studies suggest an association between low vitamin D levels and risk factors for cardiovascular disease, but a causal relationship has not been established, and clinical trials and meta-analyses have not demonstrated convincing evidence that vitamin D therapy improves cardiovascular outcomes. Some evidence suggests that vitamin D status is a biomarker of lifestyle, since unhealthy and sedentary lifestyles are associated with vitamin D insufficiency or deficiency and are also risk factors for cardiovascular complications.
C1 [Gunta, Sujana S.; Mak, Robert H.] Univ Calif San Diego, Div Pediat Nephrol, La Jolla, CA 92093 USA.
[Thadhani, Ravi I.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Nephrol,Dept Med, Boston, MA 02115 USA.
RP Mak, RH (reprint author), Univ Calif San Diego, Div Pediat Nephrol, 9500 Gilman Dr,MC 0634, La Jolla, CA 92093 USA.
EM romak@ucsd.edu
FU NIDDK NIH HHS [R01DK084974, K24DK094872‑01, U01 DK‑3‑012]; NIEHS NIH HHS
[P30 ES002109]
NR 119
TC 25
Z9 25
U1 1
U2 16
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1759-5061
J9 NAT REV NEPHROL
JI Nat. Rev. Nephrol.
PD JUN
PY 2013
VL 9
IS 6
BP 337
EP 347
DI 10.1038/nrneph.2013.74
PG 11
WC Urology & Nephrology
SC Urology & Nephrology
GA 152BH
UT WOS:000319504000008
PM 23609564
ER
PT J
AU McKenna, MJ
AF McKenna, Michael J.
TI In Memory of Saumil Nalin Merchant, M.D. Obituary
SO OTOLOGY & NEUROTOLOGY
LA English
DT Biographical-Item
C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02115 USA.
RP McKenna, MJ (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02115 USA.
EM michael_mckenna@meei.harvard.edu
NR 1
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1531-7129
J9 OTOL NEUROTOL
JI Otol. Neurotol.
PD JUN
PY 2013
VL 34
IS 4
BP 595
EP 596
DI 10.1097/MAO.0b013e318287c9a1
PG 2
WC Clinical Neurology; Otorhinolaryngology
SC Neurosciences & Neurology; Otorhinolaryngology
GA 146AV
UT WOS:000319062100006
ER
PT J
AU Dilwali, S
Lysaght, A
Roberts, D
Barker, FG
McKenna, MJ
Stankovic, KM
AF Dilwali, Sonam
Lysaght, Andrew
Roberts, Daniel
Barker, Fred G., II
McKenna, Michael J.
Stankovic, Konstantina M.
TI Sporadic Vestibular Schwannomas Associated With Good Hearing Secrete
Higher Levels of Fibroblast Growth Factor 2 Than Those Associated With
Poor Hearing Irrespective of Tumor Size
SO OTOLOGY & NEUROTOLOGY
LA English
DT Article
DE Acoustic neuroma; Cytokine array; FGF2; Hearing loss; Sporadic
vestibular schwannoma
ID NEUROFIBROMATOSIS TYPE-2 GENE; ACOUSTIC NEUROMAS; HAIR-CELLS; NOISE
EXPOSURE; EXPRESSION; PROLIFERATION; INHIBITION; DISEASE; COCHLEA;
CANCER
AB Hypothesis: We hypothesize that the severity of hearing loss (HL) associated with sporadic vestibular schwannomas (VS) is correlated with tumor secretion of proteins with ototoxic or otoprotective potential.
Background: Because the recognition that HL associated with VS is not solely due to compression of the auditory nerve, elucidating the mechanism by which VS cause HL has been an important task. We previously showed that VS stratified by hearing have differential gene expression. We now focus on identifying differentially expressed proteins in tumor secretions.
Methods: Fresh surgical specimens of VS were incubated in sterile PBS at 37 degrees C to collect secretions. The specimens were divided into a group associated with good hearing (GH, word recognition >= 70% and pure-tone average <= 30 dB, n = 11) or poor hearing (PH, n = 10). The groups were compared using a customized cytokine array. Statistically significant results were verified with an enzyme-linked immunosorbent assay on a different set of secretions (n = 8 for GH and n = 10 for PH group).
Results: Of the 37 molecules we studied, 9 were significantly expressed in secretions from VS compared with secretions from control nerves. Secretion of fibroblast growth factor 2 (FGF2) was 3.5-fold higher in VS associated with GH versus PH based on cytokine array analysis (p = 0.02), which was validated with enzyme-linked immunosorbent assay.
Conclusion: This study highlights FGF2, a mitogen known to protect the auditory nerve, as a potential tumor-secreted mediator of hearing protection in VS. If FGF2's significant role in hearing protection in patients with VS is validated, then FGF2 could be used as a biomarker for HL in VS, and therapeutic targeting of the FGF2 signaling pathway may reduce HL due to VS.
C1 [Dilwali, Sonam; Lysaght, Andrew; Stankovic, Konstantina M.] Harvard Univ, Sch Med, Program Speech & Hearing Biosci & Technol, Cambridge, MA 02138 USA.
[Dilwali, Sonam; Lysaght, Andrew; Stankovic, Konstantina M.] MIT, Cambridge, MA 02139 USA.
[Dilwali, Sonam; Lysaght, Andrew; Roberts, Daniel; McKenna, Michael J.; Stankovic, Konstantina M.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Eaton Peabody Labs, Boston, MA 02114 USA.
[Roberts, Daniel; McKenna, Michael J.; Stankovic, Konstantina M.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA.
[Barker, Fred G., II] Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA.
[Barker, Fred G., II] Harvard Univ, Sch Med, Dept Surg Neurosurg, Boston, MA USA.
RP Stankovic, KM (reprint author), 243 Charles St, Boston, MA 02114 USA.
EM konstantina_stankovic@meei.harvard.edu
FU National Institute on Deafness and Other Communication Disorders [T32 DC
00038, K08DC010419]; Bertarelli Foundation
FX This project was supported by National Institute on Deafness and Other
Communication Disorders Grants T32 DC 00038 (S.D. and A.L.) and
K08DC010419 (K.M.S.), and the Bertarelli Foundation (K.M.S.).
NR 43
TC 8
Z9 8
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1531-7129
J9 OTOL NEUROTOL
JI Otol. Neurotol.
PD JUN
PY 2013
VL 34
IS 4
BP 748
EP 754
DI 10.1097/MAO.0b013e31828048ec
PG 7
WC Clinical Neurology; Otorhinolaryngology
SC Neurosciences & Neurology; Otorhinolaryngology
GA 146AV
UT WOS:000319062100030
PM 23512073
ER
PT J
AU Mougey, EB
Chen, C
Tantisira, KG
Blake, KV
Peters, SP
Wise, RA
Weiss, ST
Lima, JJ
AF Mougey, E. B.
Chen, C.
Tantisira, K. G.
Blake, K. V.
Peters, S. P.
Wise, R. A.
Weiss, S. T.
Lima, J. J.
TI Pharmacogenetics of asthma controller treatment
SO PHARMACOGENOMICS JOURNAL
LA English
DT Article
DE asthma; Caucasians; controller; genes; pharmacogenetics; polymorphisms
ID AIRWAY SMOOTH-MUSCLE; MUSCARINIC RECEPTOR SUBTYPES; IMPROVED
LUNG-FUNCTION; GUINEA-PIG TRACHEA; INHALED CORTICOSTEROIDS; PERSISTENT
ASTHMA; POLYMORPHISM; MONTELUKAST; ASSOCIATION; SALMETEROL
AB The interpatient variability in response to asthma controllers is significant and associates with pharmacogenomic variability. The goal of the present study was to identify novel variants that associate with response to common asthma controllers: fluticasone, combination of fluticasone + salmeterol and montelukast with single nucleotide polymorphisms (SNPs) in beta 2-adrenergic receptor, corticosteroid and leukotriene pathway candidate genes. Participants in a large clinical trial of step-down strategies volunteered for this pharmacogenetic study. A total of 169 SNPs in 26 candidate genes were genotyped in 189 Caucasian participants with asthma who took either fluticasone (100 mu g bid), fluticasone propionate (100 mu g) + salmeterol (50 mu g) (FP/Salm) or montelukast (5 or 10 mg) each night for 16 weeks. Primary outcomes were the slopes of plots of Asthma Control Questionnaire (ACQ) scores versus time following randomization; and the percent change in percent predicted FEV1 (Delta FEV1% pred) from enrollment to the end of the study. Associations between SNPs and outcomes were analyzed using general linear models. False discovery rate and Bonferroni corrections were used to correct for multiple comparisons. In all, 16 SNPs in seven genes were significantly associated with outcomes. For FP/Salm, three SNPs in CHRM2 associated with ACQ slope (P = 2.8 x 10(-5)), and rs1461496 in HSPA8 associated with Delta FEV1% pred. For fluticasone, five SNPs in CRHR1 (P = 1.9 x 10(-4)), and three SNPs in COL2A1 associated with ACQ slope and Delta FEV1% pred, respectively. For montelukast, four SNPs in CHRM2 associated with Delta FEV1% pred and predicted an opposite effect compared with fluticasone (P = 9 x 10(-3)). The present study indentified several novel SNPs that associate with response to common asthma controllers, and support further pharmacogenomic study and the use of genetic variants to personalize asthma treatment.
C1 [Mougey, E. B.; Blake, K. V.; Peters, S. P.; Wise, R. A.; Lima, J. J.] ALA Asthma Clin Res Ctr, Jacksonville, FL USA.
[Mougey, E. B.; Blake, K. V.; Lima, J. J.] Nemours Childrens Clin, Ctr Pharmacogenet & Translat Res, Jacksonville, FL 32207 USA.
[Chen, C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat,Sch Publ Hlth, Boston, MA 02115 USA.
[Tantisira, K. G.; Weiss, S. T.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab, Boston, MA 02115 USA.
[Peters, S. P.] Wake Forest Univ, Translat Sci Inst, Hlth Sci Ctr, Ctr Genom & Personalized Med Res, Winston Salem, NC 27109 USA.
[Wise, R. A.] Johns Hopkins Univ, Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Wise, R. A.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
RP Lima, JJ (reprint author), Nemours Childrens Clin, Ctr Pharmacogenet & Translat Res, 807 Childrens Way, Jacksonville, FL 32207 USA.
EM Jlima@nemours.org
OI Wise, Robert/0000-0002-8353-2349
FU Merck; Boehringer-Ingelheim; GSK; Merck Forest; National Institutes of
Health [R01HL071394, R01HL074755, K23HL081245, R01HL092197,
U01HL065899]; American Lung Association
FX Edward Mougey and John Lima received funding from Merck to characterize
associations between transporter SNPs, and the pharmacokinetics and
pharmacodynamics of montelukast. Stephen Peters received compensation as
a consultant to the ALA-ACRC DCC. Robert Wise received compensation as a
consultant to the following companies: Astra Zeneca,
Boehringer-Ingelheim, GSK, Novartis, Sunovion, Centocor, Genentech,
Medimmune, Intermune and Pfizerone. Dr Wise is also funded by the
following companies: Boehringer-Ingelheim, GSK, Merck Forest.; We
acknowledge the ALA-ACRC investigators and research teams who conducted
the LOCCS and LODO trials. We would also like to acknowledge Stacey Gray
for help with preparation of the manuscript. This work was supported by
the National Institutes of Health (R01HL071394, R01HL074755,
K23HL081245, R01HL092197, and U01HL065899) and the American Lung
Association.
NR 57
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U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1470-269X
J9 PHARMACOGENOMICS J
JI Pharmacogenomics J.
PD JUN
PY 2013
VL 13
IS 3
BP 242
EP 250
DI 10.1038/tpj.2012.5
PG 9
WC Genetics & Heredity; Pharmacology & Pharmacy
SC Genetics & Heredity; Pharmacology & Pharmacy
GA 151GL
UT WOS:000319448600006
PM 22370858
ER
PT J
AU Perlis, RH
Fijal, B
Dharia, S
Houston, JP
AF Perlis, R. H.
Fijal, B.
Dharia, S.
Houston, J. P.
TI Pharmacogenetic investigation of response to duloxetine treatment in
generalized anxiety disorder
SO PHARMACOGENOMICS JOURNAL
LA English
DT Article
DE anxiety; CRF receptor type 1; duloxetine; single nucleotide
polymorphisms
ID MAJOR DEPRESSIVE DISORDER; PLACEBO-CONTROLLED TRIAL; ANTIDEPRESSANT
TREATMENT; DOUBLE-BLIND; ASSOCIATION; ADULTS; GENE
AB We examined genetic associations with duloxetine response in generalized anxiety disorder (GAD). Three pooled studies in patients with GAD receiving duloxetine 60-120mg per day (N=164) or placebo (N=95) were used. Associations between 825 single-nucleotide polymorphisms (SNPs) in 61 candidate genes with change in Hamilton Anxiety Scale scores were examined with set-based testing (adjusted for the number of SNPs within each gene); sets with two-sided adjusted P <= 0.05 were examined using repeated measure analysis. Follow-up analysis explored associations of these SNPs with change in Hamilton Rating Scale for Depression-Anxiety Subscale in a 6-week study in duloxetine-treated patients with major depressive disorder (MDD) (N=241). Variants in corticotropin-releasing hormone receptor 1 (CRHR1), dopamine receptor D3 (DRD3), nuclear receptor subfamily group C, member 1 (NR3C1) and phosphodiesterase 1A (PDE1A) were associated with duloxetine response in GAD. Only rs4792888 in CRHR1 showed modest evidence of association with duloxetine response in MDD (P=0.029 in GAD, P=0.054 in MDD). In conclusion, CRHR1 variation merits investigation in pathophysiology of anxiety and its treatment response.
C1 [Perlis, R. H.] Massachusetts Gen Hosp, Dept Psychiat, Psychiat Pharmacogen Lab, Boston, MA 02114 USA.
[Perlis, R. H.] Harvard Univ, Sch Med, Boston, MA USA.
[Fijal, B.] Eli Lilly & Co, Indianapolis, IN 46285 USA.
[Dharia, S.] PharmaNet i3, Ann Arbor, MI USA.
[Houston, J. P.] Lilly USA LLC, Indianapolis, IN 46285 USA.
[Houston, J. P.] Indiana Univ Sch Med, Dept Psychiat, Indianapolis, IN USA.
RP Houston, JP (reprint author), Lilly USA LLC, Lilly Corp Ctr Mail Code 4103, Indianapolis, IN 46285 USA.
EM houston_john_p@lilly.com
FU Eli Lilly and Company
FX We thank Dr Alexandra Heinloth, Ms Laura Tyler and Ms Barbara McLean for
writing and editorial assistance. The parent studies were registered at:
http://www.clinicaltrials.gov/ct2/home: NCT00122850, NCT00122863,
NCT00122837, and NCT00191061. This work was supported by Eli Lilly and
Company and/or any of its subsidiaries.
NR 22
TC 11
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U1 1
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1470-269X
J9 PHARMACOGENOMICS J
JI Pharmacogenomics J.
PD JUN
PY 2013
VL 13
IS 3
BP 280
EP 285
DI 10.1038/tpj.2011.62
PG 6
WC Genetics & Heredity; Pharmacology & Pharmacy
SC Genetics & Heredity; Pharmacology & Pharmacy
GA 151GL
UT WOS:000319448600011
PM 22249355
ER
PT J
AU Gordon, CR
Susarla, SM
Yaremchuk, MJ
AF Gordon, Chad R.
Susarla, Srinivas M.
Yaremchuk, Michael J.
TI Reply: Quantitative Assessment of Medial Orbit Fracture Repair Using
Computer-Designed Anatomical Plates
SO PLASTIC AND RECONSTRUCTIVE SURGERY
LA English
DT Letter
C1 [Gordon, Chad R.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Susarla, Srinivas M.; Yaremchuk, Michael J.] Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, Dept Surg, Boston, MA 02116 USA.
RP Yaremchuk, MJ (reprint author), Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, Dept Surg, WACC 435, Boston, MA 02116 USA.
EM dr.y@dryaremchuk.com
OI Susarla, Srinivas/0000-0003-0155-8260
NR 1
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0032-1052
J9 PLAST RECONSTR SURG
JI Plast. Reconstr. Surg.
PD JUN
PY 2013
VL 131
IS 6
BP 912E
EP 913E
DI 10.1097/PRS.0b013e31828bd2ee
PG 3
WC Surgery
SC Surgery
GA 152YG
UT WOS:000319567500006
PM 23714814
ER
PT J
AU Heit, YI
Lancerotto, L
Del Vecchio, DA
Orgill, DP
AF Heit, Yvonne I.
Lancerotto, Luca
Del Vecchio, Dan A.
Orgill, Dennis P.
TI Reply: The Effects of Negative Pressure on Blood Supply and the
Adipogenic Role of Edema
SO PLASTIC AND RECONSTRUCTIVE SURGERY
LA English
DT Letter
C1 [Heit, Yvonne I.] Univ Magdeburg, Dept Plast Aesthet & Hand Surg, D-39106 Magdeburg, Germany.
[Lancerotto, Luca] Univ Padua, Clin Plast Surg, Padua, Italy.
[Del Vecchio, Dan A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg, Boston, MA USA.
[Orgill, Dennis P.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Plast Surg, Boston, MA 02115 USA.
RP Orgill, DP (reprint author), 75 Francis St, Boston, MA 02115 USA.
EM dorgill@partners.org
OI Orgill, Dennis/0000-0002-8279-7310
NR 1
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0032-1052
J9 PLAST RECONSTR SURG
JI Plast. Reconstr. Surg.
PD JUN
PY 2013
VL 131
IS 6
BP 932E
EP 932E
DI 10.1097/PRS.0b013e31828bd2b3
PG 1
WC Surgery
SC Surgery
GA 152YG
UT WOS:000319567500024
PM 23714832
ER
PT J
AU Reish, RG
Damjanovic, B
Austen, WG
Winograd, J
Liao, EC
Cetrulo, CL
Balkin, DM
Colwell, AS
AF Reish, Richard G.
Damjanovic, Branimir
Austen, William G., Jr.
Winograd, Jonathan
Liao, Eric C.
Cetrulo, Curtis L.
Balkin, Daniel M.
Colwell, Amy S.
TI Infection following Implant-Based Reconstruction in 1952 Consecutive
Breast Reconstructions: Salvage Rates and Predictors of Success
SO PLASTIC AND RECONSTRUCTIVE SURGERY
LA English
DT Article
ID ACELLULAR DERMAL MATRIX; COMPLICATIONS; PROSTHESIS; MANAGEMENT;
ALLODERM; SURGEONS; ENOUGH; RISK
AB Background: Few studies address salvage rates for infection in implant-based breast reconstruction. An understanding of success rates and clinical predictors of failure may help guide management.
Method: A retrospective analysis of multisurgeon consecutive implant reconstructions from 2004 to 2010 was performed.
Results: Immediate implant-based reconstructions (n = 1952) were performed in 1241 patients. Ninety-nine reconstruction patients (5.1 percent) were admitted for breast erythema and had a higher incidence of smoking (p = 0.007), chemotherapy (p = 0.007), radiation therapy (p = 0.001), and mastectomy skin necrosis (p < 0.0001). There was no difference in age, body mass index, or acellular dermal matrix usage. With intravenous antibiotics, 25 (25.3 percent) reconstruction patients cleared the infection, whereas 74 (74.7 percent) underwent attempted operative salvage (n = 18) or explantation (n = 56). Patients who failed to clear infection had a higher mean white blood cell count at admission (p < 0.0001). Of the attempted operative salvage group, 12 cleared the infection with immediate implant exchange and six eventually lost the implant. Patients who failed implant salvage were more likely to have methicillin-resistant Staphylococcus aureus (p = 0.004). The total explantation rate was 3.2 percent. Following explantation, 32 patients underwent attempted secondary tissue expander insertion. Twenty-six were successful and six had recurrent infection and implant loss. There were no differences in time interval to tissue expander insertion between successful and unsuccessful secondary operations.
Conclusions: Salvage with intravenous antibiotics and implant exchange was successful in 37.3 percent of patients. Smoking, irradiation, chemotherapy, and mastectomy skin necrosis were predictors for developing infection. Patients with a higher white blood cell count at admission and methicillin-resistant S. aureus were more likely to fail implant salvage. There was no association with time interval to tissue expander insertion and secondary explantation.
C1 [Reish, Richard G.; Damjanovic, Branimir; Austen, William G., Jr.; Winograd, Jonathan; Liao, Eric C.; Cetrulo, Curtis L.; Balkin, Daniel M.; Colwell, Amy S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg, Boston, MA 02114 USA.
RP Colwell, AS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg, 15 Parkman St, Boston, MA 02114 USA.
EM acolwell@partners.org
NR 20
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U1 1
U2 5
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 JUN
PY 2013
VL 131
IS 6
BP 1223
EP 1230
DI 10.1097/PRS.0b013e31828bd377
PG 8
WC Surgery
SC Surgery
GA 152YG
UT WOS:000319567500036
PM 23714788
ER
PT J
AU Schacht, JP
Anton, RF
Randall, PK
Li, XB
Henderson, S
Myrick, H
AF Schacht, Joseph P.
Anton, Raymond F.
Randall, Patrick K.
Li, Xingbao
Henderson, Scott
Myrick, Hugh
TI Effects of a GABA-ergic medication combination and initial alcohol
withdrawal severity on cue-elicited brain activation among
treatment-seeking alcoholics
SO PSYCHOPHARMACOLOGY
LA English
DT Article
DE Alcoholism; Anticonvulsant; Craving; Neuroimaging; Relapse
ID ANTERIOR CINGULATE CORTEX; COMPULSIVE DRINKING SCALE; PREFRONTAL CORTEX;
DEPENDENT INDIVIDUALS; ABSTINENT ALCOHOLICS; ETHANOL WITHDRAWAL;
RECEPTOR FUNCTION; GENE-EXPRESSION; DOUBLE-BLIND; GABAPENTIN
AB Many studies have reported medication effects on alcohol cue-elicited brain activation or associations between such activation and subsequent drinking. However, few have combined the methodological rigor of a randomized clinical trial (RCT) with follow-up assessments to determine whether cue-elicited activation predicts relapse during treatment, the crux of alcoholism.
This study analyzed functional magnetic resonance imaging (fMRI) data from 48 alcohol-dependent subjects enrolled in a 6-week RCT of an investigational pharmacotherapy.
Subjects were randomized, based on their level of alcohol withdrawal (AW) at study entry, to receive either a combination of gabapentin (GBP; up to 1,200 mg for 39 days) and flumazenil (FMZ) infusions (2 days) or two placebos. Midway through the RCT, subjects were administered an fMRI alcohol cue reactivity task.
There were no main effects of medication or initial AW status on cue-elicited activation, but these factors interacted, such that the GBP/FMZ/higher AW and placebo/lower AW groups, which had previously been shown to have relatively reduced drinking, demonstrated greater dorsal anterior cingulate cortex (dACC) activation to alcohol cues. Further analysis suggested that this finding represented differences in task-related deactivation and was associated with greater control over alcohol-related thoughts. Among study completers, regardless of medication or AW status, greater left dorsolateral prefrontal cortex (DLPFC) activation predicted more post-scan heavy drinking.
These data suggest that alterations in task-related deactivation of dACC, a component of the default mode network, may predict better alcohol treatment response, while activation of DLPFC, an area associated with selective attention, may predict relapse drinking.
C1 [Schacht, Joseph P.; Anton, Raymond F.; Randall, Patrick K.; Li, Xingbao; Henderson, Scott; Myrick, Hugh] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA.
[Myrick, Hugh] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA.
RP Schacht, JP (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, 171 Ashley Ave, Charleston, SC 29425 USA.
EM schacht@musc.edu
FU National Institute on Alcohol Abuse and Alcoholism [T32 AA007474, K05
AA017435]; Hythiam, Inc.
FX This work was conducted under an unrestricted grant from Hythiam, Inc.
This funding source had no involvement in the study design, in the
collection, analysis, and interpretation of data, in the writing of the
paper, or in the decision to submit for publication. Drs. Schacht and
Anton are supported by grants from the National Institute on Alcohol
Abuse and Alcoholism (T32 AA007474 and K05 AA017435). Portions of this
work were presented as a poster at the 34th Annual Meeting of the
Research Society on Alcoholism (June 2011, Atlanta, GA, USA).
NR 57
TC 10
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U1 10
U2 16
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0033-3158
J9 PSYCHOPHARMACOLOGY
JI Psychopharmacology
PD JUN
PY 2013
VL 227
IS 4
BP 627
EP 637
DI 10.1007/s00213-013-2996-x
PG 11
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 150XF
UT WOS:000319424200006
PM 23389755
ER
PT J
AU Doyle, PJ
Hula, WD
Hula, SNA
Stone, CA
Wambaugh, JL
Ross, KB
Schumacher, JG
AF Doyle, Patrick J.
Hula, William D.
Hula, Shannon N. Austermann
Stone, Clement A.
Wambaugh, Julie L.
Ross, Katherine B.
Schumacher, James G.
TI Self- and surrogate-reported communication functioning in aphasia
SO QUALITY OF LIFE RESEARCH
LA English
DT Article
DE Outcomes assessment; Self-assessment; Factor analysis; Aphasia
ID QUALITY-OF-LIFE; STROKE IMPACT SCALE; MEASUREMENT INVARIANCE; FACTORIAL
INVARIANCE; PSYCHOMETRIC EVALUATION; OUTCOME MEASURE; RASCH ANALYSIS;
CES-D; PROXY; RELIABILITY
AB To evaluate the dimensionality and measurement invariance of the aphasia communication outcome measure (ACOM), a self- and surrogate-reported measure of communicative functioning in aphasia.
Responses to a large pool of items describing communication activities were collected from 133 community-dwelling persons with aphasia of a parts per thousand yen 1 month post-onset and their associated surrogate respondents. These responses were evaluated using confirmatory and exploratory factor analysis. Chi-square difference tests of nested factor models were used to evaluate patient-surrogate measurement invariance and the equality of factor score means and variances. Association and agreement between self- and surrogate reports were examined using correlation and scatterplots of pairwise patient-surrogate differences.
Three single-factor scales (Talking, Comprehension, and Writing) approximating patient-surrogate measurement invariance were identified. The variance of patient-reported scores on the Talking and Writing scales was higher than surrogate-reported variances on these scales. Correlations between self- and surrogate reports were moderate-to-strong, but there were significant disagreements in a substantial number of individual cases.
Despite minimal bias and relatively strong association, surrogate reports of communicative functioning in aphasia are not reliable substitutes for self-reports by persons with aphasia. Furthermore, although measurement invariance is necessary for direct comparison of self- and surrogate reports, the costs of obtaining invariance in terms of scale reliability and content validity may be substantial. Development of non-invariant self- and surrogate report scales may be preferable for some applications.
C1 [Doyle, Patrick J.; Hula, William D.] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA 15213 USA.
[Doyle, Patrick J.; Hula, William D.] Univ Pittsburgh, Dept Commun Sci & Disorders, Pittsburgh, PA USA.
[Hula, Shannon N. Austermann] VA Pittsburgh Healthcare Syst, Res Serv, Pittsburgh, PA USA.
[Stone, Clement A.] Univ Pittsburgh, Dept Educ Psychol, Pittsburgh, PA USA.
[Wambaugh, Julie L.] VA Salt Lake City Healthcare Syst, Res Serv, Salt Lake City, UT USA.
[Wambaugh, Julie L.] Univ Utah, Dept Commun Sci & Disorders, Salt Lake City, UT USA.
[Ross, Katherine B.] Phoenix VA Healthcare Syst, Audiol & Speech Pathol, Phoenix, AZ USA.
[Schumacher, James G.] VA Pittsburgh Healthcare Syst, Audiol & Speech Pathol, Pittsburgh, PA USA.
RP Hula, WD (reprint author), VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA 15213 USA.
EM william.hula@va.gov
FU VA Rehabilitation Research & Development Merit Review Award [C6098R];
Career Development Award [6210 M]; VA Pittsburgh Healthcare System
Geriatric Research Education and Clinical Center
FX This work was supported by VA Rehabilitation Research & Development
Merit Review Award C6098R, Career Development Award 6210 M, and the VA
Pittsburgh Healthcare System Geriatric Research Education and Clinical
Center. An earlier version of this work was presented at the Clinical
Aphasiology Conference, May 27, 2010, Isle of Palms, SC, USA. The
contents of this paper do not represent the views of the Department of
Veterans Affairs or the United States Government.
NR 58
TC 3
Z9 3
U1 0
U2 7
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0962-9343
J9 QUAL LIFE RES
JI Qual. Life Res.
PD JUN
PY 2013
VL 22
IS 5
BP 957
EP 967
DI 10.1007/s11136-012-0224-5
PG 11
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 152FQ
UT WOS:000319516800004
PM 22729711
ER
PT J
AU Cella, D
Butt, Z
Kindler, HL
Fuchs, CS
Bray, S
Barlev, A
Oglesby, A
AF Cella, David
Butt, Zeeshan
Kindler, Hedy Lee
Fuchs, Charles S.
Bray, Sarah
Barlev, Arie
Oglesby, Alan
TI Validity of the FACT Hepatobiliary (FACT-Hep) questionnaire for
assessing disease-related symptoms and health-related quality of life in
patients with metastatic pancreatic cancer
SO QUALITY OF LIFE RESEARCH
LA English
DT Article
DE Health-related quality of life; Questionnaire; Pancreatic cancer;
Patient-reported outcomes
ID FUNCTIONAL ASSESSMENT; INSTRUMENTS; THERAPY; VALIDATION; INDEX
AB Evaluate reliability and validity of the Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) questionnaire and its derivative FACT Hepatobiliary Symptom Indexes (FHSI-18 and FHSI-8) in people with metastatic pancreatic cancer.
Self-reported questionnaire data from a randomized controlled Phase II study evaluating the efficacy and safety of conatumumab (AMG 655), ganitumab (AMG 479) or placebo combined with gemcitabine were evaluated. The following were assessed: internal consistency, using Cronbach's alpha; discriminant validity, comparing baseline patient-reported outcomes (PRO) scores across Eastern Cooperative Oncology Group (ECOG) performance status (PS) levels; and ability to detect change, comparing change from baseline PRO score at each cycle across PS and tumour response groups.
The analysis included 96 patients. All scale scores demonstrated good internal consistency (Cronbach's alpha > 0.7) and discriminant validity. Baseline scores were significantly poorer among patients with PS = 1 versus patients with PS = 0 (e.g. difference in FACT-Hep total score -17.27; p < 0.001). Ability to detect change was established for Cycles 2/3 versus baseline; PRO scores reduced in the PS-worsened group versus the PS-stable group (e.g. difference in FACT-Hep total score -24.29; p < 0.001). All PRO scale scores showed significant decline for progressive disease versus stable disease (e.g. difference in FACT-Hep total score -12.58; p = 0.004). Changes on the FHSI-18 and FHSI-8 scales were similar in magnitude whether ECOG improved or worsened.
FACT-Hep detects change and is a reliable and valid instrument for measuring health-related quality of life in patients with metastatic pancreatic cancer.
C1 [Cella, David; Butt, Zeeshan] Northwestern Univ, Feinberg Sch Med, Dept Med Social Sci, Chicago, IL 60611 USA.
[Kindler, Hedy Lee] Univ Chicago, Med Ctr, Chicago, IL 60637 USA.
[Fuchs, Charles S.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Bray, Sarah] Amgen Inc, Cambridge, England.
[Barlev, Arie; Oglesby, Alan] Amgen Inc, Thousand Oaks, CA 91320 USA.
RP Cella, D (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Med Social Sci, 720 N Lake Shore Dr,7th Floor, Chicago, IL 60611 USA.
EM d-cella@northwestern.edu
FU Amgen Inc.; National Center for Research Resources, National Institutes
of Health [KL2RR025740]
FX Medical writing assistance was provided by ApotheCom ScopeMedical Ltd,
funded by Amgen Inc. All authors had full access to the data and had
final responsibility for the decision to submit the manuscript. This
study was funded by Amgen Inc. Zeeshan Butt's work on this manuscript
was supported in part by grant KL2RR025740 from the National Center for
Research Resources, National Institutes of Health.
NR 22
TC 6
Z9 6
U1 1
U2 4
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0962-9343
J9 QUAL LIFE RES
JI Qual. Life Res.
PD JUN
PY 2013
VL 22
IS 5
BP 1105
EP 1112
DI 10.1007/s11136-012-0217-4
PG 8
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 152FQ
UT WOS:000319516800019
PM 22678353
ER
PT J
AU Kopans, DB
AF Kopans, Daniel B.
TI Digital Breast Tomosynthesis: A Better Mammogram
SO RADIOLOGY
LA English
DT Letter
C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA.
RP Kopans, DB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 5 Parkman St,Suite 219, Boston, MA 02114 USA.
EM dkopans@partners.org
NR 3
TC 5
Z9 5
U1 0
U2 13
PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0033-8419
J9 RADIOLOGY
JI Radiology
PD JUN
PY 2013
VL 267
IS 3
BP 968
EP 969
PG 3
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 151FF
UT WOS:000319445400041
PM 23704296
ER
PT J
AU Wicky, S
Pinto, EG
Oklu, R
AF Wicky, Stephan
Pinto, Erique Guedes
Oklu, Rahmi
TI Catheter-Directed Thrombolysis of Arterial Thrombosis
SO SEMINARS IN THROMBOSIS AND HEMOSTASIS
LA English
DT Article
DE thrombosis; catheter-directed thrombolysis; artery
ID ACUTE LIMB ISCHEMIA; PERIPHERAL ARTERIAL; RANDOMIZED TRIAL;
LOWER-EXTREMITY; ANGIOJET; SYSTEM; THROMBECTOMY; SURGERY;
THROMBOEMBOLECTOMY; STREPTOKINASE
AB Thrombotic or embolic arterial occlusive disease can lead to profound ischemia and, without emergent revascularization, is associated with significant morbidity and mortality. Significant advances in the management of arterial occlusive disease range from newer thrombolytic agents to innovative catheter designs to enhance thrombolysis and thrombectomy. Most of these advances have been directed toward the management of acute limb ischemia; therefore, we review the management of limb ischemia with emphasis on endovascular interventions.
C1 [Wicky, Stephan; Pinto, Erique Guedes; Oklu, Rahmi] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Vasc Imaging & Intervent, Boston, MA 02114 USA.
RP Oklu, R (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Vasc Imaging & Intervent, 55 Fruit St,290 Gray Bigelow, Boston, MA 02114 USA.
EM roklu@partners.org
NR 32
TC 6
Z9 7
U1 0
U2 1
PU THIEME MEDICAL PUBL INC
PI NEW YORK
PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA
SN 0094-6176
J9 SEMIN THROMB HEMOST
JI Semin. Thromb. Hemost.
PD JUN
PY 2013
VL 39
IS 4
BP 441
EP 445
DI 10.1055/s-0033-1334482
PG 5
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 152AM
UT WOS:000319501600014
PM 23483456
ER
PT J
AU Oklu, R
Wicky, S
AF Oklu, Rahmi
Wicky, Stephan
TI Catheter-Directed Thrombolysis of Deep Venous Thrombosis
SO SEMINARS IN THROMBOSIS AND HEMOSTASIS
LA English
DT Article
DE thrombosis; catheter-directed thrombolysis; vein; DVT
ID PERCUTANEOUS MECHANICAL THROMBECTOMY; TISSUE-PLASMINOGEN-ACTIVATOR; VASC
INTERV RADIOL; QUALITY IMPROVEMENT GUIDELINES; RANDOMIZED
CONTROLLED-TRIAL; VEIN-THROMBOSIS; PHARMACOMECHANICAL THROMBECTOMY;
POSTTHROMBOTIC SYNDROME; PULMONARY-EMBOLISM; OF-LIFE
AB Venous thrombosis is a major public health problem associated with significant morbidity and mortality and has a substantial impact on the quality of life. Over the years, it has becomemore apparent that anticoagulation alone in the treatment of deep venous thrombosis (DVT) is insufficient in the prevention of postthrombotic syndrome, which adversely impacts the quality of life of the patient, and it is insufficient in preventing recurrence of DVT. With the advent of innovative catheter designs to deliver thrombolytic therapies in the treatment of DVT, there have been significant advances in the management of DVT. We review the management of DVT with emphasis on catheter-directed interventions.
C1 [Oklu, Rahmi; Wicky, Stephan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc Imaging & Intervent, Boston, MA USA.
RP Oklu, R (reprint author), Massachusetts Gen Hosp, Div Vasc Imaging & Intervent, 55 Fruit St,290 Gray Bigelow, Boston, MA 02114 USA.
EM roklu@partners.org
NR 48
TC 8
Z9 11
U1 0
U2 9
PU THIEME MEDICAL PUBL INC
PI NEW YORK
PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA
SN 0094-6176
J9 SEMIN THROMB HEMOST
JI Semin. Thromb. Hemost.
PD JUN
PY 2013
VL 39
IS 4
BP 446
EP 451
DI 10.1055/s-0033-1334142
PG 6
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 152AM
UT WOS:000319501600015
PM 23483455
ER
PT J
AU Sun, N
Liu, Y
Qin, L
Lee, H
Weissleder, R
Ham, D
AF Sun, Nan
Liu, Yong
Qin, Ling
Lee, Hakho
Weissleder, Ralph
Ham, Donhee
TI Small NMR biomolecular sensors
SO SOLID-STATE ELECTRONICS
LA English
DT Article; Proceedings Paper
CT 42nd European Solid-State Device Research Conference (ESSDERC)
CY SEP, 2012
CL Bordeaux, FRANCE
DE Nuclear magnetic resonance (NMR); Radio-frequency (RF) integrated
circuits; CMOS integrated circuits; Biomolecular sensing; Biosensor
Magnetic particles
ID NUCLEAR-MAGNETIC-RESONANCE; CMOS TECHNOLOGY; CELLS; MANIPULATION;
OSCILLATORS; BIOSENSOR; HYBRID; SYSTEM; NOISE
AB By combining the physics of nuclear magnetic resonance (NMR) and silicon radio-frequency (RF) integrated circuits, we recently created progressively smaller NMR systems, which we originally reported in Refs. [1-4 Our strategy for NMR system miniaturization proved effective, culminating in the smallest prototype 13,4] that weighs 0.1 kg and can be held at the palm of the hand. These small, low-cost NMR systems can be useful as biomolecular sensors in the personalized medicine setting, and we demonstrated their ability to detect proteins, compounds, and human cancer cells. The present paper, which is not a new technical contribution, reviews these developments. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Sun, Nan] Univ Texas Austin, Dept Elect & Comp Engn, Austin, TX 78712 USA.
[Liu, Yong] IBM Corp, Thomas J Watson Res Ctr, Yorktown Hts, NY 10598 USA.
[Qin, Ling; Ham, Donhee] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
[Lee, Hakho; Weissleder, Ralph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA.
RP Sun, N (reprint author), Univ Texas Austin, Dept Elect & Comp Engn, Austin, TX 78712 USA.
EM nansun@mail.utexas.edu; donhee@seas.harvard.edu
RI Liu, Yong/J-3636-2014
NR 37
TC 9
Z9 9
U1 5
U2 21
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0038-1101
J9 SOLID STATE ELECTRON
JI Solid-State Electron.
PD JUN
PY 2013
VL 84
BP 13
EP 21
DI 10.1016/j.sse.2013.02.005
PG 9
WC Engineering, Electrical & Electronic; Physics, Applied; Physics,
Condensed Matter
SC Engineering; Physics
GA 152QV
UT WOS:000319547100003
ER
PT J
AU Devan, WJ
Falcone, GJ
Anderson, CD
Jagiella, JM
Schmidt, H
Hansen, BM
Jimenez-Conde, J
Giralt-Steinhauer, E
Cuadrado-Godia, E
Soriano, C
Ayres, AM
Schwab, K
Kassis, SB
Valant, V
Pera, J
Urbanik, A
Viswanathan, A
Rost, NS
Goldstein, JN
Freudenberger, P
Stogerer, EM
Norrving, B
Tirschwell, DL
Selim, M
Brown, DL
Silliman, SL
Worrall, BB
Meschia, JF
Kidwell, CS
Montaner, J
Fernandez-Cadenas, I
Delgado, P
Greenberg, SM
Roquer, J
Lindgren, A
Slowik, A
Schmidt, R
Woo, D
Rosand, J
Biffi, A
AF Devan, William J.
Falcone, Guido J.
Anderson, Christopher D.
Jagiella, Jeremiasz M.
Schmidt, Helena
Hansen, Bjorn M.
Jimenez-Conde, Jordi
Giralt-Steinhauer, Eva
Cuadrado-Godia, Elisa
Soriano, Carolina
Ayres, Alison M.
Schwab, Kristin
Kassis, Sylvia Baedorf
Valant, Valerie
Pera, Joanna
Urbanik, Andrzej
Viswanathan, Anand
Rost, Natalia S.
Goldstein, Joshua N.
Freudenberger, Paul
Stoegerer, Eva-Maria
Norrving, Bo
Tirschwell, David L.
Selim, Magdy
Brown, Devin L.
Silliman, Scott L.
Worrall, Bradford B.
Meschia, James F.
Kidwell, Chelsea S.
Montaner, Joan
Fernandez-Cadenas, Israel
Delgado, Pilar
Greenberg, Steven M.
Roquer, Jaume
Lindgren, Arne
Slowik, Agnieszka
Schmidt, Reinhold
Woo, Daniel
Rosand, Jonathan
Biffi, Alessandro
CA Int Stroke Genetics Consortium
TI Heritability Estimates Identify a Substantial Genetic Contribution to
Risk and Outcome of Intracerebral Hemorrhage
SO STROKE
LA English
DT Article
DE common genetic variants; genetics; genes; heritability; intracerebral
hemorrhage; stroke
ID APOLIPOPROTEIN-E GENOTYPE; COMMON SNPS EXPLAIN; AMYLOID ANGIOPATHY;
HEMATOMA EXPANSION; ALZHEIMER-DISEASE; LARGE PROPORTION; INCREASES RISK;
HUMAN HEIGHT; ASSOCIATION; WARFARIN
AB Background and Purpose-Previous studies suggest that genetic variation plays a substantial role in occurrence and evolution of intracerebral hemorrhage (ICH). Genetic contribution to disease can be determined by calculating heritability using family-based data, but such an approach is impractical for ICH because of lack of large pedigree-based studies. However, a novel analytic tool based on genome-wide data allows heritability estimation from unrelated subjects. We sought to apply this method to provide heritability estimates for ICH risk, severity, and outcome.
Methods-We analyzed genome-wide genotype data for 791 ICH cases and 876 controls, and determined heritability as the proportion of variation in phenotype attributable to captured genetic variants. Contribution to heritability was separately estimated for the APOE (encoding apolipoprotein E) gene, an established genetic risk factor, and for the rest of the genome. Analyzed phenotypes included ICH risk, admission hematoma volume, and 90-day mortality.
Results-ICH risk heritability was estimated at 29% (SE, 11%) for non-APOE loci and at 15% (SE, 10%) for APOE. Heritability for 90-day ICH mortality was 41% for non-APOE loci and 10% (SE, 9%) for APOE. Genetic influence on hematoma volume was also substantial: admission volume heritability was estimated at 60% (SE, 70%) for non-APOE loci and at 12% (SE, 4%) for APOE.
Conclusions-Genetic variation plays a substantial role in ICH risk, outcome, and hematoma volume. Previously reported risk variants account for only a portion of inherited genetic influence on ICH pathophysiology, pointing to additional loci yet to be identified.
C1 [Devan, William J.; Falcone, Guido J.; Anderson, Christopher D.; Ayres, Alison M.; Schwab, Kristin; Kassis, Sylvia Baedorf; Valant, Valerie; Viswanathan, Anand; Rost, Natalia S.; Greenberg, Steven M.; Roquer, Jaume; Biffi, Alessandro] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Devan, William J.; Falcone, Guido J.; Anderson, Christopher D.; Roquer, Jaume; Biffi, Alessandro] Massachusetts Gen Hosp, Hemorrhag Stroke Res Grp, Boston, MA 02114 USA.
[Devan, William J.; Falcone, Guido J.; Anderson, Christopher D.; Kassis, Sylvia Baedorf; Valant, Valerie; Rost, Natalia S.; Roquer, Jaume; Biffi, Alessandro] Massachusetts Gen Hosp, Div Neurocrit Care & Emergency Neurol, Dept Neurol, Boston, MA 02114 USA.
[Goldstein, Joshua N.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.
[Devan, William J.; Falcone, Guido J.; Anderson, Christopher D.; Kassis, Sylvia Baedorf; Valant, Valerie; Rost, Natalia S.; Roquer, Jaume; Biffi, Alessandro] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
[Jagiella, Jeremiasz M.; Pera, Joanna; Slowik, Agnieszka] Jagiellonian Univ, Coll Med, Dept Neurol, Krakow, Poland.
[Schmidt, Helena; Freudenberger, Paul] Med Univ Graz, Inst Mol Biol & Med Biochem, Graz, Austria.
[Hansen, Bjorn M.; Norrving, Bo; Lindgren, Arne] Lund Univ, Dept Clin Sci Lund, Lund, Sweden.
[Hansen, Bjorn M.; Norrving, Bo; Lindgren, Arne] Skane Univ Hosp, Dept Neurol, Lund, Sweden.
[Jimenez-Conde, Jordi; Giralt-Steinhauer, Eva; Cuadrado-Godia, Elisa; Soriano, Carolina; Roquer, Jaume] Univ Autonoma Barcelona, Neurovasc Res Unit, Dept Neurol, E-08193 Barcelona, Spain.
[Jimenez-Conde, Jordi; Giralt-Steinhauer, Eva; Cuadrado-Godia, Elisa; Soriano, Carolina; Rosand, Jonathan] Univ Autonoma Barcelona, Program Inflammat & Cardiovasc Disorders, Inst Hosp Mar Invest Med, E-08193 Barcelona, Spain.
[Urbanik, Andrzej; Schmidt, Reinhold] Med Univ Graz, Dept Radiol, Graz, Austria.
[Stoegerer, Eva-Maria] Med Univ Graz, Dept Neurol, Graz, Austria.
[Tirschwell, David L.] Univ Washington, Harborview Med Ctr, Stroke Ctr, Seattle, WA 98104 USA.
[Selim, Magdy] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA.
[Brown, Devin L.] Univ Michigan Hlth Syst, Dept Neurol, Stroke Program, Ann Arbor, MI USA.
[Silliman, Scott L.] Univ Florida, Coll Med, Dept Neurol, Jacksonville, FL USA.
[Worrall, Bradford B.] Univ Virginia Hlth Syst, Dept Neurol & Publ Hlth Sci, Charlottesville, VA USA.
[Meschia, James F.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA.
[Kidwell, Chelsea S.] Georgetown Univ, Med Ctr, Dept Neurol, Washington, DC 20007 USA.
[Montaner, Joan; Fernandez-Cadenas, Israel; Delgado, Pilar] Univ Autonoma Barcelona, Neurovasc Res Lab, Hosp Vall dHebron, Inst Recerca, E-08193 Barcelona, Spain.
[Montaner, Joan; Fernandez-Cadenas, Israel; Delgado, Pilar] Univ Autonoma Barcelona, Neurovasc Unit, Hosp Vall dHebron, Inst Recerca, E-08193 Barcelona, Spain.
[Woo, Daniel] Univ Cincinnati, Coll Med, Dept Neurol, Cincinnati, OH 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 JIMENEZ-CONDE, JORDI/C-1941-2012; Montaner, Joan/D-3063-2015; Goldstein,
Joshua/H-8953-2016; IBIS, NEUROVASCULAR/O-1855-2015; Falcone,
Guido/L-2287-2016;
OI Falcone, Guido/0000-0002-6407-0302; Hansen, Bjorn/0000-0001-8661-9063;
Brown, Devin/0000-0002-9815-3421; Norrving, Bo/0000-0002-8024-5096;
Ayres, Alison/0000-0002-5492-1695; Anderson,
Christopher/0000-0002-0053-2002
FU National Institutes of Health-National Institute of Neurological
Disorders and Stroke grant [R01NS059727]; Keane Stroke Genetics Research
Fund; Edward and Maybeth Sonn Research Fund; University of Michigan
General Clinical Research Center grant [M01 RR000042]; National Center
for Research Resources; Spain's Ministry of Health (Ministerio de
Sanidad y Consumo, Instituto de Salud Carlos III, Red HERACLES)
[RD06/0009]; Polish Ministry of Education grant [N N402 083934]; Swedish
Research Council [K2010-61X-20378-04-3]; Swedish Stroke Association;
Lund University; King Gustav V and Queen Victoria's foundations;
EUSTROKE 7FP Health [F2-08-202213]; Spanish Government [PI10/01212];
Austrian Science Fund (FWF) [P20545-P05, P13180]; Medical University of
Graz; American Heart Association/Bugher Foundation Centers for Stroke
Prevention Research [0775011 N]; American Brain Foundation Clinical
Research Training Fellowship; National Institutes of Health-National
Institute of Neurological Disorders and Stroke [R01NS059727,
1K23NS064052, 5K23NS059774, 5R01AG026484-08, U01NS069208, U01NS069763,
R01NS063925]; National Institutes of Health [5R01NS070834-03]; Miguel
Servet program from the Spanish Ministry of Health [CP09/136]; CSL
Behring; Hoffman La-Roche
FX All funding entities had no involvement in design, collection, analysis,
and interpretation, writing of the report, and in the decision to submit
the article for publication. Genetics of Cerebral Hemorrhage on
Anticoagulation: This study was funded by the National Institutes of
Health-National Institute of Neurological Disorders and Stroke grant
R01NS059727, the Keane Stroke Genetics Research Fund, the Edward and
Maybeth Sonn Research Fund, by the University of Michigan General
Clinical Research Center grant M01 RR000042, and by a grant from the
National Center for Research Resources. Hospital del Mar Intracerebral
Hemorrhage (ICH) Study: This study was funded by Spain's Ministry of
Health (Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III,
Red HERACLES RD06/0009. FEDER). The Jagiellonian University Hemorrhagic
Stroke Study: This study is supported by the Polish Ministry of
Education grant N N402 083934. The Lund Stroke Register ICH Study: This
study was funded by the Swedish Research Council (K2010-61X-20378-04-3),
the Swedish Stroke Association, the Lund University, and the King Gustav
V and Queen Victoria's foundations. The Hospital Vall d'Hebron ICH
Study: This study received the European Stroke Network grants EUSTROKE
7FP Health F2-08-202213 and the Spanish Government grant PI10/01212. The
Medical University of Graz ICH Study: Control subjects of this study are
from the Austrian Stroke Prevention Study, a population-based study
funded by the Austrian Science Fund (FWF) grants P20545-P05 and P13180.
The Medical University of Graz supports the databank of the Austrian
Stroke Prevention Study. The authors are supported by the American Heart
Association/Bugher Foundation Centers for Stroke Prevention Research
(0775011 N; Drs Biffi and Anderson), an American Brain Foundation
Clinical Research Training Fellowship (Dr Anderson), the National
Institutes of Health-National Institute of Neurological Disorders and
Stroke (Dr Rost [1K23NS064052], Dr Goldstein [5K23NS059774], Dr
Greenberg [5R01AG026484-08], and Dr Roquer [R01NS059727, U01NS069208,
U01NS069763, R01NS063925]), the National Institutes of Health
(5R01NS070834-03; Dr Greenberg), and the Miguel Servet program from the
Spanish Ministry of Health (CP09/136; Dr Delgado).; Dr Goldstein has
received consultancy fees, travel and accommodation expenses
reimbursement, and grant support from CSL Behring. Dr Greenberg has
received consultancy fees and support from Hoffman La-Roche. The other
authors have no conflicts to report.
NR 29
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U1 0
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 JUN
PY 2013
VL 44
IS 6
BP 1578
EP U191
DI 10.1161/STROKEAHA.111.000089
PG 11
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 151MU
UT WOS:000319465400022
PM 23559261
ER
PT J
AU Brouwers, HB
Backes, D
Kimberly, WT
Schwab, K
Romero, JM
Velthuis, BK
Klijn, CJM
Ogilvy, CS
Regli, L
Greenberg, SM
Rosand, J
Rinkel, GJE
Goldstein, JN
AF Brouwers, H. Bart
Backes, Daan
Kimberly, W. Taylor
Schwab, Kristin
Romero, Javier M.
Velthuis, Birgitta K.
Klijn, Catharina J. M.
Ogilvy, Christopher S.
Regli, Luca
Greenberg, Steven M.
Rosand, Jonathan
Rinkel, Gabriel J. E.
Goldstein, Joshua N.
TI Computed Tomography Angiography Spot Sign Does Not Predict Case Fatality
in Aneurysmal Subarachnoid Hemorrhage With Intraparenchymal Extension
SO STROKE
LA English
DT Article
DE CTA spot sign; in-hospital death; intracerebral hemorrhage; subarachnoid
hemorrhage
ID ACUTE INTRACEREBRAL HEMORRHAGE; IN-HOSPITAL MORTALITY; HEMATOMA
EXPANSION; IDENTIFIES PATIENTS; HIGHEST RISK; OUTCOMES; SCORE
AB Background and Purpose-Many patients with aneurysmal subarachnoid hemorrhage (SAH) with intraparenchymal extension develop early hematoma expansion, which is not explained by aneurysmal rerupture in half of cases. In patients with primary intracerebral hemorrhage, the computed tomography angiography (CTA) spot sign predicts hematoma expansion and poor outcome. We conducted a 2-center prospective cohort study to evaluate whether CTA spot sign predicts case fatality in aneurysmal subarachnoid hemorrhage with intraparenchymal extension.
Methods-We studied consecutive patients with aneurysmal subarachnoid hemorrhage with intraparenchymal extension. Two experienced readers, blinded to clinical data, analyzed CTAs for spot sign presence. We assessed the proportion of patients with the CTA spot sign and tested its association with in-hospital and 90-day case fatality, using univariable and multivariable logistic regression.
Results-In 32 of 236 patients (14%), we found at least 1 spot sign. Acute surgical hematoma evacuation with aneurysm occlusion occurred in 120 patients (51%). The overall in-hospital case fatality rate was 37%. The CTA spot sign was not associated with in-hospital (multivariable odds ratio, 0.51 [95% confidence interval, 0.06-3.26]) or 90-day (multivariable odds ratio, 0.59 [0.21-1.65]) case fatality.
Conclusions-The found frequency of CTA spot signs is lower after aneurysmal than primary intracerebral hemorrhage and is not associated with in-hospital or 90-day case fatality in patients with aneurysmal subarachnoid hemorrhage with intraparenchymal extension.
C1 [Brouwers, H. Bart; Kimberly, W. Taylor; Rosand, Jonathan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA 02114 USA.
[Brouwers, H. Bart; Kimberly, W. Taylor; Schwab, Kristin; Greenberg, Steven M.; Rosand, Jonathan; Goldstein, Joshua N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA.
[Brouwers, H. Bart; Ogilvy, Christopher S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02114 USA.
[Romero, Javier M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA.
[Goldstein, Joshua N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02114 USA.
[Brouwers, H. Bart; Backes, Daan; Klijn, Catharina J. M.; Regli, Luca; Rinkel, Gabriel J. E.] Rudolf Magnus Inst Neurosci, Dept Neurol & Neurosurg, NL-3508 TA Utrecht, Netherlands.
[Velthuis, Birgitta K.] Univ Utrecht, Univ Med Ctr Utrecht, Dept Radiol, Utrecht, Netherlands.
[Regli, Luca] Univ Zurich, Univ Zurich Hosp, Dept Neurosurg, Zurich, Switzerland.
RP Brouwers, HB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res,Rosand Lab, 185 Cambridge St,CPZN 6818, Boston, MA 02114 USA.
EM brouwers@chgr.mgh.harvard.edu
RI Klijn, C.J.M. (Karin)/E-1700-2016; Goldstein, Joshua/H-8953-2016
FU National Institutes of Health-National Institute of Neurological
Disorders and Stroke (NIH-NINDS) [R01NS073344, R01NS059727,
5K23NS059774]; American Heart Association Grant [0755984T]; Andrew D.
Heitman Neurovascular Research Fund; NIH-NINDS SPOTRIAS fellowship
[P50NS051343]; NIH; AHA; NINDS
FX The project described was supported by grant numbers R01NS073344,
R01NS059727, and 5K23NS059774 from the National Institutes of
Health-National Institute of Neurological Disorders and Stroke
(NIH-NINDS), American Heart Association Grant Number 0755984T, and the
Andrew D. Heitman Neurovascular Research Fund. Dr Brouwers was supported
by the NIH-NINDS SPOTRIAS fellowship grant P50NS051343. Dr Kimberly
received a research grant from Andrew D. Heitman Neurovascular Research
Fund. Dr Greenberg received a research grant from NIH. Dr Rosand
received a research grant from NIH and AHA; Dr Goldstein received a
research grant from NINDS.
NR 16
TC 2
Z9 2
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
J9 STROKE
JI Stroke
PD JUN
PY 2013
VL 44
IS 6
BP 1590
EP 1594
DI 10.1161/STROKEAHA.111.000586
PG 5
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 151MU
UT WOS:000319465400024
PM 23572475
ER
PT J
AU Adib-Samii, P
Rost, N
Traylor, M
Devan, W
Biffi, A
Lanfranconi, S
Fitzpatrick, K
Bevan, S
Kanakis, A
Valant, V
Gschwendtner, A
Malik, R
Richie, A
Gamble, D
Segal, H
Parati, EA
Ciusani, E
Holliday, EG
Maguire, J
Wardlaw, J
Worrall, B
Bis, J
Wiggins, KL
Longstreth, W
Kittner, SJ
Cheng, YC
Mosley, T
Falcone, GJ
Furie, KL
Leiva-Salinas, C
Lau, BC
Khan, MS
Sharma, P
Fornage, M
Mitchell, BD
Psaty, BM
Sudlow, C
Levi, C
Boncoraglio, GB
Rothwell, PM
Meschia, J
Dichgans, M
Rosand, J
Markus, HS
AF Adib-Samii, Poneh
Rost, Natalia
Traylor, Matthew
Devan, William
Biffi, Alessandro
Lanfranconi, Silvia
Fitzpatrick, Kaitlin
Bevan, Steve
Kanakis, Allison
Valant, Valerie
Gschwendtner, Andreas
Malik, Rainer
Richie, Alexa
Gamble, Dale
Segal, Helen
Parati, Eugenio A.
Ciusani, Emilio
Holliday, Elizabeth G.
Maguire, Jane
Wardlaw, Joanna
Worrall, Bradford
Bis, Joshua
Wiggins, Kerri L.
Longstreth, Will
Kittner, Steve J.
Cheng, Yu-Ching
Mosley, Thomas
Falcone, Guido J.
Furie, Karen L.
Leiva-Salinas, Carlos
Lau, Benison C.
Khan, Muhammed Saleem
Sharma, Pankaj
Fornage, Myriam
Mitchell, Braxton D.
Psaty, Bruce M.
Sudlow, Cathie
Levi, Christopher
Boncoraglio, Giorgio B.
Rothwell, Peter M.
Meschia, James
Dichgans, Martin
Rosand, Jonathan
Markus, Hugh S.
CA Australian Stroke Genetics Collabo
Wellcome Trust Case-Control Consor
METASTROKE
Int Stroke Genetics Consortium
TI 17q25 Locus Is Associated With White Matter Hyperintensity Volume in
Ischemic Stroke, But Not With Lacunar Stroke Status
SO STROKE
LA English
DT Article
DE genetics; Genome-wide Association Study; leukoaraiosis; small-vessel
disease; stroke
ID GENOME-WIDE ASSOCIATION; ATRIAL-FIBRILLATION; RISK; METAANALYSIS;
CLASSIFICATION; POPULATION; EXPRESSION; SUBTYPES; COHORT; MRI
AB Background and Purpose-Recently, a novel locus at 17q25 was associated with white matter hyperintensities (WMH) on MRI in stroke-free individuals. We aimed to replicate the association with WMH volume (WMHV) in patients with ischemic stroke. If the association acts by promoting a small vessel arteriopathy, it might be expected to also associate with lacunar stroke.
Methods-We quantified WMH on MRI in the stroke-free hemisphere of 2588 ischemic stroke cases. Association between WMHV and 6 single-nucleotide polymorphisms at chromosome 17q25 was assessed by linear regression. These single-nucleotide polymorphisms were also investigated for association with lacunar stroke in 1854 cases and 51 939 stroke-free controls from METASTROKE. Meta-analyses with previous reports and a genetic risk score approach were applied to identify other novel WMHV risk variants and uncover shared genetic contributions to WMHV in community participants without stroke and ischemic stroke.
Results-Single-nucleotide polymorphisms at 17q25 were associated with WMHV in ischemic stroke, the most significant being rs9894383 (P=0.0006). In contrast, there was no association between any single-nucleotide polymorphism and lacunar stroke. A genetic risk score analysis revealed further genetic components to WMHV shared between community participants without stroke and ischemic stroke.
Conclusions-This study provides support for an association between the 17q25 locus and WMH. In contrast, it is not associated with lacunar stroke, suggesting that the association does not act by promoting small-vessel arteriopathy or the same arteriopathy responsible for lacunar infarction.
C1 [Adib-Samii, Poneh; Traylor, Matthew; Lanfranconi, Silvia; Bevan, Steve; Markus, Hugh S.] St Georges Univ London, Stroke & Dementia Res Ctr, London, England.
[Rost, Natalia; Devan, William; Biffi, Alessandro; Fitzpatrick, Kaitlin; Kanakis, Allison; Valant, Valerie; Falcone, Guido J.; Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Rost, Natalia; Devan, William; Biffi, Alessandro; Fitzpatrick, Kaitlin; Kanakis, Allison; Valant, Valerie; Falcone, Guido J.; Rosand, Jonathan] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Rost, Natalia] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[Gschwendtner, Andreas; Malik, Rainer; Dichgans, Martin] Univ Munich, Inst Stroke & Dementia Res, Klinikum Univ Munchen, Munich, Germany.
[Richie, Alexa; Gamble, Dale; Maguire, Jane] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA.
[Segal, Helen; Rothwell, Peter M.] Univ Oxford, Nuffield Dept Neurosci, Stroke Prevent Res Unit, Oxford OX1 2JD, England.
[Parati, Eugenio A.; Boncoraglio, Giorgio B.] Fdn IRCCS Ist Neurol Carlo Besta, Dept Cerebrovasc Dis, Milan, Italy.
[Ciusani, Emilio] Fdn IRCCS Ist Neurol Carlo Besta, Lab Clin Pathol & Med Genet, Milan, Italy.
[Holliday, Elizabeth G.; Levi, Christopher] Univ Newcastle, Ctr Clin Epidemiol & Biostat, Hunter Med Res Inst, Callaghan, NSW 2308, Australia.
[Holliday, Elizabeth G.; Levi, Christopher] Univ Newcastle, Sch Med & Publ Hlth, Callaghan, NSW 2308, Australia.
[Meschia, James] Univ Newcastle, Prior Res Ctr Translat Neurosci & Mental Hlth, Callaghan, NSW 2308, Australia.
[Meschia, James] Univ Newcastle, Fac Hlth, Sch Nursing & Midwifery, Callaghan, NSW 2308, Australia.
[Wardlaw, Joanna; Levi, Christopher] Univ Edinburgh, Div Clin Neurosci, Edinburgh, Midlothian, Scotland.
[Wardlaw, Joanna; Levi, Christopher] Univ Edinburgh, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland.
[Worrall, Bradford] Univ Virginia, Charlottesville, VA USA.
[Bis, Joshua; Wiggins, Kerri L.; Longstreth, Will] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Kittner, Steve J.; Cheng, Yu-Ching] Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA.
[Kittner, Steve J.] Vet Affairs Med Ctr, Baltimore, MD USA.
[Mosley, Thomas] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA.
[Furie, Karen L.] Brown Univ, Dept Neurol, Providence, RI 02912 USA.
[Leiva-Salinas, Carlos; Lau, Benison C.] Univ Virginia, Dept Radiol, Charlottesville, VA USA.
[Khan, Muhammed Saleem; Sharma, Pankaj] Univ London Imperial Coll Sci Technol & Med, ICCRU, London, England.
[Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Houston, TX USA.
[Psaty, Bruce M.] Grp Hlth Res Inst, Grp Hlth, Seattle, WA USA.
[Rosand, Jonathan] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
RP Markus, HS (reprint author), Univ London, London SW17 0RE, England.
EM hmarkus@sgul.ac.uk
RI Boncoraglio, Giorgio/B-8647-2011; Blackwell, Jenefer/H-3015-2015;
Falcone, Guido/L-2287-2016;
OI Mitchell, Braxton/0000-0003-4920-4744; Falcone,
Guido/0000-0002-6407-0302; Wardlaw, Joanna/0000-0002-9812-6642; Traylor,
Matthew/0000-0001-6624-8621; Gillman, Matthew/0000-0002-2340-6930;
Plomin, Robert/0000-0002-0756-3629; Bevan, Steve/0000-0003-0490-6830
FU Stroke Association; MRC (Training Fellowship); NINDS [K23NS064052];
Wellcome Trust (WTCCC2); Intramural Research Program (NIA); Intramural
Research Program (MGH); Intramural Research Program (ISGS); National
Institute for Neurological Disorders and Stroke (SWISS); National
Institute for Neurological Disorders and Stroke (GASROS); National
Institute for Neurological Disorders and Stroke (ISGS); National
Institute for Neurological Disorders and Stroke (CHS); National
Institute for Neurological Disorders and Stroke (HVH); National
Institute for Neurological Disorders and Stroke (GEOS); Bugher
Foundation of the American Heart Association; MGH Deane Institute for
Integrative Study of Atrial Fibrillation and Stroke (GASROS); National
Institutes of Health Genes, Environment and Health Initiative, Medical
Research Service of the Department of Veterans Affairs and Centers for
Disease Control (GEOS); National Health & Medical Research Council
(ASGC); Italian Ministry of Health (Milan); National Human Genome
Research Institute (GASROS); National Human Genome Research Institute
(ARIC); National Heart, Lung, and Blood Institute (ARIC); National
Heart, Lung, and Blood Institute (CHS); National Heart, Lung, and Blood
Institute (HVH); Henry Smith Charity; British Council (BRAINS)
FX The principal funding for this study was provided by the Stroke
Association. The authors are supported by MRC (Training Fellowship, Dr
Adib-Samii) and NINDS (K23NS064052, Dr Rost). Funding for collection,
genotyping, and analysis of stroke samples was provided by Wellcome
Trust (WTCCC2), the Intramural Research Program (NIA; MGH, ISGS),
National Institute for Neurological Disorders and Stroke (SWISS, GASROS,
ISGS, CHS, HVH, GEOS), Bugher Foundation of the American Heart
Association, MGH Deane Institute for Integrative Study of Atrial
Fibrillation and Stroke (GASROS), National Institutes of Health Genes,
Environment and Health Initiative, Medical Research Service of the
Department of Veterans Affairs and Centers for Disease Control (GEOS),
National Health & Medical Research Council (ASGC), Italian Ministry of
Health (Milan), National Human Genome Research Institute (GASROS),
ARIC), National Heart, Lung, and Blood Institute (ARIC, CHS, HVH), Henry
Smith Charity, and the British Council (BRAINS).
NR 35
TC 21
Z9 21
U1 0
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 JUN
PY 2013
VL 44
IS 6
BP 1609
EP +
DI 10.1161/STROKEAHA.113.679936
PG 31
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 151MU
UT WOS:000319465400028
PM 23674528
ER
PT J
AU Dirnagl, U
Hakim, A
Macleod, M
Fisher, M
Howells, D
Alan, SM
Steinberg, G
Planas, A
Boltze, J
Savitz, S
Iadecola, C
Meairs, S
AF Dirnagl, Ulrich
Hakim, Antoine
Macleod, Malcolm
Fisher, Marc
Howells, David
Alan, Stuart M.
Steinberg, Gary
Planas, Anna
Boltze, Johannes
Savitz, Sean
Iadecola, Costantino
Meairs, Stephen
TI A Concerted Appeal for International Cooperation in Preclinical Stroke
Research
SO STROKE
LA English
DT Article
DE cerebral ischemia; roadblock; translational medicine
ID TISSUE-PLASMINOGEN-ACTIVATOR; ACUTE ISCHEMIC-STROKE; NEUROLOGICAL
DISEASE; NEUROVASCULAR UNIT; CLINICAL STROKE; EMBOLIC STROKE;
CARDIAC-ARREST; THROMBOLYSIS; MECHANISMS; BEDSIDE
C1 [Dirnagl, Ulrich] Charite, Ctr Stroke Res, Dept Neurol & Expt Neurol, D-10098 Berlin, Germany.
[Hakim, Antoine] Ottawa Hosp Res Inst, Ottawa, ON, Canada.
[Macleod, Malcolm] Univ Edinburgh, Ctr Clin Brain Sci, Div Clin Neurosci, Edinburgh, Midlothian, Scotland.
[Fisher, Marc] Univ Massachusetts, Sch Med, Worcester, MA USA.
[Howells, David] Melbourne Brain Ctr, Florey Inst Neurosci & Mental Hlth, Heidelberg, Vic, Australia.
[Alan, Stuart M.] Univ Manchester, Fac Life Sci, Manchester, Lancs, England.
[Steinberg, Gary] Stanford Univ, Sch Med, Dept Neurosurg, Stanford Stroke Ctr, Stanford, CA 94305 USA.
[Steinberg, Gary] Stanford Univ, Sch Med, Stanford Inst Neuroinnovat & Translat Neurosci, Stanford, CA 94305 USA.
[Planas, Anna] Univ Barcelona, Invest Biomed August Pi & Sunyer IDIBAPS, E-08007 Barcelona, Spain.
[Boltze, Johannes] Fraunhofer Inst Cell Therapy & Immunol, Leipzig, Germany.
[Boltze, Johannes] Translat Ctr Regenerat Med, Leipzig, Germany.
[Boltze, Johannes] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Boltze, Johannes] Harvard Univ, Sch Med, Boston, MA USA.
[Savitz, Sean] Univ Texas Med Sch Houston, Stroke Team, Dept Neurol, Houston, TX USA.
[Iadecola, Costantino] Weill Cornell Med Coll, Brain & Mind Res Inst, New York, NY USA.
[Meairs, Stephen] Heidelberg Univ, Dept Neurol, Univ Med Mannheim, Heidelberg, Germany.
RP Dirnagl, U (reprint author), Charite, Ctr Stroke Res Berlin, Dept Neurol & Expt Neurol, Campus Mitte, D-10098 Berlin, Germany.
EM Ulrich.dirnagl@charite.de
RI Planas, Anna /J-5991-2014;
OI Planas, Anna /0000-0002-6147-1880; Howells, David/0000-0002-2512-7724;
Dirnagl, Ulrich/0000-0003-0755-6119; Macleod, Malcolm
Robert/0000-0001-9187-9839
FU Medical Research Council [G0800803]; NINDS NIH HHS [R01 NS034179, R01
NS073666]; National Centre for the Replacement, Refinement and Reduction
of Animals in Research [NC/L000970/1]
NR 66
TC 39
Z9 39
U1 1
U2 14
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
J9 STROKE
JI Stroke
PD JUN
PY 2013
VL 44
IS 6
BP 1754
EP 1760
DI 10.1161/STROKEAHA.113.000734
PG 7
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 151MU
UT WOS:000319465400054
PM 23598526
ER
PT J
AU Horgan, S
Meireles, OR
Jacobsen, GR
Sandler, BJ
Ferreres, A
Ramamoorthy, S
Savides, T
Katagiri, T
Dotai, T
Sedrak, M
Majid, SF
Nijhawan, S
Talamini, MA
AF Horgan, Santiago
Meireles, Ozanan R.
Jacobsen, Garth R.
Sandler, Bryan J.
Ferreres, Alberto
Ramamoorthy, Sonia
Savides, Thomas
Katagiri, Toshio
Dotai, Takayuki
Sedrak, Michael
Majid, Saniea F.
Nijhawan, Sheetal
Talamini, Mark A.
TI Broad clinical utilization of NOTES: is it safe?
SO SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES
LA English
DT Article; Proceedings Paper
CT Annual Meeting of the
Society-of-American-Gastrointestinal-and-Endoscopic-Surgeons (SAGES)
CY MAR 30-APR 02, 2011
CL San Antonio, TX
SP Soc Amer Gastrointestinal & Endoscop Surg (SAGES)
DE Achalasia; Cholecystectomy; Clinical papers/trials/research; Endoscopy;
NOTES; Obesity
ID ENDOSCOPIC CHOLECYSTECTOMY; PORCINE MODEL; SURGERY; SURVIVAL
AB Natural orifice transluminal endoscopic surgery (NOTES) has been the focus of several studies as a less invasive alternative to conventional laparoscopy to access and treat intracavitary organs. For the last 5 years, much has been accomplished with animal studies, yet the clinical utilization of this novel technique is still modest. After 2 years of experience in the laboratory, we started our clinical experience. We report our experience with clinical utilization of NOTES procedures from 2007 to 2010.
Under UCSD institutional review board-approved trials, 104 patients were enrolled under seven different NOTES protocols from 2007 to 2010, where a NOTES procedure was offered as an alternative to conventional treatments. The treated pathologies were cholelithiasis, biliary dyskinesia, acute and chronic appendicitis, ventral hernias, morbid obesity, and achalasia. The access routes included transgastric (TG), transvaginal (TV), transesophageal (TE), and perirectal (PR).
Among the 104 patients enrolled, 103 underwent a surgical procedure starting with diagnostic laparoscopy, and 94 cases were deemed appropriate to proceed via a NOTES approach. There were 9 aborted NOTES procedures at the time of the initial peritoneoscopy before creating a NOTES access route. The reasons to not proceed with a NOTES procedure in the TV cholecystectomy group (n = 5) were a large amount of pelvic adhesions in 4 patients and a severe inflammation of the gallbladder in 1 patient. In the TG cholecystectomy group (n = 1), it was severe inflammation of the gallbladder. In the TG appendectomy group (n = 1), it was the presence of localized peritonitis. In the TE endoscopic myotomy group (n = 2), it was the presence of megaesophagus with an inability to clean the esophagus of food debris. The NOTES procedures performed were 48 TV cholecystectomies, 4 TV appendectomies, 8 TG cholecystectomies, 2 PR peritoneoscopies, 3 TG appendectomies, 3 TV ventral hernia repairs, 5 TE endoscopic myotomies, 3 TV sleeve gastrectomies, and 18 TG sleeve gastrectomies. The average body mass indexes for those in the sleeve gastrectomy group was 42.1 kg/m(2) (TG route) and 40.6 kg/m(2) (TV route). There were no intraoperative complication and no conversions to standard laparoscopy during these procedures. The average hospital stay was 1-2 days. One patient who underwent TV cholecystectomy required an emergency department visit for nausea and vomiting. To date, 3 patients who underwent TV cholecystectomy have become pregnant and delivered normally.
NOTES is safe, feasible, and reproducible with previous training in the laboratory and a consistent team at a high-volume center. Prospective randomized studies of a large patient population are necessary to assess long-term results.
C1 [Horgan, Santiago; Jacobsen, Garth R.; Sandler, Bryan J.; Ferreres, Alberto; Ramamoorthy, Sonia; Savides, Thomas; Katagiri, Toshio; Dotai, Takayuki; Sedrak, Michael; Majid, Saniea F.; Nijhawan, Sheetal; Talamini, Mark A.] Univ Calif San Diego, Dept Surg, Div Minimally Invas Surg, San Diego, CA 92103 USA.
[Meireles, Ozanan R.] Harvard Univ, Sch Med, Dept Surg, Div Minimally Invas Surg,Massachusetts Gen Hosp, Boston, MA 02115 USA.
RP Meireles, OR (reprint author), Harvard Univ, Sch Med, Dept Surg, Div Minimally Invas Surg,Massachusetts Gen Hosp, Boston, MA 02115 USA.
EM shorgan@ucsd.edu; omeireles@partners.org
NR 16
TC 9
Z9 11
U1 0
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0930-2794
J9 SURG ENDOSC
JI Surg. Endosc.
PD JUN
PY 2013
VL 27
IS 6
BP 1872
EP 1880
DI 10.1007/s00464-012-2736-z
PG 9
WC Surgery
SC Surgery
GA 150AF
UT WOS:000319361900004
PM 23479251
ER
PT J
AU Lane, BF
Wong-You-Cheong, JJ
Javitt, MC
Glanc, P
Brown, DL
Dubinsky, T
Harisinghani, MG
Harris, RD
Khati, NJ
Mitchell, DG
Pandharipande, PV
Pannu, HK
Podrasky, AE
Shipp, TD
Siegel, CL
Simpson, L
Wall, DJ
Zelop, CM
AF Lane, Barton F.
Wong-You-Cheong, Jade J.
Javitt, Marcia C.
Glanc, Phyllis
Brown, Douglas L.
Dubinsky, Theodore
Harisinghani, Mukesh G.
Harris, Robert D.
Khati, Nadia J.
Mitchell, Donald G.
Pandharipande, Pari V.
Pannu, Harpreet K.
Podrasky, Anne E.
Shipp, Thomas D.
Siegel, Cary Lynn
Simpson, Lynn
Wall, Darci J.
Zelop, Carolyn M.
TI ACR Appropriateness Criteria (R) First Trimester Bleeding
SO ULTRASOUND QUARTERLY
LA English
DT Article
DE Appropriateness Criteria; vaginal bleeding; early pregnancy; ectopic
pregnancy; threatened abortion; first trimester bleeding
ID EARLY INTRAUTERINE PREGNANCY; GESTATIONAL TROPHOBLASTIC DISEASE;
EMBRYONIC HEART-RATE; ECTOPIC PREGNANCY; INTRADECIDUAL SIGN;
1ST-TRIMESTER PREGNANCIES; INTERSTITIAL PREGNANCY; TRANSVAGINAL US;
ENDOVAGINAL US; CORPUS-LUTEUM
AB Vaginal bleeding is not uncommon in the first trimester of pregnancy. Ultrasound is the foremost modality for evaluating normal development of the gestational sac and embryo and for discriminating the causes of bleeding. While correlation with quantitative beta HCG and clinical presentation is essential, sonographic criteria permit diagnosis of failed pregnancies, ectopic pregnancy, gestational trophoblastic disease and spontaneous abortion. The American College of Radiology Appropriateness Criteria guidelines have been updated to incorporate recent data. A failed pregnancy may be diagnosed when there is absence of cardiac activity in an embryo exceeding 7 mm in crown rump length or absence of an embryo when the mean sac diameter exceeds 25 mm. In a stable patient with no intrauterine pregnancy and normal adnexae, close monitoring is advised. The diagnosis of ectopic pregnancy should be based on positive findings rather than on the absence of an intrauterine sac above a threshold level of beta HCG. Following abortion, ultrasound can discriminate retained products of conception from clot and arteriovenous fistulae. The American College of Radiology Appropriateness Criteria (R) are evidence-based guidelines for specific clinical conditions that are reviewed every two years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.
C1 [Lane, Barton F.; Wong-You-Cheong, Jade J.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
[Javitt, Marcia C.] Walter Reed Natl Mil Med Ctr, Bethesda, MD USA.
[Glanc, Phyllis] Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada.
[Brown, Douglas L.; Wall, Darci J.] Mayo Clin, Rochester, MN USA.
[Dubinsky, Theodore] Univ Washington, Sch Med, Seattle, WA USA.
[Harisinghani, Mukesh G.; Pandharipande, Pari V.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Harris, Robert D.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA.
[Khati, Nadia J.] George Washington Univ Hosp, Washington, DC USA.
[Mitchell, Donald G.] Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA.
[Pannu, Harpreet K.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Podrasky, Anne E.] Baptist Hosp Miami, South Miami Ctr Women & Infants, Miami, FL USA.
[Shipp, Thomas D.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Siegel, Cary Lynn] Washington Univ, Med Ctr, Mallinckrodt Inst Radiol, St Louis, MO 63110 USA.
[Simpson, Lynn] Columbia Univ, New York, NY USA.
[Zelop, Carolyn M.] Valley Hosp, Ridgewood, NJ USA.
RP Wong-You-Cheong, JJ (reprint author), Univ Maryland, Med Ctr, Dept Diagnost Radiol, 22 S Greene St, Baltimore, MD 21201 USA.
EM jwong@umm.edu
NR 61
TC 2
Z9 2
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0894-8771
J9 ULTRASOUND Q
JI Ultrasound Q.
PD JUN
PY 2013
VL 29
IS 2
BP 91
EP 96
DI 10.1097/RUQ.0b013e31829158c2
PG 6
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 152AZ
UT WOS:000319503100002
PM 23665531
ER
PT J
AU Gavin, J
Gu, XK
Gornik, HL
Olin, JW
Kim, ESH
Mace, PD
Gray, BH
Bachrach, JM
Jaff, MR
McBane, RD
Matsumoto, AH
Kline-Rogers, E
Froehlich, JB
AF Gavin, Jordan
Gu, Xiaokui
Gornik, Heather L.
Olin, Jeffrey W.
Kim, Esther S. H.
Mace, Pamela D.
Gray, Bruce H.
Bachrach, J. Michael
Jaff, Michael R.
McBane, Robert D.
Matsumoto, Alan H.
Kline-Rogers, Eva
Froehlich, James B.
TI Factors associated with delay in diagnosis of patients with
fibromuscular dysplasia: A report from the United States Registry for
Fibromuscular Dysplasia
SO VASCULAR MEDICINE
LA English
DT Meeting Abstract
C1 [Gavin, Jordan; Gu, Xiaokui; Kline-Rogers, Eva; Froehlich, James B.] Univ Michigan, Ann Arbor, MI 48109 USA.
[Gornik, Heather L.; Kim, Esther S. H.; Mace, Pamela D.] Cleveland Clin, Cleveland, OH 44106 USA.
[Olin, Jeffrey W.] Mt Sinai, New York, NY USA.
[Gray, Bruce H.] Greenville Hosp Syst, Greenville, SC USA.
[Bachrach, J. Michael] North Cent Heart, Sioux Falls, SD USA.
[Jaff, Michael R.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[McBane, Robert D.] Mayo Clin, Rochester, MN USA.
[Matsumoto, Alan H.] Univ Virginia, Charlottesville, VA USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1358-863X
J9 VASC MED
JI Vasc. Med.
PD JUN
PY 2013
VL 18
IS 3
BP 156
EP 157
PG 2
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 153MS
UT WOS:000319606800018
ER
PT J
AU van der Pluijm, W
Di Eusanio, M
Fattori, R
Voehringer, M
Myrmel, T
Peterson, MD
O'Gara, P
Russo, MJ
Evangelista, A
Montgomery, DG
Eagle, KA
Isselbacher, EM
Nienaber, CA
AF van der Pluijm, Wouter
Di Eusanio, Marco
Fattori, Rossella
Voehringer, Matthias
Myrmel, Truls
Peterson, Mark D.
O'Gara, Patrick
Russo, Mark J.
Evangelista, Arturo
Montgomery, Daniel G.
Eagle, Kim A.
Isselbacher, Eric M.
Nienaber, Christoph A.
TI Vessel involvement in Marfan syndrome patients
SO VASCULAR MEDICINE
LA English
DT Meeting Abstract
C1 [van der Pluijm, Wouter; Montgomery, Daniel G.; Eagle, Kim A.] Univ Michigan, Ann Arbor, MI 48109 USA.
[Di Eusanio, Marco; Fattori, Rossella] Univ Hosp S Orsola, Bologna, Italy.
[Voehringer, Matthias] Robert Bosch Krankenhaus, Stuttgart, Germany.
[Myrmel, Truls] Univ Tromso Hosp, N-9012 Tromso, Norway.
[Peterson, Mark D.] St Michaels Hosp, Toronto, ON M5B 1W8, Canada.
[O'Gara, Patrick] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Russo, Mark J.] Univ Chicago, Chicago, IL 60637 USA.
[Evangelista, Arturo] Hosp Gen Univ Vall dHebron, Barcelona, Spain.
[Isselbacher, Eric M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Nienaber, Christoph A.] Univ Rostock, D-18055 Rostock, Germany.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1358-863X
J9 VASC MED
JI Vasc. Med.
PD JUN
PY 2013
VL 18
IS 3
BP 161
EP 161
PG 1
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 153MS
UT WOS:000319606800027
ER
PT J
AU Weinberg, I
Gu, XK
Giri, J
Olin, JW
Froehlich, J
Gornik, HL
Rogers, KR
Jaff, MR
AF Weinberg, Ido
Gu, Xiaokui
Giri, Jay
Olin, Jeffery W.
Froehlich, James
Gornik, Heather L.
Rogers, Kevin R.
Jaff, Michael R.
TI Patterns of medication use in 615 patients with fibromuscular dysplasia.
A report of the United States Registry for Fibromuscular Dysplasia
SO VASCULAR MEDICINE
LA English
DT Meeting Abstract
C1 [Weinberg, Ido; Jaff, Michael R.] Massachusetts Gen Hosp, Inst Heart Vasc & Stroke Care, Boston, MA 02114 USA.
[Gu, Xiaokui; Froehlich, James] Univ Michigan, Ctr Cardiovasc, Ann Arbor, MI 48109 USA.
[Giri, Jay] Univ Penn, Div Cardiol, Philadelphia, PA 19104 USA.
[Olin, Jeffery W.] Mt Sinai New York, Zena & Michael Wiener Cardiovasc Inst, New York, NY USA.
[Olin, Jeffery W.] Mt Sinai New York, Marie Josee & Henry R Kravis Ctr Cardiovasc Hlth, New York, NY USA.
[Gornik, Heather L.] Case Western Reserve Univ, Cleveland Clin, Inst Heart & Vasc, Cleveland, OH 44106 USA.
[Gornik, Heather L.] Case Western Reserve Univ, Cleveland Clin, Lerner Coll Med, Cleveland, OH 44106 USA.
[Rogers, Kevin R.] Univ Colorado, Div Cardiol, Denver, CO 80202 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1358-863X
J9 VASC MED
JI Vasc. Med.
PD JUN
PY 2013
VL 18
IS 3
BP 168
EP 168
PG 1
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 153MS
UT WOS:000319606800041
ER
PT J
AU Bergman, BG
Greene, MC
Hoeppner, BB
Slaymaker, V
Kelly, JF
AF Bergman, B. G.
Greene, M. C.
Hoeppner, B. B.
Slaymaker, V.
Kelly, J. F.
TI PSYCHIATRIC COMORBIDITY AND 12-STEP PARTICIPATION: A LONGITUDINAL
INVESTIGATION OF TREATED YOUNG ADULTS
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 [Bergman, B. G.; Greene, M. C.; Hoeppner, B. B.; Slaymaker, V.; Kelly, J. F.] Massachusetts Gen Hosp, Ctr Addict Med, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 16A
EP 16A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998300022
ER
PT J
AU Labbe, AK
Greene, MC
Bergman, BG
Hoeppner, BB
Kelly, JF
AF Labbe, A. K.
Greene, M. C.
Bergman, B. G.
Hoeppner, B. B.
Kelly, J. F.
TI DOES AGE MATTER? THE EFFECT OF AGE COMPOSTION OF 12-STEP GROUPS ON YOUNG
ADULT PARTICIPATION AND SUBSTANCE USE OUTCOME
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 [Labbe, A. K.; Greene, M. C.; Bergman, B. G.; Hoeppner, B. B.; Kelly, J. F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Ctr Addict Med, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 16A
EP 16A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998300023
ER
PT J
AU Batki, SL
Lasher, BA
Metzler, T
Heinz, AJ
Herbst, E
Waldrop, A
Neylan, TC
Kalapatapu, R
AF Batki, S. L.
Lasher, B. A.
Metzler, T.
Heinz, A. J.
Herbst, E.
Waldrop, A.
Neylan, T. C.
Kalapatapu, R.
TI PREDICTORS OF OUTCOME IN A PILOT CONTROLLED TRIAL OF TOPIRAMATE FOR
ALCOHOL DEPENDENCE IN VETERANS WITH PTSD
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 [Batki, S. L.; Lasher, B. A.; Metzler, T.; Heinz, A. J.; Herbst, E.; Waldrop, A.; Neylan, T. C.; Kalapatapu, R.] San Francisco VA Med Ctr, UCSF Dept Psychiat, Addict Res Program, San Francisco, CA 94121 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 17A
EP 17A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998300026
ER
PT J
AU Santos, GM
Lasher, A
Heinz, AJ
Kalapatapu, R
Herbst, E
Metzler, T
Waldrop, A
Neylan, TC
Tarasovsky, G
Prathikanti, S
Jatlow, P
Batki, SL
AF Santos, G-M
Lasher, A.
Heinz, A. J.
Kalapatapu, R.
Herbst, E.
Metzler, T.
Waldrop, A.
Neylan, T. C.
Tarasovsky, G.
Prathikanti, S.
Jatlow, P.
Batki, S. L.
TI URINARY ETHYL GLUCURONIDE AND ETHYL SULFATE TESTING TO EVALUATE THE
EFFICACY OF TOPIRAMATE TREATMENT OF ALCOHOL DEPENDENCE IN VETERANS WITH
PTSD
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 [Santos, G-M; Lasher, A.; Heinz, A. J.; Kalapatapu, R.; Herbst, E.; Metzler, T.; Waldrop, A.; Neylan, T. C.; Tarasovsky, G.; Prathikanti, S.; Jatlow, P.; Batki, S. L.] San Francisco VA Med Ctr, UCSF Dept Psychiat, Addict Res Program, San Francisco, CA 94121 USA.
NR 0
TC 1
Z9 1
U1 1
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 19A
EP 19A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998300036
ER
PT J
AU Chen, S
Charness, ME
AF Chen, S.
Charness, M. E.
TI ANTAGONISM OF ALCOHOL INHIBITION OF L1-MEDIATED CELL ADHESION AND AXON
OUTGROWTH IN CEREBELLAR GRANULE NEURONS
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 Harvard Univ, Sch Med, VA Boston Healthcare Syst, West Roxbury, MA 02132 USA.
Harvard Univ, Sch Med, Dept Neurol, West Roxbury, MA 02132 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 49A
EP 49A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998300156
ER
PT J
AU Dou, X
Menkari, CE
Charness, ME
AF Dou, X.
Menkari, C. E.
Charness, M. E.
TI MULTIPLE KINASES REGULATE L1 SENSITIVITY TO ETHANOL THROUGH
PHOSPHORYLATION OF THE L1 CYTOPLASMIC DOMAIN
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 [Dou, X.; Menkari, C. E.; Charness, M. E.] Harvard Univ, Sch Med, Dept Neurol, VA Boston Healthcare Syst, West Roxbury, MA 02132 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 111A
EP 111A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998300403
ER
PT J
AU Below, MC
Brandon, KO
Goldman, MS
AF Below, M. C.
Brandon, K. O.
Goldman, M. S.
TI GROUPDRINK: SOCIAL FACILITATION OF DRINKING IN COLLEGE STUDENTS
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 [Below, M. C.; Brandon, K. O.; Goldman, M. S.] Univ S Florida, Dept Psychol, Alcohol & Subst Use Res Inst, Tampa, FL 33620 USA.
[Below, M. C.; Brandon, K. O.; Goldman, M. S.] VA Boston Healthcare Syst, Jamaica Plain, MA 02130 USA.
NR 0
TC 0
Z9 0
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 156A
EP 156A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998300584
ER
PT J
AU Wilhelm, CJ
Hashimoto, JG
Andrew, MR
Roberts, ML
Loftis, JM
Wiren, KM
AF Wilhelm, C. J.
Hashimoto, J. G.
Andrew, M. R.
Roberts, M. L.
Loftis, J. M.
Wiren, K. M.
TI PRO-INFLAMMATORY ACTIVATION FOLLOWING CHRONIC INTOXICATION IN FEMALE BUT
NOT MALE MICE
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 Portland VA Med Ctr, Res Serv, Portland, OR 97239 USA.
Oregon Hlth & Sci Univ, Portland, OR 97239 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 171A
EP 171A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998300641
ER
PT J
AU Rasmussen, DD
Kincaid, CL
Froehlich, JC
AF Rasmussen, D. D.
Kincaid, C. L.
Froehlich, J. C.
TI PRAZOSIN DECREASES ALCOHOL DRINKING DURING WITHDRAWAL IN RATS WITH A
PROLONGED HISTORY OF VOLUNTARY HIGH ALCOHOL DRINKING AND DEPENDENCE
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 VA Puget Sound Hlth Care Syst, VISN Mental Illness Res Educ & Clin Ctr MIRECC 20, Seattle, WA 98108 USA.
Univ Washington, Dept Psychiat, Seattle, WA 98108 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 174A
EP 174A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998300656
ER
PT J
AU Rasmussen, DD
Kincaid, CL
Froehlich, JC
AF Rasmussen, D. D.
Kincaid, C. L.
Froehlich, J. C.
TI PRAZOSIN plus NALTREXONE DECREASES ALCOHOL DRINKING MORE EFFECTIVELY
THAN DOES EITHER DRUG ALONE IN P RATS WITH HISTORY OF PROLONGED ALCOHOL
DEPENDENCE
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 VA Puget Sound Hlth Care Syst, VISN Mental Illness Res Educ & Clin Ctr MIRECC 20, Seattle, WA 98108 USA.
Univ Washington, Dept Psychiat, Seattle, WA 98108 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 175A
EP 175A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998300657
ER
PT J
AU Cates, LN
Nadav, T
Crabbe, JC
Phillips, TJ
Roberts, AJ
AF Cates, L. N.
Nadav, T.
Crabbe, J. C.
Phillips, T. J.
Roberts, A. J.
TI FENOFIBRATE, BUT NOT TESAGLITAZAR, REDUCED ETHANOL DRINKING IN HIGH
DRINKING-IN-THE-DARK MICE
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 [Cates, L. N.; Nadav, T.; Crabbe, J. C.; Phillips, T. J.; Roberts, A. J.] Scripps Res Inst, La Jolla, CA 92037 USA.
[Cates, L. N.; Nadav, T.; Crabbe, J. C.; Phillips, T. J.; Roberts, A. J.] Oregon Hlth & Sci Univ, Portland, OR 97239 USA.
[Cates, L. N.; Nadav, T.; Crabbe, J. C.; Phillips, T. J.; Roberts, A. J.] Portland VA Med Ctr, Portland, OR 97239 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 245A
EP 245A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998301123
ER
PT J
AU Gubner, NR
Phillips, TJ
AF Gubner, N. R.
Phillips, T. J.
TI THE EFFECT OF NICOTINE IN COMBINATION WITH ETHANOL ON THE DEVELOPMENT OF
BEHAVIORAL SENSITIZATION
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 [Gubner, N. R.; Phillips, T. J.] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Portland Alcohol Res Ctr, Dept Behav Neurosci, Portland, OR 97239 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 248A
EP 248A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998301135
ER
PT J
AU Buck, KJ
Walter, NAR
Denmark, DL
AF Buck, K. J.
Walter, N. A. R.
Denmark, D. L.
TI SUPRAMOLECULAR ORGANIZATION OF MITOCHONDRIAL RESPIRATORY CHAIN COMPLEXES
EXHIBITS STRAIN-DEPENDENCE IN C57BL6/J AND DBA/2J MOUSE BRAIN
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 Portland VA Med Ctr, Dept Behav Neurosci, Portland, OR 97239 USA.
Portland VA Med Ctr, Portland Alcohol Res Ctr, Portland, OR 97239 USA.
Oregon Hlth & Sci Univ, Portland, OR 97239 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 253A
EP 253A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998301153
ER
PT J
AU Leite-Morris, KA
AF Leite-Morris, K. A.
TI NEUROCHEMISTRY AND NEUROPHARMACOLOGY OF THE GABA-B RECEPTOR IN A RODENT
MODEL OF ALCOHOL BINDGE DRINKING
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 [Leite-Morris, K. A.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA.
[Leite-Morris, K. A.] Boston Univ, Sch Med, Dept Pharmacol, Boston, MA 02118 USA.
[Leite-Morris, K. A.] Boston Univ, Sch Med, Dept Expt Therapeut, Boston, MA 02118 USA.
[Leite-Morris, K. A.] VA Boston Healthcare Syst, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 255A
EP 255A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998301160
ER
PT J
AU Simpson, TL
Stappenbeck, CA
Luterek, JA
Lehavot, K
Kaysen, DL
AF Simpson, T. L.
Stappenbeck, C. A.
Luterek, J. A.
Lehavot, K.
Kaysen, D. L.
TI AN EVENT LEVEL EVALUATION OF THE INTERPLAY BETWEEN PTSD SYMPTOMS AND
ALCOHOL CONSUMPTION AMONG INDIVIDUALS WITH COMORBID PTSD AND ALCOHOL
DEPENDENCE
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 [Simpson, T. L.; Stappenbeck, C. A.; Luterek, J. A.; Lehavot, K.; Kaysen, D. L.] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 270A
EP 270A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998301221
ER
PT J
AU Lapham, GT
Rubinsky, AD
Hawkins, EJ
Williams, EC
Kivlahan, DJ
Bradley, KA
AF Lapham, G. T.
Rubinsky, A. D.
Hawkins, E. J.
Williams, E. C.
Kivlahan, D. J.
Bradley, K. A.
TI ANNUAL ALCOHOL SCREENING MAY NOT BE NECESSARY FOR NONDRINKERS WITH
MULTIPLE PRIOR NEGATIVE SCREENS
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 [Lapham, G. T.; Rubinsky, A. D.; Hawkins, E. J.; Williams, E. C.; Kivlahan, D. J.; Bradley, K. A.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Ctr Excellence, Seattle, WA 98101 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 286A
EP 286A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998301286
ER
PT J
AU Kelly, JF
Hoeppner, BB
AF Kelly, J. F.
Hoeppner, B. B.
TI DO MEN AND WOMEN BENEFIT DIFFERENTLY FROM ALCOHOLICS ANONYMOUS? A
MODERATED MULTIPLE MEDIATION ANALYSIS IN A LARGE CLINICAL SAMPLE
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 36th Annual Scientific Meeting of the Research-Society-on-Alcoholism
CY JUN 22-26, 2013
CL Orlando, FL
SP Res Soc Alcoholism
C1 [Kelly, J. F.; Hoeppner, B. B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2013
VL 37
SU 2
SI SI
BP 292A
EP 292A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 145EU
UT WOS:000318998301309
ER
PT J
AU Walkey, AJ
Greiner, MA
Heckbert, SR
Jensen, PN
Piccini, JP
Sinner, MF
Curtis, LH
Benjamin, EJ
AF Walkey, Allan J.
Greiner, Melissa A.
Heckbert, Susan R.
Jensen, Paul N.
Piccini, Jonathan P.
Sinner, Moritz F.
Curtis, Lesley H.
Benjamin, Emelia J.
TI Atrial fibrillation among Medicare beneficiaries hospitalized with
sepsis: Incidence and risk factors
SO AMERICAN HEART JOURNAL
LA English
DT Article
ID ICD-9-CM CODES; UNITED-STATES; HEART; EPIDEMIOLOGY; OUTCOMES; SURGERY;
STROKE; COHORT; GUIDELINES; ACCURACY
AB Background Newly diagnosed atrial fibrillation (AF) during severe sepsis is associated with increased risks of in-hospital stroke and mortality. However, the prevalence, incidence, and risk factors associated with AF during the sepsis syndromes are unclear.
Methods We identified patients with preexisting, newly diagnosed, or no AF in a nationally representative 5% sample of Medicare beneficiaries hospitalized with sepsis between 2004 and 2007. We identified multivariable-adjusted demographic and clinical characteristics associated with development of newly diagnosed AF during a sepsis hospitalization.
Results A total of 60,209 beneficiaries had a sepsis hospitalization. Mean age was 80.2 years, 44.4% were men, and 83.1% were white. Atrial fibrillation occurred during 25.5% (95% CI 25.2-25.9) of sepsis hospitalizations, including 18.3% (18.0%-18.7%) with preexisting AF and 7.2% (7.0%-7.4%) with newly diagnosed AF. Patients with sepsis requiring intensive care had a greater risk of newly diagnosed AF (10.7%, 95% CI 10.3%-11.1%) compared with patients who did not require intensive care (4.4%, 4.2%-4.5%, P < .001). In multivariable analysis, factors associated with newly diagnosed AF during sepsis included older age, white race, acute organ dysfunction, intensive care unit admission, mechanical ventilation, right heart catheterization, diagnosis of endocarditis, and coronary artery bypass graft surgery. Cardiovascular comorbid conditions generally were not associated with increased risk for newly diagnosed AF during sepsis.
Conclusions Atrial fibrillation is common among critically ill patients with sepsis. Acute factors, rather than preexisting cardiovascular comorbid conditions, are associated with increased risk for newly diagnosed AF during sepsis, suggesting that mechanisms of newly diagnosed AF during sepsis may differ from the general population of patients with AF.
C1 [Walkey, Allan J.] Boston Univ, Sch Med, Dept Med, Pulm Ctr, Boston, MA 02118 USA.
[Walkey, Allan J.] Boston Univ, Sch Med, Dept Med, Sect Pulm & Crit Care Med, Boston, MA 02118 USA.
[Greiner, Melissa A.; Piccini, Jonathan P.; Curtis, Lesley H.] Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA.
[Heckbert, Susan R.; Jensen, Paul N.] Univ Washington, Dept Epidemiol, Sch Publ Hlth, Seattle, WA 98195 USA.
[Piccini, Jonathan P.; Curtis, Lesley H.] Duke Univ, Sch Med, Dept Med, Durham, NC 27706 USA.
[Sinner, Moritz F.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA.
[Sinner, Moritz F.] Univ Munich, Univ Hosp Grosshadern, Dept Med 1, Munich, Germany.
[Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Sect Cardiovasc Med, Boston, MA 02118 USA.
[Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Sect Prevent Med, Boston, MA 02118 USA.
[Benjamin, Emelia J.] Boston Univ, Dept Epidemiol, Sch Publ Hlth, Boston, MA USA.
RP Walkey, AJ (reprint author), 72 East Concord St,R-304, Boston, MA 02118 USA.
EM alwalkey@bu.edu
OI Walkey, Allan/0000-0003-4685-6894; Benjamin, Emelia/0000-0003-4076-2336
FU Bayer HealthCare; Boston Scientific; Johnson Johnson
FX Dr Piccini reported receiving research support from Bayer HealthCare,
Boston Scientific, and Johnson & Johnson and receiving personal income
for participation on an advisory board for Sanofi-Aventis. Dr Curtis
reported receiving research support from Johnson & Johnson. Drs Piccini
and Curtis have made available online detailed listings of financial
disclosures (http://www.dcri.duke.edu/about-us/conflict-of-interest/).
No other disclosures were reported.
NR 32
TC 26
Z9 26
U1 0
U2 9
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-8703
J9 AM HEART J
JI Am. Heart J.
PD JUN
PY 2013
VL 165
IS 6
BP 949
EP +
DI 10.1016/j.ahj.2013.03.020
PG 10
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 151DD
UT WOS:000319439900017
PM 23708166
ER
PT J
AU Albayrak, O
Putter, C
Volckmar, AL
Cichon, S
Hoffmann, P
Nothen, MM
Jockel, KH
Schreiber, S
Wichmann, HE
Faraone, SV
Neale, BM
Herpertz-Dahlmann, B
Lehmkuhl, G
Sinzig, J
Renner, TJ
Romanos, M
Warnke, A
Lesch, KP
Reif, A
Schimmelmann, BG
Scherag, A
Hebebrand, J
Hinney, A
AF Albayrak, Oezguer
Puetter, Carolin
Volckmar, Anna-Lena
Cichon, Sven
Hoffmann, Per
Noethen, Markus M.
Joeckel, Karl-Heinz
Schreiber, Stefan
Wichmann, H-Erich
Faraone, Stephen V.
Neale, Benjamin M.
Herpertz-Dahlmann, Beate
Lehmkuhl, Gerd
Sinzig, Judith
Renner, Tobias J.
Romanos, Marcel
Warnke, Andreas
Lesch, Klaus-Peter
Reif, Andreas
Schimmelmann, Benno G.
Scherag, Andre
Hebebrand, Johannes
Hinney, Anke
CA Psychiat GWAS Consortium ADHD Subg
TI Common obesity risk alleles in childhood attention-deficit/hyperactivity
disorder
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS
LA English
DT Article
DE body mass index; inattention; genetic risk factor; genome wide
association study; weight regulation
ID GENOME-WIDE ASSOCIATION; DEFICIT HYPERACTIVITY DISORDER; FACTOR GENE
BDNF; BODY-MASS INDEX; NEUROTROPHIC FACTOR; CONDUCT DISORDER; GROWTH
DEFICITS; CHILDREN; ADHD; ADOLESCENTS
AB Children with attention-deficit/hyperactivity disorder (ADHD) have a higher rate of obesity than children without ADHD. Obesity risk alleles may overlap with those relevant for ADHD. We examined whether risk alleles for an increased body mass index (BMI) are associated with ADHD and related quantitative traits (inattention and hyperactivity/impulsivity). We screened 32 obesity risk alleles of single nucleotide polymorphisms (SNPs) in a genome-wide association study (GWAS) for ADHD based on 495 patients and 1,300 population-based controls and performed in silico analyses of the SNPs in an ADHD meta-analysis comprising 2,064 trios, 896 independent cases, and 2,455 controls. In the German sample rs206936 in the NUDT3 gene (nudix; nucleoside diphosphate linked moiety X-type motif 3) was associated with ADHD risk (OR: 1.39; P=3.4x104; Pcorr=0.01). In the meta-analysis data we found rs6497416 in the intronic region of the GPRC5B gene (G protein-coupled receptor, family C, group 5, member B; P=7.2x104; Pcorr=0.02) as a risk allele for ADHD. GPRC5B belongs to the metabotropic glutamate receptor family, which has been implicated in the etiology of ADHD. In the German sample rs206936 (NUDT3) and rs10938397 in the glucosamine-6-phosphate deaminase 2 gene (GNPDA2) were associated with inattention, whereas markers in the mitogen-activated protein kinase 5 gene (MAP2K5) and in the cell adhesion molecule 2 gene (CADM2) were associated with hyperactivity. In the meta-analysis data, MAP2K5 was associated with inattention, GPRC5B with hyperactivity/impulsivity and inattention and CADM2 with hyperactivity/impulsivity. Our results justify further research on the elucidation of the common genetic background of ADHD and obesity. (c) 2013 Wiley Periodicals, Inc.
C1 [Albayrak, Oezguer; Volckmar, Anna-Lena; Hebebrand, Johannes; Hinney, Anke] Univ Duisburg Essen, Dept Child & Adolescent Psychiat Psychotherapy &, LVR Klinikum Essen, D-45147 Essen, Germany.
[Puetter, Carolin; Joeckel, Karl-Heinz; Scherag, Andre] Univ Duisburg Essen, Inst Med Informat Biometry & Epidemiol, D-45147 Essen, Germany.
[Cichon, Sven] Res Ctr Julich, Struct & Funct Org Brain, Inst Neurosci & Med INM 1, Julich, Germany.
[Cichon, Sven; Hoffmann, Per; Noethen, Markus M.] Univ Bonn, Inst Human Genet, Bonn, Germany.
[Hoffmann, Per; Noethen, Markus M.] Univ Bonn, Life & Brain Ctr, Dept Genom, Bonn, Germany.
[Schreiber, Stefan] Univ Hosp Schleswig Holstein, Inst Clin Mol Biol, Popgen Study Grp, Kiel, Germany.
[Wichmann, H-Erich] German Res Ctr Environm Hlth, Helmholtz Ctr Munich, Inst Epidemiologyl, KORA Study Grp, Munich, Germany.
[Faraone, Stephen V.] SUNY Upstate Med Univ, Syracuse, NY 13210 USA.
[Neale, Benjamin M.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Neale, Benjamin M.] Broad Inst Harvard & Massachusetts Inst Technol, Cambridge, MA USA.
[Herpertz-Dahlmann, Beate] Rhein Westfal TH Aachen, Dept Child & Adolescent Psychiat, Aachen, Germany.
[Lehmkuhl, Gerd; Sinzig, Judith] Univ Cologne, Dept Child & Adolescent Psychiat, Cologne, Germany.
[Sinzig, Judith] LVR Linikum Bonn, Dept Child & Adolescent Psychiat & Psychotherapy, Bonn, Germany.
[Renner, Tobias J.; Romanos, Marcel; Warnke, Andreas] Univ Wurzburg, Dept Child & Adolescent Psychiat, Wurzburg, Germany.
[Romanos, Marcel] Univ Munich, Dept Child & Adolescent Psychiat, Munich, Germany.
[Lesch, Klaus-Peter; Reif, Andreas] Univ Wurzburg, Dept Psychiat & Psychotherapy, Wurzburg, Germany.
[Schimmelmann, Benno G.] Univ Bern, Univ Hosp Child & Adolescent Psychiat, CH-3012 Bern, Switzerland.
RP Albayrak, O (reprint author), Univ Duisburg Essen, Dept Child & Adolescent Psychiat Psychotherapy &, LVR Klinikum Essen, Wickenburgstr 21, D-45147 Essen, Germany.
EM oezguer.albayrak@uni-due.de
RI Romanos, Marcel/D-7695-2017; Hinney, Anke/D-6953-2011; Renner,
Tobias/I-2120-2013; Lesch, Klaus-Peter/J-4906-2013; Cichon,
Sven/H-8803-2013; Cichon, Sven/B-9618-2014; Schreiber,
Stefan/B-6748-2008
OI Sinzig, Judith/0000-0002-3693-3318; Hinney, Anke/0000-0001-5659-0706;
Scherag, Andre/0000-0002-9406-4704; Nothen, Markus/0000-0002-8770-2464;
Faraone, Stephen/0000-0002-9217-3982; Lesch,
Klaus-Peter/0000-0001-8348-153X; Cichon, Sven/0000-0002-9475-086X;
Cichon, Sven/0000-0002-9475-086X; Schreiber, Stefan/0000-0003-2254-7771
FU German Ministry for Education and Research (National Genome Research Net
plus) [01GS0820, 01KU0903]; German Research Foundation [DFG HE 1446/9-1,
KFO 125/1-1, SCHA 542/10-2, ME 1923/5-1, ME 1923/5-3]; European
Community [245009]; US National of Institute of Health [R13MH059126,
R01MH62873, R01MH081803, K23MH066275]; Children's Hospital of
Philadelphia [UL1-RR-024134]; NHMRC (Australia); Sidney Sax Public
Health Fellowship [443036]
FX Grant sponsor: German Ministry for Education and Research (National
Genome Research Net plus); Grant numbers: 01GS0820, 01KU0903; Grant
sponsor: German Research Foundation; Grant numbers: DFG HE 1446/9-1, KFO
125/1-1, SCHA 542/10-2, ME 1923/5-1, ME 1923/5-3; Grant sponsor:
European Community's Seventh Framework Programme (FP7/2007-2013); Grant
number: 245009; Grant sponsor: US National of Institute of Health
Grants; Grant numbers: R13MH059126, R01MH62873, R01MH081803,
K23MH066275; Grant sponsor: Children's Hospital of Philadelphia; Grant
number: UL1-RR-024134; Grant sponsor: NHMRC (Australia) and Sidney Sax
Public Health Fellowship; Grant number: 443036.
NR 78
TC 22
Z9 22
U1 0
U2 19
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1552-4841
J9 AM J MED GENET B
JI Am. J. Med. Genet. B
PD JUN
PY 2013
VL 162B
IS 4
BP 295
EP 305
DI 10.1002/ajmg.b.32144
PG 11
WC Genetics & Heredity; Psychiatry
SC Genetics & Heredity; Psychiatry
GA 150UF
UT WOS:000319416100001
PM 23533005
ER
PT J
AU Pato, MT
Sobell, JL
Medeiros, H
Abbott, C
Sklar, BM
Buckley, PF
Bromet, EJ
Escamilla, MA
Fanous, AH
Lehrer, DS
Macciardi, F
Malaspina, D
McCarroll, SA
Marder, SR
Moran, J
Morley, CP
Nicolini, H
Perkins, DO
Purcell, SM
Rapaport, MH
Sklar, P
Smoller, JW
Knowles, JA
Pato, CN
AF Pato, Michele T.
Sobell, Janet L.
Medeiros, Helena
Abbott, Colony
Sklar, Brooke M.
Buckley, Peter F.
Bromet, Evelyn J.
Escamilla, Michael A.
Fanous, Ayman H.
Lehrer, Douglas S.
Macciardi, Fabio
Malaspina, Dolores
McCarroll, Steve A.
Marder, Stephen R.
Moran, Jennifer
Morley, Christopher P.
Nicolini, Humberto
Perkins, Diana O.
Purcell, Shaun M.
Rapaport, Mark H.
Sklar, Pamela
Smoller, Jordan W.
Knowles, James A.
Pato, Carlos N.
CA Genomic Psychiat Cohort Consortium
TI The genomic psychiatry cohort: Partners in discovery
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS
LA English
DT Article
DE genetic epidemiology; schizophrenia; bipolar disorder; repository
ID BIPOLAR-DISORDER; DIAGNOSTIC INTERVIEW; WIDE ASSOCIATION; COMMON
VARIANTS; SCHIZOPHRENIA; RELIABILITY; RISK; FEATURES; LINKAGE; SYSTEM
AB The Genomic Psychiatry Cohort (GPC) is a longitudinal resource designed to provide the necessary population-based sample for large-scale genomic studies, studies focusing on Research Domain Criteria (RDoC) and/or other alternate phenotype constructs, clinical and interventional studies, nested casecontrol studies, long-term disease course studies, and genomic variant-to-phenotype studies. We provide and will continue to encourage access to the GPC as an international resource. DNA and other biological samples and diagnostic data are available through the National Institute of Mental Health (NIMH) Repository. After appropriate review and approval by an advisory board, investigators are able to collaborate in, propose, and co-lead studies involving cohort participants. (c) 2013 Wiley Periodicals, Inc.
C1 [Pato, Michele T.; Sobell, Janet L.; Medeiros, Helena; Abbott, Colony; Sklar, Brooke M.; Knowles, James A.; Pato, Carlos N.] Univ So Calif, Dept Psychiat & Behav Sci, Los Angeles, CA 90033 USA.
[Buckley, Peter F.] Georgia Regents Univ, Dept Psychiat, Augusta, GA USA.
[Bromet, Evelyn J.] SUNY Stony Brook, Dept Psychiat & Behav Sci, Stony Brook, NY 11794 USA.
[Escamilla, Michael A.] Texas Tech Univ, Hlth Sci Ctr, Dept Psychiat, El Paso, TX USA.
[Fanous, Ayman H.] Vet Adm Med Ctr, Dept Psychiat, Washington, DC 20422 USA.
[Lehrer, Douglas S.] Wright State Univ, Dept Psychiat, Dayton, OH 45435 USA.
[Macciardi, Fabio] Univ Calif Irvine, Dept Psychiat, Irvine, CA 92717 USA.
[Malaspina, Dolores] NYU, Dept Psychiat, New York, NY 10016 USA.
[McCarroll, Steve A.; Moran, Jennifer] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA.
[McCarroll, Steve A.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA.
[Marder, Stephen R.] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA.
[Morley, Christopher P.] SUNY Upstate Med Univ, Dept Family Med, Syracuse, NY 13210 USA.
[Morley, Christopher P.] SUNY Upstate Med Univ, Dept Publ Hlth & Prevent Med, Syracuse, NY 13210 USA.
[Morley, Christopher P.] SUNY Upstate Med Univ, Dept Psychiat & Behav Sci, Syracuse, NY 13210 USA.
[Nicolini, Humberto] Carracci Med Grp, Mexico City, DF, Mexico.
[Perkins, Diana O.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA.
[Purcell, Shaun M.] Massachusetts Gen Hosp, Ctr Human Genome Res, Boston, MA 02114 USA.
[Rapaport, Mark H.] Emory Univ, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA.
[Sklar, Pamela] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA.
[Smoller, Jordan W.] Harvard Univ, Dept Psychiat, Boston, MA 02115 USA.
RP Pato, CN (reprint author), Univ So Calif, Dept Psychiat & Behav Sci, 2250 Alcazar St, Los Angeles, CA 90033 USA.
RI Macciardi, Fabio/N-3768-2014; Morley, Christopher P/K-1907-2014;
OI Macciardi, Fabio/0000-0003-0537-4266; Lehrer,
Douglas/0000-0002-3014-9119; Morley, Christopher P/0000-0003-0185-7148;
Nicolini, Humberto/0000-0003-2494-0067; Moran,
Jennifer/0000-0002-5664-4716
FU NIH [MH085548, MH085542]; Stanley Center for Psychiatric Research; Broad
Institute of MIT; Broad Institute of Harvard
FX Grant sponsor: NIH; Grant numbers: MH085548; MH085542; Grant sponsor:
Stanley Center for Psychiatric Research; Grant sponsor: Broad Institute
of MIT and Harvard.
NR 35
TC 12
Z9 12
U1 1
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1552-4841
J9 AM J MED GENET B
JI Am. J. Med. Genet. B
PD JUN
PY 2013
VL 162B
IS 4
BP 306
EP 312
DI 10.1002/ajmg.b.32160
PG 7
WC Genetics & Heredity; Psychiatry
SC Genetics & Heredity; Psychiatry
GA 150UF
UT WOS:000319416100002
PM 23650244
ER
PT J
AU Stewart, SE
Mayerfeld, C
Arnold, PD
Crane, JR
O'Dushlaine, C
Fagerness, JA
Yu, D
Scharf, JM
Chan, E
Kassam, F
Moya, PR
Wendland, JR
Delorme, R
Richter, MA
Kennedy, JL
Veenstra-VanderWeele, J
Samuels, J
Greenberg, BD
McCracken, JT
Knowles, JA
Fyer, AJ
Rauch, SL
Riddle, MA
Grados, MA
Bienvenu, OJ
Cullen, B
Wang, Y
Shugart, YY
Piacentini, J
Rasmussen, S
Nestadt, G
Murphy, DL
Jenike, MA
Cook, EH
Pauls, DL
Hanna, GL
Mathews, CA
AF Stewart, S. E.
Mayerfeld, C.
Arnold, P. D.
Crane, J. R.
O'Dushlaine, C.
Fagerness, J. A.
Yu, D.
Scharf, J. M.
Chan, E.
Kassam, F.
Moya, P. R.
Wendland, J. R.
Delorme, R.
Richter, M. A.
Kennedy, J. L.
Veenstra-VanderWeele, J.
Samuels, J.
Greenberg, B. D.
McCracken, J. T.
Knowles, J. A.
Fyer, A. J.
Rauch, S. L.
Riddle, M. A.
Grados, M. A.
Bienvenu, O. J.
Cullen, B.
Wang, Y.
Shugart, Y. Y.
Piacentini, J.
Rasmussen, S.
Nestadt, G.
Murphy, D. L.
Jenike, M. A.
Cook, E. H.
Pauls, D. L.
Hanna, G. L.
Mathews, C. A.
TI Meta-analysis of association between obsessive-compulsive disorder and
the 3 ' region of neuronal glutamate transporter gene SLC1A1
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS
LA English
DT Article
DE obsessive-compulsive disorder; OCD; candidate gene; meta-analysis;
SLC1A1; glutamate
ID COMPLEX SEGREGATION ANALYSIS; FAMILY-BASED ASSOCIATION; OPEN-LABEL
TRIAL; GENDER-RELATED DIFFERENCES; GENOME-WIDE ASSOCIATION; OCD-LIKE
BEHAVIORS; PEDIATRIC PROBANDS; LINKAGE ANALYSIS; CANDIDATE GENE;
COMORBIDITY
AB The neuronal glutamate transporter gene SLC1A1 is a candidate gene for obsessive-compulsive disorder (OCD) based on linkage studies and convergent evidence implicating glutamate in OCD etiology. The 3 end of SLC1A1 is the only genomic region with consistently demonstrated OCD association, especially when analyzing male-only probands. However, specific allele associations have not been consistently replicated, and recent OCD genome-wide association and meta-analysis studies have not incorporated all previously associated SLC1A1 SNPs. To clarify the nature of association between SLC1A1 and OCD, pooled analysis was performed on all available relevant raw study data, comprising a final sample of 815 trios, 306 cases and 634 controls. This revealed weak association between OCD and one of nine tested SLC1A1 polymorphisms (rs301443; uncorrected P=0.046; non-significant corrected P). Secondary analyses of male-affecteds only (N=358 trios and 133 cases) demonstrated modest association between OCD and a different SNP (rs12682807; uncorrected P=0.012; non-significant corrected P). Findings of this meta-analysis are consistent with the trend of previous candidate gene studies in psychiatry and do not clarify the putative role of SLC1A1 in OCD pathophysiology. Nonetheless, it may be important to further examine the potential associations demonstrated in this amalgamated sample, especially since the SNPs with modest associations were not included in the more highly powered recent GWAS or in a past meta-analysis including five SLC1A1 polymorphisms. This study underscores the need for much larger sample sizes in future genetic association studies and suggests that next-generation sequencing may be beneficial in examining the potential role of rare variants in OCD. (c) 2013 Wiley Periodicals, Inc.
C1 [Stewart, S. E.; Rauch, S. L.; Jenike, M. A.] McLean Hosp, Belmont, MA 02178 USA.
[Stewart, S. E.; Rauch, S. L.; Jenike, M. A.; Pauls, D. L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Stewart, S. E.; Mayerfeld, C.; Crane, J. R.; Fagerness, J. A.; Yu, D.; Scharf, J. M.; Rauch, S. L.; Murphy, D. L.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA.
[Stewart, S. E.; Scharf, J. M.; Jenike, M. A.; Pauls, D. L.] Harvard Univ, Sch Med, Boston, MA USA.
[Stewart, S. E.; Chan, E.; Kassam, F.] Univ British Columbia, Vancouver, BC V5Z 4H4, Canada.
[Stewart, S. E.] British Columbia Mental Hlth & Addict Res Inst Va, Vancouver, BC, Canada.
[Arnold, P. D.] Hosp Sick Children, Program Genet & Genome Biol, Toronto, ON M5G 1X8, Canada.
[Arnold, P. D.; Richter, M. A.; Kennedy, J. L.] Univ Toronto, Dept Psychiat, Toronto, ON, Canada.
[O'Dushlaine, C.; Scharf, J. M.] Broad Inst MIT & Harvard, Program Med & Populat Genet, Boston, MA USA.
[Scharf, J. M.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Scharf, J. M.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA.
[Moya, P. R.; Wendland, J. R.; Shugart, Y. Y.; Murphy, D. L.] NIMH, Intramural Res Program, Bethesda, MD 20892 USA.
[Wendland, J. R.] F Hoffmann La Roche & Co Ltd, Pharma Res & Early Dev, CNS Clin Biomarker Grp, CH-4002 Basel, Switzerland.
[Delorme, R.] Robert Debre Hosp, AP HP, Dept Child & Adolescent Psychiat, INSERM,U955, Paris, France.
[Delorme, R.] Inst Mondor Rech Biomed, Creteil, France.
[Delorme, R.] French Natl Sci Fdn, Fdn Fondamental, Paris, France.
[Richter, M. A.] Sunnybrook Hlth Sci Ctr, Dept Psychiat, Clin OCD & Related Disorders, Toronto, ON M4N 3M5, Canada.
[Kennedy, J. L.] Ctr Addict & Mental Hlth, Psychiat Neurogenet Lab, Toronto, ON, Canada.
[Veenstra-VanderWeele, J.] Vanderbilt Kennedy Ctr Res Human Dev, Dept Psychiat, Nashville, TN USA.
[Veenstra-VanderWeele, J.] Vanderbilt Kennedy Ctr Res Human Dev, Dept Pediat, Nashville, TN USA.
[Veenstra-VanderWeele, J.] Vanderbilt Kennedy Ctr Res Human Dev, Dept Pharmacol, Nashville, TN USA.
[Veenstra-VanderWeele, J.] Vanderbilt Brain Inst, Nashville, TN USA.
[Samuels, J.; Riddle, M. A.; Grados, M. A.; Bienvenu, O. J.; Cullen, B.; Wang, Y.; Rasmussen, S.; Nestadt, G.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA.
[Greenberg, B. D.] Butler Hosp, Brown Med Sch, Dept Psychiat & Human Behav, Providence, RI 02906 USA.
[McCracken, J. T.; Piacentini, J.] Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA.
[Knowles, J. A.] Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Keck Sch Med, Zilkha Neurogenet Inst, Los Angeles, CA 90024 USA.
[Fyer, A. J.] Columbia Univ, Dept Psychiat, Coll Phys & Surg, New York, NY USA.
[Fyer, A. J.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA.
[Rauch, S. L.] Partners Psychiat & Mental Hlth, Belmont, MA USA.
[Cook, E. H.] Univ Illinois, Dept Psychiat, Inst Juvenile Res, Chicago, IL 60612 USA.
[Hanna, G. L.] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA.
[Mathews, C. A.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA.
RP Stewart, SE (reprint author), Univ British Columbia, Dept Psychiat, A3-118,West 28th Ave, Vancouver, BC V5Z 4H4, Canada.
EM evelyn.stewart@ubc.ca
RI Stewart, Evelyn/K-6961-2014; Veenstra-VanderWeele, Jeremy/K-1935-2015;
OI Veenstra-VanderWeele, Jeremy/0000-0002-6349-1076; Samuels,
Jack/0000-0002-6715-7905; Hanna, Gregory/0000-0002-0742-6990; Stewart,
S. Evelyn/0000-0002-0994-6383
FU Eli Lilly Canada Inc; Ontario Mental Health Foundation;
Obsessive-Compulsive Foundation; Novartis; Seaside Therapeutics; Roche;
Forest; Cyberonics; Medtronic
FX Grant sponsor: Eli Lilly Canada Inc, Ontario Mental Health Foundation
and the Obsessive-Compulsive Foundation; Grant sponsor: Novartis,
Seaside Therapeutics, Roche, and Forest; Grant sponsor: Cyberonics and
Medtronic.
NR 87
TC 27
Z9 28
U1 1
U2 23
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1552-4841
J9 AM J MED GENET B
JI Am. J. Med. Genet. B
PD JUN
PY 2013
VL 162B
IS 4
BP 367
EP 379
DI 10.1002/ajmg.b.32137
PG 13
WC Genetics & Heredity; Psychiatry
SC Genetics & Heredity; Psychiatry
GA 150UF
UT WOS:000319416100005
PM 23606572
ER
PT J
AU Tirumani, SH
Shinagare, AB
Sakellis, C
Saboo, SS
Jagannathan, JP
Krajewski, KM
Ramaiya, NH
AF Tirumani, Sree Harsha
Shinagare, Atul B.
Sakellis, Christopher
Saboo, Sachin S.
Jagannathan, Jyothi P.
Krajewski, Katherine M.
Ramaiya, Nikhil H.
TI Merkel Cell Carcinoma: A Primer for the Radiologist
SO AMERICAN JOURNAL OF ROENTGENOLOGY
LA English
DT Review
DE Merkel cell carcinoma; PET/CT; sentinel lymph node biopsy
ID OF-THE-LITERATURE; SINGLE INSTITUTION; CASE SERIES; RADIATION; SKIN;
DIAGNOSIS; HEAD; NECK; CHEMOTHERAPY; MANAGEMENT
AB OBJECTIVE. Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine tumor. The purpose of this review is to provide a comprehensive description of the staging, workup, treatment, and follow-up of MCC.
CONCLUSION. Sentinel lymph node mapping and PET/CT are the cornerstones of staging of MCC. MCC is a radiosensitive tumor, and hence radiotherapy plays a major role in its management. Close follow-up with PET/CT helps in detecting recurrences of MCC.
C1 [Tirumani, Sree Harsha; Sakellis, Christopher; Jagannathan, Jyothi P.; Krajewski, Katherine M.; Ramaiya, Nikhil H.] Harvard Univ, Dana Farber Canc Inst, Sch Med, Dept Imaging, Boston, MA 02215 USA.
[Tirumani, Sree Harsha; Shinagare, Atul B.; Sakellis, Christopher; Saboo, Sachin S.; Jagannathan, Jyothi P.; Krajewski, Katherine M.; Ramaiya, Nikhil H.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02215 USA.
RP Tirumani, SH (reprint author), Harvard Univ, Dana Farber Canc Inst, Sch Med, Dept Imaging, 450 Brookline Ave, Boston, MA 02215 USA.
EM stirumani@partners.org
NR 56
TC 7
Z9 7
U1 1
U2 5
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 JUN
PY 2013
VL 200
IS 6
BP 1186
EP 1196
DI 10.2214/AJR.12.9884
PG 11
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 151GC
UT WOS:000319447700025
PM 23701052
ER
PT J
AU Kang, SK
Huang, WC
Lee, VS
Chandarana, H
AF Kang, Stella K.
Huang, William C.
Lee, Vivian S.
Chandarana, Hersh
TI MR Renographic Measurement of Renal Function in Patients Undergoing
Partial Nephrectomy
SO AMERICAN JOURNAL OF ROENTGENOLOGY
LA English
DT Review
DE MR renography; partial nephrectomy; renal function
ID GLOMERULAR-FILTRATION-RATE; CHRONIC KIDNEY-DISEASE; CONTRAST-ENHANCED
MRI; RADICAL NEPHRECTOMY; CELL CARCINOMA; UNITED-STATES; RISK-FACTORS;
DYNAMIC MRI; MORTALITY; MODEL
AB OBJECTIVE. The purpose of this review is to describe the role of functional renal MRI, or MR renography, in the care of patients with renal masses undergoing partial nephrectomy.
CONCLUSION. MR renography can be used to monitor renal functional outcome for patients undergoing partial nephrectomy and may help guide patient selection in this population with elevated risk of chronic kidney disease.
C1 [Kang, Stella K.; Chandarana, Hersh] NYU, Dept Radiol, Langone Med Ctr, New York, NY 10016 USA.
[Huang, William C.] NYU, Langone Med Ctr, Dept Urol, New York, NY USA.
[Lee, Vivian S.] Univ Utah Hlth Sci, Dept Radiol, Salt Lake City, UT USA.
RP Kang, SK (reprint author), Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent Radiol, Dept Radiol, White Bldg,Rm 270,55 Fruit St, Boston, MA 02114 USA.
EM skang4@partners.org
RI Kang, Stella/O-7003-2015;
OI Chandarana, Hersh/0000-0002-6807-4589; Kang, Stella/0000-0003-2402-3787;
Huang, William/0000-0001-5261-0650
FU NIDDK NIH HHS [R01 DK063183, R01 DK088375]
NR 41
TC 2
Z9 2
U1 0
U2 5
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 JUN
PY 2013
VL 200
IS 6
BP 1204
EP 1209
DI 10.2214/AJR.12.10276
PG 6
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 151GC
UT WOS:000319447700027
PM 23701054
ER
PT J
AU Kreydin, EI
Barrisford, GW
Feldman, AS
Preston, MA
AF Kreydin, Evgeniy I.
Barrisford, Glen W.
Feldman, Adam S.
Preston, Mark A.
TI Testicular Cancer: What the Radiologist Needs to Know
SO AMERICAN JOURNAL OF ROENTGENOLOGY
LA English
DT Review
DE CT; diagnosis; diagnostic performance; evidence-based medicine; MRI;
staging; testicular cancer; testis cancer
ID GERM-CELL TUMORS; POSITRON-EMISSION-TOMOGRAPHY; CLINICAL-PRACTICE
GUIDELINES; LYMPH-NODE METASTASES; EUROPEAN CONSENSUS CONFERENCE; TESTIS
CANCER; STAGE-I; COMPUTED-TOMOGRAPHY; RADIATION-EXPOSURE; VIABLE TUMOR
AB OBJECTIVE. The purpose of this article is to review current imaging techniques and evolving technologies that are being used for detection and management of testicular cancer.
CONCLUSION. The primary goal of cancer imaging is accurate disease characterization at diagnosis and through all stages of management. Knowledge of the disease and diagnostic performance characteristics of each technique is critical to identify the appropriate modality for staging disease and to monitor for treatment response and recurrence that may dictate further intervention.
C1 [Kreydin, Evgeniy I.; Barrisford, Glen W.; Feldman, Adam S.; Preston, Mark A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA.
RP Preston, MA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Urol, GRB 1102,55 Fruit St, Boston, MA 02114 USA.
EM mpreston1@partners.org
NR 65
TC 7
Z9 8
U1 0
U2 10
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 JUN
PY 2013
VL 200
IS 6
BP 1215
EP 1225
DI 10.2214/AJR.12.10319
PG 11
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 151GC
UT WOS:000319447700029
PM 23701056
ER
PT J
AU Uppot, RN
Gervais, DA
AF Uppot, Raul N.
Gervais, Debra A.
TI Imaging-Guided Adrenal Tumor Ablation
SO AMERICAN JOURNAL OF ROENTGENOLOGY
LA English
DT Review
DE cryoablation; functioning adrenal tumors; microwave ablation;
radiofrequency ablation; renal tumors
ID PERCUTANEOUS RADIOFREQUENCY ABLATION; IRREVERSIBLE ELECTROPORATION;
METASTATIC PHEOCHROMOCYTOMA; MICROWAVE ABLATION; ADRENOCORTICAL
CARCINOMA; RENAL TUMORS; NEOPLASMS; CRYOABLATION; EXPERIENCE;
HYPERTENSION
AB OBJECTIVE. The purpose of this review is to describe the indications for and approach to imaging-guided ablation of the adrenal gland.
CONCLUSION. Imaging-guided radiofrequency ablation of the adrenal glands is an effective procedure in the local control of primary or metastatic adrenal malignancy and is an alternative minimally invasive therapy for functioning adrenal tumors. Potential complications of hypertensive crises can be managed by preprocedure administration of alpha- and beta-blockers in coordination with the anesthesiology department.
C1 [Uppot, Raul N.; Gervais, Debra A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Div Abdominal Imaging & Intervent, Boston, MA 02114 USA.
[Gervais, Debra A.] Harvard Univ, Sch Med, Div Pediat Imaging, Dept Radiol, Boston, MA 02114 USA.
RP Uppot, RN (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Div Abdominal Imaging & Intervent, 55 Fruit St,White 270, Boston, MA 02114 USA.
EM ruppot@partners.org
NR 49
TC 9
Z9 9
U1 0
U2 6
PU AMER ROENTGEN RAY SOC
PI RESTON
PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA
SN 0361-803X
J9 AM J ROENTGENOL
JI Am. J. Roentgenol.
PD JUN
PY 2013
VL 200
IS 6
BP 1226
EP 1233
DI 10.2214/AJR.12.10328
PG 8
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 151GC
UT WOS:000319447700030
PM 23701057
ER
PT J
AU Elmi, A
Hedgire, SS
Pargaonkar, V
Cao, K
McDermott, S
Harisinghani, M
AF Elmi, Azadeh
Hedgire, Sandeep S.
Pargaonkar, Vivek
Cao, Kai
McDermott, Shaunagh
Harisinghani, Mukesh
TI Is Early Colonoscopy Beneficial in Patients With CT-Diagnosed
Diverticulitis?
SO AMERICAN JOURNAL OF ROENTGENOLOGY
LA English
DT Article
DE cancer; colon; CT; diverticular disease; diverticulitis; endoscopy
ID COLORECTAL-CANCER; COLON-CANCER; SIGMOID DIVERTICULITIS; CONTRAST ENEMA;
HELICAL CT; DISEASE; DIFFERENTIATION; RISK
AB OBJECTIVE. The purpose of this study was to establish CT criteria as an indication for colonoscopy in patients with acute diverticulitis.
MATERIALS AND METHODS. The study was composed of patients diagnosed with acute diverticulitis on contrast-enhanced CT (CECT) from January 2000 to December 2004. Patients without subsequent colonoscopy were excluded. Findings on CT were correlated with patient outcomes over follow-up. Sensitivity, specificity, and predictive values of the imaging parameters for prediction of colon cancer were calculated. Outcomes were also compared between men and women.
RESULTS. Of 1034 patients with a CT diagnosis of diverticulitis, 402 (235 women and 167 men; mean age, 63.3 years) had available endoscopic colonic evaluation after CECT. The mean follow-up was 5.3 years. Seventy-eight patients had polyps (71% adenomatous) and nine patients (2.2%) were diagnosed with colon cancer (seven women, two men). The odds ratio for diagnosis of colon cancer was 23.35 in patients with mesenteric or retroperitoneal lymphnodes, 4.67 for abscess, and 24.43 in patients with obstruction and localized mass reported on CT. A significant correlation was found between the location of diverticulitis and cancer (p < 0.001). The diagnosis of cancer was made within 6 months from the date of CECT in eight patients. The odds of cancer were 2.5 times higher in women.
CONCLUSION. On the basis of the significant correlation of complicated diverticulitis or presence of lymph nodes with new diagnoses of colon cancer, we recommend early colonoscopy in patients with wall thickness more than 6 mm, abscess, obstruction, or lymph nodes seen on CECT.
C1 [Elmi, Azadeh; Hedgire, Sandeep S.; Pargaonkar, Vivek; Cao, Kai; McDermott, Shaunagh; Harisinghani, Mukesh] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Abdominal Imaging & Intervent Radiol, Boston, MA 02114 USA.
RP Elmi, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Abdominal Imaging & Intervent Radiol, 55 Fruit St,White 270, Boston, MA 02114 USA.
EM aelmi@partners.org
NR 23
TC 18
Z9 18
U1 0
U2 5
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 JUN
PY 2013
VL 200
IS 6
BP 1269
EP 1274
DI 10.2214/AJR.12.9539
PG 6
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 151GC
UT WOS:000319447700036
PM 23701063
ER
PT J
AU Pandharipande, PV
Eisenberg, JD
Avery, LL
Gunn, ML
Kang, SK
Megibow, AJ
Turan, EA
Harvey, HB
Kong, CY
Dowling, EC
Halpern, EF
Donelan, K
Gazelle, GS
AF Pandharipande, Pari V.
Eisenberg, Jonathan D.
Avery, Laura L.
Gunn, Martin L.
Kang, Stella K.
Megibow, Alec J.
Turan, Ekin A.
Harvey, H. Benjamin
Kong, Chung Yin
Dowling, Emily C.
Halpern, Elkan F.
Donelan, Karen
Gazelle, G. Scott
TI How Radiation Exposure Histories Influence Physician Imaging Decisions:
A Multicenter Radiologist Survey Study
SO AMERICAN JOURNAL OF ROENTGENOLOGY
LA English
DT Article
DE CT; physician decision making; radiation-induced cancer risks; survey
research
ID SUNK COST; IONIZING-RADIATION; QUALITY-ASSURANCE; CANCER-RISKS
AB OBJECTIVE. The purpose of this article is to evaluate the influence of patient radiation exposure histories on radiologists' imaging decisions.
MATERIALS AND METHODS. We conducted a physician survey study in three academic medical centers. Radiologists were asked to make an imaging recommendation for a hypothetical patient with a history of multiple CT scans. We queried radiologists' decision making, evaluating whether they incorporated cancer risks from previous imaging, reported acceptance (or rejection) of the linear no-threshold model, and understood linear no-threshold model implications in this setting. Consistency between radiologists' decisions and their linear no-threshold model beliefs was evaluated; those acting in accordance with the linear no-threshold model were expected to disregard previously incurred cancer risks. A Fisher exact test was used to verify the generalizability of results across institutions and training levels (residents, fellows, and attending physicians).
RESULTS. Fifty-six percent (322/578) of radiologists completed the survey. Most (92% [295/322]) incorporated risks from the patient's exposure history during decision making. Most (61% [196/322]) also reported acceptance of the linear no-threshold model. Fewer (25% [79/322]) rejected the linear no-threshold model; 15% (47/322) could not judge. Among radiologists reporting linear no-threshold model acceptance or rejection, the minority (36% [98/275]) made decisions that were consistent with their linear no-threshold model beliefs. This finding was not statistically different across institutions (p = 0.070) or training levels (p = 0.183). Few radiologists (4% [13/322]) had an accurate understanding of linear no-threshold model implications.
CONCLUSION. Most radiologists, when faced with patient exposure histories, make decisions that contradict their self-reported acceptance of the linear no-threshold model and the linear no-threshold model itself. These findings underscore a need for educational initiatives.
C1 [Pandharipande, Pari V.; Eisenberg, Jonathan D.; Turan, Ekin A.; Harvey, H. Benjamin; Kong, Chung Yin; Dowling, Emily C.; Halpern, Elkan F.; Donelan, Karen; Gazelle, G. Scott] Massachusetts Gen Hosp, Dept Radiol, Inst Technol Assessment, Boston, MA 02114 USA.
[Pandharipande, Pari V.; Eisenberg, Jonathan D.; Avery, Laura L.; Kang, Stella K.; Turan, Ekin A.; Kong, Chung Yin; Dowling, Emily C.; Halpern, Elkan F.; Gazelle, G. Scott] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Pandharipande, Pari V.; Avery, Laura L.; Harvey, H. Benjamin; Kong, Chung Yin; Halpern, Elkan F.; Donelan, Karen; Gazelle, G. Scott] Harvard Univ, Sch Med, Boston, MA USA.
[Eisenberg, Jonathan D.] Univ Massachusetts, Sch Med, Boston, MA 02125 USA.
[Gunn, Martin L.] Univ Washington, Dept Radiol, Seattle, WA 98195 USA.
[Kang, Stella K.; Megibow, Alec J.] NYU, Dept Radiol, Langone Med Ctr, New York, NY 10016 USA.
[Donelan, Karen] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA.
RP Pandharipande, PV (reprint author), Massachusetts Gen Hosp, Dept Radiol, Inst Technol Assessment, 101 Merrimac St,10th Fl, Boston, MA 02114 USA.
EM pari@mgh-ita.org
RI Kang, Stella/O-7003-2015;
OI Gunn, Martin/0000-0001-9879-8660
FU National Cancer Institute [K07CA133097, K25CA133141]; Medical Imaging
and Technology Alliance; GE Healthcare
FX This study was supported in part by the National Cancer Institute
(awards K07CA133097 to P. V. Pandharipande and K25CA133141 to C. Y.
Kong). The research content is solely the responsibility of the authors
and does not necessarily represent the official views of the National
Cancer Institute or the National Institutes of Health. P. V.
Pandharipande receives research funding from the Medical Imaging and
Technology Alliance for unrelated research. E. F. Halpern is a
consultant for Hologic. K. Donelan receives research funding from GE
Healthcare and from the Medical Imaging and Technology Alliance for
unrelated research. G. S. Gazelle is a consultant for GE Healthcare.
NR 19
TC 15
Z9 15
U1 0
U2 2
PU AMER ROENTGEN RAY SOC
PI RESTON
PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA
SN 0361-803X
J9 AM J ROENTGENOL
JI Am. J. Roentgenol.
PD JUN
PY 2013
VL 200
IS 6
BP 1275
EP 1283
DI 10.2214/AJR.12.10011
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 151GC
UT WOS:000319447700037
PM 23701064
ER
PT J
AU Caplan, L
Clegg, DO
Inman, RD
AF Caplan, Liron
Clegg, Daniel O.
Inman, Robert D.
TI Ankylosing Spondylitis Clinical Registries: Principles, Practices and
Possibilities
SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES
LA English
DT Article; Proceedings Paper
CT 10th Annual Meeting of the
SPondyloArthritis-Research-and-Treatment-Network
(SPARTAN)-Group-for-Research-and-Assessment-of-Psoriasis-and-Psoriatic-A
rthritis (GRAPPA)
CY JUL 27-28, 2012
CL Portland, OR
SP SPondyloArthritis Res & Treatment Network (SPARTAN), Grp Res & Assessment Psoriasis & Psoriat Arthrit (GRAPPA)
DE Clinical registry; Spondyloathritis; Ankylosing spondylitis
AB The need for a rigorously developed longitudinal registry of patients with spondyloarthritis (SpA) is clear and urgent. Like randomized controlled trials, registries rely on a prospective, systematic protocol-driven approach to data acquisition to assess outcomes for a prescribed cohort of patients. Registries seek to capture large numbers of patients across large geographic zones and can serve as a valuable resource for patient advocacy, patient education and support, incidence and prevalence, and broad demographic profiles. Building on 3 existing registries the Prospective Study of Outcomes in Ankylosing Spondylitis, the Program to Understand the Longterm Outcomes of Spondyloarthritis (PULSAR) and the University Health Network Spondyloarthritis Program-these registries and the Spondylitis Association of America propose to form a combined registry of North American SpA patients. The combined registry would, ideally, complement ongoing clinical goals and improve patient care.
C1 [Caplan, Liron] Univ Colorado, Denver Vet Affairs Med Ctr, Denver, CO 80202 USA.
[Clegg, Daniel O.] Univ Utah, Sch Med, George E Whalen Salt Lake Vet Affairs Med Ctr, Salt Lake City, UT USA.
[Inman, Robert D.] Univ Toronto, Toronto, ON, Canada.
RP Clegg, DO (reprint author), Univ Utah Hlth Care, 50 North Med Dr, Salt Lake City, UT 84132 USA.
EM daniel.clegg@hsc.utah.edu
NR 1
TC 2
Z9 2
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0002-9629
J9 AM J MED SCI
JI Am. J. Med. Sci.
PD JUN
PY 2013
VL 345
IS 6
BP 437
EP 439
DI 10.1097/MAJ.0b013e3182937335
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 151CH
UT WOS:000319437700005
PM 23841118
ER
PT J
AU Melo, MFV
Eikermann, M
AF Melo, Marcos F. Vidal
Eikermann, Matthias
TI Protect the Lungs during Abdominal Surgery It May Change the
Postoperative Outcome
SO ANESTHESIOLOGY
LA English
DT Editorial Material
ID RESPIRATORY-DISTRESS-SYNDROME; LOWER TIDAL VOLUMES; MECHANICAL
VENTILATION; INJURY; SURFACTANT; PRESSURE; MODEL
C1 [Melo, Marcos F. Vidal] Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA.
[Melo, Marcos F. Vidal] Harvard Univ, Sch Med, Boston, MA USA.
[Eikermann, Matthias] Univ Klinikum Essen, Univ Duisburg Essen, Klin Anasthesiol & Intensivmed, Essen, Germany.
RP Melo, MFV (reprint author), Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA.
EM meikermann@partners.org
NR 16
TC 5
Z9 6
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0003-3022
J9 ANESTHESIOLOGY
JI Anesthesiology
PD JUN
PY 2013
VL 118
IS 6
BP 1254
EP 1257
DI 10.1097/ALN.0b013e3182910309
PG 4
WC Anesthesiology
SC Anesthesiology
GA 149PZ
UT WOS:000319334700005
PM 23535504
ER
PT J
AU Brueckmann, B
Villa-Uribe, JL
Bateman, BT
Rosse-Sundrup, MG
Hess, DR
Schlett, CL
Eikermann, M
AF Brueckmann, Britta
Villa-Uribe, Jose L.
Bateman, Brian T.
Rosse-Sundrup, Martina G.
Hess, Dean R.
Schlett, Christopher L.
Eikermann, Matthias
TI Development and Validation of a Score for Prediction of Postoperative
Respiratory Complications
SO ANESTHESIOLOGY
LA English
DT Article
ID MAJOR NONCARDIAC SURGERY; OBSTRUCTIVE SLEEP-APNEA; TRACHEAL INTUBATION;
UNPLANNED INTUBATION; RISK STRATIFICATION; FAILURE; MORTALITY; OUTCOMES;
SYSTEM; INDEX
AB Background: Postoperative respiratory failure is associated with increased morbidity and mortality, as well as high costs of hospital care.
Methods: Using electronic anesthesia records, billing data, and chart review, the authors developed and validated a score predicting reintubation in the hospital after primary extubation in the operating room, leading to unplanned mechanical ventilation within the first 3 postoperative days. Using multivariable logistic regression analysis, independent predictors were determined and a score postulated and validated.
Results: In the entire cohort (n = 33,769 surgical cases within 29,924 patients), reintubation occurred in 137 cases (0.41%). Of those, 16%, (n = 22) died subsequently, whereas the mortality in patients who were not reintubated was 0.26% (P < 0.0001). Independent predictors for reintubation were: American Society of Anesthesiologist Score 3 or more, emergency surgery, high-risk surgical service, history of congestive heart failure, and chronic pulmonary disease. A point value of 3, 3, 2, 2, and 1 were assigned to these predictors, respectively, based on their beta coefficient in the predictive model. The score yielded a calculated area under the curve of 0.81, whereas each point increment was associated with a 1.7-fold (odds ratio: 1.72 [95% CI, 1.55-1.91]) increase in the odds for reintubation in the training dataset. Using the validation dataset (n = 16,884), the score had an area under the curve of 0.80 and similar estimated probabilities for reintubation.
Conclusion: The authors developed and validated a score for the prediction of postoperative respiratory complications, a simple, 11-point score that can be used preoperatively by anesthesiologists to predict severe postoperative respiratory complications.
C1 [Brueckmann, Britta; Villa-Uribe, Jose L.; Bateman, Brian T.; Rosse-Sundrup, Martina G.; Hess, Dean R.; Schlett, Christopher L.; Eikermann, Matthias] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02115 USA.
RP Eikermann, M (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02115 USA.
EM meiker-mann@partners.org
NR 31
TC 46
Z9 49
U1 2
U2 10
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0003-3022
J9 ANESTHESIOLOGY
JI Anesthesiology
PD JUN
PY 2013
VL 118
IS 6
BP 1276
EP 1285
DI 10.1097/ALN.0b013e318293065c
PG 10
WC Anesthesiology
SC Anesthesiology
GA 149PZ
UT WOS:000319334700009
PM 23571640
ER
PT J
AU Bakaeen, FG
Chu, D
Kelly, RF
Ward, HB
Jessen, ME
Chen, GJ
Petersen, NJ
Holman, WL
AF Bakaeen, Faisal G.
Chu, Danny
Kelly, Rosemary F.
Ward, Herbert B.
Jessen, Michael E.
Chen, G. John
Petersen, Nancy J.
Holman, William L.
TI Performing Coronary Artery Bypass Grafting Off-Pump May Compromise
Long-Term Survival in a Veteran Population
SO ANNALS OF THORACIC SURGERY
LA English
DT Article; Proceedings Paper
CT 49th Annual Meeting of the Society-of-Thoracic-Surgeons
CY JAN 26-30, 2013
CL Los Angeles, CA
SP Soc Thorac Surg
ID ON-PUMP; RANDOMIZED-TRIAL; REDUCE MORBIDITY; CARDIAC-SURGERY; OUTCOMES;
REVASCULARIZATION; MORTALITY; METAANALYSIS; STROKE; PATENCY
AB Background. There are ample data regarding the short-term outcomes of on-pump and off-pump coronary artery bypass grafting (CABG), but little is known about the long-term survival associated with these approaches.
Methods. Using the Veterans Affairs (VA) Continuous Improvement in Cardiac Surgery Program, we identified all VA patients (n = 65,097) who underwent primary isolated CABG from October 1997 to April 2011. The primary outcome measure was all-cause mortality. Age, 17 preoperative risk factors, and year of operation were used to calculate propensity scores for each patient. A greedy-match algorithm using the propensity scores matched 8,911 off-pump with 26,733 on-pump patients. Survival functions were estimated by the Kaplan-Meier method and compared by using the log-rank test.
Results. In the complete cohort, off-pump was used in 11,629 of 65,097 (17.9%) operations. For the matched cohort, the median follow-up was 6.7 years (interquartile range, 3.72 to 9.35 years). Risk-adjusted mortality did not differ significantly between the off-pump and on-pump groups at 1 year (4.67% vs 4.78%; risk ratio [RR], 0.98; 95% confidence interval [CI], 0.88 to 1.09) or 3 years (9.21% vs 8.89%; RR, 1.04; 95% CI, 0.96 to 1.12). However, risk-adjusted mortality was higher in the off-pump group at 5 years (14.47% vs 13.45%; RR, 1.08; 95% CI 1.02 to 1.15) and 10 years (25.18% vs 23.57%; RR, 1.07; 95% CI, 1.03 to 1.12). Overall, the hazard ratio for off-pump vs on-pump was 1.06 (95% CI, 1.00 to 1.13; p = 0.04).
Conclusions. Off-pump CABG may be associated with decreased long-term survival. Further studies are needed to identify the reasons behind this finding. (C) 2013 by The Society of Thoracic Surgeons
C1 Michael E DeBakey VA Med Ctr, Baylor Coll Med, Michael E DeBakey Dept Surg, Div Cardiothorac Surg, Houston, TX USA.
St Lukes Episcopal Hosp, Texas Heart Inst, Dept Cardiovasc Surg, Houston, TX USA.
Univ Minnesota, Minneapolis Vet Affairs Med Ctr, Div Cardiothorac Surg, Minneapolis, MN USA.
Univ Texas SW Med Ctr Dallas, Div Cardiothorac Surg, Dallas, TX 75390 USA.
Houston Vet Affairs Hlth Serv Res & Dev Ctr Excel, Houston, TX USA.
Univ Alabama Birmingham, Dept Cardiothorac Surg, Birmingham, AL USA.
Birmingham Vet Affairs Med Ctr, Birmingham, AL USA.
RP Bakaeen, FG (reprint author), Baylor Coll Med, Michael E DeBakey Dept Surg, Div Cardiothorac Surg, Houston, TX 77005 USA.
EM fbakaeen@bcm.edu
NR 29
TC 16
Z9 17
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0003-4975
J9 ANN THORAC SURG
JI Ann. Thorac. Surg.
PD JUN
PY 2013
VL 95
IS 6
BP 1952
EP 1960
DI 10.1016/j.athoracsur.2013.02.064
PG 9
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA 149QF
UT WOS:000319335400027
PM 23647861
ER
PT J
AU Zartman, AL
Hilsabeck, RC
Guarnaccia, CA
Houtz, A
AF Zartman, Andrea L.
Hilsabeck, Robin C.
Guarnaccia, Charles A.
Houtz, Andrew
TI The Pillbox Test: An Ecological Measure of Executive Functioning and
Estimate of Medication Management Abilities
SO ARCHIVES OF CLINICAL NEUROPSYCHOLOGY
LA English
DT Article
DE Assessment; Executive functions; Test construction
ID COGNITIVE FUNCTION; OLDER-ADULTS; ALZHEIMERS-DISEASE; PERFORMANCE;
IMPAIRMENT; DECLINE; PREDICTORS; MEMORY; SCHIZOPHRENIA; ASSOCIATION
AB Studies indicate that executive functioning (EF) is a strong predictor of everyday function. However, assessment can be problematic as no single standardized instrument is known to measure all EF domains simultaneously. Thus, the Pillbox Test was developed as a new measure tapping four EF factors through the real-time assessment of medication management, a complex instrumental activity of daily living. The Pillbox Test showed good criterion-related validity and was effective in differentiating graduated levels of executive dysfunction between a mixed neurological group, medical control group, and healthy community control group. This test also showed good convergent validity as it correlated significantly in expected directions with established EF measures in all four of selected EF domains and the Direct Assessment of Functional Status. Finally, a receiver operator characteristic curve found a sensitivity of 75 and specificity of 87.5, suggesting that the Pillbox Test is a promising new ecological measure of EF.
C1 [Zartman, Andrea L.; Guarnaccia, Charles A.] Univ N Texas, Dept Psychol, Denton, TX 76203 USA.
[Hilsabeck, Robin C.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Hilsabeck, Robin C.] South Texas Vet Hlth Care Syst, San Antonio, TX USA.
[Houtz, Andrew] Cognit Solut, Ft Worth, TX USA.
RP Zartman, AL (reprint author), VA North Texas Hlth Care Syst, Mental Hlth 4500 S Lancaster Rd 116A, Dallas, TX 75216 USA.
EM andrea.zartman@va.gov
NR 64
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Z9 7
U1 4
U2 16
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0887-6177
J9 ARCH CLIN NEUROPSYCH
JI Arch. Clin. Neuropsychol.
PD JUN
PY 2013
VL 28
IS 4
BP 307
EP 319
DI 10.1093/arclin/act014
PG 13
WC Psychology, Clinical; Psychology
SC Psychology
GA 148XI
UT WOS:000319281500001
PM 23502807
ER
PT J
AU Thaler, NS
Goldstein, G
Pettegrew, JW
Luther, JF
Reynolds, CR
Allen, DN
AF Thaler, Nicholas S.
Goldstein, Gerald
Pettegrew, Jay W.
Luther, James F.
Reynolds, Cecil R.
Allen, Daniel N.
TI Developmental Aspects of Working and Associative Memory
SO ARCHIVES OF CLINICAL NEUROPSYCHOLOGY
LA English
DT Article
DE Learning and memory; Assessment
ID SHORT-TERM-MEMORY; TEMPORAL-LOBE; BRIEF-HISTORY; LONG-TERM
AB Developmental differences between working and long-term associative memory were evaluated through a cross-sectional age difference study based on data from a memory batterys standardization sample. The scores of 856 children and adolescents ranging from 5 to 17 years of age were compared on memory subtests that assess verbal working and long-term memory. Data were examined using curve fitting and ANOVA procedures that evaluated age group and years of age differences. The major finding was that the developmental trajectories across age differed substantially between the two memory domains. The working memory trajectory was linear until age 11, whereas the long-term memory trajectory was curvilinear with an inflection point at age 8. Both trajectories plateaued after age 11. ANOVAs produced significant interactions between tests of working and associative memory with age, supporting the view that the age trajectories had differing courses. The results are discussed in terms of neurobiological implications for the two memory systems studied.
C1 [Thaler, Nicholas S.; Allen, Daniel N.] Univ Nevada, Las Vegas, NV 89154 USA.
[Goldstein, Gerald; Luther, James F.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA.
[Pettegrew, Jay W.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA.
[Reynolds, Cecil R.] Texas A&M Univ, College Stn, TX USA.
RP Goldstein, G (reprint author), VA Pittsburgh Healthcare Syst, 7180 Highland Dr, Pittsburgh, PA 15206 USA.
EM ggold@nb.net
FU Mental Illness Research, Education, and Clinical Center (MIRECC)
VISN-IV, Pittsburgh, PA; Medical Research Service, Department of
Veterans Affairs
FX This research was supported by the Mental Illness Research, Education,
and Clinical Center (MIRECC) VISN-IV, Pittsburgh, PA, and by the Medical
Research Service, Department of Veterans Affairs.
NR 28
TC 3
Z9 3
U1 0
U2 11
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0887-6177
J9 ARCH CLIN NEUROPSYCH
JI Arch. Clin. Neuropsychol.
PD JUN
PY 2013
VL 28
IS 4
BP 348
EP 355
DI 10.1093/arclin/acs114
PG 8
WC Psychology, Clinical; Psychology
SC Psychology
GA 148XI
UT WOS:000319281500004
PM 23341435
ER
PT J
AU Meadows, ME
Chang, G
Jones, JA
Antin, JR
Orav, EJ
AF Meadows, Mary-Ellen
Chang, Grace
Jones, Jennifer A.
Antin, Joseph R.
Orav, E. John
TI Predictors of Neuropsychological Change in Patients with Chronic
Myelogenous Leukemia and Myelodysplastic Syndrome
SO ARCHIVES OF CLINICAL NEUROPSYCHOLOGY
LA English
DT Article
DE Cancer; Neuropsychology; Hematological malignancy; Cognition; Cancer
treatment; Hematopoietic stem cell transplantation
ID STEM-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; SELECTIVE
REMINDING TEST; QUALITY-OF-LIFE; CANCER-PATIENTS; COGNITIVE FUNCTION;
NORMATIVE DATA; ADULT SURVIVORS; VERBAL FLUENCY; CHEMOTHERAPY
AB This study examined the course of neuropsychological functioning in patients with chronic myelogeous leukemia (n 91) or myelodysplastic syndrome (n 15) who underwent standard treatment for their disease or allogeneic hematopoietic stem cell transplantation (HSCT) at baseline, 12 months, and 18 months post-treatment. At baseline, 23 of the participants (n 75) in the longitudinal sample had Z-scores on at least one of the neuropsychological tests that were 1.4. Participants in the study showed improvement over baseline at the 12 and 18 months assessments. The average Z-scores for the six cognitive domains in the longitudinal data set over the course of the study ranged from 0.89 to 0.59. Significant predictors of change in neuropsychological test scores included age, with older participants showing less improvement over time. Other predictors included baseline cognitive domains (language, memory, and attention), previous cocaine use, disease status, intelligence quotient, and quality of life measures. Findings support previous studies in patients with hematological malignancies who showed cognitive impairments at baseline prior to HSCT. However, there was little evidence for further cognitive decline over the course of 18 months.
C1 [Meadows, Mary-Ellen] Brigham & Womens Hosp, Div Cognit & Behav Neurol, Boston, MA 02115 USA.
[Meadows, Mary-Ellen; Chang, Grace; Jones, Jennifer A.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
[Meadows, Mary-Ellen; Chang, Grace; Antin, Joseph R.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA.
[Antin, Joseph R.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Orav, E. John] Harvard Univ, Sch Med, Dept Med Biostat, Boston, MA USA.
RP Meadows, ME (reprint author), Brigham & Womens Hosp, Div Cognit & Behav Neurol, 221 Longwood Ave, Boston, MA 02115 USA.
EM mmeadows@partners.org
FU American Cancer Society [RSG-01-246-01-PBP]; National Institute on
Alcohol Abuse and Alcoholism [K24 AA 000289]
FX This work was supported in part by the American Cancer Society
(RSG-01-246-01-PBP to GC) and the National Institute on Alcohol Abuse
and Alcoholism (K24 AA 000289 to GC).
NR 56
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Z9 3
U1 0
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0887-6177
J9 ARCH CLIN NEUROPSYCH
JI Arch. Clin. Neuropsychol.
PD JUN
PY 2013
VL 28
IS 4
BP 363
EP 374
DI 10.1093/arclin/acs141
PG 12
WC Psychology, Clinical; Psychology
SC Psychology
GA 148XI
UT WOS:000319281500006
PM 23391504
ER
PT J
AU Goyal, RK
Chaudhury, A
AF Goyal, Raj K.
Chaudhury, Arun
TI Structure activity relationship of synaptic and junctional
neurotransmission
SO AUTONOMIC NEUROSCIENCE-BASIC & CLINICAL
LA English
DT Review
DE Postsynaptic potentials; Junction potentials; Smooth muscle
neuromuscular transmission; Autonomic ganglia; Enteric nervous system;
Nonsynaptic neurotransmission; Modes of neurotransmission
ID ENTERIC NERVOUS-SYSTEM; GUINEA-PIG ILEUM; NICOTINIC
ACETYLCHOLINE-RECEPTORS; SMOOTH-MUSCLE-CELLS; NITRIC-OXIDE SYNTHASE;
DENSE-CORED VESICLES; PURINERGIC NEUROMUSCULAR-TRANSMISSION; ELECTRON
MICROSCOPIC IDENTIFICATION; INHIBITORY POSTSYNAPTIC POTENTIALS;
SYMPATHETIC PREGANGLIONIC NEURONS
AB Chemical neurotransmission may include transmission to local or remote sites. Locally, contact between 'bare' portions of the bulbous nerve terminal termed a varicosity and the effector cell may be in the form of either synapse or non-synaptic contact. Traditionally, all local transmissions between nerves and effector cells are considered synaptic in nature. This is particularly true for communication between neurons. However, communication between nerves and other effectors such as smooth muscles has been described as nonsynaptic or junctional in nature. Nonsynaptic neurotransmission is now also increasingly recognized in the CNS. This review focuses on the relationship between structure and function that orchestrate synaptic and junctional neurotransmissions. A synapse is a specialized focal contact between the presynaptic active zone capable of ultrafast release of soluble transmitters and the postsynaptic density that cluster ionotropic receptors. The presynaptic and the postsynaptic areas are separated by the 'closed' synaptic cavity. The physiological hallmark of the synapse is ultrafast postsynaptic potentials lasting milliseconds. In contrast, junctions are juxtapositions of nerve terminals and the effector cells without clear synaptic specializations and the junctional space is 'open' to the extracellular space. Based on the nature of the transmitters, postjunctional receptors and their separation from the release sites, the junctions can be divided into 'close' and 'wide' junctions. Functionally, the 'close' and the 'wide' junctions can be distinguished by postjunctional potentials lasting similar to 1 s and tens of seconds, respectively. Both synaptic and junctional communications are common between neurons; however, junctional transmission is the rule at many neuro-non-neural effectors. Published by Elsevier B.V.
C1 [Goyal, Raj K.] VA Boston Healthcare Syst, GI Div, Ctr Swallowing & Motil Disorders, Boston, MA USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Goyal, RK (reprint author), Harvard Univ, Sch Med, VA Med Ctr, 1400 VFW Pkwy, W Roxbury, MA 02132 USA.
EM raj_goyal@hms.harvard.edu
FU National Institute of Diabetes and Digestive and Kidney Diseases
[DK-062867]
FX This work was supported by a National Institute of Diabetes and
Digestive and Kidney Diseases grant (DK-062867). The authors wish to
thank Antonietta D'Urso for help with preparation of manuscript. We also
thank Dr. Joel Bornstein for his constructive criticisms.
NR 231
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Z9 11
U1 2
U2 21
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1566-0702
EI 1872-7484
J9 AUTON NEUROSCI-BASIC
JI Auton. Neurosci-Basic Clin.
PD JUN
PY 2013
VL 176
IS 1-2
BP 11
EP 31
DI 10.1016/j.autneu.2013.02.012
PG 21
WC Neurosciences
SC Neurosciences & Neurology
GA 151UO
UT WOS:000319485900004
PM 23535140
ER
PT J
AU Sylvia, L
AF Sylvia, L.
TI NEWTx Program for Bipolar Disorders
SO BIPOLAR DISORDERS
LA English
DT Meeting Abstract
CT 10th International Conference on Bipolar Disorder of the
International-Society-for-Bipolar-Disorders
CY JUN 13-16, 2013
CL Miami Beach, FL
SP Int Soc Bipolar Disorders
DE nutrition; exercise; bipolar disorder; cognitive behavioral therapy
C1 [Sylvia, L.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 1
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1398-5647
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD JUN
PY 2013
VL 15
SU 1
SI SI
BP 10
EP 10
PG 1
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 156MR
UT WOS:000319826800007
ER
PT J
AU Thase, ME
AF Thase, M. E.
TI Clustering of depressive and manic symptoms in bipolar disorder
SO BIPOLAR DISORDERS
LA English
DT Meeting Abstract
CT 10th International Conference on Bipolar Disorder of the
International-Society-for-Bipolar-Disorders
CY JUN 13-16, 2013
CL Miami Beach, FL
SP Int Soc Bipolar Disorders
DE bipolar affective disorder; depression; hypomania; mania; mixed states
C1 [Thase, M. E.] Univ Penn, Philadelphia VA Med Ctr, Perelman Sch Med, Philadelphia, PA 19104 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1398-5647
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD JUN
PY 2013
VL 15
SU 1
SI SI
BP 18
EP 18
PG 1
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 156MR
UT WOS:000319826800029
ER
PT J
AU Reilly-Harrington, NA
Sylvia, LG
Leon, AC
Shesler, LW
Ketter, TA
Bowden, CL
Calabrese, JR
Friedman, ES
Ostacher, MJ
Iosifescu, DV
Rabideau, D
Nierenberg, AA
AF Reilly-Harrington, N. A.
Sylvia, L. G.
Leon, A. C.
Shesler, L. W.
Ketter, T. A.
Bowden, C. L.
Calabrese, J. R.
Friedman, E. S.
Ostacher, M. J.
Iosifescu, D. V.
Rabideau, D.
Nierenberg, A. A.
TI The medication recommendation tracking form: a novel tool for tracking
changes in prescribed medication, clinical decision making, and use in
comparative effectiveness research
SO BIPOLAR DISORDERS
LA English
DT Meeting Abstract
CT 10th International Conference on Bipolar Disorder of the
International-Society-for-Bipolar-Disorders
CY JUN 13-16, 2013
CL Miami Beach, FL
SP Int Soc Bipolar Disorders
DE bipolar; comparative effectiveness; training; assessment; methodology
C1 [Reilly-Harrington, N. A.; Sylvia, L. G.; Leon, A. C.; Shesler, L. W.; Ketter, T. A.; Bowden, C. L.; Calabrese, J. R.; Friedman, E. S.; Ostacher, M. J.; Iosifescu, D. V.; Rabideau, D.; Nierenberg, A. A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1398-5647
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD JUN
PY 2013
VL 15
SU 1
SI SI
BP 20
EP 21
PG 2
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 156MR
UT WOS:000319826800035
ER
PT J
AU Thase, ME
AF Thase, M. E.
TI Clinical perspective on RDoC and ROAMER utility
SO BIPOLAR DISORDERS
LA English
DT Meeting Abstract
CT 10th International Conference on Bipolar Disorder of the
International-Society-for-Bipolar-Disorders
CY JUN 13-16, 2013
CL Miami Beach, FL
SP Int Soc Bipolar Disorders
DE bipolar disorder; depression; dimensional assessment; RDOCs; ROAMER;
cognitive dysfunction; insomnia
C1 [Thase, M. E.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Thase, M. E.] Philadelphia VA Med Ctr, Philadelphia, PA USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1398-5647
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD JUN
PY 2013
VL 15
SU 1
SI SI
BP 37
EP 37
PG 1
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 156MR
UT WOS:000319826800079
ER
PT J
AU Iosifescu, DV
Gilmer, W
Fan, A
Rappaport, M
Deckersbach, T
Nierenberg, AA
AF Iosifescu, D. V.
Gilmer, W.
Fan, A.
Rappaport, M.
Deckersbach, T.
Nierenberg, A. A.
TI Memantine, a glutamate NMDA receptor antagonist, for cognitive deficits
in euthymic bipolar subjects
SO BIPOLAR DISORDERS
LA English
DT Meeting Abstract
CT 10th International Conference on Bipolar Disorder of the
International-Society-for-Bipolar-Disorders
CY JUN 13-16, 2013
CL Miami Beach, FL
SP Int Soc Bipolar Disorders
DE memantine; glutamate NMDA receptor antagonist; cognition; attention;
memory; social function
C1 [Iosifescu, D. V.] Mt Sinai Sch Med, New York, NY USA.
[Gilmer, W.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Fan, A.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA.
[Rappaport, M.] Emory Univ, Sch Med, Atlanta, GA USA.
[Deckersbach, T.] Harvard Univ, Sch Med, Boston, MA USA.
[Deckersbach, T.; Nierenberg, A. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 1
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1398-5647
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD JUN
PY 2013
VL 15
SU 1
SI SI
BP 40
EP 40
PG 1
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 156MR
UT WOS:000319826800084
ER
PT J
AU Biederman, J
AF Biederman, J.
TI Further evidence for robust familiality of pediatric bipolar-I disorder
SO BIPOLAR DISORDERS
LA English
DT Meeting Abstract
CT 10th International Conference on Bipolar Disorder of the
International-Society-for-Bipolar-Disorders
CY JUN 13-16, 2013
CL Miami Beach, FL
SP Int Soc Bipolar Disorders
DE familiality meta-analysis
C1 [Biederman, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1398-5647
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD JUN
PY 2013
VL 15
SU 1
SI SI
BP 63
EP 64
PG 2
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 156MR
UT WOS:000319826800139
ER
PT J
AU Stange, JP
Sylvia, L
Magalhaes, PVS
Frank, E
Otto, MW
Miklowitz, DJ
Berk, M
Nierenberg, AA
Deckersbach, T
AF Stange, J. P.
Sylvia, L.
Magalhaes, P. V. S.
Frank, E.
Otto, M. W.
Miklowitz, D. J.
Berk, M.
Nierenberg, A. A.
Deckersbach, T.
TI Extreme attributions predict transition from depression to mania in
bipolar disorder: results from STEP-BD
SO BIPOLAR DISORDERS
LA English
DT Meeting Abstract
CT 10th International Conference on Bipolar Disorder of the
International-Society-for-Bipolar-Disorders
CY JUN 13-16, 2013
CL Miami Beach, FL
SP Int Soc Bipolar Disorders
DE attributional style; cognitive flexibility; course of illness; mania;
depression
C1 [Stange, J. P.] Temple Univ, Philadelphia, PA 19122 USA.
[Sylvia, L.; Nierenberg, A. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Magalhaes, P. V. S.] Hosp Clin Porto Alegre, Natl Inst Translat Med, Porto Alegre, RS, Brazil.
[Frank, E.] Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Pittsburgh, PA USA.
[Otto, M. W.] Boston Univ, Boston, MA 02215 USA.
[Miklowitz, D. J.] Univ Calif Los Angeles, Sch Med, Dept Psychiat, Los Angeles, CA 90024 USA.
[Berk, M.] Deakin Univ, Geelong, Vic 3217, Australia.
[Deckersbach, T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
RI Magalhaes, Pedro/A-8519-2008
OI Magalhaes, Pedro/0000-0002-5644-6357
NR 0
TC 0
Z9 0
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1398-5647
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD JUN
PY 2013
VL 15
SU 1
SI SI
BP 78
EP 78
PG 1
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 156MR
UT WOS:000319826800174
ER
PT J
AU Eisner, L
Gironde, S
Deckersbach, T
AF Eisner, L.
Gironde, S.
Deckersbach, T.
TI Enhancing emotion regulation in bipolar disorder
SO BIPOLAR DISORDERS
LA English
DT Meeting Abstract
CT 10th International Conference on Bipolar Disorder of the
International-Society-for-Bipolar-Disorders
CY JUN 13-16, 2013
CL Miami Beach, FL
SP Int Soc Bipolar Disorders
DE mindfulness; emotion regulation; distress tolerance; group therapy
C1 [Eisner, L.; Deckersbach, T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bipolar Clin, Boston, MA USA.
[Eisner, L.; Deckersbach, T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Res Program, Boston, MA USA.
[Gironde, S.] McLean Hosp, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1398-5647
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD JUN
PY 2013
VL 15
SU 1
SI SI
BP 97
EP 98
PG 2
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 156MR
UT WOS:000319826800223
ER
PT J
AU Biederman, J
Woodworth, K
Martelon, M
AF Biederman, J.
Woodworth, K.
Martelon, M.
TI Personal and familial correlates of the child behavior checklist
(CBCL)-severe dysregulation profile
SO BIPOLAR DISORDERS
LA English
DT Meeting Abstract
CT 10th International Conference on Bipolar Disorder of the
International-Society-for-Bipolar-Disorders
CY JUN 13-16, 2013
CL Miami Beach, FL
SP Int Soc Bipolar Disorders
DE mood disorders; severity of illness index; screening instrument
C1 [Biederman, J.; Woodworth, K.; Martelon, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 1
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1398-5647
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD JUN
PY 2013
VL 15
SU 1
SI SI
BP 112
EP 112
PG 1
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 156MR
UT WOS:000319826800260
ER
PT J
AU Wozniak, J
Hernandez, M
AF Wozniak, J.
Hernandez, M.
TI High level of persistence of pediatric bipolar-1 disorder from childhood
onto adolescent years: a four year prospective longitudinal follow-up
study
SO BIPOLAR DISORDERS
LA English
DT Meeting Abstract
CT 10th International Conference on Bipolar Disorder of the
International-Society-for-Bipolar-Disorders
CY JUN 13-16, 2013
CL Miami Beach, FL
SP Int Soc Bipolar Disorders
DE bipolar disorder; children; adolescent; course; follow-up
C1 [Wozniak, J.; Hernandez, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1398-5647
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD JUN
PY 2013
VL 15
SU 1
SI SI
BP 116
EP 116
PG 1
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 156MR
UT WOS:000319826800269
ER
PT J
AU Fried, R
Biederman, J
Kenworthy, T
Wozniak, J
AF Fried, R.
Biederman, J.
Kenworthy, T.
Wozniak, J.
TI Distinguishing the executive functioning deficits of pediatric bipolar
disorder from attention deficit hyperactivity disorder utilizing
computerized assessment
SO BIPOLAR DISORDERS
LA English
DT Meeting Abstract
CT 10th International Conference on Bipolar Disorder of the
International-Society-for-Bipolar-Disorders
CY JUN 13-16, 2013
CL Miami Beach, FL
SP Int Soc Bipolar Disorders
DE neuropsychology; CANTAB; executive funcitning; bipolar youth
C1 [Fried, R.; Biederman, J.; Kenworthy, T.; Wozniak, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 1
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1398-5647
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD JUN
PY 2013
VL 15
SU 1
SI SI
BP 128
EP 128
PG 1
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 156MR
UT WOS:000319826800298
ER
PT J
AU Ketter, TA
Sachs, G
Lu, K
Laszlovszky, I
Nagy, K
Starace, A
Durgam, S
AF Ketter, T. A.
Sachs, G.
Lu, K.
Laszlovszky, I.
Nagy, K.
Starace, A.
Durgam, S.
TI Long-term safety and tolerability of open-label cariprazine in patients
with bipolar I disorder
SO BIPOLAR DISORDERS
LA English
DT Meeting Abstract
CT 10th International Conference on Bipolar Disorder of the
International-Society-for-Bipolar-Disorders
CY JUN 13-16, 2013
CL Miami Beach, FL
SP Int Soc Bipolar Disorders
DE cariprazine; bipolar disorder; acute mania; clinical trial
C1 [Ketter, T. A.] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
[Sachs, G.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Lu, K.; Starace, A.; Durgam, S.] Forest Res Inst, Jersey City, NJ USA.
[Laszlovszky, I.; Nagy, K.] Gedeon Richter Plc, Budapest, Hungary.
NR 0
TC 0
Z9 1
U1 1
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1398-5647
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD JUN
PY 2013
VL 15
SU 1
SI SI
BP 134
EP 134
PG 1
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 156MR
UT WOS:000319826800312
ER
PT J
AU Loebel, A
Cucchiaro, J
Silva, R
Hsu, J
Sarma, K
Sachs, G
Calabrese, JR
AF Loebel, A.
Cucchiaro, J.
Silva, R.
Hsu, J.
Sarma, K.
Sachs, G.
Calabrese, J. R.
TI Lurasidone adjunctive to lithium or valproate for the treatment of
bipolar I depression: results of a 6-week, double-blind,
placebo-controlled study
SO BIPOLAR DISORDERS
LA English
DT Meeting Abstract
CT 10th International Conference on Bipolar Disorder of the
International-Society-for-Bipolar-Disorders
CY JUN 13-16, 2013
CL Miami Beach, FL
SP Int Soc Bipolar Disorders
DE bipolar disorder; depression; atypical antipsychotics; randomized
clinical trial
C1 [Loebel, A.; Cucchiaro, J.; Silva, R.; Hsu, J.; Sarma, K.] Sunovion Pharmaceut Inc, Ft Lee, NJ USA.
[Sachs, G.] Massachusetts Gen Hosp, Bipolar Clin, Boston, MA 02114 USA.
[Sachs, G.] Massachusetts Gen Hosp, Res Program, Boston, MA 02114 USA.
[Calabrese, J. R.] Univ Hosp Case Med Ctr, Cleveland, OH USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1398-5647
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD JUN
PY 2013
VL 15
SU 1
SI SI
BP 137
EP 138
PG 2
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 156MR
UT WOS:000319826800322
ER
PT J
AU Loebel, A
Cucchiaro, J
Silva, R
Sarma, K
Kroger, H
Calabrese, JR
Sachs, G
AF Loebel, A.
Cucchiaro, J.
Silva, R.
Sarma, K.
Kroger, H.
Calabrese, J. R.
Sachs, G.
TI Lurasidone monotherapy for the treatment of bipolar I depression:
results of a 6-week, double-blind, placebo-controlled study
SO BIPOLAR DISORDERS
LA English
DT Meeting Abstract
CT 10th International Conference on Bipolar Disorder of the
International-Society-for-Bipolar-Disorders
CY JUN 13-16, 2013
CL Miami Beach, FL
SP Int Soc Bipolar Disorders
DE bipolar disorder; depression; atypical antipsychotics; randomized
clinical trial
C1 [Loebel, A.; Cucchiaro, J.; Silva, R.; Sarma, K.; Kroger, H.] Sunovion Pharmaceut Inc, Ft Lee, NJ USA.
[Calabrese, J. R.] Univ Hosp Case Med Ctr, Cleveland, OH USA.
[Sachs, G.] Massachusetts Gen Hosp, Bipolar Clin, Boston, MA 02114 USA.
[Sachs, G.] Massachusetts Gen Hosp, Res Program, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1398-5647
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD JUN
PY 2013
VL 15
SU 1
SI SI
BP 138
EP 138
PG 1
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 156MR
UT WOS:000319826800323
ER
PT J
AU Sachs, G
Siu, C
Cucchiaro, J
Silva, R
Grossman, F
Hsu, J
Kalali, A
Loebel, A
AF Sachs, G.
Siu, C.
Cucchiaro, J.
Silva, R.
Grossman, F.
Hsu, J.
Kalali, A.
Loebel, A.
TI Effect of personality traits on treatment outcomes in bipolar depression
SO BIPOLAR DISORDERS
LA English
DT Meeting Abstract
CT 10th International Conference on Bipolar Disorder of the
International-Society-for-Bipolar-Disorders
CY JUN 13-16, 2013
CL Miami Beach, FL
SP Int Soc Bipolar Disorders
DE bipolar depression; personality traits; treatment outcomes
C1 [Sachs, G.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Siu, C.] Data Power Inc, Flemington, NJ USA.
[Cucchiaro, J.; Silva, R.; Grossman, F.; Hsu, J.; Loebel, A.] Sunivion Pharmaceut Inc, Ft Lee, NJ USA.
Quintiles, San Diego, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1398-5647
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD JUN
PY 2013
VL 15
SU 1
SI SI
BP 139
EP 139
PG 1
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 156MR
UT WOS:000319826800325
ER
PT J
AU Deckersbach, T
Peters, A
Sylvia, L
Urdahl, A
Magalhaes, PVS
Otto, MW
Frank, E
Miklowitz, DJ
Berk, M
Kinrys, G
Nierenberg, AA
AF Deckersbach, T.
Peters, A.
Sylvia, L.
Urdahl, A.
Magalhaes, P. V. S.
Otto, M. W.
Frank, E.
Miklowitz, D. J.
Berk, M.
Kinrys, G.
Nierenberg, A. A.
TI The role of co-morbid anxiety in psychosocial treatment for acute
bipolar depression
SO BIPOLAR DISORDERS
LA English
DT Meeting Abstract
CT 10th International Conference on Bipolar Disorder of the
International-Society-for-Bipolar-Disorders
CY JUN 13-16, 2013
CL Miami Beach, FL
SP Int Soc Bipolar Disorders
DE lamotrigine; adolescents; depression; bipolar
C1 [Deckersbach, T.] Harvard Univ, Sch Med, Boston, MA USA.
[Deckersbach, T.; Sylvia, L.; Kinrys, G.; Nierenberg, A. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Peters, A.] Univ Illinois, Chicago, IL USA.
[Urdahl, A.] Childrens Hosp Wisconsin, Community Serv, Milwaukee, WI 53201 USA.
[Magalhaes, P. V. S.] Hosp Clin Porto Alegre, Natl Inst Translat Med, Porto Alegre, RS, Brazil.
[Otto, M. W.] Boston Univ, Boston, MA 02215 USA.
[Frank, E.] Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Pittsburgh, PA USA.
[Miklowitz, D. J.] Univ Calif Los Angeles, Sch Med, Dept Psychiat, Los Angeles, CA 90024 USA.
[Berk, M.] Deakin Univ, Geelong, Vic 3217, Australia.
RI Magalhaes, Pedro/A-8519-2008
OI Magalhaes, Pedro/0000-0002-5644-6357
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1398-5647
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD JUN
PY 2013
VL 15
SU 1
SI SI
BP 146
EP 146
PG 1
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 156MR
UT WOS:000319826800343
ER
PT J
AU Sylvia, L
Salcedo, S
Peters, AT
Magalhaes, PVS
Frank, E
Miklowitz, DJ
Otto, MW
Berk, M
Bernstein, EE
Nierenberg, AA
Deckersbach, T
AF Sylvia, L.
Salcedo, S.
Peters, A. T.
Magalhaes, P. V. S.
Frank, E.
Miklowitz, D. J.
Otto, M. W.
Berk, M.
Bernstein, E. E.
Nierenberg, A. A.
Deckersbach, T.
TI Sleep disturbance moderates psychotherapy outcomes in patients with
bipolar disorder: a STEP-BD report
SO BIPOLAR DISORDERS
LA English
DT Meeting Abstract
CT 10th International Conference on Bipolar Disorder of the
International-Society-for-Bipolar-Disorders
CY JUN 13-16, 2013
CL Miami Beach, FL
SP Int Soc Bipolar Disorders
DE sleep disturbance; insomnia; hypersomnia; psychotherapy; depressive
episode
C1 [Sylvia, L.; Salcedo, S.; Otto, M. W.; Bernstein, E. E.; Nierenberg, A. A.; Deckersbach, T.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Peters, A. T.] Univ Illinois, Chicago, IL USA.
[Magalhaes, P. V. S.] Hosp Clin Porto Alegre, Natl Inst Translat Med, Porto Alegre, RS, Brazil.
[Frank, E.] Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Pittsburgh, PA USA.
[Miklowitz, D. J.] Univ Calif Los Angeles, Sch Med, Dept Psychiat, Los Angeles, CA 90024 USA.
[Berk, M.] Deakin Univ, Geelong, Vic 3217, Australia.
[Deckersbach, T.] Harvard Univ, Sch Med, Boston, MA USA.
RI Magalhaes, Pedro/A-8519-2008
OI Magalhaes, Pedro/0000-0002-5644-6357
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1398-5647
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD JUN
PY 2013
VL 15
SU 1
SI SI
BP 147
EP 147
PG 1
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 156MR
UT WOS:000319826800345
ER
PT J
AU Sylvia, L
Leon, A
Nierenberg, AA
Bowden, C
Friedman, E
Greiter, E
Iosifescu, DV
Thase, ME
Ketter, TA
Calabrese, JR
Rabideau, D
Ostacher, M
Reilly-Harrington, NA
AF Sylvia, L.
Leon, A.
Nierenberg, A. A.
Bowden, C.
Friedman, E.
Greiter, E.
Iosifescu, D. V.
Thase, M. E.
Ketter, T. A.
Calabrese, J. R.
Rabideau, D.
Ostacher, M.
Reilly-Harrington, N. A.
TI Predictors and outcomes of quality of life and life functioning in
bipolar disorder
SO BIPOLAR DISORDERS
LA English
DT Meeting Abstract
CT 10th International Conference on Bipolar Disorder of the
International-Society-for-Bipolar-Disorders
CY JUN 13-16, 2013
CL Miami Beach, FL
SP Int Soc Bipolar Disorders
DE bipolar disorder; life functioning; quality of life; lithium
C1 [Sylvia, L.; Nierenberg, A. A.; Greiter, E.; Rabideau, D.; Reilly-Harrington, N. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Leon, A.] Weill Cornell Med Coll, New York, NY USA.
[Bowden, C.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Friedman, E.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA.
[Iosifescu, D. V.] Mt Sinai Sch Med, New York, NY USA.
[Thase, M. E.] Univ Penn, Philadelphia VA Med Ctr, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Ketter, T. A.; Ostacher, M.] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
[Calabrese, J. R.] Univ Hosp Case Med Ctr, Cleveland, OH USA.
[Reilly-Harrington, N. A.] Harvard Univ, Sch Med, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1398-5647
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD JUN
PY 2013
VL 15
SU 1
SI SI
BP 148
EP 148
PG 1
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 156MR
UT WOS:000319826800348
ER
PT J
AU Kozhevnikov, M
Kozhevnikov, M
Yu, CJ
Blazhenkova, O
AF Kozhevnikov, Maria
Kozhevnikov, Michael
Yu, Chen Jiao
Blazhenkova, Olesya
TI Creativity, visualization abilities, and visual cognitive style
SO BRITISH JOURNAL OF EDUCATIONAL PSYCHOLOGY
LA English
DT Article
ID MENTAL-IMAGERY; SPATIAL VISUALIZATION; DOMAIN SPECIFICITY; OBJECT;
METAANALYSIS; POTENTIALS; VALIDITY
AB Background Despite the recent evidence for a multi-component nature of both visual imagery and creativity, there have been no systematic studies on how the different dimensions of creativity and imagery might interrelate. Aims The main goal of this study was to investigate the relationship between different dimensions of creativity (artistic and scientific) and dimensions of visualization abilities and styles (object and spatial). In addition, we compared the contributions of object and spatial visualization abilities versus corresponding styles to scientific and artistic dimensions of creativity. Samples Twenty-four undergraduate students (12 females) were recruited for the first study, and 75 additional participants (36 females) were recruited for an additional experiment. Method Participants were administered a number of object and spatial visualization abilities and style assessments as well as a number of artistic and scientific creativity tests. Results The results show that object visualization relates to artistic creativity and spatial visualization relates to scientific creativity, while both are distinct from verbal creativity. Furthermore, our findings demonstrate that style predicts corresponding dimension of creativity even after removing shared variance between style and visualization ability. The results suggest that styles might be a more ecologically valid construct in predicting real-life creative behaviour, such as performance in different professional domains.
C1 [Kozhevnikov, Maria; Yu, Chen Jiao] Natl Univ Singapore, Dept Psychol, Singapore 117570, Singapore.
[Kozhevnikov, Maria] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA.
[Kozhevnikov, Michael] Norfolk State Univ, Dept Engn, Norfolk, VA USA.
[Blazhenkova, Olesya] Sabanci Univ, Fac Arts & Social Sci, Istanbul, Turkey.
RP Kozhevnikov, M (reprint author), Natl Univ Singapore, Dept Psychol, Block AS4,Level 2,9 Arts Link, Singapore 117570, Singapore.
EM mkozhevn@nmr.mgh.harvard.edu
RI Blazhenkova, Olesya/H-8367-2016
OI Blazhenkova, Olesya/0000-0002-9513-7258
NR 52
TC 15
Z9 15
U1 3
U2 30
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0007-0998
EI 2044-8279
J9 BRIT J EDUC PSYCHOL
JI Br. J. Educ. Psychol.
PD JUN
PY 2013
VL 83
IS 2
BP 196
EP 209
DI 10.1111/bjep.12013
PG 14
WC Psychology, Educational
SC Psychology
GA 148WC
UT WOS:000319277900002
PM 23692530
ER
PT J
AU Galsky, MD
Hendricks, R
Svatek, R
Bangs, R
Hoffman-Censits, J
Clement, J
Dreicer, R
Guancial, E
Hahn, N
Lerner, SP
O'Donnell, PH
Quale, DZ
Siefker-Radtke, A
Shipley, W
Sonpavde, G
Vaena, D
Vinson, J
Rosenberg, J
AF Galsky, Matthew D.
Hendricks, Ryan
Svatek, Robert
Bangs, Rick
Hoffman-Censits, Jean
Clement, Jessica
Dreicer, Robert
Guancial, Elizabeth
Hahn, Noah
Lerner, Seth P.
O'Donnell, Peter H.
Quale, Diane Zipursky
Siefker-Radtke, Arlene
Shipley, William
Sonpavde, Guru
Vaena, Daniel
Vinson, Jacob
Rosenberg, Jonathan
TI Critical analysis of contemporary clinical research in muscle-invasive
and metastatic urothelial cancer
SO CANCER
LA English
DT Article
DE bladder cancer; urothelial cancer; metastatic; clinical trials
ID BLADDER-CANCER; NEOADJUVANT CHEMOTHERAPY; PHASE-III; METHOTREXATE;
VINBLASTINE; CISPLATIN; CLINICALTRIALS.GOV; DOXORUBICIN; CARCINOMA;
TRIAL
AB BACKGROUND There have been no improvements in the treatment of metastatic urothelial cancer in the past several decades. A census of contemporary clinical research in this disease was performed to identify potential barriers and opportunities. METHODS These authors performed a search for clinical trials exploring interventions in muscle-invasive and metastatic urothelial cancer, using the ClinicalTrials.gov registry. Data extracted from the registry included title, recruitment status, interventions, sponsor, phase, enrollment, study design, and study sites. RESULTS Among 120 eligible trials exploring interventions in muscle-invasive and metastatic urothelial cancer, 73% were phase 2 and 73% were nonrandomized. The majority (63%) involved treatment in the metastatic disease state. The median planned enrollment size per trial was 45 patients (interquartile range, 47 patients). The majority of trials (55%) involved 3 study sites. Trials most commonly explored interventions in the first-line metastatic (30%) or second-line metastatic (37%) settings. Targeted therapeutics were studied in 58% of the trials. Among 56 trials that completed enrollment, the median time to complete accrual was 50 months (range, 10-109 months), and these trials enrolled a median of 40 patients per trial (interquartile range, 44 patients). CONCLUSIONS The majority of contemporary clinical trials in muscle-invasive and metastatic urothelial cancer are small, nonrandomized, phase 2 trials involving 1 to 3 study sites. Enhanced communication and collaboration among the urothelial cancer community, and other stakeholders, is needed to facilitate the design and conduct of trials capable of expediting progress in this disease. Cancer 2013;119:19941998. (c) 2013 American Cancer Society.
C1 [Galsky, Matthew D.; Hendricks, Ryan] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY 10029 USA.
[Svatek, Robert] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Bangs, Rick; Quale, Diane Zipursky] Bladder Canc Advocacy Network, Bethesda, MD USA.
[Hoffman-Censits, Jean] Jefferson Kimmel Canc Ctr, Philadelphia, PA USA.
[Clement, Jessica] Univ Connecticut, Ctr Hlth, Farmington, CT USA.
[Dreicer, Robert] Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA.
[Guancial, Elizabeth] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Hahn, Noah] Indiana Univ, IU Simon Canc Ctr, Indianapolis, IN 46204 USA.
[Lerner, Seth P.] Baylor Coll Med, Houston, TX 77030 USA.
[O'Donnell, Peter H.] Univ Chicago, Chicago, IL 60637 USA.
[Siefker-Radtke, Arlene] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Shipley, William] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Sonpavde, Guru] Univ Alabama Birmingham, Birmingham, AL USA.
[Vaena, Daniel] Univ Iowa, Iowa City, IA USA.
[Vinson, Jacob; Rosenberg, Jonathan] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
RP Galsky, MD (reprint author), Mt Sinai Sch Med, Tisch Canc Inst, 1 Gustave L Levy Pl, New York, NY 10029 USA.
EM matthew.galsky@mssm.edu
NR 13
TC 5
Z9 5
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0008-543X
J9 CANCER-AM CANCER SOC
JI Cancer
PD JUN 1
PY 2013
VL 119
IS 11
BP 1994
EP 1998
DI 10.1002/cncr.27973
PG 5
WC Oncology
SC Oncology
GA 148VU
UT WOS:000319277000012
PM 23456777
ER
PT J
AU Cury, FL
Hunt, D
Roach, M
Shipley, W
Gore, E
Hsu, IC
Krisch, RE
Seider, MJ
Sandler, H
Lawton, C
AF Cury, Fabio L.
Hunt, Daniel
Roach, Mack, III
Shipley, William
Gore, Elizabeth
Hsu, I-Chow
Krisch, Robert E.
Seider, Michael J.
Sandler, Howard
Lawton, Colleen
TI Prostate-specific antigen response after short-term hormone therapy plus
external-beam radiotherapy and outcome in patients treated on Radiation
Therapy Oncology Group study 9413
SO CANCER
LA English
DT Article
DE prostate cancer; radiation therapy; androgen-deprivation therapy;
prostate-specific antigen; prediction of outcomes
ID NEOADJUVANT ANDROGEN DEPRIVATION; CANCER-SPECIFIC MORTALITY; PHASE-III
TRIAL; SUPPRESSION THERAPY; DOSE RADIOTHERAPY; PRETREATMENT PSA;
FAILURE; VELOCITY; DISEASE; RISK
AB BACKGROUND The objective of this study was to assess the impact of a prostate-specific antigen (PSA) complete response (PSA-CR), measured at the end of external-beam radiotherapy and short-term hormone therapy, on treatment outcomes. METHODS The phase 3 Radiation Therapy Oncology Group 9413 trial, as part of its original protocol, used the assessment of PSA-CR (ie, PSA 0.3 ng/mL) at the end of short-term HT as a secondary endpoint. Short-term HT consisted of futamide plus a lutenizing hormone-releasing hormone agonist for 4 months. The Kaplan-Meier method was used to estimate overall survival (OS) and disease-free survival. Cumulative incidence was used to estimate biochemical failure, distant metastasis, and disease-specific survival. Univariate and multivariate analyses were performed to correlate PSA-CR after short-term hormone therapy with all endpoints, and the following variables were considered for analysis: PSA at baseline, Gleason score, treatment arm, age, and baseline testosterone status. Phoenix consensus definition was used to define PSA failure. RESULTS For 1070 evaluable patients, the median PSA at the end of short-term hormone therapy was 0.2 ng/mL. In total, 744 patients (70%) had a PSA-CR. At a median follow-up of 7.2 years, failure to obtain a PSA-CR was associated significantly with worse disease-specific survival (P = .0003; hazard ratio [HR], 2.03; 95% confidence interval [CI], 1.38-2.97), with worse disease-free survival (P = .003; HR, 1.28; 95% CI, 1.09-1.50), and with a higher incidence of distant metastasis (P = .0002; HR, 1.92; 95% CI, 1.37-2.69) and biochemical failure (P < .0001; HR, 1.57; 95% CI, 1.29-1.91). Other factors that were associated with worse disease-specific survival were Gleason scores from 8 to 10 (P = .0002; HR, 3.06; 95% CI, 1.71-5.47) and PSA levels >20 ng/mL (P = .04; HR, 1.55; 95% CI, 1.02-2.30). CONCLUSIONS The current results indicated that failure to obtain a PSA-CR (PSA 0.3 ng/mL) after short-term hormone therapy and external-beam radiotherapy appears to be an independent predictor of unfavorable outcomes and could help identify patients who may benefit from the addition of long-term androgen ablation. Cancer 2013;119:19992004. (c) 2013 American Cancer Society.
C1 [Cury, Fabio L.] McGill Univ, Ctr Hlth, Montreal, PQ, Canada.
[Hunt, Daniel] Ctr Stat, Radiat Therapy Oncol Grp, Philadelphia, PA USA.
[Roach, Mack, III; Hsu, I-Chow] Univ Calif San Francisco, Dept Radiat Oncol, Helen Diller Comprehens Canc Ctr, San Francisco, CA USA.
[Shipley, William] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Gore, Elizabeth; Lawton, Colleen] Med Coll Wisconsin, Madison, WI USA.
[Krisch, Robert E.] Hosp Univ Penn, Philadelphia, PA 19104 USA.
[Seider, Michael J.] Akron City Hosp, Akron, OH USA.
[Sandler, Howard] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA.
RP Cury, FL (reprint author), 1650 Cedar Ave,D5-400, Montreal, PQ H3G 1A4, Canada.
EM fabio.cury@muhc.mcgill.ca
FU RTOG [U10 CA21661]; Community Clinical Oncology Program from the
National Cancer Institute [U10 CA37422]; Pennsylvania Department of
Health Formula Grant [4100050889]
FX This trial was conducted by the Radiation Therapy Oncology Group (RTOG)
and was supported by RTOG grant U10 CA21661, Community Clinical Oncology
Program grant U10 CA37422 from the National Cancer Institute, and the
2009 Pennsylvania Department of Health Formula Grant 4100050889.
NR 23
TC 5
Z9 6
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0008-543X
J9 CANCER-AM CANCER SOC
JI Cancer
PD JUN 1
PY 2013
VL 119
IS 11
BP 1999
EP 2004
DI 10.1002/cncr.28019
PG 6
WC Oncology
SC Oncology
GA 148VU
UT WOS:000319277000013
PM 23504930
ER
PT J
AU Zhu, JY
Sharma, DB
Chen, AB
Johnson, BE
Weeks, JC
Schrag, D
AF Zhu, Junya
Sharma, Dhruv B.
Chen, Aileen B.
Johnson, Bruce E.
Weeks, Jane C.
Schrag, Deborah
TI Comparative effectiveness of three platinum-doublet chemotherapy
regimens in elderly patients with advanced nonsmall cell lung cancer
SO CANCER
LA English
DT Article
DE nonsmall cell lung cancer; survival; first-line chemotherapy;
platinum-doublet; propensity score analysis; SEER-Medicare
ID PHASE-III TRIAL; PACLITAXEL PLUS CARBOPLATIN; RANDOMIZED
CONTROLLED-TRIALS; SEER-MEDICARE DATA; LEUKEMIA GROUP-B; PROPENSITY
SCORE; COMORBIDITY INDEX; MULTICENTER TRIAL; CISPLATIN; COMBINATION
AB BACKGROUND Randomized trials report equivalent efficacy among various combinations of platinum-based regimens in advanced nonsmall cell lung cancer (NSCLC). Their relative effectiveness and comparability based on squamous versus nonsquamous histology is uncertain. METHODS The authors used the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked data to identify first-line chemotherapy agents administered to Medicare beneficiaries with stage IIIB or IV NSCLC diagnosed from 2000 to 2007. Overall survival was compared between patients who received the 3 most common regimens: carboplatin-paclitaxel, carboplatin-gemcitabine, and carboplatin-docetaxel. Stratified analyses distinguished between the outcomes of patients with squamous versus nonsquamous cell histology. Multivariable Cox proportional hazards models and propensity score analyses facilitated adjustment for imbalance in measurable patient characteristics. RESULTS Of the 15,318 patients who received first-line chemotherapy, 43.1% received carboplatin-paclitaxel, 14.3% received carboplatin-gemcitabine, 8.5% received carboplatin-docetaxel, and 34.1% received other regimens. The median survival was 8.0 months (interquartile range [IQR], 3.5-17.4 months) for carboplatin-paclitaxel, 7.3 months (IQR, 3.4-15.2 months) for carboplatin-gemcitabine, and 7.5 months (IQR, 3.2-16.0 months) for carboplatin-docetaxel. Both multivariable and propensity score-adjusted Cox models demonstrated a slight inferiority associated with carboplatin-gemcitabine or carboplatin-docetaxel versus carboplatin-paclitaxel, with a hazard ratio of 1.10 (95% confidence interval, 1.04-1.15) and 1.09 (95% confidence interval, 1.02-1.16), respectively, in propensity score-stratified models. Among the subgroup of 2063 patients with squamous carcinoma, propensity score-stratified analyses had a higher risk of death (hazard ratio, 1.20; 95% confidence interval, 1.07-1.35) associated with carboplatin-gemcitabine versus carboplatin-paclitaxel. CONCLUSIONS Carboplatin-paclitaxel was associated with slightly better survival compared with carboplatin-gemcitabine or carboplatin-docetaxel within the Medicare population with advanced NSCLC, and this was most pronounced for patients who had squamous cell histology. Cancer 2013;119:20482060. (c) 2013 American Cancer Society.
C1 [Zhu, Junya] Dana Farber Canc Inst, Ctr Patient Safety, Boston, MA 02215 USA.
[Sharma, Dhruv B.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA.
[Chen, Aileen B.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02215 USA.
[Johnson, Bruce E.; Weeks, Jane C.; Schrag, Deborah] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Johnson, Bruce E.; Weeks, Jane C.; Schrag, Deborah] Harvard Univ, Sch Med, Boston, MA USA.
[Johnson, Bruce E.; Weeks, Jane C.; Schrag, Deborah] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Internal Med, Boston, MA 02115 USA.
RP Zhu, JY (reprint author), Dana Farber Canc Inst, Ctr Patient Safety, 450 Brookline Ave, Boston, MA 02215 USA.
EM junya_zhu@dfci.harvard.edu
OI Chen, Aileen/0000-0002-5385-3360
FU Agency for Healthcare Research and Quality (AHRQ) as part of the
Developing Evidence to Inform Decisions about Effectiveness (DEcIDE)
program [HHSA290201000006I]; National Cancer Institute (NCI)
[RC2CA148185-01]; NCI [PO1-CA134294]; Sanofi; Genentech; Astra Zeneca
FX This project was funded under contract no. HHSA290201000006I (to Drs.
Schrag and Schneeweiss) from the Agency for Healthcare Research and
Quality (AHRQ) as part of the Developing Evidence to Inform Decisions
about Effectiveness (DEcIDE) program. Project support was also obtained
from the National Cancer Institute (NCI) RC2CA148185-01 (to Dr. Weeks).
Dr. Sharma was supported by NCI grant PO1-CA134294. The authors of this
report are responsible for its content. Statements in the report should
not be construed as endorsement by the AHRQ, the NCI, or the U.S.
Department of Health and Human Services.; Dr. Johnson is a paid
consultant to Sanofi, Genentech, and Astra Zeneca.
NR 54
TC 10
Z9 10
U1 0
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0008-543X
J9 CANCER-AM CANCER SOC
JI Cancer
PD JUN 1
PY 2013
VL 119
IS 11
BP 2048
EP 2060
DI 10.1002/cncr.28022
PG 13
WC Oncology
SC Oncology
GA 148VU
UT WOS:000319277000019
PM 23564469
ER
PT J
AU Rhondali, W
Perez-Cruz, P
Hui, D
Chisholm, GB
Dalal, S
Baile, W
Chittenden, E
Bruera, E
AF Rhondali, Wadih
Perez-Cruz, Pedro
Hui, David
Chisholm, Gary B.
Dalal, Shalini
Baile, Walter
Chittenden, Eva
Bruera, Eduardo
TI Patientphysician communication about code status preferences A
Randomized Controlled Trial
SO CANCER
LA English
DT Article
DE code status; advanced cancer; communication; patient preferences;
randomized controlled trial
ID NOT-RESUSCITATE ORDERS; BREAKING BAD-NEWS; SYMPTOM ASSESSMENT SCALE;
LIFE DECISION-MAKING; INTENSIVE-CARE-UNIT; CANCER-PATIENTS; PATIENT
PREFERENCES; PALLIATIVE CARE; CARDIOPULMONARY-RESUSCITATION;
CLINICAL-TRIALS
AB BACKGROUND Code status discussions are important in cancer care, but the best modality for such discussions has not been established. The objective of this study was to determine the impact of a physician ending a code status discussion with a question (autonomy approach) versus a recommendation (beneficence approach) on patients' do-not-resuscitate (DNR) preference. METHODS Patients in a supportive care clinic watched 2 videos showing a physicianpatient discussion regarding code status. Both videos were identical except for the ending: one ended with the physician asking for the patient's code status preference and the other with the physician recommending DNR. Patients were randomly assigned to watch the videos in different sequences. The main outcome was the proportion of patients choosing DNR for the video patient. RESULTS A total of 78 patients completed the study, and 74% chose DNR after the question video, whereas 73% chose DNR after the recommendation video. Median physician compassion score was very high and not different for both videos. All 30 of 30 patients who had chosen DNR for themselves and 30 of 48 patients who had not chosen DNR for themselves chose DNR for the video patient (100% versus 62%). Age (odds ratio=1.1/year) and white ethnicity (odds ratio=9.43) predicted DNR choice for the video patient. CONCLUSIONS Ending DNR discussions with a question or a recommendation did not impact DNR choice or perception of physician compassion. Therefore, both approaches are clinically appropriate. All patients who chose DNR for themselves and most patients who did not choose DNR for themselves chose DNR for the video patient. Age and race predicted DNR choice. Cancer 2013;119:20672073. (c) 2013 American Cancer Society.
C1 [Rhondali, Wadih; Perez-Cruz, Pedro; Hui, David; Dalal, Shalini; Bruera, Eduardo] Univ Texas MD Anderson Canc Ctr, Dept Palliat Care & Rehabil Med, Houston, TX 77030 USA.
[Rhondali, Wadih] Hosp Civils Lyon, Ctr Hosp Lyon Sud, Dept Palliat Care, Lyon, France.
[Perez-Cruz, Pedro] Pontificia Univ Catolica Chile, Fac Med, Dept Med Interna, Programa Med Paliat, Santiago, Chile.
[Chisholm, Gary B.] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA.
[Baile, Walter] Univ Texas MD Anderson Canc Ctr, Dept Behav Sci, Houston, TX 77030 USA.
[Chittenden, Eva] Massachusetts Gen Hosp, Dept Palliat Care, Boston, MA 02114 USA.
RP Bruera, E (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Palliat Care & Rehabil Med, Unit 1414, 1515 Holcombe Blvd, Houston, TX 77030 USA.
EM ebruera@mdanderson.org
RI Rhondali, Wadih/K-2348-2013
OI Rhondali, Wadih/0000-0001-7740-1476
FU National Institutes of Health [R01NR010162-01A1, R01CA1222292.01,
R01CA12 4481-01]; University of Texas MD Anderson Cancer Center support
grant [CA 016672]
FX Dr. Bruera is supported in part by National Institutes of Health grants
R01NR010162-01A1, R01CA1222292.01, and R01CA12 4481-01 and in part by
the University of Texas MD Anderson Cancer Center support grant CA
016672.
NR 46
TC 11
Z9 11
U1 3
U2 15
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0008-543X
EI 1097-0142
J9 CANCER-AM CANCER SOC
JI Cancer
PD JUN 1
PY 2013
VL 119
IS 11
BP 2067
EP 2073
DI 10.1002/cncr.27981
PG 7
WC Oncology
SC Oncology
GA 148VU
UT WOS:000319277000021
PM 23564395
ER
PT J
AU Kang, JX
Liu, A
AF Kang, Jing X.
Liu, Angela
TI The role of the tissue omega-6/omega-3 fatty acid ratio in regulating
tumor angiogenesis
SO CANCER AND METASTASIS REVIEWS
LA English
DT Review
DE Omega-3 fatty acids; Omega-6 fatty acids; Fatty acid ratio;
Angiogenesis; Cancer; Inflammation
ID FAT-1 TRANSGENIC MICE; ENDOTHELIAL GROWTH-FACTOR; PROSTATE-CANCER;
ARACHIDONIC-ACID; LIPID MEDIATORS; CELL MIGRATION; BREAST-CANCER;
IN-VIVO; VEGF-C; ELEVATED OMEGA-3-FATTY-ACIDS
AB Angiogenesis is a necessary step in tumor growth and metastasis. It is well established that the metabolites of omega-6 and omega-3 fatty acids, which must be obtained through the diet and cannot be synthesized de novo in mammals, have differential effects on cellular processes. Omega-6 fatty acid (n-6 FA)-derived metabolites promote angiogenesis by increasing growth factor expression whereas omega-3 fatty acids (n-3 FA) have anti-angiogenic and antitumor properties. However, most studies thus far have failed to account for the role of the n-6 FA/n-3 FA ratio in angiogenesis and instead examined the absolute levels of n-6 and n-3 FA. This review highlights the biochemical interactions between n-6 and n-3 FA and focuses on how the n-6/n-3 FA ratio in tissues modulates tumor angiogenesis. We suggest that future work should consider the n-6/n-3 FA ratio to be a key element in experimental design and analysis. Furthermore, we recommend that clinical interventions should aim to both reduce n-6 metabolites and simultaneously increase n-3 FA intake.
C1 [Kang, Jing X.; Liu, Angela] Harvard Univ, Sch Med, Boston, MA USA.
[Kang, Jing X.; Liu, Angela] Massachusetts Gen Hosp, Lab Lipid Med & Technol, Charlestown, MA 02129 USA.
RP Kang, JX (reprint author), Massachusetts Gen Hosp, Lab Lipid Med & Technol, 149-13th St,Room 4001, Charlestown, MA 02129 USA.
EM kang.jing@mgh.harvard.edu
NR 97
TC 19
Z9 21
U1 2
U2 45
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0167-7659
EI 1573-7233
J9 CANCER METAST REV
JI Cancer Metastasis Rev.
PD JUN
PY 2013
VL 32
IS 1-2
SI SI
BP 201
EP 210
DI 10.1007/s10555-012-9401-9
PG 10
WC Oncology
SC Oncology
GA 147DQ
UT WOS:000319146200015
PM 23090260
ER
PT J
AU Peisley, A
Hur, S
AF Peisley, Alys
Hur, Sun
TI Multi-level regulation of cellular recognition of viral dsRNA
SO CELLULAR AND MOLECULAR LIFE SCIENCES
LA English
DT Review
DE Antiviral innate immunity; Double-stranded RNA; PKR; OAS; ADAR; TLR3;
RIG-I; MDA5
ID DOUBLE-STRANDED-RNA; TOLL-LIKE RECEPTOR-3; PROTEIN-KINASE PKR; 2'-5'
OLIGOADENYLATE SYNTHETASE; ANTIVIRAL INNATE IMMUNITY; HEPATITIS-DELTA
VIRUS; INDUCIBLE GENE-I; RIG-I; BINDING DOMAIN; MESSENGER-RNA
AB Effective antiviral immunity depends on accurate recognition of viral RNAs by the innate immune system. Double-stranded RNA (dsRNA) often accumulates in virally infected cells and was initially considered a unique viral signature that was sufficient to initiate antiviral response through dsRNA receptors and dsRNA-dependent effectors such as Toll-like receptor 3, retinoic acid inducible gene-1, protein kinase RNA-activated and oligoadenylate synthetase. However, dsRNA is also present in many cellular RNAs, raising a question of how these receptors and effectors discriminate between viral and cellular dsRNAs. Accumulating evidence suggests that innate immune sensors detect not only dsRNA structure but also other and often multiple features of RNA such as length, sequence, cellular location, post-transcriptional processing and modification, which are divergent between viral and cellular RNAs. This review summarizes recent findings on the substrate specificities of a few selected dsRNA-dependent effectors and receptors, which have revealed more complex mechanisms involved in cellular discrimination between self and non-self RNA.
C1 [Peisley, Alys; Hur, Sun] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Peisley, Alys; Hur, Sun] Childrens Hosp, Program Cellular & Mol Med, Ctr Life Sci Boston, Boston, MA 02115 USA.
RP Hur, S (reprint author), Childrens Hosp, Program Cellular & Mol Med, Ctr Life Sci Boston, 3 Blackfan Circle, Boston, MA 02115 USA.
EM hur@idi.harvard.edu
NR 158
TC 9
Z9 9
U1 0
U2 17
PU SPRINGER BASEL AG
PI BASEL
PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND
SN 1420-682X
J9 CELL MOL LIFE SCI
JI Cell. Mol. Life Sci.
PD JUN
PY 2013
VL 70
IS 11
BP 1949
EP 1963
DI 10.1007/s00018-012-1149-4
PG 15
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 148CK
UT WOS:000319220100006
PM 22960755
ER
PT J
AU Valente, AJ
Yoshida, T
Izadpanah, R
Delafontaine, P
Siebenlist, U
Chandrasekar, B
AF Valente, Anthony J.
Yoshida, Tadashi
Izadpanah, Reza
Delafontaine, Patrice
Siebenlist, Ulrich
Chandrasekar, Bysani
TI Interleukin-18 enhances IL-18R/Noxl binding, and mediates
TRAF3IP2-dependent smooth muscle cell migration. Inhibition by
simvastatin
SO CELLULAR SIGNALLING
LA English
DT Article
DE Interleukin-18; TRAF3IP2; Nox1; Oxidative stress; SMC migration;
Vascular diseases
ID KAPPA-B KINASE; NADPH OXIDASE; CIKS ACT1; EXPRESSION; NOX1; ACTIVATION;
STATINS; PROTEIN; ATHEROSCLEROSIS; PROLIFERATION
AB We investigated the role of TRAF3 interacting protein 2 (TRAF3IP2), a redox-sensitive adapter protein and an upstream regulator of IKK and JNK in interleukin (IL)-18 induced smooth muscle cell migration, and the mechanism of its inhibition by simvastatin. The pleiotropic cytokine IL-18 induced human coronary artery SMC migration through the induction of TRAF3IP2. IL-18 induced Nox1-dependent ROS generation, TRAF3IP2 expression, and IKK/NF-kappa B and JNK/AP-1 activation. IL-18 induced its own expression and that of its receptor subunit IL-18R alpha. Using co-IP/IB and GST pull-down assays, we show for the first time that the subunits of the IL-18R heterodimer physically associate with Nox1 under basal conditions, and IL-18 appears to enhance their binding. Importantly, the HMG-coA reductase inhibitor simvastatin attenuated IL-18-induced TRAF3IP2 induction. These inhibitory effects were reversed by mevalonate and geranylgeranylpyrophosphate (GGPP), but not by famesylpyrophosphate (FPP). Interestingly, simvastatin, GGPP, FPP, or Rac1 inhibition did not modulate ectopically expressed TRAF3IP2. These results demonstrate that the promigratory effects of IL-18 are mediated through TRAF3IP2 in a redox-sensitive manner, and this may involve IL-18R/Nox1 physical association. Further, Simvastatin inhibits inducible, but not ectopically-xpressed TRAF3IP2. Targeting TRAF3IP2 may blunt progression of hyperplastic vascular diseases in vivo. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Valente, Anthony J.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Valente, Anthony J.] South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA.
[Yoshida, Tadashi; Izadpanah, Reza; Delafontaine, Patrice; Chandrasekar, Bysani] Tulane Univ, Sch Med, Inst Heart & Vasc, New Orleans, LA 70112 USA.
[Siebenlist, Ulrich] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
[Chandrasekar, Bysani] Southeast Louisiana Vet Hlth Care Syst, Res Serv, New Orleans, LA 70161 USA.
RP Chandrasekar, B (reprint author), Tulane Univ, Sch Med, Inst Heart & Vasc, 1430 Tulane Ave,SL-48, New Orleans, LA 70112 USA.
EM bchandra@tulane.edu
FU Department of Veterans Affairs Research Career Scientist award; VA
Office of Research and Development Biomedical Laboratory Research and
Development Service Award [1I01BX000246]; NIH/NHLBI [HL-86787]; NHLBI
[HL-70241, HL-80682]
FX BC is a recipient of the Department of Veterans Affairs Research Career
Scientist award, and is supported by VA Office of Research and
Development Biomedical Laboratory Research and Development Service Award
1I01BX000246 and the NIH/NHLBI grant HL-86787. The contents of this
report do not represent the views of the Department of Veterans Affairs
or the United States Government. PD is supported by NHLBI grants
HL-70241 and HL-80682. The authors gratefully acknowledge the excellent
technical assistance of Maria Gamez.
NR 27
TC 8
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 0898-6568
J9 CELL SIGNAL
JI Cell. Signal.
PD JUN
PY 2013
VL 25
IS 6
BP 1447
EP 1456
DI 10.1016/j.cellsig.2013.03.007
PG 10
WC Cell Biology
SC Cell Biology
GA 147OD
UT WOS:000319176000013
PM 23541442
ER
PT J
AU Leung, DT
Uddin, T
Xu, P
Aktar, A
Johnson, RA
Rahman, MA
Alam, MM
Bufano, MK
Eckhoff, G
Wu-Freeman, Y
Yu, YN
Sultana, T
Khanam, F
Saha, A
Chowdhury, F
Khan, AI
Charles, RC
LaRocque, RC
Harris, JB
Calderwood, SB
Kovac, P
Qadri, F
Ryan, ET
AF Leung, Daniel T.
Uddin, Taher
Xu, Peng
Aktar, Amena
Johnson, Russell A.
Rahman, Mohammad Arif
Alam, Mohammad Murshid
Bufano, Meagan Kelly
Eckhoff, Grace
Wu-Freeman, Ying
Yu, Yanan
Sultana, Tania
Khanam, Farhana
Saha, Amit
Chowdhury, Fahima
Khan, Ashraf I.
Charles, Richelle C.
LaRocque, Regina C.
Harris, Jason B.
Calderwood, Stephen B.
Kovac, Pavol
Qadri, Firdausi
Ryan, Edward T.
TI Immune Responses to the O-Specific Polysaccharide Antigen in Children
Who Received a Killed Oral Cholera Vaccine Compared to Responses
following Natural Cholera Infection in Bangladesh
SO CLINICAL AND VACCINE IMMUNOLOGY
LA English
DT Article
ID MEMORY B-CELL; INFLUENZAE TYPE-B; CONJUGATE VACCINE; PNEUMOCOCCAL
POLYSACCHARIDES; CAPSULAR POLYSACCHARIDE; HOUSEHOLD CONTACTS;
ANTIBODY-RESPONSES; ESCHERICHIA-COLI; HEALTHY-CHILDREN; IMMUNOGENICITY
AB Current oral cholera vaccines induce lower levels of protective efficacy and shorter durations of protection in young children than in adults. Immunity against cholera is serogroup specific, and immune responses to Vibrio cholerae lipopolysaccharide (LPS), the antigen that mediates serogroup-specific responses, are associated with protection against disease. Despite this, responses against V. cholerae O-specific polysaccharide (OSP), a key component of the LPS responsible for specificity, have not been characterized in children. Here, we report a comparison of polysaccharide antibody responses in children from a region in Bangladesh where cholera is endemic, including infants (6 to 23 months, n = 15), young children (24 to 59 months, n = 14), and older children (5 to 15 years, n = 23) who received two doses of a killed oral cholera vaccine 14 days apart. We found that infants and young children receiving the vaccine did not mount an IgG, IgA, or IgM antibody response to V. cholerae OSP or LPS, whereas older children showed significant responses. In comparison to the vaccinees, young children with wild-type V. cholerae O1 Ogawa infection did mount significant antibody responses against OSP and LPS. We also demonstrated that OSP responses correlated with age in vaccinees, but not in cholera patients, reflecting the ability of even young children with wild-type cholera to develop OSP responses. These differences might contribute to the lower efficacy of protection rendered by vaccination than by wild-type disease in young children and suggest that efforts to improve lipopolysaccharide-specific responses might be critical for achieving optimal cholera vaccine efficacy in this younger age group.
C1 [Leung, Daniel T.; Uddin, Taher; Aktar, Amena; Johnson, Russell A.; Rahman, Mohammad Arif; Alam, Mohammad Murshid; Sultana, Tania; Khanam, Farhana; Saha, Amit; Chowdhury, Fahima; Khan, Ashraf I.; Qadri, Firdausi] ICDDR B, Ctr Vaccine Sci, Dhaka, Bangladesh.
[Leung, Daniel T.; Bufano, Meagan Kelly; Wu-Freeman, Ying; Yu, Yanan; Sultana, Tania; Charles, Richelle C.; LaRocque, Regina C.; Harris, Jason B.; Calderwood, Stephen B.; Ryan, Edward T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[Leung, Daniel T.; Eckhoff, Grace; Charles, Richelle C.; LaRocque, Regina C.; Calderwood, Stephen B.; Ryan, Edward T.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Xu, Peng; Kovac, Pavol] NIDDK, LBC, NIH, Bethesda, MD USA.
[Harris, Jason B.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
[Calderwood, Stephen B.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA.
[Ryan, Edward T.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA.
RP Leung, DT (reprint author), ICDDR B, Ctr Vaccine Sci, Dhaka, Bangladesh.
EM dleung@partners.org
RI Kovac, Pavol/B-8813-2008; Xu, Peng/K-7036-2012;
OI Kovac, Pavol/0000-0001-5044-3449; leung, daniel/0000-0001-8401-0801
FU ICDDR; Intramural Research Program of the National Institutes of Health;
NIDDK; National Institutes of Health; National Institute of Allergy &
Infectious Diseases [U01 AI058935, R03 AI063079, U01 AI077883, K08
AI089721, K08AI100923]; Fogarty International Center, Training Grant in
Vaccine Development and Public Health [TW005572]; Career Development
Award [K01 TW07409, TW07144]; Fogarty International Clinical Research
Scholars award [R24 TW007988]; Swedish International Development
Cooperation Agency; Physician Scientist Early Career Award from the
Howard Hughes Medical Institute; Thrasher Research Fund Early Career
Award; American Society for Tropical Medicine & Hygiene-Burroughs
Wellcome Fund
FX This work was supported by the ICDDR, B and its donors, which provide
unrestricted support to ICDDR, B for its operations and research.
Current donors providing unrestricted support include the Australian
Agency for International Development (AusAID), the government of the
People's Republic of Bangladesh, the Canadian International Development
Agency (CIDA), the Swedish International Development Cooperation Agency
(SIDA), and the Department for International Development, United Kingdom
(DFID). This study was also supported by grants from the Intramural
Research Program of the National Institutes of Health, NIDDK, and
extramural grants from the National Institutes of Health, including the
National Institute of Allergy & Infectious Diseases (U01 AI058935 [to
S.B.C. and E.T.R.], R03 AI063079 [to F.Q.], U01 AI077883 [to E.T.R.],
K08 AI089721 [to R.C.C.], and K08AI100923 [to D.T.L.]) and the Fogarty
International Center, Training Grant in Vaccine Development and Public
Health (TW005572 [to T.U., M.M.A., F.K., and F.Q.]), a Career
Development Award (K01 TW07409 [to J.B.H.] and TW07144 [to R.C.L.]), and
a Fogarty International Clinical Research Scholars award (R24 TW007988
[to R.A.J. and T.U.]), as well as by the Swedish International
Development Cooperation Agency (to F.Q.), a Physician Scientist Early
Career Award from the Howard Hughes Medical Institute (to R.C.L.), a
Thrasher Research Fund Early Career Award (to D.T.L.), and a
postdoctoral fellowship in tropical infectious diseases from the
American Society for Tropical Medicine & Hygiene-Burroughs Wellcome Fund
(to D.T.L.).
NR 53
TC 9
Z9 9
U1 2
U2 7
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 1556-6811
J9 CLIN VACCINE IMMUNOL
JI Clin. Vaccine Immunol.
PD JUN
PY 2013
VL 20
IS 6
BP 780
EP 788
DI 10.1128/CVI.00035-13
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 151HO
UT WOS:000319451500002
PM 23515016
ER
PT J
AU Diaz, PI
Hong, BY
Frias-Lopez, J
Dupuy, AK
Angeloni, M
Abusleme, L
Terzi, E
Ioannidou, E
Strausbaugh, LD
Dongari-Bagtzoglou, A
AF Diaz, Patricia I.
Hong, Bo-Young
Frias-Lopez, Jorge
Dupuy, Amanda K.
Angeloni, Mark
Abusleme, Loreto
Terzi, Evimaria
Ioannidou, Effie
Strausbaugh, Linda D.
Dongari-Bagtzoglou, Anna
TI Transplantation-Associated Long-Term Immunosuppression Promotes Oral
Colonization by Potentially Opportunistic Pathogens without Impacting
Other Members of the Salivary Bacteriome
SO CLINICAL AND VACCINE IMMUNOLOGY
LA English
DT Article
ID ORGAN-TRANSPLANTATION; INFECTION; MICROBIOME; RECIPIENTS; PERIODONTITIS;
COMMUNITIES; MICROFLORA; FLORA
AB Solid-organ transplant recipients rely on pharmacological immunosuppression to prevent allograft rejection. The effect of such chronic immunosuppression on the microflora at mucosal surfaces is not known. We evaluated the salivary bacterial microbiome of 20 transplant recipients and 19 nonimmunosuppressed controls via 454 pyrosequencing of 16S rRNA gene amplicons. Alpha-diversity and global community structure did not differ between transplant and control subjects. However, principal coordinate analysis showed differences in community membership. Taxa more prevalent in transplant subjects included operational taxonomic units (OTUs) of potentially opportunistic Gammaproteobacteria such as Klebsiella pneumoniae, Pseudomonas fluorescens, Acinetobacter species, Vibrio species, Enterobacteriaceae species, and the genera Acinetobacter and Klebsiella. Transplant subjects also had increased proportions of Pseudomonas aeruginosa, Acinetobacter species, Enterobacteriaceae species, and Enterococcus faecalis, among other OTUs, while genera with increased proportions included Klebsiella, Acinetobacter, Staphylococcus, and Enterococcus. Furthermore, in transplant subjects, the dose of the immunosuppressant prednisone positively correlated with bacterial richness, while prednisone and mycophenolate mofetil doses positively correlated with the prevalence and proportions of transplant-associated taxa. Correlation network analysis of OTU relative abundance revealed a cluster containing potentially opportunistic pathogens as transplant associated. This cluster positively correlated with serum levels of C-reactive protein, suggesting a link between the resident flora at mucosal compartments and systemic inflammation. Network connectivity analysis revealed opportunistic pathogens as highly connected to each other and to common oral commensals, pointing to bacterial interactions that may influence colonization. This work demonstrates that immunosuppression aimed at limiting T-cell-mediated responses creates a more permissive oral environment for potentially opportunistic pathogens without affecting other members of the salivary bacteriome.
C1 [Diaz, Patricia I.; Hong, Bo-Young; Angeloni, Mark; Abusleme, Loreto; Ioannidou, Effie; Dongari-Bagtzoglou, Anna] Univ Connecticut, Ctr Hlth, Dept Oral Hlth & Diagnost Sci, Div Periodontol, Farmington, CT USA.
[Frias-Lopez, Jorge] Forsyth Inst, Dept Microbiol, Cambridge, MA USA.
[Dupuy, Amanda K.; Strausbaugh, Linda D.] Univ Connecticut, Ctr Appl Genet & Technol, Storrs, CT USA.
[Abusleme, Loreto] Univ Chile, Fac Dent, Lab Oral Microbiol, Santiago, Chile.
[Terzi, Evimaria] Boston Univ, Dept Comp Sci, Boston, MA 02215 USA.
RP Diaz, PI (reprint author), Univ Connecticut, Ctr Hlth, Dept Oral Hlth & Diagnost Sci, Div Periodontol, Farmington, CT USA.
EM pdiaz@uchc.edu; adongari@uchc.edu
FU National Institutes of Health (NIH) [R21DE016466, R01DE021578]
FX This study was supported by grants R21DE016466 and R01DE021578 from the
National Institutes of Health (NIH).
NR 43
TC 16
Z9 16
U1 1
U2 24
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 1556-6811
J9 CLIN VACCINE IMMUNOL
JI Clin. Vaccine Immunol.
PD JUN
PY 2013
VL 20
IS 6
BP 920
EP 930
DI 10.1128/CVI.00734-12
PG 11
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 151HO
UT WOS:000319451500020
PM 23616410
ER
PT J
AU Kocsis, B
Brown, RE
McCarley, RW
Hajos, M
AF Kocsis, Bernat
Brown, Ritchie E.
McCarley, Robert W.
Hajos, Mihaly
TI Impact of Ketamine on Neuronal Network Dynamics: Translational Modeling
of Schizophrenia-Relevant Deficits
SO CNS NEUROSCIENCE & THERAPEUTICS
LA English
DT Review
DE Gamma oscillation; Mismatch negativity; N-methyl-d-aspartate receptors
receptors; P300; Theta rhythm
ID NMDA RECEPTOR HYPOFUNCTION; PARVALBUMIN-CONTAINING INTERNEURONS; MEDIAL
PREFRONTAL CORTEX; HIPPOCAMPAL THETA-RHYTHM; STEADY-STATE RESPONSES; RAT
VISUAL-CORTEX; LOW-DOSE KETAMINE; GAMMA-OSCILLATIONS; MISMATCH
NEGATIVITY; WORKING-MEMORY
AB Subanesthetic doses of the psychomimetic, ketamine, have been used for many years to elicit behavioral effects reminiscent of schizophrenia in both healthy humans and in animal models of the disease. More recently, there has been a move toward the use of simple neurophysiological measures (event-related potentials, brain oscillations) to assay the functional integrity of neuronal circuits in schizophrenia as these measures can be assessed in patients, healthy controls, intact animals, and even in brain slices. Furthermore, alterations of these measures are correlated with basic information processing deficits that are now considered central to the disease. Thus, here we review recent studies that determine the effect of ketamine on these measures and discuss to what extent they recapitulate findings in patients with schizophrenia. In particular, we examine methodological differences between human and animal studies and compare in vivo and in vitro effects of ketamine. Ketamine acts on multiple cortical and subcortical sites, as well as on receptors other than the N-methyl-d-aspartate receptor. Acute ketamine models' changes correlated with psychotic states (e.g. increased baseline gamma-band oscillations), whereas chronic ketamine causes cortical circuit changes and neurophysiological deficits (e.g. impaired event-related gamma-band oscillations) correlated with cognitive impairments in schizophrenia.
C1 [Kocsis, Bernat] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Lab Neurophysiol,Dept Psychiat, Boston, MA 02215 USA.
[Brown, Ritchie E.; McCarley, Robert W.] VA Boston Healthcare Syst, Dept Psychiat, Lab Neurosci, Brockton, MA USA.
[Brown, Ritchie E.; McCarley, Robert W.] Harvard Univ, Sch Med, Brockton, MA 02401 USA.
[Hajos, Mihaly] Yale Univ, Sch Med, Comparat Med Sect, Brady Mem Lab, New Haven, CT 06510 USA.
RP Kocsis, B (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Lab Neurophysiol,Dept Psychiat, 330 Brookline Ave,CLS 710, Boston, MA 02215 USA.
EM bernat_kocsis@hms.harvard.edu
RI McCarley, Robert/N-5562-2014;
OI McCarley, Robert/0000-0001-5705-7495; Brown, Ritchie/0000-0002-7164-4132
FU Department of Veterans Affairs Medical Research Service Award; National
Institute of Health [MH087777, HL095491, MH039683, MH094803]
FX This work was supported by a Department of Veterans Affairs Medical
Research Service Award (to RWM) and grants from the National Institute
of Health: MH087777 (BK), HL095491 (BK and RWM), MH039683 (RWM),
MH094803 (REB).
NR 209
TC 33
Z9 33
U1 2
U2 20
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1755-5930
J9 CNS NEUROSCI THER
JI CNS Neurosci. Ther.
PD JUN
PY 2013
VL 19
IS 6
SI SI
BP 437
EP 447
DI 10.1111/cns.12081
PG 11
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 149US
UT WOS:000319347500009
PM 23611295
ER
PT J
AU Finnerty, CC
Jeschke, MG
Qian, WJ
Kaushal, A
Xiao, WZ
Liu, T
Gritsenko, MA
Moore, RJ
Camp, DG
Moldawer, LL
Elson, C
Schoenfeld, D
Gamelli, R
Gibran, N
Klein, M
Arnoldo, B
Remick, D
Smith, RD
Davis, R
Tompkins, RG
Herndon, DN
AF Finnerty, Celeste C.
Jeschke, Marc G.
Qian, Wei-Jun
Kaushal, Amit
Xiao, Wenzhong
Liu, Tao
Gritsenko, Marina A.
Moore, Ronald J.
Camp, David G., II
Moldawer, Lyle L.
Elson, Constance
Schoenfeld, David
Gamelli, Richard
Gibran, Nicole
Klein, Matthew
Arnoldo, Brett
Remick, Daniel
Smith, Richard D.
Davis, Ronald
Tompkins, Ronald G.
Herndon, David N.
CA Investigators Inflammation & Host
TI Determination of Burn Patient Outcome by Large-Scale Quantitative
Discovery Proteomics
SO CRITICAL CARE MEDICINE
LA English
DT Article
DE biomarker; burn; inflammation; liquid chromatography-mass spectrometry;
plasma proteins; proteomic profiling
ID ACTIVATED PROTEIN-C; MASS-SPECTROMETRY; INSULIN THERAPY; SEVERE SEPSIS;
INJURY; INFLAMMATION; MANAGEMENT; SUPPORT; TRAUMA; TIME
AB Objectives: Emerging proteomics techniques can be used to establish proteomic outcome signatures and to identify candidate biomarkers for survival following traumatic injury. We applied high-resolution liquid chromatography-mass spectrometry and multiplex cytokine analysis to profile the plasma proteome of survivors and nonsurvivors of massive burn injury to determine the proteomic survival signature following a major burn injury.
Design: Proteomic discovery study.
Setting: Five burn hospitals across the United States.
Patients: Thirty-two burn patients (16 nonsurvivors and 16 survivors), 19-89 years old, were admitted within 96 hours of injury to the participating hospitals with burns covering more than 20% of the total body surface area and required at least one surgical intervention.
Interventions: None.
Measurements and Main Results: We found differences in circulating levels of 43 proteins involved in the acute-phase response, hepatic signaling, the complement cascade, inflammation, and insulin resistance. Thirty-two of the proteins identified were not previously known to play a role in the response to burn. Interleukin-4, interleukin-8, granulocyte macrophage colony-stimulating factor, monocyte chemotactic protein-1, and beta 2-microglobulin correlated well with survival and may serve as clinical biomarkers.
Conclusions: These results demonstrate the utility of these techniques for establishing proteomic survival signatures and for use as a discovery tool to identify candidate biomarkers for survival. This is the first clinical application of a high-throughput, large-scale liquid chromatography-mass spectrometry-based quantitative plasma proteomic approach for biomarker discovery for the prediction of patient outcome following burn, trauma, or critical illness. (Crit Care Med 2013; 41: 1421-1434)
C1 [Finnerty, Celeste C.; Herndon, David N.] Univ Texas Med Branch, Dept Surg, Galveston, TX 77555 USA.
[Finnerty, Celeste C.; Herndon, David N.] Shriners Hosp Children, Galveston, TX 77550 USA.
[Finnerty, Celeste C.] Univ Texas Med Branch, Sealy Ctr Mol Med, Inst Translat Sci, Galveston, TX 77555 USA.
[Jeschke, Marc G.] Univ Toronto, Sunnybrook Hlth Sci Ctr, Ross Tilley Burn Ctr, Toronto, ON, Canada.
[Jeschke, Marc G.] Univ Toronto, Div Plast Surg, Toronto, ON, Canada.
[Qian, Wei-Jun; Liu, Tao; Gritsenko, Marina A.; Moore, Ronald J.; Camp, David G., II; Smith, Richard D.] Pacific NW Natl Lab, Div Biol Sci, Richland, WA 99352 USA.
[Qian, Wei-Jun; Liu, Tao; Gritsenko, Marina A.; Moore, Ronald J.; Camp, David G., II; Smith, Richard D.] Pacific NW Natl Lab, Environm Mol Sci Lab, Richland, WA 99352 USA.
[Kaushal, Amit; Xiao, Wenzhong; Davis, Ronald] Stanford Univ, Sch Med, Stanford Genome Technol Ctr, Stanford, CA 94305 USA.
[Moldawer, Lyle L.] Univ Florida, Coll Med, Dept Surg, Gainesville, FL USA.
[Elson, Constance; Schoenfeld, David; Tompkins, Ronald G.] Shriners Hosp Children, Massachusetts Gen Hosp, Dept Surg, Boston, MA USA.
[Elson, Constance; Schoenfeld, David; Tompkins, Ronald G.] Harvard Univ, Sch Med, Boston, MA USA.
[Gamelli, Richard] Loyola Univ, Stritch Sch Med, Dept Surg, Maywood, IL 60153 USA.
[Gibran, Nicole; Klein, Matthew] Univ Washington, Harborview Med Ctr, Sch Med, Dept Surg, Seattle, WA 98104 USA.
[Arnoldo, Brett] Univ Texas SW Med Ctr Dallas, Dept Surg, Dallas, TX 75390 USA.
[Remick, Daniel] Boston Univ, Sch Med, Boston, MA 02118 USA.
RP Finnerty, CC (reprint author), Univ Texas Med Branch, Dept Surg, Galveston, TX 77555 USA.
EM ccfinner@utmb.edu
RI Smith, Richard/J-3664-2012;
OI Smith, Richard/0000-0002-2381-2349; Remick, Daniel/0000-0002-2615-3713
FU National Institute of General Medical Sciences [U54 GM-62119-04, P50
GM-60338, R01 GM-56687, T32 GM-008256, 8 P41 GM103493-10]; National
Institutes of Health National Center for Research Resources [RR018522,
5P41RR018522-10]; NIH [KL2RR029875, UL1RR029876]; U.S. Department of
Energy [DE-AC05-76RL01830]
FX Supported, in part, by a Large Scale Collaborative Research Grant from
the National Institute of General Medical Sciences (U54 GM-62119-04)
awarded to Dr. Tompkins at the Massachusetts General Hospital, Boston,
MA and in part, by research grants awarded to Dr. Herndon at the
University of Texas Medical Branch, Galveston, TX, by the National
Institute of General Medical Sciences (P50 GM-60338, R01 GM-56687, T32
GM-008256). Portions of the research were supported by a grant from the
National Institutes of Health National Center for Research Resources
(RR018522 and 5P41RR018522-10) and National Institute of General Medical
Sciences (8 P41 GM103493-10). Dr. Finnerty is an ITS Career Development
Scholar supported, in part, by NIH KL2RR029875 and NIH UL1RR029876.
LC-MS proteomic analyses were performed in the Environmental Molecular
Sciences Laboratory, a U.S. Department of Energy national scientific
user facility located at the Pacific Northwest National Laboratory in
Richland, WA. The Pacific Northwest National Laboratory is a
multiprogram national laboratory operated by Battelle Memorial Institute
for the U.S. Department of Energy under Contract DE-AC05-76RL01830.
NR 27
TC 19
Z9 20
U1 1
U2 15
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 JUN
PY 2013
VL 41
IS 6
BP 1421
EP 1434
DI 10.1097/CCM.0b013e31827c072e
PG 14
WC Critical Care Medicine
SC General & Internal Medicine
GA 148TC
UT WOS:000319269400024
PM 23507713
ER
PT J
AU Akgun, KM
Tate, JP
Pisani, M
Fried, T
Butt, AA
Gibert, CL
Huang, L
Rodriguez-Barradas, MC
Rimland, D
Justice, AC
Crothers, K
AF Akguen, Kathleen M.
Tate, Janet P.
Pisani, Margaret
Fried, Terri
Butt, Adeel A.
Gibert, Cynthia L.
Huang, Laurence
Rodriguez-Barradas, Maria C.
Rimland, David
Justice, Amy C.
Crothers, Kristina
TI Medical ICU Admission Diagnoses and Outcomes in Human Immunodeficiency
Virus-Infected and Virus-Uninfected Veterans in the Combination
Antiretroviral Era
SO CRITICAL CARE MEDICINE
LA English
DT Article
DE 30-day mortality; comorbidity; human immunodeficiency virus; medical
ICU; Veterans Aging Cohort Study Index
ID INTENSIVE-CARE-UNIT; HIV-NEGATIVE VETERANS; CIGARETTE-SMOKING; THERAPY
ERA; HEPATITIS-C; MORTALITY; SURVIVAL; IMPACT; COHORT; RISK
AB Objectives: Human immunodeficiency virus (HIV)-infected (HIV+) patients on combination antiretroviral therapy are living longer but have increased risk for aging-associated disease which may lead to increasing critical care requirements. We compare medical ICU admission characteristics and outcomes among HIV infected and demographically similar uninfected patients (uninfected) and considered whether an index which combines routine clinical biomarkers (the Veterans Aging Cohort Study Index) predicts 30-day medical ICU mortality.
Design: Observational data analyses (Veterans Aging Cohort Study).
Setting: Eight Veterans Affairs medical centers nationwide.
Patients: HIV infected and uninfected with a medical ICU admission between 2002 and 2010.
Intervention: None.
Measurements and Main Results: Medical ICU admission was determined using bedsection (Veterans Affairs) and revenue center codes (Medicare). For Veterans Affairs admissions, we used clinical data to calculate Veterans Aging Cohort Study Index scores and multivariable logistic regression to determine factors associated with 30-day mortality. Overall, 539 of 3,620 (15%) HIV infected and 375 of 3,639 (10%) uninfected had a medical ICU admission; 72% and 78%, respectively, were Veterans Affairs based. HIV+ patients were younger at admission (p < 0.0001). Although most HIV+ patients were on antiretroviral therapy (71%) with undetectable HIV-1 RNA (54%), compared with uninfected they were more commonly admitted with respiratory diagnoses or infections (21% vs. 12%), were more likely to require mechanical ventilation (17% vs. 9%; p = 0.001), and had a higher mortality rate (18.6% vs. 11.2%, p = 0.003). Cardiovascular diagnoses were less common among HIV infected (18% vs. 29%; p < 0.0001). In logistic regression (c-statistic 0.87), a 5-point increment in Veterans Aging Cohort Study Index was associated with an odds ratio of death of 1.22 (95% confidence interval 1.14-1.30) among HIV infected and of 1.50 (95% confidence interval 1.29-1.76) among uninfected; infection/sepsis and respiratory diagnoses were also associated with mortality.
Conclusions: Medical ICU admission was frequent, 30-day mortality higher, and mechanical ventilation more common in HIV infected compared with uninfected. The Veterans Aging Cohort Study Index calculated at medical ICU admission predicted 30-day mortality for HIV infected and uninfected. As more individuals age with HIV, their requirements for medical ICU care may be greater than demographically similar uninfected individuals.
C1 [Akguen, Kathleen M.; Tate, Janet P.; Justice, Amy C.] VA Connecticut Healthcare Syst, Dept Internal Med, West Haven, CT USA.
[Akguen, Kathleen M.; Tate, Janet P.; Pisani, Margaret; Fried, Terri; Justice, Amy C.] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA.
[Fried, Terri] VA Connecticut Healthcare Syst, Clin Epidemiol Res Ctr, West Haven, CT USA.
[Butt, Adeel A.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15213 USA.
[Butt, Adeel A.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA.
[Butt, Adeel A.] Sheikh Khalifa Med City, Abu Dhabi, U Arab Emirates.
[Gibert, Cynthia L.] VAMC, Dept Med, Washington, DC USA.
[Gibert, Cynthia L.] George Washington Univ, Washington, DC USA.
[Huang, Laurence] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Rodriguez-Barradas, Maria C.] Baylor Coll Med, Michael E De Bakey VAMC, Houston, TX 77030 USA.
[Rodriguez-Barradas, Maria C.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA.
[Rimland, David] Atlanta VA, Dept Med, Decatur, GA USA.
[Rimland, David] Emory Univ, Decatur, GA USA.
[Crothers, Kristina] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA.
RP Akgun, KM (reprint author), VA Connecticut Healthcare Syst, Dept Internal Med, West Haven, CT USA.
EM kathleen.akgun@yale.edu
RI Andrade, Hugo/M-6631-2013;
OI Andrade, Hugo/0000-0001-6781-6125; Crothers,
Kristina/0000-0001-9702-0371
FU Association of Subspecialty Physicians and CHEST Foundation of the
American College of Chest Physicians T. Franklin Williams Award;
National Institutes of Health, National Heart, Lung, and Blood Institute
[K24 HL087713, R01 HL090342]; National Institute on Alcohol Abuse and
Alcoholism [5U01AA013566-05]; National Institutes of Health; ASP-ACCP;
Merck; ATS
FX Supported, in part, by Association of Subspecialty Physicians and CHEST
Foundation of the American College of Chest Physicians T. Franklin
Williams Award (KMA); National Institutes of Health, National Heart,
Lung, and Blood Institute K24 HL087713 (LH); National Institute on
Alcohol Abuse and Alcoholism 5U01AA013566-05 (AJ); and National
Institutes of Health, National Heart, Lung, and Blood Institute R01
HL090342 (KC).; Drs. Akgun, Tate, Gibert, Huang, Rodriguez-Barradas,
Rimland, Justice, and Crothers received grant support from the National
Institutes of Health. Dr. Akgun received grant support from ASP-ACCP (T
Franklin Williams Award). Dr. Butt received grant support from Merck.
Dr. Rodriguez-Barradas received support for travel from NIH. Dr. Butt
lectured for Gilead. Dr. Crothers received educational presentation
funding from ATS.
NR 48
TC 26
Z9 27
U1 1
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 JUN
PY 2013
VL 41
IS 6
BP 1458
EP 1467
DI 10.1097/CCM.0b013e31827caa46
PG 10
WC Critical Care Medicine
SC General & Internal Medicine
GA 148TC
UT WOS:000319269400028
PM 23507717
ER
PT J
AU Clark, BJ
Williams, A
Feemster, LMC
Bradley, KA
Macht, M
Moss, M
Burnham, EL
AF Clark, Brendan J.
Williams, Andre
Feemster, Laura M. Cecere
Bradley, Katharine A.
Macht, Madison
Moss, Marc
Burnham, Ellen L.
CA NHLBI ARDS Network Investigators
TI Alcohol Screening Scores and 90-Day Outcomes in Patients With Acute Lung
Injury
SO CRITICAL CARE MEDICINE
LA English
DT Article
DE acute lung injury; alcohol misuse; alcohol use disorder; alcohol use
disorders identification test; unhealthy alcohol use
ID RESPIRATORY-DISTRESS-SYNDROME; DISORDERS IDENTIFICATION TEST;
MECHANICALLY VENTILATED PATIENTS; CRITICALLY-ILL PATIENTS; RISK-FACTORS;
TEST AUDIT; EPITHELIAL PERMEABILITY; HOSPITAL MORTALITY;
CIGARETTE-SMOKING; CLINICAL-TRIAL
AB Objectives: The effects of excess alcohol consumption (alcohol misuse) on outcomes in patients with acute lung injury have been inconsistent, and there are no studies examining this association in the era of low tidal volume ventilation and a fluid conservative strategy. We sought to determine whether validated scores on the Alcohol Use Disorders Identification Test that correspond to past-year abstinence (zone 1), low-risk drinking (zone 2), mild to moderate alcohol misuse (zone 3), and severe alcohol misuse (zone 4) are associated with poor outcomes in patients with acute lung injury.
Design: Secondary analysis.
Setting: The Acute Respiratory Distress Syndrome Network, a consortium of 12 university centers (44 hospitals) dedicated to the conduct of multicenter clinical trials in patients with acute lung injury.
Subjects: Patients meeting consensus criteria for acute lung injury enrolled in one of three recent Acute Respiratory Distress Syndrome Network clinical trials.
Interventions: None.
Measurements and Main Results: Of 1,133 patients enrolled in one of three Acute Respiratory Distress Syndrome Network studies, 1,037 patients had an Alcohol Use Disorders Identification Test score available for analysis. Alcohol misuse was common with 70 (7%) of patients having Alcohol Use Disorders Identification Test scores in zone 3 and 129 (12%) patients in zone 4. There was a U-shaped association between validated Alcohol Use Disorders Identification Test zones and death or persistent hospitalization at 90 days (34% in zone 1, 26% in zone 2, 27% in zone 3, 36% in zone 4; p < 0.05 for comparison of zone 1 to zone 2 and zone 4 to zone 2). In a multiple logistic regression model, there was a significantly higher odds of death or persistent hospitalization in patients having Alcohol Use Disorders Identification Test zone 4 compared with those in zone 2 (adjusted odds ratio 1.70; 95% confidence interval 1.00, 2.87; p = 0.048).
Conclusions: Severe but not mild to moderate alcohol misuse is independently associated with an increased risk of death or persistent hospitalization at 90 days in acute lung injury patients.
C1 [Clark, Brendan J.; Macht, Madison; Moss, Marc; Burnham, Ellen L.] Univ Colorado Denver, Dept Med, Div Pulm Sci & Crit Care Med, Aurora, CO USA.
[Williams, Andre] Natl Jewish Hlth, Dept Biostat & Bioinformat, Denver, CO USA.
[Feemster, Laura M. Cecere] VA Puget Sound Healthcare Syst, Hlth Serv Res & Dev, Seattle, WA USA.
[Feemster, Laura M. Cecere] Univ Washington, Dept Med, Div Pulm & Crit Care Med, Seattle, WA USA.
[Bradley, Katharine A.] Grp Hlth Res Inst, Seattle, WA USA.
RP Clark, BJ (reprint author), Univ Colorado Denver, Dept Med, Div Pulm Sci & Crit Care Med, Aurora, CO USA.
EM brendan.clark@ucdenver.edu
FU National Institutes of Health [K24-HL-089223, R24-AA-019661-01A1, N01
HR56167]; VA HSRD fellowship [TPM 61-037]; National Heart and Lung Bloos
Institute; VA HSRD Fellowship
FX Supported, in part, by National Institutes of Health (K24-HL-089223,
R24-AA-019661-01A1) and National Institutes of Health contract N01
HR56167; VA HSR&D fellowship (TPM 61-037) to Dr. Cecere.; Dr. Clark
received grant support from the National Heart and Lung Bloos Institute.
Dr. Feemster received grant support and funding for research for this
study from the VA HSR&D Fellowship. Dr. Burnham received travel support
from NIH.
NR 58
TC 14
Z9 14
U1 1
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0090-3493
J9 CRIT CARE MED
JI Crit. Care Med.
PD JUN
PY 2013
VL 41
IS 6
BP 1518
EP 1525
DI 10.1097/CCM.0b013e318287f1bb
PG 8
WC Critical Care Medicine
SC General & Internal Medicine
GA 148TC
UT WOS:000319269400035
PM 23538449
ER
PT J
AU Jin, J
Phitayakorn, R
Wilhelm, S
McHenry, CR
AF Jin, Judy
Phitayakorn, Roy
Wilhelm, Scott
McHenry, Christopher R.
TI Advances in management of thyroid cancer
SO CURRENT PROBLEMS IN SURGERY
LA English
DT Review
ID FINE-NEEDLE-ASPIRATION; POSITRON-EMISSION-TOMOGRAPHY; RECOMBINANT HUMAN
THYROTROPIN; DIFFUSE SCLEROSING VARIANT; RADIOACTIVE IODINE THERAPY;
STIMULATING HORMONE-LEVEL; LYMPH-NODE DISSECTION; HYPERFRACTIONATED
ACCELERATED RADIOTHERAPY; HISTONE DEACETYLASE INHIBITOR; SUFFICIENT
SURGICAL-TREATMENT
C1 [Jin, Judy] Cleveland Clin Fdn, Dept Endocrine Surg, Cleveland, OH 44195 USA.
[Phitayakorn, Roy] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
[Wilhelm, Scott; McHenry, Christopher R.] Case Western Reserve Univ, Sch Med, Cleveland, OH USA.
[McHenry, Christopher R.] Metrohlth Med Ctr, Cleveland, OH USA.
RP Jin, J (reprint author), Cleveland Clin Fdn, Dept Endocrine Surg, 9500 Euclid Ave, Cleveland, OH 44195 USA.
OI Phitayakorn, Roy/0000-0002-8327-1484
NR 288
TC 5
Z9 7
U1 0
U2 14
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0011-3840
EI 1535-6337
J9 CURR PROB SURG
JI Curr. Probl. Surg.
PD JUN
PY 2013
VL 50
IS 6
BP 241
EP 289
DI 10.1067/j.cpsurg.2013.02.001
PG 49
WC Surgery
SC Surgery
GA 149IG
UT WOS:000319311600002
PM 23672743
ER
PT J
AU Le, XN
Pugach, EK
Hettmer, S
Storer, NY
Liu, JN
Wills, AA
DiBiase, A
Chen, EY
Ignatius, MS
Poss, KD
Wagers, AJ
Langenau, DM
Zon, LI
AF Le, Xiuning
Pugach, Emily K.
Hettmer, Simone
Storer, Narie Y.
Liu, Jianing
Wills, Airon A.
DiBiase, Antony
Chen, Eleanor Y.
Ignatius, Myron S.
Poss, Kenneth D.
Wagers, Amy J.
Langenau, David M.
Zon, Leonard I.
TI A novel chemical screening strategy in zebrafish identifies common
pathways in embryogenesis and rhabdomyosarcoma development
SO DEVELOPMENT
LA English
DT Article
DE RAS; Embryogenesis; Rhabdomyosarcoma; Translational control; Zebrafish
ID TRANSLATION INITIATION; TRANSGENIC ZEBRAFISH; CHLOROMETHYL KETONE;
SIGNALING PATHWAYS; RAS ONCOGENES; MAP KINASE; IN-VIVO; CANCER; TARGETS;
MTOR
AB The zebrafish is a powerful genetic model that has only recently been used to dissect developmental pathways involved in oncogenesis. We hypothesized that operative pathways during embryogenesis would also be used for oncogenesis. In an effort to define RAS target genes during embryogenesis, gene expression was evaluated in Tg(hsp70-HRAS(G12V)) zebrafish embryos subjected to heat shock. dusp6 was activated by RAS, and this was used as the basis for a chemical genetic screen to identify small molecules that interfere with RAS signaling during embryogenesis. A KRAS(G12D)-induced zebrafish embryonal rhabdomyosarcoma was then used to assess the therapeutic effects of the small molecules. Two of these inhibitors, PD98059 and TPCK, had anti-tumor activity as single agents in both zebrafish embryonal rhabdomyosarcoma and a human cell line of rhabdomyosarcoma that harbored activated mutations in NRAS. PD98059 inhibited MEK1 whereas TPCK suppressed S6K1 activity; however, the combined treatment completely suppressed eIF4B phosphorylation and decreased translation initiation. Our work demonstrates that the activated pathways in RAS induction during embryogenesis are also important in oncogenesis and that inhibition of these pathways suppresses tumor growth.
C1 [Le, Xiuning; Pugach, Emily K.; Storer, Narie Y.; DiBiase, Antony; Zon, Leonard I.] Harvard Univ, Sch Med, Stem Cell Program, Boston, MA 02115 USA.
[Le, Xiuning; Pugach, Emily K.; Storer, Narie Y.; DiBiase, Antony; Zon, Leonard I.] Harvard Univ, Sch Med, Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA.
[Le, Xiuning; Pugach, Emily K.; Storer, Narie Y.; DiBiase, Antony; Zon, Leonard I.] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Dana Farber Canc Inst,Howard Hughes Med Inst, Boston, MA 02115 USA.
[Hettmer, Simone; Liu, Jianing; Wagers, Amy J.] Harvard Univ, Harvard Stem Cell Inst, Joslin Diabet Ctr, Howard Hughes Med Inst,Dept Stem Cell & Regenera, Boston, MA 02115 USA.
[Wills, Airon A.; Poss, Kenneth D.] Duke Univ, Med Ctr, Howard Hughes Med Inst, Dept Cell Biol, Durham, NC 27710 USA.
[Chen, Eleanor Y.; Ignatius, Myron S.; Langenau, David M.] Massachusetts Gen Hosp, Dept Pathol, Mol Pathol Unit, Charlestown, MA 02129 USA.
[Chen, Eleanor Y.; Ignatius, Myron S.; Langenau, David M.] Harvard Stem Cell Inst, Boston, MA 02114 USA.
RP Zon, LI (reprint author), Harvard Univ, Sch Med, Stem Cell Program, Boston, MA 02115 USA.
EM zon@enders.tch.harvard.edu
FU National Institutes of Health [5 R01 CA103846-10, K01AR05562190,
R01CA154923, R21CA156056, 1U54CA168512, RO1 HL088582-01S1, GM074057,
HL081674]; Howard Hughes Medical Institute; American Cancer Society;
Harvard Stem Cell Institute; Sarcoma Foundation of America; Alex
Lemonade Stand Foundation; Stand Up To Cancer-American Association for
Cancer Research Innovative Research Grant [SU2C-AACR-IRG1111]; Hope
Street Kids; P.A.L.S.
FX L.I.Z. is supported by the National Institutes of Health [5 R01
CA103846-10] and Howard Hughes Medical Institute. D. M. L. is supported
by the National Institutes of Health [K01AR05562190, R01CA154923,
R21CA156056 and 1U54CA168512], The American Cancer Society, The Harvard
Stem Cell Institute, The Sarcoma Foundation of America, and Alex
Lemonade Stand Foundation. A.J.W. is supported by a Stand Up To
Cancer-American Association for Cancer Research Innovative Research
Grant [SU2C-AACR-IRG1111] and the National Institutes of Health [RO1
HL088582-01S1]. K. D. P. is supported by the National Institutes of
Health [GM074057 and HL081674]. S. H. is supported by Hope Street Kids
and P.A.L.S. Bermuda/St. Baldrick's. Deposited in PMC for release after
6 months.
NR 40
TC 21
Z9 22
U1 0
U2 13
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 0950-1991
J9 DEVELOPMENT
JI Development
PD JUN 1
PY 2013
VL 140
IS 11
BP 2354
EP 2364
DI 10.1242/dev.088427
PG 11
WC Developmental Biology
SC Developmental Biology
GA 145UK
UT WOS:000319043400011
PM 23615277
ER
PT J
AU Altman, RK
Danik, SB
Barrett, CD
AF Altman, Robert K.
Danik, Stephan B.
Barrett, Conor D.
TI Uncontrolled forward motion of an ablation catheter through a recently
available deflectable sheath
SO EUROPACE
LA English
DT Editorial Material
C1 [Altman, Robert K.; Danik, Stephan B.; Barrett, Conor D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA.
RP Barrett, CD (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA.
EM cdbarrett@partners.org
OI Altman, Robert/0000-0002-1612-3561
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1099-5129
J9 EUROPACE
JI Europace
PD JUN
PY 2013
VL 15
IS 6
BP 786
EP 786
DI 10.1093/europace/eut008
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 151NW
UT WOS:000319468300008
PM 23362018
ER
PT J
AU Kuntz, J
Gupta, R
Schonberg, SO
Semmler, W
Kachelriess, M
Bartling, S
AF Kuntz, Jan
Gupta, Rajiv
Schoenberg, Stefan O.
Semmler, Wolfhard
Kachelriess, Marc
Bartling, Soenke
TI Real-time X-ray-based 4D image guidance of minimally invasive
interventions
SO EUROPEAN RADIOLOGY
LA English
DT Article
DE Intervention guidance; 4D imaging; Compressed sensing; Catheter lab;
Minimally invasive
ID COMPRESSED SENSING PICCS; RECONSTRUCTION ALGORITHMS; CT FLUOROSCOPY;
PERFORMANCE; RADIATION; SCANNER; BEAM
AB A new technology is introduced that enables real-time 4D (three spatial dimensions plus time) X-ray guidance for vascular catheter interventions with acceptable levels of ionising radiation.
The enabling technology is a combination of low-dose tomographic data acquisition with novel compressed sensing reconstruction and use of prior image information. It was implemented in a prototype set-up consisting of a gantry-based flat detector system. In pigs (n = 5) angiographic interventions were simulated. Radiation dosage on a per time base was compared with the "gold standard" of X-ray projection imaging.
Contrary to current image guidance methods that lack permanent 4D updates, the spatial position of interventional instruments could be resolved in continuous, spatial 4D guidance; the movement of the guide wire as well as the expansion of stents could be precisely tracked in 3D angiographic road maps. Dose rate was 23.8 mu Gy/s, similar to biplane standard angiographic fluoroscopy, which has a dose rate of 20.6 mu Gy/s.
Real-time 4D X-ray image-guidance with acceptable levels of radiation has great potential to significantly influence the field of minimally invasive medicine by allowing faster and safer interventions and by enabling novel, much more complex procedures for vascular and oncological minimally invasive therapy.
aEuro cent Real-time 4D (three spatial dimensions plus time) angiographic intervention guidance is realistic.
aEuro cent Low-dose tomographic data acquisition with special compressed sensing-based algorithms is enabled.
aEuro cent Compared with 4D CT fluoroscopy, this method reduces radiation to acceptable levels.
aEuro cent Once implemented, vascular interventions may become safer and faster.
aEuro cent More complex intervention approaches may be developed.
C1 [Kuntz, Jan; Semmler, Wolfhard; Kachelriess, Marc; Bartling, Soenke] German Canc Res Ctr, Dept Med Phys Radiol, D-69120 Heidelberg, Germany.
[Gupta, Rajiv] Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, Sch Med, Boston, MA 02114 USA.
[Schoenberg, Stefan O.; Bartling, Soenke] Heidelberg Univ, Med Fac Mannheim, Inst Clin Radiol & Nucl Med, D-68167 Mannheim, Germany.
RP Bartling, S (reprint author), German Canc Res Ctr, Dept Med Phys Radiol, Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
EM j.kuntz@dkfz.de; rgupta1@partners.org; stefan.schoenberg@umm.de;
semmler.office@dkfz.de; marc.kachelriess@dkfz.de; soenkebartling@gmx.de
OI Bartling, Sonke/0000-0001-5434-9433
FU DFG (German Research Foundation) [KA 1678/6-1, BA 3546/2-1]; Siemens
Healthcare
FX The research is funded by DFG (German Research Foundation) grant (KA
1678/6-1 and BA 3546/2-1) and Siemens Healthcare. We acknowledge Stefan
Sawall's support in the creation of the reconstruction algorithm and his
contribution to the discussion of the methodology. We thank Dr. Michaela
Socher and Roland Galmbacher for animal handling. Furthermore, we would
like to acknowledge Barbara Flach and Rolf Kueres for help during
experimental set-ups and discussion of future developments. We would
like to thank Dr. Michael Grasruck, Dr. Andreas Maier and Dr. Yiannis
Kyriakou for extensive help with the experimental set-up, as well as
discussion of applications, clinical implementation and future
developments.
NR 25
TC 4
Z9 4
U1 0
U2 11
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0938-7994
J9 EUR RADIOL
JI Eur. Radiol.
PD JUN
PY 2013
VL 23
IS 6
BP 1669
EP 1677
DI 10.1007/s00330-012-2761-2
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 148TP
UT WOS:000319270800025
PM 23314598
ER
PT J
AU Newmark, RE
Schon, K
Ross, RS
Stern, CE
AF Newmark, Randall E.
Schon, Karin
Ross, Robert S.
Stern, Chantal E.
TI Contributions of the hippocampal subfields and entorhinal cortex to
disambiguation during working memory
SO HIPPOCAMPUS
LA English
DT Article
DE high-resolution fMRI; dentate gyrus; CA3; CA1; delayed match-to-sample
ID MEDIAL TEMPORAL-LOBE; LONG-TERM-MEMORY; COMPLEMENTARY-LEARNING-SYSTEMS;
HIGH-RESOLUTION FMRI; LAYER-III NEURONS; TO-SAMPLE TASK; DENTATE GYRUS;
PATTERN SEPARATION; PERIRHINAL CORTEX; PERSISTENT ACTIVITY
AB The hippocampus and medial temporal lobes (MTL) support the successful formation of new memories without succumbing to interference from related, older memories. Computational models and animal findings have implicated the dentate gyrus (DG), CA3, CA1, and entorhinal cortex (EC) in the disambiguation and encoding of well-established, episodic events that share common elements. However, it is unknown if these hippocampal subfields and MTL (entorhinal, perirhinal, parahippocampal) cortices also contribute during working memory when overlapping stimuli that share related features are rapidly encoded and subsequently maintained over a brief temporal delay. We hypothesized that activity in CA3/DG hippocampal subfields would be greater for the rapid encoding of stimuli with overlapping features than for the rapid encoding of stimuli with distinct features. In addition, we predicted that CA1 and EC, regions that are associated with creating long-term episodic representations, would show greater sustained activity across both encoding and delay periods for representations of stimuli with overlapping features than for those with distinct features. We used high-resolution fMRI during a delayed matching-to-sample (DMS) task using face pairs that either shared (overlapping condition, OL) or did not share (non-overlapping condition, NOL) common elements. We contrasted the OL condition with the NOL condition separately at sample (encoding) and during a brief delay (maintenance). At sample, we observed activity localized to CA3/DG, the subiculum, and CA1. At delay, we observed activity localized to the subiculum and CA1 and activity within the entorhinal, perirhinal, and parahippocampal cortices. Our findings are consistent with our hypotheses and suggest that CA3/DG, CA1 and the subiculum support the disambiguation and encoding of overlapping representations while CA1, subiculum and entorhinal cortex maintain these overlapping representations during working memory. (c) 2013 Wiley Periodicals, Inc.
C1 [Newmark, Randall E.; Schon, Karin; Ross, Robert S.; Stern, Chantal E.] Boston Univ, Dept Psychol, Ctr Memory & Brain, Boston, MA 02215 USA.
[Newmark, Randall E.; Stern, Chantal E.] Boston Univ, Grad Program Neurosci, Boston, MA 02215 USA.
[Newmark, Randall E.; Schon, Karin; Ross, Robert S.; Stern, Chantal E.] Boston Univ, CELEST, Boston, MA 02215 USA.
[Newmark, Randall E.; Schon, Karin; Ross, Robert S.; Stern, Chantal E.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA.
[Newmark, Randall E.; Schon, Karin; Ross, Robert S.; Stern, Chantal E.] Harvard Univ, Sch Med, Charlestown, MA USA.
RP Stern, CE (reprint author), Ctr Memory & Brain, 2 Cummington Mall,109, Boston, MA 02215 USA.
EM chantal@bu.edu
OI Schon, Karin/0000-0003-2963-8449; Ross, Robert/0000-0002-3987-881X
FU National Science Foundation Science of Learning Center [NSF SMA-0835976,
NSF SBE-0354378]; NIH NCRR; NCRR Biomedical Technology Program of the
National Center for Research Resources [NIH S10RR021110, P41RR14075]
FX Grant sponsor: National Science Foundation Science of Learning Center;
Grant number: NSF SMA-0835976 and NSF SBE-0354378; Grant sponsors: NIH
NCRR Shared Instrumentation Grant Program and/or High-End
Instrumentation Grant Program and NCRR Biomedical Technology Program of
the National Center for Research Resources; Grant numbers: NIH
S10RR021110 and P41RR14075.
NR 99
TC 20
Z9 20
U1 3
U2 26
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1050-9631
J9 HIPPOCAMPUS
JI Hippocampus
PD JUN
PY 2013
VL 23
IS 6
BP 467
EP 475
DI 10.1002/hipo.22106
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA 149CJ
UT WOS:000319295300005
PM 23504938
ER
PT J
AU Garvin, EC
Cannuscio, CC
Branas, CC
AF Garvin, Eugenia C.
Cannuscio, Carolyn C.
Branas, Charles C.
TI Greening vacant lots to reduce violent crime: a randomised controlled
trial
SO INJURY PREVENTION
LA English
DT Article
ID NEIGHBORHOOD DISORDER; COLLECTIVE EFFICACY; INNER-CITY; FEAR; HEALTH;
ENVIRONMENT; OUTCOMES; STRESS; INJURY; SPACES
AB Background Vacant lots are often overgrown with unwanted vegetation and filled with trash, making them attractive places to hide illegal guns, conduct illegal activities such as drug sales and prostitution, and engage in violent crime. There is some evidence that greening vacant lots is associated with reductions in violent crime.
Methods We performed a randomised controlled trial of vacant lot greening to test the impact of this intervention on police reported crime and residents' perceptions of safety and disorder. Greening consisted of cleaning the lots, planting grass and trees, and building a wooden fence around the perimeter. We randomly allocated two vacant lot clusters to the greening intervention or to the control status (no intervention). Administrative data were used to determine crime rates, and local resident interviews at baseline (n = 29) and at follow-up (n = 21) were used to assess perceptions of safety and disorder.
Results Unadjusted difference-in-differences estimates showed a non-significant decrease in the number of total crimes and gun assaults around greened vacant lots compared with control. People around the intervention vacant lots reported feeling significantly safer after greening compared with those living around control vacant lots (p < 0.01).
Conclusions In this study, greening was associated with reductions in certain gun crimes and improvements in residents' perceptions of safety. A larger randomised controlled trial is needed to further investigate the link between vacant lot greening and violence reduction.
C1 [Garvin, Eugenia C.] Univ Penn, Perelman Sch Med, Robert Wood Johnson Clin Scholars, Philadelphia, PA 19104 USA.
[Cannuscio, Carolyn C.] Univ Penn, Perelman Sch Med, VA Ctr Hlth Equ Res & Promot, Dept Family Med & Community Hlth, Philadelphia, PA 19104 USA.
[Branas, Charles C.] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
RP Garvin, EC (reprint author), Univ Penn, Perelman Sch Med, Robert Wood Johnson Clin Scholars, 13th Fl Blockley Hall,423 Gaurdian Dr, Philadelphia, PA 19104 USA.
EM eugenia.garvin@uphs.upenn.edu
FU Robert Wood Johnson Health and Society Scholars Educational Fund
FX This work was supported by a grant from the Robert Wood Johnson Health
and Society Scholars Educational Fund (no grant number). The funders
played no role in study design, data collection or data analysis.
NR 40
TC 31
Z9 31
U1 6
U2 51
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1353-8047
J9 INJURY PREV
JI Inj. Prev.
PD JUN
PY 2013
VL 19
IS 3
BP 198
EP 203
DI 10.1136/injuryprev-2012-040439
PG 6
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 147YS
UT WOS:000319208700009
PM 22871378
ER
PT J
AU Peacock, ZS
Lam, DK
Cox, DP
Schmidt, BL
AF Peacock, Z. S.
Lam, D. K.
Cox, D. P.
Schmidt, B. L.
TI Metastatic epithelioid angiosarcoma to the mandible: report of a case
and review of the literature
SO INTERNATIONAL JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY
LA English
DT Review
DE epithelioid angiosarcoma; mandibular condyle; vascular malignancy; renal
cell carcinoma
ID DIFFERENTIAL-DIAGNOSIS; HEMANGIOENDOTHELIOMA; CARCINOMA; BONE
AB Angiosarcoma and its epithelioid variant are vascular malignancies that rarely affect the facial skeleton. Epithelioid angiosarcoma resembles carcinoma and can be difficult to diagnose. A case is presented of metastatic epithelioid angiosarcoma to the mandible from an angiosarcomatoid portion of renal carcinoma. The diagnostic challenge is outlined and the literature is reviewed.
C1 [Peacock, Z. S.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA.
[Lam, D. K.] Univ Calif San Francisco, Dept Oral & Maxillofacial Surg, San Francisco, CA USA.
[Cox, D. P.] Univ Calif San Francisco, Dept Orofacial Sci, San Francisco, CA 94143 USA.
[Schmidt, B. L.] NYU, Dept Oral & Maxillofacial Surg, New York, NY USA.
[Schmidt, B. L.] NYU, Bluestone Ctr Clin Res, New York, NY USA.
RP Peacock, ZS (reprint author), Massachusetts Gen Hosp, Warren 1201,55 Fruit St, Boston, MA 02114 USA.
EM zpeacock@partners.org
OI Schmidt, Brian/0000-0002-2409-8984
NR 10
TC 4
Z9 4
U1 0
U2 3
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 0901-5027
J9 INT J ORAL MAX SURG
JI Int. J. Oral Maxillofac. Surg.
PD JUN
PY 2013
VL 42
IS 6
BP 702
EP 706
DI 10.1016/j.ijom.2013.02.005
PG 5
WC Dentistry, Oral Surgery & Medicine; Surgery
SC Dentistry, Oral Surgery & Medicine; Surgery
GA 152NI
UT WOS:000319538000003
PM 23499149
ER
PT J
AU Meschia, JF
Worrall, BB
Brown, RD
Ay, H
McArdle, PF
Rundek, T
Kittner, SJ
AF Meschia, James F.
Worrall, Bradford B.
Brown, Robert D.
Ay, Hakan
McArdle, Patrick F.
Rundek, Tatjana
Kittner, Steven J.
TI NINDS stroke genetics network (SiGN) experience with the causative
classification system
SO INTERNATIONAL JOURNAL OF STROKE
LA English
DT Letter
C1 [Meschia, James F.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA.
[Worrall, Bradford B.] Univ Virginia, Charlottesville, VA USA.
[Brown, Robert D.] Mayo Clin, Rochester, MN USA.
[Ay, Hakan] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[McArdle, Patrick F.; Kittner, Steven J.] Univ Maryland, Baltimore, MD 21201 USA.
[Rundek, Tatjana] Univ Miami, Miami, FL USA.
RP Meschia, JF (reprint author), Mayo Clin, Dept Neurol, 4500 San Pablo Rd, Jacksonville, FL 32224 USA.
EM meschia.james@mayo.edu
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 1747-4930
J9 INT J STROKE
JI Int. J. Stroke
PD JUN
PY 2013
VL 8
IS 4
BP E9
EP E9
DI 10.1111/j.1747-4949.2012.00944.x
PG 1
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 150NX
UT WOS:000319398900003
PM 23692494
ER
PT J
AU Jeon, HJ
Peng, DH
Chua, HC
Srisurapanont, M
Fava, M
Bae, JN
Chang, SM
Hong, JP
AF Jeon, Hong Jin
Peng, Daihui
Chua, Hong Choon
Srisurapanont, Manit
Fava, Maurizio
Bae, Jae-Nam
Chang, Sung Man
Hong, Jin Pyo
TI Melancholic features and hostility are associated with suicidality risk
in Asian patients with major depressive disorder
SO JOURNAL OF AFFECTIVE DISORDERS
LA English
DT Article
DE Melancholic; Suicidality; Hostility; Asian; Major depressive disorder
ID INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; UNIPOLAR DEPRESSION; LIFETIME
PREVALENCE; MENTAL-DISORDERS; ANGER ATTACKS; FLUOXETINE TREATMENT;
ALCOHOL DEPENDENCE; MOOD DISORDERS; DSM-IV; IDEATION
AB Background: Suicide rates are higher in East-Asians than other populations, and especially high in Koreans. However, little is known about suicidality risk and melancholic features in Asian patients with major depressive disorder (MDD).
Method: Drug-free MDD outpatients were included from 13 centers across five ethnicities consisting of Chinese (n = 290), Korean (n = 101), Thai (n = 102), Indian (n = 27), and Malay (n = 27). All were interviewed using the Mini-International Neuropsychiatric Interview (MINI.), the Montgomery-Asberg Depression Rating Scale (MADRS), and the Symptoms Checklist 90-Revised (SCL-90-R).
Results: Of 547 subjects, 177 MDD patients showed melancholic features (32.4%). These melancholic MDD patients revealed significantly higher suicidality risk (p < 0.0001), hostility (p = 0.037), and severity of depression (p < 0.0001) than those MDD patients without melancholic features. Suicidality risk was significantly higher in MDD with melancholic features than those without in subjects with lower hostility, whereas it showed no difference in higher hostility. Adjusted odds ratios of melancholic features and hostility for moderate to high suicidality risk were 1.79 (95% CI = 1.15-2.79) and 2.45 (95% CI = 1.37-4.38), after adjusting for age, sex, education years, and depression severity. Post-hoc analyses showed that suicidality risk was higher in Korean and Chinese than that of Thai, Indian and Malay in MDD subjects with melancholic features, although depression severity showed no significant differences among the ethnicities.
Conclusions: Suicidality risk is associated with both melancholic features and hostility and it shows cross-ethnic differences in Asian MDD patients, independent of depression severity. (c) 2013 Elsevier B.V. All rights reserved.
C1 [Jeon, Hong Jin] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Psychiat,Depress Ctr, Seoul, South Korea.
[Jeon, Hong Jin; Fava, Maurizio] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program, Boston, MA USA.
[Peng, Daihui] Shanghai Jiao Tong Univ, Sch Med, Shanghai Mental Hlth Ctr, Shanghai 200030, Peoples R China.
[Chua, Hong Choon] Inst Mental Hlth, Dept Psychiat, Singapore, Singapore.
[Srisurapanont, Manit] Chiang Mai Univ, Dept Psychiat, Chiang Mai 50000, Thailand.
[Bae, Jae-Nam] Inha Univ, Dept Psychiat, Coll Med, Inchon, South Korea.
[Chang, Sung Man] Kyungpook Natl Univ, Dept Psychiat, Sch Med, Taegu, South Korea.
RP Hong, JP (reprint author), Univ Ulsan, Coll Med, Dept Psychiat, Asan Med Ctr, 388-1 Pungnap 2Dong, Seoul 138736, South Korea.
EM jphong@amc.seoul.kr
OI Bae, Jae Nam/0000-0002-5024-6231; Srisurapanont,
Manit/0000-0001-6203-1206
FU Lundbeck; Duke-National University of Singapore Office of Clinical
Research; Basic Science Research Program through the National Research
Foundation of Korea (NRF); Ministry of Education, Science and Technology
[2011-0013064]
FX This work was supported by Lundbeck and the Duke-National University of
Singapore Office of Clinical Research. Neither had a 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.; This study was supported by an unrestricted research
grants from Lundbeck and from the Duke-National University of Singapore
Office of Clinical Research. This research was also supported by the
Basic Science Research Program through the National Research Foundation
of Korea (NRF) funded by the Ministry of Education, Science and
Technology (No. 2011-0013064). We thank Aya Inamori, Research Assistant
at the MGH Depression Clinical and research Program for reviewing this
manuscript.
NR 34
TC 14
Z9 15
U1 3
U2 19
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-0327
J9 J AFFECT DISORDERS
JI J. Affect. Disord.
PD JUN
PY 2013
VL 148
IS 2-3
BP 368
EP 374
DI 10.1016/j.jad.2013.01.001
PG 7
WC Clinical Neurology; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 143ZX
UT WOS:000318909700029
PM 23414572
ER
PT J
AU Schwartz, AV
Schafer, AL
Grey, A
Vittinghoff, E
Palermo, L
Lui, LYL
Wallace, RB
Cummings, SR
Black, DM
Bauer, DC
Reid, IR
AF Schwartz, Ann V.
Schafer, Anne L.
Grey, Andrew
Vittinghoff, Eric
Palermo, Lisa
Lui, Li-Yung L.
Wallace, Robert B.
Cummings, Steven R.
Black, Dennis M.
Bauer, Douglas C.
Reid, Ian R.
TI Effects of antiresorptive therapies on glucose metabolism: Results from
the FIT, HORIZON-PFT, and FREEDOM trials
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Article
DE ANTIRESORPTIVE THERAPY; GLUCOSE; DIABETES; WEIGHT
ID FRACTURE INTERVENTION TRIAL; POSTMENOPAUSAL OSTEOPOROTIC WOMEN; YEARLY
ZOLEDRONIC ACID; BONE TURNOVER; OLDER MEN; UNDERCARBOXYLATED
OSTEOCALCIN; BIOCHEMICAL MARKERS; VERTEBRAL FRACTURES;
INSULIN-RESISTANCE; ENERGY-METABOLISM
AB In rodent models, undercarboxylated osteocalcin (ucOC) acts as a hormone that promotes insulin sensitivity and secretion. If ucOC plays a similar role in humans, then antiresorptive therapies, which reduce ucOC levels, may increase the risk of insulin resistance and diabetes. We tested whether antiresorptive therapies result in higher fasting glucose, increased weight, or greater diabetes incidence in post hoc analyses of three randomized, placebo-controlled trials in postmenopausal women: Fracture Intervention Trial (FIT) (N=6151) of alendronate (4 years), Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly Pivotal Fracture Trial (HORIZON-PFT) (N=7113) of zoledronic acid (3 years), and Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months (FREEDOM) trial (N=7076) of denosumab (3 years). Fasting glucose was measured annually in FIT and HORIZON in a subset of women, and every 6 months in FREEDOM in all participants. Weight was measured annually in all trials. Incident diabetes was identified from adverse event reports, initiation of diabetes medication, or elevated fasting glucose. Differences in fasting glucose changes from randomization to trial conclusion between treatment and placebo groups were not statistically significant: 0.47mg/dL in FIT, 0.20mg/dL in HORIZON-PFT, and 0.09mg/dL in FREEDOM, all p>0.6. Weight change differed between treatment and placebo groups in FIT (0.32kg, p=0.003) and FREEDOM (0.31kg, p=0.023) but not in HORIZON-PFT (0.15kg, p=0.132). In the three trials combined, diabetes occurred in 203 and 225 women assigned to treatment or placebo, respectively. Diabetes incidence was not increased in any of the treatment groups or in the pooled estimate (pooled relative risk [RR]=0.90; 95% confidence interval [CI] 0.741.10). Antiresorptive therapy does not have a clinically important effect on fasting glucose, weight, or diabetes risk in postmenopausal women. Contrary to predictions from mouse models, reduced bone turnover does not appear to play a significant role in glucose metabolism in humans.
C1 [Schwartz, Ann V.; Schafer, Anne L.; Vittinghoff, Eric; Palermo, Lisa; Black, Dennis M.; Bauer, Douglas C.] Univ Calif San Francisco, San Francisco, CA 94107 USA.
[Schafer, Anne L.] San Francisco VA Med Ctr, San Francisco, CA USA.
[Grey, Andrew; Reid, Ian R.] Univ Auckland, Auckland 1, New Zealand.
[Lui, Li-Yung L.; Cummings, Steven R.] Calif Pacific Med Ctr, San Francisco, CA USA.
[Wallace, Robert B.] Univ Iowa, Iowa City, IA USA.
RP Schwartz, AV (reprint author), Univ Calif San Francisco, Dept Epidemiol & Biostat, 185 Berry St,Suite 5700, San Francisco, CA 94107 USA.
EM aschwartz@psg.ucsf.edu
FU Department of Veterans Affairs [5 IK2 CX000549-02]; Merck Co., Inc.;
Novartis Pharma; Amgen Inc.
FX ALS was supported by a career development award from the Department of
Veterans Affairs (5 IK2 CX000549-02). The clinical trials were supported
by their respective sponsors. The Fracture Intervention Trial was
sponsored by Merck & Co., Inc.; Health Outcomes and Reduced Incidence
with Zoledronic Acid Once Yearly Pivotal Fracture Trial (HORIZON-PFT)
was sponsored by Novartis Pharma; and the Fracture Reduction Evaluation
of Denosumab in Osteoporosis Every 6 months (FREEDOM) trial was
sponsored by Amgen Inc. This study was not financially supported by the
trial sponsors.
NR 36
TC 40
Z9 41
U1 0
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0884-0431
EI 1523-4681
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD JUN
PY 2013
VL 28
IS 6
BP 1348
EP 1354
DI 10.1002/jbmr.1865
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 149VS
UT WOS:000319350100013
PM 23322676
ER
PT J
AU Komatsu, Y
Yu, PB
Kamiya, N
Pan, HC
Fukuda, T
Scott, GJ
Ray, MK
Yamamura, K
Mishina, Y
AF Komatsu, Yoshihiro
Yu, Paul B.
Kamiya, Nobuhiro
Pan, Haichun
Fukuda, Tomokazu
Scott, Gregory J.
Ray, Manas K.
Yamamura, Ken-ichi
Mishina, Yuji
TI Augmentation of smad-dependent BMP signaling in neural crest cells
causes craniosynostosis in mice
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Article
DE BMP; CRANIOSYNOSTOSIS; NEURAL CREST CELLS; SMAD-SIGNALING; SUTURE
ID FIBRODYSPLASIA OSSIFICANS PROGRESSIVA; CALVARIAL BONE-DEVELOPMENT; SKULL
VAULT; I RECEPTOR; OSTEOBLAST APOPTOSIS; SUTURE DEVELOPMENT; MOUSE
MODEL; KAPPA-B; FGF; GROWTH
AB Craniosynostosis describes conditions in which one or more sutures of the infant skull are prematurely fused, resulting in facial deformity and delayed brain development. Approximately 20% of human craniosynostoses are thought to result from gene mutations altering growth factor signaling; however, the molecular mechanisms by which these mutations cause craniosynostosis are incompletely characterized, and the causative genes for diverse types of syndromic craniosynostosis have yet to be identified. Here, we show that enhanced bone morphogenetic protein (BMP) signaling through the BMP type IA receptor (BMPR1A) in cranial neural crest cells, but not in osteoblasts, causes premature suture fusion in mice. In support of a requirement for precisely regulated BMP signaling, this defect was rescued on a Bmpr1a haploinsufficient background, with corresponding normalization of Smad phosphorylation. Moreover, in vivo treatment with LDN-193189, a selective chemical inhibitor of BMP type I receptor kinases, resulted in partial rescue of craniosynostosis. Enhanced signaling of the fibroblast growth factor (FGF) pathway, which has been implicated in craniosynostosis, was observed in both mutant and rescued mice, suggesting that augmentation of FGF signaling is not the sole cause of premature fusion found in this model. The finding that relatively modest augmentation of Smad-dependent BMP signaling leads to premature cranial suture fusion suggests an important contribution of dysregulated BMP signaling to syndromic craniosynostoses and potential strategies for early intervention.
C1 [Komatsu, Yoshihiro; Kamiya, Nobuhiro; Pan, Haichun; Mishina, Yuji] Univ Michigan, Sch Dent, Dept Biol & Mat Sci, Ann Arbor, MI 48109 USA.
[Komatsu, Yoshihiro; Kamiya, Nobuhiro; Fukuda, Tomokazu; Mishina, Yuji] NIEHS, Lab Reprod & Dev Toxicol, NIH, Res Triangle Pk, NC 27709 USA.
[Yu, Paul B.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA.
[Yu, Paul B.] Harvard Univ, Sch Med, Boston, MA USA.
[Kamiya, Nobuhiro] Texas Scottish Rite Hosp Children, Ctr Excellence Hip Disorders, Dallas, TX 75219 USA.
[Fukuda, Tomokazu] Tohoku Univ, Grad Sch Agr Sci, Sendai, Miyagi 980, Japan.
[Scott, Gregory J.; Ray, Manas K.; Mishina, Yuji] NIEHS, Knock Out Core, NIH, Res Triangle Pk, NC 27709 USA.
[Yamamura, Ken-ichi] Kumamoto Univ, Inst Mol Embryol & Genet, Kumamoto, Japan.
RP Mishina, Y (reprint author), Univ Michigan, Sch Dent, Dept Biol & Mat Sci, 1011 North Univ Ave, Ann Arbor, MI 48109 USA.
EM mishina@umich.edu
OI Yu, Paul/0000-0003-2145-4944
FU National Institutes of Health [K99DE021054, K08HL079943, R01AR057374,
R01DE020843, ES071003-11]; Japan Society for the Promotion of Science
FX This study was supported by the National Institutes of Health
(K99DE021054 to YK; K08HL079943 and R01AR057374 to PBY; and R01DE020843
and ES071003-11 to YM) and a fellowship from the Japan Society for the
Promotion of Science (YK).
NR 55
TC 16
Z9 16
U1 0
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0884-0431
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD JUN
PY 2013
VL 28
IS 6
BP 1422
EP 1433
DI 10.1002/jbmr.1857
PG 12
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 149VS
UT WOS:000319350100020
PM 23281127
ER
PT J
AU Hashash, JG
Nasr, JY
Francis, F
AF Hashash, J. G.
Nasr, J. Y.
Francis, Fadi
TI Gastrointestinal: Mucinous and signet cell adenocarcinoma of the
appendix
SO JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY
LA English
DT Article
C1 [Hashash, J. G.; Nasr, J. Y.] Univ Pittsburgh, Med Ctr, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA 15260 USA.
[Francis, Fadi] VA Pittsburgh Healthcare Syst, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA USA.
RP Hashash, JG (reprint author), Univ Pittsburgh, Med Ctr, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA 15260 USA.
NR 0
TC 1
Z9 2
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0815-9319
J9 J GASTROEN HEPATOL
JI J. Gastroenterol. Hepatol.
PD JUN
PY 2013
VL 28
IS 6
BP 903
EP 903
DI 10.1111/jgh.12226
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 149RX
UT WOS:000319339900004
PM 23692577
ER
PT J
AU de Mena, L
Samaranch, L
Coto, E
Cardo, LF
Ribacoba, R
Lorenzo-Betancor, O
Pastor, P
Wang, L
Irigoyen, J
Mata, IF
Diaz, M
Moris, G
Menendez, M
Corao, AI
Lorenzo, E
Alvarez, V
AF de Mena, Lorena
Samaranch, LLuis
Coto, Eliecer
Cardo, Lucia F.
Ribacoba, Rene
Lorenzo-Betancor, Oswaldo
Pastor, Pau
Wang, Li
Irigoyen, Jaione
Mata, Ignacio F.
Diaz, Marta
Moris, German
Menendez, Manuel
Corao, Ana I.
Lorenzo, Elena
Alvarez, Victoria
TI Mutational Screening of PARKIN Identified a 3 ' UTR Variant (rs62637702)
Associated with Parkinson's Disease
SO JOURNAL OF MOLECULAR NEUROSCIENCE
LA English
DT Article; Proceedings Paper
CT 11th International Symposium on VIP, PACAP and Related Peptides
CY AUG 27-31, 2013
CL Univ Pecs, Pecs, HUNGARY
HO Univ Pecs
DE Parkinson's disease; Parkin; Mutation; DNA polymorphisms; Genetic risk;
Genetics
ID ALPHA-SYNUCLEIN EXPRESSION; RISK; GENE
AB PRKN mutations have been linked to Parkinson's disease (PD). Most of the mutational screenings have focused on the coding exons. The 3' untranslated region (UTR) could also harbor functionally relevant nucleotide changes. We performed a mutational screening of PRKN in a cohort of early-onset PD patients (n = 235) from Spain. We found 16 mutations (five new): 16 patients (7 %) carried two mutations and only one mutation was found in 28 (12 %). Patients with two mutations had significantly lower mean age (30 +/- 9 years) compared to patients with one (40 +/- 7) or no mutation (42 +/- 7). We found a total of 15 nucleotide variants (three new) in the 3' UTR region. The frequency of carriers of the rare rs62637702 G allele (*94A/G) was significantly lower among the patients compared to healthy controls (n = 418) (0.03 vs. 0.004; p < 0.001), suggesting a protective role for this allele. In order to investigate the basal effect of this variant, we performed luciferase assays. No different basal activity was observed between the two alleles. In conclusion, the rs62637702 polymorphism was associated with PD. This could be a surrogate marker for disease risk, in linkage disequilibrium with other non-identified functional variant.
C1 [de Mena, Lorena; Coto, Eliecer; Cardo, Lucia F.; Diaz, Marta; Corao, Ana I.; Alvarez, Victoria] Hosp Univ Cent Asturias, Genet Mol Lab Med, Oviedo, Spain.
[Samaranch, LLuis; Lorenzo-Betancor, Oswaldo; Pastor, Pau; Irigoyen, Jaione; Lorenzo, Elena] Univ Navarra, CIMA, Ctr Appl Med Res, Neurogenet Lab,Div Neurosci, E-31080 Pamplona, Spain.
[Ribacoba, Rene; Moris, German; Menendez, Manuel] Hosp Univ Cent Asturias, Asturias, Spain.
[Ribacoba, Rene; Moris, German; Menendez, Manuel] Hosp Univ Alvarez Buylla Mieres, Asturias, Spain.
[Coto, Eliecer] Univ Oviedo, Dept Med, Oviedo, Spain.
[Lorenzo-Betancor, Oswaldo; Pastor, Pau; Irigoyen, Jaione; Lorenzo, Elena] Univ Navarra, Sch Med, Clin Univ Navarra, Dept Neurol, E-31080 Pamplona, Spain.
[Wang, Li] Univ Utah, Sch Med, Dept Med, Huntsman Canc Inst, Salt Lake City, UT USA.
[Wang, Li] Univ Utah, Sch Med, Dept Oncol Sci, Huntsman Canc Inst, Salt Lake City, UT USA.
[Mata, Ignacio F.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA.
[Mata, Ignacio F.] Univ Washington, Sch Med, Dept Neurol, Seattle, WA USA.
[Alvarez, Victoria] Hosp Cent Asturias Maternidad, Oviedo 33006, Spain.
RP Alvarez, V (reprint author), Hosp Cent Asturias Maternidad, Oviedo 33006, Spain.
EM victoria.alvarez@sespa.princast.es
RI Pastor, Pau/C-9834-2009;
OI Pastor, Pau/0000-0002-7493-8777; Moris, German/0000-0001-7608-2194;
Fernandez Mata, Ignacio/0000-0003-1198-0633
FU Spanish Fondo de Investigaciones Sanitarias-Fondos FEDER European Union
[FIS-05/008, 08/0915, 11/0093]; FICYT-Principado de Asturias; Spanish
Ministry of Science and Technology; European Social Fund; Spanish
Ministry of Education and Science [SAF2006-10126]; Fundacio La Marato de
TV3 [061131]; UTE project FIMA, Spain; Fundacion Parkinson Asturias;
Obra Social Cajastur
FX The authors thank the Fundacion Parkinson Asturias and Obra Social
Cajastur for their support. This work was supported by grants from the
Spanish Fondo de Investigaciones Sanitarias-Fondos FEDER European Union
(FIS-05/008, 08/0915, and 11/0093). LFC and LDM are predoctoral
fellowships of FICYT-Principado de Asturias. LS held a Torres Quevedo
fellowship from the Spanish Ministry of Science and Technology,
co-financed by the European Social Fund. This study was supported by a
grant from the Spanish Ministry of Education and Science (SAF2006-10126:
2006-2009), by the project 061131 from the Fundacio La Marato de TV3 and
by the UTE project FIMA, Spain to PP. We thank all participating
subjects and their relatives for their contribution to the study. We
thank Drs. Maria A. Pastor, Jose Obeso, Maria R Luquin, Maria C
Rodriguez-Oroz, and Mario Riverol for recruiting some subjects for the
study.
NR 21
TC 3
Z9 3
U1 0
U2 1
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 0895-8696
EI 1559-1166
J9 J MOL NEUROSCI
JI J. Mol. Neurosci.
PD JUN
PY 2013
VL 50
IS 2
BP 264
EP 269
DI 10.1007/s12031-012-9942-y
PG 6
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 148UX
UT WOS:000319274200005
PM 23275044
ER
PT J
AU Saria, MG
Corle, C
Hu, J
Rudnick, JD
Phuphanich, S
Mrugala, MM
Crew, LK
Bota, DA
Fu, BD
Kim, RY
Brown, T
Feely, H
Brechlin, J
Brown, BD
Drappatz, J
Wen, PY
Chen, CC
Carter, B
Lee, JW
Kesari, S
AF Saria, Marlon G.
Corle, Courtney
Hu, Jethro
Rudnick, Jeremy D.
Phuphanich, Surasak
Mrugala, Maciej M.
Crew, Laura K.
Bota, Daniela A.
Fu, Beverly Dan
Kim, Ryan Y.
Brown, Tiffany
Feely, Homira
Brechlin, Joanne
Brown, Bradley D.
Drappatz, Jan
Wen, Patrick Y.
Chen, Clark C.
Carter, Bob
Lee, Jong Woo
Kesari, Santosh
TI Retrospective analysis of the tolerability and activity of lacosamide in
patients with brain tumors
SO JOURNAL OF NEUROSURGERY
LA English
DT Article
DE seizure; antiepileptic drug; primary brain tumor; oncology
ID EPILEPSY; MANAGEMENT; SEIZURES
AB Object. The object of this study was to determine the tolerability and activity of lacosamide in patients with brain tumors.
Methods. The authors reviewed the medical records at 5 US academic medical centers with tertiary brain tumor programs, seeking all patients in whom a primary brain tumor had been diagnosed and who were taking lacosamide.
Results. The authors identified 70 patients with primary brain tumors and reviewed seizure frequency and toxicities. The majority of the patients had gliomas (96%). Fifty-five (78%) had partial seizures only, and 12 (17%) had generalized seizures. Most of the patients (74%) were started on lacosamide because of recurrent seizures. Forty-six patients (66%) reported a decrease in seizure frequency, and 21 patients (30%) reported stable seizures. Most of the patients (54 [77%]) placed on lacosamide did not report any toxicities.
Conclusions. This retrospective analysis demonstrated that lacosamide was both well tolerated and active as an add-on antiepileptic drug (AED) in patients with brain tumors. Lacosamide's novel mechanism of action will allow for concurrent use with other AEDs, as documented by its activity across many different types of AEDs used in this patient population. Larger prospective studies are warranted.
C1 [Saria, Marlon G.; Corle, Courtney; Kim, Ryan Y.; Brown, Tiffany; Feely, Homira; Brechlin, Joanne; Brown, Bradley D.; Kesari, Santosh] Univ Calif San Diego, Moores Canc Ctr, Dept Neurosci, La Jolla, CA 92093 USA.
[Feely, Homira; Chen, Clark C.; Carter, Bob] Univ Calif San Diego, Moores Canc Ctr, Dept Neurosurg, La Jolla, CA 92093 USA.
[Hu, Jethro; Rudnick, Jeremy D.; Phuphanich, Surasak] Cedars Sinai Med Ctr, Dept Neurol & Neurosurg, Cochran Brain Tumor Ctr, Los Angeles, CA USA.
[Bota, Daniela A.; Fu, Beverly Dan] Univ Calif Irvine, Sch Med, Dept Neurol, Irvine, CA 92717 USA.
[Bota, Daniela A.] Univ Calif Irvine, Sch Med, Dept Neurol Surg, Irvine, CA 92717 USA.
[Bota, Daniela A.] Univ Calif Irvine, Sch Med, Chao Family Comprehens Canc Ctr, Irvine, CA 92717 USA.
[Mrugala, Maciej M.] Univ Washington, Dept Neurol, Sch Med, Seattle, WA USA.
[Crew, Laura K.] Univ Washington, Sch Med, Dept Neurol Surg, Seattle, WA 98195 USA.
[Mrugala, Maciej M.; Crew, Laura K.] Univ Washington, Sch Med, Neurooncol Ctr, Seattle, WA 98195 USA.
[Drappatz, Jan; Wen, Patrick Y.; Lee, Jong Woo] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA.
[Drappatz, Jan; Wen, Patrick Y.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
RP Kesari, S (reprint author), Univ Calif San Diego, Moores Canc Ctr, 3855 Hlth Sci Dr, La Jolla, CA 92093 USA.
EM skesari@ucsd.edu
RI Kesari, Santosh/E-8461-2013
FU NIH [3P30CA023100-25S8]; American Cancer Society; NM; Novartis; Merck;
Bristol Meyers Squibb
FX This work was supported in part by NIH Grant No. 3P30CA023100-25S8
(S.K.). Dr. Mrugala is on the speakers' bureau of and is a consultant
for UCB Pharma. Dr. Bota serves on the speakers' bureau of Merck, Roche,
and Eisai; serves on the clinical advisory board of Epitopoietic
Research Corp.; has received research support from the American Cancer
Society; and receives institutional support from the University of
California, Irvine, for stem cell research. Dr. Kesari is on the
speakers' bureau of UCB Pharma, Genentech, and Merck and has received
research support from the NM, Novartis, Merck, and Bristol Meyers
Squibb.
NR 14
TC 12
Z9 12
U1 0
U2 5
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 JUN
PY 2013
VL 118
IS 6
BP 1183
EP 1187
DI 10.3171/2013.1.JNS12397
PG 5
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA 150BY
UT WOS:000319366400008
PM 23451905
ER
PT J
AU Elder, JB
Chiocca, EA
AF Elder, J. Bradley
Chiocca, E. Antonio
TI Glioblastoma multiforme and laser interstitial thermal therapy
SO JOURNAL OF NEUROSURGERY
LA English
DT Editorial Material
ID METASTASES; LIVER; AGE
C1 [Elder, J. Bradley] Ohio State Univ, Med Ctr, Dept Neurol Surg, Columbus, OH 43210 USA.
[Chiocca, E. Antonio] Dana Farber Canc Inst, Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA.
[Chiocca, E. Antonio] Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA.
RP Elder, JB (reprint author), Ohio State Univ, Med Ctr, Dept Neurol Surg, Columbus, OH 43210 USA.
NR 10
TC 2
Z9 2
U1 0
U2 0
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 JUN
PY 2013
VL 118
IS 6
BP 1199
EP 1200
DI 10.3171/2012.9.JNS121563
PG 2
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA 150BY
UT WOS:000319366400012
PM 23560576
ER
PT J
AU Duhaime, AC
Stufflebeam, SM
AF Duhaime, Ann-Christine
Stufflebeam, Steven M.
TI Connectivity via magnetoencephalography
SO JOURNAL OF NEUROSURGERY
LA English
DT Editorial Material
ID IMAGING APPROACH; MILD; MEG
C1 [Duhaime, Ann-Christine] Massachusetts Gen Hosp, Dept Pediat Neurosurg, Boston, MA 02114 USA.
[Stufflebeam, Steven M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA.
RP Duhaime, AC (reprint author), Massachusetts Gen Hosp, Dept Pediat Neurosurg, Boston, MA 02114 USA.
NR 4
TC 0
Z9 0
U1 0
U2 2
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 JUN
PY 2013
VL 118
IS 6
BP 1304
EP 1305
DI 10.3171/2012.10.JNS121408
PG 2
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA 150BY
UT WOS:000319366400029
PM 23600936
ER
PT J
AU Yoon, MK
Parsa, AT
Horton, JC
AF Yoon, Michael K.
Parsa, Andrew T.
Horton, Jonathan C.
TI Skull thickening, paranasal sinus expansion, and sella turcica shrinkage
from chronic intracranial hypotension
SO JOURNAL OF NEUROSURGERY-PEDIATRICS
LA English
DT Article
DE enophthalmos; ventriculoperitoneal shunt; cerebrospinal fluid;
hydrocephalus; pneumocephalus; Sunken Eyes, Sagging Brain Syndrome
ID BILATERAL ENOPHTHALMOS; BRAIN-SYNDROME; HYDROCEPHALUS; SHUNTS;
MANAGEMENT; PRESSURE; VALVE
AB In children or young adults, the morphology of the skull can be altered by excessive drainage of CSF following placement of a ventriculoperitoneal (VP) shunt. In Sunken Eyes, Sagging Brain Syndrome, gradual enlargement of the orbital cavity occurs from low or negative intracranial pressure (ICP), leading to progressive bilateral enophthalmos. The authors report several heretofore unrecognized manifestations of this syndrome, which developed in a 29-year-old man with a history of VP shunt placement following a traumatic brain injury at the age of 9 years. Magnetic resonance imaging showed typical features of chronic intracranial hypotension, and lumbar puncture yielded an unrecordable subarachnoid opening pressure. The calvaria was twice its normal thickness, owing to contraction of the inner table. The paranasal sinuses were expanded, with aeration of the anterior clinoid processes, greater sphenoid wings, and temporal bones. The sella turcica showed a 50% reduction in cross-sectional area as compared with that in control subjects, resulting in partial extrusion of the pituitary gland. These new features broaden the spectrum of clinical findings associated with low ICP. Secondary installation of a valve to restore normal ICP is recommended to halt progression of these rare complications of VP shunt placement.
C1 [Yoon, Michael K.] Harvard Univ, Sch Med, Dept Ophthalmol, Cambridge, MA 02138 USA.
[Yoon, Michael K.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
[Parsa, Andrew T.] Univ Calif San Francisco, Dept Neurosurg, San Francisco, CA 94143 USA.
[Horton, Jonathan C.] Univ Calif San Francisco, Dept Ophthalmol, San Francisco, CA 94143 USA.
[Horton, Jonathan C.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA.
[Horton, Jonathan C.] Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94143 USA.
RP Horton, JC (reprint author), Univ Calif San Francisco, 10 Koret Way, San Francisco, CA 94143 USA.
EM hortonj@vision.ucsf.edu
FU National Eye Institute [EY10217]; Research to Prevent Blindness
FX This work was supported by National Eye Institute Grant No. EY10217 and
Research to Prevent Blindness.
NR 33
TC 3
Z9 3
U1 1
U2 3
PU AMER ASSOC NEUROLOGICAL SURGEONS
PI ROLLING MEADOWS
PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA
SN 1933-0707
J9 J NEUROSURG-PEDIATR
JI J. Neurosurg.-Pediatr.
PD JUN
PY 2013
VL 11
IS 6
BP 667
EP 672
DI 10.3171/2013.2.PEDS12560
PG 6
WC Clinical Neurology; Pediatrics; Surgery
SC Neurosciences & Neurology; Pediatrics; Surgery
GA 150CD
UT WOS:000319366900009
PM 23540524
ER
PT J
AU Knobe, M
Gradl, G
Maier, KJ
Drescher, W
Jansen-Troy, A
Prescher, A
Knechtel, T
Antony, P
Pape, HC
AF Knobe, Matthias
Gradl, Gertraud
Maier, Klaus-Juergen
Drescher, Wolf
Jansen-Troy, Arne
Prescher, Andreas
Knechtel, Toralf
Antony, Pia
Pape, Hans-Christoph
TI Rotationally Stable Screw-Anchor Versus Sliding Hip Screw Plate Systems
in Stable Trochanteric Femur Fractures: A Biomechanical Evaluation
SO JOURNAL OF ORTHOPAEDIC TRAUMA
LA English
DT Article
DE helical blade; hip screw; rotationally stable screw-anchor;
biomechanical testing; trochanteric fracture; cutout; migration
ID UNSTABLE INTERTROCHANTERIC FRACTURES; PERCUTANEOUS COMPRESSION PLATE;
HELICAL BLADE; INTRAMEDULLARY NAIL; CUTOUT RESISTANCE; CANCELLOUS BONE;
FEMORAL-NECK; LAG SCREWS; FIXATION; IMPLANT
AB Objectives: The rotationally stable screw-anchor plate system (RoSA) is unique in using a novel screw-blade combination. This investigation tested the hypothesis whether RoSA is advantageous over the sliding hip screw plate system (SHS) with regard to stiffness, failure load, displacement, and migration in stable trochanteric femur fractures (OTA 31A1.1).
Methods: Thirteen femur pairs (mean age = 79 years; range, 64-92 years) received implants of either the RoSA or SHS (Koenigsee Implants, Allendorf, Germany). Beginning with 300 N and under consecutive 300 N load-increase steps (2000 cycles, 0.5 Hz) the femurs were cycled until failure. Specimens were evaluated for fragment displacement in both frontal and rotational planes and for migration. A survival analysis was carried out.
Results: With regard to stiffness (526 +/- 195 N/mm vs 358 +/- 143 N/mm; P = 0.006) and the failure load (2838 +/- 781 N vs 2262 +/- 863 N; P = 0.012), the RoSA proved superior to the SHS. Furthermore, RoSA demonstrated higher rotational stability in comparison to the SHS (1800 N: 0 +/- 0 degrees vs 1.1 +/- 1.3 degrees; P = 0.015; failure point: 0 + 0 degrees vs 2.3 + 2.6 degrees; P = 0.008), measuring rotation about femoral neck axis over time. Whereas cutout occurred only in the RoSA system (n = 3; P = 0.110), the SHS underwent plastic deformation in 7 cases (n = 7; P = 0.003). In one case (7%), the insertion of the RoSA blade resulted in iatrogenic cut-through caused by a jamming of the screw and the blade.
Conclusions: The fixation of stable trochanteric femur fractures with RoSA in cadavers led to greater primary stability under cyclic load, with significant advantages with regard to stiffness, failure load, and rotational stability, compared with the SHS. A detrimental effect was its migration tendency, which began at 1800 N and occurred in the cranial direction. A meticulous insertion technique was a prerequisite to avoid iatrogenic perforation of the femoral head. Our results will have to be substantiated by further biomechanical and clinical trials using an optimized RoSA system.
C1 [Knobe, Matthias; Knechtel, Toralf; Antony, Pia; Pape, Hans-Christoph] Univ Aachen, Med Ctr, Dept Orthopaed Trauma, D-52074 Aachen, Germany.
[Gradl, Gertraud] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA.
[Maier, Klaus-Juergen] RoMed Hosp, Dept Surg, Bad Aibling, Germany.
[Drescher, Wolf] Univ Aachen, Med Ctr, Dept Orthopaed Surg, D-52074 Aachen, Germany.
[Jansen-Troy, Arne] Rhein Westfal TH Aachen, Helmholtz Inst Biomed Engn, Aachen, Germany.
[Prescher, Andreas] Univ Aachen, Med Ctr, Dept Mol & Cellular Anat, D-52074 Aachen, Germany.
RP Knobe, M (reprint author), Univ Aachen, Med Ctr, Dept Orthopaed & Trauma Surg, 30 Pauwels St, D-52074 Aachen, Germany.
EM mknobe@ukaachen.de
NR 39
TC 3
Z9 3
U1 1
U2 4
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 JUN
PY 2013
VL 27
IS 6
BP E127
EP E136
DI 10.1097/BOT.0b013e318278112a
PG 10
WC Orthopedics; Sport Sciences
SC Orthopedics; Sport Sciences
GA 151GA
UT WOS:000319447500001
PM 23114419
ER
PT J
AU Yankeelov, TE
Peterson, TE
Abramson, RG
Izquierdo-Garcia, D
Arlinghaus, LR
Li, X
Atuegwu, NC
Catana, C
Manning, HC
Fayad, ZA
Gore, JC
AF Yankeelov, Thomas E.
Peterson, Todd E.
Abramson, Richard G.
Izquierdo-Garcia, David
Arlinghaus, Lori R.
Li, Xia
Atuegwu, Nkiruka C.
Catana, Ciprian
Manning, H. Charles
Fayad, Zahi A.
Gore, John C.
TI Simultaneous PET-MRI in oncology: A solution looking for a problem (vol
30, pg 1342, 2012)
SO MAGNETIC RESONANCE IMAGING
LA English
DT Correction
C1 [Yankeelov, Thomas E.; Peterson, Todd E.; Abramson, Richard G.; Arlinghaus, Lori R.; Li, Xia; Atuegwu, Nkiruka C.; Manning, H. Charles; Gore, John C.] Vanderbilt Univ, Inst Imaging Sci, Nashville, TN 37232 USA.
[Yankeelov, Thomas E.; Peterson, Todd E.; Abramson, Richard G.; Arlinghaus, Lori R.; Li, Xia; Atuegwu, Nkiruka C.; Manning, H. Charles; Gore, John C.] Vanderbilt Univ, Dept Radiol & Radiol Sci, Nashville, TN 37232 USA.
[Yankeelov, Thomas E.; Peterson, Todd E.; Gore, John C.] Vanderbilt Univ, Dept Phys & Astron, Nashville, TN 37232 USA.
[Yankeelov, Thomas E.; Manning, H. Charles; Gore, John C.] Vanderbilt Univ, Dept Biomed Engn, Nashville, TN 37232 USA.
[Yankeelov, Thomas E.] Vanderbilt Univ, Dept Canc Biol, Nashville, TN 37232 USA.
[Izquierdo-Garcia, David; Fayad, Zahi A.] Mt Sinai Med Ctr, Translat & Mol Imaging Inst, New York, NY 10029 USA.
[Izquierdo-Garcia, David] Mt Sinai Med Ctr, Dept Radiol, New York, NY 10029 USA.
[Catana, Ciprian] Massachusetts Gen Hosp, Dept Radiol, Athinoula Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
[Catana, Ciprian] Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
[Manning, H. Charles] Vanderbilt Univ, Dept Neurosurg, Nashville, TN 37232 USA.
[Fayad, Zahi A.] Mt Sinai Med Ctr, Dept Cardiol, New York, NY 10029 USA.
[Gore, John C.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA.
RP Yankeelov, TE (reprint author), Vanderbilt Univ, Med Ctr, Inst Imaging Sci, Med Ctr AA 1105, Nashville, TN 37232 USA.
EM thomas.yankeelov@vanderbilt.edu
NR 1
TC 1
Z9 1
U1 0
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0730-725X
J9 MAGN RESON IMAGING
JI Magn. Reson. Imaging
PD JUN
PY 2013
VL 31
IS 5
BP 796
EP 796
DI 10.1016/j.mri.2013.01.015
PG 1
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 146PM
UT WOS:000319103000023
ER
PT J
AU Hausmann, LRM
Gao, S
Mor, MK
Schaefer, JH
Fine, MJ
AF Hausmann, Leslie R. M.
Gao, Shasha
Mor, Maria K.
Schaefer, James H., Jr.
Fine, Michael J.
TI Understanding Racial and Ethnic Differences in Patient Experiences With
Outpatient Health Care in Veterans Affairs Medical Centers
SO MEDICAL CARE
LA English
DT Article
DE race and ethnicity; disparities; CAHPS; health care experiences;
Veterans
ID UNITED-STATES; MANAGED CARE; SATISFACTION; DISPARITIES; ASSESSMENTS;
RACE/ETHNICITY; PERCEPTIONS; PROVIDERS
AB Background: Racial and ethnic differences in patient health care experiences have not been well examined in the Veterans Affairs (VA) Healthcare System.
Objectives: To examine racial/ethnic differences in outpatient health care experiences within and between VA medical facilities.
Research Design: We assessed within-facility and between-facility racial/ethnic differences in responses to the 2010 VA Survey of Healthcare Experiences of Patients using mixed-effects multinomial regression.
Subjects: A total of 211,459 respondents (53.2%) to a random survey of outpatients from 910 VA medical facilities (71.9% non-Hispanic white, 15.1% non-Hispanic black, 6.4% Hispanic, and 6.7% Other race/ethnicity).
Measures: Negative and positive patient-reported experiences in 8 domains of health care.
Results: Between-facility effects for black race were higher for 7 domains of negative experiences [risk differences (RDs): 0.37% to 1.64%] and lower for 6 domains of positive experiences (RDs: -0.69% to -2.54%). Between-facility effects for Hispanic ethnicity were higher for 5 domains of negative experiences (RDs: 0.60%-1.34%) and lower for 5 domains of positive experiences (RDs: -1.00% to -1.88%). Hispanic ethnicity was also associated with higher within-facility rates of positive experiences for 5 domains of care (RDs: 2.97%-4.08%). Other race/ethnicity was associated with significantly higher within-facility rates of negative experiences (RDs: 2.04%-3.95%) and lower rates of positive experiences for all 8 domains (RDs: -2.05% to -4.70%).
Conclusions: In a national random sample of Veterans managed in the VA Healthcare System, we demonstrated significant within-facility and between-facility racial and ethnic differences in outpatient health care experiences, with differing patterns for each minority group.
C1 [Hausmann, Leslie R. M.; Gao, Shasha; Mor, Maria K.; Fine, Michael J.] Univ Pittsburgh, Sch Med, Vet Affairs Pittsburgh Healthcare Syst, VA Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA.
[Hausmann, Leslie R. M.; Fine, Michael J.] Univ Pittsburgh, Sch Med, Dept Med, Div Gen Internal Med, Pittsburgh, PA 15213 USA.
[Mor, Maria K.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA.
[Schaefer, James H., Jr.] Off Informat & Analyt, Dept Vet Affairs, Durham, NC USA.
RP Hausmann, LRM (reprint author), Vet Affairs Pittsburgh Healthcare Syst, VA Ctr Hlth Equ Res & Promot, 7180 Highland Dr 151C-H, Pittsburgh, PA 15206 USA.
EM leslie.hausmann@gmail.com
FU Center for Health Equity Research and Promotion (CHERP) VISN4 Pilot
Research Program [LIP 72-051]; Veterans Affairs Health Services Research
and Development Career Development Program [RCD 06-287]
FX Supported by the Center for Health Equity Research and Promotion (CHERP)
VISN4 Pilot Research Program (LIP 72-051). L.R.M.H.'s effort was
supported by the Veterans Affairs Health Services Research and
Development Career Development Program (RCD 06-287).
NR 33
TC 14
Z9 14
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 JUN
PY 2013
VL 51
IS 6
BP 532
EP 539
DI 10.1097/MLR.0b013e318287d6e5
PG 8
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 145VD
UT WOS:000319045800010
PM 23673395
ER
PT J
AU Iezzoni, LI
Yu, J
Wint, AJ
Smeltzer, SC
Ecker, JL
AF Iezzoni, Lisa I.
Yu, Jun
Wint, Amy J.
Smeltzer, Suzanne C.
Ecker, Jeffrey L.
TI Prevalence of Current Pregnancy Among US Women With and Without Chronic
Physical Disabilities
SO MEDICAL CARE
LA English
DT Article
DE disability; pregnancy; movement difficulties; National Health Interview
Survey
ID HEALTH-CARE; MOTHERHOOD; EXPERIENCES
AB Background: The number of US women of childbearing age who have chronic physical disabilities (CPD) is increasing. However, little is known about their reproductive experiences. Historically, women with physical disabilities have confronted stigmatized attitudes about becoming pregnant.
Objectives: To explore the national prevalence of current pregnancy among women with and without CPD; examine differences in current pregnancy prevalence between these 2 groups of women.
Research Design: Bivariable and multivariable analyses of cross-sectional, nationally representative National Health Interview Survey data from 2006 to 2011.
Subjects: Forty-seven thousand six hundred twenty-nine civilian, noninstitutionalized women aged 18-49 years.
Measures: National Health Interview Survey asks women ages 18-49 if they are currently pregnant; it also asks about various movement difficulties. We used responses from 8 movement difficulty and other questions to identify women with CPD.
Results: Six thousand forty-three (12.7%) sampled women report CPD. Compared with other women, women with CPD are significantly: older; more likely to be black and less likely to be Asian or Hispanic; more likely to be divorced or separated; more likely to have less than a high school education; less likely to be employed; and have much lower incomes. Across all women, 3.5% report being currently pregnant: 3.8% of women without CPD and 2.0% with CPD. Controlling for sociodemographic factors, the adjusted odds ratio (95% confidence interval) of current pregnancy is 0.83 (95% confidence interval, 0.65-1.05; P = 0.12) for women with CPD compared with nondisabled women.
Conclusions: Women with CPD do become pregnant, and their numbers will likely grow. Obstetrical practitioners therefore require training about the special needs of these women.
C1 [Iezzoni, Lisa I.; Yu, Jun; Wint, Amy J.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA.
[Iezzoni, Lisa I.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Smeltzer, Suzanne C.] Villanova Univ, Coll Nursing, Ctr Nursing Res, Villanova, PA 19085 USA.
[Ecker, Jeffrey L.] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA.
[Ecker, Jeffrey L.] Harvard Univ, Sch Med, Dept Obstet & Gynecol, Boston, MA USA.
RP Iezzoni, LI (reprint author), Massachusetts Gen Hosp, Mongan Inst Hlth Policy, 50 Staniford St,Room 901B, Boston, MA 02114 USA.
EM liezzoni@partners.org
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development [1R21HD068756-01A1]
FX Supported by the Eunice Kennedy Shriver National Institute of Child
Health and Human Development (Grant no. 1R21HD068756-01A1).
NR 24
TC 21
Z9 21
U1 0
U2 0
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 JUN
PY 2013
VL 51
IS 6
BP 555
EP 562
DI 10.1097/MLR.0b013e318290218d
PG 8
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 145VD
UT WOS:000319045800013
PM 23604018
ER
PT J
AU Stewart, DS
Hotta, M
Desai, R
Forman, SA
AF Stewart, Deirdre S.
Hotta, Mayo
Desai, Rooma
Forman, Stuart A.
TI State-Dependent Etomidate Occupancy of Its Allosteric Agonist Sites
Measured in a Cysteine-Substituted GABA(A) Receptor
SO MOLECULAR PHARMACOLOGY
LA English
DT Article
ID ANESTHETIC BINDING-SITE; A RECEPTORS; GENERAL-ANESTHETICS; SUBUNIT
INTERFACE; AZI-ETOMIDATE; MODULATION; ACTIVATION; MUTATIONS; PROPOFOL;
MODEL
AB A central axiom of ligand-receptor theory is that agonists bind more tightly to active than to inactive receptors. However, measuring agonist affinity in inactive receptors is confounded by concomitant activation. We identified a cysteine substituted mutant g-aminobutyric acid type A (GABA(A)) receptor with unique characteristics allowing the determination of allosteric agonist site occupancy in both inactive and active receptors. Etomidate, the allosteric agonist, is an anesthetic that activates or modulates alpha 1 beta 2 gamma 2L GABA(A) receptors via transmembrane sites near beta 2M286 residues in M3 domains. Voltage-clamp electrophysiology studies of alpha 1 beta 2M286C gamma 2L receptors show that GABA is an efficacious agonist and that etomidate modulates GABA-activated activity, but direct etomidate agonism is absent. Quantitative analysis of mutant activity using an established Monod-Wyman-Changeux (MWC) allosteric model indicates that the intrinsic efficacy of etomidate, defined as its relative affinity for active versus inactive receptors, is lower than in wild-type receptors. Para-chloromercuribenzene sulfonate covalently modifies beta 2M286C side-chain sulfhydryls, irreversibly altering GABA-induced currents. Etomidate concentration dependently reduces the apparent rate of beta 2M286C-pCMBS bond formation, tracked electrophysiologically. High etomidate concentrations completely protect the beta 2M286C suflhydryl from covalent modification, suggesting close steric interactions. The 50% protective etomidate concentration (PC50) is 14 mu M in inactive receptors and 1.1 to 2.2 mu M during GABA-activation, experimentally demonstrating that activated receptors bind etomidate more avidly than do inactive receptors. The experimental PC50 values are remarkably close to, and therefore validate, MWC model predictions for etomidate dissociation constants in both inactive and active receptors. Our results support MWC models as valid frameworks for understanding the agonism, coagonism, and modulation of ligand-gated ion channels.
C1 [Hotta, Mayo; Desai, Rooma; Forman, Stuart A.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Beecher Mallinckrodt Res Labs, Boston, MA 02114 USA.
[Hotta, Mayo; Desai, Rooma; Forman, Stuart A.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
[Forman, Stuart A.] Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA.
[Stewart, Deirdre S.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA.
RP Forman, SA (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Jackson 444,55 Fruit St, Boston, MA 02114 USA.
EM saforman@partners.org
FU National Institutes of Health National Institute of General Medical
Sciences [GM58448, GM089745]
FX This work was supported by the National Institutes of Health National
Institute of General Medical Sciences [Grants GM58448 and GM089745].
NR 25
TC 9
Z9 9
U1 1
U2 5
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0026-895X
J9 MOL PHARMACOL
JI Mol. Pharmacol.
PD JUN
PY 2013
VL 83
IS 6
BP 1200
EP 1208
DI 10.1124/dmd.112.084558
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 146RY
UT WOS:000319109700005
PM 23525330
ER
PT J
AU Scharf, JM
Yu, D
Mathews, CA
Neale, BM
Stewart, SE
Fagerness, JA
Evans, P
Gamazon, E
Edlund, CK
Service, SK
Tikhomirov, A
Osiecki, L
Illmann, C
Pluzhnikov, A
Konkashbaev, A
Davis, LK
Han, B
Crane, J
Moorjani, P
Crenshaw, AT
Parkin, MA
Reus, VI
Lowe, TL
Rangel-Lugo, M
Chouinard, S
Dion, Y
Girard, S
Cath, DC
Smit, JH
King, RA
Fernandez, TV
Leckman, JF
Kidd, KK
Kidd, JR
Pakstis, AJ
State, MW
Herrera, LD
Romero, R
Fournier, E
Sandor, P
Barr, CL
Phan, N
Gross-Tsur, V
Benarroch, F
Pollak, Y
Budman, CL
Bruun, RD
Erenberg, G
Naarden, AL
Lee, PC
Weiss, N
Kremeyer, B
Berrio, GB
Campbell, DD
Silgado, JCC
Ochoa, WC
Restrepo, SCM
Muller, H
Duarte, AVV
Lyon, GJ
Leppert, M
Morgan, J
Weiss, R
Grados, MA
Anderson, K
Davarya, S
Singer, H
Walkup, J
Jankovic, J
Tischfield, JA
Heiman, GA
Gilbert, DL
Hoekstra, PJ
Robertson, MM
Kurlan, R
Liu, C
Gibbs, JR
Singleton, A
Hardy, J
Strengman, E
Ophoff, RA
Wagner, M
Moessner, R
Mirel, DB
Posthuma, D
Sabatti, C
Eskin, E
Conti, DV
Knowles, JA
Ruiz-Linares, A
Rouleau, GA
Purcell, S
Heutink, P
Oostra, BA
McMahon, WM
Freimer, NB
Cox, NJ
Pauls, DL
AF Scharf, J. M.
Yu, D.
Mathews, C. A.
Neale, B. M.
Stewart, S. E.
Fagerness, J. A.
Evans, P.
Gamazon, E.
Edlund, C. K.
Service, S. K.
Tikhomirov, A.
Osiecki, L.
Illmann, C.
Pluzhnikov, A.
Konkashbaev, A.
Davis, L. K.
Han, B.
Crane, J.
Moorjani, P.
Crenshaw, A. T.
Parkin, M. A.
Reus, V. I.
Lowe, T. L.
Rangel-Lugo, M.
Chouinard, S.
Dion, Y.
Girard, S.
Cath, D. C.
Smit, J. H.
King, R. A.
Fernandez, T. V.
Leckman, J. F.
Kidd, K. K.
Kidd, J. R.
Pakstis, A. J.
State, M. W.
Herrera, L. D.
Romero, R.
Fournier, E.
Sandor, P.
Barr, C. L.
Phan, N.
Gross-Tsur, V.
Benarroch, F.
Pollak, Y.
Budman, C. L.
Bruun, R. D.
Erenberg, G.
Naarden, A. L.
Lee, P. C.
Weiss, N.
Kremeyer, B.
Berrio, G. B.
Campbell, D. D.
Cardona Silgado, J. C.
Ochoa, W. C.
Mesa Restrepo, S. C.
Muller, H.
Valencia Duarte, A. V.
Lyon, G. J.
Leppert, M.
Morgan, J.
Weiss, R.
Grados, M. A.
Anderson, K.
Davarya, S.
Singer, H.
Walkup, J.
Jankovic, J.
Tischfield, J. A.
Heiman, G. A.
Gilbert, D. L.
Hoekstra, P. J.
Robertson, M. M.
Kurlan, R.
Liu, C.
Gibbs, J. R.
Singleton, A.
Hardy, J.
Strengman, E.
Ophoff, R. A.
Wagner, M.
Moessner, R.
Mirel, D. B.
Posthuma, D.
Sabatti, C.
Eskin, E.
Conti, D. V.
Knowles, J. A.
Ruiz-Linares, A.
Rouleau, G. A.
Purcell, S.
Heutink, P.
Oostra, B. A.
McMahon, W. M.
Freimer, N. B.
Cox, N. J.
Pauls, D. L.
CA North Amer Brain Expression
UK Human Brain Expression Database
TI Genome-wide association study of Tourette's syndrome
SO MOLECULAR PSYCHIATRY
LA English
DT Article
DE genetics; GWAS; neurodevelopmental disorder; tics; Tourette's syndrome
ID COPY NUMBER VARIANTS; COMMON VARIANTS; SLITRK1 VAR321; SCHIZOPHRENIA;
FAMILY; INDIVIDUALS; DEPENDENCE; MUTATIONS; DISORDER; POLR3B
AB Tourette's syndrome (TS) is a developmental disorder that has one of the highest familial recurrence rates among neuropsychiatric diseases with complex inheritance. However, the identification of definitive TS susceptibility genes remains elusive. Here, we report the first genome-wide association study (GWAS) of TS in 1285 cases and 4964 ancestry-matched controls of European ancestry, including two European-derived population isolates, Ashkenazi Jews from North America and Israel and French Canadians from Quebec, Canada. In a primary meta-analysis of GWAS data from these European ancestry samples, no markers achieved a genome-wide threshold of significance (P < 5 x 10(-8)); the top signal was found in rs7868992 on chromosome 9q32 within COL27A1 (P = 1.85 x 10(-6)). A secondary analysis including an additional 211 cases and 285 controls from two closely related Latin American population isolates from the Central Valley of Costa Rica and Antioquia, Colombia also identified rs7868992 as the top signal ( P = 3.6 x 10(-7) for the combined sample of 1496 cases and 5249 controls following imputation with 1000 Genomes data). This study lays the groundwork for the eventual identification of common TS susceptibility variants in larger cohorts and helps to provide a more complete understanding of the full genetic architecture of this disorder.
C1 [Scharf, J. M.; Yu, D.; Neale, B. M.; Stewart, S. E.; Fagerness, J. A.; Osiecki, L.; Illmann, C.; Crane, J.; Purcell, S.; Pauls, D. L.] Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA USA.
[Scharf, J. M.; Yu, D.; Neale, B. M.; Stewart, S. E.; Fagerness, J. A.; Osiecki, L.; Illmann, C.; Crane, J.; Purcell, S.; Pauls, D. L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Scharf, J. M.] Massachusetts Gen Hosp, Dept Neurol, Movement Disorders Unit, Boston, MA 02114 USA.
[Scharf, J. M.] Brigham & Womens Hosp, Div Cognit & Behav Neurol, Boston, MA 02115 USA.
[Scharf, J. M.; Neale, B. M.; Purcell, S.] Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Cambridge, MA USA.
[Mathews, C. A.; Reus, V. I.; Lowe, T. L.; Rangel-Lugo, M.; Lee, P. C.; Weiss, N.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA.
[Neale, B. M.; Moorjani, P.; Crenshaw, A. T.; Parkin, M. A.; Mirel, D. B.; Purcell, S.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA.
[Neale, B. M.; Purcell, S.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA.
[Stewart, S. E.] Univ British Columbia, British Columbia Mental Hlth & Addict Res Inst, Vancouver, BC V5Z 1M9, Canada.
[Evans, P.; Gamazon, E.; Tikhomirov, A.; Pluzhnikov, A.; Konkashbaev, A.; Davis, L. K.; Cox, N. J.] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA.
[Evans, P.; Gamazon, E.; Tikhomirov, A.; Pluzhnikov, A.; Konkashbaev, A.; Davis, L. K.; Cox, N. J.] Univ Chicago, Dept Med, Chicago, IL 60637 USA.
[Edlund, C. K.; Conti, D. V.] Univ So Calif, Dept Prevent Med, Div Biostat, Los Angeles, CA 90089 USA.
[Edlund, C. K.] Univ So Calif, Keck Sch Med, USC Epigenome Ctr, Los Angeles, CA 90033 USA.
[Service, S. K.; Strengman, E.; Ophoff, R. A.; Freimer, N. B.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Ctr Neurobehav Genet, Los Angeles, CA USA.
[Han, B.; Eskin, E.] Univ Calif Los Angeles, Dept Comp Sci, Los Angeles, CA 90024 USA.
[Moorjani, P.] Harvard Univ, Dept Genet, Cambridge, MA 02138 USA.
[Chouinard, S.; Dion, Y.; Girard, S.; Rouleau, G. A.] Univ Montreal, Montreal, PQ, Canada.
[Cath, D. C.; Smit, J. H.] Vrije Univ Amsterdam, Med Ctr, Dept Psychiat, Amsterdam, Netherlands.
[Cath, D. C.] Univ Utrecht, Dept Clin & Hlth Psychol, Utrecht, Netherlands.
[King, R. A.; Fernandez, T. V.; Leckman, J. F.] Yale Univ, Sch Med, Yale Child Study Ctr, New Haven, CT USA.
[Kidd, K. K.; Kidd, J. R.; Pakstis, A. J.; State, M. W.] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA.
[Herrera, L. D.; Romero, R.; Fournier, E.] Hosp Nacl Ninos Dr Carlos Saenz Herrera, San Jose, Costa Rica.
[Sandor, P.; Barr, C. L.; Phan, N.] Univ Hlth Network, Toronto Western Res Inst, Toronto, ON, Canada.
[Sandor, P.] Univ Toronto, Dept Psychiat, Div Child Psychiat, Toronto, ON, Canada.
[Barr, C. L.] Hosp Sick Children, Toronto, ON M5G 1X8, Canada.
[Gross-Tsur, V.; Pollak, Y.] Shaare Zedek Med Ctr, Neuropediat Unit, Jerusalem, Israel.
[Benarroch, F.] Hadassah Hebrew Univ, Med Ctr, Herman Dana Div Child & Adolescent Psychiat, Jerusalem, Israel.
[Budman, C. L.; Bruun, R. D.] North Shore Long Isl Jewish Med Ctr, Manhasset, NY USA.
[Budman, C. L.] Hofstra Univ, Sch Med, Hempstead, NY 11550 USA.
[Bruun, R. D.] NYU, Med Ctr, New York, NY 10016 USA.
[Erenberg, G.] Cleveland Clin, Cleveland, OH 44106 USA.
[Naarden, A. L.] Med City Dallas Hosp, Dept Clin Res, Dallas, TX USA.
[Kremeyer, B.; Campbell, D. D.; Muller, H.; Robertson, M. M.; Hardy, J.; Ruiz-Linares, A.] UCL, London, England.
[Kremeyer, B.] Wellcome Trust Sanger Inst, Cambridge, England.
[Berrio, G. B.; Cardona Silgado, J. C.; Ochoa, W. C.; Mesa Restrepo, S. C.; Valencia Duarte, A. V.] Univ Antioquia, Medellin, Colombia.
[Campbell, D. D.] Univ Hong Kong, Dept Psychiat, Hong Kong, Hong Kong, Peoples R China.
[Campbell, D. D.] Univ Hong Kong, Ctr Genom Sci, Hong Kong, Hong Kong, Peoples R China.
[Valencia Duarte, A. V.] Univ Pontificia Bolivariana, Medellin, Colombia.
[Lyon, G. J.; Leppert, M.; Morgan, J.; Weiss, R.; McMahon, W. M.] Univ Utah, Salt Lake City, UT USA.
[Lyon, G. J.] Cold Spring Harbor Lab, Stanley Inst Cognit Genom, Cold Spring Harbor, NY 11724 USA.
[Grados, M. A.; Anderson, K.; Davarya, S.; Singer, H.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Walkup, J.] Weill Cornell Med Ctr, Dept Psychiat, Div Child & Adolescent Psychiat, New York, NY USA.
[Jankovic, J.] Baylor Coll Med, Dept Neurol, Parkinsons Dis Ctr, Houston, TX 77030 USA.
[Jankovic, J.] Baylor Coll Med, Dept Neurol, Movement Disorders Clin, Houston, TX 77030 USA.
[Tischfield, J. A.; Heiman, G. A.] Rutgers State Univ, Dept Genet, Piscataway, NJ USA.
[Tischfield, J. A.; Heiman, G. A.] Rutgers State Univ, Human Genet Inst New Jersey, Piscataway, NJ USA.
[Gilbert, D. L.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA.
[Gilbert, D. L.] Univ Cincinnati, Cincinnati, OH USA.
[Hoekstra, P. J.] Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, Groningen, Netherlands.
[Robertson, M. M.] St Georges Hosp & Med Sch, London, England.
[Kurlan, R.] Overlook Hosp, Atlantic Neurosci Inst, Summit, NJ USA.
[Liu, C.] Univ Illinois, Dept Psychiat, Chicago, IL 60612 USA.
[Gibbs, J. R.; Singleton, A.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Strengman, E.; Ophoff, R. A.] Univ Med Ctr, Rudolf Magnus Inst Neurosci, Dept Psychiat, Utrecht, Netherlands.
[Wagner, M.; Moessner, R.] Univ Bonn, Dept Psychiat & Psychotherapy, Bonn, Germany.
[Posthuma, D.] Vrije Univ Amsterdam, Ctr Neurogen & Cognit Res, Dept Funct Genom, Amsterdam, Netherlands.
[Posthuma, D.; Heutink, P.] Vrije Univ Amsterdam Med Ctr, Dept Clin Genet, Sect Med Genom, Amsterdam, Netherlands.
[Posthuma, D.] Erasmus Univ, Sophia Childrens Hosp, Med Ctr, Dept Child & Adolescent Psychiat Psychol, Rotterdam, Netherlands.
[Sabatti, C.] Stanford Univ, Dept Hlth Res & Policy, Stanford, CA 94305 USA.
[Eskin, E.] Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA USA.
[Knowles, J. A.] Univ So Calif, Keck Sch Med, Zilkha Neurogenet Inst, Dept Psychiat & Behav Sci, Los Angeles, CA 90033 USA.
[Purcell, S.] Mt Sinai Sch Med, Div Psychiat Genom, New York, NY USA.
[Oostra, B. A.] Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands.
RP Pauls, DL (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA.
EM jscharf@partners.org; dpauls@pngu.mgh.harvard.edu
RI Hoekstra, Pieter/O-4396-2014; reus, victor/I-7923-2015; Gilbert,
Donald/D-6443-2016; Wagner, Michael/E-2325-2011; Trabzuni,
Daniah/C-4034-2012; Hardy, John/C-2451-2009; Traynor, Bryan/G-5690-2010;
Lyon, Gholson/D-2765-2014; Singleton, Andrew/C-3010-2009; Weale,
Michael/F-2587-2010; Stewart, Evelyn/K-6961-2014
OI Fernandez, Thomas V/0000-0003-0830-022X; Tischfield,
Jay/0000-0003-3217-8287; Gamazon, Eric/0000-0003-4204-8734; Stewart, S.
Evelyn/0000-0002-0994-6383; reus, victor/0000-0002-8193-5697; Gilbert,
Donald/0000-0002-9245-6878; Wagner, Michael/0000-0003-2589-6440;
Trabzuni, Daniah/0000-0003-4826-9570; Campbell,
Desmond/0000-0003-1085-714X; Barr, Cathy/0000-0003-0361-0106; Lyon,
Gholson/0000-0002-5869-0716; Weale, Michael/0000-0003-4593-1186;
FU NIH; Tourette Syndrome Association (TSA); Psyadon; Shire; Solway; UCB
Pharma; Janssen; Eli Lilly; Pfizer; Prestwick; Psyadon Pharmaceuticals;
Otsuka Pharmaceuticals; NINDS; TSA; Talecris Biotherapeutics;
Klingenstein Third Generation Foundation; John Wiley and Sons; McGraw
Hill; Oxford University Press; Allergan; Allon Therapeutics; Ceregene;
Chelsea Therapeutics; Diana Helis Henry Medical Research Foundation; EMD
Serono; Huntington's Disease Society of America; Huntington Study Group;
Impax Pharmaceuticals; Ipsen Limited; Lundbeck; Medtronic; Merz
Pharmaceuticals; Michael J Fox Foundation for Parkinson Research;
National Institutes of Health; National Parkinson Foundation; Neurogen;
St Jude Medical; Teva Pharmaceutical Industries; University of
Rochester; Parkinson Study Group; Tourette Syndrome Association; Judah
Foundation; NIH [NS40024, NS16648, NS037484, NS043538, MH079489,
MH085057]; Tourette Syndrome Association International Consortium for
Genetics; American Recovery and Re-investment Act (ARRA) [NS40024-07S1,
NS16648-29S1]; American Academy of Neurology Foundation Grant; National
Center for Research Resources [U54 RR020278]; New Jersey Center for
Tourette Syndrome & Associated Disorders (through New Jersey Department
of Health and Senior Services) [08-1827-FS-N-0, P01MH049351,
R01MH061940, K05MH076273, T32MH018268]; UK Medical Research Council;
Intramural Research Program of the National Institute on Aging, National
Institutes of Health, Department of Health and Human Services project
[Z01 AG000932-02]; NIH Genes, Environment and Health Initiative [GEI]
[U01 HG004422]; NIH GEI [U01HG004438]; National Institute on Alcohol
Abuse and Alcoholism; National Institute on Drug Abuse; NIH contract
[HHSN268200782096C]; NIMH; Guilford Press; Oxford Press
FX Drs Pauls, Scharf, Mathews, Cox, Freimer, McMahon, Heutink, Oostra,
Grados, King, Rouleau, Sandor and Budman have all received research
support from the NIH and the Tourette Syndrome Association (TSA) on
behalf of the TSA International Consortium for Genetics (TSAICG). Drs
Scharf, Mathews and Grados have received honoraria and travel support
from the TSA. Dr Mathews is a member of the TSA Medical Advisory Board.
Dr Sandor has received support and consulting fees from Psyadon, Shire,
Solway, UCB Pharma, Janssen, Eli Lilly, Pfizer and Prestwick. Dr Budman
has been funded by Psyadon Pharmaceuticals, Otsuka Pharmaceuticals and
NINDS and is a member of the National TSA Medical Advisory Board, LI TSA
and LI CHADD Medical Advisory Boards. Dr Hoekstra has received honoraria
for advice through Desitin, Eli Lilly and Shire. Dr Dion has received
honoraria from Biovail Pharma, Pfizer and Eli Lilly. Dr Leckman has been
funded by the NIH, the TSA, Talecris Biotherapeutics, Klingenstein Third
Generation Foundation, John Wiley and Sons, McGraw Hill and Oxford
University Press. Dr Walkup receives research support, travel support
for paid and unpaid activities, serves in an unpaid position on the
Medical Advisory Board and receives an honorarium for an Educational
Meeting from the TSA. He receives royalties from Guilford Press and
Oxford Press. He received free medication and placebo from Lilly, Pfizer
and Abbott for NIH-funded studies. Dr Jankovic has received research
grants from the following: Allergan, Allon Therapeutics, Ceregene,
Chelsea Therapeutics, Diana Helis Henry Medical Research Foundation, EMD
Serono, Huntington's Disease Society of America, Huntington Study Group,
Impax Pharmaceuticals, Ipsen Limited, Lundbeck, Medtronic, Merz
Pharmaceuticals, Michael J Fox Foundation for Parkinson Research,
National Institutes of Health, National Parkinson Foundation, Neurogen,
St Jude Medical, Teva Pharmaceutical Industries, University of Rochester
and Parkinson Study Group. He has served as a consultant or advisory
committee member for Allergan, Chelsea Therapeutics, EMD Serono,
Lundbeck, Merz Pharmaceuticals, Michael J Fox Foundation for Parkinson
Research and Teva Pharmaceutical Industries. He also serves on the
editorial boards for Elsevier, Medlink: Neurology, Neurology in Clinical
Practice, Neurotoxin Institute, Scientiae and UpToDate. Dr Knowles is on
the Scientific Advisory Committee for Next-Generation Sequencing of Life
Technologies, and is a technical advisor to SoftGenetics. Ms Anderson,
Dr Barr, Dr Benarroch, Mr Berrio, Dr Bruun, Mr Campbell, Dr Cath, Dr
Chouinard, Dr Conti, Ms Crane, Mr Crenshaw, Ms Davarya, Dr Davis, Ms
Duarte, Mr Edlund, Dr Erenberg, Dr Eskin, Dr Evans, Mr Fagerness, Dr
Fernandez, Mr Fournier, Mr Gamazon, Mr Gibbs, Dr Gilbert, Dr Girard, Dr
Gross-Tsur, Dr Han, Dr Hardy, Dr Heiman, Dr Herrera, Dr Heutink, Dr
Illmann, Dr J Kidd, Dr K Kidd, Mr. Konkashbaev, Dr Kremeyer, Dr Kurlan,
Dr Lee, Dr Leppert, Dr Liu, Dr Lowe, Dr Lyon, Dr Mirel, Dr Moessner, Ms
Moorjani, Mr Morgan, Mr Muller, Dr Naarden, Dr Neale, Dr Ochoa, Dr
Ophoff, Ms Osiecki, Dr Pakstis, Ms Parkin, Mr Phan, Dr Pluzhnikov, Dr
Pollak, Dr Posthuma, Dr Purcell, Dr Rangel-Lugo, Dr Restrepo, Dr Reus,
Ms Rivas, Dr Robertson, Ms Romero, Dr Ruiz-Linares, Dr Sabatti, Ms
Service, Mr Silgado, Dr Singer, Dr Singleton, Dr Smit, Dr State, Dr
Stewart, Mr. Strengman, Dr Tikhomirov, Dr Tischfield, Dr Wagner, Dr N
Weiss, Dr R Weiss and Ms Yu declare no conflict of interest.; We are
grateful to all the patients with Tourette's syndrome who generously
agreed to participate in this study. Furthermore, the members of the
Tourette Syndrome Association International Consortium for Genetics are
deeply indebted to the Tourette Syndrome Association for their guidance
and support. We also thank Libby Bernier and Janelle Alabiso for their
assistance in manuscript preparation and Stephan Ripke for help with
meta-analysis figures. This work was supported by a grant from the Judah
Foundation, NIH Grants NS40024 to DLP and the Tourette Syndrome
Association International Consortium for Genetics, NIH Grant NS16648 and
a grant from the Tourette Syndrome Association to DLP, NIH Grant
NS037484 to NBF, NIH Grant NS043538 to AR-L, American Recovery and
Re-investment Act (ARRA) awards NS40024-07S1 and NS16648-29S1 to DLP,
NIH Grant MH079489, and an American Academy of Neurology Foundation
Grant and NIH Grant MH085057 to JMS. The Broad Institute Center for
Genotyping and Analysis was supported by Grant U54 RR020278 from the
National Center for Research Resources. Support was also provided by the
New Jersey Center for Tourette Syndrome & Associated Disorders (through
New Jersey Department of Health and Senior Services: 08-1827-FS-N-0) to
GAH and JAT and P01MH049351, R01MH061940, K05MH076273 and T32MH018268 to
JFL. Funding support for generation of the eQTL data was provided by the
UK Medical Research Council and the Intramural Research Program of the
National Institute on Aging, National Institutes of Health, Department
of Health and Human Services project Z01 AG000932-02. Funding support
for the Study of Addiction: Genetics and Environment (SAGE) was provided
through the NIH Genes, Environment and Health Initiative [GEI] (U01
HG004422). SAGE is one of the genome-wide association studies funded as
part of the Gene Environment Association Studies (GENEVA) under GEI.
Assistance with phenotype harmonization and genotype cleaning, as well
as with general study coordination, was provided by the GENEVA
Coordinating Center (U01 HG004446). Assistance with data cleaning was
provided by the National Center for Biotechnology Information. Support
for collection of data sets and samples was provided by the
Collaborative Study on the Genetics of Alcoholism (COGA; U10 AA008401),
the Collaborative Genetic Study of Nicotine Dependence (COGEND; P01
CA089392) and the Family Study of Cocaine Dependence (FSCD; R01
DA013423). Funding support for genotyping, which was performed at the
Johns Hopkins University Center for Inherited Disease Research, was
provided by the NIH GEI (U01HG004438), the National Institute on Alcohol
Abuse and Alcoholism, the National Institute on Drug Abuse and the NIH
contract 'High throughput genotyping for studying the genetic
contributions to human disease' (HHSN268200782096C). The data sets used
for the analyses described in this manuscript were obtained from dbGaP
at
http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs0
00092.v1.p1 through dbGaP accession number phs000092.v1.p. None of the
funding agencies for this project (NINDS, NIMH, the Tourette Syndrome
Association and the Judah Foundation) had any influence or played any
role in (1) the design or conduct of the study; (2) management, analysis
or interpretation of the data; and (3) preparation, review or approval
of the manuscript.
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PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1359-4184
J9 MOL PSYCHIATR
JI Mol. Psychiatr.
PD JUN
PY 2013
VL 18
IS 6
BP 721
EP 728
DI 10.1038/mp.2012.69
PG 8
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA 151HP
UT WOS:000319451600015
PM 22889924
ER
PT J
AU Hett, EC
Slater, LH
Mark, KG
Kawate, T
Monks, BG
Stutz, A
Latz, E
Hung, DT
AF Hett, Erik C.
Slater, Louise H.
Mark, Kevin G.
Kawate, Tomohiko
Monks, Brian G.
Stutz, Andrea
Latz, Eicke
Hung, Deborah T.
TI Chemical genetics reveals a kinase-independent role for protein kinase R
in pyroptosis
SO NATURE CHEMICAL BIOLOGY
LA English
DT Article
ID ANTHRAX LETHAL TOXIN; NF-KAPPA-B; INFLAMMASOME ACTIVATION; MACROPHAGE
APOPTOSIS; MURINE MACROPHAGES; NLRP3 EXPRESSION; IKK COMPLEX; PKR; MAP;
SUSCEPTIBILITY
AB Formation of the inflammasome, a scaffolding complex that activates caspase-1, is important in numerous diseases. Pyroptotic cell death induced by anthrax lethal toxin (LT) is a model for inflammasome-mediated caspase-1 activation. We discovered 7-desacetoxy-6,7-dehydrogedunin (7DG) in a phenotypic screen as a small molecule that protects macrophages from LT-induced death. Using chemical proteomics, we identified protein kinase R (PKR) as the target of 7DG and show that RNAi knockdown of PKR phenocopies treatment with 7DG. Further, we show that PKR's role in ASC assembly and caspase-1 activation induced by several different inflammasome stimuli is independent of PKR's kinase activity, demonstrating that PKR has a previously uncharacterized role in caspase-1 activation and pyroptosis that is distinct from its reported kinase-dependent roles in apoptosis and inflammasome formation in lipopolysaccharide-primed cells. Remarkably, PKR has different roles in two distinct cell death pathways and has a broad role in inflammasome function relevant in other diseases.
C1 [Hett, Erik C.; Slater, Louise H.; Mark, Kevin G.; Kawate, Tomohiko; Hung, Deborah T.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
[Hett, Erik C.; Slater, Louise H.; Mark, Kevin G.; Kawate, Tomohiko; Hung, Deborah T.] Broad Inst MIT & Harvard, Cambridge, MA USA.
[Hett, Erik C.; Slater, Louise H.; Mark, Kevin G.; Kawate, Tomohiko; Hung, Deborah T.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA.
[Hett, Erik C.; Slater, Louise H.; Mark, Kevin G.; Kawate, Tomohiko; Hung, Deborah T.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA.
[Monks, Brian G.; Latz, Eicke] Univ Massachusetts, Sch Med, Dept Immunol & Infect Dis, Worcester, MA USA.
[Monks, Brian G.; Stutz, Andrea; Latz, Eicke] Univ Bonn, Inst Innate Immun, Bonn, Germany.
[Latz, Eicke] German Ctr Neurodegenerat Dis DZNE, Bonn, Germany.
RP Hett, EC (reprint author), Pfizer, Worldwide Med Chem, Chem Biol Grp, Cambridge, MA USA.
EM hett@molbio.mgh.harvard.edu; hung@molbio.mgh.harvard.edu
RI Monks, Brian/B-8362-2015; Latz, Eicke/H-3951-2014
OI Monks, Brian/0000-0003-4008-3093; Latz, Eicke/0000-0003-1488-5666
FU US National Institutes of Health (NIH) National Research Service Award
fellowship [F32AI084323]; NIH [U54 AI057159]
FX E.C.H. was funded by an US National Institutes of Health (NIH) National
Research Service Award fellowship F32AI084323. This work was supported
in part by NIH U54 AI057159 to D.T.H.).
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J9 NAT CHEM BIOL
JI Nat. Chem. Biol.
PD JUN
PY 2013
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EP +
DI 10.1038/NCHEMBIO.1236
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 149NS
UT WOS:000319328200012
PM 23603659
ER
PT J
AU Sokolovska, A
Becker, CE
Ip, WKE
Rathinam, VAK
Brudner, M
Paquette, N
Tanne, A
Vanaja, SK
Moore, KJ
Fitzgerald, KA
Lacy-Hulbert, A
Stuart, LM
AF Sokolovska, Anna
Becker, Christine E.
Ip, W. K. Eddie
Rathinam, Vijay A. K.
Brudner, Matthew
Paquette, Nicholas
Tanne, Antoine
Vanaja, Sivapriya K.
Moore, Kathryn J.
Fitzgerald, Katherine A.
Lacy-Hulbert, Adam
Stuart, Lynda M.
TI Activation of caspase-1 by the NLRP3 inflammasome regulates the NADPH
oxidase NOX2 to control phagosome function
SO NATURE IMMUNOLOGY
LA English
DT Article
ID TOLL-LIKE RECEPTOR; INNATE IMMUNE-SYSTEM; H+-ATPASE ACTIVITY;
PROTEOLYTIC CLEAVAGE; STAPHYLOCOCCUS-AUREUS; NALP3 INFLAMMASOME;
BACTERIAL LIGANDS; DENDRITIC CELLS; MATURATION; ACIDIFICATION
AB Phagocytosis is a fundamental cellular process that is pivotal for immunity as it coordinates microbial killing, innate immune activation and antigen presentation. An essential step in this process is phagosome acidification, which regulates many functions of these organelles that allow phagosomes to participate in processes that are essential to both innate and adaptive immunity. Here we report that acidification of phagosomes containing Gram-positive bacteria is regulated by the NLRP3 inflammasome and caspase-1. Active caspase-1 accumulates on phagosomes and acts locally to control the pH by modulating buffering by the NADPH oxidase NOX2. These data provide insight into a mechanism by which innate immune signals can modify cellular defenses and establish a new function for the NLRP3 inflammasome and caspase-1 in host defense.
C1 [Sokolovska, Anna; Becker, Christine E.; Ip, W. K. Eddie; Brudner, Matthew; Paquette, Nicholas; Tanne, Antoine; Lacy-Hulbert, Adam; Stuart, Lynda M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Sokolovska, Anna; Becker, Christine E.; Ip, W. K. Eddie; Brudner, Matthew; Paquette, Nicholas; Tanne, Antoine; Lacy-Hulbert, Adam; Stuart, Lynda M.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA.
[Sokolovska, Anna; Becker, Christine E.; Ip, W. K. Eddie; Brudner, Matthew; Paquette, Nicholas; Tanne, Antoine; Lacy-Hulbert, Adam; Stuart, Lynda M.] Harvard Univ, Sch Med, Boston, MA USA.
[Rathinam, Vijay A. K.; Vanaja, Sivapriya K.; Fitzgerald, Katherine A.] Univ Massachusetts, Sch Med, Dept Med, Div Infect Dis & Immunol, Worcester, MA USA.
[Moore, Kathryn J.] NYU, Med Ctr, Dept Med, New York, NY 10016 USA.
[Moore, Kathryn J.] NYU, Med Ctr, Dept Cell Biol, New York, NY 10016 USA.
[Stuart, Lynda M.] Broad Inst Harvard & MIT, Cambridge, MA USA.
RP Stuart, LM (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.
EM asokolovska@partners.org; lstuart@partners.org
OI Lacy-Hulbert, Adam/0000-0003-2162-0156; Moore,
kathryn/0000-0003-2505-2547
FU US National Institutes of Health; National Institute of Allergy and
Infectious Diseases [RO1 AI079198, RO1 AI093752]; National Institutes of
Health National Institute on Aging [RO1 AG020255]; Crohns' and Colitis
and Hood foundations; National Institutes of Health National Institute
of Diabetes and Digestive and Kidney Diseases [RO1 DK093695];
Massachusetts General Hospital Executive Committee on Research; New
England Regional Center of Excellence-Biodefense and Emerging Infectious
Diseases [U54 AI057159]
FX This work was funded by grants from US National Institutes of Health
National Institute of Allergy and Infectious Diseases to L.M.S. (RO1
AI079198) and K.A.F. (RO1 AI093752), National Institutes of Health
National Institute on Aging to K.J.M. (RO1 AG020255), grants from the
Crohns' and Colitis and Hood foundations and National Institutes of
Health National Institute of Diabetes and Digestive and Kidney Diseases
to A.L.-H. (RO1 DK093695), and postdoctoral fellowships from
Massachusetts General Hospital Executive Committee on Research to A.S.
and New England Regional Center of Excellence-Biodefense and Emerging
Infectious Diseases (U54 AI057159 to N.P.). Electron microscopy was
performed by M. McKee in the Microscopy Core of the Center for Systems
Biology.
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SN 1529-2908
J9 NAT IMMUNOL
JI Nat. Immunol.
PD JUN
PY 2013
VL 14
IS 6
BP 543
EP +
DI 10.1038/ni.2595
PG 13
WC Immunology
SC Immunology
GA 146RG
UT WOS:000319107600007
PM 23644505
ER
PT J
AU Mingueneau, M
Kreslavsky, T
Gray, D
Heng, T
Cruse, R
Ericson, J
Bendall, S
Spitzer, M
Nolan, G
Kobayashi, K
von Boehmer, H
Mathis, D
Benoist, C
Best, AJ
Knell, J
Goldrath, A
Jojic, V
Koller, D
Shay, T
Regev, A
Cohen, N
Brennan, P
Brenner, M
Kim, F
Rao, TN
Wagers, A
Heng, T
Ericson, J
Rothamel, K
Ortiz-Lopez, A
Mathis, D
Bezman, NA
Sun, JC
Min-Oo, G
Kim, CC
Lanier, LL
Miller, J
Brown, B
Merad, M
Gautier, EL
Jakubzick, C
Randolph, GJ
Monach, P
Blair, DA
Dustin, ML
Shinton, SA
Hardy, RR
Laidlaw, D
Collins, J
Gazit, R
Rossi, DJ
Malhotra, N
Sylvia, K
Kang, J
Kreslavsky, T
Fletcher, A
Elpek, K
Bellemare-Pelletier, A
Malhotra, D
Turley, S
AF Mingueneau, Michael
Kreslavsky, Taras
Gray, Daniel
Heng, Tracy
Cruse, Richard
Ericson, Jeffrey
Bendall, Sean
Spitzer, Matt
Nolan, Garry
Kobayashi, Koichi
von Boehmer, Harald
Mathis, Diane
Benoist, Christophe
Best, Adam J.
Knell, Jamie
Goldrath, Ananda
Jojic, Vladimir
Koller, Daphne
Shay, Tal
Regev, Aviv
Cohen, Nadia
Brennan, Patrick
Brenner, Michael
Kim, Francis
Rao, Tata Nageswara
Wagers, Amy
Heng, Tracy
Ericson, Jeffrey
Rothamel, Katherine
Ortiz-Lopez, Adriana
Mathis, Diane
Bezman, Natalie A.
Sun, Joseph C.
Min-Oo, Gundula
Kim, Charlie C.
Lanier, Lewis L.
Miller, Jennifer
Brown, Brian
Merad, Miriam
Gautier, Emmanuel L.
Jakubzick, Claudia
Randolph, Gwendalyn J.
Monach, Paul
Blair, David A.
Dustin, Michael L.
Shinton, Susan A.
Hardy, Richard R.
Laidlaw, David
Collins, Jim
Gazit, Roi
Rossi, Derrick J.
Malhotra, Nidhi
Sylvia, Katelyn
Kang, Joonsoo
Kreslavsky, Taras
Fletcher, Anne
Elpek, Kutlu
Bellemare-Pelletier, Angelique
Malhotra, Deepali
Turley, Shannon
CA Immunological Genome Consortium
TI The transcriptional landscape of alpha beta T cell differentiation
SO NATURE IMMUNOLOGY
LA English
DT Article
ID SELECTION IN-VIVO; GENE-EXPRESSION ANALYSIS; NEGATIVE SELECTION;
POSITIVE SELECTION; PRE-TCR; C-MYC; CLONAL DELETION; LYMPHOCYTE
DEVELOPMENT; INDUCED PROLIFERATION; THYMOCYTE SELECTION
AB The differentiation of abT cells from thymic precursors is a complex process essential for adaptive immunity. Here we exploited the breadth of expression data sets from the Immunological Genome Project to analyze how the differentiation of thymic precursors gives rise to mature T cell transcriptomes. We found that early T cell commitment was driven by unexpectedly gradual changes. In contrast, transit through the CD4(+)CD8(+) stage involved a global shutdown of housekeeping genes that is rare among cells of the immune system and correlated tightly with expression of the transcription factor c-Myc. Selection driven by major histocompatibility complex (MHC) molecules promoted a large-scale transcriptional reactivation. We identified distinct signatures that marked cells destined for positive selection versus apoptotic deletion. Differences in the expression of unexpectedly few genes accompanied commitment to the CD4(+) or CD8(+) lineage, a similarity that carried through to peripheral T cells and their activation, demonstrated by mass cytometry phosphoproteomics. The transcripts newly identified as encoding candidate mediators of key transitions help define the 'known unknowns' of thymocyte differentiation.
C1 [Mingueneau, Michael; Cruse, Richard; Ericson, Jeffrey; Mathis, Diane; Benoist, Christophe; Heng, Tracy; Ericson, Jeffrey; Rothamel, Katherine; Ortiz-Lopez, Adriana; Mathis, Diane] Harvard Univ, Sch Med, Dept Microbiol & Immunol, Div Immunol, Boston, MA 02115 USA.
[Kreslavsky, Taras; Kobayashi, Koichi; von Boehmer, Harald; Kreslavsky, Taras; Fletcher, Anne; Elpek, Kutlu; Bellemare-Pelletier, Angelique; Malhotra, Deepali; Turley, Shannon] Dana Farber Canc Inst, Boston, MA USA.
[Gray, Daniel] Univ Melbourne, Dept Med Biol, Parkville, Vic 3052, Australia.
[Gray, Daniel] Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Mol Genet Canc Div, Parkville, Vic 3050, Australia.
[Gray, Daniel] Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Div Immunol, Parkville, Vic 3050, Australia.
[Heng, Tracy] Monash Univ, Dept Anat & Dev Biol, Clayton, Vic, Australia.
[Bendall, Sean; Spitzer, Matt; Nolan, Garry] Stanford Univ, Sch Med, Dept Microbiol & Immunol, Palo Alto, CA 94304 USA.
[Kobayashi, Koichi] Texas A&M Hlth Sci Ctr, Dept Microbial & Mol Pathogenesis, College Stn, TX USA.
[Best, Adam J.; Knell, Jamie; Goldrath, Ananda] Univ Calif San Diego, Div Biol Sci, La Jolla, CA 92093 USA.
[Jojic, Vladimir; Koller, Daphne] Stanford Univ, Dept Comp Sci, Stanford, CA 94305 USA.
[Shay, Tal; Regev, Aviv] MIT, Broad Inst, Cambridge, MA 02139 USA.
[Shay, Tal; Regev, Aviv] MIT, Dept Biol, Cambridge, MA USA.
[Cohen, Nadia; Brennan, Patrick; Brenner, Michael] Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA.
[Kim, Francis; Rao, Tata Nageswara; Wagers, Amy] Joslin Diabet Ctr, Boston, MA 02215 USA.
[Bezman, Natalie A.; Sun, Joseph C.; Min-Oo, Gundula; Kim, Charlie C.; Lanier, Lewis L.] Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA.
[Miller, Jennifer; Brown, Brian; Merad, Miriam; Gautier, Emmanuel L.; Jakubzick, Claudia; Randolph, Gwendalyn J.] Mt Sinai Hosp, Icahn Med Inst, New York, NY 10029 USA.
[Gautier, Emmanuel L.; Randolph, Gwendalyn J.] Washington Univ, Dept Pathol & Immunol, St Louis, MO USA.
[Monach, Paul] Boston Univ, Dept Med, Boston, MA 02215 USA.
[Blair, David A.; Dustin, Michael L.] NYU, Sch Med, Skirball Inst Biomol Med, New York, NY USA.
[Shinton, Susan A.; Hardy, Richard R.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
[Laidlaw, David] Brown Univ, Dept Comp Sci, Providence, RI 02912 USA.
[Collins, Jim] Boston Univ, Howard Hughes Med Inst, Dept Biomed Engn, Boston, MA 02215 USA.
[Gazit, Roi; Rossi, Derrick J.] Childrens Hosp, Program Mol Med, Boston, MA 02115 USA.
[Malhotra, Nidhi; Sylvia, Katelyn; Kang, Joonsoo] Univ Massachusetts, Sch Med, Dept Pathol, Worcester, MA 01605 USA.
[Kreslavsky, Taras; Fletcher, Anne; Elpek, Kutlu; Bellemare-Pelletier, Angelique; Malhotra, Deepali; Turley, Shannon] Harvard Univ, Sch Med, Boston, MA USA.
RP Benoist, C (reprint author), Harvard Univ, Sch Med, Dept Microbiol & Immunol, Div Immunol, Boston, MA 02115 USA.
EM cbdm@hms.harvard.edu; cbdm@hms.harvard.edu
RI Gray, Daniel/A-3293-2013; Gautier, Emmanuel L./E-2259-2017;
OI Gray, Daniel/0000-0002-8457-8242; Gautier, Emmanuel
L./0000-0003-2976-7566; Malhotra, Deepali/0000-0002-8215-7639; Dustin,
Michael/0000-0003-4983-6389; Miller, Jennifer/0000-0002-3591-369X
FU US National Institutes of Health [AI072073]; Human Frontier Science
Program [HFSP-LT000096]; National Health and Medical Research Council
[637353]; Australian Research Council [LP110201169]
FX We thank K. Hattori, A. Ortiz-Lopez and N. Asinovski for technical
assistance with mice and antibodies; J. Moore and A. Kressler for flow
cytometry; and C. Laplace for assistance with figure preparation.
Supported by the US National Institutes of Health (AI072073), the Human
Frontier Science Program (HFSP-LT000096 to M. M.), the National Health
and Medical Research Council (637353 to D.G.) and the Australian
Research Council (LP110201169 to, T.H.).
NR 92
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U1 0
U2 41
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 JUN
PY 2013
VL 14
IS 6
BP 619
EP +
DI 10.1038/ni.2590
PG 16
WC Immunology
SC Immunology
GA 146RG
UT WOS:000319107600015
PM 23644507
ER
PT J
AU Kargi, AY
Merriam, GR
AF Kargi, Atil Y.
Merriam, George R.
TI Diagnosis and treatment of growth hormone deficiency in adults
SO NATURE REVIEWS ENDOCRINOLOGY
LA English
DT Article
ID QUALITY-OF-LIFE; TRAUMATIC BRAIN-INJURY; GH REPLACEMENT THERAPY;
BONE-MINERAL DENSITY; INTIMA-MEDIA THICKNESS; CARDIOVASCULAR RISK
MARKERS; PLACEBO-CONTROLLED TRIAL; INSULIN TOLERANCE-TEST; LONG-TERM
MORTALITY; BODY-MASS INDEX
AB The availability of synthetic recombinant human growth hormone (GH) in potentially unlimited quantities since the 1980s has improved understanding of the many nonstatural effects of GH on metabolism, body composition, physical and psychological function, as well as the consequences of GH deficiency in adult life. Adult GH deficiency is now recognized as a distinct if nonspecific syndrome with considerable adverse health consequences. GH replacement therapy in lower doses than those used in children can reverse many of these abnormalities and restore functional capacities toward or even to normal; if dosed appropriately, GH therapy has few adverse effects. Although some doubts remain about possible long-term risks of childhood GH therapy, most registries of adult GH replacement therapy, albeit limited in study size and duration, have not shown an increased incidence of cancers or of cardiovascular morbidity or mortality.
C1 [Kargi, Atil Y.] Univ Miami, Miller Sch Med, Div Endocrinol Diabet & Metab, Miami, FL 33136 USA.
[Merriam, George R.] Vet Affairs Puget Sound Hlth Care Syst, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA.
[Merriam, George R.] Univ Washington, Sch Med, Seattle, WA 98195 USA.
RP Merriam, GR (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Div Metab Endocrinol & Nutr, Box 356426, Seattle, WA 98195 USA.
EM merriam@uw.edu
FU National Institute of Aging, US National Institutes of Health
FX The authors thank P. Asberry, S. Brickle, M. Kletke and L. Smith for
their assistance with the work of the research group. The authors
gratefully acknowledge research support from the National Institute of
Aging, US National Institutes of Health, and from the facilities and
resources of the US Department of Veterans Affairs Puget Sound Health
Care System.
NR 136
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U1 0
U2 9
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1759-5029
EI 1759-5037
J9 NAT REV ENDOCRINOL
JI Nat. Rev. Endocrinol.
PD JUN
PY 2013
VL 9
IS 6
BP 335
EP 345
DI 10.1038/nrendo.2013.77
PG 11
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 149QK
UT WOS:000319335900007
PM 23629539
ER
PT J
AU Cahan, P
Daley, GQ
AF Cahan, Patrick
Daley, George Q.
TI Origins and implications of pluripotent stem cell variability and
heterogeneity
SO NATURE REVIEWS MOLECULAR CELL BIOLOGY
LA English
DT Review
ID GENE-EXPRESSION SIGNATURES; TRANSCRIPTIONAL REGULATORY CIRCUITRY; HUMAN
SOMATIC-CELLS; MOUSE ES CELLS; SELF-RENEWAL; COPY NUMBER; REGENERATIVE
MEDICINE; MOLECULAR SIGNATURE; IPS CELLS; DIFFERENTIATION PROPENSITY
AB Pluripotent stem cells constitute a platform to model disease and developmental processes and can potentially be used in regenerative medicine. However, not all pluripotent cell lines are equal in their capacity to differentiate into desired cell types in vitro.
Genetic and epigenetic variations contribute to functional variability between cell lines and heterogeneity within clones. These genetic and epigenetic variations could 'lock' the pluripotency network resulting in residual pluripotent cells or alter the signalling response of developmental pathways leading to lineage bias. The molecular contributors to functional variability and heterogeneity in both embryonic stem (ES) cells and induced pluripotent stem (iPS) cells are only beginning to emerge, yet they are crucial to the future of the stem cell field.
C1 [Daley, George Q.] Childrens Hosp, Howard Hughes Med Inst, Stem Cell Transplantat Program, Div Pediat Hematol & Oncol,Manton Ctr Orphan Dis, Boston, MA 02115 USA.
Harvard Univ, Dana Farber Canc Inst, Harvard Stem Cell Inst, Dept Biol Chem & Mol Pharmacol,Med Sch, Boston, MA 02115 USA.
RP Daley, GQ (reprint author), Childrens Hosp, Howard Hughes Med Inst, Stem Cell Transplantat Program, Div Pediat Hematol & Oncol,Manton Ctr Orphan Dis, Boston, MA 02115 USA.
EM george.daley@childrens.harvard.edu
OI Cahan, Patrick/0000-0003-3652-2540
FU US National Institutes of Health (NIH) [UO 1-HL100001, R24-DK092760,
P50HG005550, RC2-HL102815, RC4DK 090913]; Roche Foundation for Anemia
Research; Alex's Lemonade Stand Foundation; Doris Duke Charitable
Foundation; Ellison Medical Foundation; National Heart, Lung, and Blood
Institute (NHLBI) [T32HL007623, 2T32HL66987-11]
FX G.Q.D. is supported by grants from the US National Institutes of Health
(NIH) (UO 1-HL100001 Progenitor cell biology consortium, R24-DK092760,
P50HG005550 and special funds from the ARRA stimulus package-
RC2-HL102815, RC4DK 090913), the Roche Foundation for Anemia Research,
Alex's Lemonade Stand Foundation, Doris Duke Charitable Foundation and
the Ellison Medical Foundation. G.Q.D. is an affiliate member of the
Broad Institute and an investigator of the Manton Center for Orphan
Disease Research and the Howard Hughes Medical Institute. P.C. is
supported by grants T32HL007623 and 2T32HL66987-11 from the National
Heart, Lung, and Blood Institute (NHLBI). The authors would like to
thank R. Zhao and A. De Los Angeles for helpful discussions.
NR 116
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U1 5
U2 88
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1471-0072
J9 NAT REV MOL CELL BIO
JI Nat. Rev. Mol. Cell Biol.
PD JUN
PY 2013
VL 14
IS 6
BP 357
EP 368
DI 10.1038/nrm3584
PG 12
WC Cell Biology
SC Cell Biology
GA 151LO
UT WOS:000319462200012
PM 23673969
ER
PT J
AU Kilbride, RD
Reynolds, AS
Szaflarski, JP
Hirsch, LJ
AF Kilbride, R. D.
Reynolds, A. S.
Szaflarski, J. P.
Hirsch, L. J.
TI Clinical Outcomes Following Prolonged Refractory Status Epilepticus
(PRSE)
SO NEUROCRITICAL CARE
LA English
DT Article
DE Status epilepticus; PRSE; Neuro ICU; Outcomes
ID COMA
AB To define the clinical profile and outcome of patients in prolonged refractory status epilepticus (PRSE), and investigate possible predictors of outcome.
We reviewed 63 consecutive patients with PRSE cared for in the medical and neurointensive care units of three academic medical centers over a 9-year period. For this multi-center retrospective cohort study, PRSE was defined as SE that persisted despite at least 1 week of induced coma. Variables examined for their relationship to outcome included etiology, EEG, neuroimaging, and age.
Forty-two (66 %) of 63 patients in PRSE survived to discharge from hospitalization. Fourteen (22 %) patients had a good outcome (mRS a parts per thousand currency sign 3) at last available follow up (at least 6 months post-PRSE). Of these, 6 (10 %) individuals had no significant disability and were able to carry out all usual activities (mRS = 1). Normal neuroimaging and a reactive EEG at onset of PRSE were associated with good outcome. Good or excellent clinical outcomes were possible in patients in PRSE for up to 79 days, and in patients up to 69 years old.
Good outcome is not unusual in PRSE, including in some older patients, in a variety of diagnoses, and despite months of coma.
C1 [Kilbride, R. D.] Massachusetts Gen Hosp, Div Epilepsy, Boston, MA 02114 USA.
[Reynolds, A. S.] Neurol Inst, Comprehens Epilepsy Ctr, New York, NY 10032 USA.
[Szaflarski, J. P.] Univ Alabama Birmingham, Dept Neurol, Birmingham, AL 35294 USA.
[Hirsch, L. J.] Yale Univ, Sch Med, Comprehens Epilepsy Ctr, Div Epilepsy & EEG,Crit Care EEG Program, New Haven, CT 06510 USA.
RP Kilbride, RD (reprint author), Massachusetts Gen Hosp, Div Epilepsy, 55 Fruit St, Boston, MA 02114 USA.
EM rkilbride@partners.org
OI Reynolds, Alexandra/0000-0002-6364-6250
FU American Epilepsy Society
FX This study was conducted on behalf of the Critical Care EEG Monitoring
Research Consortium. The Critical Care EEG Monitoring Research
Consortium receives support from the American Epilepsy Society.
NR 12
TC 13
Z9 15
U1 0
U2 2
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 1541-6933
J9 NEUROCRIT CARE
JI Neurocrit. Care
PD JUN
PY 2013
VL 18
IS 3
BP 374
EP 385
DI 10.1007/s12028-013-9823-4
PG 12
WC Critical Care Medicine; Clinical Neurology
SC General & Internal Medicine; Neurosciences & Neurology
GA 147II
UT WOS:000319159600013
PM 23479069
ER
PT J
AU Schorge, JO
AF Schorge, John O.
TI Nonsurgical Treatment of Endometrial Hyperplasia Is the Road Less
Traveled the One We Should be Taking More?
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Editorial Material
ID CANCER; ADENOCARCINOMA; HYSTERECTOMY; PROGESTIN; OUTCOMES
C1 Massachusetts Gen Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, Boston, MA 02114 USA.
RP Schorge, JO (reprint author), Massachusetts Gen Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, Boston, MA 02114 USA.
EM jschorge@partners.org
NR 10
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-7844
J9 OBSTET GYNECOL
JI Obstet. Gynecol.
PD JUN
PY 2013
VL 121
IS 6
BP 1155
EP 1157
DI 10.1097/AOG.0b013e3182951846
PG 3
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 151BR
UT WOS:000319436100002
PM 23812445
ER
PT J
AU Orrell, C
Levison, J
Ciaranello, A
Bekker, LG
Kuritzkes, DR
Freedberg, KA
Wood, R
AF Orrell, Catherine
Levison, Julie
Ciaranello, Andrea
Bekker, Linda-Gail
Kuritzkes, Daniel R.
Freedberg, Kenneth A.
Wood, Robin
TI Resistance in Pediatric Patients Experiencing Virologic Failure With
First-line and Second-line Antiretroviral Therapy
SO PEDIATRIC INFECTIOUS DISEASE JOURNAL
LA English
DT Article
DE pediatric; antiretroviral therapy; genotype; resource-limited setting;
virologic failure; resistance
ID DRUG-RESISTANCE; CHILDREN
AB We examined HIV-1 resistance in children failing first-line and second-line antiretroviral therapy in South Africa, all with clade C virus. Those exposed to full-dose ritonavir had multiple protease resistance mutations. Nineteen percent had wild-type virus. Appropriate antiretroviral therapy sequencing in sub-Saharan African children is essential for prolong treatment options.
C1 [Orrell, Catherine; Bekker, Linda-Gail; Wood, Robin] Univ Cape Town, Fac Hlth Sci, Inst Infect Dis & Mol Med, Desmond Tutu HIV Ctr, ZA-7925 Cape Town, South Africa.
[Levison, Julie; Ciaranello, Andrea; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[Levison, Julie; Ciaranello, Andrea; Kuritzkes, Daniel R.; Freedberg, Kenneth A.] Harvard Univ, Sch Med, Boston, MA USA.
[Levison, Julie; Ciaranello, Andrea; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Med Practice Evaluat Ctr, Boston, MA 02114 USA.
[Levison, Julie; Kuritzkes, Daniel R.; Freedberg, Kenneth A.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA.
[Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA.
[Freedberg, Kenneth A.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA.
RP Orrell, C (reprint author), Univ Cape Town, Fac Hlth Sci, Inst Infect Dis & Mol Med, Desmond Tutu HIV Ctr, Anzio Rd, ZA-7925 Cape Town, South Africa.
EM catherine.orrell@hiv-research.org.za
OI Orrell, Catherine/0000-0003-1134-7475
FU ARRA PEPFAR [R01 AI085736, K01 AI078754]; IMPAACT network (NIAID);
IMPAACT network (National Institute of Child Health and Human
Development); AIDS Clinical Trials Group (National Institutes of Health)
[UM1 AI068636]
FX This work was completed through support from an ARRA PEPFAR supplement
to National Institute of Allergy and Infectious Diseases (NIAID) R01
AI085736 to K.A.F., K01 AI078754 and IMPAACT network (NIAID and National
Institute of Child Health and Human Development) to A.L.C. and by a
Virology Specialty Laboratory subcontract from the AIDS Clinical Trials
Group (National Institutes of Health grant UM1 AI068636) to D.R.K. The
authors have no other funding or conflicts of interest to disclose.
NR 10
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U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0891-3668
J9 PEDIATR INFECT DIS J
JI Pediatr. Infect. Dis. J.
PD JUN
PY 2013
VL 32
IS 6
BP 644
EP 647
DI 10.1097/INF.0b013e3182829092
PG 4
WC Immunology; Infectious Diseases; Pediatrics
SC Immunology; Infectious Diseases; Pediatrics
GA 147ZR
UT WOS:000319211700018
PM 23303240
ER
PT J
AU Yuen, KCJ
Biller, BMK
Katznelson, L
Rhoads, SA
Gurel, MH
Chu, O
Corazzini, V
Spiller, K
Gordon, MB
Salvatori, R
Cook, DM
AF Yuen, Kevin C. J.
Biller, Beverly M. K.
Katznelson, Laurence
Rhoads, Sharon A.
Gurel, Michelle H.
Chu, Olivia
Corazzini, Valentina
Spiller, Kellie
Gordon, Murray B.
Salvatori, Roberto
Cook, David M.
TI Clinical characteristics, timing of peak responses and safety aspects of
two dosing regimens of the glucagon stimulation test in evaluating
growth hormone and cortisol secretion in adults
SO PITUITARY
LA English
DT Article
DE Glucagon stimulation test; Growth hormone; Growth hormone deficiency;
Central adrenal insufficiency; Cortisol
ID GH DEFICIENCY; (GH)-RELEASING HORMONE; ENDOCRINE-SOCIETY; DIAGNOSIS;
ACTH; ARGININE; RELEASE; TIME; MEN
AB Weight-based (WB: 0.03 mg/kg) and fixed dose (FD: 1-1.5 mg) regimens of the glucagon stimulation test (GST) have been used to evaluate GH and cortisol secretion in children and adults, respectively. However, experience of the WB regimen in assessing GH and cortisol secretion in adults are limited. We describe a multicenter experience using WB and FD regimens in evaluating GH and cortisol secretion in adults suspected of GH deficiency and central adrenal insufficiency. Retrospective case series of GSTs (n = 515) performed at five tertiary centers. Peak and nadir glucose, and peak GH and peak cortisol responses occurred later with WB (mean dose: 2.77 mg) compared to FD (mean dose: 1.20 mg) regimens. Main side-effects were nausea and vomiting, particularly in younger females. Nausea was comparable but vomiting was more frequent in the WB regimen (WB: 10.0 % vs FD: 2.4 %; P < 0.05). Peak and nadir glucose, Delta GH, and peak and Delta cortisol were higher in the WB regimen. In both regimens, age correlated negatively with peak cortisol levels, and body mass index (BMI), fasting, peak and nadir glucose correlated negatively with peak GH levels. WB and FD regimens can induce adult GH and cortisol secretion, but peak responses occur later in the WB regimen. Both regimens are relatively safe, and vomiting was more prevalent in the WB regimen. As age, BMI, and glucose tolerance negatively correlated with peak GH and cortisol levels, the WB regimen may be more effective than the FD regimen in older overweight glucose intolerant patients.
C1 [Yuen, Kevin C. J.; Rhoads, Sharon A.; Cook, David M.] Oregon Hlth & Sci Univ, Dept Med, Div Endocrinol Diabet & Clin Nutr, Portland, OR 97239 USA.
[Biller, Beverly M. K.; Gurel, Michelle H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02459 USA.
[Katznelson, Laurence; Chu, Olivia] Stanford Univ, Sch Med, Dept Med, Div Endocrinol, Stanford, CA 94305 USA.
[Katznelson, Laurence; Chu, Olivia] Stanford Univ, Sch Med, Dept Neurosurg, Div Endocrinol, Stanford, CA 94305 USA.
[Corazzini, Valentina; Salvatori, Roberto] Johns Hopkins Sch Med, Dept Med, Div Endocrinol, Baltimore, MD 21287 USA.
[Spiller, Kellie; Gordon, Murray B.] Allegheny Gen Hosp, Div Endocrinol, Pittsburgh, PA 15212 USA.
RP Yuen, KCJ (reprint author), Oregon Hlth & Sci Univ, Dept Med, Div Endocrinol Diabet & Clin Nutr, 3181 SW Sam Jackson Pk Rd,Mailcode L607, Portland, OR 97239 USA.
EM yuenk@ohsu.edu
FU Novo Nordisk
FX KCJY, BMKB and MBG have received research grants and consulting
honoraria from Novo Nordisk. RS and DMC have received consulting
honoraria from Novo Nordisk. This research did not receive any specific
grant from any funding agency in the public, commercial or non-profit
sector.
NR 30
TC 13
Z9 13
U1 1
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1386-341X
J9 PITUITARY
JI Pituitary
PD JUN
PY 2013
VL 16
IS 2
BP 220
EP 230
DI 10.1007/s11102-012-0407-7
PG 11
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 149CL
UT WOS:000319295500013
PM 22806554
ER
PT J
AU Yu, ZT
Liu, B
Mukherjee, P
Newburg, DS
AF Yu, Zhuo-Teng
Liu, Bo
Mukherjee, Purna
Newburg, David S.
TI Trametes versicolor Extract Modifies Human Fecal Microbiota Composition
In vitro
SO PLANT FOODS FOR HUMAN NUTRITION
LA English
DT Article
DE Trametes versicolor; PSP; Fecal microbiota; In vitro fermentation
ID BETA-GALACTOSIDASE; FERMENTATION; PROBIOTICS; PREBIOTICS; GROWTH;
CANCER; RATS
AB Trametes versicolor is a mushroom used as a traditional Chinese medicine (Yun-zhi) for a wide array of seemingly disparate conditions. We hypothesized that many of its multiple purported activities could be mediated through stimulation of beneficial mutualist components of the microbiota. Human fecal microbiota was cultured anaerobically to determine its ability to ferment a common extract of T. versicolor, designated polysaccharide peptide (PSP), and the ability of PSP to alter the composition of the microbial community. The presence of PSP and fructooligosaccharides (FOS, a common prebiotic) in the medium, but not cellulose, significantly increased levels of Bifidobacterium spp. PSP also elevated Lactobacillus spp., while reducing Clostridium spp., Staphylococcus spp. and Enterococcus spp. Levels of Streptococcus spp., Bacteroides spp. and Escherichia did not significantly change. Fermentation of PSP increased the concentration of organic acids (lactate and short-chain fatty acids), decreased the pH, and induced beta-galactosidase and beta-glucosidase activities. The genera of the human microbiota that are promoted by FOS and other prebiotics are also stimulated by the Trametes versicolor extract, PSP. Thus, Trametes versicolor, a common East Asian botanical, contains putative prebiotic agents that alter human gut microbiota and pH. This prebiotic-like activity may help explain some of the plethora of the health benefits attributed to this traditional Chinese medicine.
C1 [Yu, Zhuo-Teng; Liu, Bo; Newburg, David S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat Gastroenterol & Nutr, Boston, MA 02129 USA.
RP Newburg, DS (reprint author), Boston Coll, Dept Biol, Program Glycobiol, Higgins Hall,140 Commonwealth Ave, Chestnut Hill, MA 02467 USA.
EM david.newburg@bc.edu
FU NIH [HD013021, HD059140, AI075563]
FX We thank Winsor Health Products, Ltd. for their gift of PSP and partial
support, Dr. Gherman Wiederschain for helpful assistance with the
manuscript, and the NIH for grants HD013021, HD059140, and AI075563.
NR 20
TC 4
Z9 6
U1 2
U2 27
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0921-9668
J9 PLANT FOOD HUM NUTR
JI Plant Food Hum. Nutr.
PD JUN
PY 2013
VL 68
IS 2
BP 107
EP 112
DI 10.1007/s11130-013-0342-4
PG 6
WC Plant Sciences; Chemistry, Applied; Food Science & Technology; Nutrition
& Dietetics
SC Plant Sciences; Chemistry; Food Science & Technology; Nutrition &
Dietetics
GA 149BY
UT WOS:000319294200002
PM 23435630
ER
EF