FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Speliotes, EK
AF Speliotes, Elizabeth K.
TI Genetics of Common Obesity and Nonalcoholic Fatty Liver Disease
SO GASTROENTEROLOGY
LA English
DT Editorial Material
ID GENOME-WIDE ASSOCIATION; NEUROTROPHIC FACTOR; BODY-WEIGHT; FTO GENE;
LOCI; MICE; STEATOHEPATITIS; VARIANTS; TRAITS; SCAN
C1 Massachusetts Gen Hosp, Dept Gastroenterol, Boston, MA 02114 USA.
RP Speliotes, EK (reprint author), Massachusetts Gen Hosp, Dept Gastroenterol, 55 Fruit St, Boston, MA 02114 USA.
EM espeliotes@partners.org
FU NIDDK NIH HHS [K23 DK080145-01, F32 DK079466, K23 DK080145, F32
DK079466-01]
NR 20
TC 11
Z9 11
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 0016-5085
J9 GASTROENTEROLOGY
JI Gastroenterology
PD MAY
PY 2009
VL 136
IS 5
BP 1492
EP 1495
DI 10.1053/j.gastro.2009.03.020
PG 4
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 440WQ
UT WOS:000265730800006
PM 19324104
ER
PT J
AU El-Serag, HB
Johnson, ML
Hachem, C
Morgana, RO
AF El-Serag, Hashem B.
Johnson, Michael L.
Hachem, Christine
Morgana, Robert O.
TI Statins Are Associated With a Reduced Risk of Hepatocellular Carcinoma
in a Large Cohort of Patients With Diabetes
SO GASTROENTEROLOGY
LA English
DT Article
ID COA REDUCTASE INHIBITORS; COENZYME-A REDUCTASE; SCANDINAVIAN SIMVASTATIN
SURVIVAL; COMBINATION THERAPY; PHARMACY RECORDS; FOLLOW-UP; CELLS;
CANCER; APOPTOSIS; PROLIFERATION
AB Background & Aims: Experimental studies indicate a potential cancer prevention effect for statins. Given the increasing prevalence of statin use, and the increasing incidence of hepatocellular carcinoma (HCC), the potential association between statins and HCC is an important issue to examine. Methods: We conducted a matched case-control study nested within a cohort of patients with diabetes. Cases comprised incident HCC at least 6 months after entry in the cohort. Controls were identified by incidence density sampling from patients who remained at risk at the date of the HCC diagnosis matched by age and sex. We identified fined statin prescriptions as well as several potential confounding conditions, medications, as well as propensity score to use statins. Odds ratios (ORs) as estimates of the relative risk for HCC associated with statin use and 95% confidence intervals were obtained using conditional logistic regression. Results: We examined 1303 cases and 5212 controls. The mean age was 72 years and 99% were men. A significantly smaller proportion of cases (34.3%) had at least one filled prescription for statins than controls (53.1%). There were no significant associations between HCC and nonstatin cholesterol- or triglyceride-lowering medications. The unadjusted OR for any statin prescription was 0.46 (9S% confidence interval, 0.40-0.517) and the adjusted OR was 0.74 (95% confidence interval, 0.64-0.87). To reduce the potential confounding effect of existing liver disease, we ran the analyses in a subgroup of patients without recorded liver disease; the ORs were slightly attenuated but remained highly significant for any statin prescription (0.63; 95% confidence interval, 0.50-0.78). Conclusions: Statin use is associated with a significant reduction in the risk of HCC among patients with diabetes.
C1 [El-Serag, Hashem B.; Hachem, Christine; Morgana, Robert O.] Michael E DeBakey Vet Affairs Med Ctr, Gastroenterol Sect, Houston, TX 77030 USA.
[El-Serag, Hashem B.; Hachem, Christine; Morgana, Robert O.] Michael E DeBakey Vet Affairs Med Ctr, Sect Hlth Serv Res, Houston, TX 77030 USA.
[El-Serag, Hashem B.; Hachem, Christine; Morgana, Robert O.] Baylor Coll Med, Houston, TX 77030 USA.
[Johnson, Michael L.] Univ Houston, Coll Pharm, Dept Clin Sci & Adm, Houston, TX 77030 USA.
RP El-Serag, HB (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Gastroenterol Sect, 2002 Holcombe Blvd, Houston, TX 77030 USA.
EM hasheme@bcm.tmc.edu
FU Department of Veterans Affairs; Health Services Research and Development
Service [IIR 02-081]; American College of Gastroenterology; National
Institutes of Health [K24DK078154-03]
FX This research was supported in part by the Department of Veterans
Affairs, Health Services Research and Development Service (IIR 02-081),
and by a grant from the American College of Gastroenterology. Dr
EI-Serag is supported by a National Institutes of Health grant
(K24DK078154-03).
NR 28
TC 129
Z9 134
U1 1
U2 4
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0016-5085
J9 GASTROENTEROLOGY
JI Gastroenterology
PD MAY
PY 2009
VL 136
IS 5
BP 1601
EP 1608
DI 10.1053/j.gastro.2009.01.053
PG 8
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 440WQ
UT WOS:000265730800023
PM 19208359
ER
PT J
AU Verzi, MP
Stanfel, MN
Moses, KA
Kim, BM
Zhang, Y
Schwartz, RJ
Shivdasani, RA
Zimmer, WE
AF Verzi, Michael P.
Stanfel, Monique N.
Moses, Kelvin A.
Kim, Byeong-Moo
Zhang, Yan
Schwartz, Robert J.
Shivdasani, Ramesh A.
Zimmer, Warren E.
TI Role of the Homeodomain Transcription Factor Bapx1 in Mouse Distal
Stomach Development
SO GASTROENTEROLOGY
LA English
DT Article
ID EMBRYONAL GUT DEVELOPMENT; TARGETED DISRUPTION; AXIAL SKELETON; HOMEOBOX
GENE; HOX GENES; SPLEEN; EXPRESSION; MICE; DROSOPHILA; BAGPIPE
AB Background & Aims: Expansion and patterning of the endoderm generate a highly ordered, multiorgan digestive system in vertebrate animals. Among distal foregut derivatives, the gastric corpus, antrum, pylorus, and duodenum are distinct structures with sharp boundaries. Some homeodomain transcription factors expressed in gut mesenchyme convey positional information required for anterior-posterior patterning of the digestive tract. Barx1, in particular, controls stomach differentiation and morphogenesis. The Nirenberg and Kim homeobox gene Bapx1 (NW-2) has an established role in skeletal development, but its function in the mammalian gut is less clear. Methods: We generated a Bapx1(Cre) knock-in allele to fate map Bapx1-expressing cells and evaluate its function in gastrointestinal development. Results: Bapx1-expressing cells populate the gut mesenchyme with a rostral boundary in the hindstomach near the junction of the gastric corpus and antrum. Smooth muscle differentiation and distribution of early regional markers are ostensibly normal in Bapx1(Cre/Cre) gut, but there are distinctive morphologic abnormalities near this rostral Bapx1 domain: the antral segment of the stomach is markedly shortened, and the pyloric constriction is lost. Comparison of expression domains and examination of stomach phenotypes in single and compound Barx1 and Bapx1 mutant mice suggests a hierarchy between these 2 factors; Bapx1 expression is lost in the absence of Barx1. Conclusions: This study reveals the nonredundant requirement for Bapx1 in distal stomach development, places it within a Barx1-dependent pathway, and illustrates the pervasive influence of gut mesenchyme homeobox genes on endoderm differentiation and digestive organogenesis.
C1 [Verzi, Michael P.; Kim, Byeong-Moo; Shivdasani, Ramesh A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Verzi, Michael P.; Kim, Byeong-Moo; Shivdasani, Ramesh A.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
[Stanfel, Monique N.; Moses, Kelvin A.; Schwartz, Robert J.] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA.
[Zhang, Yan; Zimmer, Warren E.] Texas A&M Univ, Coll Med, Dept Syst Biol & Translat Med, College Stn, TX 77843 USA.
[Schwartz, Robert J.; Zimmer, Warren E.] Texas A&M Univ, Coll Med, Ctr Environm & Rural Hlth, College Stn, TX 77843 USA.
[Schwartz, Robert J.] Texas A&M Univ, Hlth Sci Ctr, Inst Biosci & Technol, Houston, TX USA.
RP Zimmer, WE (reprint author), Texas A&M Hlth Sci, 310B Joe H Reynolds Bldg, College Stn, TX 77843 USA.
EM ramesh_shivdasani@dfcl.harvard.edu; wezimmer@medicine.tamhsc.edu
FU NCI NIH HHS [R01 CA095608, R01CA095608]; NHLBI NIH HHS [P01 HL067155,
P01 HL049953, P01HL067155, P01HL49953]; NIDDK NIH HHS [R01 DK061139, R01
DK061139-04S1, R01DK061139, T32 DK007477, T32 DK007696, T32DK07477,
T32DK07696]; NIEHS NIH HHS [P30 ES009106, P30 ES09106]
NR 38
TC 27
Z9 29
U1 0
U2 2
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0016-5085
J9 GASTROENTEROLOGY
JI Gastroenterology
PD MAY
PY 2009
VL 136
IS 5
BP 1701
EP 1710
DI 10.1053/j.gastro.2009.01.009
PG 10
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 440WQ
UT WOS:000265730800033
PM 19208343
ER
PT J
AU Plentz, R
Park, JS
Rhim, AD
Abravanel, D
Hezel, AF
Sharma, SV
Gurumurthy, S
Deshpande, V
Kenific, C
Settleman, J
Majumder, PK
Stanger, BZ
Bardeesy, N
AF Plentz, Ruben
Park, Ji-Sun
Rhim, Andrew D.
Abravanel, Daniel
Hezel, Aram F.
Sharma, Sreenath V.
Gurumurthy, Sushma
Deshpande, Vikram
Kenific, Candia
Settleman, Jeffrey
Majumder, Pradip K.
Stanger, Ben Z.
Bardeesy, Nabeel
TI Inhibition of gamma-Secretase Activity Inhibits Tumor Progression in a
Mouse Model of Pancreatic Ductal Adenocarcinoma
SO GASTROENTEROLOGY
LA English
DT Article
ID CELL DIFFERENTIATION; INTRAEPITHELIAL NEOPLASIA; ENDOCRINE DEVELOPMENT;
ACINAR-CELLS; NOTCH; CANCER; ACTIVATION; GROWTH; INDUCTION; FATE
AB Background & Aim: The Notch signaling pathway is required for the expansion of undifferentiated pancreatic progenitor cells during embryonic development and has been implicated in the progression of pancreatic ductal adenocarcinoma (PDAC). The interaction of Notch ligands with their receptors promotes a gamma-secretase-dependent cleavage of the Notch receptor and release of the Notch intracellular domain, which translocates to the nucleus and activates transcription. We investigated the role of this pathway in PDAC progression. Methods: We tested the effects of a gamma-secretase inhibitor (GSI) that blocks Notch signaling in PDAC cell lines and a genetically engineered mouse model of PDAC (Kras p53 L/+ mice). Results: Notch signaling was activated in PDAC precursors and advanced tumors. The GSI inhibited the growth of premalignant pancreatic duct-derived cells in a Notch-dependent manner. Additionally, in a panel of over 400 human solid tumorderived cell lines, PDAC cells, as a group, were more sensitive to the GSI than any other tumor type. Finally, the GSI completely inhibited tumor development in the genetically engineered model of invasive PDAC (P <.005, chi(2) test; compared with mice exposed to vehicle). Conclusions: These results suggest that Notch signaling is required for PDAC progression. Pharmacologic targeting of this pathway offers therapeutic potential in this treatment-refractory malignancy.
C1 [Plentz, Ruben; Park, Ji-Sun; Hezel, Aram F.; Sharma, Sreenath V.; Gurumurthy, Sushma; Settleman, Jeffrey; Bardeesy, Nabeel] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Canc Ctr, Boston, MA 02114 USA.
[Rhim, Andrew D.; Abravanel, Daniel; Stanger, Ben Z.] Univ Penn, Sch Med, Div Gastroenterol, Philadelphia, PA 19104 USA.
[Rhim, Andrew D.; Abravanel, Daniel; Stanger, Ben Z.] Univ Penn, Sch Med, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA.
[Sharma, Sreenath V.; Settleman, Jeffrey] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Therapeut, Boston, MA 02114 USA.
[Deshpande, Vikram] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Kenific, Candia] Merck Res Labs, Dept Neuropharmacol, Boston, MA USA.
[Majumder, Pradip K.] Merck Res Labs, Dept Oncol Pharmacol, Boston, MA USA.
RP Bardeesy, N (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Canc Ctr, CPZN4216,185 Cambridge St, Boston, MA 02114 USA.
EM bstanger@exchange.upenn.edu; Bardeesy.Nabeel@MGH.Harvard.edu
FU NCI NIH HHS [5K01CA104647, 5P01CA117969, K01 CA104647, P01 CA117969, R01
CA133557]; NIDDK NIH HHS [T32-DK007066, T32 DK007066]
NR 49
TC 88
Z9 89
U1 0
U2 8
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 MAY
PY 2009
VL 136
IS 5
BP 1741
EP 1749
DI 10.1053/j.gastro.2009.01.008
PG 9
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 440WQ
UT WOS:000265730800037
PM 19208345
ER
PT J
AU Taylor-Young, P
Hildebrandt, E
AF Taylor-Young, Patricia
Hildebrandt, Eugenie
TI The Multidimensional Burden of Hepatitis C and Its Treatment A Case
Study
SO GASTROENTEROLOGY NURSING
LA English
DT Article
ID ANTIVIRAL TREATMENT; UNITED-STATES; DEPRESSION; PREVALENCE; MANAGEMENT;
INFECTION; VETERANS
AB The purpose of this case study was to gain an in-depth understanding of the mental, physical, and emotional burden of being infected with the hepatitis C virus (HCV) from the perspective of an individual living with the disease and undergoing antiviral treatment. Interviews were conducted during and after antiviral therapy with 1 participant chosen from a Midwest HCV clinic population. Interviews were audio recorded, transcribed verbatim, and coded. Content analysis and thematic analysis were performed. The participant reviewed and validated the themes and the interpretation of the themes. Ten categories were identified, which were subsequently integrated in 4 themes: (1) transition or process of change, (2) maintaining control over one's life, (3) social support and communication, and (4) side effects. The results of this study can assist healthcare providers to understand what individuals experience in the course of HCV infection and its treatment. This knowledge will assist them to provide effective patient-centered care. To provide such care, it is imperative that healthcare providers understand the physical, psychological, social, and professional impact that the diagnosis of HCV infection and antiviral therapy has on individuals.
C1 [Taylor-Young, Patricia] Portland VA Med Ctr, Portland, OR 97239 USA.
[Hildebrandt, Eugenie] Univ Wisconsin, Coll Nursing, Milwaukee, WI 53201 USA.
RP Taylor-Young, P (reprint author), Portland VA Med Ctr, 3710 SW US Vet Hosp Rd P2NR, Portland, OR 97239 USA.
EM patricia.tayloryoung@va.gov
NR 28
TC 7
Z9 7
U1 1
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1042-895X
J9 GASTROENTEROL NURS
JI Gastroenterol. Nurs.
PD MAY-JUN
PY 2009
VL 32
IS 3
BP 180
EP 187
PG 8
WC Gastroenterology & Hepatology; Nursing
SC Gastroenterology & Hepatology; Nursing
GA 458JV
UT WOS:000267015300003
PM 19506434
ER
PT J
AU Fasanella, KE
McGrath, KM
Sanders, M
Brody, D
Domsic, R
Khalid, A
AF Fasanella, Kenneth E.
McGrath, Kevin M.
Sanders, Michael
Brody, Debra
Domsic, Robyn
Khalid, Asif
TI Pancreatic endocrine tumor EUS-guided FNA DNA microsatellite loss and
mortality
SO GASTROINTESTINAL ENDOSCOPY
LA English
DT Article; Proceedings Paper
CT Digestive Disease Week Meeting/109th Annual Meeting of the
American-Gastroenterological-Association
CY MAY 17-22, 2008
CL San Diego, CA
SP Amer Gastroenterol Assoc
ID CHROMOSOME 1Q; HETEROZYGOSITY; DIAGNOSIS; INSULINOMAS; PROGRESSION;
MALIGNANCY; DELETION; CRITERIA; SYSTEM
AB Background: The clinical course of pancreatic endocrine tumors (PET) depends on tumor size, the presence Of invasion or metastasis, the Ki-67 index, mitose's per high power field, and mutational damage. Most of this information is not available before surgery for clinical decision making or prognostication.
Objective: To evaluate PET FUS-guided FNA (EUS-FNA) microsatellite loss analysis in the context of PET-related mortality.
Design: A single institution retrospective cohort.
Patients: Patients with PET diagnosed by EUS-FNA who underwent DNA microsatellite loss analysis and at least 1 year of follow-up or subsequent death.
Intervention: PET microsatellite loss analysis and current clinical status were compared
Results: Twenty-nine patients were included in the final analysis; the mean age of the patients was 57 years, and 10 were women (35%). The mean follow-up was 33.7 months (median 30 months, range 2-66 months). Twelve patients had disease progression, and 8 died, all from disease-specific causes. Malignant PET contained multiple microsatellite losses, with a median fractional allelic loss (FAL) of 0.37 (range 0.12-0.69, interquartile range [IQR] 0.23-0.42), significantly different from benign PET, median FAL 0 (range 0-0.18, IQR 0-0.08, P < .0001). Survival analysis revealed a significant difference in disease recurrence progression at 2 years (P < .0001) and in the 5-year survival between patients with FAL <= 0.2 compared with 0.2 (P <.0001). Logistic regression could not he performed because of the perfect association between an FAL > 0.2 of the perfect association between an FAL > 0.2 and disease status or mortality.
Limitations: Retrospective design, referral bias, and DNA analysis availability.
Conclusions: PET EUS-FNA microsatellite loss analysis provides preoperative prognostic information. An FAL > 0.2 is not only associated with disease progression but also with mortality (Gastrointest Endosc 2009:69:1074-80.)
C1 [Khalid, Asif] Univ Pittsburgh, C Wing PUH, Dept Med, Med Ctr, Pittsburgh, PA 15213 USA.
[Khalid, Asif] VA Pittsburgh Healthcare Syst, Med Specialty Serv Line, Pittsburgh, PA 15213 USA.
RP Khalid, A (reprint author), Univ Pittsburgh, C Wing PUH, Dept Med, Med Ctr, M2,200 Lothrop St, Pittsburgh, PA 15213 USA.
EM khalida@upmc.edu
RI Fasanella, Kenneth/I-2781-2012
NR 23
TC 10
Z9 10
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0016-5107
J9 GASTROINTEST ENDOSC
JI Gastrointest. Endosc.
PD MAY
PY 2009
VL 69
IS 6
BP 1074
EP 1080
DI 10.1016/j.gie.2008.06.023
PG 7
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 441KC
UT WOS:000265766700014
PM 19152901
ER
PT J
AU Khalid, A
Zahid, M
Finkelstein, SD
LeBlanc, JK
Kaushik, N
Ahmad, N
Brugge, WR
Edmundowicz, SA
Hawes, RH
McGrath, KM
AF Khalid, Asif
Zahid, Maliha
Finkelstein, Sydney D.
LeBlanc, Julia K.
Kaushik, Neeraj
Ahmad, Nuzhat
Brugge, William R.
Edmundowicz, Steven A.
Hawes, Robert H.
McGrath, Kevin M.
TI Pancreatic cyst fluid DNA analysis in evaluating pancreatic cysts: a
report of the PANDA study
SO GASTROINTESTINAL ENDOSCOPY
LA English
DT Article; Proceedings Paper
CT Digestive Disease Week Meeting/108th Annual Meeting of the
American-Gastroenterological-Association
CY MAY 19-24, 2007
CL Washington, DC
SP Amer Gastroenterol Assoc, Amer Assoc Study Liver Dis, Amer Soc Gastrointestinal Endoscopy, Soc Surg Alimentary Tract
ID PAPILLARY-MUCINOUS TUMORS; NEOPLASMS; ADENOCARCINOMA; PROGRESSION;
EXPRESSION; LESIONS; P53
AB Background: The role of pancreatic cyst fluid DNA analysis in evaluating cysts remains unclear.
Objective: Our purpose was to evaluate the utility of a detailed DNA analysis of pancreatic cyst fluid to diagnose mucinous and malignant cyst.
Design: Prospective, multicenter study.
Patients: Patients with pancreatic cysts presenting for EUS evaluation.
Intervention: EUS-guided pancreatic cyst aspirates cytology evaluation, carcinoembryonic antigen (CEA) level determination, and a detailed DNA analysis; incorporating DNA quantification, k-ras mutation and multiple allelic has analysis, mutational amplitude, and sequence determination.
Main Outcome Measurements: Cyst fluid analysis compared with surgical pathologic or malignant cytologic examination
Results: The study cohort consisted of 113 patients with 40 malignant, 48 premalignant, and 25 benign cyst Cyst fluid k-ras mutation was helpful in the diagnosis of mucinous cysts (odds ratio 20.9, specificity 96%), whereas receiver-operator characteristic curve analysis indicated optimal cutoff points For allelic loss amplitude (area under the curve [AUC] 0.79; optimal value > 65%) and CEA (AUC 0.74; optimal value > 148 ng/ml). Components of DNA analysis detecting malignant cysts included allelic loss amplitude over 82% (AUC 0.9) and high DNA amount (optical density ratio > 10, AUC 0.79). The criteria of a high amplitude k-ras mutation followed by allelic loss showed maximum specificity (96%) for malignancy. All malignant cysts with negative cytology evaluation (10/40) could be diagnosed as malignant by using DNA analysis.
Limitations: United follow-up, selection bias.
Conclusions: Elevated amounts of pancreatic cyst fluid DNA hi,high-amplitude mutations, Mid specific mutation acquistion sequences we indicators of malignancy. The presence of a k-ras mutation is also indicative of a mucinous cyst. DNA analysis should be considered when cyst cytologic examination is negative for malignancy. (Gastrointest Endosc 2009;69:1095-102.)
C1 [Khalid, Asif] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA.
[Zahid, Maliha] Univ Pittsburgh, Med Ctr, Dept Human Genet & Biochem, Pittsburgh, PA USA.
[Finkelstein, Sydney D.] RedPath Integrated Pathol, Pittsburgh, PA USA.
[LeBlanc, Julia K.] Indiana Univ Hosp, Dept Med, Indianapolis, IN 46202 USA.
[Ahmad, Nuzhat] Hosp Univ Penn, Dept Med, Philadelphia, PA 19104 USA.
[Brugge, William R.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Edmundowicz, Steven A.] Barnes Jewish Hosp, Dept Med, St Louis, MO 63110 USA.
[Hawes, Robert H.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA.
RP Khalid, A (reprint author), PUH, C Wing, M2,200 Lothrop St, Pittsburgh, PA 15213 USA.
EM khalida@upmc.edu
OI Edmundowicz, Steven/0000-0002-6541-3485
NR 11
TC 183
Z9 185
U1 1
U2 7
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0016-5107
J9 GASTROINTEST ENDOSC
JI Gastrointest. Endosc.
PD MAY
PY 2009
VL 69
IS 6
BP 1095
EP 1102
DI 10.1016/j.gie.2008.07.033
PG 8
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 441KC
UT WOS:000265766700017
PM 19152896
ER
PT J
AU Sampaio, AS
Miguel, EC
Borcato, S
Batistuzzo, M
Fossaluza, V
Geller, DA
Hounie, AG
AF Sampaio, Aline S.
Miguel, Euripedes C.
Borcato, Sonia
Batistuzzo, Marcelo
Fossaluza, Victor
Geller, Daniel A.
Hounie, Ana G.
TI Perinatal risk factors and obsessive-compulsive spectrum disorders in
patients with rheumatic fever
SO GENERAL HOSPITAL PSYCHIATRY
LA English
DT Article
ID TOURETTES-SYNDROME; POLYMORPHISMS; ASSOCIATION; EXPRESSION; ALPHA
C1 [Sampaio, Aline S.; Miguel, Euripedes C.; Borcato, Sonia; Batistuzzo, Marcelo; Fossaluza, Victor; Hounie, Ana G.] Univ Sao Paulo, Sch Med, Dept Psychiat, Hosp Clin, BR-05403010 Sao Paulo, Brazil.
[Sampaio, Aline S.; Miguel, Euripedes C.; Borcato, Sonia; Batistuzzo, Marcelo; Fossaluza, Victor; Hounie, Ana G.] Univ Sao Paulo, Sch Med, Inst Psychiat, Hosp Clin, BR-05403010 Sao Paulo, Brazil.
[Geller, Daniel A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA.
RP Sampaio, AS (reprint author), Univ Sao Paulo, PROTOC, Inst Psiquiatria, Fac Med, Rua Dr Ovidio Pires Campos 785,3 A,S 07,Cerqueira, BR-05403010 Sao Paulo, Brazil.
EM alinestsampaio@gmail.com
RI Miguel, Euripedes/B-2871-2008; SAMPAIO, ALINE/M-1229-2013; Fossaluza,
Victor/B-3377-2014; Batistuzzo, Marcelo/H-7790-2015
OI SAMPAIO, ALINE/0000-0001-5568-6167; Fossaluza,
Victor/0000-0002-9328-0210;
FU CAPES/PRODOC, FAPESP [98/15013-9, 2005/55628-8]; CNPq
FX This work was supported by grants from CAPES/PRODOC, FAPESP (grants
98/15013-9 and 2005/55628-8) and CNPq.
NR 20
TC 3
Z9 3
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0163-8343
J9 GEN HOSP PSYCHIAT
JI Gen. Hosp. Psych.
PD MAY-JUN
PY 2009
VL 31
IS 3
BP 288
EP 291
DI 10.1016/j.genhosppsych.2008.08.003
PG 4
WC Psychiatry
SC Psychiatry
GA 445DF
UT WOS:000266029200012
PM 19410109
ER
PT J
AU Burke, GV
Wong, DA
Saunders, CS
Pierre, JM
AF Burke, Guenevere V.
Wong, Donovan A.
Saunders, C. Scott
Pierre, Joseph M.
TI Self-limited erythema multiforme with risperidone
SO GENERAL HOSPITAL PSYCHIATRY
LA English
DT Article
C1 [Wong, Donovan A.; Saunders, C. Scott; Pierre, Joseph M.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA.
[Burke, Guenevere V.; Wong, Donovan A.; Saunders, C. Scott; Pierre, Joseph M.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA.
RP Pierre, JM (reprint author), VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd,Bldg 210, Los Angeles, CA 90073 USA.
EM joseph.pierre2@va.gov
NR 6
TC 0
Z9 0
U1 1
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0163-8343
J9 GEN HOSP PSYCHIAT
JI Gen. Hosp. Psych.
PD MAY-JUN
PY 2009
VL 31
IS 3
BP 295
EP 296
DI 10.1016/j.genhosppsych.2008.08.008
PG 2
WC Psychiatry
SC Psychiatry
GA 445DF
UT WOS:000266029200014
PM 19410111
ER
PT J
AU Liu, CY
Yang, Q
Cupples, LA
Melgs, JB
Dupuis, J
AF Liu, Chunyu
Yang, Qiong
Cupples, L. Adrienne
Melgs, James B.
Dupuis, Josee
TI Selection of the Most Informative Individuals From Families With
Multiple Siblings for Association Studies
SO GENETIC EPIDEMIOLOGY
LA English
DT Article
DE linkage analysis; association study; linkage disequilibrium;
identity-by-descent (IBD)
ID QUANTITATIVE-TRAIT LOCI; LINKAGE DISEQUILIBRIUM; POWER; PAIRS
AB Association analyses may follow an initial linkage analysis for mapping and identifying genes underlying complex quantitative traits and may be conducted on unrelated subsets of individuals where only one member of a family is included. We evaluate two methods to select one sibling per sibship when multiple siblings are available: (1) one sibling with the most extreme trait value; and (2) one sibling using a combination score statistic based on extreme trait values and identity-by-descent sharing information. We compare the type 1 error and power. Furthermore, we compare these selection strategies with a strategy that randomly selects one sibling per sibship and with an approach that includes all siblings, using both simulation Study and an application to fasting blood glucose in the Framingham Heart Study. When genetic effect is homogeneous, we find that using the combination score call increase power by 30-40% compared to a random selection strategy, and loses only 8-13% of power compared to the full sibship analysis, across all additive models considered, but offers at least 50% genotyping cost saving. In the presence of genetic heterogeneity, the score of fers a 50% increase in power over a random selection strategy, but there is substantial loss compared to the full sibship analysis. In application to fasting blood sample, two SNPs are found in common for the selection strategies and the full sample among the 10 highest ranked single nucleotide polymorphisms. The EV strategy tends to agree with the IBD-EV strategy and the analysis of the full sample. Genet. Epidemiol. 33:299-307, 2009. (C) 2008 Wiley-Liss, Inc.
C1 [Liu, Chunyu] Biogen Idec, Dept Drug Discovery, Genet & Genom, Cambridge, MA USA.
[Yang, Qiong; Cupples, L. Adrienne; Dupuis, Josee] Boston Univ, Dept Biostat, Boston, MA 02215 USA.
[Melgs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA.
[Melgs, James B.] Harvard Univ, Sch Med, Boston, MA USA.
RP Liu, CY (reprint author), Biogen Idec, Dept Drug Discovery, Genet & Genom, 12 Cambridge Ctr, Cambridge, MA USA.
EM chunyu.liu@biogenidec.com
RI Yang, Qiong/G-5438-2014;
OI Dupuis, Josee/0000-0003-2871-3603
FU NIH NCRR [1S10RR163736-01A1]; National Heart, Lung and Blood Institute's
Framingham Heart Study [N01-HC-25195]; American Diabetes Association
FX Contract grant sponsor: NIH NCRR; Contract grant number:
1S10RR163736-01A1; Contract grant sponsor: National Heart, Lung and
Blood Institute's Framingham Heart Study; Contract grant number:
N01-HC-25195; Contract grant sponsor: American Diabetes Association.
NR 18
TC 0
Z9 0
U1 0
U2 0
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD MAY
PY 2009
VL 33
IS 4
BP 299
EP 307
DI 10.1002/gepi.20380
PG 9
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 440UJ
UT WOS:000265724900003
PM 19025786
ER
PT J
AU Norman, PJ
Abi-Rached, L
Gendzekhadze, K
Hammond, JA
Moesta, AK
Sharma, D
Graef, T
McQueen, KL
Guethlein, LA
Carrington, CVF
Chandanayingyong, D
Chang, YH
Crespi, C
Saruhan-Direskeneli, G
Hameed, K
Kamkamidze, G
Koram, KA
Layrisse, Z
Matamoros, N
Mila, J
Park, MH
Pitchappan, RM
Ramdath, DD
Shiau, MY
Stephens, HAF
Struik, S
Tyan, D
Verity, DH
Vaughan, RW
Davis, RW
Fraser, PA
Riley, EM
Ronaghi, M
Parham, P
AF Norman, Paul J.
Abi-Rached, Laurent
Gendzekhadze, Ketevan
Hammond, John A.
Moesta, Achim K.
Sharma, Deepti
Graef, Thorsten
McQueen, Karina L.
Guethlein, Lisbeth A.
Carrington, Christine V. F.
Chandanayingyong, Dasdayanee
Chang, Yih-Hsin
Crespi, Catalina
Saruhan-Direskeneli, Guher
Hameed, Kamran
Kamkamidze, Giorgi
Koram, Kwadwo A.
Layrisse, Zulay
Matamoros, Nuria
Mila, Joan
Park, Myoung Hee
Pitchappan, Ramasamy M.
Ramdath, D. Dan
Shiau, Ming-Yuh
Stephens, Henry A. F.
Struik, Siske
Tyan, Dolly
Verity, David H.
Vaughan, Robert W.
Davis, Ronald W.
Fraser, Patricia A.
Riley, Eleanor M.
Ronaghi, Mostafa
Parham, Peter
TI Meiotic recombination generates rich diversity in NK cell receptor
genes, alleles, and haplotypes
SO GENOME RESEARCH
LA English
DT Article
ID IG-LIKE RECEPTORS; MAJOR HISTOCOMPATIBILITY COMPLEX; COPY-NUMBER
VARIATION; NATURAL-KILLER-CELLS; MODERN HUMAN ORIGINS; HUMAN
COLOR-VISION; HLA-B; CUTTING EDGE; INHIBITORY RECEPTORS; STRUCTURAL
VARIATION
AB Natural killer (NK) cells contribute to the essential functions of innate immunity and reproduction. Various genes encode NK cell receptors that recognize the major histocompatibility complex (MHC) Class I molecules expressed by other cells. For primate NK cells, the killer-cell immunoglobulin-like receptors (KIR) are a variable and rapidly evolving family of MHC Class I receptors. Studied here is KIR3DL1/S1, which encodes receptors for highly polymorphic human HLA-A and -B and comprises three ancient allelic lineages that have been preserved by balancing selection throughout human evolution. While the 3DS1 lineage of activating receptors has been conserved, the two 3DL1 lineages of inhibitory receptors were diversified through inter-lineage recombination with each other and with 3DS1. Prominent targets for recombination were D0-domain polymorphisms, which modulate enhancer function, and dimorphism at position 283 in the D2 domain, which influences inhibitory function. In African populations, unequal crossing over between the 3DL1 and 3DL2 genes produced a deleted KIR haplotype in which the telomeric "half'' was reduced to a single fusion gene with functional properties distinct from its 3DL1 and 3DL2 parents. Conversely, in Eurasian populations, duplication of the KIR3DL1/S1 locus by unequal crossing over has enabled individuals to carry and express alleles of all three KIR3DL1/S1 lineages. These results demonstrate how meiotic recombination combines with an ancient, preserved diversity to create new KIR phenotypes upon which natural selection acts. A consequence of such recombination is to blur the distinction between alleles and loci in the rapidly evolving human KIR gene family.
C1 [Norman, Paul J.; Abi-Rached, Laurent; Gendzekhadze, Ketevan; Hammond, John A.; Moesta, Achim K.; Sharma, Deepti; Graef, Thorsten; McQueen, Karina L.; Guethlein, Lisbeth A.; Parham, Peter] Stanford Univ, Sch Med, Dept Biol Struct, Stanford, CA 94305 USA.
[Norman, Paul J.; Abi-Rached, Laurent; Gendzekhadze, Ketevan; Hammond, John A.; Moesta, Achim K.; Sharma, Deepti; Graef, Thorsten; McQueen, Karina L.; Guethlein, Lisbeth A.; Parham, Peter] Stanford Univ, Sch Med, Dept Microbiol & Immunol, Stanford, CA 94305 USA.
[Carrington, Christine V. F.; Ramdath, D. Dan] Univ W Indies, Fac Med Sci, Dept Preclin Sci, St Augustine, Trinid & Tobago.
[Chandanayingyong, Dasdayanee] Mahidol Univ, Dept Transfus Med, Fac Med, Bangkok 10070, Thailand.
[Chandanayingyong, Dasdayanee] Mahidol Univ, Siriraj Hosp, Bangkok 10070, Thailand.
[Chang, Yih-Hsin] Chung Shan Med Univ, Sch Med Lab & Biotechnol, Taichung 402, Taiwan.
[Crespi, Catalina; Mila, Joan] Hosp Univ Son Dureta, Serv Immunol, Palma De Mallorca 07014, Spain.
[Saruhan-Direskeneli, Guher] Istanbul Univ, Istanbul Fac Med, Dept Physiol, TR-34093 Istanbul, Turkey.
[Hameed, Kamran] Aga Khan Univ Hosp, Dept Med, Karachi 74800, Pakistan.
[Kamkamidze, Giorgi] REA Ctr, Dept Clin Immunol, GE-0160 Tbilisi, Rep of Georgia.
[Koram, Kwadwo A.] Univ Ghana, Noguchi Mem Inst Med Res, Legon LG581, Ghana.
[Layrisse, Zulay] Venezuelan Res Inst IVIC, Ctr Med Expt Miguel Layrisse, Caracas 21827, Venezuela.
[Park, Myoung Hee] Seoul Natl Univ, Coll Med, Dept Lab Med, Seoul 110744, South Korea.
[Pitchappan, Ramasamy M.] Madurai Kamaraj Univ, Ctr Adv Studies Funct Genom, Sch Biol Sci, Madurai 625021, Tamil Nadu, India.
[Shiau, Ming-Yuh] Hung Kuang Univ, Taichung 433, Taiwan.
[Stephens, Henry A. F.] Royal Free & Univ Coll Med Sch, Ctr Nephrol, London NW3 2QG, England.
[Stephens, Henry A. F.] Royal Free & Univ Coll Med Sch, Anthony Nolan Trust, London NW3 2QG, England.
[Struik, Siske; Riley, Eleanor M.] London Sch Hyg & Trop Med, Dept Infect & Trop Med, London WC1E 7HT, England.
[Tyan, Dolly] Stanford Univ, Dept Pathol, Sch Med, Stanford, CA 94305 USA.
[Verity, David H.] Moorfields Eye Hosp, London EC1V 2PD, England.
[Vaughan, Robert W.] Guys & St Thomas Fdn Trust & Kings Coll, Clin Transplantat Lab, London SE1 9RT, England.
[Davis, Ronald W.; Ronaghi, Mostafa] Stanford Univ, Stanford Genome Technol Ctr, Sch Med, Palo Alto, CA 94304 USA.
[Fraser, Patricia A.] Immune Dis Inst, Boston, MA 02115 USA.
RP Parham, P (reprint author), Stanford Univ, Sch Med, Dept Biol Struct, Stanford, CA 94305 USA.
EM peropa@stanford.edu
RI Abi-Rached, Laurent/H-7236-2012; Park, Myoung Hee/J-5483-2012; Riley,
Eleanor/C-8960-2013; Crespi, Catalina/A-5543-2013;
OI Riley, Eleanor/0000-0003-3447-3570; Crespi,
Catalina/0000-0003-0781-9708; Moesta, Achim/0000-0001-9995-8398
FU NIAID NIH HHS [T32 AI007290]
NR 79
TC 45
Z9 47
U1 0
U2 9
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI WOODBURY
PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA
SN 1088-9051
J9 GENOME RES
JI Genome Res.
PD MAY
PY 2009
VL 19
IS 5
BP 757
EP 769
DI 10.1101/gr.085738.108
PG 13
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
GA 440AA
UT WOS:000265668800009
PM 19411600
ER
PT J
AU Olawaiye, AB
Boruta, DM
AF Olawaiye, Alexander B.
Boruta, David M., II
TI Management of women with clear cell endometrial cancer A Society of
Gynecologic Oncology (SGO) review
SO GYNECOLOGIC ONCOLOGY
LA English
DT Review
DE Clear cell; Staging; Radiotherapy; Chemotherapy
ID PEGYLATED LIPOSOMAL DOXORUBICIN; CLINICAL STAGE-I; PHASE-III TRIAL;
PACLITAXEL PLUS FILGRASTIM; RADIATION-THERAPY; HIGH-RISK; 1ST-LINE
CHEMOTHERAPY; CLINICOPATHOLOGICAL FEATURES; POSTOPERATIVE RADIATION;
ADJUVANT TREATMENT
AB Objective. Clear cell endometrial cancer (CCE) is an uncommon but important disease because of its aggressive behavior. Furthermore, prospective, randomized studies are either too difficult or impossible because of the small number of women affected. This review explores the differences between clear cell and endometrioid endometrial cancer. In addition, it uses available evidence to determine the best approach to management.
Methods. Medline was searched between January 1, 1966 and December 31, 2008 for all publications in English where the studied population included women diagnosed with CCE. Qualifying studies must have had at least 30 patients.
Results. Clear cell histology is diagnosed in less than 6% of all endometrial cancers and its incidence increases with age. Diagnosis can be made using the same tests that are used in the diagnosis of other types of endometrial cancer. Clear cell histology is morphologically and genetically different from the more prevalent endometrioid endometrial cancer histology. It shares many similarities with clear cell neoplasms of the ovary and kidney. Comprehensive surgical staging is critical in order to plan appropriate postoperative management. Adjuvant pelvic and/or whole abdominal radiotherapy have not been shown to be clearly beneficial ill women diagnosed with clear cell endometrial cancer. Adjuvant chemotherapy with cisplatinum, taxol and doxorubicin either in a doublet or triplet combination has demonstrated efficacy.
Conclusions. Women diagnosed with CCE require comprehensive surgical staging. Platinum based adjuvant chemotherapy in a doublet or triplet format in combination with paclitaxel and/or doxorubicin should be considered as part of treatment of these women. Careful long term surveillance following treatment is indicated given the higher rate of recurrence compared to endometrioid endometrial cancer. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Olawaiye, Alexander B.] Univ Pittsburgh, Med Ctr, Magee Womens Hosp, Dept Obstet Gynecol & Reprod Sci,Div Gynecol Onco, Pittsburgh, PA 15213 USA.
[Boruta, David M., II] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet Gynecol & Reprod Biol,Div Gynecol Onc, Boston, MA 02114 USA.
RP Olawaiye, AB (reprint author), Univ Pittsburgh, Med Ctr, Magee Womens Hosp, Dept Obstet Gynecol & Reprod Sci,Div Gynecol Onco, 300 Halket St, Pittsburgh, PA 15213 USA.
EM olawaiyea@upmc.edu; DBORUTA@PARTNERS.ORG
NR 60
TC 37
Z9 37
U1 0
U2 2
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD MAY
PY 2009
VL 113
IS 2
BP 277
EP 283
DI 10.1016/j.ygyno.2009.02.003
PG 7
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 436GJ
UT WOS:000265400400024
PM 19251307
ER
PT J
AU Pearson, SD
Lieber, SR
AF Pearson, Steven D.
Lieber, Sarah R.
TI Financial Penalties For The Unhealthy? Ethical Guidelines For Holding
Employees Responsible For Their Health
SO HEALTH AFFAIRS
LA English
DT Article
AB As health care costs continue to rise, an increasing number of self-insured employers are using financial rewards or penalties to promote healthy behavior and control costs. These incentive programs have triggered a backlash from those concerned that holding employees responsible for their health, particularly through the use of penalties, violates individual liberties and discriminates against the unhealthy. This paper offers an ethical analysis of employee health incentive programs and presents an argument for a set of conditions under which penalties can be used in an ethical and responsible way to contain health care costs and encourage healthy behavior among employees. [Health Affairs 28, no. 3 (2009): 845-852; 10.1377/hlthaff.28.3.845]
C1 [Pearson, Steven D.] Massachusetts Gen Hosp, Inst Clin & Econ Review, Boston, MA 02114 USA.
RP Pearson, SD (reprint author), NIH, Ctr Clin, Dept Bioeth, Bldg 10, Bethesda, MD 20892 USA.
EM spearson@icer-review.org; Lieber@post.harvard.edu
FU National Institutes of Health (NIH)
FX This research was supported in part by the Intramural Research Program
of the National Institutes of Health (NIH). The opinions expressed are
the authors' own. They do not represent any position or policy of the
NIH, Public Health Service, or Department of Health and Human Services.
NR 20
TC 22
Z9 23
U1 0
U2 4
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 MAY-JUN
PY 2009
VL 28
IS 3
BP 845
EP 852
DI 10.1377/hlthaff.28.3.845
PG 8
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA 441OV
UT WOS:000265779400030
PM 19414897
ER
PT J
AU Wolf, EJ
Mori, DL
AF Wolf, Erika J.
Mori, DeAnna L.
TI Avoidant Coping as a Predictor of Mortality in Veterans With End-Stage
Renal Disease
SO HEALTH PSYCHOLOGY
LA English
DT Article
DE end-stage renal disease; avoidant coping; mortality; COPE
ID URBAN HEMODIALYSIS-PATIENTS; BEHAVIORAL COMPLIANCE;
PSYCHOLOGICAL-FACTORS; PATIENT ADHERENCE; PRACTICE PATTERNS; DEPRESSION;
SURVIVAL; TRANSPLANTATION; STRATEGIES; DIALYSIS
AB Objective: The aim of this study was to examine the role of active and avoidant coping strategies in predicting mortality in 61 veterans with end-stage renal disease. Design: Participants completed a self-report measure of coping strategies (The COPE; Carver, Scheier, & Weintraub, 1989) and were interviewed as part of a structured assessment to determine their appropriateness for renal transplant. On average, participants were then followed for 9 years via medical record review to determine mortality status. Main Outcome Measures: Mortality, as predicted by factor scores on active and avoidant coping factors estimated via confirmatory factor analysis of select COPE subscales. Results: A Cox regression revealed that a unit change in avoidant coping was associated with a 114% increase in odds of mortality, even after controlling for variance attributable to demographic variables. There was also a statistical trend indicating that this association might be mediated by poor attendance at medical appointments. Active coping did not predict mortality. Conclusion: Results demonstrate the importance of assessing coping style in this population; clinical implications of these findings and possible mechanisms of this effect are discussed.
C1 [Wolf, Erika J.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA.
[Mori, DeAnna L.] Boston Univ, Sch Med, Boston, MA 02215 USA.
[Wolf, Erika J.] Boston Univ, Dept Psychol, Boston, MA 02215 USA.
RP Mori, DL (reprint author), VA Boston Healthcare Syst 116B, 150 S Huntington Ave, Boston, MA 02130 USA.
EM deanna.mori@va.gov
OI Wolf, Erika/0000-0003-2666-2435
FU National Institute of Mental Health [5F31MH074267]
FX This research was supported, in part, by National Institute of Mental
Health Grant 5F31MH074267 awarded to Erika J. Wolf.
NR 40
TC 13
Z9 14
U1 5
U2 10
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0278-6133
J9 HEALTH PSYCHOL
JI Health Psychol.
PD MAY
PY 2009
VL 28
IS 3
BP 330
EP 337
DI 10.1037/a0013583
PG 8
WC Psychology, Clinical; Psychology
SC Psychology
GA 445XM
UT WOS:000266084800009
PM 19450039
ER
PT J
AU Smith, JG
Lowe, JK
Kovvali, S
Maller, JB
Salit, J
Daly, MJ
Stoffel, M
Altshuler, DM
Friedman, JM
Breslow, JL
Newton-Cheh, C
AF Smith, J. Gustav
Lowe, Jennifer K.
Kovvali, Sirisha
Maller, Julian B.
Salit, Jacqueline
Daly, Mark J.
Stoffel, Markus
Altshuler, David M.
Friedman, Jeffrey M.
Breslow, Jan L.
Newton-Cheh, Christopher
TI Genome-wide association study of electrocardiographic conduction
measures in an isolated founder population: Kosrae
SO HEART RHYTHM
LA English
DT Article
DE Conduction; Electrocardiography; Electrophysiology; Genetics; Ion
channels
ID SICK SINUS SYNDROME; CHANNEL GENE SCN5A; ATRIAL-FIBRILLATION; CARDIAC
CONDUCTION; HEART-FAILURE; WHOLE-GENOME; VARIABILITY; MUTATIONS;
VARIANTS; DISEASE
AB BACKGROUND Cardiac conduction, as assessed by electrocardiographic PR interval and QRS duration, is an important electrophysiological trait and a determinant of arrhythmia risk.
OBJECTIVE We sought to identify common genetic determinants of these measures.
METHODS We examined 1604 individuals from the island of Kosrae, Federated States of Micronesia, an isolated founder population. We adjusted for covariates and estimated the heritability of quantitative electrocardiographic QRS duration and PR interval and, secondarily, its subcomponents, P-wave duration and PR segment. Finally, we performed a genome-wide association study (GWAS) in a subset of 1262 individuals genotyped using the Affymetrix GeneChip Human Mapping 500K microarray.
RESULTS The heritability of PR interval was 34% (standard error [SE] 5%, P = 4 x 10(-18)); of PR segment, 31% (SE 6%, P = 3.2 x 10(-13)); and of P-wave duration, 17% (SE 5%, P = 5.8 x 10(-6)), but the heritablitity of QRS duration was only 3% (SE 4%, P = .20). Hence, GWAS was performed only for the PR interval and its subcomponents. A total of 338,049 single nucleotide polymorphisms (SNPs) passed quality filters. For the PR interval, the most significantly associated SNPs were located in and downstream of the alpha-subunit of the cardiac voltage-gated sodium channel gene SCN5A, with a 4.8 ms (SE 1.0) or 0.23 standard deviation increase in adjusted PR interval for each minor allele copy of rs7638909 (P = 1.6 x 10(-6), minor allele frequency 0.40). These SNPs were also associated with P-wave duration (P = 1.5 x 10(-4)) and PR segment (P = .01) but not with QRS duration (P >= .22).
CONCLUSIONS The PR interval and its subcomponents showed substantial heritability in a South Pacific islander population and were associated with common genetic variation in SCN5A.
C1 [Newton-Cheh, Christopher] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Ctr Human Genet Res, Boston, MA 02114 USA.
[Lowe, Jennifer K.; Altshuler, David M.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
[Smith, J. Gustav; Lowe, Jennifer K.; Kovvali, Sirisha; Maller, Julian B.; Daly, Mark J.; Altshuler, David M.; Newton-Cheh, Christopher] MIT, Cambridge, MA 02139 USA.
[Maller, Julian B.] Univ Oxford, Dept Stat, Oxford OX1 3TG, England.
[Stoffel, Markus] Swiss Fed Inst Technol, Inst Mol Syst Biol, Zurich, Switzerland.
[Breslow, Jan L.] Rockefeller Univ, Biochem Genet & Metab Lab, New York, NY 10021 USA.
[Salit, Jacqueline; Friedman, Jeffrey M.] Rockefeller Univ, Mol Genet Lab, New York, NY 10021 USA.
RP Newton-Cheh, C (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Ctr Human Genet Res, 185 Cambridge St,CPZN 5-242, Boston, MA 02114 USA.
EM cnewtoncheh@chgr.mgh.harvard.edu
RI Altshuler, David/A-4476-2009; Breslow, Jan/B-7544-2008;
OI Altshuler, David/0000-0002-7250-4107; Maller, Julian/0000-0002-1565-9559
FU National Institutes of Health [NIH K23-HL-080025]; Doris Duke Charitable
Foundation Clinical Scientist Development; Burroughs Wellcome Fund
Career; Basic Research front the Massachusetts Biomedical Research
Corporation; Burroughs Wellcome Fund Clinical Scholar in Translational
Research and a Distinguished Clinical Scholar of the Doris Duke
Charitable Foundation; Starr Foundation; Howard Hughes Medical Institute
FX Dr. Newton-Cheh was supported by National Institutes of Health grant no,
NIH K23-HL-080025. a Doris Duke Charitable Foundation Clinical Scientist
Development Award. and a Burroughs Wellcome Fund Career Award for
Medical Scientists. J.K. Lowe was supported by a Tosteson Post-Doctoral
Fellowship for Basic Research front the Massachusetts Biomedical
Research Corporation. Dr. Altshuler is a Burroughs Wellcome Fund
Clinical Scholar in Translational Research and a Distinguished Clinical
Scholar of the Doris Duke Charitable Foundation. The genome-wide
association scan on Kosrae was supported by grants from the Starr
Foundation and Howard Hughes Medical Institute.
NR 37
TC 35
Z9 35
U1 0
U2 2
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 MAY
PY 2009
VL 6
IS 5
BP 634
EP 641
DI 10.1016/j.hrthm.2009.02.022
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 440VY
UT WOS:000265729000011
PM 19389651
ER
PT J
AU Andersson, KL
Chung, RT
AF Andersson, Karin L.
Chung, Raymond T.
TI Monitoring During and After Antiviral Therapy for Hepatitis B
SO HEPATOLOGY
LA English
DT Article; Proceedings Paper
CT NIH Consensus Development Conference on Management of Hepatitis B Virus
CY OCT 20-22, 2008
CL Bethesda, MD
SP Natl Inst Hlth
ID TERM-FOLLOW-UP; ALANINE AMINOTRANSFERASE LEVELS; VIRUS-DNA; LAMIVUDINE
THERAPY; PEGINTERFERON ALPHA-2A; VIROLOGICAL RESPONSE; ADEFOVIR
DIPIVOXIL; LIVER FIBROSIS; STIFFNESS MEASUREMENT; SUSTAINED RESPONSE
AB Recent studies suggest that long-term suppression of viral replication is critical to reducing the complications of chronic hepatitis B virus (HBV) infection. Monitoring for continued virological response during and after treatment is essential because current treatment options have limited success in achieving durable endpoints, and antiviral resistance may emerge during long-term therapy. Methods of monitoring treatment response include tests for serum aminotransferase levels, HBV DNA level, hepatitis B e antigen (HBeAg) and antibody (anti-HBe), hepatitis B surface antigen (HBsAg) or antibody (anti-HBs), and liver histology. Virological suppression and loss of HBeAg or HBsAg with or without seroconversion play a prominent role in decision-making regarding the success and duration of antiviral therapy. Guidelines recommend that testing for serum markers be repeated every 12-24 weeks during antiviral therapy and every 6-12 months afterward. Recent data also suggest that serum HBV DNA levels should be assessed at weeks 12 and 24 of therapy, because early viral response may predict the likelihood of sustained response and antiviral resistance. The use of serum HBV DNA levels for this purpose requires an assay with a wide range of quantification, such as real-time polymerase chain reaction assays, which have a 7-8 log(10) dynamic range. Newer, investigational methods for monitoring treatment response include quantitative measurement of HBsAg, HBeAg, and intrahepatic covalently closed circular DNA. Conclusions. Better methods for defining durable treatment endpoints are needed. Other areas requiring further research include the optimal treatment duration and the establishment of the optimal use of early viral kinetics for decision-making during antiviral therapy. (HEPATOLOGY 2009;49:S166-S173.)
C1 [Andersson, Karin L.; Chung, Raymond T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA.
RP Chung, RT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA.
EM rtchung@partners.org
FU NIDDK NIH HHS [U01 DK082919-01, U01 DK082919, DK-82919]
NR 49
TC 21
Z9 23
U1 0
U2 1
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD MAY
PY 2009
VL 49
IS 5
BP S166
EP S173
DI 10.1002/hep.22899
PG 8
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 439ZZ
UT WOS:000265668700020
PM 19399793
ER
PT J
AU Dienstag, JL
AF Dienstag, Jules L.
TI Benefits and Risks of Nucleoside Analog Therapy for Hepatitis B
SO HEPATOLOGY
LA English
DT Article; Proceedings Paper
CT NIH Consensus Development Conference on Management of Hepatitis B Virus
CY OCT 20-22, 2008
CL Bethesda, MD
SP Natl Inst Hlth
ID SEVERELY DECOMPENSATED CIRRHOSIS; AWAITING LIVER-TRANSPLANTATION;
TENOFOVIR DISOPROXIL FUMARATE; LONG-TERM THERAPY; ADEFOVIR DIPIVOXIL;
LAMIVUDINE TREATMENT; VIROLOGICAL RESPONSE; ENTECAVIR THERAPY; HBV
INFECTION; GLOBE TRIAL
AB Five oral agents have been approved for the treatment of chronic hepatitis B, ranging in virological potency, clinical efficacy, barrier to resistance, and side-effect profile. The degree of histological, biochemical, and serological improvement with therapy generally corresponds to the degree of suppression of serum hepatitis B virus (HBV) DNA achieved with therapy. Conversely, for agents with a low barrier to resistance, the profundity of HBV DNA suppression in individual patients correlates inversely with the likelihood of resistance. The durability of hepatitis B e antigen (HBeAg) responses after a consolidation period of an additional 6-12 months of therapy is similar to 80% in western populations, lower in Asian populations. Loss of hepatitis B surface antigen (HBsAg) during a year of oral-agent therapy is limited, except with the most potent agents, but extending therapy for a second year and beyond can yield frequencies of HBsAg responses close to those reported in trials of interferon-based therapy. The oral agents are approved for 1-2 years of therapy, but treatment is continued indefinitely in the majority of patients (except for the similar to 20% of patients who are HBeAg-reactive who achieve a durable HBeAg response). HBeAg responses and virological/biochemical benefit continue to be maintained and to increase with continued therapy beyond the first year. Data continue to accumulate supporting the link between long-term HBV DNA suppression and reduction in hepatic fibrosis, hepatic decompensation, and liver-related mortality. All the benefits of a single year of injectable peginterferon therapy can be achieved with the newer, low-resistance oral agents continued beyond the first year, without interferon side effects. Future studies are needed to develop drug regimens that are even more effective in achieving clinical endpoints, that are not hampered by resistance, and that are more confined in treatment duration but are more durable. (HEPATOLOGY 2009;49: S112-S121.)
C1 [Dienstag, Jules L.] Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, Boston, MA 02114 USA.
[Dienstag, Jules L.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Dienstag, Jules L.] Harvard Univ, Sch Med, Off Dean Med Educ, Boston, MA USA.
RP Dienstag, JL (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, Jackson 7,55 Fruit St, Boston, MA 02114 USA.
EM jdienstag@partners.org
FU NCRR NIH HHS [M01RR-01066]; NIDDK NIH HHS [1U01-DK08-2919,
N01-DK-9-2319]
NR 58
TC 51
Z9 55
U1 0
U2 0
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD MAY
PY 2009
VL 49
IS 5
BP S112
EP S121
DI 10.1002/hep.22920
PG 10
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 439ZZ
UT WOS:000265668700014
PM 19399795
ER
PT J
AU Bennetto-Hood, C
Johnson, VA
King, JR
Hoesley, CJ
Acosta, EP
AF Bennetto-Hood, Chantelle
Johnson, Victoria A.
King, Jennifer R.
Hoesley, Craig J.
Acosta, Edward P.
TI Novel Methodology for Antiretroviral Quantitation in the Female Genital
Tract
SO HIV CLINICAL TRIALS
LA English
DT Article
DE antiretroviral; drug monitoring; women
ID IMMUNODEFICIENCY-VIRUS TYPE-1; CERVICOVAGINAL SECRETIONS; HIV-1 RNA;
HIV-1-INFECTED WOMEN; BLOOD; THERAPY; SEMEN; PLASMA; MEN
AB Purpose: Challenges exist regarding antiretroviral quantitation in the female genital tract. Endocervical wicking using sterile tear flow test strips is an alternative to conventional methods due to the consistent sample volume obtained. Methods: A novel method for measuring antiretrovirals in cervicovaginal secretions using Sno-strip (R) wicking was developed and tested by spiking Sno-strips (R) with known concentrations of tenofovir, nevirapine, atazanavir, lopinavir, and ritonavir in blank cervicovaginal lavage fluid. Drug concentrations were determined by high-performance liquid chromatography with ultraviolet or mass spectrometry detection. Results: Mean extraction recoveries were 91% for tenofovir, 89% for nevirapine, 63% for atazanavir, 60% for lopinavir, and 61% for ritonavir relative to controls. Freezing spiked samples for 24 hours at -80 degrees C had no effect on recovery. Conclusions: Results suggest that the antiretrovirals tested can be efficiently extracted from Sno-strips (R), although a greater percentage of tenofovir and nevirapine was recovered. Storage of Sno-strip (R) samples up to 24 hours before analysis showed no difference in the percentage of drug recovered compared with immediate analysis. Quantitating antiretroviral penetration into the female genital tract may assist in determining optimal therapeutic antiretroviral regimens to both decrease the risk of HIV transmission and prevent development of HIV drug resistance.
C1 [Bennetto-Hood, Chantelle; King, Jennifer R.; Acosta, Edward P.] Univ Alabama, Div Clin Pharmacol, Sch Med, Birmingham, AL 35294 USA.
[Johnson, Victoria A.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA.
[Johnson, Victoria A.; Hoesley, Craig J.] Univ Alabama, Div Infect Dis, Sch Med, Birmingham, AL 35294 USA.
RP Acosta, EP (reprint author), Univ Alabama, Div Clin Pharmacol, Sch Med, 1530 3rd Ave S,VH 116, Birmingham, AL 35294 USA.
EM eacosta@uab.edu
FU National Institute of Allergy and Infectious Diseases [U01AI38858];
Birmingham VA Medical Center; UAB CFAR core clinic and laboratory
facilities; [P30 AI27767]
FX This work was supported by Dr. Victoria A. Johnson's VA Merit Review
entitled "Drug Resistance in Genital Tract Viruses Derived from
HIV-Infected Women." The pharmacology laboratory was supported, in part,
by the Adult: AIDS Clinical Trials Group Central Grant U01AI38858 of the
National Institute of Allergy and Infectious Diseases. Dr. Johnson also
acknowledges P30 AI27767 and the Birmingham VA Medical Center and UAB
CFAR core clinic and laboratory facilities.
NR 17
TC 3
Z9 3
U1 0
U2 0
PU THOMAS LAND PUBLISHERS, INC
PI ST LOUIS
PA 255 JEFFERSON RD, ST LOUIS, MO 63119 USA
SN 1528-4336
J9 HIV CLIN TRIALS
JI HIV Clin. Trials
PD MAY-JUN
PY 2009
VL 10
IS 3
BP 193
EP 199
DI 10.1310/hct1003-193
PG 7
WC Infectious Diseases; Pharmacology & Pharmacy
SC Infectious Diseases; Pharmacology & Pharmacy
GA 471SP
UT WOS:000268078900008
PM 19632958
ER
PT J
AU Huppert, TJ
Allen, MS
Diamond, SG
Boas, DA
AF Huppert, Theodore J.
Allen, Monica S.
Diamond, Solomon G.
Boas, David A.
TI Estimating Cerebral Oxygen Metabolism From fMRI With a Dynamic
Multicompartment Windkessel Model
SO HUMAN BRAIN MAPPING
LA English
DT Article
DE cerebral metabolism; functional neuroimaging; vascular modeling
ID NEAR-INFRARED SPECTROSCOPY; MEAN TRANSIT-TIME; BLOOD-VOLUME;
OXIDATIVE-METABOLISM; OPTICAL PATHLENGTH; HEMODYNAMIC-RESPONSE;
FUNCTIONAL MRI; BRAIN-FUNCTION; BALLOON MODEL; BASE-LINE
AB Stimulus evoked changes in cerebral blood flow, volume, and oxygenation arise from responses to underlying neuronally mediated changes in vascular tone and cerebral oxygen metabolism. There is increasing evidence that the magnitude and temporal characteristics of these evoked hemodynamic changes are additionally influenced by the local properties of the vasculature including the levels of baseline cerebral blood flow, volume, and blood oxygenation. In this work, we utilize a physiologically motivated vascular model to describe the temporal characteristics of evoked hemodynamic responses and their expected relationships to the structural and biomechanical properties of the underlying vasculature. We use this model in a temporal curve-fitting analysis of the high-temporal resolution functional MRI data to estimate the underlying cerebral vascular and metabolic responses in the brain. We present evidence for the feasibility of our model-based analysis to estimate transient changes in the cerebral metabolic rate of oxygen (CMRO(2)) in the human motor cortex from combined pulsed arterial spin labeling (ASL) and blood oxygen level dependent (BOLD) MRI. We examine both the numerical characteristics of this model and present experimental evidence to support this model by examining concurrently measured ASL, BOLD, and near-infrared spectroscopy to validate the calculated changes in underlying CMRO(2). Hum Brain Mapp 30:1548-1567, 2009. (C) 2008 Wiley-Liss, Inc.
C1 [Huppert, Theodore J.] Univ Pittsburgh, UPMC Presbyterian, Dept Radiol, Pittsburgh, PA 15213 USA.
[Huppert, Theodore J.; Diamond, Solomon G.; Boas, David A.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA.
[Allen, Monica S.] Univ Texas Arlington, Dept Elect Engn, Arlington, TX 76019 USA.
[Diamond, Solomon G.] Dartmouth Coll, Thayer Sch Engn, Dept Engn, Hanover, NH 03755 USA.
[Boas, David A.] MGH, HMS, Dept Radiol, Cambridge, MA USA.
RP Huppert, TJ (reprint author), Univ Pittsburgh, UPMC Presbyterian, Dept Radiol, 200 Lothrop St, Pittsburgh, PA 15213 USA.
EM huppertt@upmc.edu
OI Diamond, Solomon/0000-0002-7589-2942
FU Howard Hughes Medical Institute predoctorial fellowship program; Rudolph
Hermann Doctoral fellowship; National Institutes of Health
[R01-EB002482, R01-EB000790, T32-CA09502, P41-RR14075]; NCRR, MIND
Institute
FX The Howard Hughes Medical Institute predoctorial fellowship program
funded T.J.H. M.S.A. was funded by the Rudolph Hermann Doctoral
fellowship at UTA. The authors thank Christiana Andre, Danny Joseph, Div
Bolar, and Drs. Maria Franceschini, Rick Hoge for their assistance with
the collection of this data. The authors also thank Heval Benav and Drs.
Simon Arridge, Ville Kolehmainen, and Joe Mandeville for helpful
discussion of this manuscript.
NR 59
TC 28
Z9 28
U1 0
U2 5
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1065-9471
J9 HUM BRAIN MAPP
JI Hum. Brain Mapp.
PD MAY
PY 2009
VL 30
IS 5
BP 1548
EP 1567
DI 10.1002/hbm.20628
PG 20
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 440VK
UT WOS:000265727600013
PM 18649348
ER
PT J
AU Taube, R
Zhu, Q
Marasco, WA
AF Taube, R.
Zhu, Q.
Marasco, W. A.
TI Lentivirus Display: Stable Expression of Human Antibodies on the Surface
of Human Cells and Virus Particles
SO HUMAN GENE THERAPY
LA English
DT Meeting Abstract
CT 6th Annual Conference of the Israeli-Society-of-Gene-and-Cell-Therapy
CY MAY 04, 2009
CL Ben Gurion Univ, Beer Sheva, ISRAEL
SP Israel Soc Gene & Cell Therapy
HO Ben Gurion Univ
C1 [Zhu, Q.; Marasco, W. A.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Taube, R.] Ben Gurion Univ Negev, Div Basic Sci, IL-84105 Beer Sheva, Israel.
EM rantaube@bgu.ac.il
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1043-0342
J9 HUM GENE THER
JI Hum. Gene Ther.
PD MAY
PY 2009
VL 20
IS 5
BP 537
EP 537
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 445DU
UT WOS:000266030700027
ER
PT J
AU Kallio, SP
Jakkula, E
Purcell, S
Suvela, M
Koivisto, K
Tienari, PJ
Elovaara, I
Pirttila, T
Reunanen, M
Bronnikov, D
Viander, M
Meri, S
Hillert, J
Lundmark, F
Harbo, HF
Lorentzen, AR
De Jager, PL
Daly, MJ
Hafler, DA
Palotie, A
Peltonen, L
Saarela, J
AF Kallio, Suvi P.
Jakkula, Eveliina
Purcell, Shaun
Suvela, Minna
Koivisto, Keijo
Tienari, Pentti J.
Elovaara, Irina
Pirttila, Tuula
Reunanen, Mauri
Bronnikov, Denis
Viander, Markku
Meri, Seppo
Hillert, Jan
Lundmark, Frida
Harbo, Hanne F.
Lorentzen, Aslaug R.
De Jager, Philip L.
Daly, Mark J.
Hafler, David A.
Palotie, Aarno
Peltonen, Leena
Saarela, Janna
TI Use of a genetic isolate to identify rare disease variants: C7 on 5p
associated with MS
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; TURKISH MULTIPLE-SCLEROSIS;
COMPLEMENT-SYSTEM; FAMILIAL HYPERCHOLESTEROLEMIA; HAPLOTYPE
RECONSTRUCTION; LINKAGE DISEQUILIBRIUM; INTERLEUKIN-7 RECEPTOR;
DIAGNOSTIC-CRITERIA; GENOME SCREEN; AXONAL INJURY
AB Large case-control genome-wide association studies primarily expose common variants contributing to disease pathogenesis with modest effects. Thus, alternative strategies are needed to tackle rare, possibly more penetrant alleles. One strategy is to use special populations with a founder effect and isolation, resulting in allelic enrichment. For multiple sclerosis such a unique setting is reported in Southern Ostrobothnia in Finland, where the prevalence and familial occurrence of multiple sclerosis (MS) are exceptionally high. Here, we have studied one of the best replicated MS loci, 5p, and monitored for haplotypes shared among 72 regional MS cases, the majority of which are genealogically distantly related. The haplotype analysis over the 45 Mb region, covering the linkage peak identified in Finnish MS families, revealed only modest association at IL7R (P = 0.04), recently implicated in MS, whereas most significant association was found with one haplotype covering the C7-FLJ40243 locus (P = 0.0001), 5.1 Mb centromeric of IL7R. The finding was validated in an independent sample from the isolate and resulted in an odds ratio of 2.73 (P = 0.000003) in the combined data set. The identified relatively rare risk haplotype contains C7 (complement component 7), an important player of the innate immune system. Suggestive association with alleles of the region was seen also in more heterogeneous populations. Interestingly, also the complement activity correlated with the identified risk haplotype. These results suggest that the MS predisposing locus on 5p is more complex than assumed and exemplify power of population isolates in the identification of rare disease alleles.
C1 [Kallio, Suvi P.; Jakkula, Eveliina; Suvela, Minna; Bronnikov, Denis; Peltonen, Leena] Biomedicum, FIMM, Helsinki, Finland.
[Kallio, Suvi P.; Jakkula, Eveliina; Bronnikov, Denis; Peltonen, Leena] Univ Helsinki, Dept Med Genet, Helsinki, Finland.
[Tienari, Pentti J.] Univ Helsinki, Mol Neurol Res Program, Helsinki, Finland.
[Meri, Seppo] Univ Helsinki, Dept Bacteriol & Immunol, Helsinki, Finland.
[Palotie, Aarno] Univ Helsinki, Finnish Genome Ctr, Helsinki, Finland.
[Palotie, Aarno] Univ Helsinki, FIMM, Helsinki, Finland.
[Palotie, Aarno] Univ Helsinki, Dept Clin Chem, SF-00100 Helsinki, Finland.
[Kallio, Suvi P.; Jakkula, Eveliina; Suvela, Minna; Bronnikov, Denis; Peltonen, Leena; Saarela, Janna] Biomedicum, Natl Inst Hlth & Welf, Helsinki, Finland.
[Jakkula, Eveliina; Purcell, Shaun; De Jager, Philip L.; Daly, Mark J.; Hafler, David A.; Palotie, Aarno; Peltonen, Leena] Harvard & MIT, Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
[Purcell, Shaun; Daly, Mark J.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[De Jager, Philip L.; Daly, Mark J.] Harvard Univ, Sch Med, Partners Healthcare Ctr Genet & Genom, Boston, MA USA.
[Koivisto, Keijo] Seinajoki Cent Hosp, Dept Neurol, Seinajoki, Finland.
[Elovaara, Irina] Tampere Univ Hosp, Dept Neurol, Tampere, Finland.
[Elovaara, Irina; Saarela, Janna] Univ Tampere, Sch Med, FIN-33101 Tampere, Finland.
[Pirttila, Tuula] Kuopio Univ Hosp, Dept Neurol & Neurosci, SF-70210 Kuopio, Finland.
[Reunanen, Mauri] Oulu Univ Hosp, Dept Neurol, Oulu, Finland.
[Viander, Markku] Univ Turku, Dept Med Microbiol & Immunol, Turku, Finland.
[Hillert, Jan; Lundmark, Frida] Karolinska Univ, Huddinge Hosp, Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
[Lorentzen, Aslaug R.] Univ Oslo, Ulleval Univ Hosp, Dept Neurol, Fac Div, Oslo, Norway.
[Lorentzen, Aslaug R.] Univ Oslo, Rikshosp, Univ Hosp, Inst Immunol, N-0027 Oslo, Norway.
[De Jager, Philip L.; Hafler, David A.] Brigham & Womens Hosp, Ctr Neurol Dis, Dept Neurol, Boston, MA 02115 USA.
[Palotie, Aarno; Peltonen, Leena] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
RP Peltonen, L (reprint author), Biomedicum, FIMM, Helsinki, Finland.
EM leena@sanger.ac.uk
RI Tienari, Pentti/A-4893-2012; Saarela, Janna/E-5369-2014;
OI Saarela, Janna/0000-0002-0853-6219
FU National Institutes of Health [RO1 NS 43559]; Center of Excellence for
Disease Genetics of the Academy of Finland; Sigrid Juselius Foundation;
Biocentrum Helsinki Foundation; Helsinki University Central Hospital
Research Foundation; Multiple Sclerosis Foundation of USA; Harry Weaver
Neuroscience Scholar Award; National Multiple Sclerosis Society;
Neuropromise EU project [LSHMCT2005-018637]; National Center for
Research Resources [U54 RR020278]; SGENE EU project
[LSHM-CT-2006-037761]; Simons Foundation [R01MH71425-01A1]
FX This work was supported by National Institutes of Health ( grant RO1 NS
43559), Center of Excellence for Disease Genetics of the Academy of
Finland, the Sigrid Juselius Foundation, the Biocentrum Helsinki
Foundation, Helsinki University Central Hospital Research Foundation,
the Multiple Sclerosis Foundation of USA, a Harry Weaver Neuroscience
Scholar Award from National Multiple Sclerosis Society ( P. L. D.) and
the Neuropromise EU project ( grant LSHMCT2005-018637). The Broad
Institute Center for Genotyping and Analysis is supported by the
National Center for Research Resources ( grant U54 RR020278). The
genotyping of the Health 2000 controls was funded by the SGENE EU
project (LSHM-CT-2006-037761) and Simons Foundation (R01MH71425-01A1).
NR 60
TC 17
Z9 17
U1 0
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD MAY 1
PY 2009
VL 18
IS 9
BP 1670
EP 1683
DI 10.1093/hmg/ddp073
PG 14
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 431WS
UT WOS:000265096100013
PM 19221116
ER
PT J
AU Velez, JCQ
Ryan, KJ
Harbeson, CE
Bland, AM
Budisavljevic, MN
Arthur, JM
Fitzgibbon, WR
Raymond, JR
Janech, MG
AF Velez, Juan Carlos Q.
Ryan, Kevin J.
Harbeson, Caroline E.
Bland, Alison M.
Budisavljevic, Milos N.
Arthur, John M.
Fitzgibbon, Wayne R.
Raymond, John R.
Janech, Michael G.
TI Angiotensin I Is Largely Converted to Angiotensin (1-7) and Angiotensin
(2-10) by Isolated Rat Glomeruli
SO HYPERTENSION
LA English
DT Article; Proceedings Paper
CT 62nd Annual Fall Conference and Scientific Sessions of the
American-Heart-Association-Council-for-High-Blood-Pressure-Research
CY SEP 17-20, 2008
CL Atlanta, GA
SP Amer Heart Assoc Council High Blood Presure Res
DE renin-angiotensin system; neprilysin; aminopeptidase A;
angiotensin-converting enzyme; angiotensin II; podocytes; des-Asp
(1)-angiotensin I
ID RENOVASCULAR HYPERTENSION; FLUID CONCENTRATIONS; ANESTHETIZED RATS;
PROXIMAL TUBULES; AMINOPEPTIDASE-A; MESANGIAL CELLS; KIDNEY; CONVERSION;
ENZYME; CHYMASE
AB Intraglomerular renin-angiotensin system enzyme activities have been examined previously using glomerular lysates and immune-based assays. However, preparation of glomerular extracts compromises the integrity of their anatomic architecture. In addition, antibody-based assays focus on angiotensin (Ang) II detection, ignoring the generation of other Ang I-derived metabolites, some of which may cross-react with Ang II. Therefore, our aim was to examine the metabolism of Ang I in freshly isolated intact glomeruli using matrix-assisted laser desorption ionization time of flight mass spectrometry as an analytic method. Glomeruli from male Sprague-Dawley rats were isolated by sieving and incubated in Krebs buffer in the presence of 1 mu mol/L of Ang I for 15 to 90 minutes, with or without various peptidase inhibitors. Peptide sequences were confirmed by matrix-assisted laser desorption ionization time of flight tandem mass spectrometry or linear-trap-quadrupole mass spectrometry. Peaks were quantified using customized valine-(13)C(center dot 15)N-labeled peptides as standards. The most prominent peaks resulting from Ang I cleavage were 899 and 1181 m/z, corresponding with Ang (1-7) and Ang (2-10), respectively. Smaller peaks for Ang II, Ang (1-9), and Ang (3-10) also were detected. The disappearance of Ang I was significantly reduced during inhibition of aminopeptidase A or neprilysin. In contrast, captopril did not alter Ang I degradation. Furthermore, during simultaneous inhibition of aminopeptidase A and neprilysin, the disappearance of Ang I was markedly attenuated compared with all of the other conditions. These results suggest that there is prominent intraglomerular conversion of Ang I to Ang (2-10) and Ang (1-7), mediated by aminopeptidase A and neprilysin, respectively. Formation of these alternative Ang peptides may be critical to counterbalance the local actions of Ang II. Enhancement of these enzymatic activities may constitute potential therapeutic targets for Ang II-mediated glomerular diseases. (Hypertension. 2009; 53: 790-797.)
C1 [Velez, Juan Carlos Q.; Ryan, Kevin J.; Harbeson, Caroline E.; Bland, Alison M.; Budisavljevic, Milos N.; Arthur, John M.; Fitzgibbon, Wayne R.; Raymond, John R.; Janech, Michael G.] Med Univ S Carolina, Div Nephrol, Dept Med, Charleston, SC 29425 USA.
[Velez, Juan Carlos Q.; Budisavljevic, Milos N.; Arthur, John M.; Raymond, John R.; Janech, Michael G.] Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, Med & Res Serv, Charleston, SC 29425 USA.
RP Velez, JCQ (reprint author), Med Univ S Carolina, Div Nephrol, Dept Med, 96 Jonathan Lucas St,CSB,Room 829, Charleston, SC 29425 USA.
EM velezj@musc.edu
RI Velez, Juan Carlos/N-3782-2016;
OI Janech, Michael/0000-0002-3202-4811
FU NIDDK NIH HHS [K08 DK080944-01, K08 DK080944]
NR 35
TC 25
Z9 26
U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0194-911X
J9 HYPERTENSION
JI Hypertension
PD MAY
PY 2009
VL 53
IS 5
BP 790
EP 797
DI 10.1161/HYPERTENSIONAHA.109.128819
PG 8
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 436XW
UT WOS:000265450400010
PM 19289651
ER
PT J
AU Sun, N
Liu, Y
Lee, H
Weissleder, R
Ham, D
AF Sun, Nan
Liu, Yong
Lee, Hakho
Weissleder, Ralph
Ham, Donhee
TI CMOS RF Biosensor Utilizing Nuclear Magnetic Resonance
SO IEEE JOURNAL OF SOLID-STATE CIRCUITS
LA English
DT Article; Proceedings Paper
CT IEEE Radio Frequency Integrated Circuits Symposium (RFIC)
CY JUN 15-17, 2008
CL Atlanta, GA
DE Biosensor; CMOS integrated circuit; low noise amplifier; nuclear
magnetic resonance; RF transceiver
ID NOISE
AB We report on a CMOS RF transceiver designed for detection of biological objects such as cancer marker proteins. Its main function is to manipulate and monitor RF dynamics of protons in water via nuclear magnetic resonance (NMR). Target objects alter the proton dynamics, which is the basis for our biosensing. The RF transceiver has a measured receiver noise figure of 0.7 dB. This high sensitivity enabled construction of an entire NMR system around the RF transceiver in a 2-kg portable platform, which is 60 times lighter, 40 times smaller, yet 60 times more mass sensitive than a state-of-the-art commercial benchtop system. Sensing 20 fmol and 1.4 ng of avidin (protein) in a 5 mu L sample volume, our system represents a circuit designer's approach to pursue low-cost diagnostics in a portable platform.
C1 [Sun, Nan; Ham, Donhee] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
[Lee, Hakho; Weissleder, Ralph] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA.
RP Sun, N (reprint author), Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
EM nansun@seas.har-vard.edu; donhee@seas.harvard.edu
RI Liu, Yong/J-3636-2014
NR 19
TC 52
Z9 52
U1 1
U2 9
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA
SN 0018-9200
J9 IEEE J SOLID-ST CIRC
JI IEEE J. Solid-State Circuit
PD MAY
PY 2009
VL 44
IS 5
BP 1629
EP 1643
DI 10.1109/JSSC.2009.2017007
PG 15
WC Engineering, Electrical & Electronic
SC Engineering
GA 443UP
UT WOS:000265936600028
ER
PT J
AU Cai, GF
Freeman, GJ
AF Cai, Guifang
Freeman, Gordon J.
TI The CD160, BTLA, LIGHT/HVEM pathway: a bidirectional switch regulating
T-cell activation
SO IMMUNOLOGICAL REVIEWS
LA English
DT Review
DE CD160; BTLA; HVEM; LIGHT; coinhibition; costimulation
ID HERPESVIRUS ENTRY MEDIATOR; TUMOR-NECROSIS-FACTOR;
LYMPHOTOXIN-BETA-RECEPTOR; GPI-ANCHORED PROTEINS; TNF FAMILY MEMBER; MHC
CLASS-I; CHRONIC VIRAL-INFECTION; NEWLY IDENTIFIED MEMBER; LYMPHOCYTE
ATTENUATOR; B-LYMPHOCYTE
AB CD160 is a newly identified ligand for HVEM (herpes virus entry mediator). Previously identified HVEM ligands include BTLA (B- and T-lymphocyte attenuator), LIGHT (lymphotoxin-like, exhibits inducible expression, and competes with herpes simplex virus glycoprotein D for HVEM, a receptor expressed by T lymphocytes) and LT alpha (lymphotoxin-alpha). The binding of LIGHT or LT alpha to HVEM delivers a costimulatory signal, whereas the binding of BTLA or CD160 to HVEM delivers a coinhibitory signal. Thus, HVEM is a bidirectional switch regulating T-cell activation in a costimulatory or coinhibitory fashion whose outcome depends on the ligand engaged. The cysteine-rich domain 1 (CRD1) of HVEM is essential for the binding of coinhibitory ligands CD160 and BTLA but not costimulatory ligand LIGHT. Deletion or blockade of HVEM CRD1 abolishes the binding of CD160 and BTLA, but not LIGHT, and converts HVEM to a dominant costimulatory molecule, possibly through the loss of negative signaling by CD160/BTLA. Therapies targeting the CRD1 of HVEM to block BTLA and CD160 binding are being developed to enhance immune responses and vaccination.
C1 [Cai, Guifang; Freeman, Gordon J.] Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst,Dept Med, Boston, MA 02115 USA.
RP Freeman, GJ (reprint author), Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst,Dept Med, Boston, MA 02115 USA.
EM gordon_freeman@dfci.harvard.edu
NR 145
TC 94
Z9 103
U1 1
U2 14
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0105-2896
J9 IMMUNOL REV
JI Immunol. Rev.
PD MAY
PY 2009
VL 229
BP 244
EP 258
DI 10.1111/j.1600-065X.2009.00783.x
PG 15
WC Immunology
SC Immunology
GA 436JG
UT WOS:000265409800016
PM 19426226
ER
PT J
AU Kinsey, BM
Jackson, DC
Orson, FM
AF Kinsey, Berma M.
Jackson, David C.
Orson, Frank M.
TI Anti-drug vaccines to treat substance abuse
SO IMMUNOLOGY AND CELL BIOLOGY
LA English
DT Review
DE anti drug; drugs; vaccine; substance abuse
ID NICOTINE CONJUGATE VACCINE; MONOCLONAL-ANTIBODIES; ACTIVE IMMUNIZATION;
TOBACCO DEPENDENCE; COCAINE ADDICTION; METHAMPHETAMINE; RATS;
IMMUNOGENICITY; PROTECTS; EFFICACY
AB Substance abuse is a growing world-wide problem. The big four drugs of abuse that might lend themselves to immunotherapy are nicotine, cocaine, morphine/heroin and methamphetamine. Tobacco abuse has a well-known enormous impact on major chronic cardiovascular and pulmonary diseases, while the last three, aside from their neuropsychological effects, are illegal, leading to crime and incarceration as well as the transmission of viral diseases. Having an efficient vaccine that would generate antibodies to sequester the drug and prevent its access to the brain could go a long way toward helping a motivated addict quit the addiction. This review will discuss what has been done to bring such vaccines to human use, and what the challenges are for the future of this promising intervention. Immunology and Cell Biology ( 2009) 87, 309-314; doi:10.1038/icb.2009.17; published online 31 March 2009
C1 [Kinsey, Berma M.] Baylor Coll Med, MEDVAMC, Dept Internal Med, Houston, TX 77030 USA.
[Kinsey, Berma M.; Orson, Frank M.] Michael E DeBakey Vet Affairs Med Ctr, Res Serv, Houston, TX USA.
[Jackson, David C.] Univ Melbourne, Dept Microbiol & Immunol, Parkville, Vic 3052, Australia.
[Orson, Frank M.] Baylor Coll Med, Dept Immunol, Houston, TX 77030 USA.
[Orson, Frank M.] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA.
RP Kinsey, BM (reprint author), Baylor Coll Med, MEDVAMC, Dept Internal Med, Room 221,Bldg 109,2002 Holcombe Blvd, Houston, TX 77030 USA.
EM bkinsey@bcm.tmc.edu
OI Jackson, David/0000-0001-7255-270X
FU Department of Veterans Affairs (VA) Merit Review Program
FX This study was supported by the Department of Veterans Affairs (VA)
Merit Review Program.
NR 53
TC 33
Z9 35
U1 3
U2 7
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0818-9641
J9 IMMUNOL CELL BIOL
JI Immunol. Cell Biol.
PD MAY-JUN
PY 2009
VL 87
IS 4
BP 309
EP 314
DI 10.1038/icb.2009.17
PG 6
WC Cell Biology; Immunology
SC Cell Biology; Immunology
GA 447RF
UT WOS:000266208800008
PM 19333250
ER
PT J
AU Bhuiyan, TR
Lundin, SB
Khan, AI
Lundgren, A
Harris, JB
Calderwood, SB
Qadri, F
AF Bhuiyan, Taufiqur Rahman
Lundin, Samuel B.
Khan, Ashraful Islam
Lundgren, Anna
Harris, Jason B.
Calderwood, Stephen B.
Qadri, Firdausi
TI Cholera Caused by Vibrio cholerae O1 Induces T-Cell Responses in the
Circulation
SO INFECTION AND IMMUNITY
LA English
DT Article
ID IMMUNE-RESPONSES; INFLAMMATORY MEDIATORS; HELICOBACTER-PYLORI;
ANTIBODY-RESPONSES; TOXIN; DISEASE; HEMAGGLUTININ; BANGLADESH; CHILDREN;
DIARRHEA
AB Considerable effort is being made to understand the acute and memory antibody responses in natural cholera infection, while rather less is known about the roles of cellular immune responses involving T and B lymphocytes. We studied responses in adult patients hospitalized with cholera caused by Vibrio cholerae O1. Peripheral blood mononuclear cells from patients (n = 15) were analyzed by flow cytometry after stimulation with V. cholerae O1 membrane protein (MP) or toxin-coregulated pilus antigen (TcpA). The gamma interferon (IFN-gamma) and interleukin-13 (IL-13) responses in stimulated-lymphocyte supernatants were studied. The responses were compared with those of healthy controls (n = 10). Patients responded with increased frequencies of gut-homing CD4(+) T cells (CD4(+) beta 7(+)), gut-homing CD8(+) T cells (CD8(+) beta 7(+)), and gut-homing B cells (CD19(+) beta 7(+)) at the early and/or late convalescent stages compared to the acute stage. After stimulation with MP or TcpA, proliferation of CD4(+) and CD8(+) T cells was increased at the acute stage and/or early convalescent stage compared to healthy controls. Increased IL-13 and IFN-gamma responses were observed after antigenic stimulation at the acute and convalescent stages compared to healthy controls. Thus, increases in the levels of gut-homing T and B cells, as well as involvement of CD8 and CD4 Th1-mediated (IFN-gamma) and CD4 Th2-mediated (IL-13) cytokine responses, take place in acute dehydrating disease caused by V. cholerae O1. Further studies are needed to determine if such responses are also stimulated after immunization with oral cholera vaccines and if these responses play a role in protection following exposure to cholera.
C1 [Bhuiyan, Taufiqur Rahman; Khan, Ashraful Islam; Qadri, Firdausi] Int Ctr Diarrhoeal Dis Res, Div Sci Lab, Immunol Lab, Dhaka 1000, Bangladesh.
[Bhuiyan, Taufiqur Rahman; Lundin, Samuel B.; Lundgren, Anna] Univ Gothenburg, Inst Biomed, Dept Microbiol & Immunol, S-40530 Gothenburg, Sweden.
[Harris, Jason B.; Calderwood, Stephen B.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
RP Qadri, F (reprint author), Int Ctr Diarrhoeal Dis Res, Div Sci Lab, Immunol Lab, GPO Box 128, Dhaka 1000, Bangladesh.
EM fqadri@icddrb.org
FU Swedish Agency; Sida-SAREC [INT-ICDDR, B-HN-01-AV]; National Institutes
of Health [U01 AI058935]
FX This study was conducted at the ICDDR, B Centre for Health and
Population Research with support from grants from the Swedish Agency for
Research Cooperation with Developing Countries (Sida-SAREC grant
INT-ICDDR, B-HN-01-AV) and the National Institutes of Health (grant U01
AI058935).
NR 26
TC 19
Z9 19
U1 1
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0019-9567
J9 INFECT IMMUN
JI Infect. Immun.
PD MAY
PY 2009
VL 77
IS 5
BP 1888
EP 1893
DI 10.1128/IAI.01101-08
PG 6
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 434MX
UT WOS:000265279900017
PM 19237532
ER
PT J
AU Stein, DJ
Lydiard, RB
Herman, BK
Mandel, FS
AF Stein, Dan J.
Lydiard, R. Bruce
Herman, Barry K.
Mandel, Francine S.
TI Impact of gastrointestinal symptoms on response to pregabalin in
generalized anxiety disorder: results of a six-study combined analysis
SO INTERNATIONAL CLINICAL PSYCHOPHARMACOLOGY
LA English
DT Article
DE gastrointestinal symptoms; generalized anxiety disorder; pregabalin
ID IRRITABLE-BOWEL-SYNDROME; DOUBLE-BLIND; PRIMARY-CARE; DEPRESSION;
MULTICENTER; VENLAFAXINE; PREVALENCE; MANAGEMENT; EFFICACY
AB The objective of the study was to evaluate the response of generalized anxiety disorder (GAD) patients with prominent gastrointestinal (GO symptoms to pregabalin (PGB) treatment. Data were pooled from six double-blind, placebo (PBO)-controlled, 4-6 week trials in outpatients who met Diagnostic and Statistical Manual of Mental Disorders, 4th edition criteria for GAD with a minimum Hamilton Anxiety Rating Scale (HAM-A) total score of 20. Treatment response was evaluated for three PGB fixed-dosage groups: 150, 300-450, and 600 mg/day, and for fixed doses of a benzodiazepine (alprazolam, 1.5 mg/day; lorazepam, 6 mg/day). A GI-high subgroup (high GI symptomatology) was defined by a baseline HAM-A item-11 (G 1) score of 3 or greater (severe/very severe). At baseline, 301 patients (16.2%) met criteria for the GI-high subgroup. Baseline characteristics were approximately similar for the four study treatments in the GI-high subgroup. For the GI-high subgroup, last observation carried forward (LOCF) endpoint reduction in HAM-A was significantly higher on PGB-300/450-13.8 +/- 1.2 and PGB-600 - 14.7 +/- 1.0 compared with PBO - 10.1 +/- 0.9 (P< 0.01 for both comparisons); but the difference on PGB-150 did not achieve significance (- 13.5 +/- 11.6; P=0.083). Also in the GI-high subgroup, endpoint reduction in HAM-A item-11 was significantly higher on PGB-300/450 compared with PBO (- 1.93 +/- 0.16 vs. - 1.52 +/- 0.13; P= 0.04), but did not achieve significance on PG B-600 mg (- 1.89 +/- 0.14; P= 0.06), or PG B-150 mg (- 1.90 +/- 0.23; P= 0.16). In the GI-high subgroup, treatment with a benzodiazepine was not associated with significant endpoint reduction in either the HAM-A total score or the HAM-A item-11 score. Patients in the GI-high subgroup had higher discontinuation rates when treated with benzodiazepines, whereas treatment with PGB 300-600 mg/day was not associated with treatment-emergent worsening in GI symptoms compared with placebo. Treatment with PGB improved overall levels of anxiety, as well as specifically improving GI symptoms. Int Clin Psychopharmacol 24:126-132 (C) 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins.
C1 [Herman, Barry K.; Mandel, Francine S.] Pfizer Inc, Pfizer Global Pharmaceut, New York, NY 10017 USA.
[Stein, Dan J.] Univ Cape Town, ZA-7925 Cape Town, South Africa.
[Lydiard, R. Bruce] Ralph H Johnson VA Med Ctr, Charleston, SC USA.
RP Herman, BK (reprint author), Pfizer Inc, Pfizer Global Pharmaceut, 235 E 42nd St,9th Floor,Off 101,Mailstop 235-9-39, New York, NY 10017 USA.
EM barry.herman@pfizer.com
RI Stein, Dan/A-1752-2008
OI Stein, Dan/0000-0001-7218-7810
FU Pfizer Inc.
FX The study was funded by Pfizer Inc., and editorial support was provided
by Edward Schweizer, MD and funded by Pfizer Inc.
NR 23
TC 9
Z9 9
U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0268-1315
J9 INT CLIN PSYCHOPHARM
JI Int. Clin. Psychopharmacol.
PD MAY
PY 2009
VL 24
IS 3
BP 126
EP 132
DI 10.1097/YIC.0b013e3283249c7b
PG 7
WC Pharmacology & Pharmacy; Psychiatry
SC Pharmacology & Pharmacy; Psychiatry
GA 438FH
UT WOS:000265540800003
PM 19352198
ER
PT J
AU Flavin, R
Smyth, P
Barrett, C
Russell, S
Wen, H
Wei, JJ
Laios, A
O'Toole, S
Ring, M
Denning, K
Li, J
Aherne, S
Sammarae, D
Aziz, NA
Alhadi, A
Finn, SP
Loda, M
Sheppard, B
Sheils, O
O'Leary, JJ
AF Flavin, Richard
Smyth, Paul
Barrett, Ciara
Russell, S.
Wen, Hannah
Wei, Jianjun
Laios, Alex
O'Toole, Sharon
Ring, M.
Denning, K.
Li, J.
Aherne, S.
Sammarae, D.
Aziz, N. A.
Alhadi, A.
Finn, Sephen P.
Loda, M.
Sheppard, B.
Sheils, Orla
O'Leary, John J.
TI miR-29b Expression Is Associated With Disease-Free Survival in Patients
With Ovarian Serous Carcinoma
SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER
LA English
DT Article
DE Micro-RNA; Ovarian serous carcinoma; Biomarkers
ID CHRONIC LYMPHOCYTIC-LEUKEMIA; HUMAN LUNG CANCERS; MICRORNA EXPRESSION;
REDUCED EXPRESSION; GENE-EXPRESSION; POOR-PROGNOSIS; GROWTH-FACTOR;
CELL-LINES; SIGNATURE; PROFILES
AB Micro-RNAs are a group of small noncoding RNAs approximately 22 nucleotides in length. Recent work has shown differential expression of mature micro-RNAs in human cancers. We characterized the alteration in expression of miR-29b in ovarian serous carcinoma. miR-29b expression was analyzed using quantitative stem-loop reverse transcriptase polymerase chain reaction on a set of 50 formal in-fixed, paraffin-embedded ovarian serous carcinoma samples. Protein expression of p53, estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, Ki-67, and insulinlike growth factor I was quantified in the corresponding tissue microarray. The expression profile of miR-29b was correlated with clinicopathological and patient survival data. We provide definitive evidence that miR-29b is down-regulated in a significant proportion of ovarian serous carcinomas and is associated with specific clinicopathological features, most notably high miR-29b expression being associated with reduced disease-free survival.
C1 [Flavin, Richard] St James Hosp, Dept Histopathol, Trinity Coll, Phase Trinity Ctr Hlth Sci 3, Dublin 8, Ireland.
[Wen, Hannah] Trinity Coll Dublin, Dept Obstet & Gynaecol, Dublin, Ireland.
[Wei, Jianjun] Northwestern Univ, Dept Pathol, Chicago, IL 60611 USA.
[Laios, Alex; O'Toole, Sharon; Sammarae, D.; Aziz, N. A.; Alhadi, A.; Sheppard, B.] NYU, Dept Pathol, New York, NY 10016 USA.
[Finn, Sephen P.; Loda, M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Flavin, R (reprint author), St James Hosp, Dept Histopathol, Trinity Coll, Phase Trinity Ctr Hlth Sci 3, Jamess St, Dublin 8, Ireland.
EM flavinr@tcd.ie
RI Sheils, Orla Sheils/B-8461-2015;
OI Sheils, Orla Sheils/0000-0002-4493-9496; Finn,
Stephen/0000-0002-8628-5814; o toole, sharon/0000-0002-9260-3225
FU HRB Ireland Clinical Research Fellowship [CRT/2006/10]; The Emer Casey
Foundation Ireland
FX Dr Richard Flavin is funded by an HRB Ireland Clinical Research
Fellowship Under Grant No. CRT/2006/10. The authors would like to
acknowledge The Emer Casey Foundation Ireland.
NR 69
TC 36
Z9 40
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1048-891X
J9 INT J GYNECOL CANCER
JI Int. J. Gynecol. Cancer
PD MAY
PY 2009
VL 19
IS 4
BP 641
EP 647
DI 10.1111/IGC.0b013e3181a48cf9
PG 7
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 457ZF
UT WOS:000266976800024
PM 19509563
ER
PT J
AU Nam, SW
Jo, YS
Eun, JW
Song, JY
Ryu, KS
Lee, JY
Lee, JM
MacLaughlin, DT
Kim, JH
AF Nam, Suk Woo
Jo, Yun Sung
Eun, Jung Woo
Song, Jae Yen
Ryu, Ki Sung
Lee, Jung Young
Lee, Joon Mo
MacLaughlin, David T.
Kim, Jang Heub
TI Identification of large-scale characteristic genes of Mullerian
inhibiting substance in human ovarian cancer cells
SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
LA English
DT Article
DE Mullerian inhibiting substance; OVCAR-8 cell line; DNA microarray; cell
cycle
ID II RECEPTOR; HEPATOCELLULAR-CARCINOMA; INDEPENDENT MECHANISM; SEXUAL
DEVELOPMENT; MOLECULAR-CHANGES; IN-VIVO; EXPRESSION; GROWTH; TARGET;
DIFFERENTIATION
AB The purpose of this study was to investigate the large-scale characteristic molecular signature of Mullerian inhibiting substance (MIS) in human ovarian cancer cells through expression genomics. To understand the comprehensive molecular mechanisms by which MIS inhibits ovarian cancer cell growth, we identified the large-scale characteristic molecular changes elicited by MIS in the human ovarian cancer cell line OVCAR-8, using DNA microarray analysis. Combined serial gene expression analysis from 0 to 96 h after MIS treatment of OVCAR-8 cells resulted in 759 genes which showed at least a 2-fold change in overexpression or underexpression compared to non-treatment groups. Of the 759 outlier genes, 498 genes were mapped to known biological cellular processes, and the resultant major pathways included metabolism, signal transduction, cell growth and apoptosis. Among these pathways, 68 genetic elements were dissected as cell cycle-related genes induced by MIS. Although cellular phenotypic changes by MIS were observed after 24 h of treatment, the characteristic large-scale molecular changes were observed from 48 to 96 h of exposure to MIS. This finding may imply that the suppressive role of MIS on ovarian cancer cells could be cumulative in that the metabolic disturbance of MIS is followed by arrest at the G1/S cell cycle checkpoint. We suggest 759 outlier genes comprise the characteristic molecular signature of MIS, which may be responsible for the suppressive effect on OVCAR-8 cells. Although the precise biological mechanisms underlying these outlier genes should be validated, the genetic elements described herein provide promising therapeutic interventions for ovarian cancer.
C1 [Jo, Yun Sung; Song, Jae Yen; Ryu, Ki Sung; Lee, Joon Mo; Kim, Jang Heub] Catholic Univ Korea, Coll Med, Dept Obstet & Gynecol, Seoul 150713, South Korea.
[Nam, Suk Woo; Eun, Jung Woo; Lee, Jung Young] Catholic Univ Korea, Microdissect Genom Res Inst, Dept Pathol, Seoul 150713, South Korea.
[MacLaughlin, David T.] Massachusetts Gen Hosp, Pediat Surg Res Lab, Boston, MA 02114 USA.
[MacLaughlin, David T.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Kim, JH (reprint author), Catholic Univ Korea, Coll Med, Dept Obstet & Gynecol, 62 Yeouido Dong, Seoul 150713, South Korea.
EM janghkim@catholic.ac.kr
FU Korea Ministry of Environment; Korea Science & Engineering Foundation
(KOSEF) through the Cell Death Disease Research Center
FX This work was supported by the Korea Ministry of Environment as 'The
Eco-technopia 21 project' and by the Korea Science & Engineering
Foundation (KOSEF) through the Cell Death Disease Research Center at The
Catholic University of Korea.
NR 36
TC 4
Z9 5
U1 0
U2 0
PU SPANDIDOS PUBL LTD
PI ATHENS
PA POB 18179, ATHENS, 116 10, GREECE
SN 1107-3756
EI 1791-244X
J9 INT J MOL MED
JI Int. J. Mol. Med.
PD MAY
PY 2009
VL 23
IS 5
BP 589
EP 596
DI 10.3892/ijmm_00000168
PG 8
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 434FU
UT WOS:000265261400003
PM 19360316
ER
PT J
AU Warden, D
Rush, AJ
Wisniewski, SR
Lesser, IM
Kornstein, SG
Balasubramani, GK
Thase, ME
Preskorn, SH
Nierenberg, AA
Young, EA
Shores-Wilson, K
Trivedi, MH
AF Warden, Diane
Rush, A. John
Wisniewski, Stephen R.
Lesser, Ira M.
Kornstein, Susan G.
Balasubramani, G. K.
Thase, Michael E.
Preskorn, Sheldon H.
Nierenberg, Andrew A.
Young, Elizabeth A.
Shores-Wilson, Kathy
Trivedi, Madhukar H.
TI What predicts attrition in second step medication treatments for
depression?: a STAR*D Report
SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
LA English
DT Article; Proceedings Paper
CT 4th Biennial Conference of the
International-Society-of-Affective-Disorders
CY MAR 14-17, 2008
CL Cape Town, SOUTH AFRICA
SP Int Soc Affect Disorders
DE Adherence; attrition; antidepressants; depression; predictors
ID SEQUENCED TREATMENT ALTERNATIVES; DIAGNOSTIC SCREENING QUESTIONNAIRE;
MEASUREMENT-BASED CARE; ILLNESS RATING-SCALE; REPORT QIDS-SR; QUICK
INVENTORY; PSYCHOMETRIC EVALUATION; CLINICAL-PRACTICE; SYMPTOMATOLOGY;
OUTPATIENTS
AB Attrition rates are high during treatment for major depressive disorder (MDD), and patients who drop out are less likely to reach remission. This report evaluates the incidence, timing, and predictors of attrition during second-step medication treatment. Outpatients in the multisite Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study receiving a medication augmentation (n=563) or medication switch (n=723) for non-psychotic MDD after an unsatisfactory outcome with citalopram were evaluated to determine attrition rates and pretreatment sociodemographic or clinical predictors of attrition. Twenty percent of participants receiving a medication augmentation and 27% receiving a medication switch dropped Out before 12 wk in the second treatment step. Remission rates were lower for dropouts [7% vs. 43%, (medication augmentation); 12% vs. 31% (medication switch)]. For medication augmentation, Black and other non-Caucasian races, Hispanic ethnicity, younger age, family history of drug abuse, concurrent drug abuse, sociodemographic disadvantage, less symptom improvement with initial citalopram treatment, and greater symptom severity when beginning augmentation were associated with attrition. For medication switch, Black and other non-Caucasian races, younger age, more melancholic features, and lower exit doses but more severe side-effects with citalopram treatment were associated with attrition. Minority status, younger age, and greater difficulty with the first treatment step are risk factors for attrition in the second treatment step. Focus on patients with attrition risk factors for medication augmentation or switch strategies may enhance retention and improve outcomes.
C1 [Warden, Diane; Rush, A. John; Shores-Wilson, Kathy; Trivedi, Madhukar H.] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA.
[Rush, A. John] Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Dallas, TX 75390 USA.
[Wisniewski, Stephen R.; Balasubramani, G. K.] Univ Pittsburgh, Grad Sch Publ Hlth, Epidemiol Data Ctr, Pittsburgh, PA USA.
[Lesser, Ira M.] UCLA Med Ctr, Dept Psychiat, Torrance, CA USA.
[Lesser, Ira M.] UCLA Med Ctr, Los Angeles Biomed Res Inst Harbor, Torrance, CA USA.
[Kornstein, Susan G.] Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA USA.
[Thase, Michael E.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA.
[Preskorn, Sheldon H.] Univ Kansas, Sch Med, Dept Psychiat & Behav Sci, Wichita, KS 67214 USA.
[Nierenberg, Andrew A.] Massachusetts Gen Hosp, Clin Psychopharmacol Unit, Boston, MA 02114 USA.
[Young, Elizabeth A.] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA.
[Young, Elizabeth A.] Univ Michigan, Mental Hlth Res Inst, Ann Arbor, MI 48109 USA.
RP Warden, D (reprint author), Univ Texas SW Med Ctr Dallas, Dept Psychiat, 5323 Harry Hines Blvd, Dallas, TX 75390 USA.
EM Diane.Warden@UTSouthwestern.edu
RI Preskorn, Sheldon/L-9839-2016;
OI Wisniewski, Stephen/0000-0002-3877-9860; Rush,
Augustus/0000-0003-2004-2382; Goundappa K,
Balasubramani/0000-0001-7221-1825
FU NIMH NIH HHS [N01MH90003]
NR 42
TC 42
Z9 43
U1 3
U2 7
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 MAY
PY 2009
VL 12
IS 4
BP 459
EP 473
DI 10.1017/S1461145708009073
PG 15
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 449BM
UT WOS:000266305800003
PM 18611293
ER
PT J
AU Herrera, VM
Casas, JP
Miranda, JJ
Perel, P
Pichardo, R
Gonzalez, A
Sanchez, JR
Ferreccio, C
Aguilera, X
Silva, E
Orostegui, M
Gomez, LF
Chirinos, JA
Medina-Lezama, J
Perez, CM
Suarez, E
Ortiz, AP
Rosero, L
Schapochnik, N
Ortiz, Z
Ferrante, D
Diaz, M
Bautista, LE
AF Herrera, V. M.
Casas, J. P.
Miranda, J. J.
Perel, P.
Pichardo, R.
Gonzalez, A.
Sanchez, J. R.
Ferreccio, C.
Aguilera, X.
Silva, E.
Orostegui, M.
Gomez, L. F.
Chirinos, J. A.
Medina-Lezama, J.
Perez, C. M.
Suarez, E.
Ortiz, A. P.
Rosero, L.
Schapochnik, N.
Ortiz, Z.
Ferrante, D.
Diaz, M.
Bautista, L. E.
CA Latin Amer Consortium Studies
TI Interethnic differences in the accuracy of anthropometric indicators of
obesity in screening for high risk of coronary heart disease
SO INTERNATIONAL JOURNAL OF OBESITY
LA English
DT Article
DE coronary heart disease; screening; ethnic group; Latin America; NHANES
ID BODY-MASS INDEX; NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH;
METABOLIC SYNDROME; MYOCARDIAL-INFARCTION; MULTIPLE IMPUTATION;
CARDIOVASCULAR RISK; AFRICAN-AMERICANS; FAT DISTRIBUTION; PREVALENCE
AB Background: Cut points for defining obesity have been derived from mortality data among Whites from Europe and the United States and their accuracy to screen for high risk of coronary heart disease (CHD) in other ethnic groups has been questioned.
Objective: To compare the accuracy and to define ethnic and gender-specific optimal cut points for body mass index (BMI), waist circumference (WC) and waist-to-hip ratio (WHR) when they are used in screening for high risk of CHD in the Latin-American and the US populations.
Methods: We estimated the accuracy and optimal cut points for BMI, WC and WHR to screen for CHD risk in Latin Americans (n = 18 976), non-Hispanic Whites (Whites; n = 8956), non-Hispanic Blacks (Blacks; n 5205) and Hispanics (n = 5803). High risk of CHD was defined as a 10-year risk >= 20% (Framingham equation). The area under the receiver operator characteristic curve (AUC) and the misclassification-cost term were used to assess accuracy and to identify optimal cut points.
Results: WHR had the highest AUC in all ethnic groups (from 0.75 to 0.82) and BMI had the lowest (from 0.50 to 0.59). Optimal cut point for BMI was similar across ethnic/gender groups (27 kg/m(2)). In women, cut points for WC (94 cm) and WHR (0.91) were consistent by ethnicity. In men, cut points for WC and WHR varied significantly with ethnicity: from 91cm in Latin Americans to 102cm in Whites, and from 0.94 in Latin Americans to 0.99 in Hispanics, respectively.
Conclusion: WHR is the most accurate anthropometric indicator to screen for high risk of CHD, whereas BMI is almost uninformative. The same BMI cut point should be used in all men and women. Unique cut points for WC and WHR should be used in all women, but ethnic-specific cut points seem warranted among men. International Journal of Obesity (2009) 33, 568-576; doi:10.1038/ijo.2009.35; published online 24 February 2009
C1 [Herrera, V. M.; Bautista, L. E.] Univ Wisconsin, Dept Populat Hlth Sci, Madison, WI 53726 USA.
[Casas, J. P.; Miranda, J. J.; Perel, P.] London Sch Hyg & Trop Med, Dept Epidemiol & Populat Hlth, London WC1, England.
[Pichardo, R.] Inst Dominicano Cardiol, Santo Domingo, Dominican Rep.
[Sanchez, J. R.] Inst Nacl Salud, Ctr Nacl Alimentac & Nutr, Lima, Peru.
[Ferreccio, C.] Pontificia Univ Catolica Chile, Dept Salud Publ, Santiago, Chile.
[Aguilera, X.] Minist Salud Chile, Santiago, Chile.
[Silva, E.] Univ Zulia, Fac Med, Inst Invest & Estudios Enfermedades Cardiovasc, Maracaibo 4011, Venezuela.
[Orostegui, M.] Univ Ind Santander, Epidemiol Res Ctr, Cardiovasc Dis Epidemiol Observ, Bucaramanga, Colombia.
[Gomez, L. F.] Fdn FES Social, Hlth Div, Bogota, Colombia.
[Chirinos, J. A.] Univ Penn, Sch Med, Div Cardiol, Philadelphia, PA 19104 USA.
[Chirinos, J. A.] Philadelphia VA Med Ctr, Philadelphia, PA USA.
[Medina-Lezama, J.] Santa Maria Catholic Univ, Arequipa, Peru.
[Medina-Lezama, J.] Santa Maria Res Inst, Arequipa, Peru.
[Perez, C. M.; Suarez, E.; Ortiz, A. P.] Univ Puerto Rico, Grad Sch Publ Hlth, Dept Biostat & Epidemiol, San Juan, PR 00936 USA.
[Rosero, L.] Univ Costa Rica, Ctr Ctr Amer Poblac, San Jose, Costa Rica.
[Schapochnik, N.] Minist Salud Prov Tierra Fuego, Ushuaia, Argentina.
[Ortiz, Z.] Acad Nacl Med Buenos Aires, Inst Invest Epidemiol, Buenos Aires, DF, Argentina.
[Ferrante, D.] Minist Salud & Ambiente, Buenos Aires, DF, Argentina.
[Diaz, M.] Ctr Invest Med Acad, Montevideo, Uruguay.
RP Bautista, LE (reprint author), Univ Wisconsin, Dept Populat Hlth Sci, 610 Walnut St,703 WARF, Madison, WI 53726 USA.
EM lebautista@wisc.edu
RI Herrera, Victor/C-5602-2008; Miranda, J. Jaime/A-8482-2008; Aguilera,
Ximena/D-9861-2014
OI Miranda, J. Jaime/0000-0002-4738-5468; Aguilera,
Ximena/0000-0002-8153-6733
FU NCRR NIH HHS [P20 RR 011126, G12 RR 03051, G12 RR003051, P20 RR011126];
NIMHD NIH HHS [G12 MD007600]; Wellcome Trust [074833]
NR 49
TC 35
Z9 36
U1 2
U2 14
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0307-0565
J9 INT J OBESITY
JI Int. J. Obes.
PD MAY
PY 2009
VL 33
IS 5
BP 568
EP 576
DI 10.1038/ijo.2009.35
PG 9
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 443DF
UT WOS:000265889700008
PM 19238159
ER
PT J
AU Gizani, S
Papaioannou, W
Haffajee, AD
Kavvadia, K
Quirynen, M
Papagiannoulis, L
AF Gizani, Sotiria
Papaioannou, William
Haffajee, Anne D.
Kavvadia, Katerina
Quirynen, Marc
Papagiannoulis, Liza
TI Distribution of selected cariogenic bacteria in five different
intra-oral habitats in young children
SO INTERNATIONAL JOURNAL OF PAEDIATRIC DENTISTRY
LA English
DT Article
ID DENTAL PLAQUE; ORAL-CAVITY; CARIES; FLORA; PERIODONTOPATHOGENS;
MICROFLORA; SURFACES; SAMPLES; SALIVA; TOOTH
AB Knowledge of the colonization patterns and composition of the oral microbiota can lead to a better understanding of disease initiation.
The aim of this study was to examine the distribution of selected cariogenic bacteria in samples from five different oral habitats in young Greek children.
Ninety-three children 3-12 years old (mean + SD 7.9 +/- 2.5) (60.2% male, 39.8% female) participated and split into three different age groups: primary (3-6 years), early mixed (6-9 years), and mixed dentition (9-12 years). Samples for bacterial enumeration were taken from saliva, supragingival and subgingival plaque, tongue dorsum, and soft tissues from each child, and were further analysed using checkerboard DNA-DNA hybridization.
Mean counts and proportions of all the test bacteria differed significantly among sample locations. Cariogenic bacteria were present in almost all healthy children. Mean proportions of Streptococcus mutans isolated from soft tissue and Streptococcus sanguinis from soft tissue, subgingival and saliva samples increased significantly with age, whereas the opposite was seen for Lactobacillus acidophilus.
Cariogenic bacteria were present in almost all young children. Soft tissues, saliva, and tongue were more often colonized by cariogenic streptococcal species than teeth. These surfaces may serve as reservoirs for oral pathogens, requiring attention during preventive interventions.
C1 [Gizani, Sotiria; Kavvadia, Katerina; Papagiannoulis, Liza] Univ Athens, Dept Padiatr Dent, Athens, Greece.
[Haffajee, Anne D.] Forsyth Insitutue, Dept Periodontol, Boston, MA USA.
[Quirynen, Marc] Catholic Univ Louvain, Dept Periodontol, B-3000 Leuven, Belgium.
[Papaioannou, William] Univ Athens, Dept Prevent & Community Dent, Athens, Greece.
RP Gizani, S (reprint author), El Venizelou 199, N Smyrni 17123, Greece.
EM periowp@hol.gr
FU University of Athens Special Account for Research Grants [70/4/8887]
FX The authors would like to acknowledge the invaluable assistance provided
by E. Mandelou and T. Yaskell in the preparation and analysis of the
samples, as well as S. Poulopoulou and Assoc. Professor U. Dafni for
their statistical advice. The study was partially funded by the
University of Athens Special Account for Research Grants: 'Kapodistrias'
programme (#70/4/8887).
NR 27
TC 13
Z9 14
U1 0
U2 3
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0960-7439
J9 INT J PAEDIATR DENT
JI Int. J. Paediatr. Dent.
PD MAY
PY 2009
VL 19
IS 3
BP 193
EP 200
DI 10.1111/j.1365-263X.2008.00956.x
PG 8
WC Dentistry, Oral Surgery & Medicine; Pediatrics
SC Dentistry, Oral Surgery & Medicine; Pediatrics
GA 430UA
UT WOS:000265013200006
PM 19207737
ER
PT J
AU Nguyen, PL
Chen, MH
Hoffman, KE
Katz, MS
D'Amico, AV
AF Nguyen, Paul L.
Chen, Mlng-Hui
Hoffman, Karen E.
Katz, Matthew S.
D'Amico, Anthony V.
TI PREDICTING THE RISK OF PELVIC NODE INVOLVEMENT AMONG MEN WITH PROSTATE
CANCER IN THE CONTEMPORARY ERA
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Article
DE Pelvic lymph nodes; Prostate cancer; Prediction model; Roach formula
ID ADEQUATE STAGING PROCEDURE; RADICAL PROSTATECTOMY; GLEASON SCORE;
NEEDLE-BIOPSY; DISSECTION; LYMPHADENECTOMY; METASTASIS; SPECIMENS;
ANTIGEN
AB Purpose: The "Roach formula" for the risk of pelvic lymph node metastases [(2/3) * PSA + (Gleason score - 6) * 10] was developed in the early prostate-specific antigen (PSA) era. We examined the accuracy of this formula in contemporary patients.
Methods: We included men in the Surveillance, Epidemiology, and End Results Registry with a diagnosis of clinical T1c-T4 prostate cancer in 2004 who had a surgical lymph node evaluation, Gleason score (typically from prostatectomy), and baseline PSA level (n = 9,387). Expected and observed rates of node positivity were compared.
Results: Ninety-eight percent were clinical T1c/T2, and 97% underwent prostatectomy. Overall, 309 patients (3.291%) had positive lymph nodes. Roach scores overestimated the actual rate of positive lymph nodes in the derivation set by 16-fold for patients with Roach score less than or equal to 10%, by 7-fold for scores greater than 10-20%, and by approximately 2.5-fold for scores greater than 20%. Applying these adjustment factors to Roach scores in the validation data set yielded accurate predictions of risk. For those with Roach score less than or equal to 10%, adjusted expected risk was 0.2% and observed risk was 0.2%. For Roach score greater than 10-20%, adjusted expected risk was 2.0% and observed risk was 2.1%. For Roach score greater than 20-30%, adjusted expected risk was 9.7% and observed risk was 6.5%. For Roach score greater than 30-40%, adjusted expected risk was 13.9% and observed risk was 13.9%.
Conclusion: Applied to contemporary patients with mainly T1c/T2 disease, the Roach formula appears to overestimate pelvic lymph node risk. The adjustment factors presented here should be validated by using biopsy Gleason scores and extended lymphadenectomies. (C) 2009 Elsevier Inc.
C1 [Nguyen, Paul L.] Brigham & Womens Hosp, Dept Radiat Oncol, Harvard Radiat Oncol Program, Boston, MA 02115 USA.
[Chen, Mlng-Hui] Univ Connecticut, Dept Stat, Storrs, CT 06269 USA.
[Katz, Matthew S.] St Med Ctr, Div Radiat Oncol, Lowell, MA USA.
[D'Amico, Anthony V.] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Nguyen, PL (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, Harvard Radiat Oncol Program, 75 Francis St, Boston, MA 02115 USA.
EM pnguyen@LROC.harvard.edu
NR 20
TC 36
Z9 37
U1 0
U2 0
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 MAY 1
PY 2009
VL 74
IS 1
BP 104
EP 109
DI 10.1016/j.ijrobp.2008.07.053
PG 6
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 436GW
UT WOS:000265401700016
PM 19286330
ER
PT J
AU Kozak, KR
Adams, J
Krejcarek, SJ
Tarbell, NJ
Yock, TI
AF Kozak, Kevin R.
Adams, Judith
Krejcarek, Stephanie J.
Tarbell, Nancy J.
Yock, Torunn I.
TI A DOSIMETRIC COMPARISON OF PROTON AND INTENSITY-MODULATED PHOTON
RADIOTHERAPY FOR PEDIATRIC PARAMENINGEAL RHABDOMYOSARCOMAS
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Article
DE Comparison; Intensity-modulated radiation therapy; Parameningeal
rhabdomyosarcoma; Pediatric; Protons
ID CONFORMAL RADIATION-THERAPY; EXTERNAL-BEAM IRRADIATION;
NECK-CANCER-PATIENTS; INTERGROUP RHABDOMYOSARCOMA; CHILDHOOD-CANCER;
HEARING-LOSS; NASOPHARYNGEAL CARCINOMA; CRANIAL IRRADIATION; CHILDREN;
HEAD
AB Purpose: We compared tumor and normal tissue dosimetry of proton radiation therapy with intensity-modulated radiation therapy (IMRT) for pediatric parameningeal rhabdomyosarcomas (PRMS).
Methods and Materials: To quantify dosimetric differences between contemporary proton and photon treatment for pediatric PRMS, proton beam plans were compared with IMRT plans. Ten patients treated with proton radiation therapy at Massachusetts General Hospital had IMRT plans generated. To facilitate dosimetric comparisons, clinical target volumes and normal tissue volumes were held constant. Plans were optimized for target volume coverage and normal tissue sparing.
Results: Proton and IMRT plans provided acceptable and comparable target volume coverage, with at least 99% of the CTV receiving 95% of the prescribed dose in all cases. Improved dose conformality provided by proton therapy resulted in significant sparing of all examined normal tissues except for ipsilateral cochlea and mastoid; ipsilateral parotid gland sparing was of borderline statistical significance (p = 0.05). More profound sparing of contralateral structures by protons resulted in greater dose asymmetry between ipsilateral and contralateral retina, optic nerves, cochlea, and mastoids; dose asymmetry between ipsilateral and contralateral parotids was of borderline statistical significance (p = 0.05).
Conclusions: For pediatric PRMS, superior normal tissue sparing is achieved with proton radiation therapy compared with IMRT. Because of enhanced conformality, proton plans also demonstrate greater normal tissue dose distribution asymmetry. Longitudinal studies assessing the impact of proton radiotherapy and IMRT on normal tissue function and growth symmetry are necessary to define the clinical consequences of these differences. (C) 2009 Elsevier Inc.
C1 [Kozak, Kevin R.; Adams, Judith; Krejcarek, Stephanie J.; Tarbell, Nancy J.; Yock, Torunn I.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
RP Yock, TI (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St, Boston, MA 02114 USA.
EM tyock@partners.org
NR 38
TC 46
Z9 47
U1 0
U2 7
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 MAY 1
PY 2009
VL 74
IS 1
BP 179
EP 186
DI 10.1016/j.ijrobp.2008.06.1942
PG 8
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 436GW
UT WOS:000265401700027
PM 19019562
ER
PT J
AU Patel, AA
Wolfgang, JA
Niemierko, A
Hong, TS
Yock, T
Choi, NC
AF Patel, Abhijit A.
Wolfgang, John A.
Niemierko, Andrzej
Hong, Theodore S.
Yock, Torunn
Choi, Noah C.
TI IMPLICATIONS OF RESPIRATORY MOTION AS MEASURED BY FOUR-DIMENSIONAL
COMPUTED TOMOGRAPHY FOR RADIATION TREATMENT PLANNING OF ESOPHAGEAL
CANCER
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Article
DE Esophageal cancer; Tumor motion; Four-dimensional CT; Lymph nodes;
Internal target volume
ID INTERNAL TARGET VOLUME; LUNG-CANCER; CONFORMAL RADIOTHERAPY; MOVEMENT;
THERAPY; CHEMOTHERAPY; MOBILITY; MARGINS; TUMORS
AB Purpose: To evaluate the respiratory motion of primary esophageal cancers and pathologic celiac-region lymph nodes using time-resolved four-dimensional computed tomography (4D CT).
Methods and Materials: Respiration-synchronized 41) CT scans were obtained to quantify the motion of primary tumors located in the proximal, mid-, or distal thoracic esophagus, as well as any involved celiac-region lymph nodes. Respiratory motion was measured in the superior-inferior (SI), anterior-posterior (AP), and left-right (LR) directions and was analyzed for correlation with anatomic location. Recommended margin expansions were determined for both primary and nodal targets.
Results: Thirty patients underwent 4D CT scans at Massachusetts General Hospital for planned curative treatment of esophageal cancer. Measurements of respiratory tumor motion were obtained for I proximal, 4 mid-, and 25 distal esophageal tumors, as well as 12 involved celiac-region lymph nodes. The mean (SD) peak-to-peak displacements of all primary tumors in the SI, AP, and LR dimensions were 0.80 (0.45) cm, 0.28 (0.20) cm, and 0.22 (0.23) cm, respectively. Distal tumors were found to have significantly greater SI and AP motion than proximal or mid-esophageal tumors. The mean (SD) SI, AP, and LR peak-to-peak displacements of the celiac-region lymph nodes were 0.92 (0.56) cm, 0.46 (0.27) cm, and 0.19 (0.26) cm, respectively.
Conclusions: Margins of 1.5 cm SI, 0.75 cm AP, and 0.75 cm LR would account for respiratory tumor motion of >95% of esophageal primary tumors in the dataset. All celiac-region lymph nodes would be adequately covered with SI, AP, and LR margins of 2.25 cm, 1.0 cm, and 0.75 cm, respectively. (C) 2009 Elsevier Inc.
C1 [Choi, Noah C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
RP Choi, NC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St, Boston, MA 02114 USA.
EM nchoi@partners.org
NR 21
TC 34
Z9 43
U1 0
U2 9
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0360-3016
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD MAY 1
PY 2009
VL 74
IS 1
BP 290
EP 296
DI 10.1016/j.ijrobp.2008.12.060
PG 7
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 436GW
UT WOS:000265401700041
PM 19362248
ER
PT J
AU Downes, J
Vartoukian, SR
Dewhirst, FE
Izard, J
Chen, T
Yu, WH
Sutcliffe, IC
Wade, WG
AF Downes, Julia
Vartoukian, Sonia R.
Dewhirst, Floyd E.
Izard, Jacques
Chen, Tsute
Yu, Wen-Han
Sutcliffe, Iain C.
Wade, William G.
TI Pyramidobacter piscolens gen. nov., sp nov., a member of the phylum
'Synergistetes' isolated from the human oral cavity
SO INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY
LA English
DT Article
ID MOBILE SP NOV.; ENDODONTIC INFECTIONS; BACTERIAL DIVERSITY; EMENDED
DESCRIPTION; COMB. NOV; THERMANAEROVIBRIO; ACIDAMINOVORANS; PHYLOTYPES;
SEQUENCES; SULFUR
AB Four strains of anaerobic, Gram-negative bacilli isolated from the human oral cavity were subjected to a comprehensive range of phenotypic and genotypic tests and were found to comprise a homogeneous group distinct from any species with validly published names. 16S rRNA and 23S rRNA gene sequence analyses and DNA-DNA reassociation data revealed that the strains constituted a novel group within the phylum 'Synergistetes' and were most closely related to Jonquetella anthropi. Two libraries of randomly cloned DNA were prepared from strain W5455(T) and were sequenced to provide a genome survey as a resource for metagenomic studies. A new genus and novel species, Pyramidobacter piscolens gen. nov., sp. nov., is proposed to accommodate these strains. The genus Pyramidobacter comprises strains that are anaerobic, non-motile, asaccharolytic bacilli that produce acetic and isovaleric acids and minor to trace amounts of propionic, isobutyric, succinic and phenylacetic acids as end products of metabolism. P. piscolens gen. nov., sp. nov. produced hydrogen sulphide but was otherwise largely biochemically unreactive. Growth was stimulated by the addition of glycine to broth media. The G + C content of the DNA of the type strain was 59 mol%. The type strain of Pyramidobacter piscolens sp. nov. is W5455(T) (=DSM 21147(T)=CCUG 55836(T)).
C1 [Downes, Julia; Vartoukian, Sonia R.; Wade, William G.] Kings Coll London, Inst Dent, Infect Res Grp, London SE1 9RT, England.
[Dewhirst, Floyd E.; Izard, Jacques; Chen, Tsute; Yu, Wen-Han; Wade, William G.] Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA.
[Sutcliffe, Iain C.] Northumbria Univ, Div Biomed Sci, Sch Appl Sci, Newcastle Upon Tyne NE1 8ST, Tyne & Wear, England.
RP Wade, WG (reprint author), Kings Coll London, Inst Dent, Infect Res Grp, London SE1 9RT, England.
EM william.wade@kcl.ac.uk
RI Sutcliffe, Iain/A-5354-2009; Izard, Jacques/A-6074-2012;
OI Sutcliffe, Iain/0000-0002-9036-2683; Izard, Jacques/0000-0002-5904-5436;
Wade, William/0000-0003-2685-826X
FU NIH [DE-10374, DE-16937, DE-17106]; National Institute for Dental and
Craniofacial Research; Guy's and St Thomas' Charity [R050724]; NSF
[0228651]
FX This research was Supported by NIH grants (DE-10374, DE-16937 and
DE-17106) from the National Institute for Dental and Craniofacial
Research and a grant from the Guy's and St Thomas' Charity (ref.
R050724). Professor Hans Truper is thanked for his expert advice oil the
construction of the species name. We thank Janet Cheong, Sara Barbuto
and Erin Klein for their technical assistance with 23S rRNA gene
sequencing, and Derek Spencer for making the second genomic library. We
thank Jonathan Eisen for allowing us to use the 23S rRNA gene sequence
of S. jonesii. The genome sequencing of S. jonesii was supported by an
NSF 'Assembling the Tree of Life' grant (0228651) to Jonathan Eisen and
Naomi Ward.
NR 43
TC 39
Z9 40
U1 0
U2 4
PU SOC GENERAL MICROBIOLOGY
PI READING
PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG,
BERKS, ENGLAND
SN 1466-5026
J9 INT J SYST EVOL MICR
JI Int. J. Syst. Evol. Microbiol.
PD MAY
PY 2009
VL 59
BP 972
EP 980
DI 10.1099/ijs.0.000364-0
PG 9
WC Microbiology
SC Microbiology
GA 450UL
UT WOS:000266426400008
PM 19406777
ER
PT J
AU Seddon, JM
Reynolds, R
Maller, J
Fagerness, JA
Daly, MJ
Rosner, B
AF Seddon, Johanna M.
Reynolds, Robyn
Maller, Julian
Fagerness, Jesen A.
Daly, Mark J.
Rosner, Bernard
TI Prediction Model for Prevalence and Incidence of Advanced Age-Related
Macular Degeneration Based on Genetic, Demographic, and Environmental
Variables
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID BODY-MASS INDEX; FACTOR-H POLYMORPHISM; RISK-FACTORS; VITAMIN-C;
CIGARETTE-SMOKING; VARIANT; DIETARY; SUSCEPTIBILITY; ASSOCIATION; CFH
AB PURPOSE. The joint effects of genetic, ocular, and environmental variables were evaluated and predictive models for prevalence and incidence of AMD were assessed.
METHODS. Participants in the multicenter Age-Related Eye Disease Study (AREDS) were included in a prospective evaluation of 1446 individuals, of which 279 progressed to advanced AMD (geographic atrophy or neovascular disease) and 1167 did not progress during 6.3 years of follow-up. For prevalent AMD, 509 advanced cases were compared with 222 controls. Covariates for the incidence analysis included age, sex, education, smoking, body mass index (BMI), baseline AMD grade, and the AREDS vitamin-mineral treatment assignment. DNA specimens were evaluated for six variants in five genes related to AMD. Unconditional logistic regression analyses were performed for prevalent and incident advanced AMD. An algorithm was developed and receiver operating characteristic curves and C statistics were calculated to assess the predictive ability of risk scores to discriminate progressors from nonprogressors.
RESULTS. All genetic polymorphisms were independently related to prevalence of advanced AMD, controlling for genetic factors, smoking, BMI, and AREDS treatment. Multivariate odds ratios (ORs) were 3.5 (95% confidence interval [CI], 1.7-7.1) for CFH Y402H; 3.7 (95% CI, 1.6-8.4) for CFH rs1410996; 25.4 (95% CI, 8.6-75.1) for LOC387715 A69S (ARMS2); 0.3 (95% CI, 0.1-0.7) for C2 E318D; 0.3 (95% CI, 0.1-0.5) for CFB; and 3.6 (95% CI, 1.4-9.4) for C3 R102G, comparing the homozygous risk/protective genotypes to the referent genotypes. For incident AMD, all these variants except CFB were significantly related to progression to advanced AMD, after controlling for baseline AMD grade and other factors, with ORs from 1.8 to 4.0 for presence of two risk alleles and 0.4 for the protective allele. An interaction was seen between CFH402H and treatment, after controlling for all genotypes. Smoking was independently related to AMD, with a multiplicative joint effect with genotype on AMD risk. The C statistic for the full model with all variables was 0.831 for progression to advanced AMD.
CONCLUSIONS. Factors reflective of nature and nurture are independently related to prevalence and incidence of advanced AMD, with excellent predictive power. (Invest Ophthalmol Vis Sci. 2009;50:2044-2053) DOI:10.1167/iovs.08-3064
C1 [Maller, Julian; Fagerness, Jesen A.; Daly, Mark J.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Maller, Julian; Fagerness, Jesen A.; Daly, Mark J.] Broad Inst Harvard, Program Med & Populat Genet, Boston, MA USA.
[Maller, Julian; Fagerness, Jesen A.; Daly, Mark J.] MIT, Boston, MA USA.
[Rosner, Bernard] Harvard Univ, Sch Med, Channing Lab, Boston, MA 02115 USA.
[Seddon, Johanna M.] Tufts Univ, Tufts Med Ctr, Ophthalm Epidemiol & Genet Serv, New England Eye Ctr,Sch Med, Boston, MA 02111 USA.
RP Seddon, JM (reprint author), Tufts Univ, Tufts Med Ctr, Ophthalm Epidemiol & Genet Serv, New England Eye Ctr,Sch Med, 800 Washington St 450, Boston, MA 02111 USA.
EM jseddon@tuftsmedicalcenter.org
OI Maller, Julian/0000-0002-1565-9559
FU National Institutes of Health (NIH) National Eye Institute
[R01-EY11309]; Foundation Fighting Blindness, Owing Mills, MD;
Age-Related Macular Degeneration Research Fund; Ophthalmic Epidemiology
and Genetics Service; Tufts Medical Center; Tufts University School of
Medicine; Massachusetts Lions Eye Research Fund Inc., Northboro, MA;
National Center for Research Resources to the Broad Institute Center for
Genotyping and Analysis [U54 RR020278]; Research to Prevent Blindness
Inc., New York, NY
FX Supported by Grant R01-EY11309 from the National Institutes of Health
(NIH) National Eye Institute; the Foundation Fighting Blindness, Owing
Mills, MD; the Age-Related Macular Degeneration Research Fund,
Ophthalmic Epidemiology and Genetics Service, Tufts Medical Center,
Tufts University School of Medicine; the Massachusetts Lions Eye
Research Fund Inc., Northboro, MA; Grant U54 RR020278 from the National
Center for Research Resources to the Broad Institute Center for
Genotyping and Analysis; and unrestricted grants from Research to
Prevent Blindness Inc., New York, NY.
NR 38
TC 165
Z9 172
U1 2
U2 20
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD MAY
PY 2009
VL 50
IS 5
BP 2044
EP 2053
DI 10.1167/iovs.08-3064
PG 10
WC Ophthalmology
SC Ophthalmology
GA 436YC
UT WOS:000265451000011
PM 19117936
ER
PT J
AU Mavandadi, S
Zanjani, F
Ten Have, TR
Oslin, DW
AF Mavandadi, Shahrzad
Zanjani, Faika
Ten Have, Thomas R.
Oslin, David W.
TI Psychological Well-Being Among Individuals Aging With HIV: The Value of
Social Relationships
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article; Proceedings Paper
CT 20th Annual Meeting of the American-Association-of-Geriatric-Psychiatry
CY MAR 01-04, 2007
CL New Orleans, LA
SP Amer Assoc Geriat Psychiat
DE aging; depressive symptoms; HIV positive; positive affect; social
support
ID HUMAN-IMMUNODEFICIENCY-VIRUS; QUALITY-OF-LIFE; DEPRESSIVE SYMPTOMS;
SOCIOEMOTIONAL SELECTIVITY; ECONOMIC CIRCUMSTANCES; OLDER-ADULTS;
HEALTH-CARE; SHORT-FORM; SUPPORT; AGE
AB Objective: Utilizing a heterogenous sample of adults diagnosed with HIV infection, the current study sought to explore associations among age, various dimensions of social support, and psychological and functional well-being.
Methods: Cross-sectional data capturing subjective and instrumental support, social interaction, behavioral health service utilization, and psychological well-being (ie, positive affect and depressive symptomatology), and physical functioning, wet e collected from 109 men and women living with HIV To explore a;e group differences, participants were stratified by age (<54 vs. 55- years).
Results: Despite endorsing greater medical comorbidity, older adults reported significantly lower depressive symptomatology and greater positive affect and were less likely to report seeing a behavioral health specialist than their younger counterparts. No age group differences emerged for instrumental support or amount of social interaction. However, older adults reported higher subjective Support, which in turn was associated with lower depressive symptomatology, greater positive affect, and nonutilization of behavioral health services.
Conclusions: More attention should be paid to the social environment of individuals diagnosed with HIV as tic quality of social relationships may be particularly important for successful psychological adaptation to HIV
C1 [Mavandadi, Shahrzad; Oslin, David W.] Philadelphia VA Med Ctr, Mental Illness Res Educ & Clin Ctr, Philadelphia, PA 19104 USA.
[Zanjani, Faika] Univ Kentucky, Dept Gerontol, Lexington, KY USA.
[Ten Have, Thomas R.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[Oslin, David W.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA.
RP Mavandadi, S (reprint author), Philadelphia VA Med Ctr, Mental Illness Res Educ & Clin Ctr, 3900 Woodland Ave,116A, Philadelphia, PA 19104 USA.
EM shahrzad.mavandadi@va.gov
FU NIAID NIH HHS [P30 AI045008, P30 AI045008-10, 5P30AI045008]; NIMH NIH
HHS [P30 MH066270-05]
NR 54
TC 22
Z9 22
U1 1
U2 4
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 MAY 1
PY 2009
VL 51
IS 1
BP 91
EP 98
PG 8
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 438WD
UT WOS:000265585800014
PM 19282781
ER
PT J
AU Hayashi, A
Naseri, A
Pennesi, ME
de Juan, E
AF Hayashi, Atsushi
Naseri, Ayman
Pennesi, Mark E.
de Juan, Eugene, Jr.
TI Subretinal delivery of immunoglobulin G with gold nanoparticles in the
rabbit eye
SO JAPANESE JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
DE IgG; gold nanoparticle; rabbit; retina; subretinal delivery
ID NANOGOLD; CANCER; CELLS; TIME
AB To examine the feasibility of subretinal delivery of immunoglobulin G (IgG) adsorbed onto gold nanoparticles (GNPs) and its histologic distribution in the rabbit retina after the injection.
Goat IgG was adsorbed onto GNPs electrostatically. Goat IgG-adsorbed GNPs or buffer with goat IgG was injected into the subretinal space of rabbit eyes and followed up for 3 months by examination of fundus photographs, immunohistochemistry against goat IgG, and transmission electron microscopy (TEM). Human retinal pigment epithelial cells (ARPE-19 cells) were cultured, and cell proliferation with or without GNPs was assayed.
At 1 week after the subretinal injection of goat IgG-adsorbed GNPs, retinal degeneration was observed in the outer retina, and goat IgG was immunolabeled in the retinal pigment epithelium (RPE) and the photoreceptor cells. TEM showed GNPs located in the outer segments and in the lysosomes in the RPE at 1 month and no apparent cytotoxicity of the RPE. There were no inhibitory effects of GNPs on proliferation of ARPE-19 cells.
Goat IgG was successfully delivered into photoreceptor cells and RPE using GNPs, though retinal degeneration in the outer retina occurred in this model. This might be an alternative drug delivery method to photoreceptors and RPE.
C1 [Hayashi, Atsushi; Naseri, Ayman; Pennesi, Mark E.; de Juan, Eugene, Jr.] Univ Calif San Francisco, Dept Ophthalmol, San Francisco, CA 94143 USA.
[Naseri, Ayman] San Francisco VA Med Ctr, Dept Ophthalmol, San Francisco, CA USA.
RP Hayashi, A (reprint author), Toyama Univ, Dept Ophthalmol, 2630 Sugitani, Toyama 9300194, Japan.
EM ganka@med.u-toyama.ac.jp
NR 18
TC 14
Z9 14
U1 0
U2 7
PU SPRINGER TOKYO
PI TOKYO
PA 1-11-11 KUDAN-KITA, CHIYODA-KU, TOKYO, 102-0073, JAPAN
SN 0021-5155
J9 JPN J OPHTHALMOL
JI Jpn. J. Ophthalmol.
PD MAY
PY 2009
VL 53
IS 3
BP 249
EP 256
DI 10.1007/s10384-009-0655-x
PG 8
WC Ophthalmology
SC Ophthalmology
GA 451ZS
UT WOS:000266510000011
PM 19484444
ER
PT J
AU Sitnikova, T
Goff, D
Kuperberg, GR
AF Sitnikova, Tatiana
Goff, Donald
Kuperberg, Gina R.
TI Neurocognitive Abnormalities During Comprehension of Real-World
Goal-Directed Behaviors in Schizophrenia
SO JOURNAL OF ABNORMAL PSYCHOLOGY
LA English
DT Review
DE schizophrenia; ERPs; real-world knowledge; comprehension of
goal-directed actions; behavior abnormalities
ID EVENT-RELATED POTENTIALS; PSYCHIATRIC RATING-SCALE; PREFRONTAL CORTEX
DYSFUNCTION; CONTEXT-PROCESSING DEFICITS; NEGATIVE SYMPTOMS; BRAIN
POTENTIALS; WORKING-MEMORY; SENTENCE COMPREHENSION; CLINICAL SYMPTOMS;
NEURAL MECHANISMS
AB Origins of impaired adaptive functioning in schizophrenia remain poorly understood. Behavioral disorganization may arise from an abnormal reliance on common combinations between concepts stored in semantic memory. Avolition-apathy may be related to deficits in using goal-related requirements to flexibly plan behavior. The authors recorded event-related potentials (ERPs) in 16 patients with medicated schizophrenia and 16 healthy controls in a novel video paradigm presenting congruous or incongruous objects in real-world activities. All incongruous objects were contextually inappropriate, but the incongruous scenes varied in comprehensibility. Psychopathology was assessed with the Scales for the Assessment of Positive and Negative Symptoms (SAPS/SANS) and the Brief Psychiatric Rating Scale. In patients, an N400 ERP, thought to index activity in semantic memory, was abnormally enhanced to less comprehensible incongruous scenes, and larger N400 priming was associated with disorganization severity. A P600 ERP, which may index flexible object-action integration based on goal-related requirements, was abnormally attenuated in patients, and its smaller magnitude was associated with the SANS rating of impersistence at work or school (goal-directed behavior). Thus, distinct neurocognitive abnormalities may underlie disorganization and goal-directed behavior deficits in schizophrenia.
C1 [Sitnikova, Tatiana] Massachusetts Gen Hosp, AthinoulaA Martinos Ctr Biomed Imaging, Dept Psychiat, Charlestown, MA 02129 USA.
[Kuperberg, Gina R.] Tufts Univ, Dept Psychol, Medford, MA 02155 USA.
[Sitnikova, Tatiana] Harvard Univ, Massachusetts Gen Hosp, Dept Psychiat, Sch Med, Charlestown, MA 02129 USA.
RP Sitnikova, T (reprint author), Massachusetts Gen Hosp, AthinoulaA Martinos Ctr Biomed Imaging, Dept Psychiat, Bldg 149 2301,13th St, Charlestown, MA 02129 USA.
EM tatiana@nmr.mgh.harvard.edu
FU NIMH NIH HHS [K23 MH002034, K23 MH002034-05, MH02034, MH071635, R01
MH071635, R01 MH071635-01A1, R01 MH071635-02]
NR 177
TC 13
Z9 14
U1 3
U2 8
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0021-843X
J9 J ABNORM PSYCHOL
JI J. Abnorm. Psychol.
PD MAY
PY 2009
VL 118
IS 2
BP 256
EP 277
DI 10.1037/a0015619
PG 22
WC Psychology, Clinical; Psychology, Multidisciplinary
SC Psychology
GA 443EP
UT WOS:000265893300002
PM 19413402
ER
PT J
AU Wojnar, M
Ilgen, MA
Czyz, E
Strobbe, S
Klimkiewicz, A
Jakubczyk, A
Glass, J
Brower, KJ
AF Wojnar, Marcin
Ilgen, Mark A.
Czyz, Ewa
Strobbe, Stephen
Klimkiewicz, Anna
Jakubczyk, Andrzej
Glass, Jennifer
Brower, Kirk J.
TI Impulsive and non-impulsive suicide attempts in patients treated for
alcohol dependence
SO JOURNAL OF AFFECTIVE DISORDERS
LA English
DT Article
DE Suicide; Attempt; Alcohol dependence; Impulsive behavior; Poland
ID USE-DISORDER TREATMENT; ILLICIT DRUG-USE; RISK-FACTORS;
PERSONALITY-DISORDER; INHIBITORY CONTROL; HISTORY; AGGRESSION; BEHAVIOR;
INDIVIDUALS; ADOLESCENCE
AB Background: Suicidal behavior has been recognized as an increasing problem among alcohol-dependent subjects. The aim of the study was to identify correlates of impulsive and non-impulsive suicide attempts among a treated population of alcohol-dependent patients.
Methods: A total of 154 patients with alcohol dependence consecutively admitted for addiction treatment participated in the study. Suicidal behavior was assessed together with severity of alcohol dependence, childhood abuse, impulsivity, and family history. A stop-signal procedure was used as a behavioral measure of impulsivity.
Results and conclusions: Lifetime suicide attempts were reported by 43% of patients in alcohol treatment; of which 62% were impulsive. Compared to patients without a suicide attempt, those with a non-impulsive attempt were more likely to have a history of sexual abuse (OR=7.17), a family history of suicide (OR=4.09), and higher scores on a personality measure of impulsiveness (OR=2.27). The only significant factor that distinguished patients with impulsive suicide attempts from patients without a suicide attempt and from patients with a non-impulsive suicide attempt was a higher level of behavioral impulsivity (OR=1.84-2.42).
Limitations: Retrospective self-report of suicide attempts and family history. Lack of diagnostic measure. (C) 2008 Elsevier B.V. All rights reserved.
C1 [Wojnar, Marcin] Univ Michigan, Addict Res Ctr, Dept Psychiat, Ann Arbor, MI 48109 USA.
[Wojnar, Marcin; Klimkiewicz, Anna; Jakubczyk, Andrzej] Med Univ Warsaw, Dept Psychiat, Warsaw, Poland.
[Ilgen, Mark A.] US Dept Vet Affairs, Hlth Serv Res & Dev, Ann Arbor, MI USA.
[Glass, Jennifer] Univ Michigan, Inst Social Res, Ann Arbor, MI 48109 USA.
RP Wojnar, M (reprint author), Univ Michigan, Addict Res Ctr, Dept Psychiat, Rachel Upjohn Bldg,4250 Plymouth Rd, Ann Arbor, MI 48109 USA.
EM mwojnar@umich.edu
FU Fogarty International Center/NIDA International Substance Abuse Research
Program [D43 TW05818]; Fogarty International Center/NLAAA International
Collaborative Alcohol & Injury Research Training Program [D43 TW007569];
NIAAA [R21 AA016104]; Polish Ministry of Science and Higher Education
[2P05D 004 29]
FX Authors have not signed an agreement with any sponsor of the study
reported in this paper that has a clause which prevents them from
publishing both positive and negative results, from collaborating with
other investigators to pool data across sites, or that forbids them from
publishing without the approval of the sponsor. The views expressed in
this report are those of the authors and do not necessarily represent
those of the Supporting agencies. The supporting agencies had no further
role in study design; in the collection, analysis and interpretation of
data; in the writing of the report; and in the decision to submit the
paper for publication.
NR 58
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U1 1
U2 5
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 MAY
PY 2009
VL 115
IS 1-2
BP 131
EP 139
DI 10.1016/j.jad.2008.09.001
PG 9
WC Clinical Neurology; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 435CC
UT WOS:000265319900015
PM 18835498
ER
PT J
AU Meeker, JD
Calafat, AM
Hauser, R
AF Meeker, John D.
Calafat, Antonia M.
Hauser, Russ
TI Urinary Metabolites of Di(2-ethylhexyl) Phthalate Are Associated With
Decreased Steroid Hormone Levels in Adult Men
SO JOURNAL OF ANDROLOGY
LA English
DT Article
DE Androgen; biomarker; endocrine; environment; human; estrogen; male
reproduction; testosterone
ID MALE REPRODUCTIVE-SYSTEM; RAT GRANULOSA-CELLS; MONO-(2-ETHYLHEXYL)
PHTHALATE; QUANTITATIVE DETECTION; OXIDATIVE METABOLITES; TEMPORAL
VARIABILITY; ESTRADIOL PRODUCTION; MALE-INFERTILITY; DNA-DAMAGE;
IN-UTERO
AB Experimental animal studies have demonstrated that exposure to some phthalates may be associated with altered endocrine function and adverse effects on male reproductive development and function, but human studies are limited. In the present study, urine and serum samples were collected from 425 men recruited through a US infertility clinic. Urinary concentrations of mono(2-ethylhexyl) phthalate (MEHP), the hydrolytic metabolite of di(2-ethylhexyl) phthalate (DEHP), and other phthalate monoester metabolites were measured, along with serum levels of testosterone, estradiol, sex hormone-binding globulin (SHBG), follicle-stimulating hormone, luteinizing hormone, inhibin B, and prolactin. Two oxidized urinary metabolites of DEHP were also measured in urine from 221 of the men. In multiple regression models adjusted for potential confounders, MEHP was inversely associated with testosterone, estradiol, and free androgen index (FAI). An interquartile range increase in MEHP was associated with 3.7% (95% confidence interval [CI], -6.8% to -0.5%) and 6.8% (95% Cl, -11.2% to -2.4%) declines in testosterone and estradiol, respectively, relative to the population median hormone levels. There was limited evidence for effect modification of the inverse association between MEHP and FAI by the proportion of DEHP metabolites in the urine measured as MEHP (MEHP%), which is considered a phenotypic marker of less efficient metabolism of DEHP to its oxidized metabolites. Finally, the ratio of testosterone to estradiol was positively associated with MEHP (P = .07) and MEHP% (P = .007), suggesting potential relationships with aromatase suppression. In conclusion, these results suggest that urinary metabolites of DEHP are inversely associated with circulating steroid hormone levels in adult men. However, additional research is needed to confirm these findings.
C1 [Meeker, John D.] Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, Ann Arbor, MI 48109 USA.
[Calafat, Antonia M.] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Hauser, Russ] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA.
[Hauser, Russ] Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, Androl Lab, Boston, MA 02114 USA.
[Hauser, Russ] Massachusetts Gen Hosp, Vitro Fertilizat Unit, Boston, MA 02114 USA.
RP Meeker, JD (reprint author), Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, 6635 SPH Tower,109 S Observ St, Ann Arbor, MI 48109 USA.
EM meekerj@umich.edu
RI Perez , Claudio Alejandro/F-8310-2010;
OI Perez , Claudio Alejandro/0000-0001-9688-184X; Meeker,
John/0000-0001-8357-5085
FU National Institute of Environmental Health Sciences (NIEHS) [ES009718,
ES00002]; National Institutes of Health (NIH)
FX Supported by grants ES009718 and ES00002 from the National Institute of
Environmental Health Sciences (NIEHS), National Institutes of Health
(NIH).
NR 51
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U1 0
U2 8
PU AMER SOC ANDROLOGY, INC
PI LAWRENCE
PA C/O ALLEN PRESS, INC PO BOX 368, LAWRENCE, KS 66044 USA
SN 0196-3635
J9 J ANDROL
JI J. Androl.
PD MAY-JUN
PY 2009
VL 30
IS 3
BP 287
EP 297
DI 10.2164/jandrol.108.006403
PG 11
WC Andrology
SC Endocrinology & Metabolism
GA 439IO
UT WOS:000265621000011
PM 19059903
ER
PT J
AU Luga, A
Lerner, E
Shedd, TR
van der Schalie, WH
AF Luga, Aurel
Lerner, Ethan
Shedd, Tommy R.
van der Schalie, William H.
TI Rapid responses of a melanophore cell line to chemical contaminants in
water
SO JOURNAL OF APPLIED TOXICOLOGY
LA English
DT Article
DE Xenopus laevis; melanophore; chromatophore; toxicity; sensor; drinking
water
ID TOXICITY
AB We have evaluated a Xenopus cell line as a potential sensor for detecting toxins in water. X. laevis melanophores responded rapidly by dispersing melanosomes following exposure to six (ammonia, arsenic, copper, mercury, pentachlorophenol and phenol) of 12 tested chemicals in the desired sensitivity range. For two additional chemicals (nicotine and paraquat) the melanophore response improved upon the response capabilities of several available toxicity sensors. These results suggest that a melanophore-based sensor could be useful for the rapid assessment of chemical toxicity in drinking water. Published 2009 by John Wiley and Sons, Ltd.
C1 [Shedd, Tommy R.; van der Schalie, William H.] USA, Ctr Environm Hlth Res, Ft Detrick, MD 21702 USA.
[Luga, Aurel; Lerner, Ethan] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA.
RP Shedd, TR (reprint author), USA, Ctr Environm Hlth Res, 568 Doughten Dr, Ft Detrick, MD 21702 USA.
EM Tommy.Shedd@us.army.mil
FU US Army Medical Research and Materiel Command; National Institutes of
Health [SU01AI061420]
FX We thank Bill Dennis and Alan Rosencrance for analytical chemistry and
sample preparation support that was critical to the success of the
effort. Elgin Perry provided the statistical analysis. The views,
opinions and/or findings contained in this short communication are those
of the authors and should not be construed as official Department of the
Army position, policy or decision, unless so designated by other
official documentation. Citations of commercial organizations or trade
names in this paper do not constitute an official Department of the Army
endorsement or approval of the products or services of these
organizations. This work was supported by the US Army Medical Research
and Materiel Command and by the National Institutes of Health (grant no.
SU01AI061420).
NR 15
TC 3
Z9 3
U1 1
U2 3
PU JOHN WILEY & SONS LTD
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND
SN 0260-437X
J9 J APPL TOXICOL
JI J. Appl. Toxicol.
PD MAY
PY 2009
VL 29
IS 4
BP 346
EP 349
DI 10.1002/jat.1416
PG 4
WC Toxicology
SC Toxicology
GA 451YU
UT WOS:000266507600010
ER
PT J
AU Venkatesh, J
Kawabata, D
Kim, S
Xu, XN
Chinnasamy, P
Paul, E
Diamond, B
Grimaldi, CM
AF Venkatesh, Jeganathan
Kawabata, Daisuke
Kim, Sunjung
Xu, Xiaonan
Chinnasamy, Prameladevi
Paul, Elahna
Diamond, Betty
Grimaldi, Christine M.
TI Selective regulation of autoreactive B cells by Fc gamma RIIB
SO JOURNAL OF AUTOIMMUNITY
LA English
DT Article
DE Antibodies; Autoimmunity; Lupus; B cells; Fc receptor
ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; INTERFERON-INDUCIBLE GENE;
AUTOIMMUNE-PRONE MICE; DENDRITIC CELLS; LIPID RAFTS; NEGATIVE SELECTION;
IMMUNE-COMPLEXES; DEFICIENT MICE; DNA ANTIBODIES; UP-REGULATION
AB Fc gamma RIIB is an inhibitory receptor which plays a role in limiting B cell and DC activation. Since Fc gamma RIIB is known to dampen the signaling strength of the BCR, vie wished to determine the impact of Fc gamma RIIB on the regulation of BCRs which differ in their affinity for DNA. For these studies, Fc gamma RIIB deficient BALB/c mice were bred with mice expressing the transgene-encoded H chain of the R4A anti-DNA antibody which gives rise to BCRs which express high, low or no affinity for DNA. The deletion of Fc gamma RIIB in R4A BALB/c mice led to an alteration in the B cell repertoire, allowing for the expansion and activation of high affinity DNA-reactive B cells. By 6-8 months of age, R4A x Fc gamma RIIB(-/-) BALB/c mice spontaneously developed anti-DNA antibody titers. These mice also displayed an induction of IFN-inducible genes and an elevation in levels of the B cell survival factor, BAFF. These data demonstrate that Fc gamma RIIB preferentially limits activation of high affinity autoreactive B cells and can influence the activation of DC through an immune complex-mediated mechanism. (C) 2009 Elsevier Ltd. All rights reserved.
C1 [Venkatesh, Jeganathan; Kawabata, Daisuke; Kim, Sunjung; Chinnasamy, Prameladevi; Diamond, Betty; Grimaldi, Christine M.] Feinstein Inst Med Res, Ctr Autoimmune & Musculoskeletal Dis, Manhasset, NY 11030 USA.
[Xu, Xiaonan] Feinstein Inst Med Res, Ctr Oncol & Cell Biol, Manhasset, NY 11030 USA.
[Paul, Elahna] Massachusetts Gen Hosp, Dept Pediat Nephrol, Boston, MA 02114 USA.
RP Grimaldi, CM (reprint author), Feinstein Inst Med Res, Ctr Autoimmune & Musculoskeletal Dis, Manhasset, NY 11030 USA.
EM cgrimaldi@nshs.edu
FU NIAMS
FX This work was supported by grants from NIAMS (BD and CMG). We wish to
thank Alla Tashmukhamedova for technical assistance and Sylvia Jones for
help with the preparation of this manuscript.
NR 64
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Z9 18
U1 0
U2 2
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0896-8411
J9 J AUTOIMMUN
JI J. Autoimmun.
PD MAY-JUN
PY 2009
VL 32
IS 3-4
BP 149
EP 157
DI 10.1016/j.jaut.2009.02.009
PG 9
WC Immunology
SC Immunology
GA 451ZV
UT WOS:000266510300001
PM 19327966
ER
PT J
AU Lee, DH
Shi, JJ
Jeoung, NH
Kim, MS
Zabolotny, JM
Lee, SW
White, MF
Wei, L
Kim, YB
AF Lee, Dae Ho
Shi, Jianjian
Jeoung, Nam Ho
Kim, Min Seon
Zabolotny, Janice M.
Lee, Sam W.
White, Morris F.
Wei, Lei
Kim, Young-Bum
TI Targeted Disruption of ROCK1 Causes Insulin Resistance in Vivo
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID BINDING PROTEIN RHO; SERINE/THREONINE KINASE; PATHWAY; GTPASE; GLUT4;
PHOSPHORYLATION; TRANSLOCATION; CYTOSKELETON; ADIPOCYTES; ACTIVATION
AB Insulin signaling is essential for normal glucose homeostasis. Rho-kinase (ROCK) isoforms have been shown to participate in insulin signaling and glucose metabolism in cultured cell lines. To investigate the physiological role of ROCK1 in the regulation of whole body glucose homeostasis and insulin sensitivity in vivo, we studied mice with global disruption of ROCK1. Here we show that, at 16 - 18 weeks of age, ROCK1-deficient mice exhibited insulin resistance, as revealed by the failure of blood glucose levels to decrease after insulin injection. However, glucose tolerance was normal in the absence of ROCK1. These effects were independent of changes in adiposity. Interestingly, ROCK1 gene ablation caused a significant increase in glucose-induced insulin secretion, leading to hyperinsulinemia. To determine the mechanism(s) by which deletion of ROCK1 causes insulin resistance, we measured the ability of insulin to activate phosphatidylinositol 3-kinase and multiple distal pathways in skeletal muscle. Insulin-stimulated phosphatidylinositol 3-kinase activity associated with IRS-1 or phospho-tyrosine was also reduced similar to 40% without any alteration in tyrosine phosphorylation of insulin receptor in skeletal muscle. Concurrently, serine phosphorylation of IRS-1 at serine 632/635, which is phosphorylated by ROCK in vitro, was also impaired in these mice. Insulin-induced phosphorylation of Akt, AS160, S6K, and S6 was also decreased in skeletal muscle. These data suggest that ROCK1 deficiency causes systemic insulin resistance by impairing insulin signaling in skeletal muscle. Thus, our results identify ROCK1 as a novel regulator of glucose homeostasis and insulin sensitivity in vivo, which could lead to new treatment approaches for obesity and type 2 diabetes.
C1 [Shi, Jianjian; Wei, Lei] Indiana Univ, Sch Med, Wells Ctr Pediat Res, Riley Heart Res Ctr,Dept Pediat, Indianapolis, IN 46202 USA.
[Lee, Dae Ho; Zabolotny, Janice M.; Kim, Young-Bum] Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA.
[Lee, Dae Ho; Zabolotny, Janice M.; Kim, Young-Bum] Harvard Univ, Sch Med, Boston, MA 02215 USA.
[Jeoung, Nam Ho] Indiana Univ, Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA.
[Jeoung, Nam Ho] Richard L Roudebush Vet Affairs Med Ctr, Indianapolis, IN 46202 USA.
[Kim, Min Seon] Univ Ulsan, Coll Med, Asan Inst Life Sci, Dept Internal Med, Seoul 138736, South Korea.
[Lee, Sam W.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA.
[Lee, Sam W.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
[White, Morris F.] Childrens Hosp, Div Endocrinol, Howard Hughes Med Inst, Boston, MA 02115 USA.
[White, Morris F.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
RP Wei, L (reprint author), Indiana Univ, Sch Med, Wells Ctr Pediat Res, Riley Heart Res Ctr,Dept Pediat, 1044 W Walnut St,R4-370, Indianapolis, IN 46202 USA.
EM lewei@iupui.edu; ykim2@bidmc.harvard.edu
OI Jeoung, Nam Ho/0000-0002-7584-3761
FU National Institutes of Health [DK43051, DK38712, CA127247, HL072897,
HL085098]; American Diabetes Association [7-05-PPG-02, 1-09-RA-87];
Showalter Trust [89829]; Korean Ministry of Health and Welfare Grant
[A06-2363]; Korea Science and Engineering Foundation
[R-01-2006-000-108060-0]
FX This work was supported, in whole or in part, by National Institutes of
Health Grants DK43051 (to Y.B.K.), DK38712 (to M. F. W.), CA127247 (to
S. W. L.), and HL072897 and HL085098 (to L. W.). This work was also
supported by American Diabetes Association Grants 7-05-PPG-02 and
1-09-RA-87 (to Y.B.K.), Showalter Trust Grant 89829 (to J.S.), Korean
Ministry of Health and Welfare Grant A06-2363 (to M. S. K.), and Korea
Science and Engineering Foundation Grant R-01-2006-000-108060-0 (to M.
S. K.).
NR 34
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U1 1
U2 2
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD MAY 1
PY 2009
VL 284
IS 18
BP 11776
EP 11780
DI 10.1074/jbc.C900014200
PG 5
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 437NQ
UT WOS:000265494600009
PM 19276091
ER
PT J
AU Cogan, SF
Ehrlich, J
Plante, TD
Smirnov, A
Shire, DB
Gingerich, M
Rizzo, JF
AF Cogan, Stuart F.
Ehrlich, Julia
Plante, Timothy D.
Smirnov, Anton
Shire, Douglas B.
Gingerich, Marcus
Rizzo, Joseph F.
TI Sputtered Iridium Oxide Films for Neural Stimulation Electrodes
SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS
LA English
DT Article
DE neural stimulation; neural recording; microelectrode; iridium oxide;
sputtering
ID CHARGE-INJECTION LIMITS; ELECTRICAL-STIMULATION; INTRACORTICAL
MICROSTIMULATION; MICROELECTRODE ARRAYS; PERCEPTUAL THRESHOLDS; RETINAL
PROSTHESIS; MORPHOLOGY; CAPACITY; PULSES; SALINE
AB Sputtered iridium (oxide films (SIROFs) deposited by DC reactive sputtering from an iridium metal target have been characterized in vitro for their potential as neural recording and stimulation electrodes. SIROFs were deposited over gold metallization oil flexible multielectrode arrays fabricated oil thin (15 mu m) polyimide substrates. SIROF thickness and electrode areas of 200-1300 nm and 1960-125,600 mu m(2), respectively, were investigated. The charge-injection capacities of the SIROFs were evaluated in an inorganic interstitial fluid model in response to charge-balanced, cathodal-first current pulses. Charge injection capacities were measured as a function of cathodal pulse width (0.2-1 ins) and potential bias in the interpulse period (0.0 to 0.7 V vs. Ag/AgCl). Depending on the pulse parameters and electrode area, charge-injection capacities ranged from 1-9 mC/cm(2), comparable with activated iridium oxide films (AIROFs) pulsed under similar conditions. Other parameters relevant to the use of SIROF oil nerve electrodes, including the thickness dependence of impedance (0.05-10(5) Hz) and the current necessary to maintain a bias in the interpulse region were also determined. (C) 2008 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 89B: 353-361, 2009
C1 [Cogan, Stuart F.; Ehrlich, Julia; Plante, Timothy D.; Smirnov, Anton] EIC Labs, Norwood, MA 02062 USA.
[Shire, Douglas B.; Gingerich, Marcus] Cornell Univ, Dept Vet Affairs, Ctr Innovat Visual Rehabil, Ithaca, NY 14853 USA.
[Shire, Douglas B.; Gingerich, Marcus] Cornell Univ, Cornell NanoScale Sci & Technol Facil, Ithaca, NY 14853 USA.
[Rizzo, Joseph F.] Ctr Innovat Visual Rehabil, Dept Vet Affairs, Boston, MA 02062 USA.
[Rizzo, Joseph F.] Massachusetts Eye & Ear Infirm, Boston, MA 02062 USA.
RP Cogan, SF (reprint author), EIC Labs, Norwood, MA 02062 USA.
EM scogan@eiclabs.com
FU National Institutes of Health [C4266-C, 5R44HL071395]
FX Contract grant sponsor: Department of Veterans Affairs: Rehabilitation
Research and Development service: National Institutes of Health;
Contract grant numbers: C4266-C, 5R44HL071395
NR 38
TC 50
Z9 50
U1 2
U2 13
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1552-4973
J9 J BIOMED MATER RES B
JI J. Biomed. Mater. Res. Part B
PD MAY
PY 2009
VL 89B
IS 2
BP 353
EP 361
DI 10.1002/jbm.b.31223
PG 9
WC Engineering, Biomedical; Materials Science, Biomaterials
SC Engineering; Materials Science
GA 436VU
UT WOS:000265445000010
PM 18837458
ER
PT J
AU Hernandez-Montes, MDS
Furlong, C
Rosowski, JJ
Hulli, N
Harrington, E
Cheng, JT
Ravicz, ME
Santoyo, FM
AF del Socorro Hernandez-Montes, Maria
Furlong, Cosme
Rosowski, John J.
Hulli, Nesim
Harrington, Ellery
Cheng, Jeffrey Tao
Ravicz, Michael E.
Mendoza Santoyo, Fernando
TI Optoelectronic holographic otoscope for measurement of
nano-displacements in tympanic membranes
SO JOURNAL OF BIOMEDICAL OPTICS
LA English
DT Article
DE tympanic membrane; optoelectronic holography; interferometry; otoscope
ID HUMAN MIDDLE-EAR; TIME-AVERAGED HOLOGRAPHY; FINITE-ELEMENT METHOD;
DYNAMIC-BEHAVIOR; VIBRATION MEASUREMENT; CAT EARDRUM; INTERFEROMETRY;
TYMPANOMETRY; ADULTS; MODEL
AB Current methodologies for characterizing tympanic membrane (TM) motion are usually limited to either average acoustic estimates (admittance or reflectance) or single-point mobility measurements, neither of which suffices to characterize the detailed mechanical response of the TM to sound. Furthermore, while acoustic and single-point measurements may aid in diagnosing some middle-ear disorders, they are not always useful. Measurements of the motion of the entire TM surface can provide more information than these other techniques and may be superior for diagnosing pathology. We present advances in our development of a new compact optoelectronic holographic otoscope (OEHO) system for full field-of-view characterization of nanometer-scale sound-induced displacements of the TM surface at video rates. The OEHO system consists of a fiber optic subsystem, a compact otoscope head, and a high-speed image processing computer with advanced software for recording and processing holographic images coupled to a computer-controlled sound-stimulation and recording system. A prototype OEHO system is in use in a medical research environment to address basic science questions regarding TM function. The prototype provides real-time observation of sound-induced TM displacement patterns over a broad frequency range. Representative time-averaged and stroboscopic holographic interferometry results in animals and human cadaver samples are shown, and their potential utility is discussed. (C) 2009 Society of Photo-Optical Instrumentation Engineers. [DOI: 10.1117/1.3153898]
C1 [del Socorro Hernandez-Montes, Maria; Hulli, Nesim; Harrington, Ellery] Worcester Polytech Inst, Dept Mech Engn, Worcester, MA USA.
[Furlong, Cosme] Worcester Polytech Inst, Ctr Holog Studies & Laser MicromechaTron, Worcester, MA USA.
[del Socorro Hernandez-Montes, Maria; Mendoza Santoyo, Fernando] Ctr Invest Opt AC, Guanajuato 37150, Mexico.
[Furlong, Cosme; Rosowski, John J.; Cheng, Jeffrey Tao; Ravicz, Michael E.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA.
[Furlong, Cosme; Rosowski, John J.] MIT, Harvard Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol Program, Cambridge, MA 02139 USA.
[Rosowski, John J.; Cheng, Jeffrey Tao; Ravicz, Michael E.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA.
RP Hernandez-Montes, MDS (reprint author), AC Metrol, Ctr Invest Opt, Loma Bosque 115, Guanajuato 37150, Mexico.
EM mhernandez@cio.mx
OI Mendoza-Santoyo, Fernando/0000-0002-4596-3316
FU U. S. National Institute for Deafness and other Communicative Disorders
(NIDCD); Worcester Polytechnic Institute (WPI); Centro de
Investigaciones en Optica; Massachusetts Eye and Ear Infirmary (MEEI);
Lakshmi Mittal
FX This research was supported by the U. S. National Institute for Deafness
and other Communicative Disorders (NIDCD), Worcester Polytechnic
Institute (WPI), Centro de Investigaciones en Optica, A. C. (CIO),
Massachusetts Eye and Ear Infirmary (MEEI), and Lakshmi Mittal. We thank
Chris Scarpino of the MEEI, an alumni of WPI, for facilitating the
interactions between our two research groups. Thanks also go to
Christian Wester, Benjamin Dwyer, and Marty Maccaferri for their
contributions to this work.
NR 39
TC 27
Z9 27
U1 2
U2 5
PU SPIE-SOC PHOTOPTICAL INSTRUMENTATION ENGINEERS
PI BELLINGHAM
PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA
SN 1083-3668
J9 J BIOMED OPT
JI J. Biomed. Opt.
PD MAY-JUN
PY 2009
VL 14
IS 3
AR 034023
DI 10.1117/1.3153898
PG 9
WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine &
Medical Imaging
SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine &
Medical Imaging
GA 477RN
UT WOS:000268536300032
PM 19566316
ER
PT J
AU Deliolanis, NC
Dunham, J
Wurdinger, T
Figueiredo, JL
Tannous, BA
Ntziachristos, V
AF Deliolanis, Nikolaos C.
Dunham, Joshua
Wurdinger, Thomas
Figueiredo, Jose-Luiz
Bakhos A., Tannous
Ntziachristos, Vasilis
TI In-vivo imaging of murine tumors using complete-angle projection
fluorescence molecular tomography
SO JOURNAL OF BIOMEDICAL OPTICS
LA English
DT Article
DE fluorescence; tomography; in vivo; molecular imaging; cancer; tumor;
fluorescent proteins
ID DIFFUSE OPTICAL TOMOGRAPHY; BREAST-CANCER; RECONSTRUCTION
AB We interrogate the ability of free-space fluorescence tomography to image small animals in vivo using charge-coupled device (CCD) camera measurements over 360-deg noncontact projections. We demonstrate the performance of normalized dual-wavelength measurements that are essential for in-vivo use, as they account for the heterogeneous distribution of photons in tissue. In-vivo imaging is then showcased on mouse lung and brain tumors cross-validated by x-ray microcomputed tomography and histology. (C) 2009 Society of Photo-Optical Instrumentation Engineers. [DOI: 10.1117/1.3149854]
C1 [Deliolanis, Nikolaos C.; Ntziachristos, Vasilis] Tech Univ Munich, Helmholtz Zentrum Munchen, Inst Biol & Med Imaging, D-85764 Neuherberg, Germany.
[Deliolanis, Nikolaos C.; Dunham, Joshua; Wurdinger, Thomas; Figueiredo, Jose-Luiz; Bakhos A., Tannous; Ntziachristos, Vasilis] Harvard Univ, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA.
[Wurdinger, Thomas; Bakhos A., Tannous] Harvard Univ, Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA.
RP Deliolanis, NC (reprint author), Tech Univ Munich, Helmholtz Zentrum Munchen, Inst Biol & Med Imaging, Ingolstaedter Landstr 1, D-85764 Neuherberg, Germany.
EM n.deliolanis@helmholtz-muenchen.de
OI Deliolanis, Nikolaos/0000-0002-6392-3035
FU Marie Curie Intra-European Fellowship within the 7th European Community
Framework Programme; National Institutes of Health [RO1 EB004382-01, RO1
EB000750-01, R43-ES012360]
FX The authors would like to thank Tobias Lasser and Damon Hyde for helpful
discussions. This research was supported by a Marie Curie Intra-European
Fellowship within the 7th European Community Framework Programme, and by
National Institutes of Health grants RO1 EB004382-01, RO1 EB000750-01,
and R43-ES012360.
NR 14
TC 27
Z9 28
U1 0
U2 5
PU SPIE-SOC PHOTOPTICAL INSTRUMENTATION ENGINEERS
PI BELLINGHAM
PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA
SN 1083-3668
J9 J BIOMED OPT
JI J. Biomed. Opt.
PD MAY-JUN
PY 2009
VL 14
IS 3
AR 030509
DI 10.1117/1.3149854
PG 3
WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine &
Medical Imaging
SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine &
Medical Imaging
GA 477RN
UT WOS:000268536300006
PM 19566290
ER
PT J
AU Wu, JY
Scadden, DT
Kronenberg, HM
AF Wu, Joy Y.
Scadden, David T.
Kronenberg, Henry M.
TI Role of the Osteoblast Lineage in the Bone Marrow Hematopoietic Niches
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Article
ID STEM-CELL NICHE; PROGENITOR CELLS; SELF-RENEWAL; IN-VIVO;
DIFFERENTIATION; MICROENVIRONMENT; MICE; RECEPTOR; GENE; QUIESCENCE
C1 [Wu, Joy Y.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA.
[Scadden, David T.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA.
[Scadden, David T.] Harvard Stem Cell Inst, Cambridge, MA USA.
RP Kronenberg, HM (reprint author), Massachusetts Gen Hosp, Endocrine Unit, 50 Blossom St,Thier 1101, Boston, MA 02114 USA.
EM hkronenberg@partners.org
FU NIH [AR053781, AR054741, HL081030, DK117940]
FX The authors thank Drs. Cristina Lo Celso, Louise Purton, and Sean Wu for
thoughtful comments on this manuscript. This work was supported by NIH
Grants AR053781 and AR054741 (to J.Y.W.), HL081030 (to H.M.K. and
D.T.S.), and DK117940 (to H.M.K.).
NR 75
TC 58
Z9 60
U1 0
U2 2
PU AMER SOC BONE & MINERAL RES
PI WASHINGTON
PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA
SN 0884-0431
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD MAY
PY 2009
VL 24
IS 5
BP 759
EP 764
DI 10.1359/JBMR.090225
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 438IV
UT WOS:000265550000001
PM 19257832
ER
PT J
AU Wu, HP
Xu, GL
Li, YP
AF Wu, Haiping
Xu, Guoliang
Li, Yi-Ping
TI Atp6v0d2 Is an Essential Component of the Osteoclast-Specific Proton
Pump That Mediates Extracellular Acidification in Bone Resorption
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Article
DE Atp6v0d2; vacuolar-ATPases; osteoclasts; bone resorption; extracellular
acidification
ID VACUOLAR H+-ATPASE; V-ATPASE; TRANSLOCATING ATPASE; D-SUBUNIT;
C-SUBUNIT; STIMULATING FACTOR; MOLECULAR-CLONING; GENE-EXPRESSION; A3
ISOFORM; DIFFERENTIATION
AB Bone resorption relies on the extracellular acidification function of vacuolar (V-) ATPase proton pump(s) present in the plasma membrane of osteoclasts. The exact configuration of osteoclast-specific V-ATPases remains largely unknown. In this study, we found that Atp6v0d2 (d2), an isoform of the d subunit in the V-ATPase, showed 5-fold higher expression than that of Atp6v0d1. (d1) in mature osteoclasts, indicating a potential function in osteoclastic bone resorption. When d2 was depleted at an earl), stage of RANKL-induced osteoclast differentiation in vitro, formation of multinucleated cells was severely impaired. However, depletion of d2 at a late differentiation stage did not affect osteoclast fusion but did abolish the activity of extracellular acidification and bone resorption of mature osteoclasts. We also showed the association of the two tagged-proteins d2 and a3 when co-expressed in mammalian cells with a co-immunoprecipitation assay. Moreover, glutathione-S-transferase (GST) pull-down assay showed the direct interaction of d2 with the N terminus of Atp6v0a3 (0), which is the functionally identified osteoclast-specific component of V-ATPase. Therefore, our results show the dual function of d2 as a regulator of cell fusion in osteoclast differentiation and as an essential component of the osteoclast-specific proton pump that mediates extracellular acidification in bone resorption.
C1 [Li, Yi-Ping] Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA.
[Li, Yi-Ping] Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA.
[Wu, Haiping] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Mol Biol, Shanghai, Peoples R China.
[Wu, Haiping; Xu, Guoliang] Chinese Acad Sci, Grad Sch, Shanghai, Peoples R China.
RP Li, YP (reprint author), Forsyth Inst, Dept Cytokine Biol, 140 Fenway, Boston, MA 02115 USA.
EM ypli@forsyth.org
FU China National Science Foundation; Ministry of Science and Technology of
China [2005CB522400]; Shanghai Municipal Commission for Science and
Technology,; Max-Planck-Gesellschaft zur Forderung der Wissenschaften;
NIH [AR-44741]
FX We thank Christie Taylor and Carrie Soltanoff for manuscript assistance;
Dr. Shengmei Feng and Dr. Wei Chen for critical discussion and technical
assistance of this work; Dr. Jiuhong Kang (Institute of Biochemistry and
Cell Biology, Chinese Academy of Science, Shanghai, China) for kindly
providing the lentivirus vector and packaging plasmids; Yihui Tu for
assistance of confocal microscopy and Aqin Li for SEM assistance. Work
in G-L.X.'s laboratory is supported by grants from the China National
Science Foundation, the Ministry of Science and Technology of China
(National Basic Research Program 2005CB522400), the Shanghai Municipal
Commission for Science and Technology, and the Max-Planck-Gesellschaft
zur Forderung der Wissenschaften (the Max Planck Society for the
Advancement of Science). The work in Y-P.L.'s laboratory is supported by
NIH Grant AR-44741.
NR 56
TC 45
Z9 50
U1 0
U2 5
PU AMER SOC BONE & MINERAL RES
PI WASHINGTON
PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA
SN 0884-0431
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD MAY
PY 2009
VL 24
IS 5
BP 871
EP 885
DI 10.1359/JBMR.081239
PG 15
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 438IV
UT WOS:000265550000014
PM 19113919
ER
PT J
AU Goyal, S
Gupta, P
Ryan, CM
Kazlas, M
Noviski, N
Sheridan, RL
AF Goyal, Sunali
Gupta, Punkaj
Ryan, Colleen M.
Kazlas, Melanie
Noviski, Natan
Sheridan, Robert L.
TI Toxic Epidermal Necrolysis in Children: Medical, Surgical, and
Ophthalmologic Considerations
SO JOURNAL OF BURN CARE & RESEARCH
LA English
DT Review
ID STEVENS-JOHNSON-SYNDROME; COLONY-STIMULATING FACTOR; DOSE INTRAVENOUS
IMMUNOGLOBULINS; SCALDED SKIN SYNDROME; NECROSIS-FACTOR-ALPHA; CYTOTOXIC
T-CELLS; ERYTHEMA MULTIFORME; BURN CENTER; PULMONARY COMPLICATIONS; FAS
LIGAND
AB Toxic epidermal necrolysis is a rare acute inflammatory multisystem life-threatening condition characterized by widespread epidermal necrosis and profound toxic systemic reaction. Implicated etiologic agents in children include drugs, infections, and autoimmune diseases. The pathophysiology includes separation of the epidermis at the dermal-epidermal junction of both skin and extracutaneous epithelium and mucous membranes. The general consensus is that expeditious transfer to a burn center, maintenance of fluid and electrolyte: balance, temperature maintenance, control of evaporative losses, avoidance of use of complicating drugs as corticosteroids and topical sulfa compounds, aggressive septic surveillance, vigorous nutritional support via nasoenteric tube, early ophthalmologic consultation, and appropriate wound care with a regimen of therapy relying on basic principles of treatment of partial-thickness epidermal wounds predict better outcome in the treatment of this disease process. The course of toxic epidermal necrolysis in children, even though dramatic at onset, leads to low mortality when managed appropriately. The current limited published evidence does not clearly delineate differences in epidemiology, pathogenesis, and prognosis of severe skin reactions in children as compared with adults. In this article, we review the available literature oil the pathogenesis, clinical features, pathophysiology, treatment, and complications of this rare disease in children. (J Burn Care Res 2009;30:437-449)
C1 [Goyal, Sunali] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Schepens Eye Res Inst, Boston, MA USA.
[Gupta, Punkaj; Noviski, Natan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Pediat Crit Care, Boston, MA USA.
[Gupta, Punkaj; Noviski, Natan] Shriners Burns Hosp Childrens, Boston, MA USA.
[Kazlas, Melanie] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Pediat Ophthalmol & Strabismus Serv, Boston, MA USA.
RP Gupta, P (reprint author), 20 Staniford St, Boston, MA 02114 USA.
NR 142
TC 15
Z9 15
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1559-047X
EI 1559-0488
J9 J BURN CARE RES
JI J. Burn Care Res.
PD MAY-JUN
PY 2009
VL 30
IS 3
BP 437
EP 449
DI 10.1097/BCR.0b013e3181a28c82
PG 13
WC Emergency Medicine; Dermatology; Surgery
SC Emergency Medicine; Dermatology; Surgery
GA 444BJ
UT WOS:000265954600011
PM 19349890
ER
PT J
AU Jain, V
Pineda, R
AF Jain, Vandana
Pineda, Roberto
TI Reactivated herpetic keratitis following laser in situ keratomileusis
SO JOURNAL OF CATARACT AND REFRACTIVE SURGERY
LA English
DT Article
ID SIMPLEX-VIRUS KERATITIS; LASIK
AB A 40-year-old woman presented with an unusual form of corneal herpetic reactivation 5 weeks after laser in situ keratomileusis. The cornea showed diffuse edema and a stromal ring infiltrate (disciform in appearance). Oral antiviral and topical steroids in tapered dosages were administered. The infiltrate disappeared within 6 weeks. Progressive improvement was also seen in all the parameters on Pentacam scans, including the pachymetry, keratometry readings, and elevation on the anterior float. Herpetic reactivation may occur in many forms after excimer laser ablation. Timely diagnosis and management is crucial to maintain good structural and visual outcomes. Pentacam analysis may serve as a useful adjunct in following the progression of herpetic reactivation cases. J Cataract Refract Surg 2009; 35.-946-948 (C) 2009 ASCRS and ESCRS
C1 [Jain, Vandana; Pineda, Roberto] Massachusetts Eye & Ear Infirm, Dept Cornea, Boston, MA 02114 USA.
[Jain, Vandana] Aditya Jyot Eye Hosp, Dept Cornea & External Dis, Bombay, Maharashtra, India.
RP Pineda, R (reprint author), Massachusetts Eye & Ear Infirm, Dept Cornea, 243 Charles St, Boston, MA 02114 USA.
EM Roberto_pineda@MEEI.harvard.edu
NR 9
TC 5
Z9 6
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0886-3350
J9 J CATARACT REFR SURG
JI J. Cataract. Refract. Surg.
PD MAY
PY 2009
VL 35
IS 5
BP 946
EP 948
DI 10.1016/j.jcrs.2008.11.065
PG 3
WC Ophthalmology; Surgery
SC Ophthalmology; Surgery
GA 445LY
UT WOS:000266053500031
PM 19393899
ER
PT J
AU Cai, J
Yi, FF
Bian, ZY
Shen, DF
Yang, L
Yan, L
Tang, QZ
Yang, XC
Li, HL
AF Cai, Jun
Yi, Fang-Fang
Bian, Zhou-Yan
Shen, Di-Fei
Yang, Long
Yan, Ling
Tang, Qi-Zhu
Yang, Xin-Chun
Li, Hongliang
TI Crocetin protects against cardiac hypertrophy by blocking MEK-ERK1/2
signalling pathway
SO JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
LA English
DT Article
DE crocetin; reactive oxygen species; cardiac remodelling; fibrosis;
NF-kappa B; ERK1/2
ID ANGIOTENSIN-II; OXIDATIVE STRESS; PRESSURE-OVERLOAD; HEART-FAILURE;
REDOX REGULATION; GENE-EXPRESSION; ATHEROSCLEROSIS; GATA4; RATS;
NOREPINEPHRINE
AB Oxidative stress plays a critical role in the progression of pathological cardiac hypertrophy and heart failure. Because crocetin represses oxidative stress in vitro and in vivo, we have suggested that crocetin would repress cardiac hypertrophy by targeting oxidative stress-dependent signalling. We tested this hypothesis using primary cultured cardiac myocytes and fibroblasts and one well-established animal model of cardiac hypertrophy. The results showed that crocetin (1-10 mu M) dose-dependently blocked cardiac hypertrophy induced by angiogensin II (Ang II; 1 mu M) in vitro. Our data further revealed that crocetin (50 mg/kg/day) both prevented and reversed cardiac hypertrophy induced by aortic banding (AB), as assessed by heart weight/body weight and lung weight/body weight ratios, echocardiographic parameters and gene expression of hypertrophic markers. The inhibitory effect of crocetin on cardiac hypertrophy is mediated by blocking the reactive oxygen species (ROS)-dependent mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase-1/2 (MEK/ERK1/2) pathway and GATA binding protein 4 (GATA-4) activation. Further investigation demonstrated that crocetin inhibited inflammation by blocking nuclear factor kappa B (NF-kappa B) signalling and attenuated fibrosis and collagen synthesis by abrogating MEK-ERK1/2 signalling. Overall, our results indicate that crocetin, which is a potentially safe and inexpensive therapy for clinical use, has protective potential in targeting cardiac hypertrophy and fibrosis by suppression of ROS-dependent signalling pathways.
C1 [Cai, Jun; Yi, Fang-Fang; Yang, Long; Yang, Xin-Chun] Capital Med Univ, Beijing Chaoyang Hosp, Dept Cardiol, Beijing 100020, Peoples R China.
[Cai, Jun] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Cai, Jun] Harvard Univ, Sch Med, Boston, MA USA.
[Bian, Zhou-Yan; Shen, Di-Fei; Yan, Ling; Tang, Qi-Zhu; Li, Hongliang] Wuhan Univ, Renmin Hosp, Dept Cardiol, Wuhan 430072, Peoples R China.
[Bian, Zhou-Yan; Shen, Di-Fei; Yan, Ling; Tang, Qi-Zhu; Li, Hongliang] Wuhan Univ, Cardiovasc Res Inst, Wuhan 430072, Peoples R China.
RP Yang, XC (reprint author), Capital Med Univ, Beijing Chaoyang Hosp, Dept Cardiol, 8 Baijiazhuang Rd, Beijing 100020, Peoples R China.
EM yangxc@medmail.com.cn
FU National Natural Science Foundation of China [30600337, 30770875]
FX The authors thank Dr. Michael Raher (Cardiovascular Research Center,
Massachusetts General Hospital, Harvard Medical School) for review of
the manuscript and helpful comments. This work was supported by grants
from the National Natural Science Foundation of China (No. 30600337 and
No. 30770875) to Dr. Yang Xin-Chun.
NR 49
TC 28
Z9 32
U1 0
U2 5
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1582-1838
J9 J CELL MOL MED
JI J. Cell. Mol. Med.
PD MAY
PY 2009
VL 13
IS 5
BP 909
EP 925
DI 10.1111/j.1582-4934.2008.00620.x
PG 17
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 458AB
UT WOS:000266980300008
PM 19413885
ER
PT J
AU Venugopal, B
Mesires, NT
Kennedy, JC
Curcio-Morelli, C
Laplante, JM
Dice, JF
Slaugenhaupt, SA
AF Venugopal, Bhuvarahamurthy
Mesires, Nicholas T.
Kennedy, John C.
Curcio-Morelli, Cyntia
Laplante, Janice M.
Dice, J. Fred
Slaugenhaupt, Susan A.
TI Chaperone-Mediated Autophagy is Defective in Mucolipidosis Type IV
SO JOURNAL OF CELLULAR PHYSIOLOGY
LA English
DT Article
ID RAT-LIVER LYSOSOMES; PROTEIN TRANSLOCATION; MEMBRANE-PROTEIN; PROTECTIVE
PROTEIN; CATION CHANNEL; LATE ENDOSOMES; DEGRADATION; GENE;
IDENTIFICATION; TRAFFICKING
AB Mucolipidosis type IV (MLIV) is a lysosomal storage disorder caused by mutations in the MCOLN1 gene, a member of the transient receptor potential (TRP) cation channel gene family. The encoded protein, transient receptor potential mucolipin-1 (TRPML1), has been localized to lysosomes and late endosomes but the pathogenic mechanism by which loss of TRPML1 leads to abnormal cellular storage and neuronal cell death is still poorly understood. Yeast two-hybrid and co-immunoprecipitation (coIP) experiments identified interactions between TRPML1 and Hsc70 as well as TRPML1 and Hsp40. Hsc70 and Hsp40 are members of a molecular chaperone complex required for protein transport into the lysosome during chaperone-mediated autophagy (CMA). To determine the functional relevance of this interaction, we compared fibroblasts from MLIV patients to those from sex- and age-matched controls and show a defect in CMA in response to serum withdrawal. This defect in CMA was subsequently confirmed in purified lysosomes isolated from control and MLIV fibroblasts. We further show that the amount of lysosomal-associated membrane protein type 2A (LAMP-2A) is reduced in lysosomal membranes of MLIV fibroblasts. As a result of decreased CMA, MLIV fibroblasts have increased levels of oxidized proteins compared to control fibroblasts. We hypothesize that TRPML1 may act as a docking site for intralysosomal Hsc70 (Iy-Hsc70) allowing it to more efficiently pull in substrates for CMA. It is also possible that TRPML1 channel activity may be required for CMA. Understanding the role of TRPML1 in CMA will undoubtedly help to characterize the pathogenesis of MLIV.
C1 [Venugopal, Bhuvarahamurthy; Kennedy, John C.; Curcio-Morelli, Cyntia; Slaugenhaupt, Susan A.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Venugopal, Bhuvarahamurthy; Kennedy, John C.; Curcio-Morelli, Cyntia; Laplante, Janice M.; Slaugenhaupt, Susan A.] Harvard Univ, Sch Med, Boston, MA USA.
[Mesires, Nicholas T.; Dice, J. Fred] Tufts Univ, Sch Med, Dept Physiol, Boston, MA 02111 USA.
[Laplante, Janice M.] Brigham & Womens Hosp, Dept Med, Div Endocrinol, Boston, MA 02115 USA.
RP Slaugenhaupt, SA (reprint author), 185 Cambridge St, Boston, MA 02114 USA.
EM slaugenhaupt@chgr.mgh.harvard.edu
FU National Institute of Neurological Disorders and Stroke [NS39995]; MLIV
Foundation
FX This study was supported by National Institute of Neurological Disorders
and Stroke Grant NS39995 (S.A.S.) and the MLIV Foundation.
NR 68
TC 51
Z9 57
U1 0
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0021-9541
EI 1097-4652
J9 J CELL PHYSIOL
JI J. Cell. Physiol.
PD MAY
PY 2009
VL 219
IS 2
BP 344
EP 353
DI 10.1002/jcp.21676
PG 10
WC Cell Biology; Physiology
SC Cell Biology; Physiology
GA 425VO
UT WOS:000264666000014
PM 19117012
ER
PT J
AU Luong, MX
Tam, J
Lin, Q
Hagendoorn, J
Moore, KJ
Padera, TP
Seed, B
Fukumura, D
Kucherlapati, R
Jain, RK
AF Luong, Mai X.
Tam, Joshua
Lin, Qingcong
Hagendoorn, Jeroen
Moore, Kathryn J.
Padera, Timothy P.
Seed, Brian
Fukumura, Dai
Kucherlapati, Raju
Jain, Rakesh K.
TI Lack of Lymphatic Vessel Phenotype in LYVE-1/CD44 Double Knockout Mice
SO JOURNAL OF CELLULAR PHYSIOLOGY
LA English
DT Article
ID HYALURONAN RECEPTOR LYVE-1; VASCULAR ENDOTHELIAL-CELLS;
TUMOR-METASTASIS; GENE-EXPRESSION; PAW EDEMA; CD44; LYMPHANGIOGENESIS;
INFLAMMATION; ANGIOGENESIS; MACROPHAGES
AB Lymphatic vessels play a key role in maintaining tissue-fluid homeostasis, immune surveillance and metastasis. The hyaluronan receptor, LYVE-1, is widely used as a molecular marker for adult and embryonic lymphatic endothelium, but its physiological functions have not yet been established in vivo. In agreement with a recent report, LYVE-1(-/-) mice, which are healthy and fertile, do not display any defects related to congenital abnormalities of the lymphatic system. One hypothesis for the absence of a phenotype in LYVE-1 null mice is that other hyaluronan receptors, such as CD44, may compensate for LYVE-1. To test this hypothesis, we created LYVE-1/CD44 double knockout mice with appropriate littermate controls. Lymphatic vessel structure and function, as determined by histological methods and intravital microscopy, show that LYVE-1(-/-), CD44(-/-) and LYVE-1(-/-)/CD44(-/-) mice are indistinguishable from wild-type mice under normal conditions. Furthermore, resolution of carrageenan-induced paw edema is comparable in all genotypes. However, LYVE-1(-/-)/CD44-/- mice exhibit increased edema formation in a carrageenan-induced paw inflammation model compared to wild-type mice, but not to LYVE(-/-) or CD44(-/-) mice. These data suggest that LYVE-1 and CD44 are not required for the formation or function of lymphatics, but do not rule out a role for LYVE-1 in inflammation.
C1 [Luong, Mai X.; Tam, Joshua; Hagendoorn, Jeroen; Padera, Timothy P.; Fukumura, Dai; Jain, Rakesh K.] Massachusetts Gen Hosp, Dept Radiat Oncol, Charlestown, MA USA.
[Tam, Joshua] Massachusetts Gen Hosp, Harvard MIT Div Hlth Sci & Technol, Charlestown, MA USA.
[Lin, Qingcong] Wyeth Res, Biol Technol, Mol Genet, Cambridge, MA USA.
[Moore, Kathryn J.] Massachusetts Gen Hosp, Dept Lipid Metab, Boston, MA USA.
[Seed, Brian] Massachusetts Gen Hosp, Dept Genet, Boston, MA USA.
[Kucherlapati, Raju] Harvard Univ, Sch Med, Partners Healthcare Ctr Genet & Genom, Boston, MA 02115 USA.
RP Kucherlapati, R (reprint author), Harvard Univ, Sch Med, Ctr Genet & Genom 250, 77 Louis Pasteur Ave, Boston, MA 02115 USA.
EM rkucherlapati@partners.org; jain@steele.mgh.harvard.edu
OI Moore, kathryn/0000-0003-2505-2547; Padera, Timothy/0000-0002-3453-9384
FU NCI NIH HHS [R01 CA085140-08, P01 CA080124, P01 CA080124-05, P01
CA080124-06A2, P01 CA080124-07, P01 CA080124-08, P01-CA80124, R01
CA085140, R01 CA085140-06, R01 CA085140-07, R01 CA096915, R01-CA85140,
T32 CA073479, T32 CA073479-07, T32 CA073479-08, T32 CA073479-09, U01
CA084301, U01 CA084301-07, U01 CA084301-08, U01 CA084301-09, U01
CA084301-10, U01-CA84301]; NIDDK NIH HHS [P30 DK043351]
NR 39
TC 13
Z9 14
U1 0
U2 2
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0021-9541
J9 J CELL PHYSIOL
JI J. Cell. Physiol.
PD MAY
PY 2009
VL 219
IS 2
BP 430
EP 437
DI 10.1002/jcp.21686
PG 8
WC Cell Biology; Physiology
SC Cell Biology; Physiology
GA 425VO
UT WOS:000264666000023
PM 19170073
ER
PT J
AU Rosell, A
Arai, K
Lok, J
He, TR
Guo, SZ
Navarro, M
Montaner, J
Katusic, ZS
Lo, EH
AF Rosell, Anna
Arai, Ken
Lok, Josephine
He, Tongrong
Guo, Shuzhen
Navarro, Miriam
Montaner, Joan
Katusic, Zvonimir S.
Lo, Eng H.
TI Interleukin-1 beta augments angiogenic responses of murine endothelial
progenitor cells in vitro
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Article
DE angiogenesis; cytokine; MAP kinase; neuroinflammation; spleen; stroke
ID CEREBRAL ISCHEMIA-REPERFUSION; INDUCED MOBILIZATION; CD34(+) CELLS;
BRAIN-INJURY; BLOOD; NEOVASCULARIZATION; EXPRESSION; STROKE;
DIFFERENTIATION; TRANSPLANTATION
AB Endothelial progenitor cells (EPCs) may provide novel opportunities for therapeutic angiogenesis after ischemic diseases. However, it is unclear how the angiogenic potential of EPCs might be affected by an inflammatory environment. We examine how the potent cytokine interleukin-1 beta (IL-1 beta) affects angiovasculogenic responses in EPCs in culture. Mononuclear cells isolated from mouse spleen were plated on fibronectin-coated wells and grown in EGM-2MV media. Endothelial progenitor cells were phenotyped using multiple markers (UEA-Lectin, ac-LDL, CD133, CD34, vWillebrand Factor, Flk-1) and to identify the IL-1 Receptor-I. We quantified cell and colony counts and performed MTT (3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyl-tetrazolium bromide) and Matrigel assays, in vitro, under control and IL-1 beta (10 ng/mL) conditions. Endothelial progenitor cells exposed to IL-1 beta increased in the number of cells and colonies compared with untreated cells, without any effect on cell metabolic integrity. Furthermore, IL-1 beta treatment augmented EPC angiogenic function, significantly increasing the number of vessel-like structures in the Matrigel assay. An early phosphorylation of ERK1/2 occurred after IL-1 beta stimulation, and this pathway was inhibited if IL-1 Receptor-I was blocked. Our results suggest that IL-1 beta is a potent stimulator of in vitro angiogenesis through ERK signaling in mouse EPCs. Further studies are warranted to assess how interactions between proinflammatory environments and EPC responses may be leveraged to enhance therapeutic angiogenesis. Journal of Cerebral Blood Flow & Metabolism (2009) 29, 933-943; doi:10.1038/jcbfm.2009.17; published online 25 February 2009
C1 [Rosell, Anna; Arai, Ken; Lok, Josephine; Guo, Shuzhen; Lo, Eng H.] Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, Neuroprotect Res Lab,Med Sch, Charlestown, MA 02129 USA.
[He, Tongrong; Katusic, Zvonimir S.] Mayo Clin, Coll Med, Dept Anesthesiol, Rochester, MN USA.
[Navarro, Miriam; Montaner, Joan] Univ Autonoma Barcelona, Vall Hebron Hosp, Dept Neurol, Neurovasc Res Lab, E-08193 Barcelona, Spain.
RP Lo, EH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, Neuroprotect Res Lab,Med Sch, MGH E 149-2401, Charlestown, MA 02129 USA.
EM anna.rosell@gmail.com; Lo@helix.mgh.harvard.edu
RI Montaner, Joan/D-3063-2015; IBIS, NEUROVASCULAR/O-1855-2015
FU NIH [P01-NS55104, P50-NS10828, R37-NS37074, R01-NS48422, R01NS53560];
American Heart Association; Ministerio de Educacion y Ciencia
[EXT2006/766]; Fondo de Investigacion Sanitaria [FIS06/471]
FX Supported in part by NIH grants P01-NS55104, P50-NS10828, R37-NS37074,
R01-NS48422, R01NS53560, and a Bugher award from the American Heart
Association. AR is the recipient of a postdoctoral grant from Ministerio
de Educacion y Ciencia (EXT2006/766) and MN is the recipient of a
predoctoral grant from Fondo de Investigacion Sanitaria (FIS06/471).
NR 45
TC 33
Z9 37
U1 0
U2 2
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 MAY
PY 2009
VL 29
IS 5
BP 933
EP 943
DI 10.1038/jcbfm.2009.17
PG 11
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA 439PU
UT WOS:000265640300007
PM 19240740
ER
PT J
AU Foerch, C
Arai, K
Van Cott, EM
van Leyen, K
Lo, EH
AF Foerch, Christian
Arai, Ken
Van Cott, Elizabeth Merrill
van Leyen, Klaus
Lo, Eng H.
TI Rapid reversal of anticoagulation reduces hemorrhage volume in a mouse
model of Warfarin-associated intracerebral hemorrhage
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Article
DE anticoagulation; intracerebral hemorrhage; mouse model; warfarin
ID PROTHROMBIN COMPLEX CONCENTRATE; FRESH-FROZEN PLASMA;
ATRIAL-FIBRILLATION; EMERGENCY REVERSAL; VITAMIN-K; THERAPY; RATS;
MANAGEMENT; BERIPLEX; EFFICACY
AB Warfarin-associated intracerebral hemorrhage (W-ICH) is a severe type of stroke. There is no consensus on the optimal treatment for W-ICH. Using a mouse model, we tested whether the rapid reversal of anticoagulation using human prothrombin complex concentrate (PCC) can reduce hemorrhagic blood volume. Male CD-1 mice were treated with warfarin (2 mg/kg over 24 h), resulting in a mean (+/- s.d.) International Normalized Ratio of 3.5 +/- 0.9. First, we showed that an intravenous administration of human PCC rapidly reversed anticoagulation in mice. Second, a stereotactic injection of collagenase was administered to induce hemorrhage in the right striatum. Forty-five minutes later, the animals were randomly treated with PCC (100 U/kg) or saline IV (n = 12 per group). Twenty-four hours after hemorrhage induction, hemorrhagic blood volume was quantified using a photometric hemoglobin assay. The mean hemorrhagic blood volume was reduced in PCC-treated animals (6.5 +/- 3.1 mu L) compared with saline controls (15.3 +/- 11.2 mu L, P = 0.015). In the saline group, 45% of the mice developed large hematomas (i.e., > 15 mu L). In contrast, such extensive lesions were never found in the PCC group. We provide experimental data suggesting PCC to be an effective acute treatment for W-ICH in terms of reducing hemorrhagic blood volume. Future studies are needed to assess the therapeutic potential emerging from our finding for human W-ICH. Journal of Cerebral Blood Flow & Metabolism (2009) 29, 1015-1021; doi:10.1038/jcbfm.2009.27; published online 25 March 2009
C1 [Foerch, Christian; Arai, Ken; van Leyen, Klaus; Lo, Eng H.] Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, Sch Med,Neuroprotect Res Lab, Boston, MA 02129 USA.
[Van Cott, Elizabeth Merrill] Harvard Univ, Massachusetts Gen Hosp, Dept Pathol, Sch Med, Boston, MA 02129 USA.
RP Foerch, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, Sch Med,Neuroprotect Res Lab, Room 2414,149 13th St, Boston, MA 02129 USA.
EM foerch@em.uni-frankfurt.de
RI van Leyen, Klaus/C-9126-2013
FU 'Deutsche Forschungsgemeinschaft' (DFG); NIH [R37-NS37074, R01-NS48422,
R01-NS56458, R01-NS3560, P01NS55104]
FX Christian Foerch received the medication used in this study (the
Prothrombin Complex Concentrate 'Beriplex') as a donation from CSL
Behring, Marburg, Germany. This study was in part funded by the
'Deutsche Forschungsgemeinschaft' (DFG) and by NIH-grants R37-NS37074,
R01-NS48422, R01-NS56458, R01-NS3560 and P01NS55104. All the other
authors declare no conflicts of interest.
NR 25
TC 25
Z9 25
U1 0
U2 2
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 MAY
PY 2009
VL 29
IS 5
BP 1015
EP 1021
DI 10.1038/jcbfm.2009.27
PG 7
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA 439PU
UT WOS:000265640300015
PM 19319147
ER
PT J
AU Kahle, KT
Barnett, SN
Sassower, KC
Staley, KJ
AF Kahle, Kristopher T.
Barnett, Sarah N.
Sassower, Kenneth C.
Staley, Kevin J.
TI Decreased Seizure Activity in a Human Neonate Treated With Bumetanide,
an Inhibitor of the Na(+)-K(+)-2Cl(-) Cotransporter NKCC1
SO JOURNAL OF CHILD NEUROLOGY
LA English
DT Article
DE neonatal seizures; bumetanide; Na(+)-K(+)-2Cl cotransporter NKCC1
ID CATION-CHLORIDE COTRANSPORTERS; DEVELOPING BRAIN; NEURONAL
COMMUNICATION; GABA; EEG; PHARMACOKINETICS; DRUGS
AB Neonatal seizures have devastating consequences for brain development and are inadequately treated by available antiepileptics. In neonates, gamma-aminobutyric acid (GABA) is an excitatory neurotransmitter due to elevated levels of intraneuronal chloride achieved by robust activity of the Na(+)-K(+)-2Cl(-) cotransporter (NKCC1). This depolarizing action of GABA likely contributes to the lowered seizure threshold, increased seizure propensity, and poor efficacy of GABAergic anticonvulsants among infants. The diuretic bumetanide inhibits NKCC1 and silences seizure activity in rodent models of neonatal seizures, but its effect on seizures in human neonates is unknown. Continuous electroencephalography (EEG) monitoring was used to quantify the number, duration, and frequency of seizures 2 hours before and after the administration of bumetanide in a neonate with intractable multifocal seizures. Significant reductions in mean seizure duration and frequency were noted following treatment, with no associated clinical side effects or metabolic imbalances. These results suggest bumetanide may exert antiepileptic effects in human neonates.
C1 [Staley, Kevin J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Div Pediat Neurol, Boston, MA 02114 USA.
[Kahle, Kristopher T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA.
RP Staley, KJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Div Pediat Neurol, 55 Fruit St, Boston, MA 02114 USA.
EM kstaley@partners.org
NR 26
TC 60
Z9 63
U1 0
U2 2
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0883-0738
J9 J CHILD NEUROL
JI J. Child Neurol.
PD MAY
PY 2009
VL 24
IS 5
BP 572
EP 576
DI 10.1177/0883073809333526
PG 5
WC Clinical Neurology; Pediatrics
SC Neurosciences & Neurology; Pediatrics
GA 437RW
UT WOS:000265505600007
PM 19406757
ER
PT J
AU Kunisawa, T
Nagata, O
Nagashima, M
Mitamura, S
Ueno, M
Suzuki, A
Takahata, O
Iwasaki, H
AF Kunisawa, Takayuki
Nagata, Osamu
Nagashima, Michio
Mitamura, Sayuri
Ueno, Megumi
Suzuki, Akihiro
Takahata, Osamu
Iwasaki, Hiroshi
TI Dexmedetomidine suppresses the decrease in blood pressure during
anesthetic induction and blunts the cardiovascular response to tracheal
intubation
SO JOURNAL OF CLINICAL ANESTHESIA
LA English
DT Article
CT Annual Meeting of the Japan-Society-for-Clinical-Anesthesia
CY OCT 27, 2006
CL Asahikawa, JAPAN
SP Japan Soc Clin Anesthesia
DE Anesthesia induction; Adjuvant anesthetic sparing effect;
Dexmedetomidine
ID PERIOPERATIVE HEMODYNAMICS; ABDOMINAL HYSTERECTOMY; CARDIAC-ARREST;
REQUIREMENTS; INFUSION; HUMANS; AGONIST; ARTERY
AB Study Objective: To evaluate the effect of dexmedetomidine combined with fentanyl on hemodynamics.
Design: Prospective, double-blinded, randomized study.
Setting: Operating room of a university hospital.
Patients: 30 ASA physical status II and III patients with mild-to-moderate cardiovascular disease.
Interventions: Patients were assigned to one of three groups: Group D-F2 [dexmedetomidine, effect-site concentration (ESC) of fentanyl = two ng/mL]; Group F2 (placebo, ESC of fentanyl = two ng/mL), or Group F4 (placebo, ESC of fentanyl = 4 ng/mL).
Measurements: Dexmedetomidine (an initial dose of 1.0 mu g/kg for 10 min, followed by a continuous infusion of 0.7 mu g-kg(-1.)hr(-1)) or placebo saline was administered 15 minutes before anesthetic induction. Anesthesia was induced with propofal and fentanyl using a target-controlled infusion system. Hemodynamic parameters: systolic (SBP) and diastolic blood pressures (DBP), and heart rate (HR) during anesthetic induction were measured and the percent changes were calculated for both induction and intubation.
Main Results: After inducing anesthesia, SBP was significantly higher in Group D-F2 (127 24 mmHg) than Group F2 (90 +/- 20 mmHg) or Group F4 (77 +/- 21 mmHg). The SBP in Groups F2 and F4 reached 160 +/- 31 mmHg and 123 +/- 36 mmHg, respectively, after intubation, but no significant change in SBP was noted in Group D-F2. The percent increase in SBP due to tracheal intubation in Group D-F2 was 3% +/- 4% and was significantly lower than that of Group F2 (70% +/- 34%) or Group F4 (45% +/- 36%).
Conclusion: Dexmedetomidine combined with fentanyl during anesthetic induction suppresses the decrease in blood pressure due to anesthetic induction and also blunts the cardiovascular response to tracheal intubation. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Kunisawa, Takayuki; Mitamura, Sayuri; Ueno, Megumi; Suzuki, Akihiro; Takahata, Osamu; Iwasaki, Hiroshi] Asahikawa Med Coll, Dept Anesthesiol & Crit Care Med, Asahikawa, Hokkaido 0788510, Japan.
[Nagata, Osamu] Tokyo Metropolitan Police Hosp, Dept Anesthesia, Tokyo, Japan.
[Nagashima, Michio] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA.
[Nagashima, Michio] Harvard Univ, Sch Med, Boston, MA USA.
RP Kunisawa, T (reprint author), Asahikawa Med Coll, Dept Anesthesiol & Crit Care Med, Asahikawa, Hokkaido 0788510, Japan.
EM taka.kunisawa@nifty.ne.jp
OI Nagashima, Michio/0000-0001-7416-5367
NR 19
TC 22
Z9 48
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0952-8180
J9 J CLIN ANESTH
JI J. Clin. Anesth.
PD MAY
PY 2009
VL 21
IS 3
BP 194
EP 199
DI 10.1016/j.jclinane.2008.08.015
PG 6
WC Anesthesiology
SC Anesthesiology
GA 454MW
UT WOS:000266687300008
PM 19464613
ER
PT J
AU Gorji, R
Wang, JP
Eller, JL
Holsapple, J
AF Gorji, Reza
Wang, Jingping
Eller, Jorge L.
Holsapple, James
TI Deep hypothermic circulatory arrest for treatment of renal carcinoma
SO JOURNAL OF CLINICAL ANESTHESIA
LA English
DT Editorial Material
DE Deep hypothermic circulatory arrest, Complications; Neurosurgical
anesthesia; Renal cell carcinoma
ID GAMMA-KNIFE RADIOSURGERY; PROFOUND HYPOTHERMIA; BRAIN METASTASES; CELL
CARCINOMA; EXTRACORPOREAL CIRCULATION; ANEURYSM; SURGERY
AB The case of a 67-year-old woman with multiple medical problems who presented for resection of a metastatic renal cell carcinoma involving the posterior fossa, is presented. Anesthetic management of the patient, who suffered metastasis to the brain, and who required deep hypothermic circulatory arrest, is discussed. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Gorji, Reza] Upstate Med Univ, Dept Anesthesiol, Syracuse, NY 13210 USA.
[Wang, Jingping] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02115 USA.
[Wang, Jingping] Harvard Univ, Sch Med, Dept Anaesthesia, Boston, MA 02115 USA.
[Eller, Jorge L.] Oregon Hlth & Sci Univ, Dept Neurosurg, Portland, OR 97239 USA.
[Holsapple, James] Upstate Med Univ, Dept Neurosurg, Syracuse, NY 13210 USA.
RP Gorji, R (reprint author), Upstate Med Univ, Dept Anesthesiol, Syracuse, NY 13210 USA.
EM gorjir@upstate.edu
OI Holsapple, James/0000-0003-0419-4474
NR 14
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0952-8180
J9 J CLIN ANESTH
JI J. Clin. Anesth.
PD MAY
PY 2009
VL 21
IS 3
BP 217
EP 219
DI 10.1016/j.jclinane.2008.06.041
PG 3
WC Anesthesiology
SC Anesthesiology
GA 454MW
UT WOS:000266687300013
PM 19464618
ER
PT J
AU Nanni, S
Benvenuti, V
Grasselli, A
Priolo, C
Aiello, A
Mattiussi, S
Colussi, C
Lirangi, V
Illi, B
D'Eletto, M
Cianciulli, AM
Gallucci, M
De Carli, P
Sentinelli, S
Mottolese, M
Carlini, P
Strigari, L
Finn, S
Mueller, E
Arcangeli, G
Gaetano, C
Capogrossi, MC
Donnorso, RP
Bacchetti, S
Sacchi, A
Pontecorvi, A
Loda, M
Farsetti, A
AF Nanni, Simona
Benvenuti, Valentina
Grasselli, Annalisa
Priolo, Carmen
Aiello, Aurora
Mattiussi, Stefania
Colussi, Claudia
Lirangi, Vittoria
Illi, Barbara
D'Eletto, Manuela
Cianciulli, Anna Maria
Gallucci, Michele
De Carli, Piero
Sentinelli, Steno
Mottolese, Marcella
Carlini, Paolo
Strigari, Lidia
Finn, Stephen
Mueller, Elke
Arcangeli, Giorgio
Gaetano, Carlo
Capogrossi, Maurizio C.
Donnorso, Raffaele Perrone
Bacchetti, Silvia
Sacchi, Ada
Pontecorvi, Alfredo
Loda, Massimo
Farsetti, Antonella
TI Endothelial NOS, estrogen receptor beta, and HIFs cooperate in the
activation of a prognostic transcriptional pattern in aggressive human
prostate cancer
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID NITRIC-OXIDE SYNTHASE; HYPOXIA-INDUCIBLE FACTORS; HUMAN BREAST-CANCER;
TELOMERASE ACTIVITY; RESPONSE ELEMENT; GENE-EXPRESSION; CELLS; THERAPY;
ALPHA; OVEREXPRESSION
AB The identification of biomarkers that distinguish between aggressive and indolent forms of prostate cancer (PCa) is crucial for diagnosis and treatment. In this study, we used cultured cells derived from prostate tissue from patients with PCa to define a molecular mechanism underlying the most aggressive form of PCa that involves the functional activation of eNOS and HIFs in association with estrogen receptor beta (ER beta). Cells from patients with poor prognosis exhibited a constitutively hypoxic phenotype and increased NO production. Upon estrogen treatment, formation of ER beta/eNOS, ER beta/HIF-1 alpha, or ER beta/HIF-2 alpha combinatorial complexes led to chromatin remodeling and transcriptional induction of prognostic genes. Tissue microarray analysis, using an independent cohort of patients, established a hierarchical predictive power for these proteins, with expression of eNOS plus ER beta and nuclear eNOS plus HIF-2 alpha being the most relevant indicators of adverse clinical outcome. Genetic or pharmacologic modulation of eNOS expression and activity resulted in reciprocal conversion of the transcriptional signature in cells from patients with bad or good outcome, respectively, highlighting the relevance of eNOS in PCa progression. Our work has considerable clinical relevance, since it may enable the earlier diagnosis of aggressive PCa through routine biopsy assessment of eNOS, ER beta, and HIF-2 alpha expression. Furthermore, proposing eNOS as a therapeutic target fosters innovative therapies for PCa with NO inhibitors, which are employed in preclinical trials in non-oncological diseases.
C1 [Farsetti, Antonella] Regina Elena Canc Inst Expt Res Ctr CRS, Dept Expt Oncol, Mol Oncogenesis Lab, I-00158 Rome, Italy.
[Nanni, Simona; Benvenuti, Valentina; Grasselli, Annalisa; Priolo, Carmen; Pontecorvi, Alfredo] Univ Cattolica Sacro Cuore, Dept Endocrinol, I-00168 Rome, Italy.
[Nanni, Simona; Aiello, Aurora; Farsetti, Antonella] Natl Res Council CNR, Inst Neurobiol & Mol Med, Rome, Italy.
[Priolo, Carmen; Finn, Stephen; Mueller, Elke; Loda, Massimo] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med Oncol,Dana Farber Canc Inst, Boston, MA 02115 USA.
[Priolo, Carmen; Finn, Stephen; Mueller, Elke; Loda, Massimo] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Mattiussi, Stefania; Gaetano, Carlo; Capogrossi, Maurizio C.] Ist Dermopat Immacolata IDI, Lab Patol Vasc, Rome, Italy.
[Colussi, Claudia; Illi, Barbara] Ctr Cardiol Monzino, Milan, Italy.
[Cianciulli, Anna Maria] Regina Elena Inst Canc Res, Dept Clin Pathol, Rome, Italy.
[Gallucci, Michele; De Carli, Piero] Regina Elena Inst Canc Res, Dept Urol, Rome, Italy.
[Sentinelli, Steno; Mottolese, Marcella; Donnorso, Raffaele Perrone] Regina Elena Inst Canc Res, Dept Pathol, Rome, Italy.
[Carlini, Paolo] Regina Elena Inst Canc Res, Dept Med Oncol, Rome, Italy.
[Strigari, Lidia] Regina Elena Inst Canc Res, Lab Med Phys & Expert Syst, Rome, Italy.
[Arcangeli, Giorgio] Regina Elena Inst Canc Res, Dept Radiotherapy, Rome, Italy.
[Pontecorvi, Alfredo; Farsetti, Antonella] Regina Elena Inst Canc Res, Rome Oncogenom Ctr, Rome, Italy.
RP Farsetti, A (reprint author), Regina Elena Canc Inst Expt Res Ctr CRS, Dept Expt Oncol, Mol Oncogenesis Lab, Via Messi dOro 156, I-00158 Rome, Italy.
EM afarsetti@gmail.com
RI Strigari, Lidia/J-3541-2012; Strigari, Lidia/B-9352-2017; Gallucci,
Michele/K-9600-2016
OI Strigari, Lidia/0000-0003-4293-2298; Gallucci,
Michele/0000-0002-3637-6531
FU Associazione Iraliana Ricerca sin Cancro and Ministero del Lavoro, della
Salute a delle Politiche Sociali; Ministero dell'Istruzione,
dell'Universita e della Ricerc; NIH [SPS0CA90381, 5R01CA131945]
FX We thank F. Graham and S. Soddu for critical reading of the manuscript,
D. Del Bufalo for reagents and helpful suggestions, and all members of
the Division of Radiotherapy, Regina Elena Cancer Institute for
constructive discussions. This work was supported by research grants
from Associazione Iraliana Ricerca sin Cancro and Ministero del Lavoro,
della Salute a delle Politiche Sociali (to A. Farsetti); Ministero
dell'Istruzione, dell'Universita e della Ricerca; grants from NIH
(Specialized Programs of Research Excellence SPS0CA90381, 5R01CA131945)
and the Prostate Cancer Foundation (to M. Loda).
NR 51
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U1 0
U2 7
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
EI 1558-8238
J9 J CLIN INVEST
JI J. Clin. Invest.
PD MAY
PY 2009
VL 119
IS 5
BP 1093
EP 1108
DI 10.1172/JCI35079
PG 16
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 442LT
UT WOS:000265843400012
PM 19363294
ER
PT J
AU Hassett, MJ
Griggs, JJ
AF Hassett, Michael J.
Griggs, Jennifer J.
TI Disparities in Breast Cancer Adjuvant Chemotherapy: Moving Beyond Yes or
No
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Editorial Material
ID BODY-MASS INDEX; SOCIOECONOMIC-STATUS; RACIAL DISPARITIES;
AFRICAN-AMERICAN; DOSE-INTENSITY; SURVIVAL; QUALITY; CARE; RACE;
CARCINOMA
C1 [Hassett, Michael J.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Griggs, Jennifer J.] Univ Michigan, Ann Arbor, MI 48109 USA.
RP Hassett, MJ (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 26
TC 16
Z9 16
U1 1
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 1
PY 2009
VL 27
IS 13
BP 2120
EP 2121
DI 10.1200/JCO.2008.21.1532
PG 2
WC Oncology
SC Oncology
GA 447MK
UT WOS:000266195000004
PM 19307493
ER
PT J
AU Miksad, RA
Gonen, M
Lynch, TJ
Roberts, TG
AF Miksad, Rebecca A.
Goenen, Mithat
Lynch, Thomas J.
Roberts, Thomas G., Jr.
TI Interpreting Trial Results in Light of Conflicting Evidence: A Bayesian
Analysis of Adjuvant Chemotherapy for Non-Small-Cell Lung Cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID RANDOMIZED CLINICAL-TRIALS; B CALGB PROTOCOL-9633; RESECTED STAGE-I;
BREAST-CANCER; MEDICAL STATISTICS; CONSORT STATEMENT; DECISION-MAKING;
P-VALUES; TIME; DESIGN
AB Purpose
When successive randomized trials contradict prior evidence, clinicians may be unsure how to evaluate them: Does accumulating evidence warrant changing practice? An increasingly popular solution, Bayesian statistics quantitatively evaluate new results in context. This study provides a clinically relevant example of Bayesian methods.
Methods
Three recent non-small-cell lung cancer adjuvant chemotherapy trials were evaluated in light of prior conflicting data. Results were used from International Adjuvant Lung Trial (IALT), JBR. 10, and Adjuvant Navelbine International Trialist Association (ANITA). Prior evidence was sequentially updated to calculate the probability of each survival benefit level (overall and by stage) and variance. Sensitivity analysis was performed using expert opinion and uninformed estimates of survival benefit prior probability.
Results
The probability of a 4% survival benefit increased from 33% before IALT to 64% after IALT. After sequential updating with JBR. 10 and ANITA, this probability was 82% (hazard ratio = 0.84; 95% CI, 0.77 to 0.91). IALT produced the largest decrease in variance (61%) and decreased the chance of survival decrement to 0%. Sensitivity analysis did not support a survival benefit after IALT. However, sequential updating substantiated a 4% survival benefit and, for stage II and III, more than 90% probability of a 6% benefit and 50% probability of a 12% benefit.
Conclusion
When evaluated in context with prior data, IALT did not support a 4% survival benefit. However, sequential updating with JBR. 10 and ANITA did. A model for future assessments, this study demonstrates the unique ability of Bayesian analysis to evaluate results that contradict prior evidence.
C1 [Miksad, Rebecca A.] Harvard Univ, Beth Israel Deaconess Hosp, Dept Med, Div Hematol & Oncol,Med Sch, Boston, MA 02215 USA.
Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA.
Massachusetts Gen Hosp, Dept Med, Div Hematol & Oncol, Boston, MA 02114 USA.
Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA.
RP Miksad, RA (reprint author), Harvard Univ, Beth Israel Deaconess Hosp, Dept Med, Div Hematol & Oncol,Med Sch, 330 Brookline Ave,Shapiro 9, Boston, MA 02215 USA.
EM rmiksad@bidmc.harvard.edu
RI Miksad, Rebecca/B-8066-2009; Gonen, Mithat/E-4826-2012;
OI Miksad, Rebecca/0000-0003-3194-5122
FU National Cancer Institute [R25T CA 92203]; PhRMA Foundation
FX Supported in part by National Cancer Institute Grant No. R25T CA 92203
(R. A. M. and T. G. R.). T. G. R. was also supported in part by an
unrestricted Health Outcomes Starter grant from the PhRMA Foundation.
NR 90
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Z9 7
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 MAY 1
PY 2009
VL 27
IS 13
BP 2245
EP 2252
DI 10.1200/JCO.2008.16.2586
PG 8
WC Oncology
SC Oncology
GA 447MK
UT WOS:000266195000022
PM 19307513
ER
PT J
AU Kane, JM
Fleischhacker, WW
Hansen, L
Perlis, R
Pikalov, A
Assuncao-Talbott, S
AF Kane, John M.
Fleischhacker, Wolfgang W.
Hansen, Lars
Perlis, Roy
Pikalov, Andrei, III
Assuncao-Talbott, Sheila
TI Akathisia: An Updated Review Focusing on Second-Generation
Antipsychotics
SO JOURNAL OF CLINICAL PSYCHIATRY
LA English
DT Review
ID NEUROLEPTIC-INDUCED AKATHISIA; PLACEBO-CONTROLLED TRIAL;
TREATMENT-RESISTANT SCHIZOPHRENIA; ACUTE BIPOLAR MANIA; RANDOMIZED
CONTROLLED-TRIAL; DRUG-INDUCED AKATHISIA; SUICIDE-PREVENTION TRIAL;
BLIND OLANZAPINE TRIAL; SCHIZOAFFECTIVE DISORDER; ACUTE EXACERBATION
AB Objectives: To provide a brief description of the pathophysiology of akathisia, the challenges of diagnosing and treating this condition, and potential associated clinical issues. Also, to provide a review of the literature on the incidence of drug-induced akathisia associated with the use of second-generation antipsychotics (SGAs) and first-generation antipsychotics (FGAs).
Data Sources: English-language literature with no date restrictions cited in PubMed was searched for the keywords akathisia, placebo, neuroleptic or haloperidol, and the generic names of SGAs (clozapine, risperidone, olanzapine, quetiapine, ziprasidone, or aripiprazole).
Study Selection: Limits were set to search clinical trials, meta-analyses, or randomized controlled trials reviewing data from adult schizophrenia or bipolar disorder clinical trials. Studies including SGA comparisons with placebo and with FGAs, and also between SGAs themselves, were selected. Studies that specifically assessed akathisia (either subjectively or objectively or both) were included. Studies reporting generalized results pertaining to extrapyramidal symptoms (EPS) were excluded.
Data Extraction: The incidence of akathisia. EPS rating scores, and required medications for the management of movement disorders were reviewed.
Data Synthesis: Seventy-seven trials were included in the comparative review. Akathisia was observed with the use of all the SGAs. The akathisia incidence reported in bipolar disorder trials was generally higher compared with schizophrenia trials. The incidence reported for FGAs was consistently higher than that reported for SGAs, regardless of the patient population studied.
Conclusions: Akathisia remains a concern with the use of SGAs. More accurate and standardized evaluations are required for a better understanding of the nature and incidence of akathisia. J Clin Psychiatry 2009:70(5):627-643 (C) Copyright 2009 Physicians Postgraduate Press, Inc.
C1 [Kane, John M.] Zucker Hillside Hosp, Dept Psychiat, Glen Oaks, NY 11004 USA.
[Fleischhacker, Wolfgang W.] Med Univ, Innsbruck, Austria.
[Hansen, Lars] Univ Southampton, Royal S Hants Hosp, Southampton, Hants, England.
[Perlis, Roy] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Pikalov, Andrei, III] Otsuka Amer Pharmaceut Inc, Rockville, MD USA.
[Assuncao-Talbott, Sheila] Bristol Myers Squibb Co, Plainsboro, NJ USA.
RP Kane, JM (reprint author), Zucker Hillside Hosp, Dept Psychiat, 75-59 263rd St,Kaufmann Bldg,Suite 103, Glen Oaks, NY 11004 USA.
EM psychiatry@lij.edu
FU Janssen Cilag; Servier; Bristol-Myers Squibb/Otsuka; Otsuka America
Pharmaceuticals, Inc
FX Dr. Kane is a consultant to Bristol-Myers Squibb, Otsuka, Eli Lilly,
Pfizer, Janssen, Vanda, and Wyeth; and serves oil the advisory boards of
AstraZeneca. Bristol-Myers Squibb. and Janssen. Dr. Fleischhacker is a
consultant to Janssen, Servier, AstraZeneca, and Bristol-Myers
Squibb/Otsuka; receives grant/research support from Janssen Cilag,
Servier, and Bristol-Myers Squibb/Otsuka; receives honoraria from
Pfizer, AstraZeneca,Janssen Cilag, Bristol-Myers Squibb/Otsuka, and Eli
Lilly; and serves oil the advisory boards of Wyeth, Bristol-Myers
Squibb/Otsuka, Janssen Cilag, Eli Lilly. and Pfizer. Dr. Perlis is a
consultant for, receives honoraria from, and serves run the advisory
boards of Eli Lilly, AstraZeneca, Bristol-Myers Squibb, Pfizer, Proteus,
and GlaxoSmithKline. Dr. Pikalov is employed by and receives financial
and material support from Otsuka America Pharmaceuticals, Inc. Dr.
Assuncao-Talbot receives financial and material support its an employee
and stock shareholder of Bristol-Myers Squibb. Dr. Hansen reports no
financial or other relationship relevant to the subject of this article.
NR 163
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U2 11
PU PHYSICIANS POSTGRADUATE PRESS
PI MEMPHIS
PA P O BOX 240008, MEMPHIS, TN 38124 USA
SN 0160-6689
J9 J CLIN PSYCHIAT
JI J. Clin. Psychiatry
PD MAY
PY 2009
VL 70
IS 5
BP 627
EP 643
PG 17
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA 450TO
UT WOS:000266424000003
PM 19389331
ER
PT J
AU Biederman, J
Petty, CR
Monuteaux, MC
Evans, M
Parcell, T
Faraone, SV
Wozniak, J
AF Biederman, Joseph
Petty, Carter R.
Monuteaux, Michael C.
Evans, Margaret
Parcell, Tiffany
Faraone, Stephen V.
Wozniak, Janet
TI The Child Behavior Checklist-Pediatric Bipolar Disorder Profile Predicts
a Subsequent Diagnosis of Bipolar Disorder and Associated Impairments in
ADHD Youth Growing Up: A Longitudinal Analysis
SO JOURNAL OF CLINICAL PSYCHIATRY
LA English
DT Article
ID ATTENTION-DEFICIT HYPERACTIVITY; COMMUNITY MENTAL-HEALTH; PREPUBERTAL
CHILDREN; CONDUCT DISORDER; JUVENILE MANIA; MAJOR DEPRESSION; ONSET
MANIA; CBCL; ADOLESCENTS; COMORBIDITY
AB Objective: To examine the predictive utility of the Child Behavior Checklist-Pediatric Bipolar Disorder (CBCL-PBD) profile to help identify children at risk for bipolar disorder.
Method: Subjects were ascertained from 2 identically designed longitudinal case-control family studies of subjects (males and females aged 6-18 years) with DSM-III-R attention-deficit/hyperactivity disorder (ADHD). Based on data from the baseline assessment, ADHD subjects without a lifetime diagnosis of bipolar disorder were stratified by the presence (CBCL-PBD positive. N = 28) or absence (CBCL-PBD negative, N = 176) of a CBCL-PBD score >= 210 (total of attention, aggression, and anxious/depressed subscales). Subjects were comprehensively assessed at follow-up with structured psychiatric interviews. Data were collected from April 1988 to February 2003.
Results: Over a mean follow-up period of 7.4 years, a positive CBCL-PBD score predicted subsequent diagnoses of bipolar disorder, major depressive disorder, and conduct disorder, as well as impaired psychosocial functioning and higher risk for psychiatric hospitalization.
Conclusions: This work suggests that a positive CBCL-PBD score based on elevations on the attention problems, aggressive behavior, and anxious/depressed subscales predicts subsequent pediatric bipolar disorder and associated syndrome-congruent impairments. if confirmed in other studies, the CBCL-PBD score has the potential to help identify children at high risk to develop bipolar disorder. J Clin Psychiatry 2009:70(5):732-740 (C) Copyright 2009 Physicians Postgraduate Press, Inc.
C1 [Biederman, Joseph] Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Yawkey Ctr, Boston, MA 02114 USA.
[Biederman, Joseph; Monuteaux, Michael C.; Wozniak, Janet] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Biederman, Joseph; Monuteaux, Michael C.; Wozniak, Janet] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
[Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA.
[Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Neurosci, Syracuse, NY USA.
[Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Physiol, Syracuse, NY USA.
RP Biederman, J (reprint author), Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Yawkey Ctr, Suite 6A,Fruit St, Boston, MA 02114 USA.
EM jbiederman@partners.org
OI Faraone, Stephen/0000-0002-9217-3982
FU National Institute of Mental Health [R01HD036317, R03MH079954]
FX This project was supported by National Institute of Mental Health grants
R01HD036317 and R03MH079954.
NR 63
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U2 9
PU PHYSICIANS POSTGRADUATE PRESS
PI MEMPHIS
PA P O BOX 240008, MEMPHIS, TN 38124 USA
SN 0160-6689
J9 J CLIN PSYCHIAT
JI J. Clin. Psychiatry
PD MAY
PY 2009
VL 70
IS 5
BP 732
EP 740
PG 9
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA 450TO
UT WOS:000266424000014
PM 19389330
ER
PT J
AU Ford, JD
Elhai, JD
Ruggiero, KJ
Frueh, BC
AF Ford, Julian D.
Elhai, Jon D.
Ruggiero, Kenneth J.
Frueh, B. Christopher
TI Refining Posttraumatic Stress Disorder Diagnosis: Evaluation of Symptom
Criteria With the National Survey of Adolescents
SO JOURNAL OF CLINICAL PSYCHIATRY
LA English
DT Article
ID COMORBIDITY SURVEY REPLICATION; SCREENING INSTRUMENT; PRIMARY-CARE;
PTSD; VALIDATION; CHILDHOOD; CHILDREN; MODEL; ABUSE; RISK
AB Objective: To compare the prevalence estimates, comorbidity rates, and structural validity of a revised symptom criteria set for the diagnosis of posttraumatic stress disorder (PTSD) with those of the DSM-IV criteria in a representative community sample of adolescents.
Method: Cross-sectional data from the National Survey of Adolescents, a 1995 household probability sample of 4,023 adolescents aged 12-17 year:, were examined. DSM-IV PTSD symptoms were assessed with a modification of the National Women's Study PTSD module. Three- and 4-factor DSM-IV models were compared to a 2-factor PTSD model that deleted symptoms potentially overlapping with depression or other anxiety disorders. Comorbidity was assessed using DSM-IV criteria for major depressive episodes and substance use disorders.
Results: PTSD prevalence varied across models (ie, 5.2%-8.8%, lifetime; 3.2%-5.7%, past 6 months). When the 2-factor model was used with a proportionate symptom threshold, lifetime PTSD prevalence wits comparable to that with the 3-factor DSM-IV model, and major depressive episode comorbidity was reduced by 9%-14%. Comorbidity with substance use disorders was comparable across models. Structural validity, tested with confirmatory factor analyses, showed that the 2-factor model and a 4-factor DSM-IV model were superior to the DSM-IV 3-factor model.
Conclusions: Compared to the DSM-IV 3-factor PTSD model, a 2-factor model that removed depression and anxiety symptoms and used a proportionate symptom threshold may produce comparable lifetime PTSD prevalence estimates, reduced PTSD-depression comorbidity, and Superior structural validity (comparable to a 4-factor PTSD model) when applied to community samples of adolescents. Further research on PTSD structure and diagnosis with adolescents is warranted. J Clin Psychiatry 2009:70(5):748-755 (C) Copyright 2009 Physicians Postgraduate Press, Inc.
C1 [Ford, Julian D.] Univ Connecticut, Ctr Hlth, Dept Psychiat, Sch Med, Farmington, CT 06032 USA.
[Elhai, Jon D.] Univ S Dakota, Dept Psychol, Disaster Mental Hlth Inst, Vermillion, SD 57069 USA.
[Ruggiero, Kenneth J.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA.
[Ruggiero, Kenneth J.] Ralph H Johnson VA Med Ctr, Ctr Dis Prevent & Hlth Intervent Diverse Populat, Charleston, SC USA.
[Frueh, B. Christopher] Baylor Coll Med, Menninger Clin, Houston, TX 77030 USA.
[Frueh, B. Christopher] Baylor Coll Med, Dept Psychiat, Houston, TX 77030 USA.
[Frueh, B. Christopher] Univ Hawaii, Dept Psychol, Hilo, HI 96720 USA.
RP Ford, JD (reprint author), Univ Connecticut, Ctr Hlth, Dept Psychiat, Sch Med, 263 Farmington Ave, Farmington, CT 06032 USA.
EM ford@psychiatry.uchc.edu
FU Department of Justice Office of Juvenile Justice and Delinquency
Programs [CT-52525-JS2]
FX Work on this article was partially supported by a grant from the
Department of Justice Office of Juvenile Justice and Delinquency
Programs CT-52525-JS2 (Dr Ford, principal investigator).
NR 38
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U1 2
U2 6
PU PHYSICIANS POSTGRADUATE PRESS
PI MEMPHIS
PA P O BOX 240008, MEMPHIS, TN 38124 USA
SN 0160-6689
J9 J CLIN PSYCHIAT
JI J. Clin. Psychiatry
PD MAY
PY 2009
VL 70
IS 5
BP 748
EP 755
PG 9
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA 450TO
UT WOS:000266424000016
PM 19389336
ER
PT J
AU Kan, IP
Alexander, MP
Verfaellie, M
AF Kan, Irene P.
Alexander, Michael P.
Verfaellie, Mieke
TI Contribution of Prior Semantic Knowledge to New Episodic Learning in
Amnesia
SO JOURNAL OF COGNITIVE NEUROSCIENCE
LA English
DT Article
ID MEMORY RETRIEVAL; TEMPORAL-LOBE; SYSTEMS; DEMENTIA; CONSOLIDATION;
CONFABULATION; INSIGHTS; SCHEMAS; MODEL
AB We evaluated whether prior semantic knowledge would enhance episodic learning in amnesia. Subjects studied prices that are either congruent or incongruent with prior price knowledge for grocery and household items and then performed a forced-choice recognition test for the studied prices. Consistent with a previous report, healthy controls' performance was enhanced by price knowledge congruency; however, only a subset of amnesic patients experienced the same benefit. Whereas patients with relatively intact semantic systems, as measured by an anatomical measure (i.e., lesion involvement of anterior and lateral temporal lobes), experienced a significant congruency benefit, patients with compromised semantic systems did not experience a congruency benefit. Our findings suggest that when prior knowledge structures are intact, they can support acquisition of new episodic information by providing frameworks into which such information can be incorporated.
C1 [Kan, Irene P.] Villanova Univ, Dept Psychol, Villanova, PA 19085 USA.
[Kan, Irene P.; Verfaellie, Mieke] Boston Univ, Sch Med, Boston, MA 02215 USA.
[Kan, Irene P.; Verfaellie, Mieke] VA Boston Healthcare Syst, Memory Disorders Res Ctr, Boston, MA USA.
[Alexander, Michael P.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Cambridge, MA 02138 USA.
RP Kan, IP (reprint author), Villanova Univ, Dept Psychol, 800 Lancaster Ave, Villanova, PA 19085 USA.
EM irene.kan@villanova.edu
FU NIH [MH 57681, MH71783, HD 046442]; Office of Research and Development;
Medical Research Service; Department of Veterans Affairs
FX This research was supported by the NIH grants MH 57681 and MH71783 and
the Office of Research and Development, Medical Research Service,
Department of Veterans Affairs (awarded to M. V.) and the NIH grant HD
046442 (awarded to M. P. A.). We thank Elizabeth Martin, Karen Fossum,
and Sarah Davis for their assistance in data collection and Erin Sakai
for her assistance in preparation of this manuscript.
NR 36
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U1 3
U2 8
PU M I T PRESS
PI CAMBRIDGE
PA 238 MAIN STREET, STE 500, CAMBRIDGE, MA 02142-1046 USA
SN 0898-929X
J9 J COGNITIVE NEUROSCI
JI J. Cogn. Neurosci.
PD MAY
PY 2009
VL 21
IS 5
BP 938
EP 944
DI 10.1162/jocn.2009.21066
PG 7
WC Neurosciences; Psychology, Experimental
SC Neurosciences & Neurology; Psychology
GA 436KM
UT WOS:000265413000008
PM 18702596
ER
PT J
AU Kubert, HL
Stepp, CE
Zeitels, SM
Gooey, JE
Walsh, MJ
Prakash, SR
Hillman, RE
Heaton, JT
AF Kubert, Heather L.
Stepp, Cara E.
Zeitels, Steven M.
Gooey, John E.
Walsh, Michael J.
Prakash, S. R.
Hillman, Robert E.
Heaton, James T.
TI Electromyographic control of a hands-free electrolarynx using neck strap
muscles
SO JOURNAL OF COMMUNICATION DISORDERS
LA English
DT Article
ID TOTAL LARYNGECTOMY; REHABILITATION; COMMUNICATION; INTONATION; SPEECH
AB Three individuals with total laryngectomy were studied for their ability to control a hands-free electrolarynx (EL) using neck surface electromyography (EMG) for on/off and pitch modulation. The laryngectomy surgery of participants was modified to preserve neckstrap musculature for EMG-based EL control (EMG-EL), with muscles on one side maintaining natural innervation and those on the other side receiving a transferred recurrent laryngeal nerve (RLN). EMG from each side of the neck controlled the EMG-EL across a day of unstructured practice followed by a day of formal training, including EMG biofeedback. Using either control source, participants spoke intelligibly and fluently with the EMG-EL before formal training. This good initial performance did not consistently improve across testing for either control source in terms of voice timing, speech intelligibility, fluency, and intonation of interrogative versus declarative sentences. Neck strap muscles have activation patterns capable of simple alaryngeal voice control without requiting RLN transfer.
Learning outcomes: The reader will better understand (1) functionality of the hands-free electrolarynx (2) modification of laryngectomy surgery to preserve neck strap musculature and (3) performance of hands-free electrolarynx with different control sources. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Kubert, Heather L.; Stepp, Cara E.; Prakash, S. R.; Hillman, Robert E.; Heaton, James T.] Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA.
[Kubert, Heather L.; Hillman, Robert E.; Heaton, James T.] Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA.
[Stepp, Cara E.; Zeitels, Steven M.; Prakash, S. R.; Hillman, Robert E.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
[Zeitels, Steven M.; Hillman, Robert E.; Heaton, James T.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA.
[Gooey, John E.] VA Hlth Ctr Boston, Boston, MA USA.
[Gooey, John E.; Walsh, Michael J.] Boston Univ, Med Ctr Hosp, Dept Otolaryngol Head & Neck Surg, Boston, MA 02215 USA.
RP Heaton, JT (reprint author), MGH Voice Ctr, 1 Bowdoin Sq,11th Floor, Boston, MA 02114 USA.
EM hkubert@hotmail.com; cstepp@mit.edu; zeitels.steven@mgh.harvard.edu;
john.Gooey@med.va.gov; Mike.Walsh@bmc.org; srp@mit.edu;
hillman.robert@mgh.harvard.edu; James.Heaton@mgh.harvard.edu
FU NIDCD NIH HHS [R01 DC006449, R01 DC006449-03, R01 DC006449-06, R01
DC006449-01, R01 DC006449-04, R01-DC006449, R01 DC006449-05, R01
DC006449-02]
NR 21
TC 5
Z9 5
U1 0
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0021-9924
J9 J COMMUN DISORD
JI J. Commun. Disord.
PD MAY-JUN
PY 2009
VL 42
IS 3
BP 211
EP 225
DI 10.1016/j.jcomdis.2008.12.002
PG 15
WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation
SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation
GA 434UX
UT WOS:000265300700004
PM 19233382
ER
PT J
AU Yoon, LS
Catalano, OA
Fritz, S
Ferrone, CR
Hahn, PF
Sahani, DV
AF Yoon, Luke S.
Catalano, Onofrio A.
Fritz, Stefan
Ferrone, Cristina R.
Hahn, Peter F.
Sahani, Dushyant V.
TI Another Dimension in Magnetic Resonance Cholangiopancreatography:
Comparison of 2-and 3-Dimensional Magnetic Resonance
Cholangiopancreatography for the Evaluation of Intraductal Papillary
Mucinous Neoplasm of the Pancreas
SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY
LA English
DT Article
DE magnetic resonance cholangiopancreatography; intraductal papillary
mucinous neoplasm of the pancreas
ID NATURAL-HISTORY; DUCT; TUMOR; MANAGEMENT; SEQUENCE; MRCP; CT
AB Purpose: The purpose of this study was to compare 2-dimensional (2D) and 3D magnetic resonance cholangiopancreatography (MRCP) for image quality and diagnostic performance in the evaluation of pathologically verified intraductal papillary mucinous neoplasm (IPMN) of the pancreas.
Materials and Methods: In this institutional review board-approved retrospective review, 21 patients (14 women and 7 men; mean age, 69 years; range, 43-93 years) who underwent 2D and 3D MRCPs oil a 1.5-T system for pathologically confirmed IPMN were studied. Two-dimensional MRCP protocol included multiplanar thin- and thick-slab single-shot fast spin-echo imaging, coronal single-shot fast spin-echo, and transverse T2-weighted fast spin-echo imaging. Three-dimensional MRCP was performed using a fast-recovery fast spin-echo sequence with single-volume acquisition and maximum intensity projection reconstructions. Using a 5-point scale, 2 readers independently evaluated MRCPs for (1) image quality, (2) visualization of the pancreatic duct (PD), and (3) Visualization of the cystic lesions. Intraductal papillary mucinous neoplasm's morphological features (septa, mural nodules, and duct communication) were also graded similarly to predict benignity or malignancy. Surgical and pathological data served as reference standard. A pancreatic surgeon reviewed the 21 MRCPs to determine the usefulness of 3D MRCP compared with that of 2D MRCP for Surgical planning.
Results: Of the 21 IPMNs, 11 were side-branch IPMNs and 10 were main-duct-lesions IPMNs with side-branch involvement. A statistically significant improvement in image quality and Visualization of the PD and cystic lesion was demonstrated with 3D MRCP in comparison with that demonstrated with 2D MRCP (P <= 0.002). The morphological details of IPMN were also identified, with higher confidence with 3D MRCP in comparison with that using 2D MRCP Two-dimensional and 3D MRCPs performed similarly for predicting benign and malignant lesions, with sensitivity ranging from 50.0% to 66.7% and specificity ranging from 86.7% to 93.3%. The pancreatic surgeon preferred 3D to 2D MRCP for surgical evaluation and planning in 14 of 21 cases.
Conclusion: Compared with 2D MRCP, 3D MRCP provides better image quality, offers superior evaluation of the PD and morphological details of IPMN, and is preferred for surgical planning.
C1 [Yoon, Luke S.; Catalano, Onofrio A.; Hahn, Peter F.; Sahani, Dushyant V.] Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent, Dept Radiol, Boston, MA 02114 USA.
[Fritz, Stefan; Ferrone, Cristina R.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
RP Yoon, LS (reprint author), Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent, Dept Radiol, 55 Fruit St,White 270, Boston, MA 02114 USA.
EM lyoon@partners.org
NR 14
TC 14
Z9 15
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0363-8715
J9 J COMPUT ASSIST TOMO
JI J. Comput. Assist. Tomogr.
PD MAY-JUN
PY 2009
VL 33
IS 3
BP 363
EP 368
PG 6
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 453XU
UT WOS:000266647000008
PM 19478628
ER
PT J
AU Manolis, EN
Filippou, DK
Tsoumakas, C
Diomidous, M
Cunningham, MJ
Katostaras, T
Weber, AL
Eavey, RD
AF Manolis, Evangelos N.
Filippou, Dimitrios K.
Tsoumakas, Constantinos
Diomidous, Marianna
Cunningham, Michael J.
Katostaras, Theophanis
Weber, Alfred L.
Eavey, Roland D.
TI Radiologic Evaluation of the Ear Anatomy in Pediatric Cholesteatoma
SO JOURNAL OF CRANIOFACIAL SURGERY
LA English
DT Article
DE Cholesteatoma; acquired; congenital; computed tomography; middle ear
ID MIDDLE-EAR; COMPUTED-TOMOGRAPHY; CHILDREN; DIAGNOSIS; CT; COMPLICATIONS;
SURGERY; SCAN; MRI
AB The aim of the study was to describe computed tomography (CT) findings in middle ear cholesteatoma in pediatric patients. A cohort of 32 children with cholesteatoma (3-14 years old) entered the study. Froth them, 30 presented acquired cholesteatoma (AC), and 2 presented congenital cholesteatoma. All of the children were investigated using CT before surgery of the middle ear and mastoid. Computed tomography was performed with 1- or 2-mm axial and coronal sections of both temporal bones. Nineteen children with AC (63.3%) revealed a diffuse soft-tissue density isodense with muscle, whereas in 6 of them, the mass mimicked inflammation. The remaining revealed localized soft-tissue mass with partially lobulated contour. In AC, ossicular erosion was detected in 23 cases (76.7%), abnormal pneumatization in 19 cases (63.3%), and erosion-blunting of spur and enlargement of middle ear or mastoid in 8 cases (26.7%). The 2 congenital cholesteatomas revealed soft-tissue mass with polypoid densities, while a semicircular canal fistula was detected in one of them. High-resolution CT facilitates early diagnosis and appropriate treatment of pediatric cholesteatoma by assessing the anatomic abnormalities and the extent of disease, which are crucial in middle ear and mastoid surgery.
C1 [Manolis, Evangelos N.; Cunningham, Michael J.; Eavey, Roland D.] Harvard Univ, Sch Med, Dept Otolaryngol, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA.
[Manolis, Evangelos N.] Univ Athens, Sch Hlth Sci, Dept Anat & Histol, Nursing Fac, Athens 11527, Greece.
[Weber, Alfred L.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA.
RP Manolis, EN (reprint author), Univ Athens, Sch Hlth Sci, Dept Anat & Histol, Nursing Fac, 123 Papadiamantopoulou St, Athens 11527, Greece.
EM ENManolis@yahoo.gr
NR 26
TC 4
Z9 4
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1049-2275
J9 J CRANIOFAC SURG
JI J. Craniofac. Surg.
PD MAY
PY 2009
VL 20
IS 3
BP 807
EP 810
DI 10.1097/SCS.0b013e318184346e
PG 4
WC Surgery
SC Surgery
GA 448XN
UT WOS:000266295400022
PM 19390457
ER
PT J
AU Graham, DY
Lu, H
Yamaoka, Y
AF Graham, David Y.
Lu, Hong
Yamaoka, Yoshio
TI African, Asian or Indian enigma, the East Asian Helicobacter pylori:
facts or medical myths
SO JOURNAL OF DIGESTIVE DISEASES
LA English
DT Article
DE African enigma; Asian enigma; gastric cancer; gastritis; Helicobacter
pylori; Indian enigma; peptic ulcer
ID GASTRIC-CANCER; PEPTIC-ULCER; BIOLOGICAL-ACTIVITY; IRON-DEFICIENCY;
UNITED-STATES; CAGA; INFECTION; POLYMORPHISMS; GENES; RISK
AB Helicobacter pylori is etiologically related to peptic ulcer disease and gastric adenocarcinomas. Reports of geographical enigmas (African, Asian, Indian and Costa Rican enigmas) are based on perceptions that clinical presentations in a population or region are not as the authors expected. We discuss the background for these enigmas and examine the evidence whether they are real or are medical myths. The African enigma was challenged almost as soon as it was proposed and recent analyses of endoscopic data have confirmed it is a myth, as H. pylori-related diseases occur in Africa at the expected frequencies. The Asian and Indian enigmas relate to gastric cancer and peptic ulcers, respectively, and when one takes the patterns of gastritis in the different regions, these enigmas disappear. The pattern of gastritis underlies and predicts the clinical outcome and the predominant pattern of gastritis has been observed to change much more rapidly than can be accounted for by changes in host genetics. There is also no evidence that these changes relate to changes in the predominant H. pylori strain. The factors that link most closely to preventing an atrophic corpus are environmental, with food preservation and diet currently assuming the most prominent roles. This focus on diseases (cancer vs duodenal ulcers) instead of the underlying patterns of gastritis has fostered, and possibly helped to perpetuate, these mythical enigmas. We suggest that a better strategy would be to focus on the pathogenesis of underlying histopathologic differences which could also lead to the identification of specific chemoprevention strategies.
C1 [Graham, David Y.; Yamaoka, Yoshio] Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Houston, TX 77030 USA.
[Graham, David Y.; Yamaoka, Yoshio] Baylor Coll Med, Houston, TX 77030 USA.
[Lu, Hong] Shanghai Jiao Tong Univ, Dept Gastroenterol, Renji Hosp, Sch Med,Shanghai Inst Digest Dis, Shanghai 200030, Peoples R China.
RP Graham, DY (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Dept Med, RM 3A-320 3D,2002 Holcombe Blvd, Houston, TX 77030 USA.
EM dgraham@bcm.tmc.edu
FU Meretek; NIH [DK62813]; National Natural Science Foundation of China
[30670940]
FX In the last 2 years Dr Graham has received small amounts of grant
support and/or free drugs or urea breath tests from Meretek, BioHit for
completely investigator-controlled research. Dr Yamaoka is supported in
part by a grant from the NIH DK62813. Dr Lu is supported in part by a
grant from the National Natural Science Foundation of China (30670940).
NR 58
TC 35
Z9 38
U1 0
U2 4
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1751-2972
J9 J DIG DIS
JI J. Dig. Dis.
PD MAY
PY 2009
VL 10
IS 2
BP 77
EP 84
DI 10.1111/j.1751-2980.2009.00368.x
PG 8
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 436IN
UT WOS:000265407100001
PM 19426388
ER
PT J
AU Rempell, JS
Harris, NS
Brown, DFM
Nadel, ES
AF Rempell, Joshua S.
Harris, N. Stuart
Brown, David F. M.
Nadel, Eric S.
TI LEFT EYE PTOSIS
SO JOURNAL OF EMERGENCY MEDICINE
LA English
DT Editorial Material
ID INTERNAL CAROTID-ARTERY; BLUNT CEREBROVASCULAR INJURY; CERVICAL-SPINE
MANIPULATION; HORNERS-SYNDROME; HELICAL CT; DISSECTION; DIAGNOSIS;
THERAPY; NECK; PAIN
C1 [Rempell, Joshua S.; Nadel, Eric S.] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA.
[Rempell, Joshua S.; Harris, N. Stuart; Brown, David F. M.; Nadel, Eric S.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.
RP Nadel, ES (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St, Boston, MA 02115 USA.
NR 23
TC 0
Z9 0
U1 1
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 MAY
PY 2009
VL 36
IS 4
BP 395
EP 399
PG 5
WC Emergency Medicine
SC Emergency Medicine
GA 441JL
UT WOS:000265765000014
PM 19345048
ER
PT J
AU Schuberth, JM
Cobb, MD
Talarico, RH
AF Schuberth, John M.
Cobb, Matthew D.
Talarico, Ross H.
TI Minimally Invasive Arthroscopic-Assisted Reduction with Percutaneous
Fixation in the Management of Intra-Articular Calcaneal Fractures: A
Review of 24 Cases
SO JOURNAL OF FOOT & ANKLE SURGERY
LA English
DT Article
DE arthroscopy; Boehler's angle; comminution; complication; critical angle;
joint depression; Sanders classification
ID INTERNAL-FIXATION; SUBTALAR JOINT; CONTACT CHARACTERISTICS;
COMPUTED-TOMOGRAPHY; OPERATIVE TREATMENT; COMPLICATIONS; CLASSIFICATION;
OSTEOSYNTHESIS; VIABILITY
AB A retrospective analysis of 24 cases of minimally invasive, open reduction, and internal fixation of intra-articular calcaneal fractures is presented. Collected data included articular step-off, medial wall displacement, and Boehler's angle, in addition to other descriptive characteristics of the fracture and case series. The operative technique is described in detail including the optimal screw constructs. Arthroscopic assistance was used in 10 of the cases. The articular step-off of the posterior facet, medial wall displacement, and Boehler's angle all displayed statistically significant change between the preoperative and postoperative periods (P < .0001). These results were consistent with the goal of restoration of articular congruity, calcaneal morphology, and calcaneal height. There were no soft tissue complications. The mean overall follow-up duration was 2.8 years (range 1 to 10 years). Of the 18 patients who were followed for more than I year (range 1.0 to 10 years), none went on to subtalar fusion. The results of this study suggest that a minimally invasive approach can improve radiographic parameters consistent with the ultimate goals of operative reduction of calcaneal fractures, and can be used to achieve satisfactory results with minimal risk of wound complication. Level of Clinical Evidence: 4 (The Journal of Foot & Ankle Surgery 48(3):315-322, 2009)
C1 [Schuberth, John M.] Kaiser Fdn Hosp, Dept Orthopaed Surg, San Francisco, CA 94118 USA.
[Cobb, Matthew D.] Kaiser Fdn Hosp, Dept Podiatr Surg, Walnut Creek, CA USA.
[Talarico, Ross H.] Univ Calif San Francisco, Dept Orthoped Surg, San Francisco, CA 94143 USA.
[Talarico, Ross H.] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA.
[Talarico, Ross H.] Univ Calif San Francisco, Podiatr Surg Sect, San Francisco, CA 94143 USA.
RP Schuberth, JM (reprint author), Kaiser Fdn Hosp, Dept Orthopaed Surg, 450 6th Ave, San Francisco, CA 94118 USA.
EM Jmfoot@aol.com
NR 38
TC 38
Z9 44
U1 1
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1067-2516
J9 J FOOT ANKLE SURG
JI J. Foot Ankle Surg.
PD MAY-JUN
PY 2009
VL 48
IS 3
BP 315
EP 322
DI 10.1053/j.jfas.2009.01.002
PG 8
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA 441TG
UT WOS:000265792800005
PM 19423031
ER
PT J
AU Agopian, VG
Chen, DC
Avansino, JR
Stelzner, M
AF Agopian, Vatche G.
Chen, David C.
Avansino, Jeffrey R.
Stelzner, Matthias
TI Intestinal Stem Cell Organoid Transplantation Generates Neomucosa in
Dogs
SO JOURNAL OF GASTROINTESTINAL SURGERY
LA English
DT Article
DE Intestinal stem cell transplantation; Tissue-engineered intestine;
Bioscaffolds; Polyglycolic acid
ID ENGINEERED SMALL-INTESTINE; BILE-ACID MALABSORPTION; SMALL-BOWEL
RESECTION; MANAGEMENT; SCAFFOLDS; MODEL; REGENERATION; ENGRAFTMENT;
EPITHELIUM; REPAIR
AB Intestinal stem cell organoid transplantation generates functional intestinal neomucosa and has been used therapeutically to improve nutrient absorption and cure bile acid malabsorption in rats. We hypothesized that intestinal organoids can be harvested and transplanted to generate intestinal neomucosa in a large animal model.
In group 1, 2-month old beagles (n = 6) underwent autotransplantation of intestinal organoids prepared from a segment of their own ileum. In group 2, intestinal organoids were harvested from fetuses and allotransplanted into 10-month old mother animals (n = 4). Tissues were harvested after 4 weeks and analyzed by hematoxylin and eosin histology and fluorescent microscopy.
Large numbers of viable organoids were harvested in both groups. In group 1, no neomucosal growth was identified in any of the engraftment sites after autotransplantation of juvenile organoids. In group 2, neomucosal growth with large areas of crypts and villi was identified in 11 of 12 polyglycolic acid scaffolds after allotransplantation of fetal organoids. The neomucosa resembled normal canine mucosa in structure and composition.
Intestinal stem cell organoid transplantation can be used to generate neomucosa in dogs. This is the first report of successful generation of intestinal neomucosa using intestinal stem cell organoid transplantation in a large animal model.
C1 [Agopian, Vatche G.; Chen, David C.; Stelzner, Matthias] Univ Calif Los Angeles, Dept Surg, VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA 90095 USA.
[Avansino, Jeffrey R.] Univ Washington, Dept Surg, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA.
RP Agopian, VG (reprint author), Univ Calif Los Angeles, Dept Surg, VA Greater Los Angeles Hlth Care Syst, 10833 Conte Ave, Los Angeles, CA 90095 USA.
EM vagopian@mednet.ucla.edu
FU Clowes Career Development Award, American College of Surgeons
FX Grant support from the Clowes Career Development Award, American College
of Surgeons is acknowledged.
NR 31
TC 17
Z9 17
U1 1
U2 6
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1091-255X
J9 J GASTROINTEST SURG
JI J. Gastrointest. Surg.
PD MAY
PY 2009
VL 13
IS 5
BP 971
EP 982
DI 10.1007/s11605-009-0806-x
PG 12
WC Gastroenterology & Hepatology; Surgery
SC Gastroenterology & Hepatology; Surgery
GA 431VO
UT WOS:000265092500023
PM 19165549
ER
PT J
AU Eckman, MH
Greenberg, SM
Rosand, J
AF Eckman, Mark H.
Greenberg, Steven M.
Rosand, Jonathan
TI Should We Test for CYP2C9 Before Initiating Anticoagulant Therapy in
Patients with Atrial Fibrillation?
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Article
DE anticoagulant therapy; warfarin; genetic testing; pharmacogenetics;
decision analysis; atrial fibrillation; stroke
ID CLINICAL CLASSIFICATION SCHEMES; RANDOMIZED CONTROLLED-TRIALS;
QUALITY-OF-LIFE; INTRACEREBRAL HEMORRHAGE; RISK-FACTORS; BLEEDING
COMPLICATIONS; ANTITHROMBOTIC THERAPY; WARFARIN THERAPY; ORAL
ANTICOAGULANT; DECISION-ANALYSIS
AB Genetic variants of the warfarin sensitivity gene CYP2C9 have been associated with increased bleeding risk during warfarin initiation. Studies also suggest that such patients remain at risk throughout treatment.
Would testing patients with non-valvular atrial fibrillation (AF) for CYP2C9 before initiating warfarin improve outcomes?
Markov state transition decision model.
Ambulatory or inpatient settings necessitating new initiation of anticoagulation.
The base case was a 69-year-old man with newly diagnosed non-valvular AF. Interventions included: (1) warfarin, (2) aspirin, or (3) no antithrombotic therapy without genetic testing; and genetic testing followed by (4) aspirin or (5) no antithrombotic therapy in those with culprit CYP2C9 alleles.
Quality-adjusted life years (QALYs).
In the base case, testing and treating patients with CYP2C9*2 and/or CYP2C9*3 with aspirin rather than warfarin was best (8.97 QALYs). However, warfarin without genetic testing was a close second (8.96 QALYs), a difference of roughly 5 days. Sensitivity analyses demonstrated that genetic testing followed by aspirin was best for patients at lower risk of embolic events. Warfarin without testing was preferred if the rate of embolic events was greater than 5% per year, or the risk of major bleeding while receiving warfarin was lower.
For patients at average risk for ischemic stroke due to AF and at average risk for major hemorrhage, treatment based on genetic testing offers no benefit compared to warfarin initiation without testing. The gain from testing may be larger in patients at lower risk of embolic events or at greater risk of bleeding.
C1 [Eckman, Mark H.] Univ Cincinnati, Med Ctr, Div Gen Internal Med, Cincinnati, OH 45267 USA.
[Eckman, Mark H.] Univ Cincinnati, Med Ctr, Ctr Clin Effectiveness, Cincinnati, OH 45267 USA.
[Greenberg, Steven M.; Rosand, Jonathan] Massachusetts Gen Hosp, Dept Neurol, Res Grp, Boston, MA 02114 USA.
[Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
RP Eckman, MH (reprint author), Univ Cincinnati, Med Ctr, Div Gen Internal Med, POB 670535, Cincinnati, OH 45267 USA.
EM mark.eckman@uc.edu
FU National Institute of Diabetes and Digestive and Kidney Diseases [K23
DK075599]; National Heart, Lung, and Blood Institute [K30 HL078581-01];
Foundation for Informed Medical Decision Making.; National Institutes of
Neurological Disorders and Stroke [R01 NS059727]; Deane Institute for
Integrative Study of Atrial Fibrillation and Stroke
FX Jonathan Rosand: National Institutes of Neurological Disorders and
Stroke (R01 NS059727), and the Deane Institute for Integrative Study of
Atrial Fibrillation and Stroke.
NR 63
TC 3
Z9 3
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD MAY
PY 2009
VL 24
IS 5
BP 543
EP 549
DI 10.1007/s11606-009-0927-7
PG 7
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA 434XE
UT WOS:000265306700001
PM 19255811
ER
PT J
AU Sherbourne, CD
Asch, SM
Shugarman, LR
Goebel, JR
Lanto, AB
Rubenstein, LV
Wen, L
Zubkoff, L
Lorenz, KA
AF Sherbourne, Cathy D.
Asch, Steven M.
Shugarman, Lisa R.
Goebel, Joy R.
Lanto, Andy B.
Rubenstein, Lisa V.
Wen, Li
Zubkoff, Lisa
Lorenz, Karl A.
TI Early Identification of Co-Occurring Pain, Depression and Anxiety
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Article
DE targeted screening for pain and distress; depression; anxiety
ID PRIMARY-CARE; SYMPTOMS; ILLNESS; HEALTH; COMORBIDITY; IMPAIRMENT;
PREVALENCE; DISORDERS; SEVERITY; SCREENER
AB Depression and anxiety frequently co-occur with pain and may affect treatment outcomes. Early identification of these co-occurring psychiatric conditions during routine pain screening may be critical for optimal treatment.
To determine aspects of pain related to psychological distress, and, among distressed patients, to determine whether pain factors are related to provider identification of distress.
Cross-sectional interview of primary care patients and their providers participating in a Veteran's Administration HELP-Vets study.
A total of 528 predominately male Veterans
We measured self-reported pain, including a 0-10 numeric rating scale and interference items from the Brief Pain Inventory. To evaluate distress, brief indicators of depression, anxiety and PTSD were combined. A substantial number of patients had psychological distress (41%), which was even higher (62%) among patients with moderate-severe current pain. Only 29% of those with distress reported talking to their provider about emotional problems during their visit. In multivariate analyses, other pain factors related to distress included interference with enjoyment of life and relationships with others, pain in multiple locations and joint pains. Prior diagnoses of depression and anxiety were also related to current distress. Only prior diagnosis and patient reported headaches and sleep interference because of pain were related to provider identification of distress.
VA patients with moderate-severe pain are at high risk for psychological distress, which often goes unrecognized. Providers need to be more vigilant to mental health problems in patients experiencing high pain levels. Targeted screening for co-occurring conditions is warranted.
C1 [Sherbourne, Cathy D.; Asch, Steven M.; Shugarman, Lisa R.; Rubenstein, Lisa V.; Lorenz, Karl A.] RAND Corp, Santa Monica, CA 90407 USA.
[Asch, Steven M.; Lanto, Andy B.; Rubenstein, Lisa V.; Zubkoff, Lisa; Lorenz, Karl A.] Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
[Asch, Steven M.; Rubenstein, Lisa V.; Lorenz, Karl A.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Goebel, Joy R.] Calif State Univ Long Beach, Dept Nursing, Sch Nursing, Long Beach, CA 90840 USA.
[Wen, Li] Vet Adm Long Beach Healthcare Syst, Long Beach, CA USA.
RP Sherbourne, CD (reprint author), RAND Corp, 1776 Main St,POB 2138, Santa Monica, CA 90407 USA.
EM Cathy_Sherbourne@rand.org
FU VA HSR D [03-150]
FX Funded by the VA HSR& D 11R # 03-150.
NR 24
TC 19
Z9 26
U1 4
U2 6
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 MAY
PY 2009
VL 24
IS 5
BP 620
EP 625
DI 10.1007/s11606-009-0956-2
PG 6
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA 434XE
UT WOS:000265306700012
PM 19308333
ER
PT J
AU Keyhani, S
Federman, A
AF Keyhani, Salomeh
Federman, Alex
TI Fact or Fiction: The Need for Independent Pharmaceutical Policy Research
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Editorial Material
ID PRIVATE-SECTOR; ROFECOXIB; INNOVATION; EZETIMIBE; DOCUMENTS; NAPROXEN;
TRIAL; COSTS; PRICE; VA
C1 [Keyhani, Salomeh] Mt Sinai Sch Med, Dept Hlth Policy, New York, NY 10029 USA.
[Keyhani, Salomeh] James J Peters Vet Adm Med Ctr, Bronx, NY USA.
[Keyhani, Salomeh; Federman, Alex] Mt Sinai Sch Med, Div Gen Internal Med, New York, NY 10029 USA.
RP Keyhani, S (reprint author), Mt Sinai Sch Med, Dept Hlth Policy, Box 1077,1 Gustave L Levy Pl, New York, NY 10029 USA.
EM salomeh.keyhani@mountsinai.org
NR 27
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD MAY
PY 2009
VL 24
IS 5
BP 692
EP 694
DI 10.1007/s11606-009-0964-2
PG 3
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA 434XE
UT WOS:000265306700023
PM 19343457
ER
PT J
AU Lindenhovius, ALC
van de Luijtgaarden, K
Ring, D
Jupiter, J
AF Lindenhovius, Anneluuk L. C.
van de Luijtgaarden, Koen
Ring, David
Jupiter, Jesse
TI Open Elbow Contracture Release: Postoperative Management With and
Without Continuous Passive Motion
SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME
LA English
DT Article
DE Continuous passive motion; contracture release; elbow stiffness
ID POSTTRAUMATIC CONTRACTURE; OPERATIVE RELEASE; ANTERIOR RELEASE; LATERAL
APPROACH; STIFF ELBOW; ARTHROLYSIS; HEAD
AB Purpose Surgical contracture release can restore motion to stiff elbows. Some authors suggest that use of continuous passive motion (CPM) in postoperative management can increase ultimate mobility. This study tests the null hypothesis that there is no difference in the arc of flexion and extension between patients who used CPM and those who did not use CPM after open elbow contracture release.
Methods Sixteen patients who had an arc of flexion and extension of less than 80 degrees and used CPM after open contracture release were matched based on age, gender, diagnosis, preoperative arc of flexion and extension, and radiographic appearance (joint congruity, heterotopic bone, and arthritis) to 16 control patients who did not use CPM. Stiffness was of posttraumatic origin in 24 patients, related to primary osteoarthrosis in 4 patients, and related to heterotopic ossification after central nervous system injury or burns in 4 patients. The preoperative arc of flexion and extension averaged 38 degrees in the CPM cohort and 42 degrees in the no-CPM cohort.
Results Subsequent surgeries included procedures to address residual stiffness in 1 patient in the CPM cohort and in 3 patients in the no-CPM cohort. At an average 6 months of follow-up, there was no difference in improvement in the arc of flexion and extension (58 degrees vs 61 degrees) between the CPM and no-CPM cohorts. At the final evaluation, the improvement in arc of flexion and extension (59 degrees in both cohorts) and the final arc of flexion and extension (96 degrees vs 101 degrees) were comparable between cohorts.
Conclusions These matched retrospective data do not demonstrate a benefit of CPM in the postoperative management of elbow contracture release. (J Hand Surg 2009;34A:858-865. (C) 2009 Published by Elsevier Inc. on behalf of the American Society for Surgery of the Hand.)
Type of study/level of evidence Therapeutic III.
C1 [Ring, David] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Ring, D (reprint author), Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, 55 Fruit St, Boston, MA 02114 USA.
EM dring@partners.org
FU AD Foundation; Wright Medical; Joint Active Systems; Smith and Nephew;
Small Bone Innovations; Biomet; Acumed; Tomier
FX Unrestricted research grants were received from AD Foundation, Wright
Medical, Joint Active Systems, Smith and Nephew, Small Bone Innovations,
Biomet, Acumed, and Tomier.
NR 22
TC 16
Z9 17
U1 0
U2 1
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0363-5023
J9 J HAND SURG-AM
JI J. Hand Surg.-Am. Vol.
PD MAY-JUN
PY 2009
VL 34A
IS 5
BP 858
EP 865
DI 10.1016/j.jhsa.2009.01.003
PG 8
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA 443FO
UT WOS:000265895800008
PM 19362791
ER
PT J
AU Jawa, A
Jupiter, J
AF Jawa, Andrew
Jupiter, Jesse
TI Fracture-Associated Nerve Dysfunction
SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME
LA English
DT Article
ID SUPRACONDYLAR HUMERUS FRACTURES; CARPAL-TUNNEL-SYNDROME; DISTAL RADIUS;
PALSY; INJURIES; EXPERIENCE; CHILDREN; SHAFT; ULNAR
C1 [Jawa, Andrew] Massachusetts Gen Hosp, Dept Orthopaed Surg, Yawkey Ctr, Boston, MA 02114 USA.
RP Jawa, A (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA.
EM ajawa@partners.org
NR 19
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 MAY-JUN
PY 2009
VL 34A
IS 5
BP 924
EP 927
DI 10.1016/j.jhsa.2008.11.029
PG 4
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA 443FO
UT WOS:000265895800020
PM 19233570
ER
PT J
AU Eisenman, DP
Glik, D
Maranon, R
Gonzales, L
Asch, S
AF Eisenman, David P.
Glik, Deborah
Maranon, Richard
Gonzales, Lupe
Asch, Steven
TI Developing a Disaster Preparedness Campaign Targeting Low-Income Latino
Immigrants: Focus Group Results for Project PREP
SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED
LA English
DT Article
DE Latino health; immigrant health; disaster preparedness; formative
research
ID ETHNICITY; DISSEMINATION; PERCEPTIONS; INFORMATION
AB Low-income immigrant Latinos are particularly vulnerable to disasters because they are both ill-prepared and disproportionately affected. Disaster preparedness programs that are culturally appropriate must be developed and tested. To develop such a program, we conducted 12 focus groups with low-income immigrant Latinos to understand their perceptions and understanding of disaster preparedness, and facilitators and obstacles to it. Participants were concerned about remaining calm during an earthquake. Obstacles to storage of disaster supplies in a kit and developing a family communication plan were mentioned frequently. Misunderstandings were voiced about the proper quantity of water to store and about communication plans. Several focus groups spontaneously suggested small group discussions (platicas) as a way to learn about disaster preparedness. They wanted specific help with building their family communication plans. They rated promotoras de salud highly as potential teachers. Results Will guide the development of a disaster preparedness program tailored to the needs of low-income Latino immigrants.
C1 [Eisenman, David P.] Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90095 USA.
[Glik, Deborah; Maranon, Richard] Univ Calif Los Angeles, Sch Publ Hlth Community Hlth Sci, Los Angeles, CA 90095 USA.
[Asch, Steven] W Los Angeles Vet Adm, Dept Med, Los Angeles, CA USA.
RP Eisenman, DP (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med & Hlth Serv Res, 911 Broxton Plaza, Los Angeles, CA 90095 USA.
EM deisenman@mednet.ucla.edu
NR 37
TC 20
Z9 20
U1 1
U2 7
PU JOHNS HOPKINS UNIV PRESS
PI BALTIMORE
PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD
21218-4363 USA
SN 1049-2089
J9 J HEALTH CARE POOR U
JI J. Health Care Poor Underserved
PD MAY
PY 2009
VL 20
IS 2
BP 330
EP 345
PG 16
WC Health Policy & Services; Public, Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 443CF
UT WOS:000265887100004
PM 19395833
ER
PT J
AU Tallaj, JA
Franco, V
Rayburn, BK
Pamboukian, SV
Benza, RL
Kirklin, JK
McGiffin, DC
Smallfield, M
Bourge, RC
AF Tallaj, Jose A.
Franco, Veronica
Rayburn, Barry K.
Pamboukian, Salpy V.
Benza, Raymond L.
Kirklin, James K.
McGiffin, David C.
Smallfield, Melissa
Bourge, Robert C.
TI Safety and Efficacy of Ibutilide in Heart Transplant Recipients
SO JOURNAL OF HEART AND LUNG TRANSPLANTATION
LA English
DT Article
ID ORTHOTOPIC CARDIAC TRANSPLANTATION; ATRIAL-FLUTTER; ARRHYTHMIAS;
PREVALENCE
AB In this report we describe our experience with ibutilide, a relatively new Class III anti-arrhythmic agent, in 8 heart transplant patients with supraventricular tachycardia in various settings (3 patients with rejection, 2 after endomyocardial biopsy). Ibutilide treatment was successful in all patients, with the arrhythmia recurring early in I patient. There were no complications. J Heart Lung Transplant 2009;28:505-7. Copyright (C) 2009 by the International Society for Heart and Lung Transplantation.
C1 [Tallaj, Jose A.; Franco, Veronica; Rayburn, Barry K.; Pamboukian, Salpy V.; Benza, Raymond L.; Kirklin, James K.; McGiffin, David C.; Smallfield, Melissa; Bourge, Robert C.] Univ Alabama, Div Cardiovasc Dis, Sect Heart Failure Transplantat & Pulm Vasc Dis, Birmingham, AL 35294 USA.
[Tallaj, Jose A.] Birmingham VA Med Ctr, Birmingham, AL USA.
RP Tallaj, JA (reprint author), Univ Alabama, Div Cardiovasc Dis, Sect Heart Failure Transplantat & Pulm Vasc Dis, THT 338,703 19th St S, Birmingham, AL 35294 USA.
EM jtallaj@uab.edu
RI Franco, Veronica/E-3080-2011
NR 13
TC 0
Z9 2
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1053-2498
J9 J HEART LUNG TRANSPL
JI J. Heart Lung Transplant.
PD MAY
PY 2009
VL 28
IS 5
BP 505
EP 507
DI 10.1016/j.healun.2009.02.013
PG 3
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery;
Transplantation
SC Cardiovascular System & Cardiology; Respiratory System; Surgery;
Transplantation
GA 447DI
UT WOS:000266171400015
PM 19416781
ER
PT J
AU Lieu, C
Janssen, WJ
Saint, S
Dhaliwal, G
AF Lieu, Christopher
Janssen, William J.
Saint, Sanjay
Dhaliwal, Gurpreet
TI The Tip of the Iceberg
SO JOURNAL OF HOSPITAL MEDICINE
LA English
DT Editorial Material
ID A STREPTOCOCCAL INFECTIONS; TOXIC-SHOCK-SYNDROME; SPECTRUM
C1 [Lieu, Christopher; Janssen, William J.; Dhaliwal, Gurpreet] Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA.
[Janssen, William J.] Natl Jewish Med & Res Ctr, Dept Med, Denver, CO USA.
[Saint, Sanjay] Ann Arbor Vet Affairs Hlth Serv, Res & Dev Ctr Excellence, Ann Arbor, MI USA.
[Saint, Sanjay] Ann Arbor Vet Affairs Med Ctr, Patient Safety Enhancement Program, Ann Arbor, MI USA.
[Saint, Sanjay] Univ Michigan Hlth Syst, Dept Internal Med, Ann Arbor, MI USA.
[Dhaliwal, Gurpreet] San Francisco VA Med Ctr, Dept Med, San Francisco, CA USA.
[Dhaliwal, Gurpreet] Univ Calif San Francisco, Sch Med, San Francisco, CA USA.
RP Lieu, C (reprint author), Univ Texas MD Anderson Canc Ctr, Div Canc Med, 1515 Holcombe Blvd,Unit 10, Houston, TX 77098 USA.
EM chlieu@mdanderson.org
NR 13
TC 0
Z9 0
U1 0
U2 0
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1553-5592
J9 J HOSP MED
JI J. Hosp. Med.
PD MAY-JUN
PY 2009
VL 4
IS 5
BP 317
EP 320
DI 10.1002/jhm.471
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA 459NI
UT WOS:000267109200009
PM 19504498
ER
PT J
AU Carpenter, AC
Yang-Iott, KS
Chao, LH
Nuskey, B
Whitlow, S
Alt, FW
Bassing, CH
AF Carpenter, Andrea C.
Yang-Iott, Katherine S.
Chao, Linda H.
Nuskey, Beth
Whitlow, Scott
Alt, Frederick W.
Bassing, Craig H.
TI Assembled DJ beta Complexes Influence TCR beta Chain Selection and
Peripheral V beta Repertoire
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID T-CELL-RECEPTOR; RECOMBINATION SIGNAL SEQUENCE; MAJOR HISTOCOMPATIBILITY
COMPLEX; CHROMOSOMAL V(D)J RECOMBINATION; CODING-END SEQUENCE; ALLELIC
EXCLUSION; IMMATURE THYMOCYTES; GERMLINE TRANSCRIPTION; POSITIVE
SELECTION; GENE SEGMENTS
AB TCR beta chain repertoire of peripheral alpha beta T cells is generated through the stepwise assembly and subsequent selection of TCR beta V region exons during thymocyte development. To evaluate the influence of a two-step recombination process on V beta rearrangement and selection, we generated mice with a preassembled D beta 1J beta 1.1 complex on the J beta 1(omega) allele, an endogenous TCRP allele that lacks the D beta 2-J beta 2 cluster, creating the J beta 1(DJ beta) allele. As compared with J beta 1(omega/omega) mice, both J beta 1(DJ beta/omega) and J beta 1(DJ beta/DJ beta) mice exhibited grossly normal thymocyte development and TCR beta allelic exclusion. In addition, V beta rearrangements on J beta 1(DJ beta) and J beta 1(omega) alleles were similarly regulated by TCR beta-mediated feedback regulation. However, in-frame V beta DJ beta rearrangements were present at a higher level on the J beta 1(DJ beta) alleles of J beta 1(DJ beta/omega) alpha beta T cell hybridomas, as compared with on the J beta 1(omega) alleles. This bias was most likely due to both an increased frequency of VP-to-DJ beta rearrangements on J beta 1(DJ beta) alleles and a preferential selection of cells with in-frame V beta DJ beta exons assembled on J beta 1(DJ beta) alleles during the development of J beta 1(DJ beta/omega) alpha beta T cells. Consistent with the differential selection of in-frame V beta DJ beta rearrangements on J beta 1(DJ beta) alleles, the V beta repertoire of alpha beta T cells was significantly altered during alpha beta TCR selection in J beta 1(DJ beta/omega) and J beta 1(DJ beta/DJ beta) mice, as compared with in J beta 1(omega/omega) mice. Our data indicate that the diversity of DJ beta complexes assembled during thymocyte development influences TCR beta chain selection and peripheral VP repertoire. The Journal of Immunology, 2009, 182: 5586-5595.
C1 [Carpenter, Andrea C.; Bassing, Craig H.] Univ Penn, Immunol Grad Grp, Sch Med, Philadelphia, PA 19104 USA.
[Carpenter, Andrea C.; Yang-Iott, Katherine S.; Chao, Linda H.; Nuskey, Beth; Bassing, Craig H.] Univ Penn, Childrens Hosp Philadelphia, Abramson Family Canc Res Inst, Dept Pathol & Lab Med,Sch Med,Ctr Childhood Canc, Philadelphia, PA 19104 USA.
[Whitlow, Scott; Alt, Frederick W.] Harvard Univ, Childrens Hosp, Howard Hughes Med Inst, Immune Dis Inst,Sch Med, Boston, MA 02115 USA.
[Whitlow, Scott; Alt, Frederick W.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
RP Bassing, CH (reprint author), Childrens Hosp Philadelphia, Abramson Res Ctr 807A, 3615 Civ Ctr Blvd, Philadelphia, PA 19104 USA.
EM bassing@email.chop.edu
FU Howard Hughes Medical Institute; NIAID NIH HHS [R01 AI020047, T32
AI055428, R01 AI020047-28, AI20047]
NR 65
TC 9
Z9 9
U1 0
U2 0
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD MAY 1
PY 2009
VL 182
IS 9
BP 5586
EP 5595
DI 10.4049/jimmunol.0803270
PG 10
WC Immunology
SC Immunology
GA 563HQ
UT WOS:000275119200053
PM 19380806
ER
PT J
AU Meeran, SM
Akhtar, S
Katiyar, SK
AF Meeran, Syed M.
Akhtar, Suhail
Katiyar, Santosh K.
TI Inhibition of UVB-Induced Skin Tumor Development by Drinking Green Tea
Polyphenols Is Mediated Through DNA Repair and Subsequent Inhibition of
Inflammation
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Article
ID NECROSIS-FACTOR-ALPHA; IFN-GAMMA PRODUCTION; ULTRAVIOLET-RADIATION;
INTERLEUKIN-12-DEFICIENT MICE; PYRIMIDINE DIMERS; COX-2 EXPRESSION;
T-CELLS; CANCER; PHOTOCARCINOGENESIS; REGRESSION
AB Consumption of green tea polyphenols (GTPs) in drinking water prevents photocarcinogenesis in mice; however, the molecular mechanisms underlying this effect have not been fully elucidated. Using IL-12p40 knockout (KO) mice and their wild-type counterparts and an established photocarcinogenesis protocol, we found that although administration of GTPs (0.2%, w/v) in drinking water significantly reduced UVB-induced tumor development in wild-type mice, this treatment had a nonsignificant effect in IL-12-KO mice. GTPs resulted in reduction in the levels of markers of inflammation (cyclooxygenase-2, prostaglandin E(2), proliferating cell nuclear antigen, and cyclin D1) and proinflammatory cytokines (tumor necrosis factor-alpha, IL-6, and IL-1 beta) in chronically UVB-exposed skin and skin tumors of wild-type mice but less effective in IL-12p40-KO mice. UVB-induced DNA damage (cyclobutane pyrimidine dimers) was resolved rapidly in GTPs-treated wild-type mice than untreated wild-type mice and this resolution followed the same time course as the GTPs-induced reduction in the levels of inflammatory responses. This effect of GTPs was less pronounced in IL-12-KO mice. The above results were confirmed by treatment of IL-12-KO mice with murine recombinant IL-12 and treatment of wild-type mice with neutralizing anti-IL-12 antibody. To our knowledge, it is previously unreported that prevention of photocarcinogenesis by GTPs is mediated through IL-12-dependent DNA repair and a subsequent reduction in skin inflammation.
C1 [Meeran, Syed M.; Akhtar, Suhail; Katiyar, Santosh K.] Univ Alabama, Dept Dermatol, Birmingham, AL 35294 USA.
[Katiyar, Santosh K.] Birmingham VA Med Ctr, Birmingham, AL USA.
RP Katiyar, SK (reprint author), Univ Alabama, Dept Dermatol, 1670 Univ Blvd,Volker Hall 557,POB 202, Birmingham, AL 35294 USA.
EM skatiyar@uab.edu
FU National Center for Complementary and Alternative Medicine/NIH [1 RO1
AT002536]; Veterans Administration Merit Review Award
FX This work was supported by grants from the National Center for
Complementary and Alternative Medicine/NIH (1 RO1 AT002536, SKK) and the
Veterans Administration Merit Review Award (SKK).
NR 45
TC 61
Z9 62
U1 0
U2 8
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 MAY
PY 2009
VL 129
IS 5
BP 1258
EP 1270
DI 10.1038/jid.2008.354
PG 13
WC Dermatology
SC Dermatology
GA 447US
UT WOS:000266218000026
PM 19020550
ER
PT J
AU Hall, C
Flores, MV
Chien, A
Davidson, A
Crosier, K
Crosier, P
AF Hall, Chris
Flores, Maria Vega
Chien, Annie
Davidson, Alan
Crosier, Kathryn
Crosier, Phil
TI Transgenic zebrafish reporter lines reveal conserved Toll-like receptor
signaling potential in embryonic myeloid leukocytes and adult immune
cell lineages
SO JOURNAL OF LEUKOCYTE BIOLOGY
LA English
DT Article
DE MyD88; TLR; immunity; live imaging; neutrophils; macrophages
ID DOMAIN-CONTAINING ADAPTERS; HEMATOPOIETIC STEM-CELLS; IN-VIVO; INNATE
IMMUNITY; BONE-MARROW; GRANULOMA-FORMATION; CARDIAC MYOCYTES;
GENE-EXPRESSION; DANIO-RERIO; TNF-ALPHA
AB The immune response of a host to an invading pathogen is dependent on the capacity of its immune cell compartment to recognize highly conserved pathogen components using an ancient class of pattern recognition receptors known as Toll-like receptors (TLRs). Initiation of TLR-mediated signaling results in the induction of proinflammatory cytokines that help govern the scale and duration of any ensuing response. Specificity for TLR signaling is, in part, a result of the differential recruitment of intracellular adaptor molecules. Of these, MyD88 is required for the majority of TLR signaling. Zebrafish have been shown to possess TLRs and adaptor molecules throughout early development, including MyD88, strongly suggesting conservation of this ancient defense mechanism. However, information about which embryonic cells/tissues possess this conserved signaling potential is lacking. To help define which embryonic cells, in particular, those of the innate immune system, have the potential for MyD88-dependent, TLR-mediated signaling, we generated transgenic reporter lines using regulatory elements of the myd88 gene to drive the fluorescent reporters enhanced GFP and Discosoma red fluorescent protein 2 within live zebrafish. These lines possess fluorescently marked cells/tissues consistent with endogenous myd88 expression, including a subset of myeloid leukocytes. These innate immune cells were confirmed to express other TLR adaptors including Mal, trif, and Sarm. Live wound-healing and infection assays validated the potential of these myd88-expressing leukocytes to participate in immune responses. These lines will provide a valuable resource for further resolving the contribution of MyD88 to early vertebrate immunity. J. Leukoc. Biol. 85: 751-765; 2009.
C1 [Hall, Chris; Flores, Maria Vega; Chien, Annie; Crosier, Kathryn; Crosier, Phil] Univ Auckland, Sch Med Sci, Dept Mol Med & Pathol, Auckland 1142, New Zealand.
[Davidson, Alan] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA.
RP Crosier, P (reprint author), Univ Auckland, Sch Med Sci, Dept Mol Med & Pathol, Private Bag 92019, Auckland 1142, New Zealand.
EM ps.crosier@auckland.ac.nz
FU New Economy Research Fund, Foundation for Research Science and
Technology, New Zealand
FX Funding for this work was provided by a grant awarded to P. C. from the
New Economy Research Fund, Foundation for Research Science and
Technology, New Zealand. This work would not have been possible without
the expert management of our zebrafish facility by Alhad Mahagaonkar. We
also thank Koichi Kawakami for generously supplying the Tol2/transposase
expression vectors and Nick Trede, John Kanki, and Phil Ingham and
Stephen Renshaw for supplying the Tg(lck: GFP), Tg(rag2:GFP), and
Tg(mpx:GFP) reporter lines, respectively. We thank the Biomedical
Imaging Research Unit, School of Medical Sciences, The University of
Auckland, for their expert assistance in fluorescence and confocal
microscopy, Lisa Pullin for excellent technical assistance, and Stephen
Edgar for FACS analysis support.
NR 79
TC 38
Z9 39
U1 0
U2 6
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 MAY 1
PY 2009
VL 85
IS 5
BP 751
EP 765
DI 10.1189/jlb.0708405
PG 15
WC Cell Biology; Hematology; Immunology
SC Cell Biology; Hematology; Immunology
GA 453TM
UT WOS:000266635800003
PM 19218482
ER
PT J
AU Fujimi, S
Lapchak, PH
Zang, Y
MacConmara, MP
Maung, AA
Delisle, AJ
Mannick, JA
Lederer, JA
AF Fujimi, Satoshi
Lapchak, Peter H.
Zang, Yan
MacConmara, Malcolm P.
Maung, Adrian A.
Delisle, Adam J.
Mannick, John A.
Lederer, James A.
TI Murine dendritic cell antigen-presenting cell function is not altered by
burn injury
SO JOURNAL OF LEUKOCYTE BIOLOGY
LA English
DT Article
DE Toll-like receptors; costimulatory molecules; Th1; Th2; CD4 T cells
ID T-HELPER-CELL; INNATE IMMUNE RECOGNITION; TYROSINE KINASE-3 LIGAND;
IN-VIVO; TRAUMA PATIENTS; THERMAL-INJURY; RESPONSES; RECEPTOR; MICE;
INFECTION
AB Severe injury disrupts normal immune regulation causing a transient hyperinflammatory reaction and suppressed adaptive immune function. This report addresses the potential contribution of dendritic cells (DC) to changes in adaptive immune function after injury by specifically measuring injury-induced changes in splenic DC numbers and subsets, cell-surface markers, TLR responses, and APC function. Using a mouse burn injury model, we found that injury did not markedly alter the relative percentage of lymphoid, myeloid, or plasmacytoid DC in the spleens of burn-injured mice. Moreover, we did not observe a significant reduction in cell-surface expression of several major costimulatory molecules, CD40, CD80, CD86, programmed death 1 ligand, ICOS ligand, and B7-H3, on DC. Instead, we observed increased cell-surface expression of CD86 at 1 day after injury with no significant changes in costimulatory molecule expression at 7 days after injury, suggesting that burn injury causes an early activation of DC. In addition, injury did not suppress DC reactivity to TLR2, TLR4, or TLR9 agonists. Most important, DC prepared from injured mice were able to present peptide antigen to naive OTII TCR transgenic CD4+ T cells as efficiently and effectively as DC from sham-injured mice. We also found that CD4 T cells stimulated with antigen presented by DC from sham or burn mice showed similar levels of IL-2, IFN-gamma, IL-10, and IL-13 production. Taken together, these findings support the conclusion that DC do not acquire a suppressive phenotype following severe injury in mice. J. Leukoc. Biol. 85: 862-870; 2009.
C1 [Fujimi, Satoshi; Zang, Yan; MacConmara, Malcolm P.; Maung, Adrian A.; Delisle, Adam J.; Mannick, John A.; Lederer, James A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Surg Immunol, Boston, MA 02115 USA.
[Lapchak, Peter H.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med Rheumatol, Boston, MA 02115 USA.
[Maung, Adrian A.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
RP Lederer, JA (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Surg Immunol, 75 Francis St, Boston, MA 02115 USA.
EM jlederer@rics.bwh.harvard.edu
OI Lapchak, Peter/0000-0001-8597-088X
FU NIH [GM35633, GM57664]; Julian and Eunice Cohen and Brook Family Funds
FX This research work was supported by grant funding from NIH ( GM35633 and
GM57664) and by the Julian and Eunice Cohen and Brook Family Funds for
Surgical Research. The authors thank the Department of Traumatology,
Osaka University, Japan, for generously providing outstanding trainees
to support our research efforts.
NR 52
TC 9
Z9 9
U1 0
U2 2
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 MAY 1
PY 2009
VL 85
IS 5
BP 862
EP 870
DI 10.1189/jlb.0408257
PG 9
WC Cell Biology; Hematology; Immunology
SC Cell Biology; Hematology; Immunology
GA 453TM
UT WOS:000266635800014
PM 19228816
ER
PT J
AU Pott, GB
Chan, ED
Dinarello, CA
Shapiro, L
AF Pott, Gregory B.
Chan, Edward D.
Dinarello, Charles A.
Shapiro, Leland
TI alpha-1-Antitrypsin is an endogenous inhibitor of proinflammatory
cytokine production in whole blood
SO JOURNAL OF LEUKOCYTE BIOLOGY
LA English
DT Article
DE inflammation; dilution; serine protease inhibitor; interleukin
ID MONONUCLEAR-CELLS; GENE-EXPRESSION; HUMAN MONOCYTES; IN-VITRO;
RHEUMATOID-ARTHRITIS; FLOW-CYTOMETRY; TNF-ALPHA; DEFICIENCY;
ALPHA(1)-ANTITRYPSIN; INTERLEUKIN-18
AB Several observations suggest endogenous suppressors of inflammatory mediators are present in human blood. alpha-1-Antitrypsin (AAT) is the most abundant serine protease inhibitor in blood, and AAT possesses anti-inflammatory activity in vitro and in vivo. Here, we show that in vitro stimulation of whole blood from persons with a genetic AAT deficiency resulted in enhanced cytokine production compared with blood from healthy subjects. Using whole blood from healthy subjects, dilution of blood with RPMI tissue-culture medium, followed by incubation for 18 h, increased spontaneous production of IL-8, TNF-alpha, IL-1 beta, and IL-1R antagonist (IL-1Ra) significantly, compared with undiluted blood. Dilution-induced cytokine production suggested the presence of one or more circulating inhibitors of cytokine synthesis present in blood. Serially diluting blood with tissue-culture medium in the presence of cytokine stimulation with heat-killed Staphylococcus epidermidis (S. epi) resulted in 1.2- to 55-fold increases in cytokine production compared with S. epi stimulation alone. Diluting blood with autologous plasma did not increase the production of IL-8, TNF-alpha, IL-1 beta, or IL-1Ra, suggesting that the endogenous, inhibitory activity of blood resided in plasma. In whole blood, diluted and stimulated with S. epi, exogenous AAT inhibited IL-8, IL-6, TNF-alpha, and IL-1 beta significantly but did not suppress induction of the anti-inflammatory cytokines IL-1Ra and IL-10. These ex vivo and in vitro observations suggest that endogenous AAT in blood contributes to the suppression of proinflammatory cytokine synthesis. J. Leukoc. Biol. 85: 886-895; 2009.
C1 [Pott, Gregory B.; Chan, Edward D.; Dinarello, Charles A.; Shapiro, Leland] Univ Colorado, Denver, CO 80202 USA.
[Pott, Gregory B.; Chan, Edward D.; Shapiro, Leland] Denver Vet Affairs Med Ctr, Denver, CO USA.
[Chan, Edward D.] Natl Jewish Med & Res Ctr, Denver, CO USA.
RP Shapiro, L (reprint author), Denver Vet Affairs Med Ctr, 12700 E 19th Ave,Box B168, Aurora, CO 80045 USA.
EM leland.shapiro@uchsc.edu
FU National Institutes of Health [A115614]; Campbell Foundation
FX This work is supported by National Institutes of Health grant A115614 (
to C. A. D.) and the Campbell Foundation ( to L. S.). The authors thank
Dr. Kristin Morris and Scott Beard for reviewing the manuscript and the
AAT-deficient patients for participating in these investigations.
NR 53
TC 76
Z9 81
U1 0
U2 3
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 MAY 1
PY 2009
VL 85
IS 5
BP 886
EP 895
DI 10.1189/jlb.0208145
PG 10
WC Cell Biology; Hematology; Immunology
SC Cell Biology; Hematology; Immunology
GA 453TM
UT WOS:000266635800017
PM 19197072
ER
PT J
AU Cho, H
Ryu, S
Ackerman, JL
Song, YQ
AF Cho, H.
Ryu, S.
Ackerman, J. L.
Song, Y. -Q.
TI Visualization of inhomogeneous local magnetic field gradient due to
susceptibility contrast
SO JOURNAL OF MAGNETIC RESONANCE
LA English
DT Article
DE Internal magnetic field; Background gradient; Porous media
ID STIMULATED-ECHO METHOD; POROUS-MEDIA; DIFFUSION MEASUREMENTS; NMR;
RELAXATION; GEOMETRY; ROCKS; BONE; HE-3
AB We visualized inhomogeneous local magnetic field (internal magnetic field) gradients arising from susceptibility contrast between an array of cylindrical glass tubes (solid matrix) and surrounding water (pore fluids) in a uniform applied magnetic field. MRI was performed to determine the spatially resolved decay rates due to diffusion in the internal magnetic field which were proportional to the strength of local gradient. We also spatially resolved the interference pattern of the cross-terms between the internal and the applied field gradient in order to extract the orientation of the internal field gradient. These experimental results were found to be consistent with the theoretical calculations. This work demonstrates a simple yet representative case for visualizing the strength and orientation of the local susceptibility induced magnetic field gradients in porous media. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Cho, H.; Ryu, S.; Song, Y. -Q.] Schlumberger Doll Res Ctr, Cambridge, MA 02139 USA.
[Cho, H.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Ackerman, J. L.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
RP Song, YQ (reprint author), Schlumberger Doll Res Ctr, 1 Hampshire St, Cambridge, MA 02139 USA.
EM ysong@slb.com
RI Cho, HyungJoon/F-1423-2010; Ackerman, Jerome/E-2646-2015
OI Ackerman, Jerome/0000-0001-5176-7496
FU National Institutes of Health [EB003869]
FX We thank Dr. Lukasz Zielinski and Dr. Phillip Zhe Sun for stimulating
discussions. We also thank Dr. George Dai for his technical support and
Dr. Khushali Kotedia for proof reading the manuscript. This work is
supported in part by the National Institutes of Health (EB003869).
NR 31
TC 15
Z9 15
U1 0
U2 7
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1090-7807
J9 J MAGN RESON
JI J. Magn. Reson.
PD MAY
PY 2009
VL 198
IS 1
BP 88
EP 93
DI 10.1016/j.jmr.2009.01.024
PG 6
WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical;
Spectroscopy
SC Biochemistry & Molecular Biology; Physics; Spectroscopy
GA 433UU
UT WOS:000265232100011
PM 19231262
ER
PT J
AU Engelbrektson, A
Korzenik, JR
Pittler, A
Sanders, ME
Klaenhammer, TR
Leyer, G
Kitts, CL
AF Engelbrektson, Anna
Korzenik, Joshua R.
Pittler, Arlyn
Sanders, Mary E.
Klaenhammer, Todd R.
Leyer, Gregory
Kitts, Christopher L.
TI Probiotics to minimize the disruption of faecal microbiota in healthy
subjects undergoing antibiotic therapy
SO JOURNAL OF MEDICAL MICROBIOLOGY
LA English
DT Article
ID GRADIENT GEL-ELECTROPHORESIS; 16S RIBOSOMAL-RNA;
FRAGMENT-LENGTH-POLYMORPHISM; HUMAN INTESTINE; HUMAN FECES; TEMPORAL
STABILITY; DIVERSITY; BACTERIA; COMMUNITIES; MICROFLORA
AB A novel combination of culturing and DNA-based terminal restriction fragment length polymorphism (TRFLP) analysis was used to investigate the effect of probiotics on antibiotic-induced gut microbiota alterations to determine if a probiotic preparation containing bifidobacteria and lactobacilli, taken during and after antibiotic therapy, can minimize antibiotic disturbance of faecal microbiota. Healthy subjects administered amoxicillin/clavulanate were randomized and concomitantly received a placebo or probiotic mixture. The primary end point was similarity of faecal microbiota as determined by culturing and TRFLP from subjects taking, probiotics compared to those taking a placebo measured by comparing data from baseline to post-treatment for each subject. TRFLP analysis revealed a high subject to subject variation in the baseline faecal microbiota. The most common antibiotic-induced disturbance was a relative increase in Clostridium, Eubacterium, Bacteroides and Enterobacteraceae. The mean similarity to the baseline increased over time in both treatment groups, although the probiotic group was less disturbed according to both TRFLP and culture data. The culture method revealed that post-antibiotic faecal microbiota in probiotic-consuming subjects were more similar to the baseline microbiota than the control group (P=0.046). Changes in Enterobactereaceae (P=0.006) and Bifidobacterium (P=0.030) counts were significantly different between the groups. Analysis of TRFLP data reinforced the trend between groups but was not statistically significant (P=0.066). This study indicates this mixture of probiotics promotes a more rapid return to pre-antibiotic baseline faecal bacterial microbiota.
C1 [Kitts, Christopher L.] Calif Polytech State Univ San Luis Obispo, Environm Biotechnol Inst, San Luis Obispo, CA 93407 USA.
[Engelbrektson, Anna] Joint Genome Inst, Dept Energy, Walnut Creek, CA USA.
[Korzenik, Joshua R.] Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Boston, MA 02114 USA.
[Pittler, Arlyn] Washington Univ, Sch Med, Div Gastroenterol, St Louis, MO 63110 USA.
[Sanders, Mary E.] Dairy & Food Culture Technol, Centennial, CO USA.
[Klaenhammer, Todd R.] N Carolina State Univ, Raleigh, NC 27695 USA.
[Leyer, Gregory] Cultures Div R&D, Madison, WI USA.
RP Kitts, CL (reprint author), Calif Polytech State Univ San Luis Obispo, Environm Biotechnol Inst, San Luis Obispo, CA 93407 USA.
EM ckitts@calpoly.edu
RI Engelbrektson, Anna/K-5563-2012; Engelbrektson, Anna/F-1687-2013
FU Danisco USA, Inc.; North Carolina Dairy Foundation
FX This study was funded by Danisco USA, Inc., and the North Carolina Dairy
Foundation. The authors thank Rosemary Sanozky-Dawes (North Carolina
State University) for her technical contributions to the microbiological
aspects of this study.
NR 20
TC 38
Z9 41
U1 4
U2 13
PU SOC GENERAL MICROBIOLOGY
PI READING
PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG,
BERKS, ENGLAND
SN 0022-2615
J9 J MED MICROBIOL
JI J. Med. Microbiol.
PD MAY
PY 2009
VL 58
IS 5
BP 663
EP 670
DI 10.1099/jmm.0.47615-0
PG 8
WC Microbiology
SC Microbiology
GA 444ZH
UT WOS:000266018900018
PM 19369530
ER
PT J
AU Pino, MS
Mino-Kenudson, M
Wildemore, BM
Ganguly, A
Batten, J
Sperduti, I
Iafrate, AJ
Chung, DC
AF Pino, Maria Simona
Mino-Kenudson, Mari
Wildemore, Bernadette Mandes
Ganguly, Aniruddha
Batten, Julie
Sperduti, Isabella
Iafrate, Anthony John
Chung, Daniel C.
TI Deficient DNA Mismatch Repair Is Common in Lynch Syndrome-Associated
Colorectal Adenomas
SO JOURNAL OF MOLECULAR DIAGNOSTICS
LA English
DT Article
ID NONPOLYPOSIS COLON-CANCER; MICROSATELLITE INSTABILITY; HYPERPLASTIC
POLYPS; GENETIC ALTERATIONS; GERMLINE MUTATION; HMLH1; EXPRESSION;
HOMOLOG; PREVALENCE; PROTEIN
AB Lynch syndrome is caused by germline mutations in DNA mismatch repair (MMR) genes. Both microsatellite instability (MSI) testing and immunohistochemical analyses (IHC) of colon cancers are valuable diagnostic strategies for Lynch syndrome. We sought to determine whether these markers of MMR deficiency were also detectable in pre-cancerous colorectal adenomas. Fifteen subjects with a germline MMR gene mutation who had 44 adenomas removed during surveillance colonoscopy were identified. MSI testing and IHC for MLH1, MSH2, and MSH6 were performed. MSI was detected in 23 adenomas. There was a significant association between MSI and high-grade dysplasia (P = 0.006) and distal location (P = 0.0008). Loss of MMR protein by IHC was detected in 31 adenomas. A significant association was observed between loss of staining by IHC and high-grade dysplasia (P = 0.04). Among the 40 adenomas in which both MSI tests and IHC were performed, the presence of a germline mutation correlated with an abnormal MSI result in 58% of cases, an abnormal IHC result in 70% of cases, and either an abnormal MSI or IHC result in 73% of cases. The combination of MSI and IHC testing in colorectal adenomas is a sensitive screen for the detection of Lynch syndrome and may be particularly useful when Lynch syndrome is suspected and adenomatous polyps are the only tissues available for analysis. (J Mol Diagn 2009, 11:238-247; DOI: 10.2353.jmoldx.2009.080142)
C1 [Pino, Maria Simona; Chung, Daniel C.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
[Mino-Kenudson, Mari; Wildemore, Bernadette Mandes; Ganguly, Aniruddha; Batten, Julie; Iafrate, Anthony John] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Chung, Daniel C.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
[Pino, Maria Simona] Regina Elena Inst Canc Res, Dept Med Oncol, Rome, Italy.
[Sperduti, Isabella] Regina Elena Inst Canc Res, Dept Biostat, Rome, Italy.
RP Chung, DC (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 50 Blossom St, Boston, MA 02114 USA.
EM aiafrate@partners.org; dchung@partners.org
RI Sperduti, Isabella /K-8902-2016
OI Sperduti, Isabella /0000-0001-5115-3099
FU Kate J. and Dorothy L. Clapp Fund; NIH [CA92594]
FX Supported in part by the Kate J. and Dorothy L. Clapp Fund. D.C.C. is
supported in part by NIH CA92594.
NR 49
TC 41
Z9 44
U1 0
U2 0
PU AMER SOC INVESTIGATIVE PATHOLOGY, INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA
SN 1525-1578
J9 J MOL DIAGN
JI J. Mol. Diagn.
PD MAY
PY 2009
VL 11
IS 3
BP 238
EP 247
DI 10.2353/jmoldx.2009.080142
PG 10
WC Pathology
SC Pathology
GA 438XK
UT WOS:000265589300010
PM 19324997
ER
PT J
AU Lu, A
Hiltunen, M
Romano, DM
Soininen, H
Hyman, BT
Bertram, L
Tanzi, RE
AF Lu, Alice
Hiltunen, Mikko
Romano, Donna M.
Soininen, Hilkka
Hyman, Bradley T.
Bertram, Lars
Tanzi, Rudolph E.
TI Effects of Ubiquilin 1 on the Unfolded Protein Response
SO JOURNAL OF MOLECULAR NEUROSCIENCE
LA English
DT Article
DE UBQLN1; Ubiquilin 1; UPR; Unfolded protein response; CHOP; C/EBP
homologous protein; PDI; Protein disulfide isomerase; BiP/GRP78; AD;
Alzheimer's disease
ID FAMILIAL ALZHEIMERS-DISEASE; DISULFIDE-ISOMERASE; ENDOPLASMIC-RETICULUM;
NEUROTROPHIC FACTOR; MISSENSE MUTATIONS; UP-REGULATION; GENE; STRESS;
ASSOCIATION; DEGRADATION
AB Previous studies have implicated the unfolded protein response (UPR) in the pathogenesis of Alzheimer's disease (AD). We previously reported that DNA variants in the ubiquilin 1 (UBQLN1) gene increase the risk for AD. Since UBQLN1 has been shown to play a role in the UPR, we assessed the effects of overexpression and downregulation of UBQLN1 splice variants during tunicamycin-induced ER stress. In addition to previously described transcript variants, TV1 and TV2, we identified two novel transcript variants of UBQLN1 in brain: TV3 (lacking exons 2-4) and TV4 (lacking exon 4). Overexpression of TV1-3, but not TV4 significantly decreased the mRNA induction of UPR-inducible genes, C/EBP homologous protein (CHOP), BiP/GRP78, and protein disulfide isomerase (PDI) during the UPR. Stable overexpression of TV1-3, but not TV4, also significantly decreased the induction of CHOP protein and increased cell viability during the UPR. In contrast, downregulation of UBQLN1 did not affect CHOP mRNA induction, but instead increased PDI mRNA levels. These findings suggest that overexpression UBQLN1 transcript variants TV1-3, but not TV4, exert a protective effect during the UPR by attenuating CHOP induction and potentially increasing cell viability.
C1 [Hiltunen, Mikko; Soininen, Hilkka] Univ Kuopio, Dept Neurol, FIN-70211 Kuopio, Finland.
[Lu, Alice; Hiltunen, Mikko; Romano, Donna M.; Bertram, Lars; Tanzi, Rudolph E.] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Genet & Aging Res Unit, Charlestown, MA 02129 USA.
[Lu, Alice; Tanzi, Rudolph E.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
[Hiltunen, Mikko; Soininen, Hilkka] Kuopio Univ Hosp, Dept Neurol, Kuopio 70211, Finland.
[Hyman, Bradley T.] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Alzheimers Res Unit, Charlestown, MA 02129 USA.
RP Hiltunen, M (reprint author), Univ Kuopio, Dept Neurol, POB 1627, FIN-70211 Kuopio, Finland.
EM mhiltune@messi.uku.fi; tanzi@helix.mgh.harvard.edu
RI Bertram, Lars/K-3889-2015
OI Bertram, Lars/0000-0002-0108-124X
FU Extendicare Foundation, EVO [5772708]; Kuopio University Hospital,
Finland; Finnish Academy
FX This work was supported by the Extendicare Foundation, EVO grant 5772708
from Kuopio University Hospital, Finland, and the Finnish Academy (Mikko
Hiltunen). We thank Petra Makinen for her excellent technical help.
NR 29
TC 14
Z9 15
U1 0
U2 2
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 0895-8696
J9 J MOL NEUROSCI
JI J. Mol. Neurosci.
PD MAY
PY 2009
VL 38
IS 1
BP 19
EP 30
DI 10.1007/s12031-008-9155-6
PG 12
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 434AL
UT WOS:000265247500004
PM 18953672
ER
PT J
AU Curry, WT
Barker, FG
AF Curry, William T., Jr.
Barker, Fred G., II
TI Racial, ethnic and socioeconomic disparities in the treatment of brain
tumors
SO JOURNAL OF NEURO-ONCOLOGY
LA English
DT Review
DE Race; Ethnicity; Socioeconomic status; Health care disparities; Health
care quality
ID CANCER CLINICAL-TRIALS; PATIENT NAVIGATOR PROGRAM;
SURGEONS-ONCOLOGY-GROUP; CENTRAL-NERVOUS-SYSTEM; AGE-BASED DISPARITIES;
UNITED-STATES; HEALTH-CARE; PROVIDER CASELOAD; MALIGNANT GLIOMA;
GLIOBLASTOMA-MULTIFORME
AB Disparities in American health care based on socially-defined patient characteristics such as race, ethnicity, and socioeconomic position are well-documented. We review differences and disparities in incidence, pathobiology, processes and outcomes of care, and survival based on social factors for brain tumors of all histologies. In the US, black patients have lower incidences of most brain tumor types and lower-income patients have lower incidences of low grade glioma, meningioma and acoustic neuroma; ascertainment bias may contribute to these findings. Pathogenetic differences between malignant gliomas in patients of different races have been demonstrated, but their clinical significance is unclear. Patients in disadvantaged groups are less often treated by high-volume providers. Mortality and morbidity of initial treatment are higher for brain tumor patients in disadvantaged groups, and they present with markers of more severe disease. Long term survival differences between malignant glioma patients of different races have not yet been shown. Clinical trial enrollment appears to be lower among brain tumor patients from disadvantaged groups. We propose future research both to better define disparities and to alleviate them.
C1 [Curry, William T., Jr.; Barker, Fred G., II] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg Neurosurg,Pappas Ctr Neurooncol, Boston, MA 02114 USA.
RP Curry, WT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg Neurosurg,Pappas Ctr Neurooncol, Yawkey 9E,Fruit St, Boston, MA 02114 USA.
EM wcurry@partners.org; barker@helix.mgh.harvard.edu
NR 127
TC 29
Z9 29
U1 4
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 MAY
PY 2009
VL 93
IS 1
BP 25
EP 39
DI 10.1007/s11060-009-9840-5
PG 15
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA 443WN
UT WOS:000265941600002
PM 19430880
ER
PT J
AU Plotkin, SR
Halpin, C
Blakeley, JO
Slattery, WH
Welling, DB
Chang, SM
Loeffler, JS
Harris, GJ
Sorensen, AG
McKenna, MJ
Barker, FG
AF Plotkin, Scott R.
Halpin, Chris
Blakeley, Jaishri O.
Slattery, William H., III
Welling, D. Bradley
Chang, Susan M.
Loeffler, Jay S.
Harris, Gordon J.
Sorensen, A. Gregory
McKenna, Michael J.
Barker, Fred G., II
TI Suggested response criteria for phase II antitumor drug studies for
neurofibromatosis type 2 related vestibular schwannoma
SO JOURNAL OF NEURO-ONCOLOGY
LA English
DT Review
DE Vestibular schwannoma; Acoustic neuroma; Neurofibromatosis type 2; Trial
design; Phase II trial
ID QUALITY-OF-LIFE; ACOUSTIC NEUROMA SURGERY; PROGRESSION-FREE SURVIVAL;
POSITRON-EMISSION-TOMOGRAPHY; GAMMA-KNIFE RADIOSURGERY; CLINICAL-TRIAL
DESIGN; HIGH-GRADE GLIOMAS; CELL LUNG-CANCER; HEARING-LOSS; STEREOTACTIC
RADIOSURGERY
AB Neurofibromatosis type 2 (NF2) is a tumor suppressor gene syndrome characterized by multiple schwannomas, especially vestibular schwannomas (VS), and meningiomas. Anticancer drug trials are now being explored, but there are no standardized endpoints in NF2. We review the challenges of NF2 clinical trials and suggest possible response criteria for use in initial phase II studies. We suggest two main response criteria in such trials. Objective radiographic response is defined as a durable 20% or greater reduction in VS volume based on post-contrast T1-weighted MRI images collected with 3 mm or finer cuts through the internal auditory canal. Hearing response is defined as a statistically significant improvement in word recognition scores using 50-word recorded lists in audiology. A possible composite endpoint incorporating both radiographic response and hearing response is outlined. We emphasize pitfalls in response assessment and suggest guidelines to minimize misinterpretations of response. We also identify research goals in NF2 to facilitate future trial conduct, such as identifying the expectations for time to tumor progression and time to measurable hearing loss in untreated NF2-related VS, and the relation of both endpoints to patient prognostic factors (such as age, baseline tumor volume, and measures of disease severity). These data would facilitate future use of endpoints based on stability of tumor size and hearing, which might be more appropriate for testing certain drugs. We encourage adoption of standardized endpoints early in the development of phase II trials for this population to facilitate comparison of results across trials of different agents.
C1 [Barker, Fred G., II] Massachusetts Gen Hosp, Neurosurg Serv, Pappas Ctr Neurooncol, Boston, MA 02114 USA.
[Plotkin, Scott R.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Plotkin, Scott R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
[Halpin, Chris] Massachusetts Eye & Ear Infirm, Dept Audiol, Boston, MA 02114 USA.
[Blakeley, Jaishri O.] Johns Hopkins Med Inst, Dept Neurol, Baltimore, MD 21205 USA.
[Slattery, William H., III] House Ear Res Inst, Dept Otolaryngol, Los Angeles, CA USA.
[Welling, D. Bradley] Ohio State Univ, Dept Otolaryngol, Columbus, OH 43210 USA.
[Chang, Susan M.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA.
[Loeffler, Jay S.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Harris, Gordon J.; Sorensen, A. Gregory] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[McKenna, Michael J.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA.
RP Barker, FG (reprint author), Massachusetts Gen Hosp, Neurosurg Serv, Pappas Ctr Neurooncol, Yawkey 9E,55 Fruit St, Boston, MA 02114 USA.
EM barker@helix.mgh.harvard.edu
FU NCI NIH HHS [P30 CA006973]
NR 155
TC 24
Z9 25
U1 3
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-594X
EI 1573-7373
J9 J NEURO-ONCOL
JI J. Neuro-Oncol.
PD MAY
PY 2009
VL 93
IS 1
SI SI
BP 61
EP 77
DI 10.1007/s11060-009-9867-7
PG 17
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA 443WN
UT WOS:000265941600005
PM 19430883
ER
PT J
AU Vogelbaum, MA
Asher, AL
Kondziolka, D
Boulis, NM
Selden, NR
Hoh, BL
Barker, FG
AF Vogelbaum, Michael A.
Asher, Anthony L.
Kondziolka, Douglas
Boulis, Nicholas M.
Selden, Nathan R.
Hoh, Brian L.
Barker, Fred G., II
TI Modern treatment of cerebral metastases: Integrated Medical Learning(SM)
at CNS 2007
SO JOURNAL OF NEURO-ONCOLOGY
LA English
DT Article
DE Cerebral metastases; Stereotactic radiosurgery; Whole brain
radiotherapy; Medical education
ID WHOLE-BRAIN RADIOTHERAPY; THERAPY-ONCOLOGY-GROUP; STEREOTACTIC
RADIOSURGERY BOOST; RECURSIVE PARTITIONING ANALYSIS; QUALITY-OF-LIFE;
PHASE-III TRIAL; RADIATION-THERAPY; NEUROCOGNITIVE FUNCTION; SINGLE
METASTASES; RANDOMIZED-TRIAL
AB Introduction Cerebral metastases are a common problem and pose complex treatment decisions, with reference to local control of treated lesions, prevention of new brain metastases, and toxicity of available treatments. At the 2007 Congress of Neurological Surgeons (CNS) Annual Meeting, a novel active learning process, called Integrated Medical Learning(SM), was used to better understand contemporary practice patterns and to monitor the success of education about these critical treatment decisions. Methods CNS members received an electronically distributed premeeting survey and educational materials about single and multiple cerebral metastasis treatment; practice patterns were elicited. At the Annual Meeting, 496 surgeons were polled using handheld devices before and after surgical and radiation oncology expert presentations. Surgeons who had answered premeeting surveys received a second, postmeeting questionnaire. Results In the premeeting questionnaire (N = 214), higher current volume of practice, Tumor Section membership, and academic practice predicted more correct answers (P < 0.05 for all). Fifty five percent favored routine whole brain radiotherapy (WBRT) after metastasis resection. Thirty four percent "most often" used radiosurgery to the resection bed; these respondents cited "cognitive changes" in justifying WBRT omission. At the meeting, expert presentations were followed by audience shifts toward adjuvant WBRT after resection (P = 0.01) or radiosurgery (P < 0.001)-topics for which class I evidence was discussed. There was no shift in preference for surgery or radiosurgery (P = 0.24) or multiple metastasis treatment (P = 0.8)-topics for which clear class I evidence was not presented. Postmeeting questionnaires showed retained knowledge among meeting attendees. Conclusions Using IML, we were able to study baseline knowledge and practice patterns for an important neuro-oncological treatment decision. Evidence suggested expert presentations were effective in changing audience opinion when relevant class I evidence was presented, and that knowledge was retained postmeeting.
C1 [Barker, Fred G., II] Massachusetts Gen Hosp, Pappas Ctr Neurooncol, Boston, MA 02114 USA.
[Vogelbaum, Michael A.] Cleveland Clin Fdn, Brain Tumor & Neurooncol Ctr, Cleveland, OH 44195 USA.
[Vogelbaum, Michael A.] Cleveland Clin Fdn, Dept Neurosurg, Cleveland, OH 44195 USA.
[Asher, Anthony L.] Carolina Neurosurg & Spine Associates, Brain Tumor Program, Charlotte, NC USA.
[Kondziolka, Douglas] Univ Pittsburgh, Sch Med, Med Ctr, Dept Neurol Surg, Pittsburgh, PA USA.
[Kondziolka, Douglas] Univ Pittsburgh, Sch Med, Med Ctr, Dept Radiat Oncol, Pittsburgh, PA USA.
[Boulis, Nicholas M.] Emory Univ, Dept Neurol Surg, Atlanta, GA 30322 USA.
[Selden, Nathan R.] Oregon Hlth & Sci Univ, Dept Neurol Surg, Div Pediat Neurosurg, Portland, OR 97201 USA.
[Hoh, Brian L.] Univ Florida, Dept Neurosurg, Gainesville, FL USA.
[Barker, Fred G., II] Harvard Univ, Sch Med, Dept Surg Neurosurg, Boston, MA USA.
RP Barker, FG (reprint author), Massachusetts Gen Hosp, Pappas Ctr Neurooncol, Yawkey 9E,Fruit St, Boston, MA 02114 USA.
EM barker@helix.mgh.harvard.edu
OI Selden, Nathan/0000-0001-6108-9721
NR 74
TC 8
Z9 8
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-594X
J9 J NEURO-ONCOL
JI J. Neuro-Oncol.
PD MAY
PY 2009
VL 93
IS 1
SI SI
BP 89
EP 105
DI 10.1007/s11060-009-9833-4
PG 17
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA 443WN
UT WOS:000265941600007
PM 19430885
ER
PT J
AU Aghi, MK
Batchelor, TT
Louis, DN
Barker, FG
Curry, WT
AF Aghi, Manish K.
Batchelor, Tracy T.
Louis, David N.
Barker, Fred G., II
Curry, William T., Jr.
TI Decreased rate of infection in glioblastoma patients with allelic loss
of chromosome 10q
SO JOURNAL OF NEURO-ONCOLOGY
LA English
DT Article
DE Glioblastoma; Infection; Chromosome 10q; Helper T cells
ID ANAPLASTIC ASTROCYTOMA; MALIGNANT GLIOMA; TUMOR SPECIMENS; BRAIN-TUMORS;
T-CELLS; PTEN; CYTOKINE; SURVIVAL; HETEROZYGOSITY; MULTIFORME
AB Introduction Chromosome 10q allelic loss commonly occurs in glioblastoma. Disruption of PTEN, one of three known 10q tumor suppressor genes, affects the immune system by increasing tumor expression of immunosuppressive protein B7-H1 and by increasing tumor release of Th2-inducing cytokines. While the former might impair antitumor cellular immunity, a consideration for immunotherapy, the latter could cause 10q-maintaining tumor patients to experience comparatively higher rates of bacterial infections, a source of morbidity and mortality in glioblastoma patients. Methods We retrospectively reviewed 58 glioblastoma patients whose tumors were designated "normal-10q" (n = 16) or "LOH-10q" (n = 42) using loss of heterozygosity (LOH) assays of microsatellite markers in constitutional/tumor DNA pairs. Records were reviewed for symptomatic, microbiologically or radiographically confirmed infections in the first 2 years after diagnosis. Results Infection occurred more frequently in "normal-10q" than "LOH-10q" patients (56% vs. 14% of patients experiencing infection; P = 0.001). "Normal-10q" patients more commonly developed all four infection types studied (urinary tract = 38% vs. 13%, craniotomy wound = 19% vs. 0%, pneumonia = 19% vs. 5%, sepsis = 6% vs. 3%). "Normal-10q" and "LOH-10q" patients had similar survival, ages, chemotherapy treatment rates, and frequency of patients on dexamethasone 1 month after radiation therapy (P = 0.4-0.98), making these factors unlikely to explain the observed difference in infection rates. Conclusion While tumor mutations may inhibit antitumor immunity, the effects of these mutations on systemic immunity remain undetermined. We found higher infection rates after glioblastoma diagnosis in patients whose tumors maintained chromosome 10q than in patients whose tumors had allelic 10q loss. Differing effects of this genetic alteration on antitumor and systemic immunity may warrant further investigation, potentially providing insight into mechanisms of antitumor immunity and host defenses against local and systemic infections.
C1 [Aghi, Manish K.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA.
[Batchelor, Tracy T.; Barker, Fred G., II; Curry, William T., Jr.] Massachusetts Gen Hosp, Stephen E & Catherine Pappas Ctr Neurooncol, Boston, MA 02114 USA.
[Batchelor, Tracy T.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Louis, David N.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Louis, David N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Neurooncol Lab, Boston, MA USA.
[Barker, Fred G., II; Curry, William T., Jr.] Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA.
RP Aghi, MK (reprint author), Univ Calif San Francisco, Dept Neurol Surg, 505 Parnassus Ave Room M779, San Francisco, CA 94143 USA.
EM AghiM@neurosurg.ucsf.edu
NR 28
TC 7
Z9 7
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-594X
J9 J NEURO-ONCOL
JI J. Neuro-Oncol.
PD MAY
PY 2009
VL 93
IS 1
BP 115
EP 120
DI 10.1007/s11060-009-9826-3
PG 6
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA 443WN
UT WOS:000265941600009
PM 19430887
ER
PT J
AU Wang, Q
Tang, XN
Swanson, RA
Yenari, MA
AF Wang, Q.
Tang, X. N.
Swanson, R. A.
Yenari, M. A.
TI Pyruvate protects experimental stroke: the involvement of
anti-inflammatory mechanisms via inhibition of NF-kappa B and MMP9
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Meeting Abstract
CT 3rd International-Society-of-Neurochemistry-Special-Neurochemistry
Conference/8th International Meeting on Brain Energy Metabolism
CY JUN 27-JUL 01, 2008
CL Beijing, PEOPLES R CHINA
SP Int Soc Neurochem
C1 [Wang, Q.; Tang, X. N.; Swanson, R. A.; Yenari, M. A.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA.
[Wang, Q.; Tang, X. N.; Swanson, R. A.; Yenari, M. A.] San Francisco VA Med Ctr, San Francisco, CA USA.
[Wang, Q.; Tang, X. N.] Stanford Univ, Sch Med, Dept Anesthesia, Stanford, CA 94305 USA.
[Wang, Q.] Univ Wollongong, Fac Hlth & Behav Sci, Neurobiol Res Ctr, Wollongong, NSW, Australia.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0022-3042
J9 J NEUROCHEM
JI J. Neurochem.
PD MAY
PY 2009
VL 109
BP 278
EP 279
PG 2
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 430UF
UT WOS:000265013900079
ER
PT J
AU Tang, KS
Suh, SW
Alano, CC
Swanson, RA
Anderson, CM
AF Tang, K. S.
Suh, S. W.
Alano, C. C.
Swanson, R. A.
Anderson, C. M.
TI Astrocyte poly (ADP-ribose) polymerase-1 activation causes glutamate
excitotoxicity in neurons
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Meeting Abstract
CT 3rd International-Society-of-Neurochemistry-Special-Neurochemistry
Conference/8th International Meeting on Brain Energy Metabolism
CY JUN 27-JUL 01, 2008
CL Beijing, PEOPLES R CHINA
SP Int Soc Neurochem
C1 [Tang, K. S.; Anderson, C. M.] Univ Manitoba, Dept Pharmacol & Therapeut, Winnipeg, MB, Canada.
[Tang, K. S.; Anderson, C. M.] St Boniface Gen Hosp, Res Ctr, Div Neurodegenerat Disorders, Winnipeg, MB R2H 2A6, Canada.
[Suh, S. W.; Alano, C. C.; Swanson, R. A.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA.
[Suh, S. W.; Alano, C. C.; Swanson, R. A.] San Francisco VA Med Ctr, San Francisco, CA 94143 USA.
RI Anderson, Chris/J-7081-2014
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0022-3042
J9 J NEUROCHEM
JI J. Neurochem.
PD MAY
PY 2009
VL 109
BP 286
EP 286
PG 1
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 430UF
UT WOS:000265013900104
ER
PT J
AU McFarland, NR
Lee, JS
Hyman, BT
McLean, PJ
AF McFarland, Nikolaus R.
Lee, Jeng-Shin
Hyman, Bradley T.
McLean, Pamela J.
TI Comparison of transduction efficiency of recombinant AAV serotypes 1, 2,
5, and 8 in the rat nigrostriatal system
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Article
DE adeno-associated virus; gene therapy; Parkinson disease; striatum;
substantia nigra; transduction
ID ADENOASSOCIATED VIRUS AAV; CENTRAL-NERVOUS-SYSTEM; DOPAMINERGIC NEURON
LOSS; VIRAL VECTOR SEROTYPE-1; PARKINSONS-DISEASE; ALPHA-SYNUCLEIN;
GENE-TRANSFER; SUBSTANTIA-NIGRA; MOUSE-BRAIN; EXPRESSION
AB Enhanced delivery and expression of genes in specific neuronal systems is critical for the development of genetic models of neurodegenerative disease and potential gene therapy. Recent discovery of new recombinant adeno-associated viral (rAAV) capsid serotypes has resulted in improved transduction efficiency, but expression levels, spread of transgene, and potential toxicity can differ depending on brain region and among species. We compared the transduction efficiency of titer-matched rAAV 2/1, 2/5, and 2/8 to the commonly used rAAV2/2 in the rat nigrostriatal system via expression of the reporter transgene, enhanced green fluorescent protein. Newer rAAV serotypes 2/1, 2/5, and 2/8 demonstrated marked increase in transduction and spread of enhanced green fluorescent protein expression in dopaminergic nigrostriatal neurons and projections to the striatum and globus pallidus compared to rAAV2/2 at 2 weeks post-injection. The number of nigral cells transduced was greatest for rAAV2/1, but for serotypes 2/5 and 2/8 was still two- to threefold higher than that for 2/2. Enhanced transduction did not cause an increase in glial cell response or toxicity. New rAAV serotypes thus promise improved gene delivery to nigrostriatal system with the potential for better models and therapeutics for Parkinson disease and other neurodegenerative disorders.
C1 [McFarland, Nikolaus R.; Hyman, Bradley T.; McLean, Pamela J.] Harvard Univ, Sch Med, Charlestown, MA USA.
[McFarland, Nikolaus R.; Hyman, Bradley T.; McLean, Pamela J.] Massachusetts Gen Hosp, Dept Neurol, MIND, Charlestown, MA USA.
[Lee, Jeng-Shin] Harvard Univ, Sch Med, Dept Genet, Harvard Gene Therapy Initiat, Boston, MA USA.
[Lee, Jeng-Shin] Harvard Univ, Sch Med, Dana Farber Harvard Canc Inst, Boston, MA USA.
RP McFarland, NR (reprint author), Bldg 114,16th St 2400, Charlestown, MA 02129 USA.
EM nmcfarland@partners.org
OI McFarland, Nikolaus/0000-0002-8699-8857
FU NIH [NS038372A-08]; American Parkinson Disease Association (APDA)
FX This work was supported by NIH NS038372A-08. NRM is supported by the
American Parkinson Disease Association (APDA).
NR 31
TC 39
Z9 39
U1 0
U2 6
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0022-3042
J9 J NEUROCHEM
JI J. Neurochem.
PD MAY
PY 2009
VL 109
IS 3
BP 838
EP 845
DI 10.1111/j.1471-4159.2009.06010.x
PG 8
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 430UD
UT WOS:000265013700014
PM 19250335
ER
PT J
AU Hsieh, CL
Koike, M
Spusta, SC
Niemi, EC
Yenari, M
Nakamura, MC
Seaman, WE
AF Hsieh, Christine L.
Koike, Maya
Spusta, Steve C.
Niemi, Erene C.
Yenari, Midori
Nakamura, Mary C.
Seaman, William E.
TI A role for TREM2 ligands in the phagocytosis of apoptotic neuronal cells
by microglia
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Article
DE apoptotic neurons; microglia; phagocytosis
ID CENTRAL-NERVOUS-SYSTEM; MYELOID CELLS; IN-VIVO; FRACTALKINE RECEPTOR;
PATTERN-RECOGNITION; DENDRITIC CELLS; IMMUNE-SYSTEM; CUTTING EDGE;
DAP12; MACROPHAGES
AB Following neuronal injury, microglia initiate repair by phagocytosing dead neurons without eliciting inflammation. Prior evidence indicates triggering receptor expressed by myeloid cells-2 (TREM2) promotes phagocytosis and retards inflammation. However, evidence that microglia and neurons directly interact through TREM2 to orchestrate microglial function is lacking. We here demonstrate that TREM2 interacts with endogenous ligands on neurons. Staining with TREM2-Fc identified TREM2 ligands (TREM2-L) on Neuro2A cells and on cultured cortical and dopamine neurons. Apoptosis greatly increased the expression of TREM2-L. Furthermore, apoptotic neurons stimulated TREM2 signaling, and an anti-TREM2 mAb blocked stimulation. To examine the interaction between TREM2 and TREM2-L in phagocytosis, we studied BV2 microglial cells and their engulfment of apoptotic Neuro2A. One of our anti-TREM2 mAb, but not others, reduced engulfment, suggesting the presence of a functional site on TREM2 interacting with neurons. Further, Chinese hamster ovary cells transfected with TREM2 conferred phagocytic activity of neuronal cells demonstrating that TREM2 is both required and sufficient for competent uptake of apoptotic neuronal cells. Finally, while TREM2-L are expressed on neurons, TREM2 is not; in the brain, it is found on microglia. TREM2 and TREM2-L form a receptor-ligand pair connecting microglia with apoptotic neurons, directing removal of damaged cells to allow repair.
C1 Univ Calif San Francisco, San Francisco, CA 94143 USA.
San Francisco VA Med Ctr, San Francisco, CA USA.
RP Seaman, WE (reprint author), Vet Affairs Med Ctr, 111R,4150 Clement St, San Francisco, CA 94121 USA.
EM bseaman@medicine.ucsf.edu
FU Department of Defense [W81XWH-05-2-0094, PT075679]; NIH NINDS [R01
NS40516]; Veterans Administration; NIH NINDS NRSA [5F32NS060338]
FX The authors acknowledge and thank Dr Damiana Alvarez for her
contributions during the initial phases of this project. The authors
also thank Dr Eric Huang and Dr Jiasheng Zhang (UC San Francisco) for
their guidance in isolating ventral midbrain neurons, and we thank Dr
Daniel Cua and Dr Barbara Shaikh (Schering-Plough, Palo Alto, CA, USA)
and Dr Monica Carson (UC Riverside) for their guidance regarding
microglial isolation. We also appreciate the help of Ben Harmeling and
Dr Ken Scalapino, who operate the flow cytometry core facility at the
San Francisco VA Medical Center. This work was funded by the Department
of Defense (W81XWH-05-2-0094 and PT075679 to WES), by the NIH NINDS (R01
NS40516 to MY), and by the Veterans Administration. CLH is supported by
an NIH NINDS NRSA (5F32NS060338).
NR 42
TC 111
Z9 112
U1 0
U2 21
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0022-3042
J9 J NEUROCHEM
JI J. Neurochem.
PD MAY
PY 2009
VL 109
IS 4
BP 1144
EP 1156
DI 10.1111/j.1471-4159.2009.06042.x
PG 13
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 433EK
UT WOS:000265186900018
PM 19302484
ER
PT J
AU Wang, CSM
Burke, JR
Steffens, DC
Hulette, CM
Breitner, JCS
Plassman, BL
AF Wang, C. Sheei-Meei
Burke, J. R.
Steffens, D. C.
Hulette, C. M.
Breitner, J. C. S.
Plassman, B. L.
TI Twin pairs discordant for neuropathologically confirmed Lewy body
dementia
SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
LA English
DT Article
ID ALZHEIMERS-DISEASE; FRONTOTEMPORAL DEMENTIA; PATHOLOGICAL DIAGNOSIS;
PARKINSONS-DISEASE; RISK-FACTOR; BODIES DLB; WORK GROUP; REGISTRY;
CONCORDANCE; CONSORTIUM
AB Aim: Little is known about the concordance rate in twins for dementia with Lewy bodies (DLB). The rate of agreement between clinical and pathological diagnoses for DLB is typically low, necessitating confirmation of the diagnosis neuropathologically.
Methods: Participants were 17 twin pairs enrolled in the Duke Twins Study of Memory in Aging in which at least one member of the pair had an autopsy confirmed diagnosis of DLB, Alzheimer's disease (AD) with Lewy bodies or frontotemporal dementia with Lewy bodies. The characteristics of those with dementia were assessed and rates of concordance for pathological confirmed dementia were examined.
Results: Four monozygotic twin pairs had a proband with neuropathologically confirmed pure DLB; all remained discordant for dementia for periods up to 16 years or more. Five of 13 pairs in which the proband had AD plus DLB were concordant for dementia but only one pair was concordant for AD plus DLB, while the co-twins in the other four pairs had other types of dementia.
Conclusions: The present study indicates that even among twins, a diagnosis of DLB in one twin does not predict the same diagnosis in the other twin. Neuropathological discordance in type of dementia among monozygotic pairs hints at environmental or epigenetic factors playing a role in Lewy body pathology.
C1 [Steffens, D. C.; Plassman, B. L.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC 27701 USA.
[Wang, C. Sheei-Meei] Tainan Hosp, Dept Hlth, Dept Psychiat, Tainan, Taiwan.
[Burke, J. R.] Duke Univ, Med Ctr, Dept Neurol, Durham, NC USA.
[Hulette, C. M.] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA.
[Burke, J. R.; Hulette, C. M.] Duke Univ, Med Ctr, Joseph & Kathleen Bryan Alzheimers Dis Res Ctr, Durham, NC USA.
[Breitner, J. C. S.] Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, Seattle, WA USA.
[Breitner, J. C. S.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
RP Plassman, BL (reprint author), Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, 905 Main St,Box 41,Ste 25-D, Durham, NC 27701 USA.
EM brenda.plassman@duke.edu
RI Burke, James/E-4245-2016
OI Burke, James/0000-0002-3408-7787
FU NIH [AG-08549, AG-05128, AG-02837]; American Health Assistance
Foundation [95112]
FX NIH AG-08549 (JCSB, BLP), American Health Assistance Foundation # 95112
(JCSB) and NIH AG-05128 and AG-02837 (CMH).
NR 25
TC 11
Z9 11
U1 1
U2 4
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0022-3050
J9 J NEUROL NEUROSUR PS
JI J. Neurol. Neurosurg. Psychiatry
PD MAY
PY 2009
VL 80
IS 5
BP 562
EP 565
DI 10.1136/jnnp.2008.151654
PG 4
WC Clinical Neurology; Psychiatry; Surgery
SC Neurosciences & Neurology; Psychiatry; Surgery
GA 433ZN
UT WOS:000265244900022
PM 19372291
ER
PT J
AU McFarland, NR
Fan, ZY
Xu, K
Schwarzschild, MA
Feany, MB
Hyman, BT
McLean, PJ
AF McFarland, Nikolaus R.
Fan, Zhanyun
Xu, Kui
Schwarzschild, Michael A.
Feany, Mel B.
Hyman, Bradley T.
McLean, Pamela J.
TI alpha-Synuclein S129 Phosphorylation Mutants Do Not Alter Nigrostriatal
Toxicity in a Rat Model of Parkinson Disease
SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
LA English
DT Article
DE Adeno-associated virus; Dopamine; Lewy bodies; Striatum; Substantia
nigra; Tyrosine hydroxylase
ID COUPLED RECEPTOR KINASE-5; DOPAMINERGIC NEURON LOSS; VIRAL VECTOR
SEROTYPE-1; CENTRAL-NERVOUS-SYSTEM; LEWY BODY DISEASE; IN-VITRO; LOCUS
TRIPLICATION; OXIDATIVE STRESS; DROSOPHILA MODEL; FIBRIL FORMATION
AB Lewy bodies are found in Parkinson disease and related disorders and are extensively phosphorylated at Ser-129 (S129), but whether S129 phosphorylation mediates alpha-synuclein aggregation and neurotoxicity has been controversial. We used recombinant adeno-associated virus to overexpress alpha-synuclein in the rat nigrostriatal system. Rats were injected with recombinant adeno-associated virus 2/8 expressing either human wild-type (wt) or mutant alpha-synuclein with S129 replaced by alanine (S129A) or aspartate (S129D). Contralateral substantia nigra injections containing empty vector served as controls. Both wt and S129 mutants resulted in significant dopaminergic cell loss in the recipients by 6 weeks, but there were only small decreases in nigrostriatal terminal density and tyrosine hydroxylase expression. There were no significant differences in dopaminergic cell loss, nigrostriatal terminal density, or tyrosine hydroxylase expression among the wt and S129 mutants. Furthermore, we did not observe any differences in alpha-synuclein aggregate formation or distribution among wt and either S129 mutant. These findings contrast with those from previous studies and suggest that injections of both S129 phosphorylation mutants result in dopaminergic neurotoxicity similar to wt injections. Further study is needed to clarify the effects of these S129 Mutants and alpha-synuclein phosphorylation in mammalian systems.
C1 [McFarland, Nikolaus R.; Fan, Zhanyun; Xu, Kui; Schwarzschild, Michael A.; Hyman, Bradley T.; McLean, Pamela J.] Massachusetts Gen Hosp, Dept Neurol, MassGen Inst Neurodegenerat Dis, Charlestown, MA USA.
[McFarland, Nikolaus R.; Fan, Zhanyun; Xu, Kui; Schwarzschild, Michael A.; Hyman, Bradley T.; McLean, Pamela J.] Harvard Univ, Sch Med, Charlestown, MA USA.
[Feany, Mel B.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Feany, Mel B.] Harvard Univ, Sch Med, Boston, MA USA.
RP McFarland, NR (reprint author), Bldg 114,16th St 2400, Charlestown, MA 02129 USA.
EM mmcfarland@partners.org
OI McFarland, Nikolaus/0000-0002-8699-8857
FU NIH [NS038372A-08]; DOD [W81XWH-04-1-0881]; American Parkinson Disease
Association; Koch Jr. Fellowship
FX This study was supported by NIH NS038372A-08 (Bradley Hyman) and DOD
W81XWH-04-1-0881 (Michael Schwarzschild). Nikolaus McFarland is
supported by an American Parkinson Disease Association and the Koch Jr.
Fellowship.
NR 52
TC 62
Z9 62
U1 2
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0022-3069
J9 J NEUROPATH EXP NEUR
JI J. Neuropathol. Exp. Neurol.
PD MAY
PY 2009
VL 68
IS 5
BP 515
EP 524
PG 10
WC Clinical Neurology; Neurosciences; Pathology
SC Neurosciences & Neurology; Pathology
GA 441GZ
UT WOS:000265758600007
PM 19525899
ER
PT J
AU Auluck, P
Su, J
Lindquist, S
AF Auluck, Pavan
Su, Julie
Lindquist, Susan
TI The Relationship Between Mitochondria, Oxidative Stress, and
alpha-Synuclein Toxicity in Parkinson Disease
SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
LA English
DT Meeting Abstract
CT 85th Annual Meeting of the American-Association-of-Neuropathologists
CY JUN 11-14, 2009
CL San Antonio, TX
SP Amer Assoc Neuropathol
C1 [Auluck, Pavan] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Su, Julie; Lindquist, Susan] Whitehead Inst Biomed Res, Cambridge, MA USA.
RI Auluck, Pavan/A-1160-2010
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0022-3069
J9 J NEUROPATH EXP NEUR
JI J. Neuropathol. Exp. Neurol.
PD MAY
PY 2009
VL 68
IS 5
MA 20
BP 557
EP 557
PG 1
WC Clinical Neurology; Neurosciences; Pathology
SC Neurosciences & Neurology; Pathology
GA 441GZ
UT WOS:000265758600031
ER
PT J
AU Snuderl, M
Eichler, A
Ligon, K
Vu, Q
Silver, M
Betensky, R
Ligon, A
Wen, P
Louis, D
Iafrate, A
AF Snuderl, Matija
Eichler, April
Ligon, Keith
Vu, Quynh
Silver, Michael
Betensky, Rebecca
Ligon, Azra
Wen, Patrick
Louis, David
Iafrate, A.
TI Polysomy For Chromosomes 1 And 19 Predicts Earlier Recurrence In
Anaplastic Oligodendrogliomas With Concurrent 1p/19q Loss
SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
LA English
DT Meeting Abstract
CT 85th Annual Meeting of the American-Association-of-Neuropathologists
CY JUN 11-14, 2009
CL San Antonio, TX
SP Amer Assoc Neuropathol
C1 [Snuderl, Matija; Vu, Quynh; Louis, David; Iafrate, A.] Massachusetts Gen Hosp, Pathol Serv, Boston, MA 02114 USA.
[Eichler, April] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
[Ligon, Keith; Ligon, Azra] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Silver, Michael] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA.
[Betensky, Rebecca] Harvard Univ, Sch Publ Hlth, Dept Biostat, Cambridge, MA 02138 USA.
[Wen, Patrick] Neurooncol Dana Farber Canc Inst, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0022-3069
J9 J NEUROPATH EXP NEUR
JI J. Neuropathol. Exp. Neurol.
PD MAY
PY 2009
VL 68
IS 5
MA 43
BP 562
EP 563
PG 2
WC Clinical Neurology; Neurosciences; Pathology
SC Neurosciences & Neurology; Pathology
GA 441GZ
UT WOS:000265758600054
ER
PT J
AU Yip, S
Miao, JY
Cahill, D
Iafrate, A
Aldape, K
Nutt, C
Louis, D
AF Yip, Stephen
Miao, Jiangyong
Cahill, Daniel
Iafrate, A.
Aldape, Kenneth
Nutt, Catherine
Louis, David
TI MSH6 Somatic Mutations in Mediating Temozolomide Resistance in Recurrent
Glioblastomas
SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
LA English
DT Meeting Abstract
CT 85th Annual Meeting of the American-Association-of-Neuropathologists
CY JUN 11-14, 2009
CL San Antonio, TX
SP Amer Assoc Neuropathol
C1 [Yip, Stephen; Miao, Jiangyong; Cahill, Daniel; Iafrate, A.; Nutt, Catherine; Louis, David] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Aldape, Kenneth] Univ Texas MD Anderson Canc Ctr, Houston, TX USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0022-3069
J9 J NEUROPATH EXP NEUR
JI J. Neuropathol. Exp. Neurol.
PD MAY
PY 2009
VL 68
IS 5
MA 40
BP 562
EP 562
PG 1
WC Clinical Neurology; Neurosciences; Pathology
SC Neurosciences & Neurology; Pathology
GA 441GZ
UT WOS:000265758600051
ER
PT J
AU Teich, A
Hedley-Whyte, E
Goldman, J
AF Teich, Andrew
Hedley-Whyte, E.
Goldman, James
TI "Pontinization" of the Medulla: Two Clinical Case Studies
SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
LA English
DT Meeting Abstract
CT 85th Annual Meeting of the American-Association-of-Neuropathologists
CY JUN 11-14, 2009
CL San Antonio, TX
SP Amer Assoc Neuropathol
C1 [Teich, Andrew; Goldman, James] Columbia Univ, Div Neuropathol, New York, NY 10027 USA.
[Hedley-Whyte, E.] Massachusetts Gen Hosp, Dept Neuropathol, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0022-3069
J9 J NEUROPATH EXP NEUR
JI J. Neuropathol. Exp. Neurol.
PD MAY
PY 2009
VL 68
IS 5
MA 99
BP 577
EP 577
PG 1
WC Clinical Neurology; Neurosciences; Pathology
SC Neurosciences & Neurology; Pathology
GA 441GZ
UT WOS:000265758600109
ER
PT J
AU Kim, Y
Yip, S
Quant, E
Mobapatra, G
Louis, D
AF Kim, Yeowon
Yip, Stephen
Quant, Eudocia
Mobapatra, Gayatry
Louis, David
TI Mismatch Repair Defects in Human Glioblastomas Post-Alkylator Treatment
SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
LA English
DT Meeting Abstract
CT 85th Annual Meeting of the American-Association-of-Neuropathologists
CY JUN 11-14, 2009
CL San Antonio, TX
SP Amer Assoc Neuropathol
C1 [Quant, Eudocia] Massachusetts Gen Hosp, Mol Pathol Unit, Brain Tumor Ctr, Boston, MA 02114 USA.
[Louis, David] Massachusetts Gen Hosp, Mol Pathol Unit, Ctr Canc Res, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0022-3069
J9 J NEUROPATH EXP NEUR
JI J. Neuropathol. Exp. Neurol.
PD MAY
PY 2009
VL 68
IS 5
MA 115
BP 581
EP 582
PG 2
WC Clinical Neurology; Neurosciences; Pathology
SC Neurosciences & Neurology; Pathology
GA 441GZ
UT WOS:000265758600125
ER
PT J
AU Wig, GS
Buckner, RL
Schacter, DL
AF Wig, Gagan S.
Buckner, Randy L.
Schacter, Daniel L.
TI Repetition Priming Influences Distinct Brain Systems: Evidence From
Task-Evoked Data and Resting-State Correlations
SO JOURNAL OF NEUROPHYSIOLOGY
LA English
DT Review
ID INFERIOR PREFRONTAL CORTEX; EVENT-RELATED FMRI; TRANSCRANIAL MAGNETIC
STIMULATION; RESONANCE-IMAGING EVIDENCE; LATERAL OCCIPITAL COMPLEX;
IMPLICIT MEMORY; TEMPORAL CORTEX; FUNCTIONAL MRI; RECOGNITION MEMORY;
INFEROTEMPORAL CORTEX
AB Wig GS, Buckner RL, Schacter DL. Repetition priming influences distinct brain systems: evidence from task-evoked data and resting-state correlations. J Neurophysiol 101: 2632-2648, 2009. First published February 18, 2009; doi:10.1152/jn.91213.2008. Behavioral dissociations suggest that a single experience can separately influence multiple processing components. Here we used a repetition priming functional magnetic resonance imaging paradigm that directly contrasted the effects of stimulus and decision changes to identify the underlying brain systems. Direct repetition of stimulus features caused marked reductions in posterior regions of the inferior temporal lobe that were insensitive to whether the decision was held constant or changed between study and test. By contrast, prefrontal cortex showed repetition effects that were sensitive to the exact stimulus-to-decision mapping. Analysis of resting-state functional connectivity revealed that the dissociated repetition effects are embedded within distinct brain systems. Regions that were sensitive to changes in the stimulus correlated with perceptual cortices, whereas the decision changes attenuated activity in regions correlated with middle-temporal regions and a frontoparietal control system. These results thus explain the long-known dissociation between perceptual and conceptual components of priming by revealing how a single experience can separately influence distinct, concurrently active brain systems.
C1 [Wig, Gagan S.; Buckner, Randy L.; Schacter, Daniel L.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA.
[Buckner, Randy L.] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA.
[Buckner, Randy L.] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA.
[Wig, Gagan S.; Buckner, Randy L.; Schacter, Daniel L.] Massachusetts Gen Hosp, Athinoula Martinos Ctr Biomed Imaging, Charlestown, MA USA.
RP Wig, GS (reprint author), Harvard Univ, Dept Psychol, 33 Kirkland St, Cambridge, MA 02138 USA.
EM gwig@wjh.harvard.edu
OI Schacter, Daniel/0000-0002-2460-6061
FU Canadian Institute; Howard Hughes Medical Institute; National Institute
of Mental Health [MH-060941]
FX This work was supported by an Institute for Aging Postdoctoral
Fellowship from the Canadian Institute for Health Research to G. S. Wig,
the Howard Hughes Medical Institute, and a National Institute of Mental
Health Grant MH-060941 to D. L. Schacter.
NR 101
TC 41
Z9 42
U1 4
U2 10
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3077
J9 J NEUROPHYSIOL
JI J. Neurophysiol.
PD MAY
PY 2009
VL 101
IS 5
BP 2632
EP 2648
DI 10.1152/jn.91213.2008
PG 17
WC Neurosciences; Physiology
SC Neurosciences & Neurology; Physiology
GA 436FM
UT WOS:000265398100041
PM 19225167
ER
PT J
AU Yehuda, R
Harvey, PD
Golier, JA
Newmark, RE
Bowie, CR
Wohltmann, JJ
Grossman, RA
Schmeidler, J
Hazlett, EA
Buchsbaum, MS
AF Yehuda, Rachel
Harvey, Philip D.
Golier, Julia A.
Newmark, Randall E.
Bowie, Christopher R.
Wohltmann, Janelle J.
Grossman, Robert A.
Schmeidler, James
Hazlett, Erin A.
Buchsbaum, Monte S.
TI Changes in Relative Glucose Metabolic Rate Following Cortisol
Administration in Aging Veterans with Posttraumatic Stress Disorder: An
FDG-PET Neuroimaging Study
SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES
LA English
DT Article
ID MEDIAL PREFRONTAL CORTEX; CORTICOLIMBIC BLOOD-FLOW; MIXED LATERAL
PREFERENCE; CHILDHOOD SEXUAL-ABUSE; SCRIPT-DRIVEN IMAGERY;
HIPPOCAMPAL-FORMATION; MEMORY PERFORMANCE; ALZHEIMERS-DISEASE;
PERSONALITY-DISORDER; BASOLATERAL AMYGDALA
AB The authors aimed to examine central glucocorticoids effects by measuring relative glucose metabolic rate (rGMR) in the hippocampus, amygdala, and anterior cingulate cortex (ACC) and the relationship between amygdala and ACC activity. The participants were male combat veterans with and without PTSD, 52 to 81 years old. The authors utilized randomized, double-blind, placebo-controlled examinations of the rGMR response to 17.5 mg hydrocortisone (HCORT) using 2-Deoxy-2-[(18)F] fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) neuroimaging. Group differences in hemispheric laterality of rGMR were observed following placebo administration, reflecting lower rGMR in the right hippocampus and ventral amygdala, and higher rGMR in the left ventral amygdala in the PTSD+ group compared to the PTSD+ group. HCORT reduced these group differences in laterality. The net effect of HCORT was to restore a normal inverse association between the ACC and amygdala in the PTSD+ group, but disrupt this neural network in the PTSD- group. The magnitude of improvement in working memory correlated with greater hemispheric laterality in the dorsal amygdala following HCORT in both groups. The restorative effects of HCORT on metabolism and working memory provide a rationale for examining the therapeutic benefits of glucocorticoid manipulation in aging PTSD patients.
C1 [Yehuda, Rachel; Golier, Julia A.; Bowie, Christopher R.; Wohltmann, Janelle J.; Grossman, Robert A.; Schmeidler, James] Mt Sinai Sch Med, Dept Psychiat, Traumat Stress Studies Program, New York, NY USA.
[Yehuda, Rachel; Golier, Julia A.; Bowie, Christopher R.; Wohltmann, Janelle J.] James J Peters Bronx Vet Affairs Med Ctr, PTSD Program, Bronx, NY USA.
[Harvey, Philip D.] Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA USA.
[Newmark, Randall E.; Hazlett, Erin A.; Buchsbaum, Monte S.] Mt Sinai Sch Med, Dept Psychiat, PET Lab, New York, NY USA.
RP Yehuda, R (reprint author), Bronx VA OOMH, 130 W Kingsbridge Rd, Bronx, NY 10468 USA.
EM Rachel.Yehuda@va.gov
FU National Institute of Health [5 M01 RR00071]
FX This work was supported by a VA Merit Review Grant (RY) and, in part by
a grant (5 M01 RR00071) for the Mount Sinai General Clinical Research
Center from the National Institute of Health. The authors wish to thank
Karina Stavitsky for expert and professional coordination of this
research project, Dr. Linda Bierer for database construction, Yuliya
Torosjan for scanner operation, Dr. King-Wai Chu for program development
and support, and Drs. Lisa Tischler and Alicia Hirsch for conducting
diagnostic evaluations. Dr. Yehuda had full access to all of the data in
the study and takes responsibility for the integrity of the data and the
accuracy of the data analysis.
NR 69
TC 18
Z9 21
U1 2
U2 7
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 0895-0172
J9 J NEUROPSYCH CLIN N
JI J. Neuropsychiatr. Clin. Neurosci.
PD MAY
PY 2009
VL 21
IS 2
BP 132
EP 143
PG 12
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 472SL
UT WOS:000268152300004
PM 19622684
ER
PT J
AU Erickson, JI
Duffy, ME
Ditomassi, M
Jones, D
AF Erickson, Jeanette Ives
Duffy, Mary E.
Ditomassi, Marianne
Jones, Dorothy
TI Psychometric Evaluation of the Revised Professional Practice Environment
(RPPE) Scale
SO JOURNAL OF NURSING ADMINISTRATION
LA English
DT Article
ID INTENSIVE-CARE UNITS; NURSING WORK INDEX; CROSS-VALIDATION;
QUESTIONNAIRE; HOSPITALS; SERVICES; ISSUES
AB Objective: The purpose was to examine the psychometric properties of the Revised Professional Practice Environment (RPPE) scale.
Background: Despite renewed focus on studying health professionals' practice environments, there are still few reliable and valid instruments available to assist nurse administrators in decision making.
Methods: A psychometric evaluation using a random-sample cross-validation procedure (calibration sample [CS], n = 775; validation sample [VS], n = 775) was undertaken.
Results: Cronbach alpha internal consistency reliability of the total score (r = 0.93 [CS] and 0.92 [VS]), resulting subscale scores (r range: 0.80-0.87 [CS], 0.81-0.88 [VS]), and principal components analyses with Varimax rotation and Kaiser normalization (8 components, 59.2% variance [CS], 59.7% [VS]) produced almost identical results in both samples.
Conclusions: The multidimensional RPPE is a psychometrically sound measure of 8 components of the professional practice environment in the acute care setting and sufficiently reliable and valid for use as independent subscales in healthcare research.
C1 [Erickson, Jeanette Ives; Duffy, Mary E.; Ditomassi, Marianne; Jones, Dorothy] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Duffy, ME (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA.
EM mduffy4@partners.org
NR 24
TC 23
Z9 23
U1 1
U2 5
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 MAY
PY 2009
VL 39
IS 5
BP 236
EP 243
PG 8
WC Nursing
SC Nursing
GA 445NA
UT WOS:000266056300007
PM 19423989
ER
PT J
AU Ruggiero, SL
Dodson, TB
Assael, LA
Landesberg, R
Marx, RE
Mehrotra, B
AF Ruggiero, Salvatore L.
Dodson, Thomas B.
Assael, Leon A.
Landesberg, Regina
Marx, Robert E.
Mehrotra, Bhoomi
TI American Association of Oral and Maxillofacial Surgeons Position Paper
on Bisphosphonate-Related Osteonecrosis of the Jaws-2009 Update
SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY
LA English
DT Article
ID MULTIPLE-MYELOMA PATIENTS; PLACEBO-CONTROLLED TRIAL; BONE-MINERAL
DENSITY; LONG-TERM EFFICACY; ZOLEDRONIC ACID; RISK-FACTORS;
BREAST-CANCER; SKELETAL COMPLICATIONS; PREVENTIVE MEASURES; JAW
OSTEONECROSIS
AB Bisphosphonate-related osteonecrosis of the jaw (BRONJ) adversely affects the quality of life, producing significant morbidity in afflicted patients. Strategies for the treatment of patients with, or at risk of, BRONJ were set forth in the American Association of Oral and Maxillofacial Surgeons (AAOMS) Position Paper on Bisphsphonate-Related Osteonecrosis of the jaws (Position Paper) and approved by the Board of Trustees in September 2006.(1) The Position Paper was developed by a Task Force appointed by the Board and composed of clinicians with extensive experience in caring for these patients and basic science researchers. The knowledge base and experience in addressing BRONJ has expanded, necessitating modifications and refinements to the original Position Paper. The Task Force was reconvened in August 2008 to review the 2006 recommendations, appraise the current published data, and revise the Position Paper and recommendations, where indicated. This update contains revisions to the diagnosis and staging and management strategies and highlights the status of basic science research. AAOMS considers it vitally important that this information be disseminated to other dental and medical specialties.
C1 [Ruggiero, Salvatore L.] Long Isl Jewish Med Ctr, Div Oral & Maxillofacial Surg, Stony Brook Sch Dent Med, New Hyde Pk, NY 11042 USA.
[Ruggiero, Salvatore L.] New York Ctr Orthognath & Maxillofacial Surg, Lake Success, NY USA.
[Dodson, Thomas B.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Ctr Appl Clin Invest, Boston, MA 02114 USA.
[Dodson, Thomas B.] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA.
[Assael, Leon A.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Landesberg, Regina] Columbia Univ, Sch Dent & Oral Surg, Div Oral Maxillofacial Surg, New York, NY USA.
[Marx, Robert E.] Univ Miami, Sch Med, Div Oral & Maxillofacial Surg, Miami, FL USA.
[Mehrotra, Bhoomi] Long Isl Jewish Med Ctr, Div Med Oncol, New Hyde Pk, NY 11042 USA.
[Mehrotra, Bhoomi] Albert Einstein Coll Med, New Hyde Pk, NY USA.
RP Ruggiero, SL (reprint author), Long Isl Jewish Med Ctr, Div Oral & Maxillofacial Surg, Stony Brook Sch Dent Med, New Hyde Pk, NY 11042 USA.
EM drruggiero@nycoms.com
RI de la Flor, Maria/B-9212-2015
NR 62
TC 482
Z9 509
U1 4
U2 32
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
EI 1531-5053
J9 J ORAL MAXIL SURG
JI J. Oral Maxillofac. Surg.
PD MAY
PY 2009
VL 67
IS 5
SU 1
BP 2
EP 12
DI 10.1016/j.joms.2009.01.009
PG 11
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 439VH
UT WOS:000265655000002
PM 19371809
ER
PT J
AU Dodson, TB
AF Dodson, Thomas B.
TI Intravenous Bisphosphonate Therapy and Bisphosphonate-Related
Osteonecrosis of the Jaws
SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY
LA English
DT Article
ID MULTIPLE-MYELOMA PATIENTS; ZOLEDRONIC ACID; RISK-FACTORS; POSTMENOPAUSAL
OSTEOPOROSIS; CANCER-CHEMOTHERAPY; PREVENTIVE MEASURES; FREQUENCY;
IMPLEMENTATION; ASSOCIATION; EXPERIENCE
AB The purposes of this report are to 1) summarize the epidemiologic evidence supporting an association between intravenous bisphosphonate (BP) exposure and BP-related osteonecrosis of the jaws (BRONJ), 2) identify measurable risk factors associated with BRONJ, and 3) assess the risk of BRONJ for patients receiving intravenous BPs to manage osteoporosis. The results of this review suggest a compelling, circumstantial association between intravenous BP exposure and BRONJ. The factors consistently associated with an increased risk of BRONJ included intravenous BP exposure in the setting of malignancy and dentoalveolar procedures. Finally, intravenous BP therapy for osteoporosis does not measurably increase the risk of BRONJ among postmenopausal women. (C) 2009 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 67:44-52, 2009, Suppl 1
C1 [Dodson, Thomas B.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Ctr Appl Clin Invest, Boston, MA 02114 USA.
[Dodson, Thomas B.] Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA.
RP Dodson, TB (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Ctr Appl Clin Invest, 55 Fruit St,Warren 1201, Boston, MA 02114 USA.
EM tbdodson@partners.org
NR 31
TC 30
Z9 31
U1 0
U2 2
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0278-2391
J9 J ORAL MAXIL SURG
JI J. Oral Maxillofac. Surg.
PD MAY
PY 2009
VL 67
IS 5
BP 44
EP 52
DI 10.1016/j.joms.2008.12.004
PG 9
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 439VH
UT WOS:000265655000007
PM 19371814
ER
PT J
AU Susarla, SM
August, M
Dewsnup, N
Faquin, WC
Kaban, LB
Dodson, TB
AF Susarla, Srinivas M.
August, Meredith
Dewsnup, Nathan
Faquin, William C.
Kaban, Leonard B.
Dodson, Thomas B.
TI CD34 Staining Density Predicts Giant Cell Tumor Clinical Behavior
SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY
LA English
DT Article
ID FIBROBLAST-GROWTH-FACTOR; ANTIANGIOGENIC THERAPY; JAWS; GRANULOMA;
LESIONS
AB Purpose: To evaluate the staining density of CD34, a glycoprotein expressed in hematopoetic precursor and capillary endothelial cells, as a molecular marker for predicting clinical behavior of giant cell tumors.
Materials and Methods: This was a retrospective study of patients with giant cell lesions of the jaws treated over a 15-year period. The primary predictor variable was mean CD34 staining density. The outcome measure was giant cell tumor clinical behavior (aggressive vs nonaggressive). Bivariate analyses were computed to evaluate the association between the predictors and outcome. A receiver-operator characteristic (ROC) curve was used to establish the threshold for a positive diagnostic test. A logistic regression model was used to evaluate the association between the clinical behavior and a positive test. A value of P <= .05 was statistically significant.
Results: The study sample consisted of 32 subjects with a mean age of 24.4 +/- 19.8 years (range 2-83), including 23 females (71.8%), treated for giant cell lesions during the study period. The sample included 26 aggressive lesions and 6 nonaggressive lesions, with mean CD34 staining densities of 5.1 +/- 3.3% and 2.2 +/- 0.7%, respectively (P = .02). Using a CD34 staining level of equal to or more than 2.5% as indicative of a positive test, the sensitivity, specificity, positive and negative predictive values were 0.77, 0.83, 0.95 and 0.45, respectively. CD34 levels of more than 2.5% were significantly associated with aggressive lesions whereas CD 34 levels of less than 2.5% were associated with nonaggressive lesions (odds ratio: 16.7, P = .04).
Conclusions: CD34 staining density levels of more than 2.5% were associated with aggressive giant cell lesions. (C) 2009 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 67:951-956, 2009
C1 [Susarla, Srinivas M.; Kaban, Leonard B.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA.
[August, Meredith; Dewsnup, Nathan; Kaban, Leonard B.; Dodson, Thomas B.] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA.
[Faquin, William C.] Harvard Univ, Sch Med, Boston, MA USA.
[Dodson, Thomas B.] Massachusetts Gen Hosp, Ctr Appl Clin Invest, Boston, MA 02114 USA.
RP Susarla, SM (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, 55 Fruit St,Warren 1201, Boston, MA 02114 USA.
EM smsusarla@gmail.com
OI Susarla, Srinivas/0000-0003-0155-8260
FU Massachusetts General Hospital Department of Oral and Maxillofacial
Surgery Education and Research Fund; Oral and Maxillofacial Surgery
Foundation Fellowship in Clinical Investigation
FX This study was supported by the Massachusetts General Hospital
Department of Oral and Maxillofacial Surgery Education and Research Fund
(S.M.S., N.D.) and the Oral and Maxillofacial Surgery Foundation
Fellowship in Clinical Investigation (S.M.S.).
NR 15
TC 8
Z9 8
U1 0
U2 2
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0278-2391
J9 J ORAL MAXIL SURG
JI J. Oral Maxillofac. Surg.
PD MAY
PY 2009
VL 67
IS 5
BP 951
EP 956
DI 10.1016/j.joms.2008.12.045
PG 6
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 439VE
UT WOS:000265654700005
PM 19375002
ER
PT J
AU Kaban, LB
Seldin, EB
Kikinis, R
Yeshwant, K
Padwa, BL
Troulis, MJ
AF Kaban, Leonard B.
Seldin, Edward B.
Kikinis, Ron
Yeshwant, Krishna
Padwa, Bonnie L.
Troulis, Maria J.
TI Clinical Application of Curvilinear Distraction Osteogenesis for
Correction of Mandibular Deformities
SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY
LA English
DT Article
AB Purpose: To report the use of a semiburied curvilinear distraction device, with a 3-dimensional (3D) Computed tomography treatment planning system, for correction of mandibular deformities.
Materials and Methods: This was a retrospective evaluation of 13 consecutive patients, with syndromic and nonsyndromic micrognathia, who underwent correction by curvilinear distraction osteogenesis. A 3D computed tomography scan was obtained for each patient and imported into a 3D treatment planning system (Slicer/Osteoplan). Surgical guides were constructed to localize the osteotomy and to drill holes to secure the distractor's proximal and distal footplates to the mandible. Postoperatively, patients were followed by clinical examination and plain radiographs to ensure the desired vector of movement. At end distraction, when possible, a 3D computed tomography scan was obtained to document the final mandibular position.
Results: Of the 13 patients, 8 were females and 5 were males, with a mean age of 11.9 years (range 15 months to 39 years). All 13 underwent bilateral mandibular Curvilinear distraction. Of the 13 patients, 8 were 16 years old or younger and 5 were younger than 6 years of age. The diagnoses included Treacher Collins syndrome (n = 3), Nager syndrome (n = 3), craniofacial microsomia (n = 2), post-traumatic ankylosis (n = 1), and micrognathia (syndromic, n = 3; nonsyndromic, n = 1). The correct distractor placement, vector of movement, and final mandibular position were achieved in 10 of 13 patients. In the other 3 patients, the desired jaw position was achieved by "molding" the regenerate.
Conclusions: The use of a semiburied Curvilinear distraction device, with 3D treatment planning, is a potentially powerful tool to correct complex mandibular deformities. (C) 2009 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 67:996-1008, 2009
C1 [Kaban, Leonard B.] Harvard Univ, Massachusetts Gen Hosp, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA.
[Kikinis, Ron] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
[Kikinis, Ron; Yeshwant, Krishna] Harvard Surg Planning Lab, Boston, MA USA.
[Padwa, Bonnie L.] Harvard Univ, Childrens Hosp, Sch Dent Med, Boston, MA 02115 USA.
RP Kaban, LB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Dent Med, Dept Oral & Maxillofacial Surg, Warren 1201, Boston, MA 02114 USA.
EM LKaban@Partners.org
FU AO-ASIF Foundation (Berne, Switzerland); Synthes CMF (West Chester, PA);
Massachusetts General Hospital Center for Innovation and Minimally
Invasive Therapy in Medicine; Massachusetts General Hospital Department
of Oral and Maxillofacial Surgery Education and Research Fund; National
Institutes of Health [P41RR13218]
FX This work was supported by grants from the AO-ASIF Foundation (Berne,
Switzerland), Synthes CMF (West Chester, PA), the Massachusetts General
Hospital Center for Innovation and Minimally Invasive Therapy in
Medicine, the Massachusetts General Hospital Department of Oral and
Maxillofacial Surgery Education and Research Fund, and National
Institutes of Health grant P41RR13218 (R. Kikinis, principal
investigator).
NR 14
TC 28
Z9 30
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 0278-2391
J9 J ORAL MAXIL SURG
JI J. Oral Maxillofac. Surg.
PD MAY
PY 2009
VL 67
IS 5
BP 996
EP 1008
DI 10.1016/j.joms.2009.01.010
PG 13
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 439VE
UT WOS:000265654700012
PM 19375009
ER
PT J
AU Hosseini, A
Gill, TJ
Li, GA
AF Hosseini, Ali
Gill, Thomas J.
Li, Guoan
TI In vivo anterior cruciate ligament elongation in response to axial
tibial loads
SO JOURNAL OF ORTHOPAEDIC SCIENCE
LA English
DT Article
ID SITU FORCES; KNEE FLEXION; ANTEROMEDIAL BAND; JOINT KINEMATICS;
RECONSTRUCTION; STRAIN; BUNDLES; ACL; WEIGHTBEARING; TRANSLATION
AB The knowledge of in vivo anterior cruciate ligament (ACL) deformation is fundamental for understanding ACL injury mechanisms and for improving surgical reconstruction of the injured ACL. This study investigated the relative elongation of the ACL when the knee is subject to no load (< 10 N) and then to full body weight (axial tibial load) at various flexion angles using a combined dual fluoroscopic and magnetic resonance imaging (MRI) technique.
Nine healthy subjects were scanned with MRI and imaged when one knee was subject to no load and then to full body weight using a dual fluoroscopic system (0A degrees-45A degrees flexion angles). The ACL was analyzed using three models: a single central bundle; an anteromedial and posterolateral (double functional) bundle; and multiple (eight) surface fiber bundles.
The anteromedial bundle had a peak relative elongation of 4.4% +/- 3.4% at 30A degrees and that of the posterolateral bundle was 5.9% +/- 3.4% at 15A degrees. The ACL surface fiber bundles at the posterior portion of the ACL were shorter in length than those at the anterior portion. However, the peak relative elongation of one posterolateral fiber bundle reached more than 13% whereas one anteromedial fiber bundle reached a peak relative elongation of only about 3% at 30A degrees of flexion by increasing the axial tibial load from no load to full body weight.
The data quantitatively demonstrated that under external loading the ACL experiences nonhomogeneous elongation, with the posterior fiber bundles stretching more than the anterior fiber bundles.
C1 [Hosseini, Ali; Gill, Thomas J.; Li, Guoan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg,Bioengn Lab, Boston, MA 02114 USA.
[Hosseini, Ali] MIT, Dept Mech Engn, Cambridge, MA 02139 USA.
RP Li, GA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg,Bioengn Lab, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA.
FU NIH [R21AR051078]
FX This research was supported by NIH grant R21AR051078. The technical
assistance of Ramprasad Papannagari, Jeff Bingham, Dr. Samuel Van de
Velde, Dr. Louis E. DeFrate, Dr. Kyung Wook Nha, and Angela Moynihan is
greatly appreciated.
NR 30
TC 22
Z9 22
U1 1
U2 3
PU SPRINGER TOKYO
PI TOKYO
PA 1-11-11 KUDAN-KITA, CHIYODA-KU, TOKYO, 102-0073, JAPAN
SN 0949-2658
J9 J ORTHOP SCI
JI J. Orthop. Sci.
PD MAY
PY 2009
VL 14
IS 3
BP 298
EP 306
DI 10.1007/s00776-009-1325-z
PG 9
WC Orthopedics
SC Orthopedics
GA 458MV
UT WOS:000267029000010
PM 19499297
ER
PT J
AU Driscoll, DF
Ling, PR
Andersson, C
Bistrian, BR
AF Driscoll, David F.
Ling, Pei-Ra
Andersson, Charlotte
Bistrian, Bruce R.
TI Hepatic Indicators of Oxidative Stress and Tissue Damage Accompanied by
Systemic Inflammation in Rats Following a 24-Hour Infusion of an
Unstable Lipid Emulsion Admixture
SO JOURNAL OF PARENTERAL AND ENTERAL NUTRITION
LA English
DT Article; Proceedings Paper
CT 28th Congress of the
European-Society-of-Parenteral-and-Enteral-Nutrition
CY OCT, 2006
CL Istanbul, TURKEY
SP European Soc Parenteral & Enteral Nutr
DE large-diameter fat globules; stability; oxidative stress; hepatic
injury; systemic inflammatory response
ID CHAIN TRIGLYCERIDE EMULSIONS; TOTAL NUTRIENT ADMIXTURES;
RETICULOENDOTHELIAL SYSTEM; LONG-CHAIN; INJECTABLE EMULSIONS;
PATHOLOGICAL CONSEQUENCES; PARENTERAL-NUTRITION; STABILITY; HUMANS;
GLASS
AB Background: Use of lipid emulsions is parenteral nutrition therapy is an important source of daily energy in substitution of potentially harmful glucose calories when given in excess in the intensive care unit. When added to parenteral nutrition (PN) admixtures as a total nutrient admixture (TNA), the stability and safety of the emulsion may be compromised. Development of a rat model of a stable vs unstable lipid infusion would enable a study of the potential risk. Design: Prospective, randomized, controlled study. Methods: Surgical placement of a jugular venous catheter for the administration of TNAs was performed. Two groups were studied: a stable or s-TNA (n = 16) and an unstable or u-TNA (n = 17) as a 24-hour continuous infusion. Stability of TNAs was determined immediately before and after infusion using a laser-based method approved by the United States Pharmacopeia. Results: Blood levels of aspartate aminotransferase, glutathione-S-transferase, and C-reactive protein were significantly elevated in u-TNA vs s-TNA (P < .05). Also, liver tissue concentrations of malondialdehyde were significantly higher in the u-TNA group (P < .05), and triglyceride tissue levels were also higher in u-TNA and approached statistical significance (P = .077). Conclusions: Unstable lipid infusions over 24 hours produce evidence of hepatic accumulation of fat associated with oxidative stress, liver injury, and a low-level systemic inflammatory response. (JPEN J Parenter Enteral Nutr. 2009; 33; 327-335)
C1 [Driscoll, David F.] Harvard Univ, Sch Med, BIDMC, Boston, MA 02215 USA.
RP Driscoll, DF (reprint author), Harvard Univ, Sch Med, BIDMC, Baker Bldg,Suite 605, Boston, MA 02215 USA.
EM ddriscol@bidmc.harvard.edu
NR 27
TC 12
Z9 12
U1 0
U2 1
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0148-6071
J9 JPEN-PARENTER ENTER
JI J. Parenter. Enter. Nutr.
PD MAY-JUN
PY 2009
VL 33
IS 3
BP 327
EP 335
DI 10.1177/0148607108327155
PG 9
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 437RL
UT WOS:000265504500005
PM 19221047
ER
PT J
AU Nagao, K
Noel, LP
Noel, ME
Walton, DS
AF Nagao, Karina
Noel, Leon-Paul
Noel, Marie-Eve
Walton, David S.
TI The Spontaneous Resolution of Primary Congenital Glaucoma
SO JOURNAL OF PEDIATRIC OPHTHALMOLOGY & STRABISMUS
LA English
DT Article
CT 17th Annual Meeting of the American-Glaucoma-Society
CY MAR 01-04, 2007
CL San Francisco, CA
SP Amer Glaucoma Soc
ID IRIDOCORNEAL ANGLE
AB Purpose: To describe the ocular findings in a series of children with spontaneous resolution of primary congenital glaucoma (PCG).
Methods: The medical records of 356 patients with PCG were reviewed. Nine patients with spontaneous resolution of PCG were studied. Fourteen of 18 eyes possessed evidence of early glaucoma, were found to have normal intraocular pressures, and were clinically classified as having spontaneous resolution of PCG. None of the eyes with spontaneous resolution received surgery or any glaucoma medication.
Results: Spontaneous resolution of PCG in all nine patients was recognized after 4 months of age. At the time of diagnosis, large corneas were observed in all affected eyes and Haab's striae in 10 of 14 eyes. Intraocular pressures were normal in 14 eyes. In all 14 eyes, the anterior chambers were deep, the lenses were clear, and the angles were abnormal with the typical appearance of PCG. The eyes with spontaneous resolution of PCG possessed angle abnormalities that were less severe compared to three fellow eyes that required glaucoma treatments.
Conclusion: The occurrence of spontaneous resolution of PCG in these patients is supported by objective clinical evidence. The explanation for this spontaneous resolution is unknown. Its mechanism could be related to continued postnatal development of the angle structures in eyes possessing milder angle abnormalities. The anterior segment findings in patients with spontaneous resolution of PCG are similar to those of patients with treated PCG, the intraocular pressures are normal, the optic nerve damage is stable, and the filtration angles possess mild or moderate abnormalities.
C1 [Nagao, Karina] COE RIO, Rio De Janeiro, Brazil.
[Noel, Leon-Paul; Noel, Marie-Eve] SUNY Upstate Med Univ, Dept Ophthalmol, Syracuse, NY USA.
[Noel, Leon-Paul; Noel, Marie-Eve] SUNY Upstate Med Univ, Dept Pediat, Syracuse, NY USA.
[Walton, David S.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA.
RP Walton, DS (reprint author), 2 Longfellow Pl,Suite 201, Boston, MA 02114 USA.
NR 15
TC 8
Z9 9
U1 0
U2 0
PU SLACK INC
PI THOROFARE
PA 6900 GROVE RD, THOROFARE, NJ 08086 USA
SN 0191-3913
J9 J PEDIAT OPHTH STRAB
JI J. Pediatr. Ophthalmol. Strabismus.
PD MAY-JUN
PY 2009
VL 46
IS 3
BP 139
EP 143
DI 10.9999/01913913-20090505-04
PG 5
WC Ophthalmology; Pediatrics
SC Ophthalmology; Pediatrics
GA 444BR
UT WOS:000265955500003
PM 19496494
ER
PT J
AU Spencer, TJ
AF Spencer, Thomas J.
TI Issues in the Management of Patients with Complex ADHD Symptoms
SO JOURNAL OF PEDIATRICS
LA English
DT Article
ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT-HYPERACTIVITY
DISORDER; SUBSTANCE USE DISORDERS; OPPOSITIONAL DEFIANT DISORDER;
PLACEBO-CONTROLLED TRIAL; BIPOLAR DISORDER; CONDUCT DISORDER; MAJOR
DEPRESSION; ANTIPSYCHOTIC MEDICATIONS; METHYLPHENIDATE TREATMENT
AB Children and adolescents with attention deficit hyperactivity disorder (ADHD) have high levels of psychiatric comorbidity. The most common types of comorbidities include disruptive behavior, anxiety, and substance use disorders, as well as major depression. When comorbidities are present, impairments in school and family functioning tend to be more severe and persistent than in children who have ADHD alone. Comorbidities to ADHD are likely to go unrecognized in primary pediatric settings because clinicians may not routinely collect behavioral information, and parents are often reluctant to discuss their children's emotional problems with physicians. Although ADHD with a comorbid component is associated with poorer outcomes, many such patients can be treated successfully. Developing improved methods for the identification and appropriate treatment of comorbid conditions in children with ADHD must be a high clinical priority, because intervention can have a significant positive impact on patients' functioning and long-term outcomes. (J Pediatr 2009;154:S4-S12)
C1 [Spencer, Thomas J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA.
[Spencer, Thomas J.] Massachusetts Gen Hosp, Pediat Psychopharmacol Dept, Boston, MA 02114 USA.
RP Spencer, TJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 55 Fruit Street,Warren 705, Boston, MA 02114 USA.
EM tspencer@partners.org
NR 75
TC 1
Z9 1
U1 3
U2 4
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-3476
EI 1097-6833
J9 J PEDIATR-US
JI J. Pediatr.
PD MAY
PY 2009
VL 154
IS 5
SU S
BP S4
EP S12
DI 10.1016/j.jpeds.2009.01.016
PG 9
WC Pediatrics
SC Pediatrics
GA 437QF
UT WOS:000265501300002
ER
PT J
AU Menkens, AJ
Amelio, RC
AF Menkens, Anne J.
Amelio, Robert C.
TI Leaders and Organizations in Transition
SO JOURNAL OF PUBLIC HEALTH MANAGEMENT AND PRACTICE
LA English
DT Editorial Material
C1 [Menkens, Anne J.] Univ N Carolina, Sch Publ Hlth, N Carolina Inst Publ Hlth, Div Execut Educ, Chapel Hill, NC 27599 USA.
[Amelio, Robert C.] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Menkens, AJ (reprint author), Univ N Carolina, Sch Publ Hlth, N Carolina Inst Publ Hlth, Div Execut Educ, CB 8165, Chapel Hill, NC 27599 USA.
NR 3
TC 2
Z9 2
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1078-4659
J9 J PUBLIC HEALTH MAN
JI J. Public Health Manag. Pract.
PD MAY-JUN
PY 2009
VL 15
IS 3
BP 274
EP 277
PG 4
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 434GE
UT WOS:000265262400014
PM 19363408
ER
PT J
AU Sloan, PA
Berman, ME
Zeigler-Hill, V
Bullock, JS
AF Sloan, Paul A.
Berman, Mitchell E.
Zeigler-Hill, Virgil
Bullock, Joshua S.
TI GROUP INFLUENCES ON SELF-AGGRESSION: CONFORMITY AND DISSENTER EFFECTS
SO JOURNAL OF SOCIAL AND CLINICAL PSYCHOLOGY
LA English
DT Article
ID IDENTITY MISCLASSIFICATION; SOCIAL-INFLUENCE; DRINKING NORMS; GROUP
PRESSURE; ALCOHOL-USE; BEHAVIOR; MUTILATION; CONTAGION; SUICIDE;
DETERMINANTS
AB Evidence that intentional self-aggressive behaviors are influenced by social groups comes almost exclusively from nonexperimental retrospective studies which fail to address underlying causal processes. Recently, we conducted a study in which experimentally manipulated group norms were found to directly influence self-aggressive behavior (Sloan, Berman, Zeigler-Hill, Greer, & Mae, 2006). The present study was designed to gain a better understanding of the process by which social groups influence self-aggression. More specifically, we examined the effects of dissenters on the adoption of a self-aggressive group norm. Participants (N = 164) were assigned to one of the following conditions: a unanimous self-aggressive group, a nonunanimous group with a single dissenter in either the first or last position who did not engage in self-aggressive behavior, and a group with no systematic agreement concerning self-aggression. Self-aggression was operationally defined as the use of an extreme shock that was self-administered by the participant within the context of an attention task. Results demonstrated that the adoption of a self-aggressive group norm was significantly weakened by the presence of a dissenter. This effect was moderated by gender such that the presence of a dissenter had a greater impact on the self-aggressive behavior of women than it did for men. Clinical and theoretical implications of these findings are discussed.
C1 [Sloan, Paul A.] Michael E DeBakey Vet Affairs Med Ctr, Mental Hlth Care Line 116 CMHP, Houston, TX 77030 USA.
[Sloan, Paul A.] Baylor Coll Med, Houston, TX 77030 USA.
[Berman, Mitchell E.; Zeigler-Hill, Virgil; Bullock, Joshua S.] Univ So Mississippi, Hattiesburg, MS 39406 USA.
RP Sloan, PA (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Mental Hlth Care Line 116 CMHP, 2002 Holcombe Blvd, Houston, TX 77030 USA.
EM paul.sloan@va.gov
NR 64
TC 3
Z9 3
U1 1
U2 5
PU GUILFORD PUBLICATIONS INC
PI NEW YORK
PA 72 SPRING STREET, NEW YORK, NY 10012 USA
SN 0736-7236
J9 J SOC CLIN PSYCHOL
JI J. Soc. Clin. Psychol.
PD MAY
PY 2009
VL 28
IS 5
BP 535
EP 553
PG 19
WC Psychology, Clinical; Psychology, Social
SC Psychology
GA 453KX
UT WOS:000266610400001
ER
PT J
AU Lee, MLT
Whitmore, GA
Laden, F
Hart, JE
Garshick, E
AF Lee, Mei-Ling Ting
Whitmore, G. A.
Laden, Francine
Hart, Jaime E.
Garshick, Eric
TI A case-control study relating railroad worker mortality to diesel
exhaust exposure using a threshold regression model
SO JOURNAL OF STATISTICAL PLANNING AND INFERENCE
LA English
DT Article
CT Conference on Degradation, Damage, Fatigue and Accelerated Life Models
in Reliability Testing
CY MAY 22-24, 2006
CL Angers, FRANCE
DE Biostatistics; Cardiovascular disease; Death; Disease progression;
Environmetrics; Epidemiology; Exposure risk; First hitting time; Health
status; Healthy worker effect; Kaplan-Meier plot; Latent process; Lung
cancer; Occupational health; Stochastic process; Survival analysis;
Wiener process; Work environment
ID LUNG-CANCER; TIME MODELS; DISEASE; DRIVERS; DENMARK
AB A case-control study of lung cancer mortality in U.S. railroad workers in jobs with and without diesel exhaust exposure is reanalyzed using a new threshold regression methodology. The Study included 1256 workers who died of lung cancer and 2385 controls who died primarily of circulatory system diseases. Diesel exhaust exposure was assessed using railroad job history from the US Railroad Retirement Board and an industrial hygiene survey. Smoking habits were available from next-of-kin and potential asbestos exposure was assessed by job history review. The new analysis reassesses lung cancer mortality and examines circulatory system disease mortality. jobs with regular exposure to diesel exhaust had a survival pattern characterized by an initial delay in mortality, followed by a rapid deterioration of health prior to death. The pattern is seen in subjects dying of lung cancer, circulatory system diseases, and other causes. The unique pattern is illustrated using a new type of Kaplan-Meier survival plot in which the time scale represents a measure of disease progression rather than calendar time. The disease progression scale accounts for a healthy-worker effect when describing the effects of cumulative exposures on mortality. (C) 2008 Elsevier B.V. All rights reserved.
C1 [Lee, Mei-Ling Ting] Ohio State Univ, Coll Publ Hlth, Div Biostat, Columbus, OH 43210 USA.
[Whitmore, G. A.] McGill Univ, Desautels Fac Management, Montreal, PQ, Canada.
[Garshick, Eric] VA Boston Healthcare Syst, Med Serv, Pulm & Crit Care Med Sect, Boston, MA USA.
[Laden, Francine; Hart, Jaime E.; Garshick, Eric] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Lab, Boston, MA 02115 USA.
[Laden, Francine; Hart, Jaime E.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Epidemiol & Risk Program, Boston, MA 02115 USA.
[Laden, Francine] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
RP Lee, MLT (reprint author), Ohio State Univ, Coll Publ Hlth, Div Biostat, Columbus, OH 43210 USA.
EM meilinglee@cph.osu.edu
FU NCI NIH HHS [R01 CA079725, R01 CA079725-03]; NIOSH CDC HHS [R01
OH008649]
NR 21
TC 11
Z9 12
U1 4
U2 11
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0378-3758
J9 J STAT PLAN INFER
JI J. Stat. Plan. Infer.
PD MAY 1
PY 2009
VL 139
IS 5
BP 1633
EP 1642
DI 10.1016/j.jspi.2008.05.023
PG 10
WC Statistics & Probability
SC Mathematics
GA 418JD
UT WOS:000264143600006
PM 19221608
ER
PT J
AU Antonacci, AC
Lam, S
Lavarias, V
Homel, P
Eavey, RA
AF Antonacci, Anthony C.
Lam, Steven
Lavarias, Valentina
Homel, Peter
Eavey, Roland A.
TI A Report Card System Using Error Profile Analysis and Concurrent
Morbidity and Mortality Review: Surgical Outcome Analysis, Part II
SO JOURNAL OF SURGICAL RESEARCH
LA English
DT Review
DE error analysis; gross mortality; morbidity; report cards; surgical
outcome
ID QUALITY
AB Background. An effective report card system for adverse outcome error analysis following surgery is lacking. We hypothesized that a memorialized database could be used in conjunction with error analysis and management evaluation at Morbidity & Mortality conference to generate individualized report cards for Attending Surgeon and System performance.
Study Design. Prospectively collected data from September 2000 through April 2005 were reported following Morbidity & Mortality review on 1618 adverse outcomes, including :219 deaths, following 29,237 operative procedures, in a complete loop to approximately 60 individual surgeons and responsible system personnel.
Results. A 40% reduction of gross mortality (P<0.001) and 430% reduction of age-adjusted mortality were achieved over 4 years at the Academic Center. Quality issues were identified at a rate three times greater than required by New York State regulations and increased from a baseline 4.96% to 32.7% (odds ratio 1.94; P<0.03) irk cases associated with mortality. A detailed review demonstrated a significant increase (P<0.001) in system errors and physician-related diagnostic and judgment errors associated with mortality highlighted those practices and processes involved, and contrasted the results between academic (43% mortality improvement) and community (no improvement) hospitals.
Conclusions. The findings suggest that structured concurrent data collection combined with non-punitive error-based case review and individualized report cards can be used to provide detailed feedback on surgical performance to individual surgeons and possibly improve clinical outcomes. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Antonacci, Anthony C.] Cornell Univ, Weill Med Coll, New York, NY 10021 USA.
[Antonacci, Anthony C.] Christ Hosp, Jersey City, NJ USA.
[Antonacci, Anthony C.; Lam, Steven; Lavarias, Valentina] Lenox Hill Hosp, New York, NY 10021 USA.
[Antonacci, Anthony C.; Homel, Peter] Beth Israel Deaconess Med Ctr, New York, NY 10003 USA.
[Eavey, Roland A.] Harvard Univ, Sch Med, Dept Otol & Laryngol,Pediat Otolaryngol Serv, Massachusetts Eye & Ear Infirm,Dept Otolaryngol, Boston, MA 02115 USA.
RP Antonacci, AC (reprint author), Cornell Univ, Weill Med Coll, Dept Surg, 55 North St, Greenwich, CT 06830 USA.
EM aantonacci@gmail.com
NR 10
TC 15
Z9 15
U1 0
U2 2
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0022-4804
J9 J SURG RES
JI J. Surg. Res.
PD MAY 1
PY 2009
VL 153
IS 1
BP 95
EP 104
DI 10.1016/j.jss.2008.02.051
PG 10
WC Surgery
SC Surgery
GA 434FC
UT WOS:000265259600013
PM 18511079
ER
PT J
AU Saunders, GH
Lewis, MS
Forsline, A
AF Saunders, Gabrielle H.
Lewis, M. Samantha
Forsline, Anna
TI Expectations, Prefitting Counseling, and Hearing Aid Outcome
SO JOURNAL OF THE AMERICAN ACADEMY OF AUDIOLOGY
LA English
DT Article; Proceedings Paper
CT International Hearing Aid Research Conference
CY 2008
CL Lake Tahoe, CA
DE Counseling; expectations; hearing aids; outcome
ID AUDIOLOGICAL REHABILITATION; AMPLIFICATION; BENEFIT; ADULTS; ATTITUDES;
HANDICAP; SCALE; USERS
AB Background: Data suggest that having high expectations about hearing aids results in better overall outcome. However, some have postulated that excessively high expectations will result in disappointment and thus poor outcome. It has been suggested that counseling patients with unrealistic expectations about hearing aids prior to fitting may be beneficial. Data, however, are mixed as to the effectiveness of such counseling, in terms of both changes in expectations and final outcome.
Purpose: The primary purpose of this study was to determine whether supplementing prefitting counseling with demonstration of real-world listening can (1) alter expectations of new hearing aid users and (2) increase satisfaction over verbal-only counseling. Secondary goals of the study were to examine (1) the relationship between prefitting expectations and postfitting outcome, and (2) the effect of hearing aid fine-tuning on hearing aid outcome.
Research Design: Sixty new hearing aid users were fitted binaurally with Beltone Oria behind-the-ear digital hearing aids. Forty participants received prefitting counseling and demonstration of listening situations with the Beltone AVE (TM) (Audio Verification Environment) system; 20 received prefitting counseling without a demonstration of listening situations. Hearing aid expectations were measured at initial contact and following prefitting counseling. Reported hearing aid outcome was measured after eight to ten weeks of hearing aid use.
Study Sample: Sixty new hearing aid users aged between 55 and 81 years with symmetrical sensorineural hearing loss.
Intervention: Participants were randomly assigned to one of three experimental groups, between which the prefitting counseling and follow-up differed: Group 1 received prefitting counseling in combination with demonstration of listening situations. Additionally, if the participant had complaints about sound quality at the follow-up visit, the hearing aids were fine-tuned using the Beltone AVE system. Group 2 received prefitting counseling in combination with demonstration of listening situations with the Beltone AVE system, but no fine-tuning was provided at follow-up. Group 3 received prefitting hearing aid counseling that did not include demonstration of listening, and the hearing aids were not fine-tuned at the follow-up appointment.
Results: The results showed that prefitting hearing aid counseling had small but significant effects on expectations. The two forms of counseling did not differ in their effectiveness at changing expectations; however, anecdotally, we learned from many participants that that they enjoyed listening to the auditory demonstrations and that they found them to be an interesting listening exercise. The data also show that positive expectations result in more positive outcome and that hearing aid fine-tuning is beneficial to the user.
Conclusions: We conclude that prefitting counseling can be advantageous to hearing aid outcome and recommend the addition of prefitting counseling to address expectations associated with quality of life and self-image. The data emphasize the need to address unrealistic expectations prior to fitting hearing aids cautiously, so as not to decrease expectations to the extent of discouraging and demotivating the patient. Data also show that positive expectations regarding the impact hearing aids will have on psychosocial well-being are important for successful hearing aid outcome.
C1 [Saunders, Gabrielle H.] Portland VA Med Ctr, NCRAR, Portland, OR 97207 USA.
[Saunders, Gabrielle H.; Lewis, M. Samantha] Oregon Hlth & Sci Univ, Dept Otolaryngol Head & Neck Surg, Portland, OR 97201 USA.
[Forsline, Anna] Portland VA Med Ctr, Audiol & Speech Pathol Serv, Portland, OR 97207 USA.
RP Saunders, GH (reprint author), Portland VA Med Ctr, NCRAR, 3710 SW US Vet Hosp Rd, Portland, OR 97207 USA.
EM Gabrielle.Saunders@va.gov
NR 46
TC 20
Z9 22
U1 8
U2 26
PU AMER ACAD AUDIOLOGY
PI RESTON
PA 11730 PLAZA DR, STE 300, RESTON, VA 20190 USA
SN 1050-0545
J9 J AM ACAD AUDIOL
JI J. Am. Acad. Audiol.
PD MAY
PY 2009
VL 20
IS 5
BP 320
EP 334
DI 10.3766/jaaa.20.5.6
PG 15
WC Audiology & Speech-Language Pathology; Otorhinolaryngology
SC Audiology & Speech-Language Pathology; Otorhinolaryngology
GA 462DE
UT WOS:000267325400006
PM 19585963
ER
PT J
AU Wagner, KD
Redden, L
Kowatch, RA
Wilens, TE
Segal, S
Chang, K
Wozniak, P
Vigna, NV
Abi-Saab, W
Saltarelli, M
AF Wagner, Karen Dineen
Redden, Laura
Kowatch, Robert A.
Wilens, Timothy E.
Segal, Scott
Chang, Kiki
Wozniak, Patricia
Vigna, Namita V.
Abi-Saab, Walid
Saltarelli, Mario
TI A Double-Blind, Randomized, Placebo-Controlled Trial of Divalproex
Extended-Release in the Treatment of Bipolar Disorder in Children and
Adolescents
SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY
LA English
DT Article
DE bipolar disorder; divalproex ER; treatment
ID VALPROATE-ASSOCIATED COAGULOPATHIES; WASH-U-KSADS; RATING-SCALE; MOOD
STABILIZERS; ACUTE MANIA; LITHIUM; SODIUM; COMBINATION; RELIABILITY;
VALIDITY
AB Objective: To compare the efficacy and safety of divalproex extended-release (ER) to placebo in a 28-day double-blind study of bipolar disorder in children and adolescents and evaluate the safety of divalproex ER in a 6-month open-label extension study. Method: In the double-blind study, 150 patients (manic or mixed episode, aged 10-17 years) with baseline Young Mania Rating Scale (YMRS) score of 20 or higher were randomized to once-daily placebo or divalproex ER, which was titrated to clinical response or serum valproate concentration of 80 to 125 mu g/mL. Sixty-six patients enrolled in the extension study. Results: In the double-blind study, a treatment effect was not observed with divalproex ER based on change in mean YMRS score (divalproex ER -8.8 [n=74]; placebo -7.9 [n= 70]) or secondary measures. Divalproex was similar to placebo based on incidence of adverse events. Four subjects treated with divalproex ER and three treated with placebo discontinued because of adverse events. Mean ammonia levels increased in the divalproex ER group, but only one patient was symptomatic. In the long-term study, YMRS scores decreased modestly (2.2 points from baseline). The most common adverse events were headache and vomiting. Conclusions: The results of the study do not provide support for the use of divalproex ER in the treatment of youths with bipolar I disorder, mixed or manic state. Further controlled trials are required to confirm or refute the findings from this study. J. Am. Acad. Child Adolesc. Psychiatry, 2009;48(5):519-532.
C1 [Redden, Laura; Vigna, Namita V.; Abi-Saab, Walid; Saltarelli, Mario] Abbott Labs, Abbott Pk, IL 60064 USA.
[Kowatch, Robert A.] Univ Cincinnati, Med Ctr, Cincinnati, OH 45221 USA.
[Wilens, Timothy E.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Chang, Kiki] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
RP Wagner, KD (reprint author), Dept Psychiat & Behav Sci, 301 Univ Blvd, Galveston, TX 77555 USA.
EM kwagner@utmb.edu
FU Abbott Laboratories
FX This study was supported by a grant from Abbott Laboratories.
NR 52
TC 52
Z9 52
U1 1
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0890-8567
J9 J AM ACAD CHILD PSY
JI J. Am. Acad. Child Adolesc. Psychiatr.
PD MAY
PY 2009
VL 48
IS 5
BP 519
EP 532
DI 10.1097/CHI.0b013e31819c55ec
PG 14
WC Psychology, Developmental; Pediatrics; Psychiatry
SC Psychology; Pediatrics; Psychiatry
GA 437BO
UT WOS:000265461000009
PM 19325497
ER
PT J
AU Magro, CM
Yaniv, S
Mihm, MC
AF Magro, Cynthia M.
Yaniv, Shimrat
Mihm, Martin C.
TI The superficial atypical Spitz tumor and malignant melanoma of
superficial spreading type arising in association with the superficial
atypical Spitz tumor: A distinct form of dysplastic Spitzoid
nevomelanocytic proliferation
SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
LA English
DT Article
ID LYMPH-NODE BIOPSY; MELANOCYTIC LESIONS; DIFFERENTIAL-DIAGNOSIS; CELL
NEVUS; MUTATIONS; BRAF; VARIANTS; FEATURES; SPINDLE; RAS
AB Spitzoid lesions are diagnostically problematic because of it deceptive morphology and indeterminate behavior. The most problematic are atypical Spitz tumors whereby distinction from melanoma may be difficult. We have recognized it melanocytic lesion with a reproducible histomorphology, demonstrating characteristic demographic features, namely a predilection to involve younger female patients and common occurrence on the thigh. We have designated this lesion as the superficial atypical Spitz tumor and have encountered 27 cases. We believe that these lesions overlap histomorphologically with higher-grade dysplastic nevi and de novo intraepidermal epitheloid melanocytic dysplasia. We identified 19 additional cases that appear to represent transition into malignant melanoma of superficial spreading type arising in a background of the superficial atypical Spitz tumor. A limitation is that complete medical histories were not obtained for all patients. In conclusion, there exists a distinct subset of Spitz tumors that we designate as the superficial atypical Spitz tumor in which there is inherent dysplasia including lesions that evolve into melanoma of superficial spreading type. (J Am Acad Dermatol 2009-160:8.14-23.)
C1 [Magro, Cynthia M.] Cornell Univ, Weill Med Coll, Dept Pathol & Lab Med, Div Dermatopathol, New York, NY 10021 USA.
[Yaniv, Shimrat] Albert Einstein Coll Med, New York, NY USA.
[Mihm, Martin C.] Massachusetts Gen Hosp, Dept Dermatopathol, Boston, MA 02114 USA.
[Mihm, Martin C.] Harvard Univ, Sch Med, Boston, MA USA.
RP Magro, CM (reprint author), Weill Cornell Med Coll, Dept Dermatopathol, 1300 York Ave,F-309, New York, NY 10021 USA.
EM cym2003@med.cornell.edu
NR 22
TC 15
Z9 15
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0190-9622
J9 J AM ACAD DERMATOL
JI J. Am. Acad. Dermatol.
PD MAY
PY 2009
VL 60
IS 5
BP 814
EP 823
DI 10.1016/j.jaad.2008.10.040
PG 10
WC Dermatology
SC Dermatology
GA 438AW
UT WOS:000265529300012
PM 19389523
ER
PT J
AU Lorenz, KA
Sherbourne, CD
Shugarman, LR
Rubenstein, LV
Wen, L
Cohen, A
Goebel, JR
Hagenmeier, E
Simon, B
Lanto, A
Asch, SM
AF Lorenz, Karl A.
Sherbourne, Cathy D.
Shugarman, Lisa R.
Rubenstein, Lisa V.
Wen, Li
Cohen, Angela
Goebel, Joy R.
Hagenmeier, Emily
Simon, Barbara
Lanto, Andy
Asch, Steven M.
TI How Reliable is Pain as the Fifth Vital Sign?
SO JOURNAL OF THE AMERICAN BOARD OF FAMILY MEDICINE
LA English
DT Article
ID CANCER PAIN; ACCURACY; MODERATE; QUALITY; MILD; CARE; CUTPOINTS;
COMMUNITY; SEVERITY; VALIDITY
AB Background: Although many health care organizations require routine pain screening (eg, "5th vital sign") with the 0 to 10 numeric rating scale (NRS), its accuracy has been questioned; here we evaluated its accuracy and potential causes for error.
Methods: We randomly surveyed veterans and reviewed their charts after outpatient encounters at 2 hospitals and 6 affiliated community sites. Using correlation and receiver operating characteristic analysis, we compared the routinely measured "5th vital sign" (nurse-recorded NRS) with a research-administered NRS (research-recorded NRS) and the Brief Pain Inventory (BPI).
Results: During 528 encounters, nurse-recorded NRS and research-recorded NRS correlated moderately (r = 0.627), as did nurse-recorded NRS and BPI severity scales (r = 0.613 for pain during the last 24 hours and r = 0.588 for pain during the past week). Correlation with BPI interference was lower (r = 0.409). However, the research-recorded NRS correlated substantially with the BPI severity during the past 24 hours (r = 0.870) and BPI severity during the last week (r = 0.840). Receiver operating characteristic analysis showed similar results. Of the 98% of cases where a numeric score was recorded, 51% of patients reported their pain was rated qualitatively, rather than with a 0 to 10 scale, a practice associated with pain underestimation (chi(2) = 64.04, P < .001).
Conclusion: Though moderately accurate, the outpatient "5th vital sign" is less accurate than under ideal circumstances. Personalizing assessment is a common clinical practice but may affect the performance of research tools such as the NRS adopted for routine use. (J Am Board Fam Med 2009;22:291-8.)
C1 [Lorenz, Karl A.; Rubenstein, Lisa V.; Cohen, Angela; Hagenmeier, Emily; Simon, Barbara; Lanto, Andy; Asch, Steven M.] Vet Adm Greater Angeles Healthcare Syst, Los Angeles, CA 90064 USA.
[Lorenz, Karl A.; Sherbourne, Cathy D.; Shugarman, Lisa R.; Rubenstein, Lisa V.; Asch, Steven M.] RAND Corp, Santa Monica, CA USA.
[Lorenz, Karl A.; Rubenstein, Lisa V.; Asch, Steven M.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Goebel, Joy R.] Calif State Univ Long Beach, Dept Nursing, Long Beach, CA 90840 USA.
RP Lorenz, KA (reprint author), Vet Adm Greater Angeles Healthcare Syst, 11301 Wilshire Blvd,Code 111-G, Los Angeles, CA 90064 USA.
EM karl.lorenz@med.va.gov
OI Cohen, Angela B./0000-0002-0620-1909
FU Veterans Administration Health Services Research and Development IIR
[03-150]
FX Veterans Administration Health Services Research and Development IIR
03-150.
NR 23
TC 42
Z9 45
U1 1
U2 10
PU AMER BOARD FAMILY MEDICINE
PI LEXINGTON
PA 2228 YOUNG DR, LEXINGTON, KY 40505 USA
SN 1557-2625
J9 J AM BOARD FAM MED
JI J. Am. Board Fam. Med.
PD MAY-JUN
PY 2009
VL 22
IS 3
BP 291
EP 298
DI 10.3122/jabfm.2009.03.080162
PG 8
WC Primary Health Care; Medicine, General & Internal
SC General & Internal Medicine
GA 443VR
UT WOS:000265939400010
PM 19429735
ER
PT J
AU Olson, JA
Budd, GT
Carey, LA
Harris, LA
Esserman, LJ
Fleming, GF
Marcom, PK
Leight, GS
Giuntoli, T
Commean, P
Bae, K
Luo, JQ
Ellis, MJ
AF Olson, John A., Jr.
Budd, G. Thomas
Carey, Lisa A.
Harris, Lyndsay A.
Esserman, Laura J.
Fleming, Gini F.
Marcom, Paul K.
Leight, George S., Jr.
Giuntoli, Therese
Commean, Paul
Bae, Kyongtae
Luo, Jingqin
Ellis, Matthew J.
TI Improved Surgical Outcomes for Breast Cancer Patients Receiving
Neoadjuvant Aromatase Inhibitor Therapy: Results from a Multicenter
Phase II Trial
SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS
LA English
DT Article; Proceedings Paper
CT 120th Annual Meeting of the Southern-Surgical-Association
CY DEC, 2008
CL Palm Beach, FL
SP SE Surg Assoc
ID DOUBLE-BLIND; PREOPERATIVE TREATMENT; POSTMENOPAUSAL WOMEN; ADJUVANT
TREATMENT; ENDOCRINE THERAPY; CHEMOTHERAPY; TAMOXIFEN; ANASTROZOLE;
ARIMIDEX; MAMMOGRAPHY
AB BACKGROUND: Neoadjuvant aromatase Inhibitor therapy has been reported to improve Surgical Outcomes for postmenopausal women with clinical stage II or III hormone receptor-positive breast cancer. A multicenter phase II clinical trial was conducted to investigate the value of this approach for US surgical practice.
STUDY DESIGN: One hundred fifteen postmenopausal women with >2 cm, estrogen receptor (ER) or progesterone receptor (PgR)-positive breast cancer were enrolled in a trial of 16 to 24 weeks of letrozole 2.5 mg daily before operation.
RESULTS: One hundred six patients were eligible for primary analysis, 96 underwent operations, 7 received chemotherapy after progressive disease, and 3 did not undergo an operation. Baseline Surgical status was marginal for breast-conserving surgery (BCS) in 48 (450/8), 47 were definitely ineligible for BCS (44%), and 11 were Inoperable by standard mastectomy (10%). Overall Response Evaluation Criteria In Solid Tumors clinical response rate in the breast was 62%, with 12% experiencing progressive disease. Fifty percent underwent BCS, including 30 of 46 (65%) patients who were initially marginal for BCS and 15 of 39 (38%) patients who were Initially ineligible for BCS. All 11 inoperable patients successfully underwent operations, including 3 (27%) who had BCS. Nineteen percent of patients undergoing mastecromy had a pathologic T1 tumor, Suggesting that some highly responsive tumors were overtreated surgically.
CONCLUSIONS: Neoadjuvant aromatase inhibitor improves operability and facilitates BCS, but there was considerable variability in responsiveness. Better techniques to predict response, determine residual tumor burden before operation, and greater willingness to attempt BCS in responsive patients Could additionally improve the rate of successful BCS. (J Am Coll Surg 2009;208:906-916. 9 2009 by the American College Of Surgeons)
C1 [Giuntoli, Therese; Ellis, Matthew J.] Washington Univ, Siteman Canc Ctr, Sch Med, Dept Med,Div Oncol, St Louis, MO 63110 USA.
[Olson, John A., Jr.; Leight, George S., Jr.] Duke Univ, Med Ctr, Duke Comprehens Canc Ctr, Dept Surg, Durham, NC 27710 USA.
[Marcom, Paul K.] Duke Univ, Med Ctr, Duke Comprehens Canc Ctr, Dept Med, Durham, NC 27710 USA.
[Harris, Lyndsay A.] Dana Farber Canc Ctr, Boston, MA USA.
[Budd, G. Thomas] Cleveland Clin, Taussig Canc Ctr, Cleveland, OH 44106 USA.
[Carey, Lisa A.] Univ N Carolina, Lineberger Canc Ctr, Durham, NC USA.
[Esserman, Laura J.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Esserman, Laura J.] Helen Dillcr Family Comprehens Canc Ctr, San Francisco, CA USA.
[Fleming, Gini F.] Univ Chicago, Canc Res Ctr, Chicago, IL 60637 USA.
[Commean, Paul; Bae, Kyongtae] Washington Univ, Mallinckrodt Inst Radiol, Sch Med, St Louis, MO 63110 USA.
[Luo, Jingqin] Washington Univ, Dept Biostat, Sch Med, St Louis, MO 63110 USA.
RP Ellis, MJ (reprint author), Washington Univ, Siteman Canc Ctr, Sch Med, Dept Med,Div Oncol, Campus Box 8056,660 S Euclid Ave, St Louis, MO 63110 USA.
EM mellis@dom.wustl.edu
FU NCI NIH HHS [3P50 CA68438-07S2, P50 CA068438, R01 CA095614]; NIGMS NIH
HHS [U19 GM061388]
NR 20
TC 31
Z9 31
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1072-7515
J9 J AM COLL SURGEONS
JI J. Am. Coll. Surg.
PD MAY
PY 2009
VL 208
IS 5
BP 906
EP 914
DI 10.1016/j.jamcollsurg.2009.01.035
PG 9
WC Surgery
SC Surgery
GA 441WP
UT WOS:000265801500050
PM 19476859
ER
PT J
AU Bloom, HG
Ahmed, I
Alessi, CA
Ancoli-Israel, S
Buysse, DJ
Kryger, MH
Phillips, BA
Thorpy, MJ
Vitiello, MV
Zee, PC
AF Bloom, Harrison G.
Ahmed, Imran
Alessi, Cathy A.
Ancoli-Israel, Sonia
Buysse, Daniel J.
Kryger, Meir H.
Phillips, Barbara A.
Thorpy, Michael J.
Vitiello, Michael V.
Zee, Phyllis C.
TI Evidence-Based Recommendations for the Assessment and Management of
Sleep Disorders in Older Persons
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Review
ID RESTLESS-LEGS-SYNDROME; NURSING-HOME RESIDENTS; POSITIVE AIRWAY
PRESSURE; EXCESSIVE DAYTIME SLEEPINESS; BRIGHT-LIGHT THERAPY;
QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIAL; PERIODIC LIMB MOVEMENTS;
COMMUNITY-DWELLING ADULTS; CHEYNE-STOKES RESPIRATION
AB Sleep-related disorders are most prevalent in the older adult population. A high prevalence of medical and psychosocial comorbidities and the frequent use of multiple medications, rather than aging per se, are major reasons for this. A major concern, often underappreciated and underaddressed by clinicians, is the strong bidirectional relationship between sleep disorders and serious medical problems in older adults. Hypertension, depression, cardiovascular disease, and cerebrovascular disease are examples of diseases that are more likely to develop in individuals with sleep disorders. Conversely, individuals with any of these diseases are at a higher risk of developing sleep disorders. The goals of this article are to help guide clinicians in their general understanding of sleep problems in older persons, examine specific sleep disorders that occur in older persons, and suggest evidence- and expert-based recommendations for the assessment and treatment of sleep disorders in older persons. No such recommendations are available to help clinicians in their daily patient care practices. The four sections in the beginning of the article are titled, Background and Significance, General Review of Sleep, Recommendations Development, and General Approach to Detecting Sleep Disorders in an Ambulatory Setting. These are followed by overviews of specific sleep disorders: Insomnia, Sleep Apnea, Restless Legs Syndrome, Circadian Rhythm Sleep Disorders, Parasomnias, Hypersomnias, and Sleep Disorders in Long-Term Care Settings. Evidence- and expert-based recommendations, developed by a group of sleep and clinical experts, are presented after each sleep disorder.
C1 [Bloom, Harrison G.] Int Longev Ctr USA, New York, NY 10028 USA.
[Bloom, Harrison G.] Mt Sinai Sch Med, Brookdale Dept Geriatr & Adult Dev, New York, NY USA.
[Ahmed, Imran; Vitiello, Michael V.] Albert Einstein Coll Med, New York, NY USA.
[Alessi, Cathy A.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Alessi, Cathy A.] Vet Affairs Greater Los Angeles Healthcare Syst, Ctr Geriatr Res Educ & Clin, Los Angeles, CA USA.
[Ancoli-Israel, Sonia] Univ Calif San Diego, Sch Med, San Diego, CA 92103 USA.
[Buysse, Daniel J.] Univ Pittsburgh, Sch Med, Neurosci Clin & Translat Ctr, Pittsburgh, PA USA.
[Kryger, Meir H.] Gaylord Hosp, Gaylord Sleep Ctr, Wallingford, CT USA.
[Kryger, Meir H.] Univ Connecticut, Sch Med, Dept Med, Farmington, CT USA.
[Phillips, Barbara A.] Natl Sleep Fdn, Washington, DC USA.
[Phillips, Barbara A.] Univ Kentucky, Coll Med, Lexington, KY USA.
[Thorpy, Michael J.] Montefiore Med Ctr, Ctr Sleep Wake Disorders, Bronx, NY 10467 USA.
[Vitiello, Michael V.] Univ Washington, Seattle, WA 98195 USA.
[Zee, Phyllis C.] Northwestern Univ, Dept Neurol, Chicago, IL 60611 USA.
RP Bloom, HG (reprint author), Int Longev Ctr USA, 60 E 86th St, New York, NY 10028 USA.
EM HarrisonB@ilcusa.org
OI Vitiello, Michael/0000-0002-9776-0473
FU NIA NIH HHS [R01 AG008415, R01 AG008415-17]
NR 293
TC 130
Z9 135
U1 6
U2 39
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0002-8614
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD MAY
PY 2009
VL 57
IS 5
BP 761
EP 789
DI 10.1111/j.1532-5415.2009.02220.x
PG 29
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 440OP
UT WOS:000265709900001
PM 19484833
ER
PT J
AU Marson, DC
Martin, RC
Wadley, V
Griffith, HR
Snyder, S
Goode, PS
Kinney, FC
Nicholas, AP
Steele, T
Anderson, B
Zamrini, E
Raman, R
Bartolucci, A
Harrell, LE
AF Marson, Daniel C.
Martin, Roy C.
Wadley, Virginia
Griffith, H. Randall
Snyder, Scott
Goode, Patricia S.
Kinney, F. Cleveland
Nicholas, Anthony P.
Steele, Terri
Anderson, Britt
Zamrini, Edward
Raman, Rema
Bartolucci, Alfred
Harrell, Lindy E.
TI Clinical Interview Assessment of Financial Capacity in Older Adults with
Mild Cognitive Impairment and Alzheimer's Disease
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article
DE financial capacity; competency; clinical assessment; mild cognitive
impairment; Alzheimer's disease
ID DECISION-MAKING CAPACITY; PROTOTYPE-INSTRUMENT; ELDERLY PERSONS;
COMPETENCE; ABILITIES; DEMENTIA; CONSENT; CONSISTENCY; JUDGMENTS
AB To investigate financial capacity in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) using a clinician interview approach.
Cross-sectional.
Tertiary care medical center.
Healthy older adults (n=75) and patients with amnestic MCI (n=58), mild AD (n=97), and moderate AD (n=31).
The investigators and five study physicians developed a conceptually based, semistructured clinical interview for evaluating seven core financial domains and overall financial capacity (Semi-Structured Clinical Interview for Financial Capacity; SCIFC). For each participant, a physician made capacity judgments (capable, marginally capable, or incapable) for each financial domain and for overall capacity.
Study physicians made more than 11,000 capacity judgments across the study sample (N=261). Very good interrater agreement was obtained for the SCIFC judgments. Increasing proportions of marginal and incapable judgment ratings were associated with increasing disease severity across the four study groups. For overall financial capacity, 95% of physician judgments for older controls were rated as capable, compared with 82% for patients with MCI, 26% for patients with mild AD, and 4% for patients with moderate AD.
Physicians and other clinicians can reliably evaluate financial capacity in cognitively impaired older adults using a relatively brief, semistructured clinical interview. Patients with MCI have mild impairment in financial capacity, those with mild AD have emerging global impairment, and those with moderate AD have advanced global impairment. Patients with MCI and their families should proactively engage in financial and legal planning, given these patients' risk of developing AD and accelerated loss of financial abilities.
C1 [Marson, Daniel C.; Martin, Roy C.; Wadley, Virginia; Griffith, H. Randall; Kinney, F. Cleveland; Nicholas, Anthony P.; Bartolucci, Alfred; Harrell, Lindy E.] Univ Alabama, Dept Neurol, Alzheimers Dis Res Ctr, Birmingham, AL 35294 USA.
[Wadley, Virginia; Goode, Patricia S.] Univ Alabama, Div Gerontol Geriatr & Palliat Care, Dept Med, Birmingham, AL 35294 USA.
[Snyder, Scott] Univ Alabama, Dept Educ, Birmingham, AL 35294 USA.
[Kinney, F. Cleveland] Univ Alabama, Dept Psychiat & Behav Neurobiol, Birmingham, AL 35294 USA.
[Bartolucci, Alfred] Univ Alabama, Dept Biostat, Birmingham, AL 35294 USA.
[Goode, Patricia S.; Harrell, Lindy E.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA.
[Anderson, Britt] Univ Waterloo, Dept Psychol, Ctr Theoret Neurosci, Waterloo, ON N2L 3G1, Canada.
[Zamrini, Edward] Univ Utah Hlth Sci, Dept Neurol, Salt Lake City, UT USA.
[Raman, Rema] Univ Calif San Diego, Dept Family Med & Neurosci, San Diego, CA 92103 USA.
RP Marson, DC (reprint author), Univ Alabama, Dept Neurol, Alzheimers Dis Res Ctr, SC 650, Birmingham, AL 35294 USA.
EM dmarson@uab.edu
FU National Institute of Mental Health [MH55247]; National Institute on
Aging [AG024525, AG021927, P50AG16582]
FX Sponsor's Role: The funding source had no role in the design or conduct
of the study, data management or analysis, or manuscript preparation.
NR 35
TC 34
Z9 34
U1 4
U2 8
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0002-8614
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD MAY
PY 2009
VL 57
IS 5
BP 806
EP 814
DI 10.1111/j.1532-5415.2009.02202.x
PG 9
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 440OP
UT WOS:000265709900004
PM 19453308
ER
PT J
AU Lesselroth, BJ
Felder, RS
Adams, SM
Cauthers, PD
Dorr, DA
Wong, GJ
Douglas, DM
AF Lesselroth, Blake J.
Felder, Robert S.
Adams, Shawn M.
Cauthers, Phillip D.
Dorr, David A.
Wong, Gordon J.
Douglas, David M.
TI Design and Implementation of a Medication Reconciliation Kiosk: the
Automated Patient History Intake Device (APHID)
SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION
LA English
DT Article
ID ERRORS
AB Errors associated with medication documentation account for a substantial fraction of preventable medical errors. Hence, the Joint Commission has called for the adoption of reconciliation strategies at all United States healthcare institutions. Although studies suggest that reconciliation tools can reduce errors, it remains unclear how best to implement systems and processes that are reliable and sensitive to clinical workflow. The authors designed a primary care process that Supported reconciliation without compromising clinic efficiency. This manuscript describes the design and implementation of Automated Patient History Intake Device (APHID): ambulatory check-in kiosks that allow patients to review the names, dosage, frequency, and Pictures of their medications before their appointment. Medication lists are retrieved from the electronic health record and patient updates are captured and reviewed by providers during the clinic session. Results from the roll-in phase indicate the device is easy for patients to use and integrates well with clinic workflow. J Am Med Inform Assoc. 2009;16:300-304. DOI 10.1197/jamia.M2642.
C1 [Lesselroth, Blake J.] Portland VA Med Ctr, Dept Hosp Specialty Med, Portland, OR 97239 USA.
[Lesselroth, Blake J.; Felder, Robert S.; Adams, Shawn M.; Cauthers, Phillip D.; Dorr, David A.; Wong, Gordon J.] Portland VA Med Ctr, Portland Patient Safety Ctr Inquiry, Portland, OR 97239 USA.
[Lesselroth, Blake J.; Felder, Robert S.; Cauthers, Phillip D.; Wong, Gordon J.; Douglas, David M.] Portland VA Med Ctr, Technol & Informat Management Sect, Portland, OR 97239 USA.
[Lesselroth, Blake J.; Dorr, David A.] Oregon Hlth & Sci Univ, Dept Med Informat & Clin Epidemiol, Portland, OR 97201 USA.
RP Lesselroth, BJ (reprint author), Portland VA Med Ctr, Dept Hosp Specialty Med, Mail Code P3 MED,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA.
EM Blake.Lesselroth@va.gov
NR 9
TC 22
Z9 22
U1 0
U2 4
PU HANLEY & BELFUS-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 1067-5027
J9 J AM MED INFORM ASSN
JI J. Am. Med. Inf. Assoc.
PD MAY-JUN
PY 2009
VL 16
IS 3
BP 300
EP 304
DI 10.1197/jamia.M2642
PG 5
WC Computer Science, Information Systems; Computer Science,
Interdisciplinary Applications; Information Science & Library Science;
Medical Informatics
SC Computer Science; Information Science & Library Science; Medical
Informatics
GA 447DU
UT WOS:000266172600009
PM 19261949
ER
PT J
AU Dux, KE
Sage, RA
Gocke, SP
AF Dux, Katherine E.
Sage, Ronald A.
Gocke, Sean P.
TI Pedal Presentation of Metastatic Invasive Squamous Cell Carcinoma of the
Bladder
SO JOURNAL OF THE AMERICAN PODIATRIC MEDICAL ASSOCIATION
LA English
DT Article
ID FOOT; TUMORS; BONES; TOE
AB Squamous cell carcinoma is a malignant tumor of the squamous epithelium and can occur in many different organs. We present a case of a 61-year-old veteran with metastatic squamous cell carcinoma of the bladder with distal metastasis to the middle phalanx of the fourth toe, which is a rare occurrence in the literature. (J Am Podiatr Med Assoc 99(3): 251-253, 2009)
C1 [Dux, Katherine E.; Gocke, Sean P.] Loyola Univ, Med Ctr, Dept Orthopaed Surg & Rehabil, Maywood, IL 60153 USA.
[Sage, Ronald A.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Dept Orthoped Surg & Rehabil, Hines, IL 60141 USA.
RP Dux, KE (reprint author), Loyola Univ, Med Ctr, Dept Orthopaed Surg & Rehabil, 2160 S 1st Ave, Maywood, IL 60153 USA.
EM kduxdpm@gmail.com
NR 15
TC 0
Z9 0
U1 0
U2 0
PU AMER PODIATRIC MED ASSOC
PI BETHESDA
PA 9312 OLD GEORGETOWN ROAD, BETHESDA, MD 20814-1621 USA
SN 8750-7315
J9 J AM PODIAT MED ASSN
JI J. Am. Podiatr. Med. Assoc.
PD MAY-JUN
PY 2009
VL 99
IS 3
BP 251
EP 253
PG 3
WC Orthopedics
SC Orthopedics
GA 447UJ
UT WOS:000266217000012
PM 19448178
ER
PT J
AU Moller, CC
Flesche, J
Reiser, J
AF Moeller, Clemens C.
Flesche, Jan
Reiser, Jochen
TI Sensitizing the Slit Diaphragm with TRPC6 Ion Channels
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID FOCAL SEGMENTAL GLOMERULOSCLEROSIS; NEPHRIN; KIDNEY; ACTIN; FYN
AB Physiologic permeability of the glomerular capillary depends on the normal structure of podocyte foot processes forming a functioning slit diaphragm in between. Mutations in several podocyte genes as well as specific molecular pathways have been identified as the cause for progressive kidney failure with urinary protein loss. Podocyte injury is a hallmark of glomerular disease, which is generally displayed by the rearrangement of the podocyte slit diaphragm and the actin cytoskeleton. Recent studies demonstrate a unique role for the Ca(2+)-permeable ion channel protein TRPC6 as a regulator of glomerular ultrafiltration. In both genetic and acquired forms of proteinuric kidney disease, dysregulation of podocyte TRPC6 plays a pathogenic role. This article illustrates how recent findings add to emerging concepts in podocyte biology, particularly mechanosensation and signaling at the slit diaphragm.
C1 [Reiser, Jochen] Univ Miami, Div Nephrol & Hypertens, Leonard Miller Sch Med, Miami, FL 33136 USA.
[Moeller, Clemens C.; Flesche, Jan; Reiser, Jochen] Harvard Univ, Sch Med, Boston, MA USA.
[Moeller, Clemens C.; Flesche, Jan; Reiser, Jochen] Massachusetts Gen Hosp, Dept Med, Program Glomerular Dis, Boston, MA 02114 USA.
[Moeller, Clemens C.; Flesche, Jan; Reiser, Jochen] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA.
RP Reiser, J (reprint author), Univ Miami, Div Nephrol & Hypertens, Leonard Miller Sch Med, 1120 NW 14th St,Suite 1182 CRB C-211, Miami, FL 33136 USA.
EM jreiser@med.miami.edu
FU National Institutes of Health [DK73495]
FX J.R. is supported by a research project grants from the National
Institutes of Health (DK73495). The authors thank Jim Stanis for help
with the illustration (Figure 1).
NR 16
TC 27
Z9 33
U1 0
U2 1
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD MAY
PY 2009
VL 20
IS 5
BP 950
EP 953
DI 10.1681/ASN.2008030329
PG 4
WC Urology & Nephrology
SC Urology & Nephrology
GA 444DE
UT WOS:000265959800008
PM 18784209
ER
PT J
AU Madero, M
Wassel, CL
Peralta, CA
Najjar, SS
Sutton-Tyrrell, K
Fried, L
Canada, R
Newman, A
Shlipak, MG
Sarnak, MJ
AF Madero, Magdalena
Wassel, Christina L.
Peralta, Carmen A.
Najjar, Samer S.
Sutton-Tyrrell, Kim
Fried, Linda
Canada, Robert
Newman, Anne
Shlipak, Michael G.
Sarnak, Mark J.
CA Health ABC Study
TI Cystatin C Associates with Arterial Stiffness in Older Adults
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article; Proceedings Paper
CT 39th Annual Meeting of the American-Society-of-Nephrology/Annual Renal
Week
CY NOV 14-19, 2006
CL San Diego, CA
SP Amer Soc Nephrol
ID PULSE-WAVE VELOCITY; CHRONIC KIDNEY-DISEASE; STAGE RENAL-DISEASE;
GLOMERULAR-FILTRATION-RATE; CARDIOVASCULAR EVENTS; RISK-FACTOR;
CREATININE CLEARANCE; AORTIC STIFFNESS; MORTALITY; PRESSURE
AB Large arteries commonly become stiff in kidney failure, but few studies have investigated arterial stiffness in earlier stages of kidney disease. We evaluated the association between kidney function and aortic pulse wave velocity (aPWV) and its potential modification by race, diabetes, or coronary heart disease in older adults. We measured aPWV in 2468 participants in the Health Aging and Body Composition (Health ABC) study; mean age was 73.7 yr, 40% were black, and 24% had diabetes. After categorizing kidney function into three groups on the basis of cystatin C level, multivariable analysis revealed that the medium and high cystatin C groups associated with a 5.3% (95% confidence interval 0.8 to 10.0%) and 8.0% (95% confidence interval 2.2 to 14.1%) higher aPWV than the low cystatin C group; however, chronic kidney disease, as defined by estimated GFR <60 ml/min per 1.73 m(2), did not significantly associate with aPWV. We did not identify interactions between cystatin C and race, diabetes, or coronary heart disease. In conclusion, stiffness of large arteries, a major risk factor for cardiovascular disease, may partially mediate the association between cystatin C and cardiovascular risk in older adults.
C1 [Sarnak, Mark J.] Tufts Med Ctr, Div Nephrol, Dept Med, Boston, MA 02111 USA.
[Madero, Magdalena] Inst Nacl Cardiol Ignacio Chavez Mexico City, Dept Nephrol, Mexico City, DF, Mexico.
[Wassel, Christina L.; Peralta, Carmen A.; Shlipak, Michael G.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Wassel, Christina L.; Shlipak, Michael G.] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA.
[Wassel, Christina L.; Shlipak, Michael G.] Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94143 USA.
[Shlipak, Michael G.] San Francisco VA Med Ctr, Gen Internal Med Sect, San Francisco, CA USA.
[Najjar, Samer S.] NIA, NIH, Bethesda, MD 20892 USA.
[Sutton-Tyrrell, Kim; Newman, Anne] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA.
[Fried, Linda] Univ Pittsburgh, Sch Med, Renal Electrolyte Div, Pittsburgh, PA USA.
[Fried, Linda] VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA.
[Canada, Robert] Univ Tennessee, Hlth Sci Ctr, Memphis, TN 38163 USA.
RP Sarnak, MJ (reprint author), Tufts Med Ctr, Div Nephrol, Dept Med, Box 391,800 Washington St, Boston, MA 02111 USA.
EM msarnak@tuftsmedicalcenter.org
RI Newman, Anne/C-6408-2013
OI Newman, Anne/0000-0002-0106-1150
FU Intramural NIH HHS; NIA NIH HHS [N01-AG-6-2101, N01-AG-6-2103,
N01-AG-6-2106]; NIDDK NIH HHS [K24 DK078204]
NR 34
TC 34
Z9 37
U1 0
U2 2
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD MAY
PY 2009
VL 20
IS 5
BP 1086
EP 1093
DI 10.1681/ASN.2008030318
PG 8
WC Urology & Nephrology
SC Urology & Nephrology
GA 444DE
UT WOS:000265959800022
PM 19357259
ER
PT J
AU Ashton-Chess, J
Dugast, E
Colvin, RB
Giral, M
Foucher, Y
Moreau, A
Renaudin, K
Braud, C
Devys, A
Brouard, S
Soulillou, JP
AF Ashton-Chess, Joanna
Dugast, Emilie
Colvin, Robert B.
Giral, Magali
Foucher, Yohann
Moreau, Anne
Renaudin, Karine
Braud, Christophe
Devys, Anne
Brouard, Sophie
Soulillou, Jean-Paul
TI Regulatory, Effector, and Cytotoxic T Cell Profiles in Long-Term Kidney
Transplant Patients
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article; Proceedings Paper
CT 8th American Transplant Congress
CY MAY 31-JUN 04, 2008
CL Toronto, CANADA
SP Amer Soc Transplant Surg, Amer Soc Transplantat
ID RENAL-ALLOGRAFT REJECTION; ANTIBODY-MEDIATED REJECTION; GENE-EXPRESSION;
MESSENGER-RNA; GRANZYME-B; QUANTITATIVE DETECTION; NONINVASIVE
DIAGNOSIS; TRANSCRIPTION FACTOR; TOLERANCE; FOXP3
AB Animal studies have suggested a potential role for regulatory T cells (Tregs) in allograft tolerance, but these FOXP3+ cells seem to be an inherent component of acute rejection (AR) in human recipients of renal transplants. The balance between regulatory cells and effector/cytotoxic cells may determine graft outcome; this balance has not been described for chronic allograft injury. We investigated the expression of key regulatory, effector, and cytotoxic transcripts (i.e., FOXP3, T-bet, and granzyme B, respectively) in the grafts and peripheral blood of long-term-surviving renal transplant patients. We found that, whereas neither intragraft nor peripheral blood FOXP3 or T-bet mRNA could distinguish between rejection and nonrejection status, granzyme B (GrzB) mRNA could: It was significantly increased in the graft and significantly decreased in the peripheral blood of patients with chronic antibody-mediated rejection (CAMR). Quantifying peripheral blood GrzB mRNA demonstrated potential to aid in the noninvasive diagnosis of CAMR. In summary, these data affirm GrzB as a marker not only for AR but also for CAMR. In addition, we identified several previously unreported clinical or demographic factors influencing regulatory/effector/cytotoxic profiles in the peripheral blood, highlighting the necessity to consider confounding variables when considering the use of potential biomarkers, such as FOXP3, for diagnosis or prognosis in kidney transplantation.
C1 [Brouard, Sophie] CHU Nantes, Hotel Dieu, INSERM, ITERT,U643, F-44093 Nantes 1, France.
[Ashton-Chess, Joanna; Dugast, Emilie; Giral, Magali; Foucher, Yohann; Braud, Christophe; Brouard, Sophie; Soulillou, Jean-Paul] CHU Nantes, Inst Transplantat & Rech Transplantat, F-44035 Nantes, France.
[Ashton-Chess, Joanna; Dugast, Emilie; Giral, Magali; Foucher, Yohann; Braud, Christophe; Brouard, Sophie; Soulillou, Jean-Paul] Univ Nantes, Fac Med, Nantes, France.
[Colvin, Robert B.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Colvin, Robert B.] Harvard Univ, Sch Med, Boston, MA USA.
[Moreau, Anne; Renaudin, Karine] CHU Nantes, Serv Anat Pathol, F-44035 Nantes 01, France.
[Devys, Anne] Etab Francais Sang, Nantes, France.
RP Brouard, S (reprint author), CHU Nantes, Hotel Dieu, INSERM, ITERT,U643, 30 Bd Jean Monnet, F-44093 Nantes 1, France.
EM sophie.brouard@university-nantes.fr; paul.soulillou@university-nantes.fr
RI Foucher, Yohann/G-2714-2013; brouard, sophie/Q-1285-2016
OI Foucher, Yohann/0000-0003-0330-7457;
NR 34
TC 43
Z9 43
U1 2
U2 8
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD MAY
PY 2009
VL 20
IS 5
BP 1113
EP 1122
DI 10.1681/ASN.2008050450
PG 10
WC Urology & Nephrology
SC Urology & Nephrology
GA 444DE
UT WOS:000265959800025
PM 19357258
ER
PT J
AU Lee, PS
Sampath, K
Karumanchi, SA
Tamez, H
Bhan, I
Isakova, T
Gutierrez, OM
Wolf, M
Chang, YC
Stossel, TP
Thadhani, R
AF Lee, Po-Shun
Sampath, Kartik
Karumanchi, S. Ananth
Tamez, Hector
Bhan, Ishir
Isakova, Tamara
Gutierrez, Orlando M.
Wolf, Myles
Chang, Yuchiao
Stossel, Thomas P.
Thadhani, Ravi
TI Plasma Gelsolin and Circulating Actin Correlate with Hemodialysis
Mortality
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID CHRONIC KIDNEY-DISEASE; UBIQUITIN-PROTEASOME PATHWAY; ENDOTHELIAL
DYSFUNCTION; CARDIOVASCULAR-DISEASE; LYSOPHOSPHATIDIC ACID;
DIABETES-MELLITUS; DIALYSIS PATIENTS; SCAVENGER SYSTEM; RENAL-FAILURE;
VITAMIN-D
AB Plasma gelsolin (pGSN) binds actin and bioactive mediators to localize inflammation. Low pGSN correlates with adverse outcomes in acute injury, whereas administration of recombinant pGSN reduces mortality in experimental sepsis. We found that mean pGSN levels of 150 patients randomly selected from 10,044 starting chronic hemodialysis were 140 +/- 42 mg/L, 30 to 50% lower than levels reported for healthy individuals. In a larger sample, we performed a case-control analysis to evaluate the relationship of pGSN and circulating actin with mortality; pGSN levels were significantly lower in 114 patients who died within 1 yr of dialysis initiation than in 109 survivors (117 +/- 38 mg/L versus 147 +/- 42 mg/L, P < 0.001). pGSN levels had a graded, inverse relationship with 1-yr mortality, such that patients with pGSN < 130 mg/L experienced a > 3-fold risk for mortality compared with those with pGSN >= 150 mg/L. The 69% of patients with detectable circulating actin had lower pGSN levels than those without (127 +/- 45 mg/L versus 141 +/- 36 mg/L, P = 0.026). Compared with patients who had elevated pGSN and no detectable actin, those with low pGSN levels and detectable actin had markedly increased mortality (odds ratio 9.8, 95% confidence interval 2.9 to 33.5). Worsening renal function correlated with pGSN decline in 53 subjects with CKD not on dialysis. In summary, low pGSN and detectable circulating actin identify chronic hemodialysis patients at highest risk for 1-yr mortality.
C1 [Sampath, Kartik; Tamez, Hector; Bhan, Ishir; Isakova, Tamara; Gutierrez, Orlando M.; Wolf, Myles; Chang, Yuchiao; Thadhani, Ravi] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Lee, Po-Shun; Stossel, Thomas P.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02114 USA.
[Karumanchi, S. Ananth] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02114 USA.
[Karumanchi, S. Ananth] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02114 USA.
RP Thadhani, R (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Bullfinch 127,55 Fruit St, Boston, MA 02114 USA.
EM rthadhani@partners.org
FU American Heart Association Scientist Development Grant; Howard Hughes
Medical Institute; American Cancer Society Clinical Research
Professorship; National Institutes of Health [DK71674, HL093954]
FX This work is supported by an American Heart Association Scientist
Development Grant (P.S.L.), the Howard Hughes Medical Institute
(S.A.K.), an American Cancer Society Clinical Research Professorship
(T.P.S.), and grants (DK71674 and HL093954) from the National Institutes
of Health (R.T.). We also thank Sze-Man Tsang for her technical support.
NR 65
TC 54
Z9 61
U1 0
U2 2
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD MAY
PY 2009
VL 20
IS 5
BP 1140
EP 1148
DI 10.1681/ASN.2008091008
PG 9
WC Urology & Nephrology
SC Urology & Nephrology
GA 444DE
UT WOS:000265959800028
PM 19389844
ER
PT J
AU Burstein, HJ
AF Burstein, Harold J.
TI Do Clinical Trials Belong in Clinical Guidelines?
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.
RP Burstein, HJ (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU JONES AND BARTLETT PUBLISHERS
PI SUDBURY
PA 40 TALL PINE DR, SUDBURY, MA 01776 USA
SN 1540-1405
J9 J NATL COMPR CANC NE
JI J. Natl. Compr. Cancer Netw.
PD MAY
PY 2009
VL 7
IS 5
BP 489
EP 489
PG 1
WC Oncology
SC Oncology
GA 499ZG
UT WOS:000270265000001
PM 19460277
ER
PT J
AU Temel, JS
Greer, JA
Goldberg, S
Vogel, PD
Sullivan, M
Pirl, WF
Lynch, TJ
Christiani, DC
Smith, MR
AF Temel, Jennifer S.
Greer, Joseph A.
Goldberg, Sarah
Vogel, Paula Downes
Sullivan, Michael
Pirl, William F.
Lynch, Thomas J.
Christiani, David C.
Smith, Matthew R.
TI A Structured Exercise Program for Patients with Advanced Non-small Cell
Lung Cancer
SO JOURNAL OF THORACIC ONCOLOGY
LA English
DT Article
DE Non-small cell lung cancer; Exercise; Supportive care
ID QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIAL; HIGH-DOSE CHEMOTHERAPY;
PHYSICAL-ACTIVITY; BREAST-CANCER; PULMONARY REHABILITATION;
MEGESTROL-ACETATE; FUNCTIONAL ASSESSMENT; AEROBIC EXERCISE; OUTPATIENT
REHABILITATION
AB Introduction: Exercise improves functional outcome and symptoms for certain cancer populations, but the feasibility, efficacy, and safety of structured exercise in patients with lung cancer is unknown. In this Study, we examined the feasibility of a hospital-based exercise program for patients with advanced non-small cell lung cancer.
Methods: This study included patients with newly diagnosed advanced stage non-small cell lung cancer and Eastern Cooperative Oncology Group performance status 0-1. A physical therapist facilitated twice-weekly sessions of aerobic exercise and weight training over an 8-week period. The primary end point was feasibility of the intervention, defined as adherence to the exercise program. Secondary endpoints included functional capacity, measured by the 6-minute walk test and Muscle strength, as well as quality Of life, lung cancer symptoms and fatigue, measured by the Functional Assessment of Cancer Therapy-lung and Functional Assessment of Cancer Therapy-fatigue scales.
Results: Between October 2004 and August 2007, 25 patients enrolled in the study. All participants received anticancer therapy during the Study period. Twenty patients (80%) underwent the baseline physical therapy evaluation. Eleven patients (44%) completed all 16 sessions. An additional 6 patients attended at least 6 sessions (range, 6-15), and 2 patients only attended one session. Study completers experienced a significant reduction in lung cancer symptoms and no deterioration in their 6-minute walk test or muscle strength.
Conclusions: Although the majority of participants attempted the exercise program, less than half were able to complete the intervention. Those who completed the program experienced an improvement in their lung cancer symptoms. Community-based or briefer exercise interventions may be more feasible in this population.
C1 [Temel, Jennifer S.; Greer, Joseph A.; Goldberg, Sarah; Vogel, Paula Downes; Sullivan, Michael; Pirl, William F.; Lynch, Thomas J.; Christiani, David C.; Smith, Matthew R.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Temel, JS (reprint author), Massachusetts Gen Hosp, Yawkey 7B,55 Fruit St, Boston, MA 02114 USA.
EM jtemel@partners.org
FU Mary Ellen and Dick Denning Foundation; NIH K24 Mid-career Investigator
Award [5K24CA121990]; [5RO3CA110779]
FX Supported by 5RO3CA110779 and the Mary Ellen and Dick Denning
Foundation, and NIH K24 Mid-career Investigator Award (5K24CA121990) (to
M. R. S.).
NR 75
TC 56
Z9 57
U1 2
U2 19
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1556-0864
J9 J THORAC ONCOL
JI J. Thorac. Oncol.
PD MAY
PY 2009
VL 4
IS 5
BP 595
EP 601
PG 7
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA 438LU
UT WOS:000265557700007
PM 19276834
ER
PT J
AU Morrow, DA
Brickman, CM
Murphy, SA
Baran, K
Krakover, R
Dauerman, H
Kumar, S
Slomowitz, N
Grip, L
McCabe, CH
Salzman, AL
AF Morrow, David A.
Brickman, Chaim M.
Murphy, Sabina A.
Baran, Kenneth
Krakover, Ricardo
Dauerman, Harold
Kumar, Sujatha
Slomowitz, Natanya
Grip, Laura
McCabe, Carolyn H.
Salzman, Andrew L.
TI A randomized, placebo-controlled trial to evaluate the tolerability,
safety, pharmacokinetics, and pharmacodynamics of a potent inhibitor of
poly(ADP-ribose) polymerase (INO-1001) in patients with ST-elevation
myocardial infarction undergoing primary percutaneous coronary
intervention: results of the TIMI 37 trial
SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS
LA English
DT Article
DE Clinical trials; Myocardial infarction; Reperfusion injury;
Poly(ADP-ribose) polymerase
ID ADP-RIBOSE SYNTHETASE; REPERFUSION INJURY; ACTIVATION; HEART;
PEROXYNITRITE; CONTRACTILE; DISRUPTION; DEPLETION; MUSCLE
AB Background Reperfusion injury is a significant complication of the management of ST-elevation MI (STEMI). INO-1001 is a potent inhibitor of poly(ADP-ribose) polymerase (PARP), a mediator of oxidant-induced myocyte dysfunction during reperfusion. Methods & results We assessed the safety and pharmacokinetics of INO-1001 in a randomized, placebo-controlled, single-blind, dose-escalating trial in 40 patients with STEMI undergoing primary percutaneous coronary intervention within 24 h of onset. INO-1001 was well-tolerated. A trend toward more frequent transaminitis was observed with 800 mg. Plasma from INO1001-treated patients reduced in vitro PARP activity > 90% at all doses. Serial C-reactive protein and IL-6 levels showed a trend toward blunting of inflammation with INO-1001. The apparent median terminal half-life (t(1/2)) of INO-1001 was 7.5 (25th, 75th: 5.9, 10.2) h. Conclusions The results from this first trial of INO-1001 in STEMI support future investigation of INO-1001 as a novel treatment for reperfusion injury.
C1 [Morrow, David A.; Murphy, Sabina A.; Grip, Laura; McCabe, Carolyn H.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA.
[Brickman, Chaim M.; Kumar, Sujatha; Slomowitz, Natanya; Salzman, Andrew L.] Inotek Pharmaceut, Beverly, MA USA.
[Baran, Kenneth] St Paul Heart Clin, St Paul, MN USA.
[Krakover, Ricardo] Assaf Harofeh Med Ctr, Tel Aviv, Israel.
[Dauerman, Harold] Univ Vermont, Coll Med, Burlington, VT USA.
RP Morrow, DA (reprint author), Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA.
EM dmorrow@partners.org
FU NHLBI NIH HHS [R44 HL074684-01]
NR 15
TC 39
Z9 42
U1 0
U2 3
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0929-5305
J9 J THROMB THROMBOLYS
JI J. Thromb. Thrombolysis
PD MAY
PY 2009
VL 27
IS 4
BP 359
EP 364
DI 10.1007/s11239-008-0230-1
PG 6
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 444VV
UT WOS:000266009400001
PM 18535785
ER
PT J
AU Saylor, PJ
Smith, MR
AF Saylor, Philip J.
Smith, Matthew R.
TI Metabolic Complications of Androgen Deprivation Therapy for Prostate
Cancer
SO JOURNAL OF UROLOGY
LA English
DT Article
DE prostatic neoplasms; gonadotropin-releasing hormone agonists;
cardiovascular diseases; diabetes mellitus; obesity
ID CORONARY-HEART-DISEASE; HORMONE AGONIST TREATMENT; BONE-MINERAL DENSITY;
LEAN BODY-MASS; CARDIOVASCULAR MORTALITY; SUPPRESSION THERAPY; INSULIN
SENSITIVITY; ARTERIAL STIFFNESS; BLOOD CHOLESTEROL; RISK FACTOR
AB Purpose: Androgen deprivation therapy has a variety of well recognized adverse effects including vasomotor flushing, loss of libido, fatigue, gynecomastia, anemia and osteoporosis. This review focuses on the more recently described metabolic complications of androgen deprivation therapy including obesity, insulin resistance and lipid alterations as well as the association of androgen deprivation therapy with diabetes and cardiovascular disease.
Materials and Methods: We reviewed the medical literature using the PubMed (R) search terms prostate cancer, androgen deprivation therapy, gonadotropin-releasing hormone agonists, obesity, insulin resistance, lipids, diabetes, cardiovascular disease and myocardial infarction. We provide a focused review and our perspective on the relevant literature.
Results: Androgen deprivation therapy decreases lean mass and increases fat mass. It also decreases insulin sensitivity while increasing low density lipoprotein cholesterol, high density lipoprotein cholesterol and triglycerides. Consistent with these adverse metabolic effects, androgen deprivation therapy may be associated with a greater incidence of diabetes and cardiovascular disease. Some of these androgen deprivation therapy related metabolic changes (obesity, insulin resistance and increased triglycerides) overlap with features of the metabolic syndrome. However, in contrast to the metabolic syndrome, androgen deprivation therapy increases subcutaneous fat and high density lipoprotein cholesterol.
Conclusions: Androgen deprivation therapy increases obesity, decreases insulin sensitivity and adversely alters lipid profiles. It may be associated with a greater incidence of diabetes and cardiovascular disease. The benefits of androgen deprivation therapy should be weighed against these and other potential harms. Little is known about the optimal strategy to mitigate the adverse metabolic effects of androgen deprivation therapy. Thus, we recommend an emphasis on existing strategies for screening and treatment that have been documented to reduce the risk of diabetes and cardiovascular disease in the general population.
C1 [Saylor, Philip J.; Smith, Matthew R.] Massachusetts Gen Hosp, Ctr Canc, Dept Oncol, Boston, MA 02114 USA.
RP Saylor, PJ (reprint author), Massachusetts Gen Hosp, Ctr Canc, Dept Med Oncol, 55 Fruit St,POB 2-221, Boston, MA 02114 USA.
EM psaylor@partners.org
FU National Institutes of Health [5K24CA12199002]; Prostate Cancer
Foundation; Armstrong Foundation
FX Supported by a National Institutes of Health K24 Midcareer Investigator
Award (5K24CA12199002), and grants from the Prostate Cancer Foundation
and Lance Armstrong Foundation.
NR 57
TC 118
Z9 121
U1 2
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5347
J9 J UROLOGY
JI J. Urol.
PD MAY
PY 2009
VL 181
IS 5
BP 1998
EP 2006
DI 10.1016/j.juro.2009.01.047
PG 9
WC Urology & Nephrology
SC Urology & Nephrology
GA 431PJ
UT WOS:000265074800008
PM 19286225
ER
PT J
AU Twiss, C
Kilpatrick, L
Craske, M
Buffington, CAT
Ornitz, E
Rodriguez, LV
Mayer, EA
Naliboff, BD
AF Twiss, Christian
Kilpatrick, Lisa
Craske, Michelle
Buffington, C. A. Tony
Ornitz, Edward
Rodriguez, Larissa V.
Mayer, Emeran A.
Naliboff, Bruce D.
TI Increased Startle Responses in Interstitial Cystitis: Evidence for
Central Hyperresponsiveness to Visceral Related Threat
SO JOURNAL OF UROLOGY
LA English
DT Article
DE cystitis; interstitial; sensory gating; startle reaction; reflex
ID ANXIETY DISORDERS; PELVIC PAIN; FEAR; AMYGDALA; HYPERSENSITIVITY; INDEX;
IBS
AB Purpose: Hypersensitivity to visceral stimuli in interstitial cystitis/painful bladder syndrome may result from enhanced responsiveness of affective circuits (including the amygdala complex) and associated central pain amplification. Potentiation of the eyeblink startle reflex under threat is mediated by output from the amygdala complex and, therefore, represents a noninvasive marker to study group differences in responsiveness in this brain circuit.
Materials and Methods: Acoustic startle responses were examined in female patients with interstitial cystitis/painful bladder syndrome (13) and healthy controls (16) during context threat (application of muscle stimulation electrodes to the lower abdomen overlying the bladder), and cued conditions for safety (no stimulation possible), anticipation and imminent threat of aversive abdominal stimulation over the bladder.
Results: Patients showed significantly greater startle responses during nonimminent threat conditions (baseline, safe and anticipation periods) while both groups showed similar robust startle potentiation during the imminent threat condition. Higher rates of anxiety and depression symptoms in the patient group did not account for the group differences in startle reflex magnitude.
Conclusions: Compared to controls, female patients with interstitial cystitis/painful bladder syndrome showed increased activation of a defensive emotional circuit in the context of a threat of abdominal pain. This pattern is similar to that previously reported in patients with anxiety disorders as well as those with irritable bowel syndrome. Since these circuits have an important role in central pain amplification related to affective and cognitive processes, these results support the hypothesis that the observed abnormality may be involved in the enhanced perception of bladder signals associated with interstitial cystitis/painful bladder syndrome.
C1 [Kilpatrick, Lisa; Craske, Michelle; Buffington, C. A. Tony; Ornitz, Edward; Mayer, Emeran A.; Naliboff, Bruce D.] Univ Calif Los Angeles, Ctr Neurobiol Stress, David Geffen Sch Med, Los Angeles, CA 90073 USA.
[Kilpatrick, Lisa; Mayer, Emeran A.] Univ Calif Los Angeles, Dept Med, David Geffen Sch Med, Los Angeles, CA 90073 USA.
[Mayer, Emeran A.] Univ Calif Los Angeles, Dept Physiol, David Geffen Sch Med, Los Angeles, CA 90073 USA.
[Ornitz, Edward; Mayer, Emeran A.; Naliboff, Bruce D.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, David Geffen Sch Med, Los Angeles, CA 90073 USA.
[Twiss, Christian; Rodriguez, Larissa V.] Univ Calif Los Angeles, Dept Urol, David Geffen Sch Med, Los Angeles, CA 90073 USA.
[Mayer, Emeran A.] Univ Calif Los Angeles, Brain Res Inst, David Geffen Sch Med, Los Angeles, CA 90073 USA.
[Craske, Michelle] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90073 USA.
[Naliboff, Bruce D.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
[Buffington, C. A. Tony] Ohio State Univ, Dept Vet Clin Sci, Coll Vet Med, Columbus, OH 43210 USA.
RP Naliboff, BD (reprint author), Univ Calif Los Angeles, Ctr Neurobiol Stress, David Geffen Sch Med, CURE Bld 115,Room 223,11301 Wilshire Blvd, Los Angeles, CA 90073 USA.
EM naliboff@ucla.edu
RI Buffington, Tony/B-7135-2009; Kilpatrick, Lisa/E-6995-2015
FU NCCIH NIH HHS [R24 AT002681, R24 AT002681-04, R24AT002681]; NIDDK NIH
HHS [P50 DK064539, P50 DK064539-06, P50 DK64539]; NINR NIH HHS
[NR007768, R01 NR007768, R01 NR007768-03]
NR 27
TC 22
Z9 22
U1 2
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5347
J9 J UROLOGY
JI J. Urol.
PD MAY
PY 2009
VL 181
IS 5
BP 2127
EP 2133
DI 10.1016/j.juro.2009.01.025
PG 7
WC Urology & Nephrology
SC Urology & Nephrology
GA 431PJ
UT WOS:000265074800056
PM 19286199
ER
PT J
AU Zawacki, WJ
Walker, G
DeVasher, E
Halpern, EF
Waltman, AC
Wicky, ST
Ryan, DP
Kalva, SP
AF Zawacki, Walter J.
Walker, Gregory
DeVasher, Emily
Halpern, Elkan F.
Waltman, Arthur C.
Wicky, Stephan T.
Ryan, David P.
Kalva, Sanjeeva P.
TI Wound Dehiscence or Failure to Heal following Venous Access Port
Placement in Patients Receiving Bevacizumab Therapy
SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY
LA English
DT Article
ID INTERVENTIONAL RADIOLOGISTS
AB PURPOSE: To determine the incidence of wound dehiscence or failure to heal after port placement in patients receiving bevacizumab therapy. A hypothesis was tested that the mean interval between bevacizumab administration and port placement was shorter in patients who had dehiscence than in those who did not.
MATERIALS AND METHODS: Medical records of all patients who had venous access ports placed from July 2006 through December 2007 were retrospectively reviewed. A total of 195 ports were placed in 189 patients (106 men) who were treated with bevacizumab within 120 days of port placement. The incidence of wound dehiscence and the significance of dose timing relative to port placement in these patients were calculated.
RESULTS: Six of 195 ports (3.1%) were associated with wound dehiscence requiring port removal. The mean interval between bevacizumab dosing and port placement in patients without dehiscence (n = 189) was 16.9 days. The mean interval in patients with dehiscence (n = 6) was 10.8 days. A two-tailed Wilcoxon test was performed, which yielded a P value of .0150. A statistically significant difference in the mean interval between bevacizumab dosing and port placement exists between patients with dehiscence and those without.
CONCLUSIONS: Wound dehiscence after port placement was related to timing of bevacizumab therapy. Patients receiving bevacizumab within 10 days of port placement had a higher incidence of wound dehiscence.
C1 [Zawacki, Walter J.; Walker, Gregory; DeVasher, Emily; Halpern, Elkan F.; Waltman, Arthur C.; Wicky, Stephan T.; Ryan, David P.; Kalva, Sanjeeva P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
RP Zawacki, WJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,GRB 290, Boston, MA 02114 USA.
EM wzawacki@partners.org
NR 9
TC 18
Z9 18
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 MAY
PY 2009
VL 20
IS 5
BP 624
EP 627
DI 10.1016/j.jvir.2009.01.022
PG 4
WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular
Disease
SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System &
Cardiology
GA 440LD
UT WOS:000265700900009
PM 19328717
ER
PT J
AU Salazar, GM
Faintuch, S
Gladstone, SR
Lang, EV
AF Salazar, Gloria M.
Faintuch, Salomao
Gladstone, Steve R.
Lang, Elvira V.
TI In Vitro Analysis of Downstream Particulates with Mechanical
Thrombectomy Devices: Comparison of 20-kHz Sonothrombolytic and Rotating
Dispersion Wire Systems
SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY
LA English
DT Article
ID DEEP VENOUS THROMBOSIS; CATHETER-DIRECTED THROMBOLYSIS; RHEOLYTIC
THROMBECTOMY; DISTAL EMBOLIZATION; PROTECTION; ANGIOPLASTY; OCCLUSIONS;
EMBOLISM; SAFETY; ARTERY
AB PURPOSE: To assess the potential of macroembolization, the authors compared the downstream particulate profile generated with use of two thrombectomy devices, a 20-kHz ultrasound-based sonothrombolytic (ST) device and a rotating dispersion wire (RDW).
MATERIALS AND METHODS: An arterial flow model was pressurized to 100 mm Hg and perfused with 1,000 mL/min normal saline. Tubing containing 7-mm x 30-cm bovine thrombus proximal to a 75% stenosis was inserted distal to a nonstenosed bypass. The effluent was passed successively through 1,000-, 500-, and 200-mu m filters and a particle analyzer. The ST device and RDW were activated for 10 and 15 minutes, respectively, in randomized sequences of experimental sets with and without the use of 10-mg tissue-type plasminogen activator (tPA). Results are expressed as means and standard deviations of fraction of lysed clot in each category.
RESULTS: The ST device produced significantly fewer particulates larger than 1,000 mu m (1.3% +/- 1.4) than did the RDW (16.8% +/- 8.4, P < .001) and significantly more particulates smaller than 10 mu m (90.7% +/- 7.6) than did the RDW (73.9% +/- 9.5; P <.001) at comparable thrombolytic efficacy (P =.982) and without significant effect from tPA (P =.988). There were no significant differences between particles measuring 500-1,000 mu m (ST device: 0.3% +/- 0.3, RDW: 0.4% +/- 0.3; P =.653) and those measuring 10-199 mu m (ST device: 7.5% +/- 7.5, RDW: 8.6% +/- 3.8; P =.624). The amount of particles on the 200-mu m filter after RDW activation (0.4% 0.3) exceeded those trapped after use of the ST device (0.1% +/- 0.1, P =.007) but contributed relatively little overall.
CONCLUSIONS: In this in vitro model, the use of the ST device resulted in fewer large particulates than did the use of the RDW, with more clots being reduced to less than 10 mu m.
C1 [Salazar, Gloria M.; Faintuch, Salomao; Lang, Elvira V.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA.
[Gladstone, Steve R.; Lang, Elvira V.] OmniSon Med Technol, Williamstown, MA USA.
RP Salazar, GM (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,GRB 290A, Boston, MA 02114 USA.
EM gmsalazar@partners.org
NR 20
TC 3
Z9 3
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1051-0443
J9 J VASC INTERV RADIOL
JI J. Vasc. Interv. Radiol.
PD MAY
PY 2009
VL 20
IS 5
BP 634
EP 639
DI 10.1016/j.jvir.2008.12.416
PG 6
WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular
Disease
SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System &
Cardiology
GA 440LD
UT WOS:000265700900011
PM 19324573
ER
PT J
AU Siddiqi, NH
Devlin, PM
AF Siddiqi, Nasir H.
Devlin, Phillip M.
TI Radiation Lobectomy-A Minimally Invasive Treatment Model for Liver
Cancer: Case Report
SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY
LA English
DT Article
ID HEPATOCELLULAR-CARCINOMA; MICROSPHERES; THERAPY
AB Chemotherapy-resistant colon carcinoma metastases to a patient's right hepatic lobe progressed after right lobar radioembolization with yttrium-90. The metastasis-free left lobe had adequate volume as a future liver remnant. Repeat right lobar radioembolization with supratherapeutic activity of (90)y caused shrinking of the tumors and the right lobe with no adverse outcome. With an adequate tumor-free future liver remnant, one hepatic lobe bearing a large tumor burden may be administered supratherapeutic activity of (90)Y, risking lobar ablation for greater probability of tumor eradication. This is analogous to hepatic lobectomy. This case is presented as a proof of principle.
C1 [Siddiqi, Nasir H.] Washington Univ, Sch Med, Mallinckrodt Inst Radiol, Div Vasc & Intervent Radiol, St Louis, MO 63110 USA.
[Devlin, Phillip M.] Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Div Brachytherapy,Dept Radiat Oncol, Boston, MA USA.
RP Siddiqi, NH (reprint author), Washington Univ, Sch Med, Mallinckrodt Inst Radiol, Div Vasc & Intervent Radiol, 510 S Kingshighway Blvd, St Louis, MO 63110 USA.
EM siddiqin@mir.wustl.edu
NR 15
TC 15
Z9 15
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1051-0443
J9 J VASC INTERV RADIOL
JI J. Vasc. Interv. Radiol.
PD MAY
PY 2009
VL 20
IS 5
BP 664
EP 669
DI 10.1016/j.jvir.2009.01.023
PG 6
WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular
Disease
SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System &
Cardiology
GA 440LD
UT WOS:000265700900017
PM 19328722
ER
PT J
AU Visser, JJ
Williams, M
Kievit, J
Bosch, JL
AF Visser, Jacob J.
Williams, Martine
Kievit, Jur
Bosch, Johanna L.
CA 4-A Study Grp
TI Prediction of 30-day mortality after endovascular repair or open surgery
in patients with ruptured abdominal aortic aneurysms
SO JOURNAL OF VASCULAR SURGERY
LA English
DT Article
ID RISK-SCORING METHODS; FEASIBILITY; VALIDATION; SYSTEMS; TRIALS; TOOL
AB Objective: To validate the Glasgow Aneurysm Score (GAS) in patients with ruptured abdominal aortic aneurysms (AAAs) treated with endovascular repair or open surgery and to update the GAS so that it predicts 30-day mortality for patients with ruptured AAA treated with endovascular repair or open surgery.
Methods: In a multicenter prospective observational study, 233 consecutive patients with ruptured AAAs were evaluated; 32 patients did not survive to repair and statistical analysis was performed using collected data on 201 patients. All patients who were treated with endovascular repair (n = 58) or open surgery (n = 143) were included. The GAS was calculated for each patient. The area under the receiver operating characteristics curve (AUC) was used to indicate discriminative ability. We tested for interactions between risk factors and the procedure performed. The GAS was updated to predict 30-day mortality after endovascular repair or open surgery in patients with ruptured AAAs using logistic regression analysis.
Results: Thirty-day mortality was 15/58 (26%) for patients treated with endovascular repair and 57/143 (40%) for patients treated with open surgery (P = .06). The AUC for GAS was 0.69. No relevant interactions were found. The updated prediction rule (AUC = 0.70) clan be calculated with the following formula: + 7 for open surgery + age in years + 17 for shock + 7 for myocardial disease + 10 for cerebrovascular disease + 14 for renal insufficiency.
Conclusion: We showed limited discriminative ability of the GAS and therefore updated the GAS by adding the type of procedure performed. This updated prediction rule predicts 30-day mortality for patients with ruptured AAAs treated with endovascular repair or open surgery. (J Vase Surg 2009;49:1093-9.)
C1 [Visser, Jacob J.; Bosch, Johanna L.] Erasmus MC, Dept Epidemiol & Biostat, Rotterdam, Netherlands.
[Visser, Jacob J.; Bosch, Johanna L.] Erasmus MC, Dept Radiol, Rotterdam, Netherlands.
[Williams, Martine] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Inst Technol Assessment, Cambridge, MA 02138 USA.
[Williams, Martine] Univ Med Ctr, Dept Surg, Nijmegen, Netherlands.
[Kievit, Jur] Catharina Hosp, Dept Surg, Eindhoven, Netherlands.
RP Visser, JJ (reprint author), Care of van Sambeek MRHM, Catharina Hosp, Dept Surg Vasc Surg, Michelangelolaan 2, NL-5623 EJ Eindhoven, Netherlands.
EM marc.v.sambeek@cze.nl
FU Erasmus MC Health Care Efficiency; "Lijf en Leven" Foundation
FX The study was funded by Erasmus MC Health Care Efficiency grant and an
Unrestricted educational grant from the "Lijf en Leven" Foundation.
NR 27
TC 30
Z9 33
U1 0
U2 3
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0741-5214
J9 J VASC SURG
JI J. Vasc. Surg.
PD MAY
PY 2009
VL 49
IS 5
BP 1093
EP 1099
DI 10.1016/j.jvs.2008.12.027
PG 7
WC Surgery; Peripheral Vascular Disease
SC Surgery; Cardiovascular System & Cardiology
GA 441BQ
UT WOS:000265744700001
PM 19394540
ER
PT J
AU Chang, CK
Chuter, TAM
Niemann, CU
Shlipak, MG
Cohen, MJ
Reilly, LM
Hiramoto, JS
AF Chang, Catherine K.
Chuter, Timothy A. M.
Niemann, Claus U.
Shlipak, Michael G.
Cohen, Mitchell J.
Reilly, Linda M.
Hiramoto, Jade S.
TI Systemic inflammation, coagulopathy, and acute renal insufficiency
following endovascular thoracoabdominal aortic aneurysm repair
SO JOURNAL OF VASCULAR SURGERY
LA English
DT Article
ID GLOMERULAR-FILTRATION-RATE; ZENITH STENT GRAFT; CYSTATIN-C; BIOLOGICAL
RESPONSES; SURGERY; INJURY; REINTERVENTION; CREATININE; BIOMARKERS;
FAILURE
AB Objective: To characterize the inflammatory and coagulopathic response after endovascular thoracoabdominal aortic aneurysm (TAAA) repair and to evaluate the effect of the response on postoperative renal function.
Methods. From July 2005 to June 2008, 42 patients underwent elective endovascular repair of a TAAA using custom designed multi-branched stent-grafts at a single academic institution. Four patients were excluded from the analysis. White blood cell count (WBC), platelet count, prothrombin time (PT), and creatinine were measured in all patients. In the last nine patients, interleukin-6 (IEL-6), protein C, Factor V, cl-dimers, cystatin C, and neutrophil gelatinase-associated lipocatin (NGAL) levels were also measured. Change in lab values were expressed as a percentage of baseline values.
Results. The 30-day mortality rate was 5% (2/38). All patients (n = 38) had a higher WBC (mean +/- SD: 139 +/- 80%, P < .0001), lower platelet count (56 +/- 15%, P < .0001), and higher PT (median: 17%, Interquartile range (IQR) 12%-22%, P < .0001) after stent-graft insertion. Twelve of 38 patients (32%) developed postoperative acute renal insufficiency (>50% rise in creatinine). Patients with renal insufficiency had significantly larger changes in WBC (178 +/- 100% vs 121 +/- 64%, P = .04) and platelet count (64 +/- 17% vs 52 +/- 12%, P = .02) compared with those without renal insufficiency. All patients (n = 9) had significant increases in NGAL (182 +/- 115%, P = .008) after stent-graft insertion. Six of nine patients (67%) had increased cystatin C (35 +/- 43%, P = .04) after stent-graft insertion, with a greater rise in those with postoperative renal insufficiency (87 +/- 32% vs 8 +/- 13%, P = .02). IEL-6 levels were markedly increased in all patients (n = 9) after repair (9840 +/- 6160%, P = .008). Protein C (35 +/- 10%, P = .008) and Factor V levels (28 +/- 20%, P = .008) were uniformly decreased, while d-dimers were elevated after repair in all patients (310 +/- 213%, P = .008).
Conclusions. Leukocytosis and thrombocytopenia were uniform following endovascular TAAA repair, and the severity of the response correlated with post-operative renal dysfunction. Elevation of a sensitive marker of renal injury (NGAL) suggests that renal injury may occur in all patients after stent-graft insertion. (J Vasc Surg 2009;49:1140-6.)
C1 [Chang, Catherine K.; Chuter, Timothy A. M.; Reilly, Linda M.; Hiramoto, Jade S.] Univ Calif San Francisco, Div Vasc Surg, Dept Surg, San Francisco, CA 94143 USA.
[Niemann, Claus U.] Univ Calif San Francisco, Dept Anesthesia & Perioperat Care, San Francisco, CA 94143 USA.
[Niemann, Claus U.] Univ Calif San Francisco, Div Transplantat, Dept Surg, San Francisco, CA 94143 USA.
[Shlipak, Michael G.] San Francisco VA Med Ctr, Gen Internal Med Sect, San Francisco, CA USA.
RP Hiramoto, JS (reprint author), Univ Calif San Francisco, Div Vasc Surg, Dept Surg, 400 Parnassus Ave,A-581, San Francisco, CA 94143 USA.
EM Jade.Hiramoto@ucsfmedctr.org
FU National Institutes of Health (NIH)/National Center for Research
Resources (NCRR)/OD University of California, Sail Francisco
(UCSF)-Clinical and Translational Science Institute (CTSI) [KL2
RR024130]; NIH [K08 GM-085689]; Hellman Award; Research Evaluation and
Allocation Committee, San Francisco, CA; Foundation of Anesthesia
Research and Education; Foundation for Accelerated Vascular Research,
San Francisco; American Heart Association
FX This project was Supported by National Institutes of Health
(NIH)/National Center for Research Resources (NCRR)/OD University of
California, Sail Francisco (UCSF)-Clinical and Translational Science
Institute (CTSI) Grant Number KL2 RR024130 (Dr Hiramoto) and NIH K08
GM-085689 (Dr Cohen). Its contents arc the responsibility of the authors
and do not necessarily represent the official views of the NIH. This
stud), was also supported in part by grants from the Hellman Award, Sail
Francisco, CA (Dr Hiramoto); the Research Evaluation and Allocation
Committee, San Francisco, CA (Dr Hirarnoto); the Foundation of
Anesthesia Research and Education, Rochester, MN (Dr Niemann); the
International Anesthesia Research Society, Cleveland, OH (Dr Niemann);
the Foundation for Accelerated Vascular Research, San Francisco, CA (Drs
Chang and Chuter); and the Established Investigator Award from the
American Heart Association (Dr Shlipak). The Clinical-trials.gov number
is: NCT00483249.
NR 29
TC 33
Z9 36
U1 0
U2 3
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0741-5214
J9 J VASC SURG
JI J. Vasc. Surg.
PD MAY
PY 2009
VL 49
IS 5
BP 1140
EP 1146
DI 10.1016/j.jvs.2008.11.102
PG 7
WC Surgery; Peripheral Vascular Disease
SC Surgery; Cardiovascular System & Cardiology
GA 441BQ
UT WOS:000265744700009
PM 19394543
ER
PT J
AU Kassa, A
Finzi, A
Pancera, M
Courter, JR
Smith, AB
Sodroski, J
AF Kassa, Aemro
Finzi, Andres
Pancera, Marie
Courter, Joel R.
Smith, Amos B., III
Sodroski, Joseph
TI Identification of a Human Immunodeficiency Virus Type 1 Envelope
Glycoprotein Variant Resistant to Cold Inactivation
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID ENTRY INHIBITOR SENSITIVITY; HUMAN MONOCLONAL-ANTIBODIES; DEPENDENT DNA
POLYMERASE; SOLUBLE CD4; HIV-1 GP120; CELL-LINE; NONNEUTRALIZING
ANTIBODIES; NEUTRALIZING ANTIBODY; TRANSMEMBRANE PROTEIN; CYTOPLASMIC
DOMAIN
AB The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein trimer consists of gp120 and gp41 subunits and undergoes a series of conformational changes upon binding to the receptors, CD4 and CCR5/CXCR4, that promote virus entry. Surprisingly, we found that the envelope glycoproteins of some HIV-1 strains are functionally inactivated by prolonged incubation on ice. Serial exposure of HIV-1 to extremes of temperature, followed by expansion of replication-competent viruses, allowed selection of a temperature-resistant virus. The envelope glycoproteins of this virus resisted cold inactivation due to a single passage-associated change, H66N, in the gp120 exterior envelope glycoprotein. Histidine 66 is located within the gp41-interactive inner domain of gp120 and, in other studies, has been shown to decrease the sampling of the CD4-bound conformation by unliganded gp120. Substituting asparagine or other amino acid residues for histidine 66 in cold-sensitive HIV-1 envelope glycoproteins resulted in cold-stable phenotypes. Cold inactivation of the HIV-1 envelope glycoproteins occurred even at high pH, indicating that protonation of histidine 66 is not necessary for this process. Increased exposure of epitopes in the ectodomain of the gp41 transmembrane envelope glycoprotein accompanied cold inactivation, but shedding of gp120 did not. An amino acid change in gp120 (S375W) that promotes the CD4-bound state or treatment with soluble CD4 or a small-molecule CD4 mimic resulted in increased cold sensitivity. These results indicate that the CD4-bound intermediate of the HIV-1 envelope glycoproteins is cold labile; avoiding the CD4-bound state increases temperature stability.
C1 [Kassa, Aemro; Finzi, Andres; Pancera, Marie; Sodroski, Joseph] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
[Courter, Joel R.; Smith, Amos B., III] Univ Penn, Dept Chem, Philadelphia, PA 19104 USA.
[Kassa, Aemro; Sodroski, Joseph] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA.
RP Sodroski, J (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St,CLS 1010, Boston, MA 02115 USA.
EM joseph_sodroski@dfci.harvard.edu
FU NIH [AI24755, AI39420, AI40895, GM56550]; Center for HIV/AIDS Vaccine
Immunology [AI67854]; Center for AIDS Research [AI42848]; Bristol-Myers
Squibb Foundation; International AIDS Vaccine Initiative
FX This work was supported by NIH grants (AI24755, AI39420, AI40895, and
GM56550), by a Center for HIV/AIDS Vaccine Immunology grant (AI67854),
by a Center for AIDS Research grant (AI42848), by an unrestricted
research grant from the Bristol-Myers Squibb Foundation, by a gift from
the late William F. McCarty-Cooper, and by funds from the International
AIDS Vaccine Initiative.
NR 79
TC 23
Z9 23
U1 0
U2 4
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD MAY 1
PY 2009
VL 83
IS 9
BP 4476
EP 4488
DI 10.1128/JVI.02110-08
PG 13
WC Virology
SC Virology
GA 431DN
UT WOS:000265041600047
PM 19211747
ER
PT J
AU Matthews, PC
Leslie, AJ
Katzourakis, A
Crawford, H
Payne, R
Prendergast, A
Power, K
Kelleher, AD
Klenerman, P
Carlson, J
Heckerman, D
Ndung'u, T
Walker, BD
Allen, TM
Pybus, OG
Goulder, PJR
AF Matthews, Philippa C.
Leslie, Alasdair J.
Katzourakis, Aris
Crawford, Hayley
Payne, Rebecca
Prendergast, Andrew
Power, Karen
Kelleher, Anthony D.
Klenerman, Paul
Carlson, Jonathan
Heckerman, David
Ndung'u, Thumbi
Walker, Bruce D.
Allen, Todd M.
Pybus, Oliver G.
Goulder, Philip J. R.
TI HLA Footprints on Human Immunodeficiency Virus Type 1 Are Associated
with Interclade Polymorphisms and Intraclade Phylogenetic Clustering
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID T-CELL RESPONSES; CHRONIC HIV-1 INFECTION; HEPATITIS-C VIRUS; LYMPHOCYTE
RESPONSE; SEQUENCE DIVERSITY; DOMINANT INFLUENCE; POPULATION-LEVEL;
VACCINE DESIGN; VIRAL LOAD; ESCAPE
AB The selection of escape mutations has a major impact on immune control of infections with viruses such as human immunodeficiency virus (HIV). Viral evasion of CD8(+) T-cell responses leaves predictable combinations of escape mutations, termed HLA "footprints." The most clearly defined footprints are those associated with HLA alleles that are linked with successful control of HIV, such as HLA-B*57. Here we investigated the extent to which HLA footprint sites in HIV type 1 (HIV-1) are associated with viral evolution among and within clades. First, we examined the extent to which amino acid differences between HIV-1 clades share identity with sites of HLA-mediated selection pressure and observed a strong association, in particular with respect to sites of HLA-B selection (P < 10(-6)). Similarly, the sites of amino acid variability within a clade were found to overlap with sites of HLA-selected mutation. Second, we studied the impact of HLA selection on interclade phylogeny. Removing the sites of amino acid variability did not significantly affect clade-specific clustering, reflecting the central role of founder effects in establishing distinct clades. However, HLA footprints may underpin founder strains, and we show that amino acid substitutions between clades alter phylogeny, underlining a potentially substantial role for HLA in driving ongoing viral evolution. Finally, we investigated the impact of HLA selection on within-clade phylogeny and demonstrate that even a single HLA allele footprint can result in significant phylogenetic clustering of sequences. In conclusion, these data highlight the fact that HLA can be a strong selection force for both intra- and interclade HIV evolution at a population level.
C1 [Matthews, Philippa C.; Leslie, Alasdair J.; Crawford, Hayley; Payne, Rebecca; Prendergast, Andrew; Klenerman, Paul; Goulder, Philip J. R.] Nuffield Dept Med, Dept Paediat, Oxford OX1 3SY, England.
[Katzourakis, Aris; Pybus, Oliver G.] Univ Oxford, Dept Zool, Oxford OX1 3SY, England.
[Power, Karen; Walker, Bruce D.; Allen, Todd M.; Goulder, Philip J. R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Res Ctr, Boston, MA USA.
[Carlson, Jonathan; Heckerman, David] Microsoft Res, Redmond, WA USA.
[Kelleher, Anthony D.] St Vincents Hosp, Ctr Immunol, Sydney, NSW 2010, Australia.
[Ndung'u, Thumbi; Walker, Bruce D.; Goulder, Philip J. R.] Univ KwaZulu Natal, Doris Duke Med Res Inst, HIV Pathogenesis Programme, Durban, South Africa.
[Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA.
RP Matthews, PC (reprint author), Nuffield Dept Med, Dept Paediat, Peter Medawar Bldg Pathogen Res,S Parks Rd, Oxford OX1 3SY, England.
EM p.matthews@doctors.org.uk; philip.goulder@paediatrics.ox.ac.uk
RI pybus, oliver/B-2640-2012; Allen, Todd/F-5473-2011;
OI Katzourakis, Aris/0000-0003-3328-6204; Matthews,
Philippa/0000-0002-4036-4269; Pybus, Oliver/0000-0002-8797-2667;
Ndung'u, Thumbi/0000-0003-2962-3992
FU National Institutes of Health [NO1-A1-15422, 2RO1AI46995-06,
R01A1067073]; Wellcome Trust; UK Medical Research Council; Mark and Lisa
Schwartz Foundation; AIDS Foundation Scientist
FX This work was funded by the National Institutes of Health ( contracts
NO1-A1-15422, 2RO1AI46995-06, and R01A1067073), the Wellcome Trust ( A.
L. and P. G.), the UK Medical Research Council ( P. M. and A. P.), and
the Mark and Lisa Schwartz Foundation. P. G. is an Elizabeth Glaser
Pediatric AIDS Foundation Scientist.
NR 40
TC 29
Z9 29
U1 0
U2 0
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD MAY 1
PY 2009
VL 83
IS 9
BP 4605
EP 4615
DI 10.1128/JVI.02017-08
PG 11
WC Virology
SC Virology
GA 431DN
UT WOS:000265041600059
PM 19244334
ER
PT J
AU Boudoux, C
Leuin, SC
Oh, WY
Suter, MJ
Desiardins, AE
Vakoc, BJ
Bourna, BE
Hartnick, CJ
Tearney, GJ
AF Boudoux, C.
Leuin, S. C.
Oh, W. Y.
Suter, M. J.
Desiardins, A. E.
Vakoc, B. J.
Bourna, B. E.
Hartnick, C. J.
Tearney, G. J.
TI Preliminary Evaluation of Noninvasive Microscopic Imaging Techniques for
the Study of Vocal Fold Development
SO JOURNAL OF VOICE
LA English
DT Article
CT 36th Annual Symposium on Care of the Professional Voice
CY JUN 01, 2007
CL Philadelphia, PA
SP Voice Fdn
DE Laryngology; Pediatric vocal fold development; Noninvasive optical
imaging; Optical coherence tomography; Reflectance confocal microscopy;
Optical coherence microscopy; Porcine vocal fold
ID OPTICAL COHERENCE TOMOGRAPHY; ENCODED CONFOCAL MICROSCOPY; IN-VIVO;
HIGH-SPEED; LAMINA PROPRIA; HUMAN-SKIN; LASER; MICROFLAP; HISTOLOGY;
LESIONS
AB Understanding pediatric voice development and laryngeal pathology is predicated on a detailed knowledge of the microanatomy of the layered structure of the vocal fold. Our current knowledge of this microanatomy and its temporal evolution is limited by the lack of pediatric specimen availability. By providing the capability to image pediatric vocal folds in vivo, a noninvasive microscopy technique could greatly expand the existing database of pediatric laryngeal microanatomy and could furthermore make longitudinal Studies possible. A variety of natural-contrast optical imaging technologies, including optical frequency domain imaging (OFDI), full-field optical coherence microscopy (FF-OCM), and spectrally encoded confocal microscopy (SECM) have been recently developed for noninvasive diagnosis in adult patients. In this paper, we demonstrate the potential of these three techniques for laryngeal investigation by obtaining images of excised porcine vocal fold samples. In our study, OFDI allowed visualization of the vocal fold architecture deep within the tissue, from the superficial mucosa to the vocalis muscle. The micron-level resolution of SECM allowed investigation of cells and extracellular matrix fibrils from the superficial mucosa to the intermediate layer of the lamina propria (LP) (350 mu m penetration depth). The large field of view (Lip to 700 Am), penetration depth (up to 500 mu m), and resolution (2 X 2 X 1 mu m [X X Y X Z]) of FF-OCM enabled comprehensive three-dimensional evaluation of the layered structure of the LP. Our results Suggest that these techniques provide important and complementary cellular and structural information, which may be useful for investigating pediatric vocal fold maturation in vivo.
C1 [Leuin, S. C.; Hartnick, C. J.] Harvard Univ, Sch Med, Dept Otolaryngol, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
[Boudoux, C.; Oh, W. Y.; Suter, M. J.; Desiardins, A. E.; Vakoc, B. J.; Bourna, B. E.; Tearney, G. J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA.
[Boudoux, C.] Ecole Polytech, Dept Engn Phys, Montreal, PQ H3C 3A7, Canada.
RP Hartnick, CJ (reprint author), Harvard Univ, Sch Med, Dept Otolaryngol, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA.
EM christopher_hartnick@meei.harvard.edu
RI Oh, Wang-Yuhl/C-2055-2011; Boudoux, Caroline/A-6399-2012
NR 46
TC 7
Z9 7
U1 1
U2 4
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0892-1997
J9 J VOICE
JI J. Voice
PD MAY
PY 2009
VL 23
IS 3
BP 269
EP 276
DI 10.1016/j.jvoice.2007.10.003
PG 8
WC Otorhinolaryngology
SC Otorhinolaryngology
GA 448IT
UT WOS:000266257000001
PM 18346865
ER
PT J
AU Wheeler, S
Bowen, JD
Maynard, C
Lowy, E
Sun, HL
Sales, AE
Smith, NL
Fihn, SD
AF Wheeler, Stephanie
Bowen, Jennie D.
Maynard, Charles
Lowy, Elliot
Sun, Haili
Sales, Anne E.
Smith, Nicholas L.
Fihn, Stephan D.
TI Women Veterans and Outcomes after Acute Myocardial Infarction
SO JOURNAL OF WOMENS HEALTH
LA English
DT Article
ID ACUTE CORONARY SYNDROMES; HEALTH-CARE-SYSTEM; QUALITY-OF-CARE;
SEX-DIFFERENCES; HOSPITAL DISCHARGE; ARTERY DISEASE; MEN; MANAGEMENT;
MORTALITY; GENDER
AB Background: Previous studies have shown that women have decreased survival and receive fewer cardiac procedures after acute myocardial infarction (AMI) compared with men, raising concerns for sexual bias in provision of care. The objective of this study is to describe clinical characteristics, treatment, and survival in women veterans compared with men after admission to VA hospitals for AMI.
Methods: This is a retrospective inception cohort study using data drawn from the VA Cardiac Care Follow-up Clinical Study, describing patients admitted for AMI to VA hospitals from October 1, 2003 to March 31, 2005. Subjects were followed for 1 year.
Results: There were 236 women and 13,259 men admitted during the study period to VA hospitals with AMI. Women were less likely to have a history of heart failure compared with men (18.2% of women vs. 27.2% of men, p = 0.002) and previous coronary artery bypass grafting (CABG) (11.4% of women vs. 19.6% of men, p=0.002). Diagnostic cardiac catheterization was similar in women and men (36.9% and 34.9%, p = 0.539). Crude in-hospital mortality was 4.2% for women and 7.6% for men (p=0.051). After adjusting for comorbidities and treatment variables, in-hospital mortality was not significantly different for women compared with men (hazard ratio [HR] 0.82, 95% confidence interval [CI] 0.60-1.12).
Conclusions: Women veterans receive a level of care similar to men veterans for MI treated in VA hospitals. Differences in mortality between women and men were not significant and do not suggest that women fare worse.
C1 [Wheeler, Stephanie; Bowen, Jennie D.; Maynard, Charles; Lowy, Elliot; Sun, Haili; Sales, Anne E.; Fihn, Stephan D.] VA Puget Sound Hlth Care Syst, VA NW Hlth Serv Res & Dev Ctr Excellence, Seattle, WA 98108 USA.
[Maynard, Charles; Smith, Nicholas L.] VA Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Seattle, WA 98108 USA.
RP Wheeler, S (reprint author), VA Puget Sound Hlth Care Syst, VA NW Hlth Serv Res & Dev Ctr Excellence, S-111-GIMC,1660 S Columbian Way, Seattle, WA 98108 USA.
EM stephanie.wheeler@med.va.gov
RI Sales, Anne/D-9678-2012; Maynard, Charles/N-3906-2015;
OI Maynard, Charles/0000-0002-1644-7814; Sales, Anne/0000-0001-9360-3334
NR 23
TC 2
Z9 2
U1 0
U2 0
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 MAY
PY 2009
VL 18
IS 5
BP 613
EP 618
DI 10.1089/jwh.2008.1073
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 446DP
UT WOS:000266100900003
PM 19392640
ER
PT J
AU Kuy, S
AF Kuy, SreyRam
TI Women Have Better Outcomes In Cholecystitis
SO JOURNAL OF WOMENS HEALTH
LA English
DT Meeting Abstract
C1 [Kuy, SreyRam] Yale Univ, Sch Med, US Dept Vet Affairs, Robert Wood Johnson Clin Scholars Program, New Haven, CT 06520 USA.
[Kuy, SreyRam] Univ Texas Hlth Sci Ctr San Antonio, Dept Surg, San Antonio, TX USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1540-9996
J9 J WOMENS HEALTH
JI J. Womens Health
PD MAY
PY 2009
VL 18
IS 5
MA 30
BP 753
EP 753
PG 1
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 446DP
UT WOS:000266100900049
ER
PT J
AU Menefee, DS
Gwynn, S
Dao, TK
Teng, E
Graham, DP
AF Menefee, Deleene S.
Gwynn, Stacy
Dao, Tam K.
Teng, Ellen
Graham, David P.
TI Preliminary Examination of Correlates of Deployment Risk and Protective
Factors and Mental Health Outcomes among OEF/OIF Women Veterans.
SO JOURNAL OF WOMENS HEALTH
LA English
DT Meeting Abstract
C1 [Menefee, Deleene S.; Gwynn, Stacy; Dao, Tam K.; Teng, Ellen; Graham, David P.] Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA.
[Menefee, Deleene S.; Dao, Tam K.; Teng, Ellen; Graham, David P.] Baylor Coll Med, Menninger Dept Psychiat & Behav Med, Houston, TX 77030 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1540-9996
J9 J WOMENS HEALTH
JI J. Womens Health
PD MAY
PY 2009
VL 18
IS 5
MA 33
BP 754
EP 754
PG 1
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 446DP
UT WOS:000266100900052
ER
PT J
AU McCarthy, MW
Pelletier, L
Morrow, L
AF McCarthy, Maureen W.
Pelletier, Linda
Morrow, Lori
TI PREOPERATIVE STOMA MARKING BEGINS THE CARE CONTINUUM
SO JOURNAL OF WOUND OSTOMY AND CONTINENCE NURSING
LA English
DT Meeting Abstract
C1 [McCarthy, Maureen W.; Pelletier, Linda; Morrow, Lori] Massachusetts Gen Hosp, Boston, MA 02114 USA.
EM mmccarthy29@partners.org; LPELLETIER@PARTNERS.ORG; lmorrow@partners.org
NR 0
TC 0
Z9 0
U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1071-5754
J9 J WOUND OSTOMY CONT
JI J. Wound Ostomy Cont. Nurs.
PD MAY-JUN
PY 2009
VL 36
IS 3
BP S44
EP S44
PG 1
WC Nursing
SC Nursing
GA 446KH
UT WOS:000266120000131
ER
PT J
AU McCarthy, MW
Pelletier, L
Morrow, L
AF McCarthy, Maureen W.
Pelletier, Linda
Morrow, Lori
TI CREATIVE AND EFFECTIVE FISTULA MANAGEMENT
SO JOURNAL OF WOUND OSTOMY AND CONTINENCE NURSING
LA English
DT Meeting Abstract
C1 [McCarthy, Maureen W.; Pelletier, Linda; Morrow, Lori] Massachusetts Gen Hosp, Boston, MA 02114 USA.
EM mmccarthy29@partners.org; LPELLETIER@PARTNERS.ORG; lmorrow@partners.org
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 1071-5754
J9 J WOUND OSTOMY CONT
JI J. Wound Ostomy Cont. Nurs.
PD MAY-JUN
PY 2009
VL 36
IS 3
BP S18
EP S19
PG 2
WC Nursing
SC Nursing
GA 446KH
UT WOS:000266120000050
ER
PT J
AU Brunelli, SM
Thadhani, R
Ikizler, TA
Feldman, HI
AF Brunelli, Steven M.
Thadhani, Ravi
Ikizler, T. Alp
Feldman, Harold I.
TI Thiazolidinedione use is associated with better survival in hemodialysis
patients with non-insulin dependent diabetes
SO KIDNEY INTERNATIONAL
LA English
DT Article
DE diabetes; dialysis; epidemiology; mortality; survival thiazolidinediones
ID IMPROVES GLYCEMIC CONTROL; CHRONIC DIALYSIS PATIENTS;
CORONARY-ARTERY-DISEASE; INTIMA-MEDIA THICKNESS; CARDIOVASCULAR-DISEASE;
PIOGLITAZONE HYDROCHLORIDE; RANDOMIZED-TRIAL; ROSIGLITAZONE; MELLITUS;
THERAPY
AB Cardiovascular mortality is especially high among dialysis patients with diabetes, as is morbidity due to protein energy wasting. Given that both of these factors may be decreased by thiazolidinedione treatment, we studied the effect of thiazolidinedione use on survival among chronic dialysis patients in a national cohort of 5290 incident dialysis patients with diabetes. Thiazolidinedione use was assessed according to prescription data, and the analyses were stratified based on insulin use due to observed interaction. In the primary analysis, thiazolidinedione treatment was associated with significantly lower all-cause mortality among insulin-free but not insulin-requiring subjects, with adjusted hazards ratios of 0.53 (0.31-0.89) and 0.82 (0.46-1.47) respectively. Sensitivity analyses found the findings to be robust with respect to confounding by indication, severity of the diabetes, potential reverse causality, and time varying exposure patterns. The mechanism of this decline in all-cause mortality will need to be examined after these studies are confirmed.
C1 [Brunelli, Steven M.; Feldman, Harold I.] Univ Penn, Sch Med, Renal Electrolyte & Hypertens Div, Philadelphia, PA 19104 USA.
[Brunelli, Steven M.; Feldman, Harold I.] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[Thadhani, Ravi] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Renal Unit,Dept Med, Boston, MA 02115 USA.
[Ikizler, T. Alp] Vanderbilt Univ, Med Ctr, Div Nephrol, Nashville, TN USA.
RP Brunelli, SM (reprint author), Harvard Univ, Sch Med, Div Renal, Brigham & Womens Hosp, 75 Francis St,MRB 4, Boston, MA 02115 USA.
EM sbrunelli@partners.org
FU NIDDK [1K23DK079056]; American Heart Association [0775021N]; National
Kidney Foundation Satellite Dialysis Research Fellowship
FX We thank Raymond Boston and Russell Localio for their advice regarding
competing risks models. This study was supported in part by awards from
the NIDDK (1K23DK079056), the American Heart Association (0775021N), and
the National Kidney Foundation Satellite Dialysis Research Fellowship)
to SMB. SMB had full access to all of the data and takes responsibility
for the integrity and accuracy of the data analysis.
NR 45
TC 25
Z9 27
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0085-2538
J9 KIDNEY INT
JI Kidney Int.
PD MAY
PY 2009
VL 75
IS 9
BP 961
EP 968
DI 10.1038/ki.2009.4
PG 8
WC Urology & Nephrology
SC Urology & Nephrology
GA 433QM
UT WOS:000265220900014
PM 19190679
ER
PT J
AU Klusmann, JH
Godinho, FJ
Heitmarm, K
Pushpanathan, T
Reinhardt, D
Orkin, SH
Li, Z
AF Klusmann, J. H.
Godinho, F. J.
Heitmarm, K.
Pushpanathan, T.
Reinhardt, D.
Orkin, S. H.
Li, Z.
TI Developmental stage-specific interplay between GATA1 and IGF signaling
during fetal hematopoiesis and leukemogenesis
SO KLINISCHE PADIATRIE
LA English
DT Meeting Abstract
C1 [Klusmann, J. H.; Godinho, F. J.; Orkin, S. H.; Li, Z.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA.
[Orkin, S. H.; Li, Z.] Harvard Univ, Sch Med, Boston, MA USA.
[Orkin, S. H.; Li, Z.] Harvard Stem Cell Inst, Boston, MA USA.
[Orkin, S. H.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Godinho, F. J.; Orkin, S. H.] Howard Hughes Med Inst, Boston, MA 02115 USA.
[Klusmann, J. H.; Heitmarm, K.; Pushpanathan, T.; Reinhardt, D.] Hannover Med Sch, Dept Pediat Hematol Oncol, D-3000 Hannover, Germany.
RI Reinhardt, Dirk/D-3939-2011
OI Reinhardt, Dirk/0000-0003-4313-9056
NR 0
TC 0
Z9 0
U1 0
U2 0
PU GEORG THIEME VERLAG KG
PI STUTTGART
PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0300-8630
J9 KLIN PADIATR
JI Klinische Padiatr.
PD MAY-JUN
PY 2009
VL 221
IS 3
MA 29
BP 200
EP 200
PG 1
WC Pediatrics
SC Pediatrics
GA 446ZL
UT WOS:000266161300045
ER
PT J
AU Pushpanathan, T
Klusmann, J
Li, Z
Bohmer, K
Godinho, FJ
Koch, ML
Orkin, SH
Reinhardt, D
AF Pushpanathan, T.
Klusmann, J.
Li, Z.
Boehmer, K.
Godinho, F. J.
Koch, M. L.
Orkin, S. H.
Reinhardt, D.
TI Oncogenic Potential of miR-125b-2 and its Target Genes in Normal and
Malignant Hematopoesis
SO KLINISCHE PADIATRIE
LA English
DT Meeting Abstract
C1 [Pushpanathan, T.; Klusmann, J.; Boehmer, K.; Koch, M. L.; Reinhardt, D.] Hannover Med Sch, Dept Pediat Hematol Oncol, D-3000 Hannover, Germany.
[Li, Z.; Orkin, S. H.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[Li, Z.; Orkin, S. H.] Harvard Stem Cell Inst, Cambridge, MA USA.
[Orkin, S. H.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Godinho, F. J.; Orkin, S. H.] Howard Hughes Med Inst, Boston, MA 02115 USA.
[Li, Z.; Godinho, F. J.; Orkin, S. H.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA.
RI Reinhardt, Dirk/D-3939-2011
OI Reinhardt, Dirk/0000-0003-4313-9056
NR 0
TC 1
Z9 1
U1 0
U2 0
PU GEORG THIEME VERLAG KG
PI STUTTGART
PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0300-8630
J9 KLIN PADIATR
JI Klinische Padiatr.
PD MAY-JUN
PY 2009
VL 221
IS 3
MA 51
BP 205
EP 205
PG 1
WC Pediatrics
SC Pediatrics
GA 446ZL
UT WOS:000266161300066
ER
PT J
AU Swan, EEL
Peppi, M
Chen, ZQ
Green, KM
Evans, JE
McKenna, MJ
Mescher, MJ
Kujawa, SG
Sewell, WF
AF Swan, Erin E. Leary
Peppi, Marcello
Chen, Zhiqiang
Green, Karin M.
Evans, James E.
McKenna, Michael J.
Mescher, Mark J.
Kujawa, Sharon G.
Sewell, William F.
TI Proteomics Analysis of Perilymph and Cerebrospinal Fluid in Mouse
SO LARYNGOSCOPE
LA English
DT Article
DE Intracochlear; drug delivery; biofouling; inner ear; protein
ID PROTEIN; ELECTROPHORESIS; PEPTIDES; SEARCH
AB Objectives: Proteins in perilymph may alter the delivery profile of implantable intracochlear drug delivery systems through biofouling. Knowledge of protein composition will help anticipate interactions with delivered agents.
Study Design: Analysis of mouse perilymph.
Methods: Protein composition of perilymph and cerebrospinal fluid (CSF) was analyzed using a capillary liquid chromatography-mass spectrometry-based iTRAQ quantitative proteomics approach. We searched against a mouse subset of the Uniprot FASTA protein database. We sampled perilymph from the apex of the mouse cochlea to minimize CSF contamination.
Results: More than 50 explicit protein isoforms were identified with very high confidence. iTRAQ reporter ions allowed determination of relative molar amounts of proteins between perilymph and CSF. Protein in perilymph was almost three times more concentrated than in CSF. More than one-third of the proteins in perilymph comprised protease inhibitors, with serpins being the predominant group. Apolipoproteins constituted 16%. Fifteen percent of the proteins were enzymes. Albumin was the most abundant single protein (14%). Proteins with relatively high perilymph/CSF ratios included broad-spectrum protease inhibitors and apolipoproteins.
Discussion: Some proteins found in perilymph, such as albumin and HMW kininogen, have been implicated in biofouling through adsorption to device materials. The relatively large quantities of apolipoprotein and albumin may serve as a reservoir for acidic and lipophillic drugs. Alpha-2-glycoprotein can bind basic drugs.
Conclusions: Perilymph is similar in protein composition to CSF, though amounts are 2.8 times higher. Protease inhibitors comprise the largest category of proteins.
C1 [Peppi, Marcello; Chen, Zhiqiang; Kujawa, Sharon G.; Sewell, William F.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA.
[Swan, Erin E. Leary; McKenna, Michael J.] Charles Stark Draper Lab Inc, Cambridge, MA 02139 USA.
[Swan, Erin E. Leary] MIT, Dept Mech Engn, Cambridge, MA 02139 USA.
[Peppi, Marcello; Chen, Zhiqiang; McKenna, Michael J.; Kujawa, Sharon G.; Sewell, William F.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA.
[Sewell, William F.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA.
[Kujawa, Sharon G.] Massachusetts Eye & Ear Infirm, Dept Audiol, Boston, MA 02114 USA.
[Green, Karin M.; Evans, James E.] Univ Massachusetts, Sch Med, Dept Mol Pharmacol & Biochem, Worcester, MA USA.
RP Sewell, WF (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA.
EM wfs@epl.meei.harvard.edu
FU National Institutes of Health (NIH) [5 R01 DC 006848-02]
FX This work was supported by Grant Number 5 R01 DC 006848-02 from the
National Institutes of Health (NIH) and its contents are solely the
responsibility of the authors and do not necessarily represent the
official views of the NIH or the U.S. government.
NR 23
TC 14
Z9 16
U1 0
U2 5
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0023-852X
J9 LARYNGOSCOPE
JI Laryngoscope
PD MAY
PY 2009
VL 119
IS 5
BP 953
EP 958
DI 10.1002/lary.20209
PG 6
WC Medicine, Research & Experimental; Otorhinolaryngology
SC Research & Experimental Medicine; Otorhinolaryngology
GA 442UL
UT WOS:000265866000019
PM 19358201
ER
PT J
AU Nadkarni, SK
Bouma, BE
de Boer, J
Tearney, GJ
AF Nadkarni, Seemantini K.
Bouma, Brett E.
de Boer, Johannes
Tearney, Guillermo J.
TI Evaluation of collagen in atherosclerotic plaques: the use of two
coherent laser-based imaging methods
SO LASERS IN MEDICAL SCIENCE
LA English
DT Review
DE Lasers; Atherosclerosis; Collagen; Smooth muscle cells; Optical
coherence tomography; Laser speckle imaging
ID INTRAVASCULAR ULTRASOUND; RAMAN-SPECTROSCOPY; CORONARY ATHEROSCLEROSIS;
BIOLOGICAL TISSUE; TOMOGRAPHY; BIREFRINGENCE; CHOLESTEROL; COMPONENTS;
THICKNESS; ARTERIES
AB Acute coronary events such as myocardial infarction are frequently caused by the rupture of unstable atherosclerotic plaque. Collagen plays a key role in determining plaque stability. Methods to measure plaque collagen content are invaluable in detecting unstable atherosclerotic plaques. Recently, novel coherent laser-based imaging techniques, such as polarization-sensitive optical coherence tomography (PSOCT) and laser speckle imaging (LSI) have been investigated, and they provide a wealth of information related to collagen content and plaque stability. Additionally, given their potential for intravascular use, these technologies will be invaluable for improving our understanding of the natural history of plaque development and rupture and, hence, enable the detection of unstable plaques. In this article we review recent developments in these techniques and potential challenges in translating these methods into intra-arterial use in patients.
C1 [Nadkarni, Seemantini K.; Bouma, Brett E.; de Boer, Johannes; Tearney, Guillermo J.] Wellman Ctr Photomed, Boston, MA USA.
RP Nadkarni, SK (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, BAR 718,40 Blossom St, Boston, MA 02114 USA.
EM snadkarni@hms.harvard.edu
RI de Boer, Johannes/B-7590-2012
OI de Boer, Johannes/0000-0003-1253-4950
FU NHLBI NIH HHS [R01 HL076398-04, R01 HL076398]
NR 44
TC 23
Z9 25
U1 2
U2 13
PU SPRINGER LONDON LTD
PI ARTINGTON
PA ASHBOURNE HOUSE, THE GUILDWAY, OLD PORTSMOUTH ROAD, ARTINGTON GU3 1LP,
GUILDFORD, ENGLAND
SN 0268-8921
J9 LASER MED SCI
JI Lasers Med. Sci.
PD MAY
PY 2009
VL 24
IS 3
BP 439
EP 445
DI 10.1007/s10103-007-0535-x
PG 7
WC Engineering, Biomedical; Surgery
SC Engineering; Surgery
GA 437PL
UT WOS:000265499300021
PM 18386093
ER
PT J
AU Bruns, I
Czibere, A
Fischer, JC
Roels, F
Cadeddu, RP
Buest, S
Bruennert, D
Huenerlituerkoglu, AN
Stoecklein, NH
Singh, R
Zerbini, LF
Jager, M
Kobbe, G
Gattermann, N
Kronenwett, R
Brors, B
Haas, R
AF Bruns, I.
Czibere, A.
Fischer, J. C.
Roels, F.
Cadeddu, R-P
Buest, S.
Bruennert, D.
Huenerlituerkoglu, A. N.
Stoecklein, N. H.
Singh, R.
Zerbini, L. F.
Jaeger, M.
Kobbe, G.
Gattermann, N.
Kronenwett, R.
Brors, B.
Haas, R.
TI The hematopoietic stem cell in chronic phase CML is characterized by a
transcriptional profile resembling normal myeloid progenitor cells and
reflecting loss of quiescence
SO LEUKEMIA
LA English
DT Article
DE CML; BCR-ABL; stem and progenitor cells; gene expression
ID PROTEIN-KINASE-C; DOWN-REGULATION; POSITIVE CELLS; IN-VITRO; BCR-ABL;
LEUKEMIA; MIGRATION; CXCR4; EXPRESSION; GENES
AB We found that composition of cell subsets within the CD34+ cell population is markedly altered in chronic phase (CP) chronic myeloid leukemia (CML). Specifically, proportions and absolute cell counts of common myeloid progenitors (CMP) and megakaryocyte-erythrocyte progenitors (MEP) are significantly greater in comparison to normal bone marrow whereas absolute numbers of hematopoietic stem cells (HSC) are equal. To understand the basis for this, we performed gene expression profiling (Affymetrix HU-133A 2.0) of the distinct CD34+ cell subsets from six patients with CP CML and five healthy donors. Euclidean distance analysis revealed a remarkable transcriptional similarity between the CML patients' HSC and normal progenitors, especially CMP. CP CML HSC were transcriptionally more similar to their progeny than normal HSC to theirs, suggesting a more mature phenotype. Hence, the greatest differences between CP CML patients and normal donors were apparent in HSC including downregulation of genes encoding adhesion molecules, transcription factors, regulators of stem-cell fate and inhibitors of cell proliferation in CP CML. Impaired adhesive and migratory capacities were functionally corroborated by fibronectin detachment analysis and transwell assays, respectively. Based on our findings we propose a loss of quiescence of the CML HSC on detachment from the niche leading to expansion of myeloid progenitors. Leukemia (2009) 23, 892-899; doi:10.1038/leu.2008.392; published online 22 January 2009
C1 [Bruns, I.; Czibere, A.; Cadeddu, R-P; Buest, S.; Bruennert, D.; Singh, R.; Kobbe, G.; Gattermann, N.; Kronenwett, R.; Haas, R.] Univ Dusseldorf, Dept Hematol Oncol & Clin Immunol, D-40255 Dusseldorf, Germany.
[Fischer, J. C.] Univ Dusseldorf, Inst Transplantat Diagnost & Cell Therapeut, D-40255 Dusseldorf, Germany.
[Roels, F.; Brors, B.] German Canc Res Ctr, D-6900 Heidelberg, Germany.
[Huenerlituerkoglu, A. N.] Stadtische Kliniken Neuss, Lukaskrankenhaus, Neuss, Germany.
[Stoecklein, N. H.] Univ Dusseldorf, Dept Gen & Visceral Surg, D-40255 Dusseldorf, Germany.
[Zerbini, L. F.] Harvard Inst Med, BIDMC Genom Ctr, Boston, MA USA.
[Jaeger, M.] Univ Dusseldorf, Dept Orthoped Surg, D-40255 Dusseldorf, Germany.
RP Bruns, I (reprint author), Univ Dusseldorf, Dept Hematol Oncol & Clin Immunol, Moorenstr 5, D-40255 Dusseldorf, Germany.
EM ingmar.bruns@med.uni-duesseldorf.de
RI Brors, Benedikt/E-5620-2013; Zerbini, Luiz /B-7720-2015;
OI Brors, Benedikt/0000-0001-5940-3101; Brunnert,
Daniela/0000-0003-0870-9578; Fischer, Johannes/0000-0002-2079-1845
FU Leukamie Liga e. V. Dusseldorf; Forschungskommission der Medizinischen
Fakultat Dusseldorf
FX The following sources of financial support to IB and AC are greatly
appreciated: Leukamie Liga e. V. Dusseldorf, Forschungskommission der
Medizinischen Fakultat Dusseldorf. We thank Anne Koch and Sabrina
Pechtel for excellent technical assistance and Dr Bernd Giebel and Dr
Frank Neumann for fruitful discussions.
NR 45
TC 44
Z9 44
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0887-6924
J9 LEUKEMIA
JI Leukemia
PD MAY
PY 2009
VL 23
IS 5
BP 892
EP 899
DI 10.1038/leu.2008.392
PG 8
WC Oncology; Hematology
SC Oncology; Hematology
GA 444UO
UT WOS:000266006100010
PM 19158832
ER
PT J
AU Tefferi, A
Levine, RL
Lim, KH
Abdel-Wahab, O
Lasho, TL
Patel, J
Finke, CM
Mullally, A
Li, CY
Pardanani, A
Gilliland, DG
AF Tefferi, A.
Levine, R. L.
Lim, K-H
Abdel-Wahab, O.
Lasho, T. L.
Patel, J.
Finke, C. M.
Mullally, A.
Li, C-Y
Pardanani, A.
Gilliland, D. G.
TI Frequent TET2 mutations in systemic mastocytosis: clinical, KITD816V and
FIP1L1-PDGFRA correlates
SO LEUKEMIA
LA English
DT Article
DE KIT; PDGFRA; JAK2; MPL; myeloproliferative; eosinophilia
ID TYROSINE KINASE MUTATION; KIT MUTATION; MYELOPROLIFERATIVE-DISORDERS;
BONE-MARROW; MYELOFIBROSIS; JAK2(V617F); FUSION; CELLS; CLASSIFICATION;
INVOLVEMENT
AB TET2 (TET oncogene family member 2) is a candidate tumor suppressor gene located at chromosome 4q24, and was recently reported to be mutated in similar to 14% of patients with JAK2V617F-positive myeloproliferative neoplasms. We used high-throughput DNA sequence analysis to screen for TET2 mutations in bone marrow-derived DNA from 48 patients with systemic mastocytosis (SM), including 42 who met the 2008 WHO (World Health Organization) diagnostic criteria for SM and 6 with FIP1L1-PDGFRA. Twelve (29%) SM, but no FIP1L1-PDGFRA patients, had TET2 mutations. A total of 17 mutations (13 frameshift, 2 nonsense and 2 missense) were documented in 2 (15%) of 13 indolent SM patients, 2 (40%) of 5 aggressive SM, and 8 (35%) of 23 SM associated with a clonal non-mast cell-lineage hematopoietic disease (P = 0.52). KITD816V was detected by PCR sequencing in 50 or 20% of patients with or without TET2 mutation (P = 0.05), respectively. Multivariable analysis showed a significant association between the presence of TET2 mutation and monocytosis (P = 0.0003) or female sex (P = 0.05). The association with monocytosis was also observed in non-indolent SM (n = 29), in which the presence of mutant TET2 did not affect survival (P = 0.98). We conclude that TET2 mutations are frequent in SM, segregate with KITD816V and influence phenotype without necessarily altering prognosis. Leukemia (2009) 23, 900-904; doi:10.1038/leu.2009.37; published online 5 March 2009
C1 [Tefferi, A.; Lim, K-H; Lasho, T. L.; Finke, C. M.; Li, C-Y; Pardanani, A.] Mayo Clin, Div Hematol, Dept Med, Rochester, MN 55905 USA.
[Tefferi, A.; Lim, K-H; Lasho, T. L.; Finke, C. M.; Li, C-Y; Pardanani, A.] Mayo Clin, Div Hematopathol, Dept Lab Med, Rochester, MN 55905 USA.
[Levine, R. L.; Abdel-Wahab, O.; Patel, J.] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10021 USA.
[Levine, R. L.; Abdel-Wahab, O.] Mem Sloan Kettering Canc Ctr, Dept Med, Leukemia Serv, New York, NY 10021 USA.
[Lim, K-H] Mackay Mem Hosp, Div Hematol Oncol, Taipei, Taiwan.
[Lim, K-H] Mackay Med Nursing & Management Coll, Taipei, Taiwan.
[Mullally, A.; Gilliland, D. G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Div Hematol,Dept Med, Boston, MA 02115 USA.
[Gilliland, D. G.] Howard Hughes Med Inst, Boston, MA 02115 USA.
RP Tefferi, A (reprint author), Mayo Clin, Div Hematol, Dept Med, 200 1st St SW, Rochester, MN 55905 USA.
EM tefferi.ayalew@mayo.edu
OI Abdel-Wahab, Omar/0000-0002-3907-6171
FU Myeloproliferative Disorders Foundation, Chicago, IL, USA
FX Adriana Heguay and Igor Dolgalev from the Memorial Sloan-Kettering
Cancer Center, New York, NY, USA are acknowledged for their assistance
with sequence analysis. The current study was supported in part by
grants from the Myeloproliferative Disorders Foundation, Chicago, IL,
USA.
NR 24
TC 140
Z9 147
U1 0
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0887-6924
J9 LEUKEMIA
JI Leukemia
PD MAY
PY 2009
VL 23
IS 5
BP 900
EP 904
DI 10.1038/leu.2009.37
PG 5
WC Oncology; Hematology
SC Oncology; Hematology
GA 444UO
UT WOS:000266006100011
PM 19262599
ER
PT J
AU Tefferi, A
Pardanani, A
Lim, KH
Abdel-Wahab, O
Lasho, TL
Patel, J
Gangat, N
Finke, CM
Schwager, S
Mullally, A
Li, CY
Hanson, CA
Mesa, R
Bernard, O
Delhommeau, F
Vainchenker, W
Gilliland, DG
Levine, RL
AF Tefferi, A.
Pardanani, A.
Lim, K-H
Abdel-Wahab, O.
Lasho, T. L.
Patel, J.
Gangat, N.
Finke, C. M.
Schwager, S.
Mullally, A.
Li, C-Y
Hanson, C. A.
Mesa, R.
Bernard, O.
Delhommeau, F.
Vainchenker, W.
Gilliland, D. G.
Levine, R. L.
TI TET2 mutations and their clinical correlates in polycythemia vera,
essential thrombocythemia and myelofibrosis
SO LEUKEMIA
LA English
DT Article
DE JAK2; MPL; myeloproliferative; polycythemia; thrombocythemia;
myelofibrosis
ID TYROSINE KINASE MUTATION; JAK2 EXON-12 MUTATIONS; ACUTE
MYELOID-LEUKEMIA; MYELOPROLIFERATIVE-DISORDERS; V617F MUTATION;
ACTIVATING MUTATION; ALLELE BURDEN; KIT MUTATION; JAK2V617F; METAPLASIA
AB High-throughput DNA sequence analysis was used to screen for TET2 mutations in bone marrow-derived DNA from 239 patients with BCR-ABL-negative myeloproliferative neoplasms (MPNs). Thirty-two mutations (19 frameshift, 10 nonsense, 3 missense; mostly involving exons 4 and 12) were identified for an overall mutational frequency of similar to 13%. Specific diagnoses included polycythemia vera (PV; n = 89), essential thrombocythemia (ET; n = 57), primary myelofibrosis (PMF; n = 60), post-PV MF (n = 14), post-ET MF (n 7) and blast phase PV/ET/MF (n = 12); the corresponding mutational frequencies were similar to 16, 5, 17, 14, 14 and 17% (P = 0.50). Mutant TET2 was detected in similar to 17 and similar to 7% of JAK2V617F-positive and-negative cases, respectively (P = 0.04). However, this apparent clustering of the two mutations was accounted for by an independent association between mutant TET2 and advanced age; mutational frequency was similar to 23% in patients >= 60 years old versus similar to 4% in younger patients (P<0.0001). The presence of mutant TET2 did not affect survival, leukemic transformation or thrombosis in either PV or PMF; a correlation with hemoglobin <10 g per 100 ml in PMF was noted (P = 0.05). We conclude that TET2 mutations occur in both JAK2V617F-positive and-negative MPN, are more prevalent in older patients, display similar frequencies across MPN subcategories and disease stages, and hold limited prognostic relevance. Leukemia (2009) 23, 905-911; doi: 10.1038/leu.2009.47;published online 5 March 2009
C1 [Tefferi, A.; Pardanani, A.; Lim, K-H; Lasho, T. L.; Gangat, N.; Finke, C. M.; Schwager, S.; Li, C-Y; Hanson, C. A.; Mesa, R.] Mayo Clin, Dept Med, Div Hematol, Rochester, MN 55905 USA.
[Tefferi, A.; Pardanani, A.; Lim, K-H; Lasho, T. L.; Gangat, N.; Finke, C. M.; Schwager, S.; Li, C-Y; Hanson, C. A.; Mesa, R.] Mayo Clin, Div Hematopathol, Dept Lab Med, Rochester, MN 55905 USA.
[Lim, K-H] Mackay Mem Hosp, Div Hematol Oncol, Taipei, Taiwan.
[Lim, K-H] Mackay Med Nursing & Management Coll, Div Hematol Oncol, Taipei, Taiwan.
[Abdel-Wahab, O.; Patel, J.; Levine, R. L.] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10021 USA.
[Abdel-Wahab, O.; Levine, R. L.] Mem Sloan Kettering Canc Ctr, Dept Med, Leukemia Serv, New York, NY 10021 USA.
[Mullally, A.; Gilliland, D. G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Div Hematol,Dept Med, Boston, MA 02115 USA.
[Bernard, O.] Hop Necker Enfants Malad, INSERM, E0210, Paris, France.
[Bernard, O.] Hop Cochin, Hematol Lab, APHP, F-75674 Paris, France.
[Bernard, O.] Univ Paris 05, Paris, France.
[Delhommeau, F.; Vainchenker, W.] Inst Gustave Roussy, INSERM, U790, F-94805 Villejuif, France.
[Gilliland, D. G.] Howard Hughes Med Inst, Boston, MA 02115 USA.
RP Tefferi, A (reprint author), Mayo Clin, Dept Med, Div Hematol, Rochester, MN 55905 USA.
EM tefferi.ayalew@mayo.edu; leviner@mskcc.org
RI Bernard, Olivier/E-5721-2016;
OI Abdel-Wahab, Omar/0000-0002-3907-6171
FU Myeloproliferative Disorders Foundation, Chicago, IL, USA; Howard Hughes
Medical Institute; Doris Duke Charitable Foundation
FX Adriana Heguy and Igor Dolgalev from Memorial Sloan-Kettering Cancer
Center, New York, NY, USA are acknowledged for their assistance with
sequence analysis. This study was supported in part by grants from the
Myeloproliferative Disorders Foundation, Chicago, IL, USA. DGG is an
investigator of the Howard Hughes Medical Institute and is a Doris Duke
Charitable Foundation
NR 36
TC 246
Z9 261
U1 2
U2 12
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0887-6924
J9 LEUKEMIA
JI Leukemia
PD MAY
PY 2009
VL 23
IS 5
BP 905
EP 911
DI 10.1038/leu.2009.47
PG 7
WC Oncology; Hematology
SC Oncology; Hematology
GA 444UO
UT WOS:000266006100012
PM 19262601
ER
PT J
AU Raje, N
Hideshima, T
Mukherjee, S
Raab, M
Vallet, S
Chhetri, S
Cirstea, D
Pozzi, S
Mitsiades, C
Rooney, M
Kiziltepe, T
Podar, K
Okawa, Y
Ikeda, H
Carrasco, R
Richardson, PG
Chauhan, D
Munshi, NC
Sharma, S
Parikh, H
Chabner, B
Scadden, D
Anderson, KC
AF Raje, N.
Hideshima, T.
Mukherjee, S.
Raab, M.
Vallet, S.
Chhetri, S.
Cirstea, D.
Pozzi, S.
Mitsiades, C.
Rooney, M.
Kiziltepe, T.
Podar, K.
Okawa, Y.
Ikeda, H.
Carrasco, R.
Richardson, P. G.
Chauhan, D.
Munshi, N. C.
Sharma, S.
Parikh, H.
Chabner, B.
Scadden, D.
Anderson, K. C.
TI Preclinical activity of P276-00, a novel small-molecule cyclin-dependent
kinase inhibitor in the therapy of multiple myeloma
SO LEUKEMIA
LA English
DT Article
DE cyclin D; cyclin-dependent kinase; multiple myeloma; P276-00; small
molecule
ID ANTITUMOR-ACTIVITY; D1 OVEREXPRESSION; PATHOGENESIS; BORTEZOMIB;
CLASSIFICATION; ABNORMALITIES; DYSREGULATION; THALIDOMIDE; IDENTIFY;
ARREST
AB Cyclin D dysregulation and overexpression is noted in the majority of multiple myeloma (MM) patients, suggesting its critical role in MM pathogenesis. Here, we sought to identify the effects of targeting cyclin D in MM. We first confirmed cyclin D mRNA overexpression in 42 of 64 (65%) patient plasma cells. Silencing cyclin D1 resulted in >50% apoptotic cell death suggesting its validity as a potential therapeutic target. We next evaluated P276-00, a clinical-grade small-molecule cyclin-dependent kinase inhibitor as a way to target the cyclins. P276-00 resulted in dose-dependent cytotoxicity in MM cells. Cell-cycle analysis confirmed either growth arrest or caspase-dependent apoptosis; this was preceded by inhibition of Rb-1 phosphorylation with associated downregulation of a range of cyclins suggesting a regulatory role of P276-00 in cell-cycle progression through broad activity. Proliferative stimuli such as interleukin-6, insulin-like growth factor-1 and bone-marrow stromal cell adherence induced cyclins; P276-00 overcame these growth, survival and drug resistance signals. Because the cyclins are substrates of proteasome degradation, combination studies with bortezomib resulted in synergism. Finally, in vivo efficacy of P276-00 was confirmed in an MM xenograft model. These studies form the basis of an ongoing phase I study in the treatment of relapsed/refractory MM. Leukemia (2009) 23, 961-970; doi:10.1038/leu.2008.378; published online 8 January 2009
C1 [Raje, N.; Mukherjee, S.; Vallet, S.; Chabner, B.; Scadden, D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc,Div Hematol Oncol, Boston, MA 02114 USA.
[Raje, N.; Hideshima, T.; Raab, M.; Vallet, S.; Chhetri, S.; Cirstea, D.; Pozzi, S.; Mitsiades, C.; Rooney, M.; Kiziltepe, T.; Podar, K.; Okawa, Y.; Ikeda, H.; Carrasco, R.; Richardson, P. G.; Chauhan, D.; Munshi, N. C.; Sharma, S.; Anderson, K. C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Malignancies,Jerome Lipper Multiple M, Boston, MA 02114 USA.
[Sharma, S.; Parikh, H.] Nicholas Piramal India Ltd, Bombay, Maharashtra, India.
RP Raje, N (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc,Div Hematol Oncol, 55 Fruit St,POB 216, Boston, MA 02114 USA.
EM nraje@partners.org
RI Pozzi, Samantha/A-7617-2012
OI Pozzi, Samantha/0000-0001-7917-1774
FU Multiple Myeloma Research Foundation Awards; ASCO Career Development
Award; Department of Veterans Affairs merit review; Leukemia and
Lymphoma Society Scholar in Translational Research Award (NCM); NIH
[P50-100707, PO1-78378, RO1-50947]
FX This work was supported by Multiple Myeloma Research Foundation Awards
(NR, NCM and KCA); ASCO Career Development Award (NR); Department of
Veterans Affairs merit review grant and the Leukemia and Lymphoma
Society Scholar in Translational Research Award (NCM); NIH grants
P50-100707 and PO1-78378 (KCA, NCM) as well as NIH grant RO1-50947
(KCA).
NR 37
TC 42
Z9 42
U1 0
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0887-6924
J9 LEUKEMIA
JI Leukemia
PD MAY
PY 2009
VL 23
IS 5
BP 961
EP 970
DI 10.1038/leu.2008.378
PG 10
WC Oncology; Hematology
SC Oncology; Hematology
GA 444UO
UT WOS:000266006100019
PM 19151776
ER
PT J
AU Randolph, C
Hilsabeck, R
Kato, A
Kharbanda, P
Li, YY
Mapelli, D
Ravdin, LD
Romero-Gomez, M
Stracciari, A
Weissenborn, K
AF Randolph, Christopher
Hilsabeck, Robin
Kato, Ainobu
Kharbanda, Parampreet
Li, Yu-Yuan
Mapelli, Daniela
Ravdin, Lisa D.
Romero-Gomez, Manuel
Stracciari, Andrea
Weissenborn, Karin
TI Neuropsychological assessment of hepatic encephalopathy: ISHEN practice
guidelines
SO LIVER INTERNATIONAL
LA English
DT Review
DE assessment; encephalopathy; hepatic; neuropsychological; outcome;
psychometric
ID QUALITY-OF-LIFE; PORTAL-SYSTEMIC ENCEPHALOPATHY; CRITICAL FLICKER
FREQUENCY; LIVER-TRANSPLANTATION; REPEATABLE BATTERY; NONALCOHOLIC
CIRRHOTICS; MAGNETIZATION-TRANSFER; CEREBRAL-DYSFUNCTION; PSYCHOMETRIC
TESTS; GLUCOSE-METABOLISM
AB Low-grade or minimal hepatic encephalopathy (MHE) is characterised by relatively mild neurocognitive impairments, and occurs in a substantial percentage of patients with liver disease. The presence of MHE is associated with a significant compromise of quality of life, is predictive of the onset of overt hepatic encephalopathy and is associated with a poorer prognosis for outcome. Early identification and treatment of MHE can improve quality of life and may prevent the onset of overt encephalopathy, but to date, there has been little agreement regarding the optimum method for detecting MHE. The International Society on Hepatic Encephalopathy and Nitrogen Metabolism convened a group of experts for the purpose of reviewing available data and making recommendations for a standardised approach for neuropsychological assessment of patients with liver disease who are at risk of MHE. Specific recommendations are presented, along with a proposed methodology for further refining these assessment procedures through prospective research.
C1 [Randolph, Christopher] Loyola Univ, Med Ctr, Dept Neurol, Maywood, IL 60153 USA.
[Hilsabeck, Robin] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA.
[Hilsabeck, Robin] S Texas Vet Hlth Care Syst, San Antonio, TX USA.
[Kato, Ainobu] Iwate Med Univ, Dept Internal Med, Morioka, Iwate, Japan.
[Kharbanda, Parampreet] Postgrad Inst Med Educ & Res, Dept Neurol, Chandigarh 160012, India.
[Li, Yu-Yuan] First Municipal Peoples Hosp Guangzhou, Dept Gastroenterol, Guangzhou, Guangdong, Peoples R China.
[Mapelli, Daniela] Univ Padua, Dept Gen Psychol, Padua, Italy.
[Ravdin, Lisa D.] Weill Cornell Med Ctr, Dept Neurol, New York, NY USA.
[Romero-Gomez, Manuel] Hosp Univ Valme, UGC Enfermedades Digestivas, Seville, Spain.
[Stracciari, Andrea] St Orsola Marcello Malpighi Hosp, Dept Neurol, Bologna, Italy.
[Weissenborn, Karin] Hannover Med Sch, Dept Neurol, D-30623 Hannover, Germany.
RP Randolph, C (reprint author), 1 E Erie,Suite 355, Chicago, IL 60611 USA.
EM crandol@lumc.edu
RI Romero Gomez, Manuel/L-8030-2014; IBIS, DIGESTIVAS/O-1913-2015;
OI MAPELLI, DANIELA/0000-0003-2168-1426
NR 70
TC 84
Z9 93
U1 3
U2 8
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1478-3223
J9 LIVER INT
JI Liver Int.
PD MAY
PY 2009
VL 29
IS 5
BP 629
EP 635
DI 10.1111/j.1478-3231.2009.02009.x
PG 7
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 430UI
UT WOS:000265014300003
PM 19302444
ER
PT J
AU Corey, KE
Shah, N
Misdraji, J
Abu Dayyeh, BK
Zheng, H
Bhan, AK
Chung, RT
AF Corey, Kathleen E.
Shah, Nirali
Misdraji, Joseph
Abu Dayyeh, Barham K.
Zheng, Hui
Bhan, Atul K.
Chung, Raymond T.
TI The effect of angiotensin-blocking agents on liver fibrosis in patients
with hepatitis C
SO LIVER INTERNATIONAL
LA English
DT Article
DE ACE inhibitors; angiotensin II receptor blocking agents; cirrhosis;
diabetes; hypertension
ID CONVERTING ENZYME-INHIBITOR; INSULIN-RESISTANCE; RECEPTOR ANTAGONIST;
PORTAL-HYPERTENSION; VIRUS-INFECTION; PROGRESSION; SYSTEM; RATS;
PERINDOPRIL; INTERFERON
AB Multiple studies implicate the renin-angiotensin system in hepatic fibrogenesis. Few studies have examined the effects of angiotensin blockade on liver fibrosis via human histology.
We studied the histological effect of angiotensin II blocking agents in chronic hepatitis C patients.
This was a retrospective study of 284 chronic hepatitis C patients from 2001 to 2006 who underwent a liver biopsy. Group I was comprised of 143 hypertensive patients who received angiotensin-blocking agents. Group II was comprised of 91 hypertensive subjects who received hypertensive agents other than angiotensin blockers. Group III was comprised of 50 non-hypertensive subjects.
The groups were similar in age, sex, hepatitis C genotype, viral load and disease duration. They varied significantly in total diabetic patients (Group I, 43; Group II, 10; Group III, 1; P=0.0001), consistent with recommended use of angiotensin-converting enzyme inhibitors in hypertensive diabetics. Non-hypertensive patients had significantly less fibrosis than hypertensive patients, regardless of antihypertensive medications (Group I, 3.20; Group II, 3.73; Group III, 2.5; P=0.0002). Group I had significantly less fibrosis than Group II (P=0.02). This finding persisted in a non-diabetic subgroup of Groups I and II (Group I, 3.07; Group II, 3.69; P=0.0129).
Patients with hepatitis C and hypertension have increased fibrosis compared with non-hypertensive patients. Hypertensive patients receiving angiotensin-blocking agents had less fibrosis than hypertensive patients who did not receive angiotensin-blocking agents. This suggests an association with hypertension, possibly via the renin-angiotensin system in the fibrosis development and suggests a beneficial role of angiotensin II blockade in hepatitis C virus-related fibrosis.
C1 [Corey, Kathleen E.; Abu Dayyeh, Barham K.; Chung, Raymond T.] Harvard Univ, Sch Med, Gastrointestinal Unit, Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Corey, Kathleen E.; Shah, Nirali; Abu Dayyeh, Barham K.; Chung, Raymond T.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Shah, Nirali] Harvard Univ, Sch Med, Dept Pediat, Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Misdraji, Joseph; Bhan, Atul K.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Zheng, Hui] Harvard Univ, Sch Med, Ctr Biostat, Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Chung, RT (reprint author), Harvard Univ, Sch Med, Gastrointestinal Unit, Massachusetts Gen Hosp, Warren 1007C,55 Fruit St, Boston, MA 02114 USA.
EM rtchung@partners.org
FU NIH [AI069939-01, DK078722]
FX Financial support: NIH AI069939-01 (RTC) and DK078722 (RTC).; Conflicts
of interest: No conflicts of interest exist.
NR 33
TC 35
Z9 36
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1478-3223
EI 1478-3231
J9 LIVER INT
JI Liver Int.
PD MAY
PY 2009
VL 29
IS 5
BP 748
EP 753
DI 10.1111/j.1478-3231.2009.01973.x
PG 6
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 430UI
UT WOS:000265014300022
PM 19220742
ER
PT J
AU Long, AA
AF Long, Aidan A.
TI Monoclonal antibodies and other biologic agents in the treatment of
asthma
SO MABS
LA English
DT Review
DE cytokine blockers; dendritic cell; monoclonal antibodies;
immunomodulators; T(H)2 cells; T(H)1 cells; airway inflammation; IgE;
omalizumab
ID NECROSIS-FACTOR-ALPHA; ANTI-IGE ANTIBODY; SEVERE PERSISTENT ASTHMA;
ALLERGIC BRONCHOPULMONARY ASPERGILLOSIS; PLACEBO-CONTROLLED TRIAL; HUMAN
EPITHELIAL-CELLS; CHURG-STRAUSS-SYNDROME; IL-5 RECEPTOR-ALPHA; AIRWAY
HYPERRESPONSIVENESS; T-CELLS
AB Asthma represents a syndrome of airway inflammatory diseases with complex pathology. The immunologic pathogenesis is being increasingly revealed and provides opportunity for targeted biological intervention. Current experience with immunomodulators as targeted therapy in asthma is described in this literature review. Targeted therapies have included strategies to activate dendritic cells through the TLR-9 receptors, to interrupt the action of T(H)2 cytokines with cytokine blockers and monoclonal antibodies, to promote development of TO responses, to block IgE mediated pathways and to block TNF alpha. Omalizumab is the only biological therapy that has an approved indication in asthma at this time. An improved understanding of the heterogeneity of asthma should allow for specific targeting of different disease phenotypes specific therapies including immunomodulators.
C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA.
RP Long, AA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol, 201,55 Fruit St, Boston, MA 02114 USA.
EM aalong@mgh.harvard.edu
NR 99
TC 13
Z9 14
U1 3
U2 4
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA
SN 1942-0862
J9 MABS
JI mAbs
PD MAY-JUN
PY 2009
VL 1
IS 3
BP 237
EP 246
PG 10
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 521CU
UT WOS:000271898000006
PM 20065638
ER
PT J
AU Noworolski, SM
Tien, PC
Merriman, R
Vigneron, DB
Qayyum, A
AF Noworolski, Susan M.
Tien, Phyllis C.
Merriman, Raphael
Vigneron, Daniel B.
Qayyum, Aliya
TI Respiratory motion-corrected proton magnetic resonance spectroscopy of
the liver
SO MAGNETIC RESONANCE IMAGING
LA English
DT Article
DE Spectroscopy; Liver; Steatosis; Nonalcoholic fatty liver disease;
Respiration; Motion correction
ID WOMENS INTERAGENCY HIV; CHRONIC HEPATITIS-C; IN-VIVO; NONALCOHOLIC
STEATOHEPATITIS; MR SPECTROSCOPY; IMAGING DATA; SIGNAL LOSS; H-1;
DISEASE; QUANTIFICATION
AB Purpose: To develop a post-processing, respiratory-motion correction algorithm for magnetic resonance spectroscopy (MRS) of the liver and to determine the incidence and impact of respiratory motion in liver MRS.
Materials and Methods: One hundred thirty-two subjects (27 healthy, 31 with nonalcoholic fatty liver disease and 74 HIV-infected with or without hepatitis C) were scanned with free breathing MRS at 1.5 T. Two spectral time series were acquired on an 8-ml single voxel using TR/TE=2500 ms/30 ms and (1) water suppression, 128 acquisitions, and (2) no water suppression, 8 acquisitions. Individual spectra were phased and frequency aligned to correct for intrallepatic motion. Next, water peaks more than 50% different from the median water peak area were identified and removed, and remaining spectra averaged to correct for presumed extrallepatic motion. Total CH(2)+CH(3) lipids to unsuppressed water ratios were compared before and after corrections.
Results: Intrahepatic-motion correction increased the signal to noise ratio (S/N) in all cases (median=11-fold). Presumed extrahepatic motion was present in 41% (54/132) of the subjects. Its correction altered the lipids/water magnitude (magnitude change: median=2.6%, maximum=290%, and was >5% in 25% of these subjects). The incidence and effect of respiratory motion on lipids/water magnitude were similar among the three groups.
Conclusion: Respiratory-motion correction of free breathing liver MRS greatly increased the S/N and, in a significant number of subjects, changed the lipids/water ratios, relevant for monitoring subjects. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Noworolski, Susan M.; Vigneron, Daniel B.; Qayyum, Aliya] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94107 USA.
[Noworolski, Susan M.; Vigneron, Daniel B.] Univ Calif San Francisco, Grad Grp Bioengn, San Francisco, CA 94107 USA.
[Tien, Phyllis C.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94107 USA.
[Tien, Phyllis C.] San Francisco VA Med Ctr, San Francisco, CA USA.
[Merriman, Raphael] Calif Pacific Med Ctr, Dept Gastroenterol, San Francisco, CA USA.
RP Noworolski, SM (reprint author), Univ Calif San Francisco, Dept Radiol & Biomed Imaging, 185 Berry St,Suite 350, San Francisco, CA 94107 USA.
EM sue@radiology.ucsf.edu
FU NCRR NIH HHS [M01 RR000071, M01 RR000079, M01 RR000083, M01-RR-00071,
M01-RR-00079, M01-RR-00083]; NIAID NIH HHS [K23 AI066943, K23 AI 66943,
K23 AI066943-05, U01 AI 34993, U01 AI 31834, U01 AI 34989, U01 AI
34994, U01 AI 35004, U01 AI 42590, U01 AI031834, U01 AI034989, U01
AI034993, U01 AI034994, U01 AI035004, U01 AI042590]; NICHD NIH HHS [P01
HD 40543, P01 HD040543, P01 HD040543-019001, U01 HD 32632, U01
HD032632]; NIDDK NIH HHS [DK 061738-SI, DK 074718-01, R01 DK074718, R01
DK074718-01A1, U01 DK061738, U01 DK061738-03S1]
NR 32
TC 16
Z9 16
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0730-725X
J9 MAGN RESON IMAGING
JI Magn. Reson. Imaging
PD MAY
PY 2009
VL 27
IS 4
BP 570
EP 576
DI 10.1016/j.mri.2008.08.008
PG 7
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 435DL
UT WOS:000265323800016
PM 18993007
ER
PT J
AU Cowley, MJ
Cotsapas, CJ
Williams, RBH
Chan, EKF
Pulvers, JN
Liu, MY
Luo, OJ
Nott, DJ
Little, PFR
AF Cowley, Mark J.
Cotsapas, Chris J.
Williams, Rohan B. H.
Chan, Eva K. F.
Pulvers, Jeremy N.
Liu, Michael Y.
Luo, Oscar J.
Nott, David J.
Little, Peter F. R.
TI Intra- and inter-individual genetic differences in gene expression
SO MAMMALIAN GENOME
LA English
DT Article
ID QUANTITATIVE TRAIT LOCI; INBRED MOUSE STRAINS; TRANSCRIPTION FACTOR;
NETWORKS; COEXPRESSION; PROFILES; DISEASE; BRAIN; YEAST; SUSCEPTIBILITY
AB Genetic variation is known to influence the amount of mRNA produced by a gene. Because molecular machines control mRNA levels of multiple genes, we expect genetic variation in components of these machines would influence multiple genes in a similar fashion. We show that this assumption is correct by using correlation of mRNA levels measured from multiple tissues in mouse strain panels to detect shared genetic influences. These correlating groups of genes (CGGs) have collective properties that on average account for 52-79% of the variability of their constituent genes and can contain genes that encode functionally related proteins. We show that the genetic influences are essentially tissue-specific and, consequently, the same genetic variations in one animal may upregulate a CGG in one tissue but downregulate the CGG in a second tissue. We further show similarly paradoxical behaviour of CGGs within the same tissues of different individuals. Thus, this class of genetic variation can result in complex inter- and intraindividual differences. This will create substantial challenges in humans, where multiple tissues are not readily available.
C1 [Cowley, Mark J.; Cotsapas, Chris J.; Williams, Rohan B. H.; Chan, Eva K. F.; Pulvers, Jeremy N.; Liu, Michael Y.; Luo, Oscar J.; Little, Peter F. R.] Univ New S Wales, Sch Biotechnol & Biomol Sci, Sydney, NSW, Australia.
[Cowley, Mark J.] St Vincents Hosp, Garvan Inst Med Res, Darlinghurst, NSW 2010, Australia.
[Cotsapas, Chris J.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Cotsapas, Chris J.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[Cotsapas, Chris J.] MIT & Harvard, Broad Inst, Cambridge, MA USA.
[Williams, Rohan B. H.; Little, Peter F. R.] Univ New S Wales, Clive & Vera Ramaciotti Ctr Gene Funct Anal, Sydney, NSW, Australia.
[Williams, Rohan B. H.] Australian Natl Univ, John Curtin Sch Med Res, Canberra, ACT 2601, Australia.
[Chan, Eva K. F.] Univ Calif Davis, Dept Plant Sci, Davis, CA 95616 USA.
[Nott, David J.] Univ New S Wales, Sch Math & Stat, Sydney, NSW, Australia.
[Nott, David J.] Dept Stat & Appl Probabil, Singapore, Singapore.
[Little, Peter F. R.] Natl Univ Singapore, Singapore 117548, Singapore.
RP Little, PFR (reprint author), Univ New S Wales, Sch Biotechnol & Biomol Sci, Sydney, NSW, Australia.
EM rohan.williams@anu.edu.au; peter.little@nus.edu.sg
RI Forkel, Stephanie/A-4018-2011; Little, Peter. F.R./C-9971-2009; Simon,
Simon/D-5128-2012; Cowley, Mark/D-4504-2012;
OI Forkel, Stephanie/0000-0003-0493-0283; Cowley, Mark/0000-0002-9519-5714;
Cotsapas, Chris/0000-0002-7772-5910
NR 55
TC 14
Z9 15
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0938-8990
EI 1432-1777
J9 MAMM GENOME
JI Mamm. Genome
PD MAY
PY 2009
VL 20
IS 5
BP 281
EP 295
DI 10.1007/s00335-009-9181-x
PG 15
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
GA 454EL
UT WOS:000266664800003
PM 19424753
ER
PT J
AU Kitambi, SS
McCulloch, KJ
Peterson, RT
Malicki, JJ
AF Kitambi, Satish S.
McCulloch, Kyle J.
Peterson, Randall T.
Malicki, Jarema J.
TI Small molecule screen for compounds that affect vascular development in
the zebrafish retina
SO MECHANISMS OF DEVELOPMENT
LA English
DT Article
DE Blood; Circulation; Intraocular; Hyaloid; Vasculature; Angiogenesis;
Chemical; Disease
ID MACULAR DEGENERATION; TRANSGENIC ZEBRAFISH; DRUG DISCOVERY; HYALOID
SYSTEM; DANIO-RERIO; CELL-DEATH; GENE; INHIBITORS; IDENTIFICATION;
EMBRYOGENESIS
AB Blood vessel formation in the vertebrate eye is a precisely regulated process. in the human retina, both an excess and a deficiency of blood vessels may lead to a loss of vision. To gain insight into the molecular basis of vessel formation in the vertebrate retina and to develop pharmacological means of manipulating this process in a living organism, we further characterized the embryonic zebrafish eye vasculature, and performed a small molecule screen for compounds that affect blood vessel morphogenesis. The screening of approximately 2000 compounds revealed four small molecules that at specific concentrations affect retinal vessel morphology but do not produce obvious changes in trunk vessels, or in the neuronal architecture of the retina. Of these, two induce a pronounced widening of vessel diameter without a substantial loss of vessel number, one compound produces a loss of retinal blood vessels accompanied by a mild increase of their diameter, and finally one other generates a severe loss of retinal vessels. This work demonstrates the utility of zebrafish as a screening tool for small molecules that affect eye vasculature and presents several compounds of potential therapeutic importance. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
C1 [Kitambi, Satish S.; McCulloch, Kyle J.; Malicki, Jarema J.] Harvard Univ, Sch Med, Dept Ophthalmol, MEEI, Boston, MA 02114 USA.
[Kitambi, Satish S.] Sodertorns Univ Coll, Sch Life Sci, Sodertorn, Sweden.
[Kitambi, Satish S.] Karolinska Inst, Dept Biosci & Nutr, S-10401 Stockholm, Sweden.
[Peterson, Randall T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
RP Malicki, JJ (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, MEEI, 243 Charles St, Boston, MA 02114 USA.
EM jarema_malicki@meei.harvard.edu
RI malicki, jarema/G-8611-2014
FU National Eye Institute [R01 EY016859]
FX We would like to thank Dr. William F. Sewell from the Department of
otolaryngology at Harvard Medical School for providing access to an
inverted microscope, Dr. Chengtian Zhao for help with designing anti-ACE
morpholino, Drs. Agneta Mode, Arindam Majumdar, and Breandan Kennedy for
comments on earlier versions of this manuscript, Drs. Jan Ake
Gustafsson, Agneta Mode, Lotta Hambraeus, Sodertoms Hogskola, and the
Department of Biosciences and Medical Nutrition at Karolinska Institutet
for funding and support. Drs. Peter Schulter, Amy Doherty, and David
Kokel from Randall Peterson lab as well as Dr. Caroline Shamu of the
Institute of Chemistry and Cell Biology at Harvard Medical School
provided valuable technical advice during this work. This project was
funded in part by a National Eye Institute award R01 EY016859 (to JM).
NR 57
TC 52
Z9 58
U1 1
U2 7
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0925-4773
J9 MECH DEVELOP
JI Mech. Dev.
PD MAY-JUN
PY 2009
VL 126
IS 5-6
BP 464
EP 477
DI 10.1016/j.mod.2009.01.002
PG 14
WC Developmental Biology
SC Developmental Biology
GA 457YU
UT WOS:000266975100016
PM 19445054
ER
PT J
AU Vogeli, C
Kang, R
Landrum, MB
Hasnain-Wynia, R
Weissman, JS
AF Vogeli, Christine
Kang, Raymond
Landrum, Mary Beth
Hasnain-Wynia, Romana
Weissman, Joel S.
TI Quality of Care Provided to Individual Patients in US Hospitals Results
From an Analysis of National Hospital Quality Alliance Data
SO MEDICAL CARE
LA English
DT Article
DE quality indicators; hospitalizations; inpatients
ID ACUTE MYOCARDIAL-INFARCTION; HEALTH-CARE; PERFORMANCE-MEASURES;
MORTALITY-RATES; UNITED-STATES; PNEUMONIA; OUTCOMES; THERAPY; TRIALS;
RISK
AB Background: There is little national data oil the characteristics of patients who receive high quality inpatient care defined as either the receipt of all appliable processes (all-or-none performance) or the proportion of applicable processes received during thier hospitalization.
Objectives: To assess the quality of care provided to patients hospitalized for acute myocardial infarction (AMI), heart failure or pneumonia, to describe variations in quality by patient and hospital characteristics, and the sensitivity of all-or-none performance to the number and type of processes.
Design and Subjects: Retrospective analysis of previously unavailable Hospital Quality Alliance patient-level data on 2.3 million individuals receiving care in non-federal US hospitals in 2005.
Measures: The proportion of patients who received all applicable care processes, and the mean proportion of applicable processes received by hospitalized patients.
C1 [Vogeli, Christine] Massachusetts Gen Hosp, Inst Hlth Policy, Dept Med, Boston, MA 02114 USA.
HRET, Amer Hosp Assoc, Chicago, IL USA.
[Landrum, Mary Beth] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
[Kang, Raymond; Hasnain-Wynia, Romana] Northwestern Univ, Feinberg Sch Med, Inst Healthcare Studies, Chicago, IL 60611 USA.
[Weissman, Joel S.] Execut Off Hlth & Human Serv, Boston, MA USA.
RP Vogeli, C (reprint author), Massachusetts Gen Hosp, Inst Hlth Policy, Dept Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA.
EM cvogeli@partners.org
FU The Commonwealth Fund; Robert Wood Johnson Foundation's Changes in
Health Care Financing and Organization (HCFO) Initiative
FX Neither funding organization was involved in the design, data
acquisition, analysis and interpretation of the data, or preparation of
the manuscript.
NR 24
TC 7
Z9 7
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0025-7079
J9 MED CARE
JI Med. Care
PD MAY
PY 2009
VL 47
IS 5
BP 591
EP 599
PG 9
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 438NY
UT WOS:000265563500013
PM 19365292
ER
PT J
AU Beddar, S
Archambault, L
Sahoo, N
Poenisch, F
Chen, GT
Gillin, MT
Mohan, R
AF Beddar, Sam
Archambault, Louis
Sahoo, Narayan
Poenisch, Falk
Chen, George T.
Gillin, Michael T.
Mohan, Radhe
TI Exploration of the potential of liquid scintillators for real-time 3D
dosimetry of intensity modulated proton beams
SO MEDICAL PHYSICS
LA English
DT Article
DE biomedical optical imaging; CCD image sensors; dosimetry; intensity
modulation; liquid scintillation detectors; Monte Carlo methods; proton
beams; radiation quenching; radiation therapy
ID DETECTORS; VERIFICATION; RADIATION; THERAPY
AB In this study, the authors investigated the feasibility of using a 3D liquid scintillator (LS) detector system for the verification and characterization of proton beams in real time for intensity and energy-modulated proton therapy. A plastic tank filled with liquid scintillator was irradiated with pristine proton Bragg peaks. Scintillation light produced during the irradiation was measured with a CCD camera. Acquisition rates of 20 and 10 frames per second (fps) were used to image consecutive frame sequences. These measurements were then compared to ion chamber measurements and Monte Carlo simulations. The light distribution measured from the images acquired at rates of 20 and 10 fps have standard deviations of 1.1% and 0.7%, respectively, in the plateau region of the Bragg curve. Differences were seen between the raw LS signal and the ion chamber due to the quenching effects of the LS and due to the optical properties of the imaging system. The authors showed that this effect can be accounted for and corrected by Monte Carlo simulations. The liquid scintillator detector system has a good potential for performing fast proton beam verification and characterization.
C1 [Beddar, Sam; Archambault, Louis; Sahoo, Narayan; Poenisch, Falk; Gillin, Michael T.; Mohan, Radhe] Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, Unit 94, Houston, TX 77030 USA.
[Chen, George T.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
RP Beddar, S (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, Unit 94, 1515 Holcombe Blvd, Houston, TX 77030 USA.
EM abeddar@mdanderson.org
FU National Cancer Institute (NCI) [1R01CA120198-01A2, 2P01CA021239-29A1];
Houston Endowment, Inc.; Award for Scientific Achievement at The
University of Texas M. D. Anderson Cancer Center
FX This work was supported in part by the National Cancer Institute (NCI)
(Grant Nos. 1R01CA120198-01A2 and 2P01CA021239-29A1). One of the authors
(L. A.) was supported in part by the Odyssey program and the Houston
Endowment, Inc. Award for Scientific Achievement at The University of
Texas M. D. Anderson Cancer Center.
NR 17
TC 27
Z9 27
U1 1
U2 3
PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS
PI MELVILLE
PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA
SN 0094-2405
J9 MED PHYS
JI Med. Phys.
PD MAY
PY 2009
VL 36
IS 5
BP 1736
EP 1743
DI 10.1118/1.3117583
PG 8
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 437ZX
UT WOS:000265526800032
PM 19544791
ER
PT J
AU Nappi, J
Yoshida, H
AF Naeppi, Janne
Yoshida, Hiroyuki
TI Virtual tagging for laxative-free CT colonography: Pilot evaluation
SO MEDICAL PHYSICS
LA English
DT Article
DE biological organs; computerised tomography; identification technology;
medical image processing; statistical analysis; virtual reality
ID COMPUTED TOMOGRAPHIC COLONOGRAPHY; COLORECTAL-CANCER; OBSERVER
PERFORMANCE; FALSE POSITIVES; AIDED DETECTION; POLYPS; COLONOSCOPY;
SEGMENTATION; FEASIBILITY; VALIDATION
AB Laxative-free computed tomographic colonography (lfCTC) could significantly improve patient adherence to colorectal screening. However, the interpretation of lfCTC data is complicated by the presence of poorly tagged feces and partial-volume artifacts that imitate colorectal lesions. The authors developed a method for virtual tagging of such artifacts. A probabilistic model of colonic wall was developed, and virtual tagging was performed on artifacts that were identified by the model. The method was evaluated with 46 clinical lfCTC cases that were prepared with dietary fecal tagging only. Visual examples show that the method can label partial-volume artifacts, poorly tagged feces, nonadhering completely untagged feces, and artifacts such as rectal tubes. The effect of virtual tagging was evaluated by comparing the detection accuracy of a fully automated polyp detection scheme without and with the method. With virtual tagging, the per-lesion detection sensitivity was 100% for lesions >= 10 mm (n=4) with 3.8 false positives per patient (per two CT scan volumes) and 90% for lesions >= 6 mm (n=10) with 5.4 false positives per patient on average. The improvement in detection performance by virtual tagging was statistically significant (p=0.03; JAFROC and JAFROC-1).
C1 [Naeppi, Janne] Massachusetts Gen Hosp, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Nappi, J (reprint author), Massachusetts Gen Hosp, 25 New Chardon St,Suite 400C, Boston, MA 02114 USA.
EM jnappi@partners.org
RI Nappi, Janne/B-9424-2008
OI Nappi, Janne/0000-0002-0108-0992
FU U. S. Public Health Service [CA095279]; American Cancer Society
[RSG-05-088-01-CCE]
FX The author thank Dr. Philippe Lefere and Dr. Stefaan Gryspeerdt
(Stedelijk Ziekenhuis, Roeselare, Belgium) and Dr. Michael Zalis
(Massachusetts General Hospital and Harvard Medical School, Boston, MA)
for providing the CTC cases for this study. This study was supported in
part by Grant No. CA095279 from the U. S. Public Health Service and by
research scholar Grant No. RSG-05-088-01-CCE from the American Cancer
Society.
NR 39
TC 13
Z9 13
U1 0
U2 1
PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS
PI MELVILLE
PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA
SN 0094-2405
J9 MED PHYS
JI Med. Phys.
PD MAY
PY 2009
VL 36
IS 5
BP 1830
EP 1838
DI 10.1118/1.3113893
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 437ZX
UT WOS:000265526800043
PM 19544802
ER
PT J
AU Daartz, J
Bangert, M
Bussiere, MR
Engelsman, M
Kooy, HM
AF Daartz, J.
Bangert, M.
Bussiere, M. R.
Engelsman, M.
Kooy, H. M.
TI Characterization of a mini-multileaf collimator in a proton beamline
SO MEDICAL PHYSICS
LA English
DT Article
DE biomedical equipment; collimators; dosimetry; proton beams; radiation
therapy
ID NEUTRON DOSE-EQUIVALENT; HEAVY-ION RADIOTHERAPY; IRRADIATION SYSTEM;
SECONDARY NEUTRON; THERAPY; EXPOSURES; MOTHER; FETUS; BEAMS; FIELD
AB A mini-multileaf collimator (MMLC) was mounted as a field shaping collimator in a proton beamline at the Massachusetts General Hospital. The purpose is to evaluate the device's dosimetric and mechanical properties for the use in a proton beamline. For this evaluation, the authors compared MMLC and brass aperture shaped dose distributions with regard to lateral and depth dose properties. The lateral fall off is generally broader with the MMLC, with difference varying with proton range from 0.2 to 1.2 mm. Central axis depth dose curves did not show a difference in peak-to-entrance ratio, peak width, distal fall off, or range. Two-dimensional dose distributions to investigate the conformity of MMLC shaped doses show that the physical leaf width of approximate to 2.5 mm does not have a significant impact. All differences seen in dose distribution shaped by the MMLC versus brass apertures were shown to be clinically insignificant. Measured neutron doses of 0.03-0.13 mSv/Gy for a closed brass beam block (depending on range) are very low compared to the previously published data. Irradiation of the tungsten MMLC, however, produced 1.5-1.8 times more neutrons than brass apertures. Exposure of the staff resulting from activation of the device is below regulatory limits. The measurements established an equivalency between aperture and MMLC shaped dose distributions.
C1 [Daartz, J.; Bussiere, M. R.; Engelsman, M.; Kooy, H. M.] Massachusetts Gen Hosp, Dept Radiat Oncol, Francis H Burr Proton Therapy Ctr, Boston, MA 02114 USA.
[Daartz, J.; Bangert, M.] German Canc Res Ctr, Dept Med Phys Radiat Oncol, D-69120 Heidelberg, Germany.
[Bussiere, M. R.; Engelsman, M.; Kooy, H. M.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Daartz, J (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Francis H Burr Proton Therapy Ctr, Boston, MA 02114 USA.
EM jdaartz@partners.org
NR 21
TC 10
Z9 10
U1 0
U2 3
PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS
PI MELVILLE
PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA
SN 0094-2405
J9 MED PHYS
JI Med. Phys.
PD MAY
PY 2009
VL 36
IS 5
BP 1886
EP 1894
DI 10.1118/1.3116382
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 437ZX
UT WOS:000265526800049
PM 19544808
ER
PT J
AU Shah, S
Kimberly, H
Marill, K
Noble, VE
AF Shah, Sachita
Kimberly, Heidi
Marill, Keith
Noble, Vicki E.
TI Ultrasound techniques to measure the optic nerve sheath: Is a
specialized probe necessary?
SO MEDICAL SCIENCE MONITOR
LA English
DT Article
CT Annual Meeting of the Society-of-Academic-Emergency-Medicine
CY MAY 16-19, 2007
CL Chicago, IL
SP Soc Acad Emergency Med
DE ultrasound; intracranial pressure (ICP); optic nerve sheath
ID RAISED INTRACRANIAL-PRESSURE; BRAIN-INJURY; DIAMETER; ULTRASONOGRAPHY;
SONOGRAPHY; AGREEMENT
AB Background: Ultrasound measurement of the optic nerve sheath diameter (ONSD) had been shown to correlate with intracranial pressure (ICP). This study looked at intra-observer and inter-observer reliability among three emergency physicians (EPs) using three different imaging protocols.
Material/Methods: Ocular ultrasound was performed in 20 healthy volunteers. Each physician obtained 3 measurements of the right eye ONSD with both the 10-5 MHz and 13-6 MHz probes using the axial imaging technique (experiment 1). The ONSD was then measured with the 10-5 MHz probe using the axial technique and the intracavitary 8-5 MHz probe using the coronal technique (experiment 2).
Results: In experiment 1, larger measurements were obtained with the standard 10-5 MHz probe with an adjusted difference of 0.21 mm (p<0.001). The standard deviation between intra-observer measurements for the 10-5 MHz probe was slightly but not significantly larger with an adjusted difference of 0.039 (p=0.10). In experiment 2, larger measurements were obtained with the standard 10-5 MHz probe with an adjusted difference of 0.91 mm (p<0.001). The standard deviation between intra-observer measurements was greater for the 10-5 MHz probe with an adjusted difference of 0.06 (p=0.03). The inter-observer measurements in experiment 2 had significantly larger variance with the 10-5 MHz probe (p=0.001).
Conclusions: These data suggest comparable precision and inter-observer reliability can be achieved. However, larger values when using the 10-5 MHz probe suggest different cut-off thresholds for normal upper limits. The coronal imaging technique demonstrated less inter-rater variance and may be a better technique when such small measurement differences are important.
C1 [Shah, Sachita; Kimberly, Heidi; Marill, Keith; Noble, Vicki E.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.
RP Noble, VE (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.
EM vnoble@partners.org
NR 14
TC 10
Z9 10
U1 0
U2 1
PU INT SCIENTIFIC LITERATURE, INC
PI ALBERTSON
PA 1125 WILLIS AVE, ALBERTSON, NY 11507 USA
SN 1234-1010
J9 MED SCI MONITOR
JI Med. Sci. Monitor
PD MAY
PY 2009
VL 15
IS 5
BP MT63
EP MT68
PG 6
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 452DK
UT WOS:000266519800018
PM 19396044
ER
PT J
AU Regensteiner, JG
Bauer, TA
Reusch, JEB
Quaife, RA
Chen, MY
Smith, SC
Miller, TM
Groves, BM
Wolfel, EE
AF Regensteiner, Judith G.
Bauer, Timothy A.
Reusch, Jane E. B.
Quaife, Robert A.
Chen, Marcus Y.
Smith, Susan C.
Miller, Tyler M.
Groves, Bertron M.
Wolfel, Eugene E.
TI Cardiac Dysfunction during Exercise in Uncomplicated Type 2 Diabetes
SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
LA English
DT Article
DE PEAK OXYGEN CONSUMPTION; TYPE 2 DIABETES MELLITUS; PULMONARY CAPILLARY
WEDGE PRESSURE; HEMODYNAMIC; MYOCARDIAL PERFUSION
ID VENTRICULAR SYSTOLIC FUNCTION; SOCIETY-OF-ECHOCARDIOGRAPHY; CORONARY
FLOW RESERVE; DOPPLER-ECHOCARDIOGRAPHY; DIASTOLIC DYSFUNCTION;
MYOCARDIAL-PERFUSION; CARDIOMYOPATHY; MELLITUS; DISEASE; NOMENCLATURE
AB REGENSTEINER, J. G., T. A. BAUER, J. E. REUSCH. R. A. QUAIFE, M. CHEN, S. C. SMITH, T. M. MILLER, B. M. GROVES, and E. E. WOLFEL. Cardiac Dysfunction during Exercise in Uncomplicated Type 2 Diabetes. Med. Sci. Sports Exerc., Vol. 41, No. 5, pp. 977-984, 2009. Purpose: Type 2 diabetes mellitus (T2DM) has been associated with reduced peak exercise capacity ((V) over dotO(2peak)). The causes of this impairment are not clearly established, but evidence Suggests that abnormalities in cardiac function play a significant role. We hypothesized that exercise would be associated with impaired cardiac function and hemodynamics in recently diagnosed T2DM, even in the absence of clinically evident cardiovascular complications. Methods: After baseline normal echocardiography screening, 10 premenopausal women with uncomplicated T2DM (average duration of diagnosed T2DM, 3.6 yr) and 10 healthy nondiabetic women of similar age, weight, and activity levels performed a peak cardiopulmonary exercise test while instrumented with all indwelling pulmonary artery catheter for assessing cardiac function. On separate days, technetium-99 sestamibi (cardolite) imaging was performed to assess myocardial perfusion at rest and peak exercise in seven T2DM and seven control patients. Results: Resting measures of cardiac hemodynamics were similar in T2DM and control Subjects. Absolute (V) over dotO(2peak) (mL.min(-1)) and peak cardiac output tended to be lower in T2DM than in control subjects but did not reach statistical significance. However, pulmonary capillary wedge pressure (PCWP) rose significantly more during exercise in T2DM than in controls (148% vs 109% increase at peak exercise, P<0.01). Normalized myocardial perfusion index was lower in persons with diabetes than in controls(11.0 +/- 3.5 x e(-9) vs 17.5 +/- 8.1 x e(-9), respectively, P < 0.05) and inversely related to peak exercise PCWP (R = -0.56, P < 0.05). Conclusions: Cardiac hemodynamics during graded exercise are altered in women with recently diagnosed T2DM as demonstrated by the disproportionate increase in PCWP at peak exercise compared with controls subjects. Cardiac abnormalities observed are potentially early signs of subclinical cardiac dysfunction associated with T2DM, which may precede the more greatly impaired cardiac function at rest and with exercise observed in longer established T2DM.
C1 [Regensteiner, Judith G.] Univ Colorado, Div Gen Internal Med, Dept Med, Sch Med,Hlth Sci Ctr, Aurora, CO 80045 USA.
[Regensteiner, Judith G.; Quaife, Robert A.; Chen, Marcus Y.; Miller, Tyler M.; Groves, Bertron M.; Wolfel, Eugene E.] Univ Colorado, Div Cardiol, Dept Med, Aurora, CO 80045 USA.
[Bauer, Timothy A.; Reusch, Jane E. B.] Univ Colorado, Div Endocrinol, Dept Med, Aurora, CO 80045 USA.
[Regensteiner, Judith G.; Reusch, Jane E. B.] Ctr Womens Hlth Res, Aurora, CO USA.
[Bauer, Timothy A.; Reusch, Jane E. B.] Denver Vet Affairs Med Ctr, Denver, CO USA.
RP Regensteiner, JG (reprint author), Univ Colorado, Div Gen Internal Med, Dept Med, Sch Med,Hlth Sci Ctr, B180,Acad Off Bldg A01,Rm 8221,12631 E 17th Ave, Aurora, CO 80045 USA.
EM judy.regensteiner@uchsc.edu
FU NIH [R55 DK53776, M01-RR00051]; VA merit review
FX Results of the current study do not constitute endorsement by the ACSM.
The authors are very grateful to the 20 participants for their
participation. Funding support was provided to Dr. Regensteiner by NIH
grant no. R55 DK53776 and by the General Clinical Research Center NIH
grant no. M01-RR00051. Dr. Reusch is supported by VA merit review
funding. The authors also thank the Medical and Nursing Staff of the
Cardiac Catheterization Laboratory and the General Clinical Research
Center who gave generously of their time for this study. The authors
also thank Vermed, Inc., for their generous donation of ECG electrodes
for all of our exercise studies.
NR 36
TC 30
Z9 30
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0195-9131
J9 MED SCI SPORT EXER
JI Med. Sci. Sports Exerc.
PD MAY
PY 2009
VL 41
IS 5
BP 977
EP 984
DI 10.1249/MSS.0b013e3181942051
PG 8
WC Sport Sciences
SC Sport Sciences
GA 435DS
UT WOS:000265324500002
PM 19346991
ER
PT J
AU Littman, AJ
Forsberg, CW
Koepsell, TD
AF Littman, Alyson J.
Forsberg, Christopher W.
Koepsell, Thomas D.
TI Physical Activity in a National Sample of Veterans
SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
LA English
DT Article
DE EXERCISE; MODERATE; VIGOROUS; BEHAVIORAL RISK FACTORS SURVEILLANCE
SYSTEM; EXERCISE MAINTENANCE
ID OF-SPORTS-MEDICINE; CARDIOVASCULAR-DISEASE; DOSE-RESPONSE;
PUBLIC-HEALTH; RECOMMENDATION
AB LITTMAN, A, J., C, W, FORSBERG, and T, D, KOEPSELL, Physical Activity in a National Sample of Veterans. Med. Sci. Sports Exerc., Vol. 41, No. 5, pp. 1006-1013, 2009. Purpose: To describe and compare the prevalence of physical activity (PA) in relation to veteran status and use of Department of Veterans Affairs (VA) facilities. Methods: Data were obtained from the 2003 Behavioral Risk Factor Surveillance System surveys of US adults. Veteran status, VA health care use, and PA were determined in 245,564 adults. Individuals were classified as inactive, insufficiently active, or meeting recommendations for moderate or strenuous PA. To adjust for confounding, we used model-based direct adjustment and chi-square tests corrected for the survey design. Results: After adjusting for age and gender, the prevalence of inactivity was significantly lower (16.2% vs 20.5%), and meeting PA recommendations was significantly greater (46.0% vs 42.0%) in veterans than in nonveterans (P < 0.0001). Compared with veterans who did not obtain their health care from the VA, VA users were more likely to be inactive (20.8% vs 14.7%) and less likely to be insufficiently active (34.1% vs 38.2%) or meet recommendations (45.1% vs 47.1%; P < 0.0001). Differences in PA levels between veterans and nonveterans and between VA users and nonusers did not change substantially after additional adjustment for education, race/ethnicity, and smoking. Conclusion: Despite the high level of PA required of active duty military personnel, only a minority of veterans met PA recommendations, and the prevalence of inactivity was particularly high in VA users. These findings suggest a large potential to increase PA and improve health in VA users.
C1 [Littman, Alyson J.] US Dept Vet Affairs, Seattle Epidemiol Res & Informat Ctr, VA Puget Sound Hlth Care Syst 152E, Seattle, WA 98101 USA.
[Littman, Alyson J.; Koepsell, Thomas D.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Koepsell, Thomas D.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
RP Littman, AJ (reprint author), US Dept Vet Affairs, Seattle Epidemiol Res & Informat Ctr, VA Puget Sound Hlth Care Syst 152E, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA.
EM alyson@u.washington.edu
FU Office of Research and Development Cooperative Studies Program,
Department of Veterans Affairs
FX The authors have no conflicts of interest to report.
NR 15
TC 21
Z9 21
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0195-9131
J9 MED SCI SPORT EXER
JI Med. Sci. Sports Exerc.
PD MAY
PY 2009
VL 41
IS 5
BP 1006
EP 1013
DI 10.1249/MSS.0b013e3181943826
PG 8
WC Sport Sciences
SC Sport Sciences
GA 435DS
UT WOS:000265324500006
PM 19346987
ER
PT J
AU Pru, JK
AF Pru, James K.
TI The risks of androgen treatment in postmenopausal women remain
controversial: a need for equitable comparisons
SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY
LA English
DT Editorial Material
ID SEXUAL DESIRE DISORDER; BREAST-CANCER; TESTOSTERONE PATCH; COMBINED
ESTROGEN; MENOPAUSAL WOMEN; RECEPTOR; THERAPY; PROLIFERATION; MICE
C1 Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Vincent Obstet & Gynecol Serv, Boston, MA 02114 USA.
RP Pru, JK (reprint author), Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Vincent Obstet & Gynecol Serv, Boston, MA 02114 USA.
NR 20
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1072-3714
J9 MENOPAUSE
JI Menopause-J. N. Am. Menopause Soc.
PD MAY-JUN
PY 2009
VL 16
IS 3
BP 430
EP 431
DI 10.1097/gme.0b013e3181a057cf
PG 2
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 443JG
UT WOS:000265905400004
PM 19265724
ER
PT J
AU Suffoletto, JA
Hess, R
AF Suffoletto, Jo-Anne
Hess, Rachel
TI Tapening versus cold turkey: symptoms versus successful discontinuation
of menopausal hormone therapy
SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY
LA English
DT Editorial Material
ID ESTROGEN PLUS PROGESTIN; CORONARY-HEART-DISEASE; POSTMENOPAUSAL WOMEN;
POSITION STATEMENT; SOCIETY; TRIAL
C1 [Suffoletto, Jo-Anne] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA.
[Hess, Rachel] Univ Pittsburgh, Dept Med, Ctr Res Hlth Care, Pittsburgh, PA USA.
[Hess, Rachel] Univ Pittsburgh, Dept Epidemiol, Ctr Res Hlth Care, Pittsburgh, PA 15261 USA.
RP Suffoletto, JA (reprint author), VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA.
FU NIA NIH HHS [K23 AG024254-05, AG024254, K23 AG024254]
NR 12
TC 5
Z9 5
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1072-3714
J9 MENOPAUSE
JI Menopause-J. N. Am. Menopause Soc.
PD MAY-JUN
PY 2009
VL 16
IS 3
BP 436
EP 437
DI 10.1097/gme.0b013e3181a057db
PG 2
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 443JG
UT WOS:000265905400007
PM 19276996
ER
PT J
AU Nakano, T
Inoue, I
Seo, M
Takahashi, S
Komoda, T
Katayama, S
AF Nakano, Takanari
Inoue, Ikuo
Seo, Makoto
Takahashi, Seiichiro
Komoda, Tsugikazu
Katayama, Shigehiro
TI Acarbose attenuates postprandial hyperlipidemia: investigation in an
intestinal absorptive cell model
SO METABOLISM-CLINICAL AND EXPERIMENTAL
LA English
DT Article
ID LIPID-METABOLISM; TRIGLYCERIDE
C1 [Nakano, Takanari; Seo, Makoto; Takahashi, Seiichiro; Komoda, Tsugikazu] Saitama Med Univ, Dept Biochem, Fac Med, Saitama 3500495, Japan.
[Nakano, Takanari] Univ Calif Los Angeles, CURE, Los Angeles, CA 90073 USA.
[Nakano, Takanari] W Los Angeles VA Med Ctr, BBRI, Los Angeles, CA 90073 USA.
[Inoue, Ikuo; Katayama, Shigehiro] Saitama Med Univ, Dept Endocrinol & Diabet, Fac Med, Saitama 3500495, Japan.
RP Nakano, T (reprint author), Saitama Med Univ, Dept Biochem, Fac Med, Saitama 3500495, Japan.
EM nk.takanari@gmail.com
NR 7
TC 1
Z9 1
U1 1
U2 3
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0026-0495
J9 METABOLISM
JI Metab.-Clin. Exp.
PD MAY
PY 2009
VL 58
IS 5
BP 583
EP 585
DI 10.1016/j.metabol.2009.02.003
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 439YL
UT WOS:000265663700001
PM 19375578
ER
PT J
AU Fitch, KV
Guggina, LM
Keough, HM
Looby, SED
Hadigan, C
Anderson, EJ
Hubbard, J
Liebau, JG
Johnsen, S
Wei, J
Makimura, H
Stanley, TL
Lo, J
Grinspoon, SK
AF Fitch, Kathleen V.
Guggina, LaUren M.
Keough, Hester M.
Looby, Sara E. Dolan
Hadigan, Colleen
Anderson, Ellen J.
Hubbard, Jane
Liebau, James G.
Johnsen, Stine
Wei, Jeffery
Makimura, Hideo
Stanley, Takara L.
Lo, Janet
Grinspoon, Steven K.
TI Decreased respiratory quotient in relation to resting energy expenditure
in HIV-infected and noninfected subjects
SO METABOLISM-CLINICAL AND EXPERIMENTAL
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; HIGH-FAT
DIET; LIPODYSTROPHY SYNDROME; INSULIN SENSITIVITY; METABOLIC SYNDROME;
CONTROLLED-TRIAL; BONE-DENSITY; WEIGHT-LOSS; WOMEN
AB The purpose of this study was to evaluate the relationship of respiratory quotient (RQ), a surrogate marker of substrate oxidation, as well as body composition and dietary intake to resting energy expenditure (REE) among HIV-infected patients in the current era of highly active antiretroviral therapy and among non-HIV-infected control subjects. Resting energy expenditure is increased in HIV-infected patients; but little is known regarding the potential contribution of altered substrate metabolism, body composition, and dietary intake to increased energy expenditure in this Population. Respiratory quotient, REE, body composition, and dietary intake parameters were assessed in 283 HIV-infected patients and 146 community-derived HIV-negative controls who were evaluated for metabolic Studies between 1998 and 2005. Respiratory quotient was lower (0.83 +/- 0.00 vs 0.85 +/- 0.01, P = .005), whereas REE adjusted for fat-free mass (FFM) was higher (31.8 +/- 0.3 vs 29.8 +/- 0.3 kcal/[d kg], P <= .0001), in HIV-infected compared with control subjects. In multivariate modeling among HIV-infected patients, including age, sex, and parameters of immune function, FFM (beta = 24.811334, P < .0001), visceral adiposity (beta = .7182746, P = .008), and total body fat (beta = 8.0506839, P = .041) were positively associated with REE. whereas RQ was negatively associated with REE (beta = -528.4808, P = .024). Overall r(2) was equal to 0.705 and P was less than .0001 for the model. In control subjects, by contrast, only visceral adiposity (beta = 1.0612073, P = .004), total body fat (beta = 15.805547, P = .010), and FFM (beta = 22.613005, P < .0001) were significant predictors of REE and there was no relationship with RQ. Overall r(2) was equal to 0.825 and P was less than .0001 for the model. These data suggest that alterations in substrate metabolism may contribute to increased REE in HIV-infected patients compared with control subjects. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Fitch, Kathleen V.; Guggina, LaUren M.; Keough, Hester M.; Looby, Sara E. Dolan; Hadigan, Colleen; Liebau, James G.; Johnsen, Stine; Wei, Jeffery; Makimura, Hideo; Stanley, Takara L.; Lo, Janet; Grinspoon, Steven K.] Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA.
[Anderson, Ellen J.; Hubbard, Jane] Massachusetts Gen Hosp, Gen Clin Res Ctr, Boston, MA 02114 USA.
[Hadigan, Colleen] NIAID, Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Grinspoon, SK (reprint author), Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA.
EM sgrinspoon@partners.org
FU National Institutes of Health (NIH) [DKRO1-49302, NIH DK-02844, NIH
T32HD-052691, NIH K24 DK064545, NIH MO1-RR01066]; Mary Fisher Clinical
AIDS Research and Education Fund
FX This work was supported by National Institutes of Health (NIH)
DKRO1-49302, NIH DK-02844, NIH T32HD-052691, NIH K24 DK064545, NIH
MO1-RR01066, and the Mary Fisher Clinical AIDS Research and Education
Fund. We wish to thank the nutrition and nursing staff of the MGH and
MIT General Clinical Research Center for their dedicated patient care.
NR 40
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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 0026-0495
J9 METABOLISM
JI Metab.-Clin. Exp.
PD MAY
PY 2009
VL 58
IS 5
BP 608
EP 615
DI 10.1016/j.metabol.2008.12.005
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 439YL
UT WOS:000265663700005
PM 19375582
ER
PT J
AU Brochmann, EJ
Behnam, K
Murray, SS
AF Brochmann, Elsa J.
Behnam, Keyvan
Murray, Samuel S.
TI Bone morphogenetic protein-2 activity is regulated by secreted
phosphoprotein-24 kd, an extracellular pseudoreceptor, the gene for
which maps to a region of the human genome important for bone quality
SO METABOLISM-CLINICAL AND EXPERIMENTAL
LA English
DT Article
ID VITAMIN-D-RECEPTOR; BAND ULTRASOUND ATTENUATION; X-RAY ABSORPTIOMETRY;
QUANTITATIVE ULTRASOUND; POSTMENOPAUSAL WOMEN; MINERAL DENSITY;
OSTEOPOROTIC FRACTURES; BINDING PEPTIDE; ELDERLY-WOMEN; II RECEPTOR
AB The material properties of bone are the sum of the complex and interrelated anabolic and catabolic processes that modulate formation and turnover. The 2q33-37 region of the human genome contains quantitative trait loci important in determining the broadband ultrasound attenuation (an index of trabecular microarchitecture, bone elasticity, and susceptibility to fracture) of the calcaneus, but no genes of significance to boric metabolism have been identified in this domain. Secreted phosphoprotein-24 kd (SPP24 or SPP2) is a novel and relatively poorly characterized growth hormone-regulated gene that maps to 2q37. The purpose of this review is to summarize the status of research related to spp24 and how it regulates bone morphogenetic protein (BMP) bioactivity in bone. SPP24 codes for an extracellular matrix protein that contains a high-affinity BMP-2-binding transforming growth factor-beta receptor 11 homology I loop similar to those identified in fetuin and the receptor itself. SPP24 is transcribed primarily in the liver and bone. High levels of spp24 (a hydroxyapatite-binding protein) arc found in bone, and small amounts are found in fetuin-mineral complexes. Full-length secretory spp24 inhibits ectopic bone formation, and overexpression of spp24 reduces murine bone mass and density. Spp24 is extremely labile to proteolysis, a process that regulates its bioactivity in vivo. For example, an 18.5-kd degradation product of spp24, designated spp 18,5, is pro-osteogenic. A synthetic cyclized Cys(1)-to-Cys(19) disulfide-bonded peptide (BMP binding peptide) corresponding to the transforming growth factor-beta receptor 11 homology 1 domain of spp24 and spp 18.5 binds BMP-2 and increases the rate and magnitude of BMP-2-mediated ectopic bone formation. Thus, the mechanism of action of spp 18.5 and spp24 may be to regulate the local bioavailability of BNIP cytokines. SPP24 is regulated by growth hormone and 3 major families of transcription factors (nuclear factor of activated T cells, CCAAT/enhancer-binding protein, Cut/Cux/CCAAT displacement protein) that regulate mesenchymal cell proliferation, embryonic patterning, and terminal differentiation. The gene contains at least 2 single nucleotide polymorphisms. Given its mechanism of action and sequence variability, SPP24 may be an interesting candidate for future studies of the genetic regulation of bone mass, particularly during periods of BMP-mediated endochondral bone growth, development, and fracture healing. Published by Elsevier Inc.
C1 [Brochmann, Elsa J.; Murray, Samuel S.] Sepulveda Ambulatory Care Clin & Nursing Home, GRECC 11E, VA Greater Los Angeles Healthcare Syst, Sepulveda, CA 91343 USA.
[Brochmann, Elsa J.; Murray, Samuel S.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA.
[Behnam, Keyvan] Lanx, Broomfield, CO 80021 USA.
RP Murray, SS (reprint author), Sepulveda Ambulatory Care Clin & Nursing Home, GRECC 11E, VA Greater Los Angeles Healthcare Syst, Sepulveda, CA 91343 USA.
EM samuel.murray@med.va.gov
FU Geriatric Research, Education, and Clinical Center of the VA Greater Los
Angeles Healthcare System; Office of Research and Development,
Department of Veterans Affairs; National Institutes of Health
[5R21AR53259]
FX Supported in part by the Geriatric Research, Education, and Clinical
Center of the VA Greater Los Angeles Healthcare System; the Office of
Research and Development, Department of Veterans Affairs; and the
National Institutes of Health (5R21AR53259). The authors wish to thank
Dr Matthew Beckman for his helpful discussion of the early observations
of Sen, Walker, and Einarson.
NR 60
TC 15
Z9 16
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 0026-0495
J9 METABOLISM
JI Metab.-Clin. Exp.
PD MAY
PY 2009
VL 58
IS 5
BP 644
EP 650
DI 10.1016/j.metabol.2009.01.001
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 439YL
UT WOS:000265663700010
PM 19375587
ER
PT J
AU Liu, MC
Chien, CC
Grigoryev, DN
Gandolfo, MT
Colvin, RB
Rabb, H
AF Liu, Manchang
Chien, Chu-Chun
Grigoryev, Dmitry N.
Gandolfo, Maria Teresa
Colvin, Robert B.
Rabb, Hamid
TI Effect of T cells on vascular permeability in early ischemic acute
kidney injury in mice
SO MICROVASCULAR RESEARCH
LA English
DT Article
DE Acute kidney injury; Gene microarray; Intracellular cytokine stain;
Ischemia-reperfusion; Vascular permeability
ID ACUTE-RENAL-FAILURE; REPERFUSION INJURY; INFLAMMATORY RESPONSES;
ENDOTHELIAL INJURY; BARRIER FUNCTION; EVANS BLUE; LYMPHOCYTES;
DYSFUNCTION; IDENTIFICATION
AB Although previous studies have demonstrated that microvascular dysfunction and inflammation occur in ischemia-reperfusion injury (IRI), the underlying mechanisms are poorly understood. We hypothesized that T cells could mediate renal vascular permeability (RVP) during IRI. We evaluated renal vascular permeability by extravasation of Evans blue dye from the kidney in CD3, CD4 or CD8 T cell deficient mice as well as in TNF receptor knock out mice in our mouse model of kidney ischemia-reperfusion injury. In wild type mice, RVP was significantly increased at 3 h, peaked at 6 h and declined by 24 h after ischemia. Immunohistochemistry revealed that CD3(+) T cells trafficked into ischemic kidney at 1 h and peaked at 6 h. Gene microarray analysis demonstrated that endothelial-related genes including TNF-alpha were upregulated in ischemic kidney. The production of TNF-alpha and IFN-gamma protein was increased in CD3 and CD4 T cells from the blood and kidney after ischemia. The rise in RVP after ischemia in wild type mice was attenuated in CD3, CD4 or CD8 T cell deficient mice as well as in TNF receptor knock out mice. The attenuation of RVP in CD3 T-cell deficient mice after ischemia was restored by adoptive transfer of T cells from WT mice. Our data demonstrate that T cells directly contribute to the increased RVP after kidney ischemia-reperfusion, potentially through T cell cytokine production. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Liu, Manchang; Chien, Chu-Chun; Grigoryev, Dmitry N.; Gandolfo, Maria Teresa; Rabb, Hamid] Johns Hopkins Univ, Sch Med, Div Nephrol, Baltimore, MD 21205 USA.
[Colvin, Robert B.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
RP Liu, MC (reprint author), Johns Hopkins Univ, Sch Med, Div Nephrol, 720 Rutland Ave, Baltimore, MD 21205 USA.
EM manchang@jhmi.edu
RI Grigoryev, Dmitry/C-9422-2015
OI Grigoryev, Dmitry/0000-0002-1849-1763
FU NHLBI; National Kidney Foundation
FX This work was supported by grants from the NHLBI (ML and HR) & National
Kidney Foundation (DG).
NR 31
TC 21
Z9 23
U1 0
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0026-2862
J9 MICROVASC RES
JI Microvasc. Res.
PD MAY
PY 2009
VL 77
IS 3
BP 340
EP 347
DI 10.1016/j.mvr.2009.01.011
PG 8
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 436QR
UT WOS:000265430200014
PM 19323971
ER
PT J
AU King, R
Hayzen, BA
Page, RN
Googe, PB
Zeagler, D
Mihm, MC
AF King, Roy
Hayzen, Brett A.
Page, Robert N.
Googe, Paul B.
Zeagler, Deborah
Mihm, Martin C., Jr.
TI Recurrent nevus phenomenon: a clinicopathologic study of 357 cases and
histologic comparison with melanoma with regression
SO MODERN PATHOLOGY
LA English
DT Article
DE recurrent nevus; pseudomelanoma; melanoma; regression
ID PIGMENTED NEVI; MELANOCYTIC NEVUS; ELECTRODESICCATION; REMOVAL
AB Recurrent nevus phenomenon and regression in melanoma may have overlapping histologic features. The clinical findings and histologic changes in 357 cases of recurrent nevus phenomenon were compared with 34 cases of melanoma with regression. Regression was defined as (1) Early: dense lymphoid infiltrates replacing nests of melanocytes, (2) Intermediate: absence/loss of tumor with replacement by mix of lymphocytes and melanophages and early fibrosis, and (3) Late: tumor absence with extensive fibrosis and telangiectasia, melanophages and epidermal effacement. Four broad histologic patterns of recurrent nevus were identified and classified into type 1: junctional melanocytic hyperplasia with effacement of the retiform epidermis and associated dermal scar, type 2: compound melanocytic proliferation with effacement of the retiform epidermis and associated dermal scar, type 3: junctional melanocytic hyperplasia with retention of the retiform epidermis, and type 4: compound melanocytic hyperplasia with retention of the retiform epidermis and scar. Melanomas with early and intermediate regression were recognizable due to the presence of residual melanoma. Melanomas with late regression had overlapping features of type 1 and 2 recurrent nevi. Type 3 recurrent nevi resembled primary melanoma with scar/fibrosis. Histologically, the vast majority of recurrent nevi are readily identifiable; however, partial biopsies or cases without prior knowledge of the original biopsy may lead to misdiagnosis. This is especially true in recurrent nevus and regression in malignant melanoma, where these two lesions share overlapping histologic features. Correlation with the clinical findings and prior biopsy will avoid these pitfalls. Modern Pathology (2009) 22, 611-617; doi: 10.1038/modpathol.2009.22; published online 6 March 2009
C1 [King, Roy; Hayzen, Brett A.; Page, Robert N.; Googe, Paul B.] Univ Tennessee, Grad Sch Med, Dept Pathol, Knoxville Dermatopathol Lab, Knoxville, TN 37919 USA.
[King, Roy; Page, Robert N.; Googe, Paul B.] Vanderbilt Univ Sch Med, Nashville, TN USA.
[Zeagler, Deborah] Florida Hosp Waterman, Tavares, FL USA.
[Mihm, Martin C., Jr.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP King, R (reprint author), Univ Tennessee, Grad Sch Med, Dept Pathol, Knoxville Dermatopathol Lab, 315 Erin Dr, Knoxville, TN 37919 USA.
EM rking@labpath.com
OI Googe, Paul/0000-0002-9185-3548
NR 13
TC 24
Z9 24
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
J9 MODERN PATHOL
JI Mod. Pathol.
PD MAY
PY 2009
VL 22
IS 5
BP 611
EP 617
DI 10.1038/modpathol.2009.22
PG 7
WC Pathology
SC Pathology
GA 439PT
UT WOS:000265640200001
PM 19270643
ER
PT J
AU Ferry, JA
Sohani, AR
Longtine, JA
Schwartz, RA
Harris, NL
AF Ferry, Judith A.
Sohani, Aliyah R.
Longtine, Janina A.
Schwartz, Robert A.
Harris, Nancy L.
TI HHV8-positive, EBV-positive Hodgkin lymphoma-like large B-cell lymphoma
and HHV8-positive intravascular large B-cell lymphoma
SO MODERN PATHOLOGY
LA English
DT Article
DE HHV8; KSHV; HIV; lymphoma; intravascular lymphoma
ID PRIMARY-EFFUSION LYMPHOMA; SARCOMA-ASSOCIATED HERPESVIRUS; MULTICENTRIC
CASTLEMANS-DISEASE; KAPOSIS-SARCOMA; DNA-SEQUENCES; SOLID LYMPHOMAS;
VARIANT; HISTOGENESIS; PATHOGENESIS; EXPRESSION
AB Human herpesvirus type 8 (HHV8), also known as Kaposi's sarcoma-associated herpesvirus, is a human c herpesvirus that underlies the pathogenesis of Kaposi's sarcoma, primary effusion lymphoma and multicentric Castleman's disease. We recently encountered two cases of HHV8-positive large B-cell lymphoma with features not previously described. The first patient was a 61-year-old immunocompetent man with an enlarged cervical lymph node containing scattered large, bizarre cells in a reactive background of lymphocytes, plasma cells and scattered regressed follicles resembling those of hyaline-vascular Castleman's disease. The appearance suggested classical Hodgkin's lymphoma, but the large cells were negative for CD15, CD30, CD20 and CD3, and positive for MUM1/IRF4, EMA, HHV8, EBER and dim IgM lambda. The second patient was a 59-year-old HIV-positive man who died after several weeks of fever, night sweats, anemia, thrombocytopenia, hepatosplenomegaly and multiorgan failure. At autopsy an intravascular large B-cell lymphoma that was positive for MUM1/IRF4, HHV8 and IgM lambda, and negative for CD20 and EBER involved multiple organs, including lung, heart, kidney, liver and spleen. On the basis of the histologic features in these two cases, the presence of HHV8 was unexpected. These cases expand the spectrum of lymphoproliferative disorders that can be associated with HHV8. Modern Pathology (2009) 22, 618-626; doi: 10.1038/modpathol.2009.36; published online 13 March 2009
C1 [Ferry, Judith A.; Sohani, Aliyah R.; Harris, Nancy L.] Massachusetts Gen Hosp, Dept Pathol, James Homer Wright Pathol Labs, Boston, MA 02114 USA.
[Longtine, Janina A.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Schwartz, Robert A.] Manchester Mem Hosp, Dept Pathol, Manchester, CT USA.
RP Ferry, JA (reprint author), Massachusetts Gen Hosp, Dept Pathol, James Homer Wright Pathol Labs, Fruit St, Boston, MA 02114 USA.
EM jferry@partners.org
NR 31
TC 22
Z9 24
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 MAY
PY 2009
VL 22
IS 5
BP 618
EP 626
DI 10.1038/modpathol.2009.36
PG 9
WC Pathology
SC Pathology
GA 439PT
UT WOS:000265640200002
PM 19287457
ER
PT J
AU Saxena, UH
Powell, CMH
Fecko, JK
Cacioppo, R
Chou, HS
Cooper, GM
Hansen, U
AF Saxena, Utsav H.
Powell, Christina M. H.
Fecko, Jill K.
Cacioppo, Roxanne
Chou, Hubert S.
Cooper, Geoffrey M.
Hansen, Ulla
TI Phosphorylation by Cyclin C/Cyclin-Dependent Kinase 2 following
Mitogenic Stimulation of Murine Fibroblasts Inhibits Transcriptional
Activity of LSF during G(1) Progression
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID THYMIDYLATE SYNTHASE EXPRESSION; MAMMALIAN-CELL CYCLE; DNA-BINDING
PROTEIN; RNA-POLYMERASE-III; RETINOBLASTOMA PROTEIN; FACTOR CP2; FAMILY;
COMPLEXES; PROMOTER; GENE
AB sTranscription factor LSF is required for progression from quiescence through the cell cycle, regulating thymidylate synthase (Tyms) expression at the G(1)/S boundary. Given the constant level of LSF protein from G(0) through S, we investigated whether LSF is regulated by phosphorylation in G(1). In vitro, LSF is phosphorylated by cyclin E/cyclin-dependent kinase 2 (CDK2), cyclin C/CDK2, and cyclin C/CDK3, predominantly on S309. Phosphorylation of LSF on S309 is maximal 1 to 2 h after mitogenic stimulation of quiescent mouse fibroblasts. This phosphorylation is mediated by cyclin C-dependent kinases, as shown by coimmunoprecipitation of LSF and cyclin C in early G(1) and by abrogation of LSF S309 phosphorylation upon suppression of cyclin C with short interfering RNA. Although mouse fibroblasts lack functional CDK3 (the partner of cyclin C in early G(1) in human cells), CDK2 compensates for this absence. By transient transfection assays, phosphorylation at S309, mediated by cyclin C overexpression, inhibits LSF transactivation. Moreover, overexpression of cyclin C and CDK3 inhibits induction of endogenous Tyms expression at the G(1)/S transition. These results identify LSF as only the second known target (in addition to pRb) of cyclin C/CDK activity during progression from quiescence to early G(1). Unexpectedly, this phosphorylation prevents induction of LSF target genes until late G(1).
C1 [Saxena, Utsav H.; Powell, Christina M. H.; Fecko, Jill K.; Cacioppo, Roxanne; Cooper, Geoffrey M.; Hansen, Ulla] Boston Univ, Dept Biol, Boston, MA 02215 USA.
[Chou, Hubert S.] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA.
[Chou, Hubert S.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
RP Hansen, U (reprint author), Boston Univ, Dept Biol, 5 Cummington St, Boston, MA 02215 USA.
EM uhansen@bu.edu
FU National Cancer Institute [CA-081157, CA-18689]
FX This work was supported by Public Health Service grants CA-081157 to U.
H. and CA-18689 to G. M. C. from the National Cancer Institute.; We
thank Essi Vulli for technical assistance in constructing plasmids; Ed
Harlow for facilitating the research in early stages; Shengjun Ren and
Barrett Rollins for providing plasmid constructs and encouragement; Phil
Hinds, Anindya Dutta, and William Kaelin for generously providing
plasmids; and Philipp Kaldis for generously providing Cdk2+/-
and Cdk2-/- MEFs.
NR 55
TC 15
Z9 15
U1 0
U2 1
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0270-7306
J9 MOL CELL BIOL
JI Mol. Cell. Biol.
PD MAY 1
PY 2009
VL 29
IS 9
BP 2335
EP 2345
DI 10.1128/MCB.00687-08
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 432AV
UT WOS:000265106800001
PM 19237534
ER
PT J
AU Vilardaga, JP
Bunemann, M
Feinstein, TN
Lambert, N
Nikolaev, VO
Engelhardt, S
Lohse, MJ
Hoffmann, C
AF Vilardaga, Jean-Pierre
Buenemann, Moritz
Feinstein, Timothy N.
Lambert, Nevin
Nikolaev, Viacheslav O.
Engelhardt, Stefan
Lohse, Martin J.
Hoffmann, Carsten
TI Minireview: GPCR and G Proteins: Drug Efficacy and Activation in Live
Cells
SO MOLECULAR ENDOCRINOLOGY
LA English
DT Review
ID RESONANCE ENERGY-TRANSFER; PARATHYROID-HORMONE RECEPTOR; HETEROTRIMERIC
G-PROTEINS; BETA-ADRENERGIC-RECEPTOR; CHRONIC HEART-FAILURE; MU-OPIOID
RECEPTORS; COUPLED-RECEPTORS; LIVING CELLS; CONFORMATIONAL STATES;
CONSTITUTIVE ACTIVITY
AB Many biochemical pathways are driven by G protein-coupled receptors, cell surface proteins that convert the binding of extracellular chemical, sensory, and mechanical stimuli into cellular signals. Their interaction with various ligands triggers receptor activation that typically couples to and activates heterotrimeric G proteins, which in turn control the propagation of secondary messenger molecules (e. g. cAMP) involved in critically important physiological processes (e. g. heart beat). Successful transfer of information from ligand binding events to intracellular signaling cascades involves a dynamic interplay between ligands, receptors, and G proteins. The development of Forster resonance energy transfer and bioluminescence resonance energy transfer-based methods has now permitted the kinetic analysis of initial steps involved in G protein-coupled receptor-mediated signaling in live cells and in systems as diverse as neurotransmitter and hormone signaling. The direct measurement of ligand efficacy at the level of the receptor by Forster resonance energy transfer is also now possible and allows intrinsic efficacies of clinical drugs to be linked with the effect of receptor polymorphisms. (Molecular Endocrinology 23: 590-599, 2009)
C1 [Vilardaga, Jean-Pierre; Feinstein, Timothy N.] Univ Pittsburgh, Dept Pharmacol & Chem Biol, Pittsburgh, PA 15213 USA.
[Vilardaga, Jean-Pierre] Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA.
[Vilardaga, Jean-Pierre] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Buenemann, Moritz; Nikolaev, Viacheslav O.; Lohse, Martin J.; Hoffmann, Carsten] Univ Wurzburg, Inst Pharmacol & Toxicol, D-97078 Wurzburg, Germany.
[Engelhardt, Stefan; Lohse, Martin J.] Univ Wurzburg, Rudolf Virchow Ctr, Deutsch Forsch Gemeinschaft Res Ctr Expt Biomed, D-97078 Wurzburg, Germany.
[Lambert, Nevin] Med Coll Georgia, Dept Pharmacol & Toxicol, Augusta, GA 30809 USA.
RP Vilardaga, JP (reprint author), Dept Pharmacol & Chem Biol, Thomas E Starzl Biochem Sci Tower,E1357,200 Lothr, Pittsburgh, PA 15261 USA.
EM jpv@pitt.edu
RI Feinstein, Timothy/G-3110-2011; Lohse, Martin/A-7160-2012;
OI Lohse, Martin/0000-0002-0599-3510; Feinstein,
Timothy/0000-0002-9801-9708
FU Department of Medicine; Massachusetts General Hospital; Department of
Pharmacology and Chemical Biology, University of Pittsburgh
FX This work was supported by start up funds from the Department of
Medicine, Massachusetts General Hospital, and the Department of
Pharmacology and Chemical Biology, University of Pittsburgh (to J.P.V.).
NR 72
TC 47
Z9 49
U1 2
U2 10
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0888-8809
J9 MOL ENDOCRINOL
JI Mol. Endocrinol.
PD MAY
PY 2009
VL 23
IS 5
BP 590
EP 599
DI 10.1210/me.2008-0204
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 438YP
UT WOS:000265593100002
PM 19196832
ER
PT J
AU Kimbrel, EA
Davis, TN
Bradner, JE
Kung, AL
AF Kimbrel, Erin A.
Davis, Tina N.
Bradner, James E.
Kung, Andrew L.
TI In Vivo Pharmacodynamic Imaging of Proteasome Inhibition
SO MOLECULAR IMAGING
LA English
DT Article
ID UBIQUITIN-INDEPENDENT SUBSTRATE; ORNITHINE-DECARBOXYLASE; DRUG
DEVELOPMENT; CANCER-THERAPY; PATHWAY; SYSTEM; HIF-1; DEGRADATION;
COMBINATION; MODULATION
AB Inhibiting the proteolytic activity of the 26S proteasome has been shown to have selective apoptotic effects on cancer cells and to be clinically efficacious in certain malignancies. There is an unmet medical need for additional proteasome inhibitors, and their development will be facilitated by surrogate markers of proteasome function. Toward this end, ectopic fusion of the destruction domain from ornithine decarboxylase (ODC) to reporter proteins is often used for assessing proteasome function. For luciferase-based reporters, we hypothesized that the oxygen-dependent destruction domain (ODD) from hypoxia-inducible factor 1 alpha (HIF-1 alpha) may provide improved sensitivity over luciferase-ODC, owing to its extremely rapid turnover by the proteasome (HIF-1a has a half-life of less than 5 minutes). In the current study, we show that ODD-luciferase affords a greater dynamic range and faster kinetics than luciferase-ODC in sensing proteasome inhibition in vitro. Importantly, ODD-luciferase also serves as an effective in vivo marker of proteasome function in xenograft tumor models, with inhibition being detected by noninvasive imaging within 3 hours of bortezomib administration. These data establish ODD-luciferase as a surrogate marker of proteasome function that can be used both in vitro and in vivo for the development of novel proteasome inhibitors.
C1 [Kung, Andrew L.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Boston, MA USA.
Broad Inst Harvard, Cambridge, MA USA.
MIT, Cambridge, MA 02139 USA.
Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA.
RP Kung, AL (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA.
EM andrew_kung@dfci.harvard.edu
OI Kung, Andrew/0000-0002-9091-488X
NR 30
TC 21
Z9 21
U1 0
U2 2
PU B C DECKER INC
PI HAMILTON
PA 50 KING STREET EAST, 2ND FLOOR, PO BOX 620, L C D 1, HAMILTON, ONTARIO
L8N 3K7, CANADA
SN 1535-3508
J9 MOL IMAGING
JI Mol. Imaging
PD MAY-JUN
PY 2009
VL 8
IS 3
BP 140
EP 147
DI 10.2310/7290.2009.00007
PG 8
WC Biochemical Research Methods; Radiology, Nuclear Medicine & Medical
Imaging
SC Biochemistry & Molecular Biology; Radiology, Nuclear Medicine & Medical
Imaging
GA 462ZE
UT WOS:000267396800002
PM 19723471
ER
PT J
AU Chiara, DC
Hong, FH
Arevalo, E
Husain, SS
Miller, KW
Forman, SA
Cohen, JB
AF Chiara, David C.
Hong, Filbert H.
Arevalo, Enrique
Husain, S. Shaukat
Miller, Keith W.
Forman, Stuart A.
Cohen, Jonathan B.
TI Time-Resolved Photolabeling of the Nicotinic Acetylcholine Receptor by
[(3)H]Azietomidate, an Open-State Inhibitor
SO MOLECULAR PHARMACOLOGY
LA English
DT Article
ID GAMMA-AMINOBUTYRIC-ACID; GENERAL-ANESTHETICS; BINDING-SITE; ION-CHANNEL;
IDENTIFICATION; AGONIST; ETOMIDATE; SUBUNIT; MUTATIONS; PORE
AB Azietomidate is a photoreactive analog of the general anesthetic etomidate that acts as a nicotinic acetylcholine receptor (nAChR) noncompetitive antagonist. We used rapid perfusion electrophysiological techniques to characterize the state dependence and kinetics of azietomidate inhibition of Torpedo californica nAChRs and time-resolved photolabeling to identify the nAChR binding sites occupied after exposure to [(3)H]azietomidate and agonist for 50 ms (open state) or at equilibrium (desensitized state). Azietomidate acted primarily as an open channel inhibitor characterized by a bimolecular association rate constant of k(+) = 5 x 10(5) M(-1) s(-1) and a dissociation rate constant of <3 s(-1). Azietomidate at 10 mu M, when perfused with acetylcholine (ACh), inhibited the ACh response by similar to 50% after 50 ms; when preincubated for 10 s, it decreased the peak initial response by similar to 15%. Comparison of the kinetics of recovery of ACh responses after exposure to ACh and azietomidate or to ACh alone indicated that at subsecond times, azietomidate inhibited nAChRs without enhancing the kinetics of agonist-induced desensitization. In nAChRs frozen after 50-ms exposure to agonist and [(3)H] azietomidate, amino acids were photolabeled in the ion channel [position M2-20 (alpha Glu-262, beta Asp-268, delta Gln-276)], in delta M1 (delta Cys-236), and in alpha MA/alpha M4 (alpha Glu-390, alpha Cys-412) that were also photolabeled in nAChRs in the equilibrium desensitized state at approximately half the efficiency. These results identify azietomidate binding sites at the extracellular end of the ion channel, in the delta subunit helix bundle, and in the nAChR cytoplasmic domain that seem similar in structure and accessibility in the open and desensitized states of the nAChR.
C1 [Chiara, David C.; Hong, Filbert H.; Cohen, Jonathan B.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA.
[Arevalo, Enrique; Husain, S. Shaukat; Miller, Keith W.; Forman, Stuart A.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA.
[Miller, Keith W.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
RP Cohen, JB (reprint author), Harvard Univ, Sch Med, Dept Neurobiol, 220 Longwood Ave, Boston, MA 02115 USA.
EM jonathan_cohen@hms.harvard.edu
FU National Institutes of Health National Institute of General Medical
Sciences [GM58448]; Howard Hughes Biomedical Research Support Program
for Medical Schools
FX This research was supported in part by the National Institutes of Health
National Institute of General Medical Sciences [Grant GM58448] and by an
award to Harvard Medical School from the Howard Hughes Biomedical
Research Support Program for Medical Schools.
NR 40
TC 21
Z9 21
U1 0
U2 2
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 MAY
PY 2009
VL 75
IS 5
BP 1084
EP 1095
DI 10.1124/mol.108.054353
PG 12
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 436VS
UT WOS:000265444800009
PM 19218367
ER
PT J
AU Tannous, BA
Christensen, AP
Pike, L
Wurdinger, T
Perry, KF
Saydam, O
Jacobs, AH
Garcia-Anoveros, J
Weissleder, R
Sena-Esteves, M
Corey, DP
Breakefield, XO
AF Tannous, Bakhos A.
Christensen, Adam P.
Pike, Lisa
Wurdinger, Thomas
Perry, Katherine F.
Saydam, Okay
Jacobs, Andreas H.
Garcia-Anoveros, Jaime
Weissleder, Ralph
Sena-Esteves, Miguel
Corey, David P.
Breakefield, Xandra O.
TI Mutant Sodium Channel for Tumor Therapy
SO MOLECULAR THERAPY
LA English
DT Article
ID SIMPLEX-VIRUS TYPE-1; CANCER GENE-THERAPY; EPSTEIN-BARR-VIRUS;
CAENORHABDITIS-ELEGANS; AMPLICON VECTORS; IN-VIVO; IODIDE SYMPORTER;
GLIOMA-CELLS; EXPRESSION; BRAIN
AB Viral vectors have been used to deliver a wide range of therapeutic genes to tumors. In this study, a novel tumor therapy was achieved by the delivery of a mammalian brain sodium channel, ASIC2a, carrying a mutation that renders it constitutively open. This channel was delivered to tumor cells using a herpes simplex virus-1/Epstein-Barr virus (HSV/EBV) hybrid amplicon vector in which gene expression was controlled by a tetracycline regulatory system (tet-on) with silencer elements. Upon infection and doxycycline induction of mutant channel expression in tumor cells, the open channel led to amiloride-sensitive sodium influx as assessed by patch clamp recording and sodium imaging in culture. Within hours, tumor cells swelled and died. In addition to cells expressing the mutant channel, adjacent, noninfected cells connected by gap junctions also died. Intratumoral injection of HSV/EBV amplicon vector encoding the mutant sodium channel and systemic administration of doxycycline led to regression of subcutaneous tumors in nude mice as assessed by in vivo bioluminescence imaging. The advantage of this direct mode of tumor therapy is that all types of tumor cells become susceptible and death is rapid with no time for the tumor cells to become resistant.
C1 [Tannous, Bakhos A.; Pike, Lisa; Wurdinger, Thomas; Perry, Katherine F.; Saydam, Okay; Sena-Esteves, Miguel; Breakefield, Xandra O.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp,Mol Neurogenet Unit, Boston, MA 02115 USA.
[Tannous, Bakhos A.; Wurdinger, Thomas; Weissleder, Ralph; Breakefield, Xandra O.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp,Ctr Mol Imaging Res, Boston, MA 02115 USA.
[Tannous, Bakhos A.; Christensen, Adam P.; Wurdinger, Thomas; Saydam, Okay; Corey, David P.; Breakefield, Xandra O.] Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA.
[Christensen, Adam P.; Corey, David P.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA.
[Jacobs, Andreas H.] MPI Neurol Res, Lab Gene Therapy & Mol Imaging, Cologne, Germany.
[Garcia-Anoveros, Jaime] Northwestern Univ, Dept Anesthesiol, Feinberg Sch Med, Chicago, IL 60611 USA.
[Weissleder, Ralph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA USA.
[Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA.
[Corey, David P.] Howard Hughes Med Inst, Chevy Chase, MD USA.
RP Tannous, BA (reprint author), Massachusetts Gen Hosp East, Dept Neurol, Mol Neurogenet Unit, Bldg 149,13th St, Boston, MA 02129 USA.
EM btannous@hms.harvard.edu
OI Corey, David/0000-0003-4497-6016
FU National Cancer Institute [CA69246, CA86355, 1K99CA126839]; NINDS
[NS44363]; Brain Tumor Society; Investigator of the Howard Hughes
Medical Institute.
FX We thank Dr Bujard for providing tetracycline regulatory elements used
in the amplicon vector and Dr Fraefel for providing the HSV-TK amplicon
plasmid; Dr Rachamimov (Pathologist at MGH) for analyzing the
hematoxylin and eosin stained sections. Nicole Lewandrowski, Juliet
Fernandez, Ozlem Senol, and Johanna M. Niers for technical help; Dr
Yellen for access to the sodium imaging microscope; Suzanne McDavitt for
skilled editorial assistance; and Igor Bagayev for assistance with
confocal microscopy. This work was supported by grants from the National
Cancer Institute (CA69246 and CA86355 to XOB and RW, and 1K99CA126839 to
BAT), from NINDS (NS44363 to JG-A) and from the Brain Tumor Society (to
B. A. T. and X. O. B.). D. P. C. is an Investigator of the Howard Hughes
Medical Institute.
NR 50
TC 12
Z9 13
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 MAY
PY 2009
VL 17
IS 5
BP 810
EP 819
DI 10.1038/mt.2009.33
PG 10
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 439PY
UT WOS:000265640700013
PM 19259066
ER
PT J
AU Anthony, RM
Maeder, ML
Joung, JK
McCray, PB
AF Anthony, Reshma M.
Maeder, Morgan L.
Joung, J. Keith
McCray, Paul B., Jr.
TI Efficient Site-Specific Breaks and Non-Homologous End-Joining in the
Human CFTR Locus by Adenovirus-Mediated Delivery of Zinc Finger
Nucleases
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 12th Annual Meeting of the American Society of Gene Therapy
CY MAY 27-30, 2009
CL San Diego, CA
SP Amer Soc Gene Therapy
C1 [Anthony, Reshma M.; McCray, Paul B., Jr.] Univ Iowa, Carver Coll Med, Dept Pediat, Iowa City, IA USA.
[Maeder, Morgan L.; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Charlestown, MA USA.
[Maeder, Morgan L.; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Canc Res, Mol Pathol Unit, Charlestown, MA USA.
[Joung, J. Keith] Harvard Univ, Sch Med, Dept Pathol, 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 MAY
PY 2009
VL 17
SU 1
MA 109
BP S43
EP S43
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 600WO
UT WOS:000278019800110
ER
PT J
AU Hardcastle, JJ
Kurozumi, K
Dmitrieva, N
Sayers, MP
Ahmad, S
Waterman, P
Weissleder, R
Chiocca, EA
Kaur, B
AF Hardcastle, Jayson J.
Kurozumi, Kazuhiko
Dmitrieva, Nina
Sayers, Martin P.
Ahmad, Sarwat
Waterman, Peter
Weissleder, Ralph
Chiocca, E. A.
Kaur, Balveen
TI Vasculostatin Expression Mediated by Oncolytic HSV Inhibits Tumor Growth
and Angiogenesis
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 12th Annual Meeting of the American Society of Gene Therapy
CY MAY 27-30, 2009
CL San Diego, CA
SP Amer Soc Gene Therapy
C1 [Hardcastle, Jayson J.; Kurozumi, Kazuhiko; Dmitrieva, Nina; Sayers, Martin P.; Chiocca, E. A.; Kaur, Balveen] Ohio State Univ, Dardinger Lab Neuro Oncol & Neurosci, Columbus, OH 43210 USA.
[Hardcastle, Jayson J.] Ohio State Univ, Integrated Biomed Sci Grad Program, Columbus, OH 43210 USA.
[Ahmad, Sarwat] Ohio State Univ, Coll Med, Columbus, OH 43210 USA.
[Hardcastle, Jayson J.; Kurozumi, Kazuhiko; Dmitrieva, Nina; Sayers, Martin P.; Ahmad, Sarwat; Chiocca, E. A.; Kaur, Balveen] James Comprehens Canc Ctr, Dept Neurol Surg, Columbus, OH USA.
[Hardcastle, Jayson J.; Kurozumi, Kazuhiko; Dmitrieva, Nina; Sayers, Martin P.; Ahmad, Sarwat; Chiocca, E. A.; Kaur, Balveen] Ohio State Univ, Med Ctr, Columbus, OH 43210 USA.
[Waterman, Peter; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA USA.
[Kurozumi, Kazuhiko] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Neurol Surg, Okayama, Japan.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2009
VL 17
SU 1
BP S303
EP S303
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 600WO
UT WOS:000278019801364
ER
PT J
AU Maeder, ML
Yeh, JRJ
Foley, JE
Zou, JH
Thibodeau-Beganny, S
Cheng, LH
Peterson, RT
Joung, JK
AF Maeder, Morgan L.
Yeh, Jing-Ruey J.
Foley, Jonathan E.
Zou, Jizhong
Thibodeau-Beganny, Stacey
Cheng, Linzhao
Peterson, Randall T.
Joung, J. Keith
TI Further Improvements and Applications of OPEN (Oligomerized Pool
ENgineering): A Rapid, Robust, and Publicly Available Method for
Engineering Customized Zinc Finger Nucleases
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 12th Annual Meeting of the American Society of Gene Therapy
CY MAY 27-30, 2009
CL San Diego, CA
SP Amer Soc Gene Therapy
C1 [Maeder, Morgan L.; Foley, Jonathan E.; Thibodeau-Beganny, Stacey; Joung, J. Keith] Harvard Univ, Sch Med, Mol Pathol Unit, Massachusetts Gen Hosp, Charlestown, MA USA.
[Peterson, Randall T.] Harvard Univ, Sch Med, Cardiovasc Res Ctr, Massachusetts Gen Hosp, Charlestown, MA USA.
[Zou, Jizhong; Cheng, Linzhao] Johns Hopkins Univ, Sch Med, Stem Cell Program, Inst Cell Engn, Baltimore, MD USA.
RI Zou, Jizhong/B-4902-2011
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 MAY
PY 2009
VL 17
SU 1
MA 415
BP S162
EP S163
PG 2
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 600WO
UT WOS:000278019800414
ER
PT J
AU Maguire, CA
Gianni, D
Meijer, DH
Breakefield, XO
Shaket, LA
Sena-Esteves, M
AF Maguire, Casey A.
Gianni, Davide
Meijer, Dimphna H.
Breakefield, Xandra O.
Shaket, Lev A.
Sena-Esteves, Miguel
TI Directed Evolution of Adeno-Associated Virus for Glioma Cell
Transduction
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 12th Annual Meeting of the American Society of Gene Therapy
CY MAY 27-30, 2009
CL San Diego, CA
SP Amer Soc Gene Therapy
C1 [Maguire, Casey A.; Gianni, Davide; Breakefield, Xandra O.; Shaket, Lev A.; Sena-Esteves, Miguel] Massachusetts Gen Hosp, Charlestown, MA USA.
[Meijer, Dimphna H.] Rudolf Magnus Inst Neurosci, NL-3508 TA Utrecht, Netherlands.
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 MAY
PY 2009
VL 17
SU 1
BP S181
EP S181
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 600WO
UT WOS:000278019801041
ER
PT J
AU Nemunaitis, J
Geevarghese, SK
Geller, DA
de Haan, HA
Iagaru, A
Knoll, A
Reid, TR
Sze, DY
Tanabe, K
AF Nemunaitis, J.
Geevarghese, S. K.
Geller, D. A.
de Haan, H. A.
Iagaru, A.
Knoll, A.
Reid, T. R.
Sze, D. Y.
Tanabe, K.
TI Phase II Efficacy Results Using an Oncolytic Herpes Simplex Virus
(NV1020) in Patients with Colorectal Cancer Metastatic to Liver (mCRC)
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 12th Annual Meeting of the American Society of Gene Therapy
CY MAY 27-30, 2009
CL San Diego, CA
SP Amer Soc Gene Therapy
C1 [Nemunaitis, J.] Mary Crowley Canc Res Ctr, Dallas, TX USA.
[Geevarghese, S. K.] Vanderbilt Univ, Nashville, TN USA.
[Geller, D. A.] Univ Pittsburgh, Pittsburgh, PA USA.
[de Haan, H. A.] MediGene Inc, San Diego, CA USA.
[Iagaru, A.; Knoll, A.] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
[Reid, T. R.] Univ Calif San Diego, San Diego, CA 92103 USA.
[Tanabe, K.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2009
VL 17
SU 1
BP S304
EP S304
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 600WO
UT WOS:000278019801365
ER
PT J
AU Sahin, A
Maxfield, S
Sanchez, CE
Bullain, SA
Baratta, B
Carter, BS
AF Sahin, Ayguen
Maxfield, Steven
Sanchez, Carlos E.
Bullain, Szofi A.
Baratta, Beth
Carter, Bob S.
TI Engineering of "3rd Generation" Chimeric Immune Receptor Expressing T
Cells for Improved Adoptive Immunotherapy Against Glioblastoma
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 12th Annual Meeting of the American Society of Gene Therapy
CY MAY 27-30, 2009
CL San Diego, CA
SP Amer Soc Gene Therapy
C1 [Sahin, Ayguen; Maxfield, Steven; Sanchez, Carlos E.; Bullain, Szofi A.; Baratta, Beth; Carter, Bob S.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2009
VL 17
SU 1
BP S217
EP S218
PG 2
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 600WO
UT WOS:000278019801144
ER
PT J
AU Scaria, A
MacLachlan, T
Lukason, M
Pechan, P
DuFresne, E
Isenberger, L
Andrews, L
Veres, G
Kim, I
Hauswirth, W
Wadsworth, S
AF Scaria, Abraham
MacLachlan, Tim
Lukason, Michael
Pechan, Peter
DuFresne, Elizabeth
Isenberger, Liz
Andrews, Laura
Veres, Gabor
Kim, Ivana
Hauswirth, William
Wadsworth, Samuel
TI Safety and Efficacy of Intravitreal Anti-VEGF Gene Delivery in Non-Human
Primates for the Treatment of Ocular Neovascularization
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 12th Annual Meeting of the American Society of Gene Therapy
CY MAY 27-30, 2009
CL San Diego, CA
SP Amer Soc Gene Therapy
C1 [Scaria, Abraham; MacLachlan, Tim; Lukason, Michael; Pechan, Peter; DuFresne, Elizabeth; Isenberger, Liz; Andrews, Laura; Wadsworth, Samuel] Genzyme Corp, Framingham, MA 01701 USA.
[Veres, Gabor] AGTC, Alachua, FL USA.
[Kim, Ivana] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
[Hauswirth, William] Univ Florida, Gainesville, FL USA.
NR 0
TC 0
Z9 0
U1 2
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 MAY
PY 2009
VL 17
SU 1
BP S287
EP S288
PG 2
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 600WO
UT WOS:000278019801326
ER
PT J
AU Skog, J
Lessard, R
Balaj, L
Breakefield, XO
AF Skog, Johan
Lessard, Ryan
Balaj, Leonora
Breakefield, Xandra O.
TI Monitoring of Transgene Expression In Vivo Via Exosomes Shed from
Transduced Cells into the Bloodstream
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 12th Annual Meeting of the American Society of Gene Therapy
CY MAY 27-30, 2009
CL San Diego, CA
SP Amer Soc Gene Therapy
C1 [Skog, Johan; Lessard, Ryan; Balaj, Leonora; Breakefield, Xandra O.] Massachusetts Gen Hosp, Charlestown, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2009
VL 17
SU 1
BP S303
EP S303
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 600WO
UT WOS:000278019801363
ER
PT J
AU Tannous, BA
Wurdinger, T
Badr, C
Breakefield, X
AF Tannous, Bakhos A.
Wurdinger, Thomas
Badr, Christian
Breakefield, Xandra
TI Blood and Urine Assay To Monitor Viral Transduction, Tumor Growth and
Stem Cells Survival and Proliferation
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 12th Annual Meeting of the American Society of Gene Therapy
CY MAY 27-30, 2009
CL San Diego, CA
SP Amer Soc Gene Therapy
C1 [Tannous, Bakhos A.; Wurdinger, Thomas; Badr, Christian; Breakefield, Xandra] Massachusetts Gen Hosp, Mol Neurogenet Unit, Boston, MA 02114 USA.
[Tannous, Bakhos A.; Wurdinger, Thomas; Badr, Christian; Breakefield, Xandra] Harvard Univ, Sch Med, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2009
VL 17
SU 1
BP S384
EP S385
PG 2
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 600WO
UT WOS:000278019801582
ER
PT J
AU Ugai, H
Wang, MH
Le, LP
Matthews, DA
Yamamoto, M
Curiel, DT
AF Ugai, Hideyo
Wang, Minghui
Le, Long P.
Matthews, David A.
Yamamoto, Masato
Curiel, David T.
TI In Vitro Trafficking of Fluorescently Labeled Minor Capsid Protein IX
and Core Protein V during Adenoviral Infection
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 12th Annual Meeting of the American Society of Gene Therapy
CY MAY 27-30, 2009
CL San Diego, CA
SP Amer Soc Gene Therapy
C1 [Ugai, Hideyo; Wang, Minghui; Curiel, David T.] Univ Alabama, Gene Therapy Ctr, Birmingham, AL USA.
[Ugai, Hideyo; Wang, Minghui; Curiel, David T.] Univ Alabama, Div Human Gene Therapy, Dept Med, Birmingham, AL USA.
[Le, Long P.] Massachusetts Gen Hosp, Pathol Serv, Boston, MA 02114 USA.
[Matthews, David A.] Univ Bristol, Sch Med Sci, Dept Cellular & Mol Med, Bristol BS8 1TD, Avon, England.
[Yamamoto, Masato] Univ Minnesota, Dept Surg, Div Basic & Translat Res, Minneapolis, MN 55455 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 MAY
PY 2009
VL 17
SU 1
MA 119
BP S46
EP S47
PG 2
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 600WO
UT WOS:000278019800120
ER
PT J
AU van Haaften, G
Dalgliesh, GL
Davies, H
Chen, L
Bignell, G
Greenman, C
Edkins, S
Hardy, C
O'Meara, S
Teague, J
Butler, A
Hinton, J
Latimer, C
Andrews, J
Barthorpe, S
Beare, D
Buck, G
Campbell, PJ
Cole, J
Forbes, S
Jia, MM
Jones, D
Kok, CY
Leroy, C
Lin, ML
McBride, DJ
Maddison, M
Maquire, S
Mclay, K
Menzies, A
Mironenko, T
Mulderrig, L
Mudie, L
Pleasance, E
Shepherd, R
Smith, R
Stebbings, L
Stephens, P
Tang, G
Tarpey, PS
Turner, R
Turrell, K
Varian, J
West, S
Widaa, S
Wray, P
Collins, VP
Ichimura, K
Law, S
Wong, J
Yuen, ST
Leung, SY
Tonon, G
DePinho, RA
Tai, YT
Anderson, KC
Kahnoski, RJ
Massie, A
Khoo, SK
Teh, BT
Stratton, MR
Futreal, PA
AF van Haaften, Gijs
Dalgliesh, Gillian L.
Davies, Helen
Chen, Lina
Bignell, Graham
Greenman, Chris
Edkins, Sarah
Hardy, Claire
O'Meara, Sarah
Teague, Jon
Butler, Adam
Hinton, Jonathan
Latimer, Calli
Andrews, Jenny
Barthorpe, Syd
Beare, Dave
Buck, Gemma
Campbell, Peter J.
Cole, Jennifer
Forbes, Simon
Jia, Mingming
Jones, David
Kok, Chai Yin
Leroy, Catherine
Lin, Meng-Lay
McBride, David J.
Maddison, Mark
Maquire, Simon
Mclay, Kirsten
Menzies, Andrew
Mironenko, Tatiana
Mulderrig, Lee
Mudie, Laura
Pleasance, Erin
Shepherd, Rebecca
Smith, Raffaella
Stebbings, Lucy
Stephens, Philip
Tang, Gurpreet
Tarpey, Patrick S.
Turner, Rachel
Turrell, Kelly
Varian, Jennifer
West, Sofie
Widaa, Sara
Wray, Paul
Collins, V. Peter
Ichimura, Koichi
Law, Simon
Wong, John
Yuen, Siu Tsan
Leung, Suet Yi
Tonon, Giovanni
DePinho, Ronald A.
Tai, Yu-Tzu
Anderson, Kenneth C.
Kahnoski, Richard J.
Massie, Aaron
Khoo, Sok Kean
Teh, Bin Tean
Stratton, Michael R.
Futreal, P. Andrew
TI Somatic mutations of the histone H3K27 demethylase gene UTX in human
cancer
SO NATURE GENETICS
LA English
DT Article
ID MYELOMA CELL-LINE; TARGET GENES; METHYLTRANSFERASE; JMJD3; MICE
AB Somatically acquired epigenetic changes are present in many cancers. Epigenetic regulation is maintained via post-translational modifications of core histones. Here, we describe inactivating somatic mutations in the histone lysine demethylase gene UTX, pointing to histone H3 lysine methylation deregulation in multiple tumor types. UTX reintroduction into cancer cells with inactivating UTX mutations resulted in slowing of proliferation and marked transcriptional changes. These data identify UTX as a new human cancer gene.
C1 [van Haaften, Gijs; Dalgliesh, Gillian L.; Davies, Helen; Chen, Lina; Bignell, Graham; Greenman, Chris; Edkins, Sarah; Hardy, Claire; O'Meara, Sarah; Teague, Jon; Butler, Adam; Hinton, Jonathan; Latimer, Calli; Andrews, Jenny; Barthorpe, Syd; Beare, Dave; Buck, Gemma; Campbell, Peter J.; Cole, Jennifer; Forbes, Simon; Jia, Mingming; Jones, David; Kok, Chai Yin; Leroy, Catherine; Lin, Meng-Lay; McBride, David J.; Maddison, Mark; Maquire, Simon; Mclay, Kirsten; Menzies, Andrew; Mironenko, Tatiana; Mulderrig, Lee; Mudie, Laura; Pleasance, Erin; Shepherd, Rebecca; Smith, Raffaella; Stebbings, Lucy; Stephens, Philip; Tang, Gurpreet; Tarpey, Patrick S.; Turner, Rachel; Turrell, Kelly; Varian, Jennifer; West, Sofie; Widaa, Sara; Wray, Paul; Stratton, Michael R.; Futreal, P. Andrew] Wellcome Trust Sanger Inst, Canc Genome Project, Hinxton, England.
[Collins, V. Peter; Ichimura, Koichi] Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England.
[Law, Simon; Wong, John] Univ Hong Kong, Queen Mary Hosp, Dept Surg, Hong Kong, Hong Kong, Peoples R China.
[Yuen, Siu Tsan; Leung, Suet Yi] Univ Hong Kong, Queen Mary Hosp, Dept Pathol, Hong Kong, Hong Kong, Peoples R China.
[Tonon, Giovanni; DePinho, Ronald A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Belfer Inst Innovat Canc Sci,Dept Med Oncol,Ctr A, Boston, MA 02115 USA.
[Tonon, Giovanni; DePinho, Ronald A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Belfer Inst Innovat Canc Sci,Dept Med & Genet,Ctr, Boston, MA 02115 USA.
[Tai, Yu-Tzu; Anderson, Kenneth C.] Dana Farber Canc Inst, Lebow Inst Myeloma Therapeut, Boston, MA 02115 USA.
[Tai, Yu-Tzu; Anderson, Kenneth C.] Dana Farber Canc Inst, Lipper Myeloma Ctr, Boston, MA 02115 USA.
[Kahnoski, Richard J.; Massie, Aaron] Spectrum Hlth Hosp, Dept Urol, Grand Rapids, MI USA.
[Khoo, Sok Kean; Teh, Bin Tean] Van Andel Inst, Canc Genet Lab, Grand Rapids, MI USA.
[Stratton, Michael R.] Inst Canc Res, Sutton, Surrey, England.
RP Stratton, MR (reprint author), Wellcome Trust Sanger Inst, Canc Genome Project, Hinxton, England.
EM mrs@sanger.ac.uk; paf@sanger.ac.uk
RI van Haaften, Gijs/G-7832-2012; Tang, Macy/B-9798-2014; Yuen , Siu
/K-6311-2014; Leung, Suet Yi/C-4340-2009; Dalgliesh, Gillian/B-7799-2008
OI van Haaften, Gijs/0000-0003-3033-0329; Dalgliesh,
Gillian/0000-0001-8526-5064
FU Wellcome Trus; EMBO fellowship; Kay Kendall Leukaemia Fund fellowship;
Robert A. and Renee E. Belfer Foundation for Innovative Cancer Science;
Leukemia and Lymphoma Society
FX Funding was provided by the Wellcome Trust. G. v. H. is supported by an
EMBO fellowship and P.J.C. by a Kay Kendall Leukaemia Fund fellowship.
R. A. D. is supported by the Robert A. and Renee E. Belfer Foundation
for Innovative Cancer Science. G. T. is supported by a fellowship from
the Leukemia and Lymphoma Society. GlaxoSmithKline provided support for
the SNP 6.0 microarray analyses. UTX antibodies were a kind gift from E.
Canaani (Weizmann Institute of Science).
NR 15
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PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
J9 NAT GENET
JI Nature Genet.
PD MAY
PY 2009
VL 41
IS 5
BP 521
EP 523
DI 10.1038/ng.349
PG 3
WC Genetics & Heredity
SC Genetics & Heredity
GA 438SL
UT WOS:000265575600011
PM 19330029
ER
PT J
AU Dankort, D
Curley, DP
Cartlidge, RA
Nelson, B
Karnezis, AN
Damsky, WE
You, MJ
DePinho, RA
McMahon, M
Bosenberg, M
AF Dankort, David
Curley, David P.
Cartlidge, Robert A.
Nelson, Betsy
Karnezis, Anthony N.
Damsky, William E., Jr.
You, Mingjian J.
DePinho, Ronald A.
McMahon, Martin
Bosenberg, Marcus
TI Braf(V600E) cooperates with Pten loss to induce metastatic melanoma
SO NATURE GENETICS
LA English
DT Article
ID CELL-CYCLE ARREST; MALIGNANT-MELANOMA; BRAF MUTATIONS; B-RAF;
MELANOCYTES; SENESCENCE; MOUSE; MICE; INHIBITOR; GENETICS
AB Mutational activation of BRAF is the earliest and most common genetic alteration in human melanoma. To build a model of human melanoma, we generated mice with conditional melanocyte-specific expression of BRaf(V600E). Upon induction of BRaf(V600E) expression, mice developed benign melanocytic hyperplasias that failed to progress to melanoma over 15-20 months. By contrast, expression of BRaf(V600E) combined with Pten tumor suppressor gene silencing elicited development of melanoma with 100% penetrance, short latency and with metastases observed in lymph nodes and lungs. Melanoma was prevented by inhibitors of mTorc1 (rapamycin) or MEK1/2 (PD325901) but, upon cessation of drug administration, mice developed melanoma, indicating the presence of long-lived melanoma-initiating cells in this system. Notably, combined treatment with rapamycin and PD325901 led to shrinkage of established melanomas. These mice, engineered with a common genetic profile to human melanoma, provide a system to study melanoma's cardinal feature of metastasis and for preclinical evaluation of agents designed to prevent or treat metastatic disease.
C1 [Dankort, David; Cartlidge, Robert A.; Karnezis, Anthony N.; McMahon, Martin] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, Canc Res Inst, San Francisco, CA 94143 USA.
[Curley, David P.; Nelson, Betsy; Damsky, William E., Jr.; Bosenberg, Marcus] Univ Vermont, Coll Med, Dept Pathol, Burlington, VT 05405 USA.
[Dankort, David; Cartlidge, Robert A.; McMahon, Martin] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, Dept Cell & Mol Pharmacol, San Francisco, CA 94143 USA.
[Karnezis, Anthony N.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, Dept Pathol, San Francisco, CA 94143 USA.
[You, Mingjian J.; DePinho, Ronald A.] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Dept Med Oncol, Boston, MA 02115 USA.
[You, Mingjian J.; DePinho, Ronald A.] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Dept Med, Boston, MA 02115 USA.
[You, Mingjian J.; DePinho, Ronald A.] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Dept Genet, Boston, MA 02115 USA.
[You, Mingjian J.; DePinho, Ronald A.] Harvard Univ, Sch Med, Boston, MA USA.
RP McMahon, M (reprint author), Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, Canc Res Inst, San Francisco, CA 94143 USA.
EM mcmahon@cc.ucsf.edu; marcus.bosenberg@yale.edu
RI McMahon, Martin/L-3303-2013;
OI McMahon, Martin/0000-0003-2812-1042; Dankort, David/0000-0002-5862-6829
FU University of California San Francisco Helen Diller Family Comprehensive
Cancer Center Mouse Pathology and Pre-Clinical Therapeutics cores;
Melanoma Research Foundation; U.C. Discovery Award; US National
Institutes of Health [CA 108972, CA 84313, CA 89124, CA 112054]
FX We thank the members of the McMahon and Bosenberg laboratories as well
as B. Bastian, L. Chin, E. Filenova, B. Hann, M. Herlyn, L. Johnson, G.
Merlino, P. P. Pandolfi, V. Hearing, M. Held, G. Kay and D. Matzen for
the provision of mouse strains, reagents, advice and support. M. M.
thanks A. Ricart and J. Sebolt-Leopold (Pfizer) for provision of
PD325901 and acknowledges the support of the University of California
San Francisco Helen Diller Family Comprehensive Cancer Center Mouse
Pathology and Pre-Clinical Therapeutics cores. R. A. D. is supported as
an American Cancer Society Research Professor. This work was supported
by grants from the Melanoma Research Foundation, U.C. Discovery Award
and from the US National Institutes of Health (CA 108972 to M. M., CA
84313 to R. A. D. and CA 89124 and CA 112054 to M. B., respectively).
NR 50
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U1 3
U2 25
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
J9 NAT GENET
JI Nature Genet.
PD MAY
PY 2009
VL 41
IS 5
BP 544
EP 552
DI 10.1038/ng.356
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA 438SL
UT WOS:000265575600015
PM 19282848
ER
PT J
AU Suzuki, H
Forrest, ARR
van Nimwegen, E
Daub, CO
Balwierz, PJ
Irvine, KM
Lassmann, T
Ravasi, T
Hasegawa, Y
de Hoon, MJL
Katayama, S
Schroder, K
Carninci, P
Tomaru, Y
Kanamori-Katayama, M
Kubosaki, A
Akalin, A
Ando, Y
Arner, E
Asada, M
Asahara, H
Bailey, T
Bajic, VB
Bauer, D
Beckhouse, AG
Bertin, N
Bjorkegren, J
Brombacher, F
Bulger, E
Chalk, AM
Chiba, J
Cloonan, N
Dawe, A
Dostie, J
Engstrom, PG
Essack, M
Faulkner, GJ
Fink, JL
Fredman, D
Fujimori, K
Furuno, M
Gojobori, T
Gough, J
Grimmond, SM
Gustafsson, M
Hashimoto, M
Hashimoto, T
Hatakeyama, M
Heinzel, S
Hide, W
Hofmann, O
Hornquist, M
Huminiecki, L
Ikeo, K
Imamoto, N
Inoue, S
Inoue, Y
Ishihara, R
Iwayanagi, T
Jacobsen, A
Kaur, M
Kawaji, H
Kerr, MC
Kimura, R
Kimura, S
Kimura, Y
Kitano, H
Koga, H
Kojima, T
Kondo, S
Konno, T
Krogh, A
Kruger, A
Kumar, A
Lenhard, B
Lennartsson, A
Lindow, M
Lizio, M
MacPherson, C
Maeda, N
Maher, CA
Maqungo, M
Mar, J
Matigian, NA
Matsuda, H
Mattick, JS
Meier, S
Miyamoto, S
Miyamoto-Sato, E
Nakabayashi, K
Nakachi, Y
Nakano, M
Nygaard, S
Okayama, T
Okazaki, Y
Okuda-Yabukami, H
Orlando, V
Otomo, J
Pachkov, M
Petrovsky, N
Plessy, C
Quackenbush, J
Radovanovic, A
Rehli, M
Saito, R
Sandelin, A
Schmeier, S
Schonbach, C
Schwartz, AS
Semple, CA
Sera, M
Severin, J
Shirahige, K
Simons, C
Laurent, GS
Suzuki, M
Suzuki, T
Sweet, MJ
Taft, RJ
Takeda, S
Takenaka, Y
Tan, K
Taylor, MS
Teasdale, RD
Tegner, J
Teichmann, S
Valen, E
Wahlestedt, C
Waki, K
Waterhouse, A
AWells, C
Winther, O
Wu, L
Yamaguchi, K
Yanagawa, H
Yasuda, J
Zavolan, M
Hume, DA
Arakawa, T
Fukuda, S
Imamura, K
Kai, C
Kaiho, A
Kawashima, T
Kawazu, C
Kitazume, Y
Kojima, M
Miura, H
Murakami, K
Murata, M
Ninomiya, N
Nishiyori, H
Noma, S
Ogawa, C
Sano, T
Simon, C
Tagami, M
Takahashi, Y
Kawai, J
Hayashizaki, Y
AF Suzuki, Harukazu
Forrest, Alistair R. R.
van Nimwegen, Erik
Daub, Carsten O.
Balwierz, Piotr J.
Irvine, Katharine M.
Lassmann, Timo
Ravasi, Timothy
Hasegawa, Yuki
de Hoon, Michiel J. L.
Katayama, Shintaro
Schroder, Kate
Carninci, Piero
Tomaru, Yasuhiro
Kanamori-Katayama, Mutsumi
Kubosaki, Atsutaka
Akalin, Altuna
Ando, Yoshinari
Arner, Erik
Asada, Maki
Asahara, Hiroshi
Bailey, Timothy
Bajic, Vladimir B.
Bauer, Denis
Beckhouse, Anthony G.
Bertin, Nicolas
Bjorkegren, Johan
Brombacher, Frank
Bulger, Erika
Chalk, Alistair M.
Chiba, Joe
Cloonan, Nicole
Dawe, Adam
Dostie, Josee
Engstrom, Par G.
Essack, Magbubah
Faulkner, Geoffrey J.
Fink, J. Lynn
Fredman, David
Fujimori, Ko
Furuno, Masaaki
Gojobori, Takashi
Gough, Julian
Grimmond, Sean M.
Gustafsson, Mika
Hashimoto, Megumi
Hashimoto, Takehiro
Hatakeyama, Mariko
Heinzel, Susanne
Hide, Winston
Hofmann, Oliver
Hornquist, Michael
Huminiecki, Lukasz
Ikeo, Kazuho
Imamoto, Naoko
Inoue, Satoshi
Inoue, Yusuke
Ishihara, Ryoko
Iwayanagi, Takao
Jacobsen, Anders
Kaur, Mandeep
Kawaji, Hideya
Kerr, Markus C.
Kimura, Ryuichiro
Kimura, Syuhei
Kimura, Yasumasa
Kitano, Hiroaki
Koga, Hisashi
Kojima, Toshio
Kondo, Shinji
Konno, Takeshi
Krogh, Anders
Kruger, Adele
Kumar, Ajit
Lenhard, Boris
Lennartsson, Andreas
Lindow, Morten
Lizio, Marina
MacPherson, Cameron
Maeda, Norihiro
Maher, Christopher A.
Maqungo, Monique
Mar, Jessica
Matigian, Nicholas A.
Matsuda, Hideo
Mattick, John S.
Meier, Stuart
Miyamoto, Sei
Miyamoto-Sato, Etsuko
Nakabayashi, Kazuhiko
Nakachi, Yutaka
Nakano, Mika
Nygaard, Sanne
Okayama, Toshitsugu
Okazaki, Yasushi
Okuda-Yabukami, Haruka
Orlando, Valerio
Otomo, Jun
Pachkov, Mikhail
Petrovsky, Nikolai
Plessy, Charles
Quackenbush, John
Radovanovic, Aleksandar
Rehli, Michael
Saito, Rintaro
Sandelin, Albin
Schmeier, Sebastian
Schonbach, Christian
Schwartz, Ariel S.
Semple, Colin A.
Sera, Miho
Severin, Jessica
Shirahige, Katsuhiko
Simons, Cas
Laurent, George St.
Suzuki, Masanori
Suzuki, Takahiro
Sweet, Matthew J.
Taft, Ryan J.
Takeda, Shizu
Takenaka, Yoichi
Tan, Kai
Taylor, Martin S.
Teasdale, Rohan D.
Tegner, Jesper
Teichmann, Sarah
Valen, Eivind
Wahlestedt, Claes
Waki, Kazunori
Waterhouse, Andrew
AWells, Christine
Winther, Ole
Wu, Linda
Yamaguchi, Kazumi
Yanagawa, Hiroshi
Yasuda, Jun
Zavolan, Mihaela
Hume, David A.
Arakawa, Takahiro
Fukuda, Shiro
Imamura, Kengo
Kai, Chikatoshi
Kaiho, Ai
Kawashima, Tsugumi
Kawazu, Chika
Kitazume, Yayoi
Kojima, Miki
Miura, Hisashi
Murakami, Kayoko
Murata, Mitsuyoshi
Ninomiya, Noriko
Nishiyori, Hiromi
Noma, Shohei
Ogawa, Chihiro
Sano, Takuma
Simon, Christophe
Tagami, Michihira
Takahashi, Yukari
Kawai, Jun
Hayashizaki, Yoshihide
CA FANTOM Consortium
Riken Omics Sci Ctr
TI The transcriptional network that controls growth arrest and
differentiation in a human myeloid leukemia cell line
SO NATURE GENETICS
LA English
DT Article
ID SERUM RESPONSE FACTOR; MONOCYTE-MACROPHAGE MATURATION; MESSENGER-RNA
EXPRESSION; FACTOR-BINDING-SITES; GENE-EXPRESSION; SIGNALING PATHWAYS;
STEM-CELLS; GENOME; PHOSPHORYLATION; PROLIFERATION
AB Using deep sequencing (deepCAGE), the FANTOM4 study measured the genome-wide dynamics of transcription-start-site usage in the human monocytic cell line THP-1 throughout a time course of growth arrest and differentiation. Modeling the expression dynamics in terms of predicted cis-regulatory sites, we identified the key transcription regulators, their time-dependent activities and target genes. Systematic siRNA knockdown of 52 transcription factors confirmed the roles of individual factors in the regulatory network. Our results indicate that cellular states are constrained by complex networks involving both positive and negative regulatory interactions among substantial numbers of transcription factors and that no single transcription factor is both necessary and sufficient to drive the differentiation process.
C1 [Hume, David A.] Univ Edinburgh, Roslin Inst, Roslin, Midlothian, Scotland.
[Hume, David A.] Univ Edinburgh, Royal Dick Sch Vet Studies, Roslin, Midlothian, Scotland.
[Suzuki, Harukazu; Forrest, Alistair R. R.; Daub, Carsten O.; Lassmann, Timo; Hasegawa, Yuki; de Hoon, Michiel J. L.; Katayama, Shintaro; Carninci, Piero; Tomaru, Yasuhiro; Kanamori-Katayama, Mutsumi; Kubosaki, Atsutaka; Ando, Yoshinari; Arner, Erik; Bertin, Nicolas; Bulger, Erika; Furuno, Masaaki; Hashimoto, Takehiro; Ishihara, Ryoko; Kawaji, Hideya; Kimura, Yasumasa; Kondo, Shinji; Lennartsson, Andreas; Lizio, Marina; Maeda, Norihiro; Nakano, Mika; Okuda-Yabukami, Haruka; Plessy, Charles; Severin, Jessica; Suzuki, Masanori; Suzuki, Takahiro; Waki, Kazunori; Waterhouse, Andrew; Yamaguchi, Kazumi; Yasuda, Jun] RIKEN, Yokohama Inst, Omics Sci Ctr, Kanagawa, Japan.
[Forrest, Alistair R. R.; Beckhouse, Anthony G.; Chalk, Alistair M.; Matigian, Nicholas A.; AWells, Christine] Griffith Univ, Eskitis Inst Cell & Mol Therapies, Nathan, Qld 4111, Australia.
[van Nimwegen, Erik; Balwierz, Piotr J.; Pachkov, Mikhail; Zavolan, Mihaela] Univ Basel, Bioctr, CH-4056 Basel, Switzerland.
[van Nimwegen, Erik; Balwierz, Piotr J.; Pachkov, Mikhail; Zavolan, Mihaela] Swiss Inst Bioinformat, Basel, Switzerland.
[Irvine, Katharine M.; Schroder, Kate; Bailey, Timothy; Bauer, Denis] Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia.
[Ravasi, Timothy; Schwartz, Ariel S.; Tan, Kai] Univ Calif San Diego, Jacobs Sch Engn, Dept Bioengn, La Jolla, CA 92093 USA.
[Akalin, Altuna; Engstrom, Par G.; Fredman, David; Lenhard, Boris] Bergen Ctr Computat Sci, Bergen, Norway.
[Asada, Maki; Asahara, Hiroshi; Hashimoto, Megumi] Natl Res Inst Child Hlth & Dev, Tokyo, Japan.
[Bajic, Vladimir B.; Dawe, Adam; Essack, Magbubah; Hide, Winston; Hofmann, Oliver; Kaur, Mandeep; Kruger, Adele; MacPherson, Cameron; Maqungo, Monique; Meier, Stuart; Radovanovic, Aleksandar; Schmeier, Sebastian; AWells, Christine] Univ Western Cape, S African Natl Bioinformat Inst, ZA-7535 Bellville, South Africa.
[Bjorkegren, Johan; Tegner, Jesper] Karolinska Univ Hosp Solna, Karolinska Inst, Dept Med, Computat Med Grp,Atherosclerosis Res Unit,Ctr Mol, Stockholm, Sweden.
[Brombacher, Frank] Univ Cape Town, Fac Hlth Sci, IIDMM, Observatory, South Africa.
[Chiba, Joe; Kimura, Ryuichiro; Nakabayashi, Kazuhiko] Tokyo Univ Sci, Dept Biol Sci & Technol, Tokyo 162, Japan.
[Cloonan, Nicole; Faulkner, Geoffrey J.; Grimmond, Sean M.; Mattick, John S.; Simons, Cas; Taft, Ryan J.] Univ Queensland, Inst Mol Biosci, Special Res Ctr Funct & Appl Genom, ARC, St Lucia, Qld, Australia.
[Dostie, Josee] McGill Univ, Dept Biochem, Montreal, PQ, Canada.
[Fink, J. Lynn; Kerr, Markus C.; Teasdale, Rohan D.] Univ Queensland, Inst Mol Biosci, Ctr Excellence Bioinformat, ARC, St Lucia, Qld, Australia.
[Fujimori, Ko] Osaka Univ Pharmaceut Sci, Lab Biodef & Regulat, Osaka 580, Japan.
[Gojobori, Takashi; Ikeo, Kazuho; Konno, Takeshi; Miyamoto, Sei; Okayama, Toshitsugu; Sera, Miho] Natl Inst Genet, Res Org Informat & Syst, Ctr Informat Biol, Shizuoka, Japan.
[Gojobori, Takashi; Ikeo, Kazuho; Konno, Takeshi; Miyamoto, Sei; Okayama, Toshitsugu; Sera, Miho] Natl Inst Genet, DDBJ, Shizuoka, Japan.
[Gough, Julian] Univ Bristol, Dept Comp Sci, Bristol, Avon, England.
[Gustafsson, Mika; Hornquist, Michael] Linkoping Univ, Dept Sci & Technol, Norrkoping, Sweden.
[Hatakeyama, Mariko; Kojima, Toshio] RIKEN, Yokohama Inst, Genom Sci Ctr, Computat & Expt Syst Biol Grp, Kanagawa, Japan.
[Heinzel, Susanne; Petrovsky, Nikolai] Flinders Univ & Med Ctr, Dept Endocrinol & Diabet, Adelaide, SA, Australia.
[Hide, Winston; Hofmann, Oliver] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Huminiecki, Lukasz] Karolinska Inst, Dept Cell & Mol Biol, Stockholm, Sweden.
[Imamoto, Naoko] RIKEN, Wako Inst, Discovery & Res Inst, Cellular Dynam Lab, Saitama, Japan.
[Inoue, Satoshi] Univ Tokyo, Grad Sch Med, Tokyo, Japan.
[Inoue, Satoshi] Univ Tokyo, Fac Med, Tokyo 113, Japan.
[Inoue, Yusuke] Gunma Univ, Fac Engn, Dept Biol & Chem Engn, Gunma, Japan.
[Iwayanagi, Takao] Hitachi Ltd, Res & Dev Grp, R&D Solut Ctr, Tokyo, Japan.
[Jacobsen, Anders; Krogh, Anders; Lindow, Morten; Nygaard, Sanne; Sandelin, Albin; Valen, Eivind; Winther, Ole] Univ Copenhagen, Dept Biol, Bioinformat Ctr, Copenhagen, Denmark.
[Jacobsen, Anders; Krogh, Anders; Lindow, Morten; Nygaard, Sanne; Sandelin, Albin; Valen, Eivind; Winther, Ole] Univ Copenhagen, Biotech Res & Innovat Ctr, Copenhagen, Denmark.
[Kimura, Syuhei] Tottori Univ, Fac Engn, Dept Informat & Knowledge Engn, Tottori 680, Japan.
[Kitano, Hiroaki] Syst Biol Inst, Shibuya Ku, Tokyo, Japan.
[Koga, Hisashi] Kazusa DNA Res Inst, Dept Human Gene Res, Chiba, Japan.
[Kumar, Ajit; Laurent, George St.] George Washington Univ, Med Ctr, Dept Biochem & Mol Biol, Washington, DC 20037 USA.
[Mar, Jessica; Quackenbush, John] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA.
[Matsuda, Hideo; Takenaka, Yoichi] Osaka Univ, Grad Sch Informat Sci & Technol, Dept Bioinformat Engn, Osaka, Japan.
[Miyamoto-Sato, Etsuko; Yanagawa, Hiroshi] Keio Univ, Fac Sci & Technol, Dept Biosci & Informat, Yokohama, Kanagawa 223, Japan.
[Nakachi, Yutaka; Okazaki, Yasushi] Saitama Med Sch, Res Ctr Genom Med, Div Funct Genom & Syst Med, Saitama, Japan.
[Orlando, Valerio] IRCCS Fdn Santa Lucia EBRI, Dulbecco Telethon Inst, Rome, Italy.
[Orlando, Valerio] IGB CNR, Naples, Italy.
[Otomo, Jun; Takeda, Shizu] Hitachi Ltd, Cent Res Labs, Tokyo, Japan.
[Rehli, Michael] Univ Regensburg, Dept Hematol & Oncol, Regensburg, Germany.
[Saito, Rintaro] Keio Univ, Fac Environm & Informat Studies, Kanagawa, Japan.
[Schonbach, Christian] Nanyang Technol Univ, Div Genom & Genet, Sch Biol Sci, Singapore, Singapore.
[Semple, Colin A.] Western Gen Hosp, Human Genet Unit, MRC, Edinburgh EH4 2XU, Midlothian, Scotland.
[Shirahige, Katsuhiko] Tokyo Inst Technol, Grad Sch Informat Sci & Engn, Dept Comp Sci, Tokyo 152, Japan.
[Sweet, Matthew J.] Univ Queensland, CRC Chron Inflammatory Dis, Sch Mol & Microbial Sci, Inst Mol Biosci, St Lucia, Qld, Australia.
[Taylor, Martin S.] EMBL European Bioinformat Inst, Cambridge, England.
[Tegner, Jesper] Linkoping Univ, Dept Phys Chem & Biol, Linkoping, Sweden.
[Teichmann, Sarah] MRC, Mol Biol Lab, Struct Studies Div, Cambridge CB2 2QH, England.
[Wahlestedt, Claes] Scripps Res Inst, Jupiter, FL USA.
RP Hume, DA (reprint author), Univ Edinburgh, Roslin Inst, Roslin, Midlothian, Scotland.
EM david.hume@roslin.ed.ac.uk; yosihide@gsc.riken.jp
RI Bertin, Nicolas/C-3025-2008; Bajic, Vladimir/D-2810-2009; Essack,
Magbubah/G-5008-2013; Plessy, Charles/N-5054-2015; de Hoon,
Michiel/N-8006-2015; Hayashizaki, Yoshihide/N-6590-2015; Suzuki,
Harukazu/N-9553-2015; Semple, Colin/A-5613-2009; Faulkner,
Geoffrey/M-3168-2014; Mattick, John/I-7789-2012; Kawai, Jun/A-6451-2016;
Okada, Mariko/N-6933-2015; Grimmond, Sean/J-5304-2016; Schmeier,
Sebastian/D-4731-2011; Kawaji, Hideya/N-5116-2015; Simons,
Cas/A-7905-2011; Hofmann, Oliver/F-1800-2013; Fredman,
David/H-3566-2013; Schroder, Kate/C-6132-2008; Lassmann,
Timo/A-8271-2008; Kimura, Yasumasa/M-9720-2013; Kerr,
Markus/A-9864-2014; Carninci, Piero/K-1568-2014; Sandelin,
Albin/G-2881-2011; Krogh, Anders/M-1541-2014; Nygaard,
Sanne/M-2569-2014; Imamoto, Naoko/A-7458-2015; Jacobsen,
Anders/K-1081-2013; Rehli, Michael/E-9093-2011; Sweet,
Matthew/F-2229-2011; Forrest, Alistair/A-6597-2008; Cloonan,
Nicole/B-5272-2008; Irvine, Katharine/A-5559-2011; AKALIN,
ALTUNA/A-4424-2012; Matigian, Nicholas/A-4935-2009; Wells,
Christine/A-5071-2010; Radovanovic, Aleksandar/D-1313-2012; Katayama,
Shintaro/F-2958-2010; Schonbach, Christian/B-1998-2009; de Hoon,
Michiel/A-6443-2013; Hume, David/C-7695-2013; Dawe, Adam/C-5295-2009;
Lennartsson, Andreas/E-7823-2011; Fink, Lynn/C-2031-2008; Teasdale,
Rohan/B-2538-2009; Bauer, Denis/C-3903-2009; Ravasi,
Timothy/B-8777-2008; Taylor, Martin/C-3825-2009; Arner,
Erik/A-1895-2010; Beckhouse, Anthony/A-2601-2010; Taft,
Ryan/B-2945-2010; Valen, Eivind/A-8617-2011; Daub, Carsten/A-7436-2010;
Hide, Winston Hide/C-7217-2009;
OI Petrovsky, Nikolai/0000-0002-1580-5245; Fujimori,
Ko/0000-0002-2506-0769; Valen, Eivind/0000-0003-1840-6108; Chalk,
Alistair/0000-0002-9630-6236; Lenhard, Boris/0000-0002-1114-1509;
Lennartsson, Andreas/0000-0002-3272-2505; Teichmann,
Sarah/0000-0002-6294-6366; Bertin, Nicolas/0000-0002-9835-9606; Bajic,
Vladimir/0000-0001-5435-4750; Engstrom, Par/0000-0001-5265-2121; van
Nimwegen, Erik/0000-0001-6338-1312; Essack,
Magbubah/0000-0003-2709-5356; Plessy, Charles/0000-0001-7410-6295;
Suzuki, Harukazu/0000-0002-8087-0836; Semple, Colin/0000-0003-1765-4118;
Faulkner, Geoffrey/0000-0001-5769-4494; Mattick,
John/0000-0002-7680-7527; Grimmond, Sean/0000-0002-8102-7998; Schmeier,
Sebastian/0000-0002-3947-8226; Kawaji, Hideya/0000-0002-0575-0308;
Simons, Cas/0000-0003-3147-8042; Hofmann, Oliver/0000-0002-7738-1513;
Fredman, David/0000-0003-3507-0554; Schroder, Kate/0000-0001-9261-3805;
Lassmann, Timo/0000-0002-0138-2691; Carninci, Piero/0000-0001-7202-7243;
Sandelin, Albin/0000-0002-7109-7378; Krogh, Anders/0000-0002-5147-6282;
Nygaard, Sanne/0000-0002-3002-6047; Imamoto, Naoko/0000-0002-2886-3022;
Jacobsen, Anders/0000-0001-6847-4980; Rehli,
Michael/0000-0003-3992-932X; Sweet, Matthew/0000-0002-0406-8139;
Forrest, Alistair/0000-0003-4543-1675; AKALIN,
ALTUNA/0000-0002-0468-0117; Matigian, Nicholas/0000-0001-7735-9415;
Wells, Christine/0000-0003-3133-3628; Radovanovic,
Aleksandar/0000-0002-8749-7608; Katayama, Shintaro/0000-0001-7581-5157;
Schonbach, Christian/0000-0002-0693-7617; Fink,
Lynn/0000-0003-2912-6048; Teasdale, Rohan/0000-0001-7455-5269; Taylor,
Martin/0000-0001-7656-330X; Arner, Erik/0000-0003-1225-4908; Beckhouse,
Anthony/0000-0002-5141-8250; Daub, Carsten/0000-0002-3295-8729; Hide,
Winston Hide/0000-0002-8621-3271; Zavolan, Mihaela/0000-0002-8832-2041
FU Ministry of Education, Culture, Sports, Science and Technology, Japan;
RIKEN Frontier Research System, Functional RNA research program;
Australian National Health and Medical Research Council [ID 428261]; SNF
[SNF 3100A0-118318]; Fondazione Telethon
FX We thank A. Ambesi, H. Atsui, M. Bansal, V. Belcastro, H. Daub, D. di
Bernardo, M. Furuya, A. Hasegawa, K. Hayashida, A. Hirakiyama, F. Hori,
K. Koseki, S. Kuhara, N. Miyamoto, S. Miyano, M. Nishikawa, C. Ohinata,
M. Persson, S. Saihara, C. Sakaba, H. Sano, E. Shibazaki, T. Takagi, K.
Toyoda, Y. Tsujimura and M. Yamamoto for discussion, encouragement and
technical assistance. We thank M. Muramatsu, T. Ogawa, Y. Sakaki and A.
Wada for support and encouragement. This work was mainly supported by
grants for the Genome Network Project from the Ministry of Education,
Culture, Sports, Science and Technology, Japan (Y. H.), Research Grant
for the RIKEN Genome Exploration Research Project from the Ministry of
Education, Culture, Sports, Science and Technology of the Japanese
Government (Y. H.) and the RIKEN Frontier Research System, Functional
RNA research program (Y. H.). A. R. R. F. is supported by a CJ Martin
Fellowship from the Australian National Health and Medical Research
Council (ID 428261). E. v. N. acknowledges support from SNF grant SNF #
3100A0-118318.
NR 49
TC 252
Z9 254
U1 1
U2 40
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
J9 NAT GENET
JI Nature Genet.
PD MAY
PY 2009
VL 41
IS 5
BP 553
EP 562
DI 10.1038/ng.375
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA 438SL
UT WOS:000265575600016
ER
PT J
AU Dejean, AS
Beisner, DR
Ch'en, IL
Kerdiles, YM
Babour, A
Arden, KC
Castrillon, DH
DePinho, RA
Hedrick, SM
AF Dejean, Anne S.
Beisner, Daniel R.
Ch'en, Irene L.
Kerdiles, Yann M.
Babour, Anna
Arden, Karen C.
Castrillon, Diego H.
DePinho, Ronald A.
Hedrick, Stephen M.
TI Transcription factor Foxo3 controls the magnitude of T cell immune
responses by modulating the function of dendritic cells
SO NATURE IMMUNOLOGY
LA English
DT Article
ID TRYPTOPHAN CATABOLISM; OXIDATIVE STRESS; MLL GENE; IN-VIVO; SURVIVAL;
AUTOIMMUNITY; ACTIVATION; PROTEINS; FAMILY; CTLA-4
AB Foxo transcription factors regulate cell cycle progression, cell survival and DNA-repair pathways. Here we demonstrate that deficiency in Foxo3 resulted in greater expansion of T cell populations after viral infection. This exaggerated expansion was not T cell intrinsic. Instead, it was caused by the enhanced capacity of Foxo3-deficient dendritic cells to sustain T cell viability by producing more interleukin 6. Stimulation of dendritic cells mediated by the coinhibitory molecule CTLA-4 induced nuclear localization of Foxo3, which in turn inhibited the production of interleukin 6 and tumor necrosis factor. Thus, Foxo3 acts to constrain the production of key inflammatory cytokines by dendritic cells and to control T cell survival.
C1 [Dejean, Anne S.; Beisner, Daniel R.; Ch'en, Irene L.; Kerdiles, Yann M.; Babour, Anna; Hedrick, Stephen M.] Univ Calif San Diego, Mol Biol Sect, Div Biol Sci, San Diego, CA 92103 USA.
[Dejean, Anne S.; Beisner, Daniel R.; Ch'en, Irene L.; Kerdiles, Yann M.; Babour, Anna; Hedrick, Stephen M.] Univ Calif San Diego, Dept Cellular & Mol Med, San Diego, CA 92103 USA.
[Arden, Karen C.] Univ Calif, San Diego Sch Med, Ludwig Inst Canc Res, La Jolla, CA USA.
[Castrillon, Diego H.; DePinho, Ronald A.] Harvard Univ, Sch Med, Dana Farber Canc Inst,Dept Adult Oncol, Ctr Appl Canc Sci,Belfer Inst Innovat Canc Sci, Boston, MA 02115 USA.
[Castrillon, Diego H.; DePinho, Ronald A.] Harvard Univ, Sch Med, Dana Farber Canc Inst,Dept Med, Ctr Appl Canc Sci,Belfer Inst Innovat Canc Sci, Boston, MA 02115 USA.
[Castrillon, Diego H.; DePinho, Ronald A.] Harvard Univ, Sch Med, Dana Farber Canc Inst,Dept Genet, Ctr Appl Canc Sci,Belfer Inst Innovat Canc Sci, Boston, MA 02115 USA.
RP Hedrick, SM (reprint author), Univ Calif San Diego, Mol Biol Sect, Div Biol Sci, San Diego, CA 92103 USA.
EM shedrick@ucsd.edu
RI Dejean, Anne/K-6739-2014
FU American Cancer Society; Robert A. and Renee E. Belfer Institute for
Innovative Cancer Research; US National Cancer Institute; Division of
Biological Sciences of the University of California, San Diego;
Fondation pour la Recherche Medicale
FX We thank J. P. Allison (Sloan-Kettering Memorial Hospital) and J. A.
Bluestone (University of California at San Diego) for CTLA-4-specific
blocking antibodies; A. Brunet (Stanford University) for Foxo3-specific
antibody; L. Lefranc, ois (University of Connecticut Health Center) for
OVA-expressing vesicular stomatitis virus; L. Mack and E. Zuniga for
assistance with virus titers; and M. Niwa for microscope facility use.
Supported by the American Cancer Society (R. A. D.), the Robert A. and
Renee E. Belfer Institute for Innovative Cancer Research (R. A. D.), the
US National Cancer Institute (R. A. D.), the Division of Biological
Sciences of the University of California, San Diego (S. M. H.) and the
Fondation pour la Recherche Medicale (A. S. D.).
NR 45
TC 115
Z9 121
U1 1
U2 7
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1529-2908
J9 NAT IMMUNOL
JI Nat. Immunol.
PD MAY
PY 2009
VL 10
IS 5
BP 504
EP 513
DI 10.1038/ni.1729
PG 10
WC Immunology
SC Immunology
GA 436EC
UT WOS:000265394400012
PM 19363483
ER
PT J
AU Stadtfeld, M
Hochedlinger, K
AF Stadtfeld, Matthias
Hochedlinger, Konrad
TI Without a trace? PiggyBac-ing toward pluripotency
SO NATURE METHODS
LA English
DT Editorial Material
ID STEM-CELLS; GENERATION
AB A transposon-based approach has been added to the growing arsenal of technologies to produce transgene-free and potentially safer induced pluripotent stem cells.
C1 [Stadtfeld, Matthias] Massachusetts Gen Hosp, Dept Med, Ctr Canc, Boston, MA 02114 USA.
Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA.
Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
RP Stadtfeld, M (reprint author), Massachusetts Gen Hosp, Dept Med, Ctr Canc, Boston, MA 02114 USA.
EM mstadtfeld@mgh.harvard.edu; khochedlinger@helix.mgh.harvard.edu
OI Stadtfeld, Matthias/0000-0002-5852-9906
NR 11
TC 8
Z9 8
U1 0
U2 7
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1548-7091
J9 NAT METHODS
JI Nat. Methods
PD MAY
PY 2009
VL 6
IS 5
BP 329
EP 330
DI 10.1038/nmeth0509-329
PG 2
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 439XS
UT WOS:000265661600009
PM 19404251
ER
PT J
AU DuBois, SG
Grier, HE
AF DuBois, Steven G.
Grier, Holcombe E.
TI The role of ifosfamide and etoposide in Ewing sarcoma
SO NATURE REVIEWS CLINICAL ONCOLOGY
LA English
DT Editorial Material
ID RECURRENT SARCOMAS; TUMOR; CHEMOTHERAPY; BENEFIT; BONE
AB The EICESS-92 trial compared the efficacy of cyclophosphamide and ifosfamide in patients with Ewing sarcoma. Subgroup analysis suggested that patients with large, localized tumors benefited from the addition of etoposide, whereas patients with metastases did not.
C1 [DuBois, Steven G.] Univ Calif San Francisco, Sch Med, San Francisco, CA USA.
[Grier, Holcombe E.] Harvard Univ, Sch Med, Boston, MA USA.
RP Grier, HE (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA.
EM holcombe_grier@dfci.harvard.edu
NR 7
TC 3
Z9 4
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1759-4774
J9 NAT REV CLIN ONCOL
JI Nat. Rev. Clin. Oncol.
PD MAY
PY 2009
VL 6
IS 5
BP 251
EP 253
DI 10.1038/nrclinonc.2009.25
PG 4
WC Oncology
SC Oncology
GA 442PT
UT WOS:000265853800005
PM 19390548
ER
PT J
AU Weisbord, SD
Palevsky, PM
AF Weisbord, Steven D.
Palevsky, Paul M.
TI ACUTE KIDNEY INJURY Intravenous fluid to prevent contrast-induced AKI
SO NATURE REVIEWS NEPHROLOGY
LA English
DT Editorial Material
ID INDUCED NEPHROPATHY; SODIUM-BICARBONATE; CORONARY-ANGIOGRAPHY;
N-ACETYLCYSTEINE; TRIAL; INTERVENTION; HYDRATION; CHLORIDE
AB Trials that compared sodium bicarbonate and sodium chloride for the prevention of contrast-induced acute kidney injury have yielded highly conflicting results. the authors of a recent meta-analysis endeavored to provide a definitive assessment of the relative efficacy of these two intravenous fluids.
C1 [Weisbord, Steven D.] Vet Affairs Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA 15240 USA.
Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA.
Univ Pittsburgh, Sch Med, Dept Med, Renal Electrolyte Div, Pittsburgh, PA USA.
RP Weisbord, SD (reprint author), Vet Affairs Pittsburgh Healthcare Syst, Renal Sect, 111F-U,Room 7E 120,Univ Dr Div, Pittsburgh, PA 15240 USA.
EM weisbordsd@upmc.edu
OI Palevsky, Paul/0000-0002-7334-5400
NR 8
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 1759-5061
J9 NAT REV NEPHROL
JI Nat. Rev. Nephrol.
PD MAY
PY 2009
VL 5
IS 5
BP 256
EP 257
DI 10.1038/nrneph.2009.26
PG 3
WC Urology & Nephrology
SC Urology & Nephrology
GA 442QA
UT WOS:000265854500007
PM 19384326
ER
PT J
AU Lal, A
Pan, YF
Navarro, F
Dykxhoorn, DM
Moreau, L
Meire, E
Bentwich, Z
Lieberman, J
Chowdhury, D
AF Lal, Ashish
Pan, Yunfeng
Navarro, Francisco
Dykxhoorn, Derek M.
Moreau, Lisa
Meire, Eti
Bentwich, Zvi
Lieberman, Judy
Chowdhury, Dipanjan
TI miR-24-mediated downregulation of H2AX suppresses DNA repair in
terminally differentiated blood cells
SO NATURE STRUCTURAL & MOLECULAR BIOLOGY
LA English
DT Article
ID EXPRESSION; MICRORNAS; PROLIFERATION; PROTEIN; RNA
AB Terminally differentiated cells have a reduced capacity to repair double-stranded breaks, but the molecular mechanism behind this downregulation is unclear. Here we find that miR-24 is upregulated during postmitotic differentiation of hematopoietic cell lines and regulates the histone variant H2AX, a protein that has a key role in the double-stranded break response. We show that the H2AX 3' untranslated region contains conserved miR-24 binding sites that are indeed regulated by miR-24. During terminal differentiation, both H2AX mRNA and protein levels are substantially reduced by miR-24 upregulation in in vitro differentiated cells; similar diminished levels are found in primary human blood cells. miR-24-mediated suppression of H2AX renders cells hypersensitive to gamma-irradiation and genotoxic drugs, a phenotype that is fully rescued by overexpression of miR-24-insensitive H2AX. Therefore, miR-24 upregulation in postreplicative cells reduces H2AX and makes them vulnerable to DNA damage.
C1 [Lal, Ashish; Navarro, Francisco; Dykxhoorn, Derek M.; Lieberman, Judy] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA.
[Lal, Ashish; Navarro, Francisco; Dykxhoorn, Derek M.; Lieberman, Judy] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
[Pan, Yunfeng; Moreau, Lisa; Chowdhury, Dipanjan] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Pan, Yunfeng; Moreau, Lisa; Chowdhury, Dipanjan] Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA USA.
[Meire, Eti; Bentwich, Zvi] Rosetta Genom, Rehovot, Israel.
RP Lieberman, J (reprint author), Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA.
EM lieberman@idi.harvard.edu; dipanjan_chowdhury@dfci.harvard.edu
RI Lieberman, Judy/A-2717-2015; Dykxhoorn, Derek/D-1357-2015
FU US National Institutes of Health [AI070302]
FX This work was supported in part by the US National Institutes of Health
grant AI070302 and a GSK-IDI Alliance grant ( to J.L.) and by a Barr
Award ( to D. C.). We thank members of the Lieberman and Chowdhury
laboratories for useful discussions.
NR 24
TC 165
Z9 171
U1 1
U2 10
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1545-9985
J9 NAT STRUCT MOL BIOL
JI Nat. Struct. Mol. Biol.
PD MAY
PY 2009
VL 16
IS 5
BP 492
EP 498
DI 10.1038/nsmb.1589
PG 7
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 447VS
UT WOS:000266220700015
PM 19377482
ER
PT J
AU Dhaese, I
Vanneste, G
Sips, P
Buys, ES
Brouckaert, P
Lefebvre, RA
AF Dhaese, Ingeborg
Vanneste, Gwen
Sips, Patrick
Buys, Emmanuel S.
Brouckaert, Peter
Lefebvre, Romain A.
TI Small intestinal motility in soluble guanylate cyclase alpha(1) knockout
mice
SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
LA English
DT Article
DE Soluble guanylate cyclase; Nitric oxide; Small intestinal motility; In
vivo; In vitro; sGC alpha(1) knockout
ID NITRIC-OXIDE; SMOOTH-MUSCLE; GASTROINTESTINAL TRANSIT; LONGITUDINAL
MUSCLE; INHIBITORY PATHWAYS; DEFICIENT MICE; RAT JEJUNUM; KINASE I;
RELAXATION; ENDOTHELIUM
AB Nitric oxide (NO) activates soluble guanylate cyclase (sGC) to produce guanosine-3',5'-cyclic-monophosphate (cGMP). The aim of this study was to investigate the nitrergic regulation of jejunal motility in sGC alpha(1) knockout (KO) mice. Functional responses to nitrergic stimuli and cGMP levels in response to nitrergic stimuli were determined in circular muscle strips. Intestinal transit was determined. Nitrergic relaxations induced by electrical field stimulation and exogenous NO were almost abolished in male KO strips, but only minimally reduced and sensitive to ODQ in female KO strips. Basal cGMP levels were decreased in KO strips, but NO still induced an increase in cGMP levels. Transit was not attenuated in male nor female KO mice. In vitro, sGC alpha(1)beta(1) is the most important isoform in nitrergic relaxation of jejunum, but nitrergic relaxation can also occur via sGC alpha(2)beta(1) activation. The latter mechanism is more pronounced in female than in male KO mice. In vivo, no important implications on intestinal motility were observed in male and female KO mice.
C1 [Buys, Emmanuel S.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Anesthesia Ctr Crit Care Res, Boston, MA 02114 USA.
[Sips, Patrick; Buys, Emmanuel S.; Brouckaert, Peter] Univ Ghent, Dept Mol Biol, B-9000 Ghent, Belgium.
[Sips, Patrick; Buys, Emmanuel S.; Brouckaert, Peter] VIB, Dept Mol Biomed Res, Ghent, Belgium.
[Dhaese, Ingeborg; Vanneste, Gwen; Lefebvre, Romain A.] Univ Ghent, Heymans Inst Pharmacol, B-9000 Ghent, Belgium.
RP Lefebvre, RA (reprint author), Pintelaan 185, B-9000 Ghent, Belgium.
EM Romain.Lefebvre@UGent.be
OI Sips, Patrick/0000-0001-9241-5980
FU Special Investigation Fund of Ghent University [GOA 1251004]; Scientific
Research Flanders [0053.02]; Interuniversity Attraction Pole Programme
[P5/20]
FX The study was financially supported by the Special Investigation Fund of
Ghent University (GOA 1251004), the fund for Scientific Research
Flanders (G. 0053.02), and by Interuniversity Attraction Pole Programme
P5/20.
NR 35
TC 6
Z9 7
U1 1
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0028-1298
J9 N-S ARCH PHARMACOL
JI Naunyn-Schmiedebergs Arch. Pharmacol.
PD MAY
PY 2009
VL 379
IS 5
BP 473
EP 487
DI 10.1007/s00210-008-0380-x
PG 15
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 423KI
UT WOS:000264494800005
PM 19052725
ER
PT J
AU Baba, Y
Nosho, K
Shima, K
Irahara, N
Kure, S
Toyoda, S
Kirkner, GJ
Goel, A
Fuchs, C
Ogino, S
AF Baba, Yoshifumi
Nosho, Katsuhiko
Shima, Kaori
Irahara, Natsumi
Kure, Shoko
Toyoda, Saori
Kirkner, Gregory J.
Goel, Ajay
Fuchs, Charles
Ogino, Shuji
TI Aurora-A Expression Is Independently Associated with Chromosomal
Instability in Colorectal Cancer
SO NEOPLASIA
LA English
DT Article
ID ISLAND METHYLATOR PHENOTYPE; FATTY-ACID SYNTHASE; MICROSATELLITE
INSTABILITY; COLON-CANCER; CENTROSOME AMPLIFICATION; POOR-PROGNOSIS;
OVARIAN-CANCER; KINASE-A; CYCLOOXYGENASE-2 EXPRESSION; EPIGENETIC
INSTABILITY
AB AURKA (the official symbol for Aurora-A, STK15, or BTAK) regulates the function of centrosomes, spindles, and kinetochores for proper mitotic progression. AURKA overexpression is observed in various cancers including colon cancer, and a link between AURKA and chromosomal instability (CIN) has been proposed. However, no study has comprehensively examined AURKA expression in relation to CIN or prognosis using a large number of tumors. Using 517 colorectal cancers in two prospective cohort studies, we detected AURKA overexpression (by immunohistochemistry) in 98 tumors (19%). We assessed other molecular events including loss of heterozygosity (LOH) in 2p, 5q, 17q, and 18q, the CpG island methylation phenotype (CIMP), and microsatellite instability (MSI). Prognostic significance of AURKA was evaluated by Cox regression and Kaplan-Meier method. In both univariate and multivariate logistic regressions, AURKA overexpression was significantly associated with CIN (defined as the presence of LOH in any of the chromosomal segments; multivariate odds ratio, 2.97; 95% confidence interval, 1.40-6.29; P = .0045). In multivariate analysis, AURKA was associated with cyclin D1 expression (P= .010) and inversely with PIK3CA mutation (P= .014), fatty acid synthase expression (P= .028), and family history of colorectal cancer (P = .050), but not with sex, age, body mass index, tumor location, stage, CIMP, MSI, KRAS, BRAF, BMI, LINE-1 hypomethylation, p53, p21, beta-catenin, or cyclooxygenase 2. AURKA was not significantly associated with clinical outcome or survival. In conclusion, AURKA overexpression is independently associated with CIN in colorectal cancer, supporting a potential role of Aurora kinase-A in colorectal carcinogenesis through genomic instability (rather than epigenomic instability).
C1 [Ogino, Shuji] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Mol Oncol Pathol,Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Ogino, S (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Mol Oncol Pathol,Dana Farber Canc Inst, 44 Binney St,Room JF 215C, Boston, MA 02115 USA.
EM shuji_ogino@dfci.harvard.edu
FU US National Institutes of Health (NIH) [P01 CA87969, P01 CA55075, P50
CA127003, K07 CA122826]; Bennett Family Fund; Entertainment Industry
Foundation; Japan Society for Promotion of Science
FX This work was supported by US National Institutes of Health (NIH) grants
P01 CA87969, P01 CA55075, P50 CA127003 (to C. S. F.), and K07 CA122826
(to S.O.) and in part by grants from the Bennett Family Fund and from
the Entertainment Industry Foundation through the National Colorectal
Cancer Research Alliance (NCCRA). K. N. was supported by a fellowship
grant from the Japan Society for Promotion of Science. The content is
solely the responsibility of the authors and does not necessarily
represent the official views of the National Cancer Institute or NIH.
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript. No conflicts of
interest exist.
NR 72
TC 61
Z9 63
U1 0
U2 3
PU NEOPLASIA PRESS
PI ANN ARBOR
PA 1150 W MEDICAL CENTER DR, MSRB III, RM 9303, ANN ARBOR, MI 48109-0648
USA
SN 1522-8002
J9 NEOPLASIA
JI Neoplasia
PD MAY
PY 2009
VL 11
IS 5
BP 418
EP 425
DI 10.1593/neo.09154
PG 8
WC Oncology
SC Oncology
GA 432AS
UT WOS:000265106500001
PM 19412426
ER
PT J
AU Lee, H
Park, JW
Kim, SP
Lo, EH
Lee, SR
AF Lee, Hyung
Park, Jong-Wook
Kim, Sang-Pyo
Lo, Eng H.
Lee, Seong-Ryong
TI Doxycycline inhibits matrix metalloproteinase-9 and laminin degradation
after transient global cerebral ischemia
SO NEUROBIOLOGY OF DISEASE
LA English
DT Article
DE Doxycycline; Matrix metalloproteinase; Neuroprotection; Global ischemia
ID DELAYED NEURONAL DEATH; BLOOD-BRAIN-BARRIER; MATRIX METALLOPROTEINASES;
GERBIL HIPPOCAMPUS; PLASMINOGEN ACTIVATORS; FOREBRAIN ISCHEMIA; DAMAGE;
INJURY; MODEL; APOPTOSIS
AB Doxycycline, a tetracycline antibiotic inhibits matrix metalloproteinase (MMP) and reduces neuronal damage in local brain ischemia. This study was undertaken to assess if doxycycline reduces delayed neuronal damage following transient global cerebral ischemia through MMIP inhibition. C57BL/6 mice were subjected to 20 min global cerebral ischemia. Doxycycline was administered to mice 30 min before and 2 h after ischemia. In TUNEL assay, damaged neurons were also apparent in the CA1 and CA2 areas and doxycycline reduced TUNEL-positive neurons. Gelatin gel and in situ zymography showed upregulation of gelatinase activity after ischemia. Doxycycline significantly inhibited MMP-9 activity in gel zymography and also suppressed in situ gelatinase activity. Laminin degradation was remarkable in CA1 and CA2 areas after ischemia and doxycycline reduced the laminin degradation and neuronal loss. Our data suggest that doxycycline may provide a neuroprotection against global cerebral ischemia since it reduces perineuronal laminin degradation by inhibiting MMP-9 activity. (C) 2008 Elsevier Inc. All rights reserved.
C1 [Lee, Seong-Ryong] Keimyung Univ, Sch Med, Dept Pharmacol, Taegu 700712, South Korea.
[Lee, Hyung; Kim, Sang-Pyo; Lee, Seong-Ryong] Keimyung Univ, Brain Res Inst, Taegu 700712, South Korea.
[Park, Jong-Wook; Lee, Seong-Ryong] Keimyung Univ, Sch Med, Chron Dis Res Ctr, Taegu 700712, South Korea.
[Lo, Eng H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroprotect Res Lab,Dept Radiol, Boston, MA USA.
[Lo, Eng H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroprotect Res Lab,Dept Neurol, Boston, MA USA.
RP Lee, SR (reprint author), Keimyung Univ, Sch Med, Dept Pharmacol, 194 Dongsan Dong, Taegu 700712, South Korea.
EM srlee@kmu.ac.kr
NR 34
TC 43
Z9 44
U1 3
U2 7
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0969-9961
J9 NEUROBIOL DIS
JI Neurobiol. Dis.
PD MAY
PY 2009
VL 34
IS 2
BP 189
EP 198
DI 10.1016/j.nbd.2008.12.012
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 442VT
UT WOS:000265869400001
PM 19200854
ER
PT J
AU Langbaum, JBS
Chen, K
Lee, W
Reschke, C
Bandy, D
Fleisher, AS
Alexander, GE
Foster, NL
Weiner, MW
Koeppe, RA
Jagust, WJ
Reiman, EM
AF Langbaum, Jessica B. S.
Chen, Kewei
Lee, Wendy
Reschke, Cole
Bandy, Dan
Fleisher, Adam S.
Alexander, Gene E.
Foster, Norman L.
Weiner, Michael W.
Koeppe, Robert A.
Jagust, William J.
Reiman, Eric M.
CA Alzheimer's Dis Neuroimaging Initi
TI Categorical and correlational analyses of baseline fluorodeoxyglucose
positron emission tomography images from the Alzheimer's Disease
Neuroimaging Initiative (ADNI)
SO NEUROIMAGE
LA English
DT Article
DE Alzheimer's disease; MCI; MMSE; Positron emission tomography
ID MILD COGNITIVE IMPAIRMENT; CEREBRAL GLUCOSE-METABOLISM; POSTERIOR
CINGULATE CORTEX; PITTSBURGH COMPOUND-B; FDG-PET; APOLIPOPROTEIN-E;
F-18-FDG PET; CLINICAL-DIAGNOSIS; DEMENTIA; MCI
AB In mostly small single-center studies, Alzheimer's disease (AD) is associated with characteristic and progressive reductions in fluorodeoxyglucose positron emission tomography (PET) measurements of the regional cerebral metabolic rate for glucose (CMRgl). The AD Neuroimaging Initiative (ADNI) is acquiring FDG PET, volumetric magnetic resonance imaging, and other biomarker measurements in a large longitudinal multi-center study of initially mildly affected probable AD (pAD) patients, amnestic mild cognitive impairment (aMCI) patients, who are at increased AD risk, and cognitively normal controls (NC), and we are responsible for analyzing the PET images using statistical parametric mapping (SPM). Here we compare baseline CMRgl measurements from 74 pAD patients and 142 aMCI patients to those from 82 NC, we correlate CMRgl with categorical and continuous measures of clinical disease severity, and we compare apolipoprotein E (APOE) epsilon 4 carriers to non-carriers in each of these subject groups. In comparison with NC, the pAD and aMCI groups each had significantly lower CMRgl bilaterally in posterior cingulate, precuneus, parietotemporal and frontal cortex. Similar reductions were observed when categories of disease severity or lower Mini-Mental State Exam (MMSE) scores were correlated with lower CMRgl. However, when analyses were restricted to the pAD patients, lower MMSE scores were significantly correlated with lower left frontal and temporal CMRgl. These findings from a large, multi-site study support previous single-site findings, supports the characteristic pattern of baseline CMRgl reductions in AD and aMCI patients, as well as preferential anterior CMRgl reductions after the onset of AD dementia. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Langbaum, Jessica B. S.; Chen, Kewei; Lee, Wendy; Reschke, Cole; Bandy, Dan; Fleisher, Adam S.; Reiman, Eric M.] Banner Alzheimers Inst, Phoenix, AZ 85006 USA.
[Langbaum, Jessica B. S.; Chen, Kewei; Lee, Wendy; Reschke, Cole; Bandy, Dan; Fleisher, Adam S.; Reiman, Eric M.] Banner Good Samaritan PET Ctr, Phoenix, AZ USA.
[Chen, Kewei] Arizona State Univ, Dept Math, Tempe, AZ 85287 USA.
[Chen, Kewei] Univ Arizona, Dept Radiol, Tucson, AZ 85724 USA.
[Alexander, Gene E.] Univ Arizona, Dept Psychol, Tucson, AZ 85721 USA.
[Alexander, Gene E.] Univ Arizona, Evelyn F McKnight Brain Inst, Tucson, AZ 85721 USA.
[Reiman, Eric M.] Univ Arizona, Dept Psychiat, Tucson, AZ USA.
[Foster, Norman L.] Univ Utah, Ctr Alzheimers Care Imaging & Res, Salt Lake City, UT USA.
[Foster, Norman L.] Univ Utah, Dept Neurol, Salt Lake City, UT USA.
[Weiner, Michael W.] San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis, San Francisco, CA USA.
[Weiner, Michael W.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Koeppe, Robert A.] Univ Michigan, Dept Radiol, Div Nucl Med, Ann Arbor, MI 48109 USA.
[Jagust, William J.] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA USA.
[Jagust, William J.] Univ Calif Berkeley, Helen Wills Neurosci Inst, Berkeley, CA USA.
[Reiman, Eric M.] Translat Genom Res Inst, Neurogen Div, Phoenix, AZ USA.
[Fleisher, Adam S.] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA.
[Langbaum, Jessica B. S.; Chen, Kewei; Lee, Wendy; Reschke, Cole; Bandy, Dan; Fleisher, Adam S.; Alexander, Gene E.; Reiman, Eric M.] Arizona Alzheimers Consortium, Phoenix, AZ USA.
RP Reiman, EM (reprint author), Banner Alzheimers Inst, 901 E Willetta St, Phoenix, AZ 85006 USA.
EM eric.reiman@bannerhealth.com
RI Scharre, Douglas/E-4030-2011; Chen, kewei/P-6304-2015
OI Chen, kewei/0000-0001-8497-3069
FU Alzheimer's Disease Neuroimaging Initiative (ADNI); NIH [U01 AG024904];
National Institute on Aging; National Institute of Biomedical Imaging
and Bioengineering (NIBIB); Pfizer Inc.; Wyeth Research; Bristol-Myers
Squibb; Eli Lilly and Company; GlaxoSmithKline; Merck Co. Inc.;
AstraZeneca AB; Novartis Pharmaceuticals Corporation; Eisai Global
Clinical Development; Elan Corporation plc; Forest Laboratories;
Institute for the Study of Aging; U.S. Food and Drug Administration
FX Data collection and sharing for this project were funded by the
Alzheimer's Disease Neuroimaging Initiative (ADNI; Principal
Investigator: MichaelWeiner; NIH grant U01 AG024904). ADNI is funded by
the National Institute on Aging, the National Institute of Biomedical
Imaging and Bioengineering (NIBIB), and through generous contributions
from the following: Pfizer Inc., Wyeth Research, Bristol-Myers Squibb,
Eli Lilly and Company, GlaxoSmithKline, Merck & Co. Inc., `AstraZeneca
AB, Novartis Pharmaceuticals Corporation, Alzheimer's Association, Eisai
Global Clinical Development, Elan Corporation plc, Forest Laboratories,
and the Institute for the Study of Aging, with participation from the
U.S. Food and Drug Administration. Industry partnerships are coordinated
through the Foundation for the National Institutes of Health. The
grantee organization is the Northern California Institute for Research
and Education, and the study is coordinated by the Alzheimer's Disease
Cooperative Study at the University of California, San Diego. ADNI data
are disseminated by the Laboratory of Neuro Imaging at the University of
California, Los Angeles.
NR 56
TC 135
Z9 136
U1 3
U2 9
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD MAY 1
PY 2009
VL 45
IS 4
BP 1107
EP 1116
DI 10.1016/j.neuroimage.2008.12.072
PG 10
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 421SL
UT WOS:000264378500007
PM 19349228
ER
PT J
AU Lu, J
Dai, G
Egi, Y
Huang, S
Kwon, SJ
Lo, EH
Kim, YR
AF Lu, Jie
Dai, Guangping
Egi, Yasu
Huang, Shuning
Kwon, Seon Joo
Lo, Eng H.
Kim, Young Ro
TI Characterization of cerebrovascular responses to hyperoxia and
hypercapnia using MRI in rat
SO NEUROIMAGE
LA English
DT Article
DE Hyperoxia; Hypercapnia; Rat; BOLD; CBV; CBF; fMRI
ID CEREBRAL-BLOOD-FLOW; NORMOBARIC HYPEROXIA; FUNCTIONAL MRI;
CARBON-DIOXIDE; INSPIRED OXYGEN; BRAIN; VOLUME; FMRI; ISCHEMIA; BOLD
AB Understanding cerebrovascular responses to hyperoxia and hypercapnia is important for investigating exogenous regulation of cerebral hemodynamics. We characterized gas-induced vascular changes in the brains of anesthetized healthy rats using magnetic resonance imaging (MRI) while the rats inhaled 100% O(2) (hyperoxia) and 5% CO(2) (hypercapnia). We used echo planar imaging (EPI), arterial spin labeling (ASL), and intravascular superparamagnetic iron oxide nanoparticles (SPION) to quantify vascular responses as measured by blood oxygenation level dependence (BOLD), cerebral blood flow (CBF), cerebral blood volume (CBV), microvascular volume (MVV), and vessel size index (VSI) in multiple brain regions. Hyperoxia resulted in a statistically significant increase in BOLD-weighted MRI signal and significant decrease in CBF and CBV (P < 0.05). During hypercapnia, we observed significant increases in BOLD signal, CBF, MVV, and CBV (P < 0.05). Despite the regional variability, general trends of vasoconstriction and vasodilation were reflected in VSI changes during O(2) and CO(2) challenges. Interestingly, there was an evident spatial disparity between the O(2) and CO(2) stimuli-induced functional activation maps; that is, cortical and subcortical regions of the brain exhibited notable differences in response to the two gases. Hemodynamic parameters measured in the cortical regions showed greater reactivity to CO(2), whereas these same parameters measured in subcortical regions showed greater responsivity to O(2). Our results demonstrate significant changes of hemodynamic MRI parameters during systemic hypercapnia and hyperoxia in normal cerebral tissue. These gas-dependent changes are spatiotemporally distinctive, suggesting important feasibility for exogenously controlling local cerebral perfusion. (C) 2008 Elsevier Inc. All rights reserved.
C1 [Lu, Jie; Egi, Yasu; Lo, Eng H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Lab Neuroprotect,Dept Neurol, Charlestown, MA 02129 USA.
[Lu, Jie; Dai, Guangping; Huang, Shuning; Kwon, Seon Joo; Kim, Young Ro] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula Martinos Ctr Biomed Imaging,Dept Radiol, Charlestown, MA 02129 USA.
[Lu, Jie] Capital Med Univ, Dept Radiol, Xuanwu Hosp, Beijing 100053, Peoples R China.
RP Kim, YR (reprint author), Harvard Univ, Sch Med, Harvard MIT HST Athinoula A Martinos Ctr Biomed I, Massachusetts Gen Hosp, Bldg 149,13th St, Charlestown, MA 02129 USA.
EM spmn@nmr.mgh.harvard.edu
FU National Institute of Health [RO1-5R01EB002066]
FX We thank Nichole Eusemann and Drs. Kwong Ken and A. Gregory Sorensen for
their critical and helpful comments. This work was supported in part by
grants from National Institute of Health (RO1-5R01EB002066).
NR 46
TC 44
Z9 45
U1 0
U2 5
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD MAY 1
PY 2009
VL 45
IS 4
BP 1126
EP 1134
DI 10.1016/j.neuroimage.2008.11.037
PG 9
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 421SL
UT WOS:000264378500009
PM 19118633
ER
PT J
AU Alpert, NM
Yuan, F
AF Alpert, Nathaniel M.
Yuan, Fang
TI A general method of Bayesian estimation for parametric imaging of the
brain
SO NEUROIMAGE
LA English
DT Article
ID DYNAMIC PET DATA; POSITRON-EMISSION-TOMOGRAPHY; SPATIAL CONSTRAINT;
RIDGE-REGRESSION; KINETIC-ANALYSIS; IMAGES; VARIABILITY; MODEL
AB We report a general method of Bayesian estimation that uses prior measurements to improve the signal-to-noise ratio of parametric images computed from dynamic PET scanning. In our method, the ordinary weighted least squares cost function is augmented by a penalty term to yield F K; S min(K){(C-f(K))(T) Omega(-1)(C)(C-f(K)) + S Phi(K, S = 0)(K-(K) over cap)(T)W(K)(-1)(K-(K) over cap) , where C is a PET concentration history and Omega(C) is its variance, f is the model of the concentration history, K = [k(1), k(2),..., k(m)](T) is the parameter vector, (K) over cap is the vector of population means for the model parameters, Omega(K) is its covariance, Phi(K)(K, S = 0) is the conventional weighted sum of squares. S > 0 is chosen to control the balance between the prior and new data. Data from a prior population of subjects are analyzed with standard methods to provide maps of the mean parameter values and their variances. As an example of this approach we used the dynamic image data of 10 normal subjects who had previously been studied with (11)C-raclopride to estimate the prior distribution. The dynamic data were transformed to stereotactic coordinates and analyzed by standard methods. The resulting parametric maps were used to compute the voxel-wise sample statistics. Then the cohort of priors was analyzed as a function of S, using nonlinear least squares estimation and the cost function shown above. As S is increased the standard error in estimating BP in single subjects was substantially reduced allowing measurement in BP in thalamus, cortex, brain stem, etc. Additional studies demonstrate that a range of S values exist for which the bias is not excessive, even when parameter values differ markedly from the sample mean. This method can be used with any kinetic model so long as it is possible to compute a map of a priori mean parameters and their variances. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Alpert, Nathaniel M.; Yuan, Fang] Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Dept Radiol, Boston, MA 02114 USA.
RP Alpert, NM (reprint author), Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Dept Radiol, 50 Fruit St, Boston, MA 02114 USA.
EM alpert@pet.mgh.harvard.edu
FU National Institute of Biomedical Imaging and Bioengineering
[5T32EB002102]
FX Dr. Yuan was supported by the Postgraduate Program in Radiological
Science, 5T32EB002102, a National Institute of Biomedical Imaging and
Bioengineering postdoctoral training grant.
NR 29
TC 7
Z9 7
U1 0
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD MAY 1
PY 2009
VL 45
IS 4
BP 1183
EP 1189
DI 10.1016/j.neuroimage.2008.12.064
PG 7
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 421SL
UT WOS:000264378500015
PM 19349233
ER
PT J
AU Liu, LP
Yenari, MA
AF Liu, Liping
Yenari, Midori A.
TI Clinical application of therapeutic hypothermia in stroke
SO NEUROLOGICAL RESEARCH
LA English
DT Article
DE Temperature; heart; brain; cooling methods; combination
ID TRANSIENT GLOBAL-ISCHEMIA; COMBINED POSTISCHEMIC HYPOTHERMIA; MILD
RESUSCITATIVE HYPOTHERMIA; HOSPITAL CARDIAC-ARREST; MODERATE
HYPOTHERMIA; COMATOSE SURVIVORS; FEASIBILITY; RATS; NEUROPROTECTION;
TEMPERATURE
AB Objective: Hypothermia has long been known to be a potent neuroprotectant. In this mini-review, we highlighted clinical experience that hypothermia protects the brain from cerebral injury. We discussed the clinical practice of hypothermia in ischemic stroke.
Results: Multiple factors play a significant role in the mechanisms. Clinical application drew first from two clinical trials with comatose patients after cardiac arrest is attractive. The Australian and European study have led to renewed interest in these patients. More and more evidences bring the insight into its effects on cerebral ischemia. The type of cooling technique to be used, the duration of cooling and speed of rewarming appear to be key factors in determining whether hypothermia is effective in preventing or mitigating neurological injury. Although until now, there are no clear therapeutic standards of the parameters in therapeutic hypothermia, it is well accepted that cooling should be initiated as soon as possible. By combining hypothermia with other neuroprotectants, it may be possible to enhance protective effects, reduce side effects and lengthen the maximum time.
Conclusion: In addition to its neuroprotective properties, hypothermia may extend the therapeutic window for other neuroprotective treatment. Thus, combination therapies with neuroprotective, anti-inflammatory and thrombolytic agents are likely to be investigated in the clinical setting in the future. [Neurol Res 2009; 31: 331-335]
C1 [Yenari, Midori A.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA.
[Liu, Liping] Capital Med Univ, Beijing Tiantan Hosp, Dept Neurol, Beijing 100050, Peoples R China.
[Yenari, Midori A.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA.
RP Yenari, MA (reprint author), San Francisco VA Med Ctr, 4150 Clement St, San Francisco, CA 94121 USA.
EM yenari@alum.mit.edu
FU NINDS NIH HHS [R01 NS040516, R01 NS040516-09]
NR 33
TC 17
Z9 19
U1 1
U2 1
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 MAY
PY 2009
VL 31
IS 4
BP 331
EP 335
DI 10.1179/174313209X444099
PG 5
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 458KV
UT WOS:000267020000002
PM 19508813
ER
PT J
AU Mesholam-Gately, RI
Giuliano, AJ
Goff, KP
Faraone, SV
Seidman, LJ
AF Mesholam-Gately, Raquelle I.
Giuliano, Anthony J.
Goff, Kirsten P.
Faraone, Stephen V.
Seidman, Larry J.
TI Neurocognition in First-Episode Schizophrenia: A Meta-Analytic Review
SO NEUROPSYCHOLOGY
LA English
DT Review
DE schizophrenia; psychosis; first-episode; neurocognition; meta-analysis
ID EXECUTIVE FUNCTIONS; MEMORY IMPAIRMENT; SOCIAL COGNITION; PROCESSING
SPEED; WORKING-MEMORY; 1ST EPISODE; FOLLOW-UP; HIGH-RISK;
NEUROPSYCHOLOGICAL DEFICITS; DIFFERENTIAL DEFICIT
AB Compromised neurocognition is a core feature of schizophrenia. Following Heinrichs and Zakzanis's (1998) seminal meta-analysis of middle-aged and predominantly chronic schizophrenia samples, the aim of this study is to provide a meta-analysis of neurocognitive findings from 47 studies of first-episode (FE) schizophrenia published through October 2007. The meta-analysis uses 43 separate samples of 2,204 FE patients with a mean age of 25.5 and 2,775 largely age- and gender-matched control participants. FE samples demonstrated medium-to-large impairments across 10 neurocognitive domains (mean effect sizes from -0.64 to -1.20). Findings indicate that impairments are reliably and broadly present by the FE, approach or match the degree of deficit shown in well-established illness, and are maximal in immediate verbal memory and processing speed. Larger IQ impairments in the FE compared to the premorbid period, but comparable to later phases of illness suggests deterioration between premorbid and FE phases followed by deficit stability at the group level. Considerable heterogeneity of effect sizes across studies, however, underscores variability in manifestations of the illness and a need for improved reporting of sample characteristics to support moderator variable analyses.
C1 [Mesholam-Gately, Raquelle I.] Harvard Univ, Massachusetts Mental Hlth Ctr, Beth Israel Deaconess Med Ctr,Dept Psychiat, Commonwealth Res Ctr,Publ Psychiat Div,Sch Med, Jamaica Plain, MA 02130 USA.
[Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat, New York, NY USA.
[Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Neurosci, New York, NY USA.
[Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Physiol, New York, NY USA.
[Seidman, Larry J.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Cambridge, MA 02138 USA.
RP Mesholam-Gately, RI (reprint author), Harvard Univ, Massachusetts Mental Hlth Ctr, Beth Israel Deaconess Med Ctr,Dept Psychiat, Commonwealth Res Ctr,Publ Psychiat Div,Sch Med, Lemuel Shattuck Hosp Campus,180 Morton St, Jamaica Plain, MA 02130 USA.
EM rmeshola@bidmc.harvard.edu
OI Faraone, Stephen/0000-0002-9217-3982
FU NIMH NIH HHS [MH 43518, MH 63951, MH 65562, P50 MH 080272]
NR 146
TC 371
Z9 375
U1 6
U2 37
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0894-4105
J9 NEUROPSYCHOLOGY
JI Neuropsychology
PD MAY
PY 2009
VL 23
IS 3
BP 315
EP 336
DI 10.1037/a0014708
PG 22
WC Psychology, Clinical; Neurosciences; Psychology
SC Psychology; Neurosciences & Neurology
GA 439XW
UT WOS:000265662000005
PM 19413446
ER
PT J
AU Glazer, G
Ponte, PR
Stuart-Shor, EM
Cooley, ME
AF Glazer, Greer
Ponte, Pat Reid
Stuart-Shor, Eileen M.
Cooley, Mary E.
TI The power of partnership: Addressing cancer health disparities through
an academic-service partnership
SO NURSING OUTLOOK
LA English
DT Article
AB Partnerships between universities and healthcare organizations help foster interdisciplinary collaboration and can yield programs to address pressing needs in both sectors. In spite of these benefits, such partnerships remain more the exception than the norm. This article describes a partnership between a comprehensive cancer center and a university-based college of nursing and health sciences that serves a diverse student population. With the support of U-56 funding, the 2 organizations collaborated to develop a new, 87-credit BS-to-PhD in Nursing program and to enhance the university's traditional PhD in nursing program. Both PhD programs prepare nurses for careers in teaching, health policy, and research related to cancer health disparities. In addition to an innovative curriculum, the programs include a mentorship that leverages the research expertise and scholarly resources of both organizations and a community outreach component that gives students experience in planning and implementing educational and risk-reduction programs addressing cancer health disparities.
C1 [Glazer, Greer; Ponte, Pat Reid; Stuart-Shor, Eileen M.; Cooley, Mary E.] Univ Massachusetts, Coll Nursing & Hlth Sci, Boston, MA 02125 USA.
[Glazer, Greer; Ponte, Pat Reid; Stuart-Shor, Eileen M.; Cooley, Mary E.] Dana Farber Canc Ctr, Patient Care Serv, Boston, MA USA.
[Glazer, Greer; Stuart-Shor, Eileen M.; Cooley, Mary E.] Dana Farber Canc Ctr, Phyllis F Cantor Ctr Res Nursing, Boston, MA USA.
[Ponte, Pat Reid] Brigham & Womens Hosp, Oncol Nursing & Clin Serv, Boston, MA 02115 USA.
RP Glazer, G (reprint author), Univ Massachusetts, Boston Coll Nursing & Hlth Sci, 100 Morrissey Blvd, Boston, MA 02125 USA.
EM Greer.glazer@umb.edu
FU NIH-/NCI [1 U56 CA11863502]; Lynch Foundation; GAANN; US Department of
Education [P200A060243]
FX The work described in this manuscript was supported in part by NIH-/NCI
Grant 1 U56 CA11863502, and by grants from the Lynch Foundation and
GAANN, US Department of Education, P200A060243.
NR 16
TC 6
Z9 6
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0029-6554
J9 NURS OUTLOOK
JI Nurs. Outlook
PD MAY-JUN
PY 2009
VL 57
IS 3
BP 123
EP 131
DI 10.1016/j.outlook.2008.07.007
PG 9
WC Nursing
SC Nursing
GA 451FX
UT WOS:000266457200003
PM 19447232
ER
PT J
AU Zhao, R
Xiang, N
Domann, FE
Zhong, WX
AF Zhao, Rui
Xiang, Nong
Domann, Fredrick E.
Zhong, Weixiong
TI Effects of Selenite and Genistein on G(2)/M Cell Cycle Arrest and
Apoptosis in Human Prostate Cancer Cells
SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL
LA English
DT Article
ID KINASE INHIBITOR GENISTEIN; CASPASE-MEDIATED APOPTOSIS; METHYLSELENINIC
ACID; UNITED-STATES; IN-VITRO; PREVENTION; SELENOMETHIONINE;
CHEMOPREVENTION; EXPRESSION; MORTALITY
AB Combination of chemopreventive agents with distinct molectilar mechanisms is considered to offer a potential for enhancing cancer prevention efficacy while minimizing toxicity. Here we report two chemopreventive agents, selenite and genistein, that have synergistic effects on apoptosis, cell cycle arrest, and associated signaling pathways in p53-expressing LNCaP and p53-null PC3 prostate cancer cells. We show that selenite induced apoptosis only, whereas genistein induced both apoptosis and G(2)/M cell cycle arrest. Combination of these two agents exhibited enhanced effects, which were slightly greater in LNCaP than PC3 cells. Selenite or genistein alone upregulated protein levels of p53 in LNCaP cells only and p21(waf1) and Bax in both cell lines. Additionally, genistein inhibited AKT phosphorylation. Downregulation of AKT by siRNA caused apoptosis and G2/M cell cycle arrest and masked the effects of genistein. Treatment with insulin-like growth factor I (IGF-I) elevated levels of total and phosphorylated AKT and suppressed the effects of genistein. Neither downregulation of AKT nor IGF-I treatment altered the cellular effects of selenite. Our study demonstrates that selenium and genistein act via different molecular mechanisms and exhibit enhanced anticancer effects, suggesting that a combination of selenium and genistein may offer better efficacy and reduction of toxicity in prostate cancer prevention.
C1 [Zhao, Rui; Xiang, Nong; Zhong, Weixiong] Univ Wisconsin, Sch Med & Publ Hlth, Dept Pathol & Lab Med, Madison, WI 53792 USA.
[Domann, Fredrick E.] Univ Iowa, Free Rad & Radiat Biol Grad Program, Iowa City, IA USA.
[Zhong, Weixiong] William S Middleton Mem Vet Adm Med Ctr, Pathol & Lab Med Serv, Madison, WI 53705 USA.
RP Zhong, WX (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Dept Pathol & Lab Med, Madison, WI 53792 USA.
EM wzhong3@wisc.edu
OI Domann, Frederick/0000-0002-0489-2179
FU NCI NIH HHS [CA114281, CA73612,, R01 CA073612-09, R01 CA073612, R01
CA073612-10, R01 CA114281, R01 CA114281-03, R01 CA114281-04, R01
CA115438, R01 CA115438-02, R01 CA115438-03, R29 CA073612, R56 CA073612]
NR 52
TC 44
Z9 48
U1 0
U2 4
PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS
PI PHILADELPHIA
PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA
SN 0163-5581
J9 NUTR CANCER
JI Nutr. Cancer
PD MAY-JUN
PY 2009
VL 61
IS 3
BP 397
EP 407
DI 10.1080/01635580802582751
PG 11
WC Oncology; Nutrition & Dietetics
SC Oncology; Nutrition & Dietetics
GA 473WM
UT WOS:000268242000014
PM 19373614
ER
PT J
AU Blackburn, GL
Hu, FB
Hutter, MM
AF Blackburn, George L.
Hu, Frank B.
Hutter, Matthew M.
TI Updated Evidence-based Recommendations for Best Practices in Weight Loss
Surgery
SO OBESITY
LA English
DT Article
ID EVIDENCE-BASED MEDICINE; BARIATRIC SURGERY; MORBID-OBESITY; MORTALITY
C1 [Blackburn, George L.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Surg,Ctr Study Nutr Med, Boston, MA 02215 USA.
[Hu, Frank B.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Hutter, Matthew M.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
RP Blackburn, GL (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Surg,Ctr Study Nutr Med, Boston, MA 02215 USA.
EM gblackbu@bidmc.harvard.edu
NR 25
TC 8
Z9 8
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1930-7381
J9 OBESITY
JI Obesity
PD MAY
PY 2009
VL 17
IS 5
BP 839
EP 841
DI 10.1038/oby.2008.572
PG 3
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 440OO
UT WOS:000265709800001
PM 19396062
ER
PT J
AU Blackburn, GL
Hutter, MM
Harvey, AM
Apovian, CM
Boulton, HRW
Cummings, S
Fallon, JA
Greenberg, I
Jiser, ME
Jones, DB
Jones, SB
Kaplan, LM
Kelly, JJ
Kruger, RS
Lautz, DB
Lenders, CM
LoNigro, R
Luce, H
McNamara, A
Mulligan, AT
Paasche-Orlow, MK
Perna, FM
Pratt, JSA
Riley, SM
Robinson, MK
Romanelli, JR
Saltzman, E
Schumann, R
Shikora, SA
Snow, RL
Sogg, S
Sullivan, MA
Tarnoff, M
Thompson, CC
Wee, CC
Ridley, N
Auerbach, J
Hu, FB
Kirle, L
Buckley, RB
Annas, CL
AF Blackburn, George L.
Hutter, Matthew M.
Harvey, Alan M.
Apovian, Caroline M.
Boulton, Hannah R. W.
Cummings, Susan
Fallon, John A.
Greenberg, Isaac
Jiser, Michael E.
Jones, Daniel B.
Jones, Stephanie B.
Kaplan, Lee M.
Kelly, John J.
Kruger, Rayford S., Jr.
Lautz, David B.
Lenders, Carine M.
LoNigro, Robert
Luce, Helen
McNamara, Anne
Mulligan, Ann T.
Paasche-Orlow, Michael K.
Perna, Frank M.
Pratt, Janey S. A.
Riley, Stancel M., Jr.
Robinson, Malcolm K.
Romanelli, John R.
Saltzman, Edward
Schumann, Roman
Shikora, Scott A.
Snow, Roger L.
Sogg, Stephanie
Sullivan, Mary A.
Tarnoff, Michael
Thompson, Christopher C.
Wee, Christina C.
Ridley, Nancy
Auerbach, John
Hu, Frank B.
Kirle, Leslie
Buckley, Rita B.
Annas, Catherine L.
TI Expert Panel on Weight Loss Surgery: Executive Report Update
SO OBESITY
LA English
DT Article
ID LAPAROSCOPIC SLEEVE GASTRECTOMY; GASTRIC BYPASS-SURGERY;
SERVICES-TASK-FORCE; LONG-TERM MORTALITY; HIGH-RISK PATIENTS;
QUALITY-OF-LIFE; BARIATRIC-SURGERY; MORBID-OBESITY; UNITED-STATES;
BILIOPANCREATIC DIVERSION
AB Rapid shifts in the demographics and techniques of weight loss surgery (WLS) have led to new issues, new data, new concerns, and new challenges. In 2004, this journal published comprehensive evidence-based guidelines on WLS. In this issue, we've updated those guidelines to assure patient safety in this fast-changing field. WLS involves a uniquely vulnerable population in need of specialized resources and ongoing multidisciplinary care. Timely best-practice updates are required to identify new risks, develop strategies to address them, and optimize treatment. Findings in these reports are based on a comprehensive review of the most current literature on WLS; they directly link patient safety to methods for setting evidence-based guidelines developed from peer-reviewed scientific publications. Among other outcomes, these reports show that WLS reduces chronic disease risk factors, improves health, and confers a survival benefit on those who undergo it. The literature also shows that laparoscopy has displaced open surgery as the predominant approach; that government agencies and insurers only reimburse procedures performed at accredited WLS centers; that best practice care requires close collaboration between members of a multidisciplinary team; and that new and existing facilities require wide-ranging changes to accommodate growing numbers of severely obese patients. More than 100 specialists from across the state of Massachusetts and across the many disciplines involved in WLS came together to develop these new standards. We expect them to have far-reaching effects of the development of health care policy and the practice of WLS.
C1 [Blackburn, George L.; Jones, Daniel B.] Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02215 USA.
[Hutter, Matthew M.; Pratt, Janey S. A.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Harvey, Alan M.] Mercy Med Ctr Catholic Hlth E, Dept Anesthesiol, Springfield, MA USA.
[Apovian, Caroline M.; Lenders, Carine M.] Boston Med Ctr, Dept Med, Boston, MA USA.
[Boulton, Hannah R. W.] S Shore Hosp, Dept Nursing, Weymouth, MA USA.
[Cummings, Susan] Massachusetts Gen Hosp, Weight Ctr, Boston, MA 02114 USA.
[Fallon, John A.] Blue Cross & Blue Shield Massachusetts, Boston, MA USA.
[Greenberg, Isaac] Tufts Univ New England Med Ctr, Obes Consult Ctr, Boston, MA USA.
[Jiser, Michael E.] Saints Med Ctr, Dept Surg, Lowell, MA USA.
[Jones, Stephanie B.] Beth Israel Deaconess Med Ctr, Dept Anesthesiol, Boston, MA 02215 USA.
[Kaplan, Lee M.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Kelly, John J.] Univ Massachusetts, Mem Med Ctr, Dept Surg, Worcester, MA 01605 USA.
[Kruger, Rayford S., Jr.] Tobey Hosp, Dept Surg, Wareham, MA USA.
[Lautz, David B.; Robinson, Malcolm K.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA.
[LoNigro, Robert] Tufts Hlth Plan, Care Management, Boston, MA USA.
[Luce, Helen] Consumer Representat, Boston, MA USA.
[McNamara, Anne] Beth Israel Deaconess Med Ctr, Dept Nursing & Surg, Boston, MA 02215 USA.
[Mulligan, Ann T.] Newton Wellesley Hosp, Dept Nursing, Newton, MA USA.
[Paasche-Orlow, Michael K.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.
[Perna, Frank M.] NCI, Hlth Promot Res Branch, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Riley, Stancel M., Jr.] Massachusetts Board Registrat Med, Patient Care Assessment Div, Boston, MA USA.
[Robinson, Malcolm K.] Baystate Med Ctr, Dept Surg, Springfield, MA 01107 USA.
[Saltzman, Edward] Tufts Univ New England Med Ctr, Dept Med, Boston, MA USA.
[Schumann, Roman] Tufts Univ New England Med Ctr, Dept Anesthesiol, Boston, MA USA.
[Shikora, Scott A.; Tarnoff, Michael] Tufts Univ New England Med Ctr, Dept Surg, Boston, MA USA.
[Snow, Roger L.] Univ Massachusetts, Sch Med, Worcester, MA USA.
[Snow, Roger L.] MassHealth, Boston, MA USA.
[Sogg, Stephanie] Massachusetts Gen Hosp, Behav Med Serv, Boston, MA 02114 USA.
[Sogg, Stephanie] Massachusetts Gen Hosp, MGH Weight Ctr, Boston, MA 02114 USA.
[Sullivan, Mary A.] Lahey Clin & Massachusetts Coalit Prevent Med Err, Div Med Specialties, Burlington, MA USA.
[Thompson, Christopher C.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Wee, Christina C.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA.
[Ridley, Nancy; Auerbach, John; Hu, Frank B.; Kirle, Leslie; Buckley, Rita B.; Annas, Catherine L.] Commonwealth Massachusetts, Betsy Lehman Ctr Patient Safety & Med Error Reduc, Boston, MA USA.
RP Blackburn, GL (reprint author), Beth Israel Deaconess Med Ctr, Dept Surg, 330 Brookline Ave, Boston, MA 02215 USA.
EM gblackbu@bidmc.harvard.edu
OI Paasche-Orlow, Michael/0000-0002-9276-7190; Apovian,
Caroline/0000-0002-8029-1922; Jones, Stephanie/0000-0001-8342-0374
NR 80
TC 54
Z9 54
U1 1
U2 4
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1930-7381
J9 OBESITY
JI Obesity
PD MAY
PY 2009
VL 17
IS 5
BP 842
EP 862
DI 10.1038/oby.2008.578
PG 21
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 440OO
UT WOS:000265709800002
PM 19396063
ER
PT J
AU Kelly, JJ
Shikora, S
Jones, DB
Hutter, MH
Robinson, MK
Romanelli, J
Buckley, F
Lederman, A
Blackburn, GL
Lautz, D
AF Kelly, John J.
Shikora, Scott
Jones, Daniel B.
Hutter, Matthew H.
Robinson, Malcolm K.
Romanelli, John
Buckley, Frederick
Lederman, Andrew
Blackburn, George L.
Lautz, David
TI Best Practice Updates for Surgical Care in Weight Loss Surgery
SO OBESITY
LA English
DT Article
ID ROUX-EN-Y; PROSPECTIVE RANDOMIZED-TRIAL; LAPAROSCOPIC GASTRIC BYPASS;
VERTICAL BANDED GASTROPLASTY; HIGH-RISK PATIENTS; BARIATRIC-SURGERY;
MORBID-OBESITY; SUPER-OBESE; BILIOPANCREATIC DIVERSION; SLEEVE
GASTRECTOMY
AB To update evidence-based best practice guidelines for surgical care in weight loss surgery (WLS). Systematic search of English-language literature on WLS in MEDLINE, EMBASE, and the Cochrane Library between April 2004 and May 2007. Use of key words to narrow the search for a selective review of abstracts, retrieval of full articles, and grading of evidence according to systems used in established evidence-based models. Evidence-based best practice recommendations from the most recent literature on surgical methods and technologies, risks and benefits, outcomes, and surgeon qualifications and credentialing. We identified >135 articles; the 65 most relevant were reviewed in detail. Regular updates of evidence-based recommendations for best practices in WLS are required to address rapid changes in surgical techniques and patient demographics. Key factors in patient safety include surgical risk factors, type of procedure, surgeon training, and facility certification.
C1 [Kelly, John J.] Univ Massachusetts, Med Ctr, Dept Surg, Worcester, MA 01605 USA.
[Shikora, Scott] Tufts Univ New England Med Ctr, Dept Surg, Boston, MA USA.
[Jones, Daniel B.; Blackburn, George L.] Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02215 USA.
[Hutter, Matthew H.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Robinson, Malcolm K.; Lautz, David] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA.
[Romanelli, John] Baystate Med Ctr, Dept Surg, Springfield, MA 01107 USA.
[Buckley, Frederick] N Shore Med Ctr, Dept Surg, Salem, MA USA.
[Lederman, Andrew] Berkshire Med Ctr, Dept Surg, Pittsfield, MA USA.
RP Kelly, JJ (reprint author), Univ Massachusetts, Med Ctr, Dept Surg, Worcester, MA 01605 USA.
EM kellyj@ummhc.org
FU NIDDK NIH HHS [P30-DK-46200]
NR 86
TC 14
Z9 14
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1930-7381
J9 OBESITY
JI Obesity
PD MAY
PY 2009
VL 17
IS 5
BP 863
EP 870
DI 10.1038/oby.2008.570
PG 8
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 440OO
UT WOS:000265709800003
PM 19396064
ER
PT J
AU Apovian, CM
Cummings, S
Anderson, W
Borud, L
Boyer, K
Day, K
Hatchigian, E
Hodges, B
Patti, ME
Pettus, M
Perna, F
Rooks, D
Saltzman, E
Skoropowski, J
Tantillo, MB
Thomason, P
AF Apovian, Caroline M.
Cummings, Sue
Anderson, Wendy
Borud, Loren
Boyer, Kelly
Day, Kristina
Hatchigian, Edward
Hodges, Barbara
Patti, Mary E.
Pettus, Mark
Perna, Frank
Rooks, Daniel
Saltzman, Edward
Skoropowski, June
Tantillo, Michael B.
Thomason, Phyllis
TI Best Practice Updates for Multidisciplinary Care in Weight Loss Surgery
SO OBESITY
LA English
DT Article
ID Y GASTRIC BYPASS; QUALITY-OF-LIFE; MORBIDLY OBESE-PATIENTS; LOW-ENERGY
DIET; BARIATRIC SURGERY; NUTRITIONAL-STATUS; NONALCOHOLIC
STEATOHEPATITIS; BILIOPANCREATIC DIVERSION; PREOPERATIVE ASSESSMENT;
CALCIUM-ABSORPTION
AB The objective of this study is to update evidence-based best practice guidelines for multidisciplinary care of weight loss surgery (WLS) patients. We performed systematic search of English-language literature on WLS, patient selection, and medical, multidisciplinary, and nutritional care published between April 2004 and May 2007 in MEDLINE and the Cochrane Library. Key words were used to narrow the search for a selective review of abstracts, retrieval of full articles, and grading of evidence according to systems used in established evidence-based models. A total of 150 papers were retrieved from the literature search and 112 were reviewed in detail. We made evidence-based best practice recommendations from the most recent literature on multidisciplinary care of WLS patients. New recommendations were developed in the areas of patient selection, medical evaluation, and treatment. Regular updates of evidence-based recommendations for best practices in multidisciplinary care are required to address changes in patient demographics and levels of obesity. Key factors in patient safety include comprehensive preoperative medical evaluation, patient education, appropriate perioperative care, and long-term follow-up.
C1 [Apovian, Caroline M.; Anderson, Wendy; Perna, Frank] Boston Univ, Med Ctr, Dept Endocrinol Diabet & Nutr, Boston, MA 02215 USA.
[Borud, Loren; Boyer, Kelly; Day, Kristina; Hatchigian, Edward; Rooks, Daniel; Skoropowski, June; Tantillo, Michael B.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Cummings, Sue] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Hodges, Barbara] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Patti, Mary E.] Joslin Diabet Ctr, Boston, MA 02215 USA.
[Pettus, Mark] Berkshire Med Ctr, Pittsfield, MA USA.
[Saltzman, Edward] Tufts Univ New England Med Ctr, Boston, MA USA.
[Thomason, Phyllis] Faulkner Hosp, Boston, MA USA.
RP Apovian, CM (reprint author), Boston Univ, Med Ctr, Dept Endocrinol Diabet & Nutr, Boston, MA 02215 USA.
EM caroline.apovian@bmc.org
OI Apovian, Caroline/0000-0002-8029-1922
FU NIDDK NIH HHS [P30-DK-46200, P30 DK046200, P30 DK046200-17]
NR 94
TC 26
Z9 26
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1930-7381
J9 OBESITY
JI Obesity
PD MAY
PY 2009
VL 17
IS 5
BP 871
EP 879
DI 10.1038/oby.2008.580
PG 9
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 440OO
UT WOS:000265709800004
PM 19396065
ER
PT J
AU Greenberg, I
Sogg, S
Perna, FM
AF Greenberg, Isaac
Sogg, Stephanie
Perna, Frank M.
TI Behavioral and Psychological Care in Weight Loss Surgery: Best Practice
Update
SO OBESITY
LA English
DT Article
ID QUALITY-OF-LIFE; NIGHT EATING SYNDROME; BARIATRIC SURGERY; GASTRIC
BYPASS; PSYCHOSOCIAL PREDICTORS; OBESITY SURGERY; MORBID-OBESITY;
MENTAL-HEALTH; CANDIDATES; DISORDERS
AB The objective of this study is to update evidence-based best practice guidelines for psychological evaluation and treatment of weight loss surgery (WLS) patients. We performed a systematic search of English-language literature on WLS and mental health, quality of life, and behavior modification published between April 2004 and May 2007 in MEDLINE and the Cochrane Library. Key words were used to narrow the search for a selective review of abstracts, retrieval of full articles, and grading of evidence according to systems used in established evidence-based models. Our literature search identified 17 articles of interest; 13 of the most relevant were reviewed in detail. From these, we developed evidence-based best practice recommendations on the psychological assessment and treatment of WLS patients. Regular updates of evidence-based recommendations for best practices in psychological care are required to address the impact of mental health on short- and long-term outcomes after WLS. Key factors in patient safety include comprehensive preoperative evaluation, use of appropriate and reliable evaluation instruments, and the development of short- and long-term treatment plans.
C1 [Greenberg, Isaac] Tufts Sch Med, Dept Psychiat, Boston, MA USA.
[Sogg, Stephanie] Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Weight Ctr, Boston, MA USA.
[Perna, Frank M.] NCI, Hlth Promot Res Branch, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
RP Greenberg, I (reprint author), Tufts Sch Med, Dept Psychiat, Boston, MA USA.
EM igreenberg@tufts-nemc.org
FU NIDDK NIH HHS [P30-DK-46200]
NR 40
TC 48
Z9 50
U1 2
U2 10
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1930-7381
J9 OBESITY
JI Obesity
PD MAY
PY 2009
VL 17
IS 5
BP 880
EP 884
DI 10.1038/oby.2008.571
PG 5
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 440OO
UT WOS:000265709800005
PM 19396066
ER
PT J
AU Wee, CC
Pratt, JS
Fanelli, R
Samour, PQ
Trainor, LS
Paasche-Orlow, MK
AF Wee, Christina C.
Pratt, Janey S.
Fanelli, Robert
Samour, Patricia Q.
Trainor, Linda S.
Paasche-Orlow, Michael K.
TI Best Practice Updates for Informed Consent and Patient Education in
Weight Loss Surgery
SO OBESITY
LA English
DT Article
ID OPEN GASTRIC BYPASS; BARIATRIC SURGERY; HEALTH LITERACY; OBESITY; RISK;
METAANALYSIS; MORTALITY; PROGRAM
AB To update evidence-based best practice guidelines for obtaining informed consent from weight loss surgery (WLS) patients, with an emphasis on appropriate content and communications approaches that might enhance patient understanding of the information, we performed a systematic search of English-language literature published between April 2004 and May 2007 in MEDLINE and the Cochrane database. Keywords included WLS and informed consent, comprehension, health literacy, and patient education; and WLS and outcomes, risk, patient safety management, and effectiveness. Recommendations are based on the most current literature and the consensus of the expert panel; they were graded according to systems used in established evidence-based models. We identified over 120 titles, 38 of which were reviewed in detail. Evidence suggests that WLS outcomes, including long-term rates of relapse, vary by procedure. For some weight loss surgeries, long-term outcomes may not be known. Risks also vary by patient and provider characteristics. Informed consent should incorporate realistic projections of the short- and long-term risks, benefits, and consequences of surgery, as well as alternatives to WLS. For consent to be informed, the education process should continue until the patient demonstrates comprehension of all relevant material and concepts. Confirmation of comprehension can protect patients engaged in the process of consent for WLS. Future research should focus on the outcomes and consequences of WLS, and different approaches that facilitate patient understanding of, and decision making about, WLS.
C1 [Wee, Christina C.] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA.
[Wee, Christina C.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA.
[Pratt, Janey S.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Pratt, Janey S.] Massachusetts Gen Hosp, MGH Weight Ctr, Boston, MA 02114 USA.
[Fanelli, Robert] Berkshire Med Ctr, Dept Surg, Pittsfield, MA USA.
[Fanelli, Robert] Univ Massachusetts, Sch Med, Dept Surg, Pittsfield, MA USA.
[Samour, Patricia Q.] Beth Israel Deaconess Med Ctr, Dept Nutr, Boston, MA 02215 USA.
[Trainor, Linda S.] Beth Israel Deaconess Med Ctr, Minimally Invas Surg & Dept Surg, Boston, MA 02215 USA.
[Paasche-Orlow, Michael K.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.
RP Wee, CC (reprint author), Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA.
EM cwee@bidmc.harvard.edu
OI Paasche-Orlow, Michael/0000-0002-9276-7190
FU NIDDK NIH HHS [P30-DK-46200]
NR 43
TC 18
Z9 18
U1 5
U2 7
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1930-7381
J9 OBESITY
JI Obesity
PD MAY
PY 2009
VL 17
IS 5
BP 885
EP 888
DI 10.1038/oby.2008.567
PG 4
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 440OO
UT WOS:000265709800006
PM 19396067
ER
PT J
AU Schumann, R
Jones, SB
Cooper, B
Kelley, SD
Bosch, MV
Ortiz, VE
Connor, KA
Kaufman, MD
Harvey, AM
Carr, DB
AF Schumann, Roman
Jones, Stephanie B.
Cooper, Bronwyn
Kelley, Scott D.
Bosch, Mark Vanden
Ortiz, Vilma E.
Connor, Kathleen A.
Kaufman, Michael D.
Harvey, Alan M.
Carr, Daniel B.
TI Update on Best Practice Recommendations for Anesthetic Perioperative
Care and Pain Management in Weight Loss Surgery, 2004-2007
SO OBESITY
LA English
DT Article
ID MORBIDLY OBESE-PATIENTS; OBSTRUCTIVE SLEEP-APNEA; LAPAROSCOPIC GASTRIC
BYPASS; END-EXPIRATORY PRESSURE; POSITIVE AIRWAY PRESSURE; BARIATRIC
SURGERY; NONINVASIVE VENTILATION; ARTERIAL OXYGENATION;
GENERAL-ANESTHESIA; PATIENT
AB To reevaluate and update evidence-based best practice recommendations published in 2004 for anesthetic perioperative care and pain management in weight loss surgery (WLS), we performed a systematic search of English-language literature on anesthetic perioperative care and pain management in WLS published between April 2004 and May 2007 in MEDLINE and the Cochrane Library. We identified relevant abstracts by using key words, retrieved full text articles, and stratified the resulting evidence according to systems used in established evidence-based models. We updated prior evidence-based best practice recommendations based upon interim literature. In instances of controversial or inadequate scientific evidence, the task force reached consensus recommendations following evaluation of the best available information and expert opinion. The search yielded 1,788 abstracts, with 162 potentially relevant titles; 45 were reviewed in detail. Despite more information on perioperative management of patients with obstructive sleep apnea (OSA), evidence to support preoperative testing and treatment or to guide perioperative monitoring is scarce. New evidence on appropriate intraoperative dosing of muscle relaxants allows for greater precision in their use during WLS. A novel application of alpha-2 agonists for perioperative anesthetic care is emerging. Key elements that may enhance patient safety include integration of the latest evidence on WLS, obesity, and collaborative multidisciplinary care into clinical care. However, large gaps remain in the evidence base.
C1 [Schumann, Roman; Carr, Daniel B.] Tufts Univ New England Med Ctr, Dept Anesthesia, Boston, MA USA.
[Jones, Stephanie B.] Beth Israel Deaconess Med Ctr, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02215 USA.
[Cooper, Bronwyn] Univ Massachusetts, Mem Med Ctr, Dept Anesthesiol, Worcester, MA 01605 USA.
[Kelley, Scott D.; Harvey, Alan M.] Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA.
[Bosch, Mark Vanden] Berkshire Hlth Syst, Dept Anesthesiol, Pittsfield, MA USA.
[Ortiz, Vilma E.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA.
[Connor, Kathleen A.] Newton Wellesley Hosp, Dept Anesthesiol, Newton, MA USA.
[Kaufman, Michael D.] Lahey Clin Fdn, Dept Anesthesiol, Burlington, MA USA.
RP Schumann, R (reprint author), Tufts Univ New England Med Ctr, Dept Anesthesia, Boston, MA USA.
EM rschumann@tufts-nemc.org
OI Jones, Stephanie/0000-0001-8342-0374
FU NIDDK NIH HHS [P30-DK-46200]
NR 52
TC 24
Z9 26
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1930-7381
J9 OBESITY
JI Obesity
PD MAY
PY 2009
VL 17
IS 5
BP 889
EP 894
DI 10.1038/oby.2008.569
PG 6
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 440OO
UT WOS:000265709800007
PM 19396068
ER
PT J
AU Pratt, JSA
Lenders, CM
Dionne, EA
Hoppin, AG
Hsu, GLK
Inge, TH
Lawlor, DF
Marino, MF
Meyers, AF
Rosenblum, JL
Sanchez, VM
AF Pratt, Janey S. A.
Lenders, Carine M.
Dionne, Emily A.
Hoppin, Alison G.
Hsu, George L. K.
Inge, Thomas H.
Lawlor, David F.
Marino, Margaret F.
Meyers, Alan F.
Rosenblum, Jennifer L.
Sanchez, Vivian M.
TI Best Practice Updates for Pediatric/Adolescent Weight Loss Surgery
SO OBESITY
LA English
DT Article
ID GASTRIC-BYPASS-SURGERY; MORBIDLY OBESE ADOLESCENTS; QUALITY-OF-LIFE;
LAPAROSCOPIC SLEEVE GASTRECTOMY; BARIATRIC SURGICAL-PATIENT; TYPE-2
DIABETES-MELLITUS; FATTY LIVER-DISEASE; OVERWEIGHT ADOLESCENTS;
METABOLIC SYNDROME; EXTREME OBESITY
AB The objective of this study is to update evidence-based best practice guidelines for pediatric/adolescent weight loss surgery (WLS). We performed a systematic search of English-language literature on WLS and pediatric, adolescent, gastric bypass, laparoscopic gastric banding, and extreme obesity published between April 2004 and May 2007 in PubMed, MEDLINE, and the Cochrane Library. Keywords were used to narrow the search for a selective review of abstracts, retrieval of full articles, and grading of evidence according to systems used in established evidence-based models. In light of evidence on the natural history of obesity and on outcomes of WLS in adolescents, guidelines for surgical treatment of obesity in this age group need to be updated. We recommend modification of selection criteria to include adolescents with BMI >= 35 and specific obesity-related comorbidities for which there is clear evidence of important short-term morbidity (i.e., type 2 diabetes, severe steatohepatitis, pseudotumor cerebri, and moderate-to-severe obstructive sleep apnea). In addition, WLS should be considered for adolescents with extreme obesity (BMI >= 40) and other comorbidities associated with long- term risks. We identified >1,085 papers; 186 of the most relevant were reviewed in detail. Regular updates of evidence-based recommendations for best practices in pediatric/adolescent WLS are required to address advances in technology and the growing evidence base in pediatric WLS. Key considerations in patient safety include carefully designed criteria for patient selection, multidisciplinary evaluation, choice of appropriate procedure, thorough screening and management of comorbidities, optimization of long-term compliance, and age-appropriate fully informed consent.
C1 [Pratt, Janey S. A.; Lawlor, David F.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Pratt, Janey S. A.; Dionne, Emily A.; Hoppin, Alison G.; Rosenblum, Jennifer L.] Massachusetts Gen Hosp, MGH Weight Ctr, Boston, MA 02114 USA.
[Lenders, Carine M.; Marino, Margaret F.; Meyers, Alan F.] Boston Med Ctr, Dept Pediat, Boston, MA USA.
[Hsu, George L. K.] Tufts Univ New England Med Ctr, Dept Psychiat, Boston, MA USA.
[Inge, Thomas H.] Cincinnati Childrens Hosp, Dept Pediat Surg, Cincinnati, OH USA.
[Sanchez, Vivian M.] Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02215 USA.
RP Pratt, JSA (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
EM jpratt@partners.org
OI Meyers, Alan/0000-0002-1138-0024; Sanchez, Vivian/0000-0001-5565-9687;
Lawlor, Debbie A/0000-0002-6793-2262
FU NIDDK NIH HHS [P30 DK040561, P30 DK040561-14, P30 DK046200, P30
DK046200-16, P30-DK-46200, R01 DK056690]
NR 89
TC 129
Z9 135
U1 0
U2 7
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1930-7381
J9 OBESITY
JI Obesity
PD MAY
PY 2009
VL 17
IS 5
BP 901
EP 910
DI 10.1038/oby.2008.577
PG 10
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 440OO
UT WOS:000265709800009
PM 19396070
ER
PT J
AU Shikora, SA
Kruger, RS
Blackburn, GL
Fallon, JA
Harvey, AM
Johnson, EQ
Kaplan, L
Mun, EC
Riley, S
Robinson, MK
Sabin, JE
Snow, RL
LoNigro, R
Steingisser, LJ
Lautz, DB
AF Shikora, Scott A.
Kruger, Rayford S., Jr.
Blackburn, George L.
Fallon, John A.
Harvey, Alan M.
Johnson, Elvira Q.
Kaplan, Lee
Mun, Edward C.
Riley, Stancel, Jr.
Robinson, Malcolm K.
Sabin, James E.
Snow, Roger L.
LoNigro, Robert
Steingisser, Lee J.
Lautz, David B.
CA Policy Access Task Grp
TI Best Practices in Policy and Access (Coding and Reimbursement) for
Weight Loss Surgery
SO OBESITY
LA English
DT Article
ID EVIDENCE-BASED MEDICINE; GASTRIC BYPASS-SURGERY; BARIATRIC SURGERY;
MORBID-OBESITY; CHILDHOOD OBESITY; ADOLESCENTS; MORTALITY; TRENDS;
PATIENT; SAFETY
AB To update evidence-based best practice guidelines for coding and reimbursement and establish policy and access standards for weight loss surgery (WLS). Systematic search of English-language literature on WLS and health-care policy, access, insurance reimbursement, coding, private payers, public policy, and mandated benefits published between April 2004 and May 2007 in MEDLINE, EMBASE, and the Cochrane Library. Use of key words to narrow the search for a selective review of abstracts, retrieval of full articles, and grading of evidence according to systems used in established evidence-based models. We identified 51 publications in our literature search; the 20 most relevant were examined in detail. These included reviews, cost-benefit analyses, and trend and cost studies from administrative databases. Literature on policy issues surrounding WLS are very sparse and largely focused on economic analyses. Reports on policy initiatives in the public and private arenas are primarily limited to narrative reviews of nonsurgical efforts to fight obesity. A substantial body of work shows that WLS improves or reverses most obesity-related comorbidities. Mounting evidence also indicates that WLS confers a significant survival advantage for those who undergo it. WLS is a viable and cost-effective treatment for an increasingly common disease, and policy decisions are more frequently being linked to incentives for national health-care goals. However, access to WLS often varies by payer and region. Currently, there are no uniform criteria for determining patient appropriateness for surgery.
C1 [Shikora, Scott A.] Tufts Med Ctr, Boston, MA USA.
[Kruger, Rayford S., Jr.] Tobey Hosp, Wareham, MA USA.
[Blackburn, George L.; Mun, Edward C.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Fallon, John A.; Steingisser, Lee J.] Blue Cross & Blue Shield Massachusetts, Boston, MA USA.
[Harvey, Alan M.; Robinson, Malcolm K.; Lautz, David B.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Johnson, Elvira Q.] Massachusetts Dietet Assoc, Reading, MA USA.
[Kaplan, Lee] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Riley, Stancel, Jr.] Board Registrat Med, Boston, MA USA.
[Sabin, James E.] Harvard Pilgrim Hlth Care, Wellesley, MA USA.
[Snow, Roger L.] Univ Massachusetts, Sch Med, Worcester, MA USA.
[Snow, Roger L.] MassHealth, Boston, MA USA.
[LoNigro, Robert] Tufts Associated Hlth Plan, Watertown, MA USA.
RP Shikora, SA (reprint author), Tufts Med Ctr, Boston, MA USA.
EM Sshikora@tuftsmedicalcenter.org
FU NIDDK NIH HHS [P30-DK-46200]
NR 49
TC 3
Z9 3
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1930-7381
J9 OBESITY
JI Obesity
PD MAY
PY 2009
VL 17
IS 5
BP 918
EP 923
DI 10.1038/oby.2008.573
PG 6
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 440OO
UT WOS:000265709800011
PM 19396072
ER
PT J
AU Hutter, MM
Jones, DB
Riley, SM
Snow, RL
Cella, RJ
Schneider, BE
Clancy, KA
AF Hutter, Matthew M.
Jones, Daniel B.
Riley, Stancel M., Jr.
Snow, Roger L.
Cella, Robert J.
Schneider, Benjamin E.
Clancy, Kerri A.
TI Best Practice Updates for Weight Loss Surgery Data Collection
SO OBESITY
LA English
DT Article
ID QUALITY IMPROVEMENT PROGRAM; BARIATRIC SURGICAL-PROCEDURES; ADULT
CARDIAC-SURGERY; PATIENT-SAFETY; VETERANS-AFFAIRS; GASTRIC BYPASS;
MORBID-OBESITY; COST-EFFECTIVENESS; OUTCOMES; MORTALITY
AB To update evidence-based best practice guidelines for collection of data on weight loss surgery (WLS). Systematic search of English-language literature in MEDLINE and the Cochrane Library on WLS and data collection, registries, risk adjustment, accreditation, benchmarks, and administrative and outcomes databases published between April 2004 and May 2007. Use of key words to narrow the search for a selective review of abstracts, retrieval of full articles, and grading of evidence according to systems used in established evidence-based models. During our search, we identified 212 papers; the 63 most relevant were reviewed in detail. Most data collection on WLS has relied on administrative data sets, single-institution studies, and other sources that are not WLS specific. A six-center, nationwide study involving data collection has been started by the longitudinal assessment of bariatric surgery, but results are not yet available. Two WLS-specific, longitudinal, national data collection systems are about to be implemented. Key factors in patient safety include data collection for all weight loss procedures; prospective, risk-adjusted, universal, benchmarked, longitudinal data collection systems; and use of WLS-specific data points that track clinical effectiveness and complications following WLS. Data collection will need to include assessments of novel therapies and specific subgroups (e.g., adolescents, the elderly, and individuals who are at the greatest risk or have the most to gain from WLS). Quality indicators, including metrics on processes of care and determination of outliers, need to be established and monitored to advance patient safety and quality improvement.
C1 [Hutter, Matthew M.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Jones, Daniel B.; Schneider, Benjamin E.] Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02215 USA.
[Riley, Stancel M., Jr.] Massachusetts Board Registrat Med, Boston, MA USA.
[Snow, Roger L.] Massachusetts Medicaid, Boston, MA USA.
[Cella, Robert J.] Berkshire Med Ctr, Dept Med, Pittsfield, MA USA.
[Clancy, Kerri A.] Brigham & Womens Hosp, Dept Nursing, Boston, MA 02115 USA.
RP Hutter, MM (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
EM mhutter@partners.org
FU NIDDK NIH HHS [P30-DK-46200]
NR 56
TC 8
Z9 8
U1 1
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1930-7381
J9 OBESITY
JI Obesity
PD MAY
PY 2009
VL 17
IS 5
BP 924
EP 928
DI 10.1038/oby.2008.568
PG 5
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 440OO
UT WOS:000265709800012
PM 19396073
ER
PT J
AU Ellsmere, JC
Thompson, CC
Brugge, WR
Chuttani, R
Desilets, DJ
Rattner, DW
Tarnoff, ME
Kaplan, LM
AF Ellsmere, James C.
Thompson, Christopher C.
Brugge, William R.
Chuttani, Ram
Desilets, David J.
Rattner, David W.
Tarnoff, Michael E.
Kaplan, Lee M.
TI Endoscopic Interventions for Weight Loss Surgery
SO OBESITY
LA English
DT Article
ID Y GASTRIC BYPASS; MORBIDLY OBESE-PATIENTS; BARIATRIC SURGERY;
INTRAGASTRIC BALLOON; TRANSORAL GASTROPLASTY; BOTULINUM TOXIN;
DOUBLE-BLIND; REDUCTION; ENDOTHERAPY; MANAGEMENT
AB In this paper we review the state-of-the-art in endoscopic interventions for obesity treatment and make best practice recommendations for weight loss surgery (WLS). We performed a systematic search of English-language literature published between April 2004 and June 2008 in MEDLINE and the Cochrane Library on WLS and endoscopic interventions, endoscopically placed devices, minimally invasive surgery, image-guided surgery, endoluminal surgery, endoscopic instrumentation, interventional gastroenterology, transluminal surgery, and natural orifice transluminal surgery. We also searched the literature on endoscopic interventions and WLS and patient safety. We identified 36 pertinent articles, all of which were reviewed in detail; assessed the current science in endoscopic interventions for WLS; and made best practice recommendations based on the latest available evidence. Our findings indicate that endoscopic interventions and endoscopically placed devices may provide valuable approaches to the management of WLS complications and the primary management of obesity. Given the rapid changes in endoscopic technologies and techniques, systematic literature review is required to address issues related to the emerging role of endoluminal surgery in the treatment of obesity. These interventions should be a high priority for development and investigation.
C1 [Ellsmere, James C.] Beth Israel Deaconess Med Ctr, Dept Surg, Sect Minimally Invas Surg, Boston, MA 02215 USA.
[Thompson, Christopher C.] Brigham & Womens Hosp, Dept Med, Div Gastroenterol, Boston, MA 02115 USA.
[Brugge, William R.; Rattner, David W.; Kaplan, Lee M.] Massachusetts Gen Hosp, Dept Med, Div Gastroenterol, Boston, MA 02114 USA.
[Chuttani, Ram] Beth Israel Deaconess Med Ctr, Dept Med, Div Gastroenterol, Boston, MA 02215 USA.
[Desilets, David J.] Baystate Med Ctr, Dept Med, Div Gastroenterol, Springfield, MA 01199 USA.
[Tarnoff, Michael E.] Tufts Med Ctr, Dept Surg, Div Minimally Invas Surg, Boston, MA USA.
RP Ellsmere, JC (reprint author), Beth Israel Deaconess Med Ctr, Dept Surg, Sect Minimally Invas Surg, 330 Brookline Ave, Boston, MA 02215 USA.
EM jellsmer@bidmc.harvard.edu
FU NIDDK NIH HHS [P30-DK-46200]
NR 37
TC 14
Z9 15
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1930-7381
J9 OBESITY
JI Obesity
PD MAY
PY 2009
VL 17
IS 5
BP 929
EP 933
DI 10.1038/oby.2008.588
PG 5
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 440OO
UT WOS:000265709800013
PM 19396074
ER
PT J
AU Bautista, LE
Casas, JP
Herrera, VM
Miranda, JJ
Perel, P
Pichardo, R
Gonzalez, A
Sanchez, JR
Ferreccio, C
Aguilera, X
Silva, E
Orostegui, M
Gomez, LF
Chirinos, JA
Medina-Lezama, J
Perez, CM
Suarez, E
Ortiz, AP
Rosero, L
Schapochnik, N
Ortiz, Z
Ferrante, D
AF Bautista, L. E.
Casas, J. P.
Herrera, V. M.
Miranda, J. J.
Perel, P.
Pichardo, R.
Gonzalez, A.
Sanchez, J. R.
Ferreccio, C.
Aguilera, X.
Silva, E.
Orostegui, M.
Gomez, L. F.
Chirinos, J. A.
Medina-Lezama, J.
Perez, C. M.
Suarez, E.
Ortiz, A. P.
Rosero, L.
Schapochnik, N.
Ortiz, Z.
Ferrante, D.
CA Investigators Latin-American
TI The Latin American Consortium of Studies in Obesity (LASO)
SO OBESITY REVIEWS
LA English
DT Review
DE Consortium; health surveys; Latin America; obesity; risk factors
ID CORONARY-HEART-DISEASE; RISK-FACTORS; METABOLIC SYNDROME; NUTRITION
TRANSITION; CARDIOVASCULAR RISK; DEVELOPING-WORLD; PREVALENCE;
DETERMINANTS; PREDICTION; EXPERIENCE
AB Current, high-quality data are needed to evaluate the health impact of the epidemic of obesity in Latin America. The Latin American Consortium of Studies of Obesity (LASO) has been established, with the objectives of (i) Accurately estimating the prevalence of obesity and its distribution by sociodemographic characteristics; (ii) Identifying ethnic, socioeconomic and behavioural determinants of obesity; (iii) Estimating the association between various anthropometric indicators or obesity and major cardiovascular risk factors and (iv) Quantifying the validity of standard definitions of the various indexes of obesity in Latin American population. To achieve these objectives, LASO makes use of individual data from existing studies. To date, the LASO consortium includes data from 11 studies from eight countries (Argentina, Chile, Colombia, Costa Rica, Dominican Republic, Peru, Puerto Rico and Venezuela), including a total of 32 462 subjects. This article describes the overall organization of LASO, the individual studies involved and the overall strategy for data analysis. LASO will foster the development of collaborative obesity research among Latin American investigators. More important, results from LASO will be instrumental to inform health policies aiming to curtail the epidemic of obesity in the region.
C1 [Bautista, L. E.; Herrera, V. M.] Univ Wisconsin, Dept Populat Hlth Sci, Madison, WI 53726 USA.
[Pichardo, R.; Gonzalez, A.] Inst Dominicano Cardiol, Santo Domingo, Dominican Rep.
[Sanchez, J. R.] Inst nacl Salud, Ctr Nacl Alimentac & Nutr, Lima, Peru.
[Ferreccio, C.] Pontificia Univ Catolica Chile, Dept Salud Publ, Santiago, Chile.
[Aguilera, X.] Ministerio Salud Chile, Santiago, Chile.
[Silva, E.] Univ Zulia, Fac Med, Inst Invest & Estudios Enfermedades Cardiovasc, Maracaibo 4011, Venezuela.
[Orostegui, M.] Univ Ind Santander, Epidemiol Res Ctr, Cardiovasc Dis Epidemiol Observ, Bucaramanga, Colombia.
[Gomez, L. F.] Fdn FES Social, Hlth Div, Bogota, Colombia.
[Chirinos, J. A.] Univ Penn, Sch Med, Div Cardiol, Philadelphia, PA 19104 USA.
[Medina-Lezama, J.] Santa Maria Catholic Univ, Arequipa, Peru.
[Perez, C. M.; Suarez, E.; Ortiz, A. P.] Univ Puerto Rico, Dept Biostat & Epidemiol, Grad Sch Publ Hlth, San Juan, PR 00936 USA.
[Rosero, L.] Univ Costa Rica, Ctr Ctr Amer Poblac, San Jose, Costa Rica.
[Schapochnik, N.] Ministerio Salud Prov Tierra Fuego, Ushuaia, Argentina.
[Ortiz, Z.] Acad Nacl Med Buenos Aires, Inst Invest Epidemiol, Buenos Aires, DF, Argentina.
[Ferrante, D.] Ministerio Salud & Ambiente, Buenos Aires, DF, Argentina.
[Casas, J. P.; Miranda, J. J.; Perel, P.] London Sch Hyg & Trop Med, Dept Epidemiol & Populat Hlth, London WC1, England.
[Chirinos, J. A.] Philadelphia VA Med Ctr, Philadelphia, PA USA.
[Medina-Lezama, J.] Santa Maria Res Inst, Arequipa, Peru.
RP Bautista, LE (reprint author), Univ Wisconsin, Dept Populat Hlth Sci, 610 Walnut St,703 WARF, Madison, WI 53726 USA.
EM lebautista@wisc.edu
RI Herrera, Victor/C-5602-2008; Miranda, J. Jaime/A-8482-2008; Aguilera,
Ximena/D-9861-2014
OI Miranda, J. Jaime/0000-0002-4738-5468; Aguilera,
Ximena/0000-0002-8153-6733
FU Ministerio de Salud de la Republica Argentina; Gobierno de la Provincia
de Tierra del Fuego; Antartida e Islas del Atlantico Sur, Argentina;
Ministerio de Salud, Chile; Secretaria Distrital de Salud de Bogota,
Colombia; Secretaria de Salud Municipal de Bucaramanga; Secretaria
Departamental de Salud de Santander, Colombia; Wellcome Trust Foundation
[072406, GR074833MA]; Sociedad Dominicana de Cardiologia; Brystol Myers
Squibb; Warners Lambert (Pfizer); Novartis; Merck Sharp Dohme and
Magnachen International; Instituto Nacional de Salud, Lima, Peru;
Instituto de Investigacion Santa Maria; Merck Sharp & Dohme Corporation;
National Institutes of Health/National Center for Research Resources
(NCRR/NIH) [G12RR03051, \P20RR011126]; Fondo Nacional de Ciencia,
Tecnologia e Innovacion (FONACIT); Fundacion Venezolana de Hipertension
Arterial (FUNDAHIPERTENSION)
FX The 'Prueba de Validacion de la Encuesta Nacional de Factores de Riesgo'
was funded by the Ministerio de Salud de la Republica Argentina and the
Gobierno de la Provincia de Tierra del Fuego, Antartida e Islas del
Atlantico Sur, Argentina. The 'Encuesta Nacional de Factores de Riesgo'
was funded by the Ministerio de Salud de la Republica Argentina. The
'Encuesta Nacional de Salud 2003' was funded by the Ministerio de Salud,
Chile. The 'Estudio CARMEN Santa Fe' was funded by the Secretaria
Distrital de Salud de Bogota, Colombia. CARMEN-Bucaramanga was funded by
the Secretaria de Salud Municipal de Bucaramanga and the Secretaria
Departamental de Salud de Santander, Colombia. The 'Costa Rica: Estudio
de Longevidad y Envejecimeinto Saludable (CRELES)' was funded by The
Wellcome Trust Foundation, grant number 072406. The 'Estudio de Factores
de Riesgo Cardiovascular en la Republica Dominicana (EFRICARD)' was
funded by the Sociedad Dominicana de Cardiologia, Brystol Myers Squibb,
Warners Lambert (Pfizer), Novartis, Merck Sharp Dohme and Magnachen
International. The 'Encuesta Nacional de Indicadores Nutricionales,
Bioquimicos, Socioeconomicos y Culturales Relacionados con las
Enfermedades Cronico Degenerativas (ENINBSC-ECNT)' was funded by the
Instituto Nacional de Salud, Lima, Peru. JJM and the 'PERU MIGRANT
study' were supported by a Wellcome Trust Research Training Fellowship
(GR074833MA). The study 'Prevalencia de Enfermedades Cardiovasculares y
Factores de Riesgo Coronario en Arequipa (PREVENCION)' was partially
supported by the Instituto de Investigacion Santa Maria. The study of
the 'Prevalence of Metabolic Syndrome and its Individual Components in
the adult population of the San Juan Metropolitan Area in Puerto Rico'
was funded by an unrestricted grant from Merck Sharp & Dohme Corporation
with additional support from the National Institutes of Health/National
Center for Research Resources (NCRR/NIH) grant awards G12RR03051 and
P20RR011126. The Zulia Coronary Heart Disease Risk Factor Study was
funded by the Fondo Nacional de Ciencia, Tecnologia e Innovacion
(FONACIT) and the Fundacion Venezolana de Hipertension Arterial
(FUNDAHIPERTENSION).
NR 44
TC 18
Z9 21
U1 3
U2 11
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1467-7881
J9 OBES REV
JI Obes. Rev.
PD MAY
PY 2009
VL 10
IS 3
BP 364
EP 370
DI 10.1111/j.1467-789X.2009.00591.x
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 437UB
UT WOS:000265511300015
PM 19438980
ER
PT J
AU Growdon, WB
Wolfberg, AJ
Goldstein, DP
Feltmate, CM
Chinchilla, ME
Lieberman, ES
Berkowitz, RS
AF Growdon, Whitfield B.
Wolfberg, Adam J.
Goldstein, Donald P.
Feltmate, Colleen M.
Chinchilla, Manuel E.
Lieberman, Ellice S.
Berkowitz, Ross S.
TI Evaluating Methotrexate Treatment in Patients With Low-Risk Postmolar
Gestational Trophoblastic Neoplasia
SO OBSTETRICAL & GYNECOLOGICAL SURVEY
LA English
DT Editorial Material
AB The response of low-risk persistent gestational trophoblastic neoplasia (GTN) to methotrexate (MTX) monotherapy is close to 100%. With use of various MTX regimens, 48%-92% of patients go into remission. There is limited data on potential clinical risk factors indicating the need for additional courses of MTX or alternative chemotherapy following an initial course of MTX. This retrospective observational study identified possible clinical factors predictive of the requirement for additional MTX or alternative chemotherapy to obtain a remission in patients with postmolar low-risk GTN who had received MTX initially. Data was analyzed for 1801 women diagnosed with molar pregnancies between 1973 and 2003. Of the 150 women in the final study population, 110 had been diagnosed as complete mole and 40 as partial mole, and all had received MTX as initial therapy for GTN. All women had low-risk disease according to the combined International Federation of Obstetrics and Gynecology (FIGO) stage and the World Health Organization prognostic scores. Remission was defined as achievement and maintenance of undetectable serum beta human chorionic gonadotropin (beta-hCG) levels for 1 year.
All 150 patients ultimately achieved remission. Of the 70 women (47%) requiring additional courses of chemotherapy including MTX, 45 (64%) required alternative chemotherapy. Multivariate analysis showed that independent prognostic factors predicting increased risk of requiring additional MTX or alternative chemotherapy were complete mole histology, presence of metastasis, single day MTX infusion and any increase in beta-hCG levels 1 week after MTX therapy. Dilatation and curettage within 1 week after the diagnosis of persistence was not an independent risk factor for additional or alternative chemotherapy. For GTN following complete mole, beta-hCG levels >= 2000 mIU/ml at 1 week post-MTX were associated with an 89% risk of requiring additional MTX chemotherapy and a 64% risk of alternative chemotherapy to achieve remission.
These data identify several independent risk factors that predispose women with low-risk GTN to require additional MTX cycles and alternative chemotherapy after initial MTX.
C1 [Growdon, Whitfield B.] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, Boston, MA 02114 USA.
Tufts Univ New England Med Ctr, Dept Obstet & Gynecol, Div Maternal Fetal Med, Boston, MA USA.
Brigham & Womens Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, Boston, MA 02115 USA.
Donald P Goldstein MD Tumor Registry, New England Trophoblast Dis Ctr, Boston, MA USA.
Harvard Univ, Dana Farber Canc Inst, Ctr Canc, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Growdon, WB (reprint author), Massachusetts Gen Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, Boston, MA 02114 USA.
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 0029-7828
J9 OBSTET GYNECOL SURV
JI Obstet. Gynecol. Surv.
PD MAY
PY 2009
VL 64
IS 5
BP 308
EP 309
PG 2
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 438OY
UT WOS:000265566200014
ER
PT J
AU Christo, K
Cord, J
Mendes, N
Miller, KK
Goldstein, MA
Klibanski, A
Misra, M
AF Christo, Karla
Cord, Jennalee
Mendes, Nara
Miller, Karen K.
Goldstein, Mark A.
Klibanski, Anne
Misra, Madhusmita
TI Acylated Ghrelin and Leptin in Adolescent Athletes With Amenorrhea,
Eumenorrheic Athletes and Controls: A Cross-Sectional Study
SO OBSTETRICAL & GYNECOLOGICAL SURVEY
LA English
DT Editorial Material
AB Previous reports suggest that adolescent endurance athletes such as gymnasts and swimmers may be at higher risk of amenorrhea (AA) than other adolescent athletes. Neuroendocrine factors that differentiate athletes with AA from eumenorrheic athletes (EA) have been investigated but are not completely understood.
Two neuroendocrine peptides, leptin and ghrelin, appear to be involved in regulation of the hypothalamo-pituitary-gonadal axis. Low leptin levels and high ghrelin levels have been implicated in the occurrence of amenorrhea in adult athletes. The investigators hypothesized that blood levels of leptin and/or ghrelin could predict levels of gonadal steroids in adolescent athletes and identify which will develop ammenorhea. This cross-sectional study compared the levels of leptin, ghrelin, and gonadal steroids among adolescent athletes with AA, EA, and nonathletic controls at a large urban hospital. The study enrolled 58 adolescent girls, 12-18 years old, including 21 AA, 19 EA and 18 nonathletic controls. There was no history of amenorrhea or menarchal delay in the nonathletic controls. Active ghrelin, leptin, estrogen (E(2)), and testosterone were measured in fasting blood.
The body mass index (BMI) in AA was significantly lower than among EA and controls at baseline (P = 0.003). Log active ghrelin levels were significantly higher in AA compared to the other two groups (P < 0.0001); the difference was maintained after controlling for BMI Z-scores (P = 0.0007). Leptin levels were lower in AA compared to the other two groups (P < 0.0001), but did not remain significant after controlling for BMI Z-scores. Total testosterone levels were lower among AA compared to the EA and controls (P = 0.002), and the differences remained significant after controlling for BMI Z-scores (P = 0.03. There was a significant trend for lower E(2) scores among AA than the EA (P = 0.07), but the effect was not significant after controlling for BMI Z-scores. Inverse associations of log active ghrelin with testosterone were noted (P = 0.05), whereas there were positive associations of leptin with testosterone (P = 0.05) and log E(2) (P = 0.01).
These data show that ghrelin and leptin are independent predictors of levels of gonadal steroids. The investigators conclude from these findings that lower leptin levels and especially higher ghrelin levels may predict which athletes will develop amenorrhea.
C1 [Christo, Karla] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
Massachusetts Gen Hosp Children, Adolescent Med Unit, Boston, MA USA.
Massachusetts Gen Hosp Children, Pediat Endocrine Unit, Boston, MA USA.
RP Christo, K (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA.
RI Mendes Estella, Nara/E-4682-2013
NR 0
TC 0
Z9 0
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-7828
J9 OBSTET GYNECOL SURV
JI Obstet. Gynecol. Surv.
PD MAY
PY 2009
VL 64
IS 5
BP 313
EP 314
PG 2
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 438OY
UT WOS:000265566200017
ER
PT J
AU Subak, LL
Wing, R
West, DS
Franklin, F
Vittinghoff, E
Creasman, JM
Richter, HE
Myers, D
Burgio, KL
Gorin, AA
Macer, J
Kusek, JW
Grady, D
Investigators, P
AF Subak, Leslee L.
Wing, Rena
West, Delia Smith
Franklin, Frank
Vittinghoff, Eric
Creasman, Jennifer M.
Richter, Hotly E.
Myers, Deborah
Burgio, Kathryn L.
Gorin, Amy A.
Macer, Judith
Kusek, John W.
Grady, Deborah
Investigators, P. R. I. D. E.
TI Weight Loss to Treat Urinary Incontinence in Overweight and Obese Women
SO OBSTETRICAL & GYNECOLOGICAL SURVEY
LA English
DT Editorial Material
AB Obesity is a strong risk factor for urinary incontinence. Although marked weight loss after bariatric surgery in morbidly obese women was associated in previous studies with a reduction in urinary incontinence, the overall evidence for a benefit of weight loss in obese women is inconclusive. In this randomized clinical trial, the Program to Reduce Incontinence by Diet and Exercise, the potential benefits of a behavioral weight-reduction intervention were compared with a structured educational program in 338 overweight and obese women with at least 10 urinary incontinence episodes per week. The study subjects were randomized to receive either an intensive 6-month weight-loss program that included diet, exercise, and behavior modification (intervention group, n = 226) or a structured education program consisting of general information about healthy eating, physical activity, and weight loss (control group, n = 112). The mean (+/- SD) age of the study subjects was 53 +/- 11 years. Body-mass index (BMI) was calculated as the weight in kilograms divided by the square of the height in meters. The primary study outcome was the change in the total number of self-reported incontinence episodes of any type (including stress and urge incontinence) recorded in a 7-day voiding diary at 6 months after randomization.
At baseline, the mean BMI and the total number of incontinence episodes per week were the same in the intervention and control groups (BMI, 36 6 vs. 36 5, respectively; incontinence episodes, 24 18 vs. 24 16, respectively). At 6 months, the mean weight loss among women in the intervention group was 8.0% (7.8 kg), whereas the mean weight loss among women in the control group was 1.6% (1.5 kg) (P < .001). There was a greater decrease in total number of incontinence episodes per week in the intervention group at 6 months compared with the control group (intervention: 47.4% vs. control: 28.1%, P = 0.01). The frequency of stress incontinence episodes was reduced more in the intervention group (57.6%) than the control group (32.7%, P = 0.02). The frequency of episodes of urge incontinence was also decreased more in the intervention group (42.4% vs. 26.0%), but the difference was not statistically significant (P = 0.14). In comparison with the control group, a higher proportion of women in the intervention group reported a clinically meaningful reduction of at least 70% in the total weekly number of episodes of any type of incontinence (P < 0.001), stress-incontinence (P = 0.009), and urge-incontinence (P = 0.04).
The investigators conclude from these findings that weight loss should be considered as a first-line treatment in overweight and obese women with incontinence.
C1 [Subak, Leslee L.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
Miriam Hosp, Providence, RI 02906 USA.
Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA.
Univ Arkansas Med Sci, Coll Publ Hlth, Little Rock, AR 72205 USA.
Univ Alabama, Birmingham, AL USA.
Ctr Geriatr Res Educ & Clin, Dept Vet Affairs, Birmingham, AL USA.
Univ Connecticut, Storrs, CT USA.
NIDDK, Bethesda, MD USA.
San Francisco VA Med Ctr, San Francisco, CA USA.
RP Subak, LL (reprint author), Univ Calif San Francisco, San Francisco, CA 94143 USA.
NR 0
TC 0
Z9 0
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-7828
J9 OBSTET GYNECOL SURV
JI Obstet. Gynecol. Surv.
PD MAY
PY 2009
VL 64
IS 5
BP 317
EP 318
PG 2
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 438OY
UT WOS:000265566200019
ER
PT J
AU Ruddy, KJ
Partridge, AH
AF Ruddy, Kathryn J.
Partridge, Ann H.
TI Breast Cancer in Young Women: Clinical Decision-Making in the Face of
Uncertainty The Peppercorn Article Reviewed
SO ONCOLOGY-NEW YORK
LA English
DT Editorial Material
C1 [Ruddy, Kathryn J.; Partridge, Ann H.] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Ruddy, KJ (reprint author), Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 10
TC 6
Z9 6
U1 1
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 MAY
PY 2009
VL 23
IS 6
BP 474
EP 477
PG 2
WC Oncology
SC Oncology
GA V18PP
UT WOS:000208017000002
PM 19544686
ER
PT J
AU Jakobiec, FA
Hanna, E
Townsend, DJ
AF Jakobiec, Frederick A.
Hanna, Eissa
Townsend, Daniel J.
TI Basal Cell Carcinoma of the Eyelid With Exceptional Histomorphologic
Expressions
SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY
LA English
DT Article
ID MICROCYSTIC ADNEXAL CARCINOMA
AB A basal cell carcinoma of the eyelid had unique and potentially confusing histopathologic features. The tumor displayed a carcinoma in situ pattern with replacement of an extensive segment of the tarsal epithelium by neoplastic basaloid cells, a finding to the best of the authors' knowledge that has not been previously documented. Within the infiltrating component of the dermis were classical solid basaloid nests and lobules; they were accompanied, however, by a separate and exceptionally prominent component of duct-like (pseudoglandular) units mimicking a microcystic adnexal carcinoma.
C1 [Jakobiec, Frederick A.; Hanna, Eissa; Townsend, Daniel J.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, David G Cogan Lab Ophthalm Pathol,Dept Ophthamol, Boston, MA 02114 USA.
RP Jakobiec, FA (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, David G Cogan Lab Ophthalm Pathol,Dept Ophthamol, 243 Charles St, Boston, MA 02114 USA.
EM fred_jakobiec@meei.harvard.edu
NR 6
TC 3
Z9 3
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0740-9303
J9 OPHTHAL PLAST RECONS
JI Ophthalmic Plast. Reconstr. Surg.
PD MAY-JUN
PY 2009
VL 25
IS 3
BP 232
EP 234
DI 10.1097/IOP.0b013e3181a33887
PG 3
WC Ophthalmology; Surgery
SC Ophthalmology; Surgery
GA 449EP
UT WOS:000266313900018
PM 19454940
ER
PT J
AU Halpin, C
Rauch, SD
AF Halpin, Chris
Rauch, Steven D.
TI Hearing aids and cochlear damage: The case against fitting the pure tone
audiogram
SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY
LA English
DT Editorial Material
AB Here we propose a different approach to hearing aids, an approach that flows logically from the pathophysiology of cochlear disorders. This approach challenges some central tenets of the industry by 1) suggesting that many, if not most, cases would be better served by flat, undistored gain across all frequencies rather than by "fitting" gain to the audiogram; and 2) suggesting that most of the improvements in hearing aid technology are targeted at reducing patient complaints as opposed to increasing measurable word recognition performance. We recommend that it is better to accommodate the damaged cochlea in these cases than to attempt to reverse-engineer the audiometric test results. (C) 2009 American Academy of Otolaryngology-Head and Neck Surgery Foundation. All rights reserved.
C1 [Halpin, Chris] Massachusetts Eye & Ear Infirm, Dept Audiol, Boston, MA 02114 USA.
[Halpin, Chris; Rauch, Steven D.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA.
RP Halpin, C (reprint author), Massachusetts Eye & Ear Infirm, Dept Audiol, 243 Charles St, Boston, MA 02114 USA.
EM cfhalpin@meei.harvard.edu
NR 8
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 0194-5998
J9 OTOLARYNG HEAD NECK
JI Otolaryngol. Head Neck Surg.
PD MAY
PY 2009
VL 140
IS 5
BP 629
EP 632
DI 10.1016/j.otohns.2008.12.020
PG 4
WC Otorhinolaryngology; Surgery
SC Otorhinolaryngology; Surgery
GA 441ZZ
UT WOS:000265810700004
PM 19393401
ER
PT J
AU Chen, L
Malarick, C
Seefeld, L
Wang, SX
Houghton, M
Mao, JR
AF Chen, Lucy
Malarick, Charlene
Seefeld, Lindsey
Wang, Shuxing
Houghton, Mary
Mao, Jianren
TI Altered quantitative sensory testing outcome in subjects with opioid
therapy
SO PAIN
LA English
DT Article
DE Opioid-induced hyperalgesia; Opioid therapy; Clinical pain; Quantitative
sensory testing
ID SHORT-TERM INFUSION; SMALL-DOSE KETAMINE; INDUCED HYPERALGESIA;
WITHDRAWAL HYPERALGESIA; MORPHINE-TOLERANCE; PHYSICAL-DEPENDENCE;
CHRONIC PAIN; REMIFENTANIL; HUMANS; RATS
AB Preclinical studies have suggested that opioid exposure may induce a paradoxical decrease in the nociceptive threshold, commonly referred as opioid-induced hyperalgesia (OIH). While OIH may have implications in acute and chronic pain management, its clinical features remain unclear. Using an office-based quantitative sensory testing (QST) method, we compared pain threshold, pain tolerance, and the degree of temporal summation of the second pain in response to thermal stimulation among three groups of subjects; those with neither pain nor opioid therapy (group 1), with chronic pain but without opioid therapy (group 2), and with both chronic pain and opioid therapy (group 3). We also examined the possible correlation between QST responses to thermal stimulation and opioid dose, opioid treatment duration, opioid analgesic type, pain duration, or gender in group 3 subjects. As compared with both group 1 (n = 41) and group 2 (n = 41) subjects, group 3 subjects (n = 58) displayed a decreased heat pain threshold and exacerbated temporal summation of the second pain to thermal stimulation. In contrast, there were no differences in cold or warm sensation among three groups. Among clinical factors, daily opioid dose consistently correlated with the decreased heat pain threshold and exacerbated temporal summation of the second pain in group 3 subjects. These results indicate that decreased hear pain threshold and exacerbated temporal summation of the second pain may be characteristic QST changes in subjects with opioid therapy. The data suggest that QST may be a useful tool in the clinical assessment of OIH. (C) 2009 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
C1 [Chen, Lucy; Malarick, Charlene; Seefeld, Lindsey; Wang, Shuxing; Houghton, Mary; Mao, Jianren] Harvard Univ, Sch Med,Dept Anesthesia & Crit Care, Massachusetts Gen Hosp, MGH Ctr Translat Pain Res, Boston, MA 02114 USA.
RP Mao, JR (reprint author), Harvard Univ, Sch Med,Dept Anesthesia & Crit Care, Massachusetts Gen Hosp, MGH Ctr Translat Pain Res, Boston, MA 02114 USA.
EM jmao@partners.org
FU NIH [DA22576]
FX This Study is supported by NIH RO1 Grant DA22576 (J.M.). We would like
to thank Drs. James Rathmell, Gary Brenner, Milan Stojanovic, Shihab
Ahmed, Padma Gulur, and Gary Polykoff and Tina Toland, B.A., M.H.A. of
the Massachusetts General Hospital Center for Pain Medicine for their
help in the Subject recruitment.
NR 39
TC 65
Z9 66
U1 0
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0304-3959
J9 PAIN
JI Pain
PD MAY
PY 2009
VL 143
IS 1-2
BP 65
EP 70
DI 10.1016/j.pain.2009.01.022
PG 6
WC Anesthesiology; Clinical Neurology; Neurosciences
SC Anesthesiology; Neurosciences & Neurology
GA 441PH
UT WOS:000265780600012
PM 19237249
ER
PT J
AU Morone, NE
Karp, JF
Lynch, CS
Bost, JE
El Khoudary, SR
Weiner, DK
AF Morone, Natalia E.
Karp, Jordan F.
Lynch, Cheryl S.
Bost, James E.
El Khoudary, Samar R.
Weiner, Debra K.
TI Impact of Chronic Musculoskeletal Pathology on Older Adults: A Study of
Differences between Knee OA and Low Back Pain
SO PAIN MEDICINE
LA English
DT Article
DE Low Back Pain; Knee Pain; Physical Function; Psychosocial Factors
ID PHYSICAL PERFORMANCE BATTERY; LOWER-EXTREMITY FUNCTION; SELF-RATED
HEALTH; GAIT SPEED; PSYCHOLOGICAL-FACTORS; BODY-COMPOSITION; EFFICACY;
DISABILITY; DEPRESSION; COMMUNITY
AB The study aimed to compare the psychological and physical characteristics of older adults with knee osteoarthritis (OA) vs those of adults with chronic low back pain (CLBP) and to identify psychological and physical predictors of function as measured by gait speed.
Secondary data analysis.
Eighty-eight older adults with advanced knee OA and 200 with CLBP who had participated in separate randomized controlled trials were selected for this study.
Inclusion criteria for both trials included age >= 65 and pain of at least moderate intensity that occurred daily or almost every day for at least the previous 3 months. Psychological constructs (catastrophizing, fear avoidance, self-efficacy, depression, affective distress) and physical measures (comorbid medical conditions, pain duration, pain severity, pain related interference, self-rated health) were obtained.
Subjects with CLBP had slower gait (0.88 m/s vs 0.96 m/s, P = 0.002) and more comorbid conditions than subjects with knee pain (mean 3.36 vs 1.97, P < 0.001). All the psychological measures were significantly worse in the CLBP group except the Multidimensional Pain Inventory-Affective Distress score. Self-efficacy, pain severity, and medical comorbidity burden were associated with slower gait regardless of the location of the pain.
Older adults with chronic pain may have distinct psychological and physical profiles that differentially impact gait speed. These findings suggest that not all pain conditions are the same in their psychological and physical characteristics and may need to be taken into consideration when developing treatment plans.
C1 [Morone, Natalia E.; Lynch, Cheryl S.; Bost, James E.; El Khoudary, Samar R.] Univ Pittsburgh, Dept Med, Div Gen Internal Med, Pittsburgh, PA USA.
[Karp, Jordan F.] Univ Pittsburgh, Dept Psychiat, Div Geriatr Med, Pittsburgh, PA USA.
[Karp, Jordan F.; Weiner, Debra K.] Univ Pittsburgh, Dept Anesthesiol, Div Geriatr Med, Pittsburgh, PA USA.
[Lynch, Cheryl S.; Weiner, Debra K.] Univ Pittsburgh, Dept Med, Div Geriatr Med, Pittsburgh, PA USA.
[El Khoudary, Samar R.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA.
[Weiner, Debra K.] VA Pittsburgh Healthcare Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA.
RP Morone, NE (reprint author), 230 McKee Pl,Suite 600, Pittsburgh, PA 15213 USA.
EM moronene@upmc.edu
OI El Khoudary Abushaban, Samar/0000-0003-2913-0821
FU National Center for Complementary and Alternative Medicine [R01AG018299,
R21AG24288]; National Institute on Aging, National Institutes of Health;
NIH Roadmap Multidisciplinary Clinical Research Career Development Award
[1KL2RR024154-03, UL1RR024153, AG 021885-05]; National Center for
Research Resources (NCRR)
FX This research was supported by research grants (R01AG018299, R21AG24288)
from the National Center for Complementary and Alternative Medicine and
the National Institute on Aging, National Institutes of Health. During
the time of this work, Drs. Morone and Karp were funded by the NIH
Roadmap Multidisciplinary Clinical Research Career Development Award
Grant (1KL2RR024154-03) from the NIH. This publication was also made
possible by Grant Number UL1RR024153 from the National Center for
Research Resources (NCRR), a component of the NIH and NIH Roadmap for
Medical Research. Its contents are solely the responsibility of the
authors and do not necessarily represent the official view of NCRR or
NIH. Dr. Lynch was supported by grant T32 AG 021885-05 from the NIH.
NR 41
TC 18
Z9 18
U1 1
U2 2
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1526-2375
J9 PAIN MED
JI Pain Med.
PD MAY-JUN
PY 2009
VL 10
IS 4
BP 693
EP 701
DI 10.1111/j.1526-4637.2009.00565.x
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 454JQ
UT WOS:000266678600014
PM 19254337
ER
PT J
AU Manchikanti, L
Derby, R
Wolfer, L
Singh, V
Datta, S
Hirsch, JA
AF Manchikanti, Laxmaiah
Derby, Richard
Wolfer, Lee
Singh, Vijay
Datta, Sukdeb
Hirsch, Joshua A.
TI Evidence-Based Medicine, Systematic Reviews, and Guidelines in
Interventional Pain Management: Part 5. Diagnostic Accuracy Studies
SO PAIN PHYSICIAN
LA English
DT Review
DE Evidence-based medicine; diagnostic studies; systematic reviews;
randomized trials; interventional pain management; standards for the
reporting of diagnostic accuracy studies (STARD)
ID LOW-BACK-PAIN; CAUDAL EPIDURAL INJECTIONS; ZYGAPOPHYSIAL JOINT PAIN;
RANDOMIZED CONTROLLED-TRIALS; MEDIAL BRANCH BLOCKS; CHRONIC SPINAL PAIN;
LOCAL-ANESTHETIC BLOCKS; OPERATING CHARACTERISTIC CURVES;
PRESSURE-CONTROLLED DISCOGRAPHY; PERIPHERAL ARTERIAL-DISEASE
AB Diagnosis is a critical component of health care. The world of diagnostic tests is highly dynamic. New tests are developed at a fast pace and technology of existing tests is continuously being improved. However, clinicians, policy makers, and patients routinely face a range of questions regarding diagnostic tests. Well designed diagnostic test accuracy studies can help in making these decisions, provided that they transparently and fully report their participants, tests, methods, and results (as facilitated). For example, by the standards for the reporting of diagnostic accuracy studies (STARD) statement.
Exaggerated and biased results from poorly designed and reported diagnostic test studies can trigger their premature dissemination and lead physicians into making in a diagnostic test is useful only to the extent that it correct treatment decisions. Thus, distinguishes between conditions or disorders that might otherwise be confused. While almost any test can differentiate healthy persons from severely affected ones, appropriate diagnostic tests should differentiate mild and moderate forms of disease.
Shortcomings in a study design and interpretation can affect estimates of diagnostic accuracy. Thus, quality diagnostic studies are essential in medicine in general and interventional pain management in particular. The STARD initiative was developed to improve the accuracy and completeness in the reporting of studies of diagnostic accuracy and provide guidance to assist in reducing the potential for bias in the study and to evaluate a study's generalizability.
In the practice of interventional pain management, in addition to diagnostic tests which include laboratory tests, imaging tests, and physical examination, diagnostic interventional techniques are crucial. Interventional techniques as a diagnostic tool in painful conditions is important due to multiple challenging clinical situations, which include the purely subjective nature of pain and underdetermined and uncertain pathophysiology in most painful spinal conditions. Precision diagnostic blocks are used to clarify these challenging clinical situations in order to determine the pathophysiology of clinical pain, the site of nociception, and the pathway of afferent neural signals.
Part 5 of evidence-based medicine (EBM) in interventional pain management describes the various aspects of diagnostic accuracy studies.
C1 [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY USA.
[Derby, Richard; Wolfer, Lee] Spinal Diagnost & Treatment Ctr, Daly City, CA USA.
[Singh, Vijay] Pain Diagnost Associates, Niagara, WI USA.
[Datta, Sukdeb] Vanderbilt Univ, Med Ctr, Nashville, TN USA.
[Hirsch, Joshua A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Hirsch, Joshua A.] Harvard Univ, Sch Med, Boston, MA USA.
RP Manchikanti, L (reprint author), 2831 Lone Oak Rd, Paducah, KY 42003 USA.
EM drlm@thepainmd.com
NR 234
TC 47
Z9 47
U1 0
U2 5
PU AM SOC INTERVENTIONAL PAIN PHYSICIANS
PI PADUCAH
PA 81 LAKEVIEW DR, PADUCAH, KY 42001 USA
SN 1533-3159
J9 PAIN PHYSICIAN
JI Pain Physician
PD MAY-JUN
PY 2009
VL 12
IS 3
BP 517
EP 540
PG 24
WC Anesthesiology; Clinical Neurology
SC Anesthesiology; Neurosciences & Neurology
GA 455NF
UT WOS:000266766800007
PM 19461821
ER
PT J
AU Manchikanti, L
Derby, R
Benyamin, RM
Helm, S
Hirsch, JA
AF Manchikanti, Laxmaiah
Derby, Richard
Benyamin, Ramsin M.
Helm, Standiford
Hirsch, Joshua A.
TI A Systematic Review of Mechanical Lumbar Disc Decompression with
Nucleoplasty
SO PAIN PHYSICIAN
LA English
DT Review
DE Intervertebral disc disease; chronic low back pain; disc herniation;
disc protrusion; radiculitis; contained disc herniation; mechanical disc
decompression; nucleoplasty; coblation technology; nucleotomy
ID LOW-BACK-PAIN; CAUDAL EPIDURAL INJECTIONS; EVIDENCE-BASED MEDICINE;
FACET JOINT INTERVENTIONS; BLIND CONTROLLED-TRIAL; MANAGING CHRONIC
PAIN; MEDIAL BRANCH BLOCKS; EQUIVALENCE TRIAL; SURGERY SYNDROME;
FOLLOW-UP
AB Background: Lumbar disc prolapse, protrusion, or extrusion account for less than 5% of all low problems but are the most common causes of nerve root pain and surgical interventions., The primary rationale for any form of surgery for disc prolapse is to relieve nerve root irritation or compression due to herniated disc material. The primary modality of treatment continues to be either open or microdiscectomy, but several alternative techniques including nucleoplasty, automated percutaneous discectomy, and laser discectomy have been described. There is a paucity of evidence for all decompression techniques, specifically alternative techniques including nucleoplasty.
Study Design: A systematic review of the literature.
Objective: To determine the effectiveness of mechanical lumbar disc decompression with nucleoplasty.
Methods: A comprehensive evaluation of the literature relating to mechanical lumbar disc decompression with nucleoplasty was performed. The literature was evaluated according to Cochrane review criteria for randomized controlled trials (RCTs), and Agency for Healthcare Research and Quality (AHRQ) criteria was utilized for observational studies. The level of evidence was classified as Level I, II, or III with 3 subcategories in Level II based on the quality of evidence developed by the United States Preventive Services Task Force (USPSTF). A literature search was conducted using only English language literature through PubMed, EMBASE, the Cochrane library, systematic reviews, and cross-references from reviews and systematic reviews.
Outcome Measures: Pain relief was the primary outcome measure. Other outcome measures were functional improvement, improvement of psychological status, opioid intake, and return to work. Short-term effectiveness was defined as one year or less, whereas, long-term effectiveness was defined as greater than one year.
Results: Based on USPSTF criteria the level of evidence for nucleoplasty is Level II-3 in managing predominantly lower extremity pain due to contained disc herniation.
Limitations: Paucity of literature, both observational and randomized.
Conclusion: This systematic review illustrates Level II-3 evidence for mechanical lumbar percutaneous disc decompression with nucleoplasty in treatment of leg pain. However, there is no evidence available in managing axial low back pain.
C1 [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY USA.
[Derby, Richard] Spinal Diagnost & Treatment Ctr, Daly City, CA USA.
[Benyamin, Ramsin M.] Millennium Pain Ctr, Bloomington, IL USA.
[Helm, Standiford] Pacific Coast Pain Management Ctr, Laguna Hills, CA USA.
[Hirsch, Joshua A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Hirsch, Joshua A.] Harvard Univ, Sch Med, Boston, MA USA.
RP Manchikanti, L (reprint author), 2831 Lone Oak Rd, Paducah, KY 42003 USA.
EM drlm@thepainmd.com
NR 81
TC 56
Z9 59
U1 0
U2 4
PU AM SOC INTERVENTIONAL PAIN PHYSICIANS
PI PADUCAH
PA 81 LAKEVIEW DR, PADUCAH, KY 42001 USA
SN 1533-3159
J9 PAIN PHYSICIAN
JI Pain Physician
PD MAY-JUN
PY 2009
VL 12
IS 3
BP 561
EP 572
PG 12
WC Anesthesiology; Clinical Neurology
SC Anesthesiology; Neurosciences & Neurology
GA 455NF
UT WOS:000266766800009
PM 19461823
ER
PT J
AU Singh, V
Manchikanti, L
Benyamin, RM
Helm, S
Hirsch, JA
AF Singh, Vijay
Manchikanti, Laxmaiah
Benyamin, Ramsin M.
Helm, Standiford
Hirsch, Joshua A.
TI Percutaneous Lumbar Laser Disc Decompression: A Systematic Review of
Current Evidence
SO PAIN PHYSICIAN
LA English
DT Review
DE Intervertebral disc disease; chronic low back pain; disc herniation;
disc protrusion; radiculitis; contained disc herniation; mechanical disc
decompression; percutaneous lumbar laser discectomy; laser assisted
spinal endoscopy
ID LOW-BACK-PAIN; CAUDAL EPIDURAL INJECTIONS; EVIDENCE-BASED MEDICINE;
FACET JOINT INTERVENTIONS; BLIND CONTROLLED-TRIAL; MANAGING CHRONIC
PAIN; MEDIAL BRANCH BLOCKS; FOLLOW-UP; EQUIVALENCE TRIAL; SURGERY
SYNDROME
AB Background: Since the descriptions by Mixter and Barr of open surgical treatment for rupture of the intervertebral disc in 1934, open surgical procedures have become a common practice. Disc herniations have been reported as being contained and non-contained. The results of open surgical discectomy for contained disc herniation have been poor. Consequently, several alternative techniques have been developed which are minimally invasive including percutaneous laser disc decompression.
Study Design: A systematic review of the literature.
Objective: The objective of this systematic review is to evaluate the clinical effectiveness of percutaneous laser discectomy in managing radicular pain secondary to contained disc herniation.
Methods: A comprehensive evaluation of the literature relating to mechanical disc decompression was performed. The literature was evaluated according to Cochrane review criteria for randomized controlled trials (RCTs), and Agency for Healthcare Research and Quality (AHRQ) criteria was utilized for observational studies.
A literature search was conducted by using only the English language literature through PubMed, EMBASE, the Cochrane library, systematic reviews, and cross references from reviews and systematic reviews.
The level of evidence was classified as Level I, II, or III with 3 subcategories in Level II based on the quality of evidence developed by the United States Preventive Services Task Force (USPSTF).
Outcome Measures: Pain relief was the primary outcome measure. Other outcome measures were functional improvement, improvement of psychological status, opioid intake, and return to work.
Short-term effectiveness was defined as one year or less, whereas, long-term effectiveness was defined as greater than one year.
Results: Based on USPSTF criteria the indicated level of evidence for percutaneous lumbar laser discectomy (PLLD) is II-2 for short- and long-term relief.
Limitations: Even though laser discectomy has been in utilization for a number of years and numerous procedures have been performed there continues to be a paucity of literature of randomized clinical trials.
Conclusion: This systematic review illustrates Level II-2 evidence for percutaneous laser disc decompression which is equivalent to automated percutaneous lumbar disc decompression.
C1 [Singh, Vijay] Pain Diagnost Associates, Niagara, WI USA.
[Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY USA.
[Benyamin, Ramsin M.] Millennium Pain Ctr, Bloomington, IL USA.
[Helm, Standiford] Pacific Coast Pain Management Ctr, Laguna Hills, CA USA.
[Hirsch, Joshua A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Hirsch, Joshua A.] Harvard Univ, Sch Med, Boston, MA USA.
RP Singh, V (reprint author), W8090 Millie Hill Estates Dr, Iron Mt, MI 49801 USA.
EM vj@wmpnet.net
NR 97
TC 60
Z9 67
U1 1
U2 3
PU AM SOC INTERVENTIONAL PAIN PHYSICIANS
PI PADUCAH
PA 81 LAKEVIEW DR, PADUCAH, KY 42001 USA
SN 1533-3159
J9 PAIN PHYSICIAN
JI Pain Physician
PD MAY-JUN
PY 2009
VL 12
IS 3
BP 573
EP 588
PG 16
WC Anesthesiology; Clinical Neurology
SC Anesthesiology; Neurosciences & Neurology
GA 455NF
UT WOS:000266766800010
PM 19461824
ER
PT J
AU Hirsch, JA
Singh, V
Falco, FJE
Benyamin, RM
Manchikanti, L
AF Hirsch, Joshua A.
Singh, Vijay
Falco, Frank J. E.
Benyamin, Ramsin M.
Manchikanti, Laxmaiah
TI Automated Percutaneous Lumbar Discectomy for the Contained Herniated
Lumbar Disc: A Systematic Assessment of Evidence
SO PAIN PHYSICIAN
LA English
DT Review
DE Intervertebral disc disease; chronic low back pain; mechanical disc
decompression; automated percutaneous lumbar discectomy; internal disc
disruption; radiculitis
ID LOW-BACK-PAIN; CAUDAL EPIDURAL INJECTIONS; EVIDENCE-BASED MEDICINE;
FACET JOINT INTERVENTIONS; BLIND CONTROLLED-TRIAL; MEDIAL BRANCH BLOCKS;
TERM FOLLOW-UP; SURGERY SYNDROME; EQUIVALENCE TRIAL; CLINICAL-TRIAL
AB Background: Lumbar disc prolapse, protrusion, and extrusion account for less than 5% of all low back problems, but are the most common causes of nerve root pain and surgical interventions. The typical rationale for traditional surgery is an effort to provide more rapid relief of pain and disability. It should be noted that the majority of patients will recover with conservative management. The primary rationale for any form of surgery for disc prolapse associated with radicular pain is to relieve nerve root irritation or compression due to herniated disc material. The primary modality of treatment continues to be either open or microdiscectomy, but several alternative techniques including automated percutaneous lumbar discectomy (APLD) have been described. However, there is a paucity of evidence for all decompression techniques, specifically alternative techniques including automated and laser discectomy.
Study Design: A systematic review of the literature.
Objective: To determine the effectiveness of APLD.
Methods: A comprehensive evaluation of the literature relating to automated lumbar disc decompression was performed. The literature was evaluated according to Cochrane review criteria for randomized controlled trials (RCTs), and Agency for Healthcare Research and Quality (AHRQ) criteria was utilized for observational studies.
A literature search was conducted of English language literature through PubMed, EMBASE, the Cochrane library, systematic reviews, and cross references from reviews and systematic reviews.
The level of evidence was classified as Level I, II, or III with 3 subcategories in Level II based on the quality of evidence developed by the United States Preventive Services Task Force (USPSTF).
Outcome Measures: Pain relief was the primary outcome measure. Other outcome measures were functional improvement, improvement of psychological status, opioid intake, and return to work.
Short-term effectiveness was defined as one-year or less, whereas, long-term effectiveness was defined as greater than one-year.
Results: Based on USPSTF criteria, the indicated evidence for APLD is Level II-2 for short- and long-term relief.
Limitations: Paucity of RCTs in the literature.
Conclusion: This systematic review indicated Level II-2 evidence for APLD. APLD may provide appropriate relief in properly selected patients with contained lumbar disc prolapse.
C1 [Hirsch, Joshua A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Hirsch, Joshua A.] Harvard Univ, Sch Med, Boston, MA USA.
[Singh, Vijay] Pain Diagnost Associates, Niagara, WI USA.
[Falco, Frank J. E.] Mid Atlantic Spine & Pain Physicians, Newark, DE USA.
[Benyamin, Ramsin M.] Millennium Pain Ctr, Bloomington, IL USA.
[Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY USA.
RP Hirsch, JA (reprint author), Massachusetts Gen Hosp, 55 Blossom St,Gray 289, Boston, MA 02114 USA.
EM jahirsch@partners.org
NR 143
TC 50
Z9 58
U1 3
U2 9
PU AM SOC INTERVENTIONAL PAIN PHYSICIANS
PI PADUCAH
PA 81 LAKEVIEW DR, PADUCAH, KY 42001 USA
SN 1533-3159
J9 PAIN PHYSICIAN
JI Pain Physician
PD MAY-JUN
PY 2009
VL 12
IS 3
BP 601
EP 620
PG 20
WC Anesthesiology; Clinical Neurology
SC Anesthesiology; Neurosciences & Neurology
GA 455NF
UT WOS:000266766800012
PM 19461826
ER
PT J
AU Fox, SA
Heritage, J
Stockdale, SE
Asch, SM
Duan, NH
Reise, SP
AF Fox, Sarah A.
Heritage, John
Stockdale, Susan E.
Asch, Steven M.
Duan, Naihua
Reise, Steven P.
TI Cancer screening adherence: Does physician-patient communication matter?
SO PATIENT EDUCATION AND COUNSELING
LA English
DT Article
DE Physician/patient communication; Cancer screening; Patient adherence
ID COLORECTAL-CANCER; HEALTH COMMUNICATION; MEDICAL VISITS; UNITED-STATES;
SELF-REPORTS; CARE; WOMEN; DISPARITIES; POPULATION; VALIDITY
AB Objective: The objective of this study was to examine the separate contributions of patients and physicians to their communication regarding cancer screening.
Methods: Research design and subjects: The authors conducted a cross-sectional analysis of survey data collected from 63 community-based primary care physicians and 904 of their female patients in Los Angeles.
Results: Patients who perceived their physicians to be enthusiastic (at any level) in their discussions of mammography or fecal occult blood tests (FOBT) were significantly more likely to report a recent test than patients who reported no discussions.
Conclusion: Physician discussions of cancer screening are important and effective even when, as in the case of mammography, screening rates are already high, or. as in the case of FOBT. rates have tended to remain low. The value of communication about screening should be taught and promoted to primary care physicians who serve as gatekeepers to screening.
Practice implications: Those who train physicians in communication skills should take into account our finding that the communication style of physicians (e.g., enthusiasm for screening) was the only patient or physician variable that both influenced screening adherence and that could be taught. (C) 2009 Published by Elsevier Ireland Ltd.
C1 [Fox, Sarah A.; Asch, Steven M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA.
[Heritage, John] Univ Calif Los Angeles, Dept Sociol, Los Angeles, CA 90095 USA.
[Stockdale, Susan E.] Univ Calif Los Angeles, Inst Neuropsychiat, Hlth Serv Res Ctr, Los Angeles, CA 90095 USA.
[Duan, Naihua] Columbia Univ, New York State Psychiat Inst, Div Biostat, Dept Psychiat & Biostat, New York, NY 10032 USA.
[Reise, Steven P.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA.
RP Fox, SA (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, VA Greater Los Angeles Healthcare Syst, Box 951736,911 Broxton, Los Angeles, CA 90095 USA.
EM s.fox@ucla.edu
FU National institutes of Health, National Cancer Institute [1 R01 CA61249]
FX This work was supported by National institutes of Health, National
Cancer Institute, Award No. 1 R01 CA61249 (SAF). The authors would like
to acknowledge the extensive editing of the original draft by Jeanette
Chung, PhD, American Medical Association, Chicago.
NR 33
TC 22
Z9 22
U1 3
U2 8
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0738-3991
J9 PATIENT EDUC COUNS
JI Patient Educ. Couns.
PD MAY
PY 2009
VL 75
IS 2
BP 178
EP 184
DI 10.1016/j.pec.2008.09.010
PG 7
WC Public, Environmental & Occupational Health; Social Sciences,
Interdisciplinary
SC Public, Environmental & Occupational Health; Social Sciences - Other
Topics
GA 437FH
UT WOS:000265471500007
PM 19250793
ER
PT J
AU Yan, BP
Rosenfield, K
Garasic, JM
de Moor, M
AF Yan, Bryan P.
Rosenfield, Kenneth
Garasic, Joseph M.
de Moor, Michael
TI Carotid Artery Stent Migration in a Child with Williams Syndrome
SO PEDIATRIC CARDIOLOGY
LA English
DT Editorial Material
DE Williams syndrome; Carotid artery stent
ID STENOSES
AB We report a case of distal migration of a stent from the brachiocephalic artery to the distal right common carotid artery 7 months after implantation in a 5-year-old child with Williams syndrome. There were no neurological sequelae and the migrated stent remained widely patent 5 years following implantation.
C1 [de Moor, Michael] MassGen Hosp Children, Div Pediat Cardiol, Boston, MA 02114 USA.
[Yan, Bryan P.; Rosenfield, Kenneth; Garasic, Joseph M.] Massachusetts Gen Hosp, Div Cardiol, Sect Vasc Med, Boston, MA 02114 USA.
[Yan, Bryan P.; Rosenfield, Kenneth; Garasic, Joseph M.; de Moor, Michael] Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP de Moor, M (reprint author), MassGen Hosp Children, Div Pediat Cardiol, Boston, MA 02114 USA.
EM mdemoor@partners.org
RI Yan, Bryan/P-5928-2015
NR 3
TC 0
Z9 0
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0172-0643
J9 PEDIATR CARDIOL
JI Pediatr. Cardiol.
PD MAY
PY 2009
VL 30
IS 4
BP 551
EP 552
DI 10.1007/s00246-009-9400-y
PG 2
WC Cardiac & Cardiovascular Systems; Pediatrics
SC Cardiovascular System & Cardiology; Pediatrics
GA 447BW
UT WOS:000266167600032
PM 19294459
ER
PT J
AU Melendez, E
Bachur, R
AF Melendez, Elliot
Bachur, Richard
TI Serious Adverse Events During Procedural Sedation With Ketamine
SO PEDIATRIC EMERGENCY CARE
LA English
DT Article
DE ketamine; laryngospasm; adverse event; procedural sedation; conscious
sedation
ID DEPARTMENT SAFETY PROFILE; EMERGENCY-DEPARTMENT; INTRAMUSCULAR KETAMINE;
DISSOCIATIVE SEDATION; INTRAVENOUS KETAMINE; PEDIATRIC SEDATION; PAINFUL
PROCEDURES; CHILDREN; MIDAZOLAM; CARE
AB Objectives: Compare the frequency of respiratory adverse events between patients who received intramuscular (IM) versus intravenous ketamine.
Methods: Case control study from 1997 to 2005 at a large urban pediatric emergency department. Adverse events were defined as apnea, hypoxemia (oximetry <93%), hypoventilation, laryngospasm, and other upper airway obstruction. Serious adverse events were defined by the level of intervention and included those cases that required positive pressure ventilation, insertion of oral or nasal airway, or endotracheal intubation. Minor adverse events were respiratory events requiring minimal intervention (stimulation, supplemental 02, airway repositioning). Controls (2: 1) were selected by the next chronological patient in the data set who received ketamine but had no respiratory adverse event.
Results: Four thousand two hundred fifty-two patients received ketamine; 102 cases (2.4%) had respiratory adverse events, including 38 patients with severe adverse events (0.9%). Interventions for the cases included supplemental 02 (59/102, 58%), airway repositioning (36/102, 35%), continuous positive airway pressure (7/102, 7%), positive pressure ventilation (33/102, 32%), nasal airway (2/102, 2%), oral airway (1/102, 1%), stimulation (11/102, 11%), and intubation (1/102, 1%). Overall, 33% of all subjects received IM ketamine including 47% of cases and 27% of controls. Intramuscular IM ketamine was associated with increased likelihood of adverse events (odds ratio [OR] 2.1, 95% Cl, 1.3-3). Twenty (69%) of the 29 patients with laryngospasm received IM ketamine (OR, 5.2; 95% CI, 2.3-11.9) and 20 (53%) of the 38 patients who had severe events were administered IM (OR, 2.4; 95% Cl, 1.2-4.9). Use of pre-sedation morphine or combined administration with midazolam and/or atropine was not associated with adverse events. Specific procedures were not associated with increased adverse events.
Conclusions: Respiratory adverse events with ketamine are uncommon. Serious events, like laryngospasm, are rare but occur more commonly with IM administration. This increased risk associated with IM administration should be considered in the sedation plan.
C1 [Melendez, Elliot] Massachusetts Gen Hosp, Div Pediat Crit Care, Dept Pediat, Boston, MA 02114 USA.
[Melendez, Elliot; Bachur, Richard] Childrens Hosp, Dept Med, Div Emergency Med, Boston, MA 02115 USA.
RP Melendez, E (reprint author), Massachusetts Gen Hosp, Div Pediat Crit Care, Dept Pediat, 175 Cambridge St,5th Floor, Boston, MA 02114 USA.
EM elliot.melendez@childrens.harvard.edu
OI Bachur, Richard/0000-0001-8831-014X
NR 17
TC 33
Z9 33
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0749-5161
J9 PEDIATR EMERG CARE
JI Pediatr. Emerg. Care
PD MAY
PY 2009
VL 25
IS 5
BP 325
EP 328
PG 4
WC Emergency Medicine; Pediatrics
SC Emergency Medicine; Pediatrics
GA 445VG
UT WOS:000266079000007
PM 19404223
ER
PT J
AU Pieretti-Vanmarcke, R
Pieretti, A
Pieretti, RV
AF Pieretti-Vanmarcke, Rafael
Pieretti, Alberto
Pieretti, Rafael V.
TI Megacalycosis: a rare condition
SO PEDIATRIC NEPHROLOGY
LA English
DT Article
DE Megacalycosis; Hydronephrosis; Ultrasound; Intravenous; Pyelogram;
Diuretic renogram
ID CONGENITAL MEGACALYCOSIS; ASSOCIATION
AB Megacalycosis is an extremely rare condition. We report our experience with two cases and discuss its pathogenesis, diagnosis and management in children. Our two patients had presented a prior diagnosis of congenital hydronephrosis. An increased number of calyces with a significant disproportion between the degree of calyceal dilatation and a mildly dilated renal pelvis were found in each case. Megacalycosis must be considered in the differential diagnosis of congenital hydronephrosis, polycalycosis, and infundibular stenosis. The diagnosis is suggested by ultrasound and confirmed by diuretic renography, intravenous pyelography or magnetic resonance urography. Voiding cystourethrography should be performed to rule out vesicoureteral reflux. A high index of suspicion is needed for the diagnosis of this condition.
C1 [Pieretti, Rafael V.] Massachusetts Gen Hosp Children, Sect Pediat Urol, Dept Pediat Surg, Boston, MA 02114 USA.
[Pieretti-Vanmarcke, Rafael] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA USA.
[Pieretti, Alberto] Cent Univ Venezuela, Caracas, Venezuela.
RP Pieretti, RV (reprint author), Massachusetts Gen Hosp Children, Sect Pediat Urol, Dept Pediat Surg, Warren 1157, Boston, MA 02114 USA.
EM rpieretti@partners.org
NR 7
TC 3
Z9 3
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0931-041X
J9 PEDIATR NEPHROL
JI Pediatr. Nephrol.
PD MAY
PY 2009
VL 24
IS 5
BP 1077
EP 1079
DI 10.1007/s00467-008-1039-z
PG 3
WC Pediatrics; Urology & Nephrology
SC Pediatrics; Urology & Nephrology
GA 423ZQ
UT WOS:000264535700021
PM 19002724
ER
PT J
AU Moore, MA
Wallace, EC
Westra, SJ
AF Moore, Michael A.
Wallace, E. Christine
Westra, Sjirk J.
TI The imaging of paediatric thoracic trauma
SO PEDIATRIC RADIOLOGY
LA English
DT Review
DE Chest; Trauma; Multidetector CT; Children
ID BLUNT CHEST TRAUMA; COMPUTED-TOMOGRAPHY; BRONCHIAL RUPTURE; AORTIC
INJURIES; DOSE REDUCTION; LUNG CONTUSION; DIAPHRAGMATIC RUPTURE;
DIAGNOSTIC-RADIOLOGY; OCCULT PNEUMOTHORAX; PULMONARY CONTUSION
AB Major chest trauma in a child is associated with significant morbidity and mortality. It is most frequently encountered within the context of multisystem injury following high-energy trauma such as a motor vehicle accident. The anatomic-physiologic make-up of children is such that the pattern of ensuing injuries differs from that in their adult counterparts. Pulmonary contusion, pneumothorax, haemothorax and rib fractures are most commonly encountered. Although clinically more serious and potentially life threatening, tracheobronchial tear, aortic rupture and cardiac injuries are seldom observed. The most appropriate imaging algorithm is one tailored to the individual child and is guided by the nature of the traumatic event as well as clinical parameters. Chest radiography remains the first and most important imaging tool in paediatric chest trauma and should be supplemented with US and CT as indicated. Multidetector CT allows for the accurate diagnosis of most traumatic injuries, but should be only used in selected cases as its routine use in all paediatric patients would result in an unacceptably high radiation exposure to a large number of patients without proven clinical benefit. When CT is used, appropriate modifications should be incorporated so as to minimize the radiation dose to the patient whilst preserving diagnostic integrity.
C1 [Moore, Michael A.; Westra, Sjirk J.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Wallace, E. Christine] UMass Mem Med Ctr, Dept Radiol, Worcester, MA USA.
[Wallace, E. Christine] Univ Massachusetts, Sch Med, Worcester, MA USA.
[Moore, Michael A.; Westra, Sjirk J.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Westra, SJ (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA.
EM swestra@partners.org
NR 78
TC 20
Z9 20
U1 0
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0301-0449
J9 PEDIATR RADIOL
JI Pediatr. Radiol.
PD MAY
PY 2009
VL 39
IS 5
BP 485
EP 496
DI 10.1007/s00247-008-1093-5
PG 12
WC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging
SC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging
GA 423ZS
UT WOS:000264535900008
PM 19151969
ER
PT J
AU Barrett, LF
AF Barrett, Lisa Feldman
TI Understanding the Mind by Measuring the Brain: Lessons From Measuring
Behavior (Commentary on Vul et al., 2009)
SO PERSPECTIVES ON PSYCHOLOGICAL SCIENCE
LA English
DT Article
ID CONSTRUCTION; MODEL
AB Throughout the history of psychology, the path of transforming the physical (muscle movements, verbal behavior, or physiological changes) into the mental has been fraught with difficulty. Over the decades, psychologists have risen to the challenge and learned a few things about how to infer the mental from measuring the physical. The Vul, Harris, Winkielman, and Pashler article (2009, this issue) points out that some of these lessons could be helpful to those of us who measure blood flow in the brain in a quest to understand the mind. Three lessons from psychometrics are discussed.
C1 [Barrett, Lisa Feldman] Massachusetts Gen Hosp, Boston Coll, Dept Psychol, Chestnut Hill, MA 02467 USA.
[Barrett, Lisa Feldman] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
RP Barrett, LF (reprint author), Massachusetts Gen Hosp, Boston Coll, Dept Psychol, Chestnut Hill, MA 02467 USA.
EM barretli@bc.edu
FU NIA NIH HHS [R01 AG030311, R01 AG030311-03]; NIH HHS [DP1 OD003312, DP1
OD003312-02]
NR 10
TC 7
Z9 7
U1 13
U2 16
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1745-6916
J9 PERSPECT PSYCHOL SCI
JI Perspect. Psychol. Sci.
PD MAY
PY 2009
VL 4
IS 3
BP 314
EP 318
DI 10.1111/j.1745-6924.2009.01131.x
PG 5
WC Psychology, Multidisciplinary
SC Psychology
GA 445EA
UT WOS:000266031300012
PM 19672318
ER
PT J
AU Cristian, A
Greenwald, BD
AF Cristian, Adrian
Greenwald, Brian D.
TI Fatigue Preface
SO PHYSICAL MEDICINE AND REHABILITATION CLINICS OF NORTH AMERICA
LA English
DT Editorial Material
C1 [Cristian, Adrian] James J Peters Vet Affairs Med Ctr, Dept Rehabil Med, Bronx, NY 10468 USA.
[Cristian, Adrian] Mt Sinai Sch Med, Dept Rehabil Med, New York, NY USA.
[Greenwald, Brian D.] Mt Sinai Med Ctr, Dept Rehabil Med, New York, NY 10029 USA.
RP Cristian, A (reprint author), James J Peters Vet Affairs Med Ctr, Dept Rehabil Med, 3d-22,130 W Kingsbridge Rd, Bronx, NY 10468 USA.
EM acristianmd@msn.com; brian.greenwald@mountsinai.org
NR 1
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 1047-9651
J9 PHYS MED REHABIL CLI
JI Phys. Med. Rehabil. Clin. N. Am.
PD MAY
PY 2009
VL 20
IS 2
BP XI
EP XII
DI 10.1016/j.pmr.2009.02.001
PG 2
WC Rehabilitation
SC Rehabilitation
GA 450KC
UT WOS:000266398400002
PM 19389612
ER
PT J
AU Kalapatapu, RK
Cristian, A
AF Kalapatapu, Raj K.
Cristian, Adrian
TI Assessment of Fatigue in Adults with Disabilities
SO PHYSICAL MEDICINE AND REHABILITATION CLINICS OF NORTH AMERICA
LA English
DT Article
DE Fatigue; Etiology; Adult; Rating scale; Assessment
ID TRAUMATIC BRAIN-INJURY; CANCER-RELATED FATIGUE; FIBROMYALGIA IMPACT
QUESTIONNAIRE; QUALITY-OF-LIFE; 1ST 2 YEARS; PRIMARY-CARE;
MULTIPLE-SCLEROSIS; FAMILY-PRACTICE; VALIDATION; SYMPTOMS
AB Fatigue is common among patients presenting to physicians. Fatigue can lead to serious public health consequences and may be caused by a vast array of etiologies. This article reviews the assessment of fatigue from the physical medicine and rehabilitation physician's perspective. The importance of a history and physical examination is emphasized, complemented by the use of laboratory studies. Rating scales used to assess fatigue from different etiologies are discussed, and patient-friendly Internet resources about fatigue are included.
C1 [Kalapatapu, Raj K.] Mt Sinai Sch Med, New York, NY 10029 USA.
[Cristian, Adrian] Mt Sinai Sch Med, Dept Rehabil Med, James J Peters Vet Affairs Med Ctr, Bronx, NY 10468 USA.
RP Kalapatapu, RK (reprint author), Mt Sinai Sch Med, 1 Gustave L Levy Pl,Box 1230, New York, NY 10029 USA.
EM rajkumar.kalapatapu@mssm.edu
NR 67
TC 0
Z9 0
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 1047-9651
J9 PHYS MED REHABIL CLI
JI Phys. Med. Rehabil. Clin. N. Am.
PD MAY
PY 2009
VL 20
IS 2
BP 313
EP +
DI 10.1016/j.pmr.2008.12.001
PG 13
WC Rehabilitation
SC Rehabilitation
GA 450KC
UT WOS:000266398400003
PM 19389613
ER
PT J
AU Tatlidede, SH
Murphy, AD
McCormack, MC
Nguyen, JT
Eberlin, KR
Randolph, MA
Moore, FD
Austen, WG
AF Tatlidede, Soner H.
Murphy, Adrian D.
McCormack, Michael C.
Nguyen, John T.
Eberlin, Kyle R.
Randolph, Mark A.
Moore, Francis D., Jr.
Austen, William G., Jr.
TI Improved Survival of Murine Island Skin Flaps by Prevention of
Reperfusion Injury
SO PLASTIC AND RECONSTRUCTIVE SURGERY
LA English
DT Article; Proceedings Paper
CT 49th Annual Meeting of the
New-England-Society-of-Plastic-and-Reconstructive-Surgeons
CY JUN 04-07, 2008
CL Manchester, VT
SP New England Soc Plast & Reconstruct Surg
ID COMPLEMENT INHIBITORY PROTEIN; REMOTE ORGAN INJURY; C-REACTIVE PROTEIN;
SKELETAL-MUSCLE; ISCHEMIA/REPERFUSION INJURY; ISCHEMIA-REPERFUSION;
MYOCARDIAL-ISCHEMIA; NATURAL ANTIBODY; INTESTINAL ISCHEMIA/REPERFUSION;
RECEPTOR TYPE-1
AB Background: Studies have demonstrated that blocking a single specificity of self-reactive immunoglobulin M with a 12-amino acid peptide mimic of the antigen of immunoglobulin M can attenuate murine intestinal and skeletal muscle injury following ischemia and reperfusion. The aim of this study was to ascertain whether peptide (P8) had protective effects in an axial island skin flap model, where tissue loss is attributed to ischemia-reperfusion injury.
Methods: Dorsal lateral thoracic artery island skin flaps (3.5 X 1.5 cm) were elevated in 82 male C57BL/6 mice and rendered ischemic for 10 hours by placing a 7-mm microclamp on the vascular pedicle followed by 7 days of reperfusion. Group I (n = 7), the sham group, had no clamp placed. Group II (n = 21) had clamp placement but no other treatment. Thirty minutes before clamp placement, group III (n = 18) received 0.25 cc of saline intravenously, group IV (n = 18) received 25 mu g/0.25 cc P8 peptide, and group V (n = 7) received 25 mu g/0.25 cc random 12-mer peptide. Animals in group VI (n = 11) underwent two cycles of 20 minutes of ischemic preconditioning before 10 hours of ischemia. After 1 week of reperfusion, percent necrosis was measured and results were compared using analysis of variance and an unpaired t test.
Results: In animals treated with P8 peptide, flap necrosis was 14.61 +/- 2.77 percent. This represents a statistically significant, 56 percent reduction in flap necrosis compared with controls (p < 0.001). Conclusion: These data demonstrate that prevention of ischemia-reperfusion injury with P8 peptide produces a significant reduction in necrosis of treated flaps. (Plast. Reconstr. Surg. 123: 1431, 2009.)
C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, Cambridge, MA 02138 USA.
Harvard Univ, Sch Med, Brigham & Womens Hosp, Cambridge, MA 02138 USA.
RP McCormack, MC (reprint author), 15 Parkman St,Wellman Bldg,Room 629, Boston, MA 02114 USA.
EM mcmccormack@partners.org
NR 43
TC 7
Z9 10
U1 0
U2 2
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 MAY
PY 2009
VL 123
IS 5
BP 1431
EP 1439
DI 10.1097/PRS.0b013e3181a071e8
PG 9
WC Surgery
SC Surgery
GA 445QZ
UT WOS:000266067900005
PM 19407613
ER
PT J
AU Cheng, CY
Kao, WHL
Patterson, N
Tandon, A
Haiman, CA
Harris, TB
Xing, C
John, EM
Ambrosone, CB
Brancati, FL
Coresh, J
Press, MF
Parekh, RS
Klag, MJ
Meoni, LA
Hsueh, WC
Fejerman, L
Pawlikowska, L
Freedman, ML
Jandorf, LH
Bandera, EV
Ciupak, GL
Nalls, MA
Akylbekova, EL
Orwoll, ES
Leak, TS
Miljkovic, I
Li, RL
Ursin, G
Bernstein, L
Ardlie, K
Taylor, HA
Boerwinckle, E
Zmuda, JM
Henderson, BE
Wilson, JG
Reich, D
AF Cheng, Ching-Yu
Kao, W. H. Linda
Patterson, Nick
Tandon, Arti
Haiman, Christopher A.
Harris, Tamara B.
Xing, Chao
John, Esther M.
Ambrosone, Christine B.
Brancati, Frederick L.
Coresh, Josef
Press, Michael F.
Parekh, Rulan S.
Klag, Michael J.
Meoni, Lucy A.
Hsueh, Wen-Chi
Fejerman, Laura
Pawlikowska, Ludmila
Freedman, Matthew L.
Jandorf, Lina H.
Bandera, Elisa V.
Ciupak, Gregory L.
Nalls, Michael A.
Akylbekova, Ermeg L.
Orwoll, Eric S.
Leak, Tennille S.
Miljkovic, Iva
Li, Rongling
Ursin, Giske
Bernstein, Leslie
Ardlie, Kristin
Taylor, Herman A.
Boerwinckle, Eric
Zmuda, Joseph M.
Henderson, Brian E.
Wilson, James G.
Reich, David
TI Admixture Mapping of 15,280 African Americans Identifies Obesity
Susceptibility Loci on Chromosomes 5 and X
SO PLOS GENETICS
LA English
DT Article
ID GENOME-WIDE SCAN; BODY-WEIGHT; FTO GENE; CART GENE; UNITED-STATES;
DISEASE GENES; FAT MASS; ASSOCIATION; VARIANTS; RISK
AB The prevalence of obesity (body mass index (BMI) >= 30 kg/m(2)) is higher in African Americans than in European Americans, even after adjustment for socioeconomic factors, suggesting that genetic factors may explain some of the difference. To identify genetic loci influencing BMI, we carried out a pooled analysis of genome-wide admixture mapping scans in 15,280 African Americans from 14 epidemiologic studies. Samples were genotyped at a median of 1,411 ancestry-informative markers. After adjusting for age, sex, and study, BMI was analyzed both as a dichotomized (top 20% versus bottom 20%) and a continuous trait. We found that a higher percentage of European ancestry was significantly correlated with lower BMI (rho = -0.042, P = 1.6 x 10(-7)). In the dichotomized analysis, we detected two loci on chromosome X as associated with increased African ancestry: the first at Xq25 (locus-specific LOD = 5.94; genome-wide score = 3.22; case-control Z = -3.94); and the second at Xq13.1 (locus-specific LOD = 2.22; case-control Z = -4.62). Quantitative analysis identified a third locus at 5q13.3 where higher BMI was highly significantly associated with greater European ancestry (locus-specific LOD = 6.27; genome-wide score = 3.46). Further mapping studies with dense sets of markers will be necessary to identify the alleles in these regions of chromosomes X and 5 that may be associated with variation in BMI.
C1 [Cheng, Ching-Yu; Kao, W. H. Linda; Brancati, Frederick L.; Coresh, Josef; Klag, Michael J.] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA.
[Cheng, Ching-Yu] Natl Yang Ming Univ, Sch Med, Dept Ophthalmol, Taipei 112, Taiwan.
[Cheng, Ching-Yu] Taipei Vet Gen Hosp, Taipei, Taiwan.
[Kao, W. H. Linda; Brancati, Frederick L.; Coresh, Josef] Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA.
[Patterson, Nick; Tandon, Arti; Freedman, Matthew L.; Ardlie, Kristin; Reich, David] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA.
[Tandon, Arti; Reich, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA.
[Haiman, Christopher A.; Ursin, Giske; Bernstein, Leslie; Henderson, Brian E.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Harris, Tamara B.; Nalls, Michael A.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Xing, Chao] Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Dallas, TX 75390 USA.
[Xing, Chao] Univ Texas SW Med Ctr Dallas, McDermott Ctr Human Growth & Dev, Dallas, TX 75390 USA.
[Xing, Chao] Univ Texas SW Med Ctr Dallas, Donald W Reynolds Cardiovasc Clin Res Ctr, Dallas, TX 75390 USA.
[John, Esther M.] No Calif Canc Ctr, Fremont, CA USA.
[John, Esther M.] Stanford Univ, Dept Hlth Res & Policy, Sch Med, Stanford, CA 94305 USA.
[John, Esther M.] Stanford Canc Ctr, Stanford, CA USA.
[Ambrosone, Christine B.; Ciupak, Gregory L.] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA.
[Press, Michael F.] Univ So Calif, Keck Sch Med, Dept Pathol, Los Angeles, CA 90033 USA.
[Parekh, Rulan S.] Johns Hopkins Univ, Dept Pediat, Baltimore, MD 21218 USA.
[Parekh, Rulan S.; Klag, Michael J.; Meoni, Lucy A.] Johns Hopkins Univ, Dept Med, Baltimore, MD 21218 USA.
[Klag, Michael J.] Johns Hopkins Univ, Dept Hlth Policy & Management, Baltimore, MD 21218 USA.
[Meoni, Lucy A.] Johns Hopkins Univ, Dept Biostat, Baltimore, MD 21218 USA.
[Hsueh, Wen-Chi; Fejerman, Laura] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Fejerman, Laura; Pawlikowska, Ludmila] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA.
[Fejerman, Laura] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA.
[Pawlikowska, Ludmila] Univ Calif San Francisco, Dept Anesthesia & Perioperat Care, San Francisco, CA 94143 USA.
[Freedman, Matthew L.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Jandorf, Lina H.] Mt Sinai Sch Med, Dept Oncol Sci, New York, NY USA.
[Bandera, Elisa V.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Canc Inst New Jersey, New Brunswick, NJ USA.
[Nalls, Michael A.] NIA, Mol Genet Sect, Neurogenet Lab, Intramural Res Program, Bethesda, MD 20892 USA.
[Akylbekova, Ermeg L.] Jackson State Univ, Jackson Heart Study Anal Grp, Jackson, MS USA.
[Orwoll, Eric S.] Oregon Hlth & Sci Univ, Oregon Clin & Translat Res Inst, Portland, OR 97201 USA.
[Leak, Tennille S.; Miljkovic, Iva; Zmuda, Joseph M.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA.
[Li, Rongling] Univ Tennessee, Dept Prevent Med, Div Biostat & Epidemiol, Memphis, TN USA.
[Ursin, Giske] Univ Oslo, Dept Nutr, Oslo, Norway.
[Bernstein, Leslie] City Hope Natl Med Ctr, Dept Canc Etiol, Div Populat Sci, Duarte, CA 91010 USA.
[Ardlie, Kristin] Genom Collaborat, Cambridge, MA USA.
[Taylor, Herman A.] Jackson State Univ, Jackson, MS USA.
[Taylor, Herman A.] Tougaloo Coll, Tougaloo, MS USA.
[Taylor, Herman A.; Wilson, James G.] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA.
[Boerwinckle, Eric] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX USA.
[Wilson, James G.] GV Sonny Montgomery Vet Affairs Med Ctr, Jackson, MS USA.
RP Cheng, CY (reprint author), Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA.
EM cycheng@jhsph.edu; wkao@jhsph.edu; reich@genetics.med.harvard.edu
RI Cheng, Ching-Yu/K-7017-2013; Bandera, Elisa/M-4169-2014;
OI Cheng, Ching-Yu/0000-0003-0655-885X; Bandera, Elisa/0000-0002-8789-2755;
Miljkovic, Iva/0000-0002-3155-9777; Fejerman, Laura/0000-0003-3179-1151;
Orwoll, Eric/0000-0002-8520-7355
FU National Heart, Lung, and Blood Institute (NHLBI) [N01-HC-55015,
N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021,
N01-HC-55022, R21DK073482, Kol DK067207, N01-HC-95170, N01-HC-95171,
N01-HC-95172]; National Cancer Institute (NCI), National Institutes of
Health (NIH) [RFA-CA-06-503, N01-CO-12400]; Northern California BCFR
site [U01 CA6941 7]; National Institute of Child Health and Human
Development [NOl-HD-3-31 75]; NCI [NOl-PC-6701 0, CA 74847, CA63464,
R01-CA100598]; California Department of Health Services [OSOG 8709];
National Institute of Environmental Health Sciences [R01-ES-07084];
California Breast Cancer Research Program [PB-0051]; National Institute
of Diabetes and Digestive and Kidney Diseases (NIDDK) [U01 DK070657,
U01DK57304, K01DK067207, U01DK57292]; National Center for Research
Resources; National Center on Minority Health and Health Disparities;
United States Army Medical Research Program; Center of Excellence for
Biobehavioral Breast Cancer Research [DAMD17-01-1-0334]; Susan Komen
Foundation for Breast Cancer Research [KG080165]; Burroughs Wellcome
Career Development Award in the Biomedical Sciences [U01-HG0041]; [RL-1
HL092550]; [U54-RR020278]; [CA 17054]; [4PB-0092]; [CA54281]; [U01
AR45580]; [U01 AR45614]; [U01 AR45632]; [U01 AR45647]; [U01
AR45654]; [U01 AR45583]; [U01 AG18197]; [U01-AG027810]; [ULl
RR024140]; [R01-AR051124]; [R01-CA63446]; [R01-CA77305]; [DAMD1
7-96-607]; [7PB-0068]; [AG05407]; [AG05394]; [AR35584]; [AR35583];
[5T32AG0001 81-19]
FX The ARIC Study was carried out as a collaborative study supported by the
National Heart, Lung, and Blood Institute (NHLBI) contracts
N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020,
N01-HC-55021 and N01-HC-55022 with support for this analysis by
R21DK073482 and Kol DK067207 (WHLK). The BCFR was supported by the
National Cancer Institute (NCI), National Institutes of Health (NIH)
under RFA-CA-06-503 and through cooperative agreements with members of
the BCFR and PIs. The Northern California BCFR site was funded by U01
CA6941 7. The Los Angeles component of the Women's Contraceptive and
Reproductive Experiences study received support from contracts with the
National Institute of Child Health and Human Development (NOl -HD-3-31
75), the NCI (NOl-PC-6701 0) and the California Department of Health
Services (OSOG 8709), and grants from the National Institute of
Environmental Health Sciences (R01-ES-07084) and the California Breast
Cancer Research Program (PB-0051). The DHS was supported by the Donald
W. Reynolds Foundation and grant 1 RL-1 HL092550 from the NIH. The FIND
Study included in this analysis was supported by the following research
grants: U01 DK070657, U01DK57304, K01DK067207 (WHLK), and U01DK57292
from the National Institute of Diabetes and Digestive and Kidney
Diseases (NIDDK) and, in part, by the Intramural Research Program of the
NIDDK; this research was supported in part by the Intramural Research
Program of the NIH, NCI, Center for Cancer Research, and has been funded
in part with federal funds from the NCI, NIH, under contract
N01-CO-12400. Research support for Health ABC was provided by the
Intramural Research Program of the National Institute on Aging, and
contracts N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106. Genotyping in
Health ABC was supported by National Center for Research Resources grant
U54-RR020278. Research support for JHS studies was provided by
R01-HL084107 (JGW) from the NHLBI and contracts N01-HC-95170,
N01-HC-95171, and N01-HC-95172 from the NHLBI and the National Center on
Minority Health and Health Disparities. The LIFE Study was supported by
grants CA 17054, CA 74847 from the NCI, and by grant 4PB-0092 from the
California Breast Cancer Research Program of the University of
California. The MEC Study was supported by NCI grants CA63464 and
CA54281. MrOS is supported by grants: U01 AR45580, U01 AR45614, U01
AR45632, U01 AR45647, U01 AR45654, U01 AR45583, U01 AG18197,
U01-AG027810, ULl RR024140 and R01-AR051124. SFBABCS was supported by
grants R01-CA63446 and R01-CA77305 from the NCI, grant DAMD1 7-96-607
from the United States Army Medical Research Program, and grant 7PB-0068
from the California Breast Cancer Research Program. SOF was supported by
grants AG05407, AR35582, AG05394, AR35584, and AR35583. The WCHS was
initially funded as part of a Center of Excellence for Biobehavioral
Breast Cancer Research (United States Army Medical Research Program,
DAMD17-01-1-0334) and subsequently by R01-CA100598 from the NCI.
Genotyping for SFBABCS and WCHS was supported by grant KG080165 from the
Susan Komen Foundation for Breast Cancer Research. DR was supported by a
Burroughs Wellcome Career Development Award in the Biomedical Sciences,
and methodological work was supported by grant U01-HG0041 68 to DR, NP
and AT. TL is postdoctoral fellow funded on 5T32AG0001 81-19, Training
in the Epidemiology of Aging.
NR 50
TC 45
Z9 45
U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7390
J9 PLOS GENET
JI PLoS Genet.
PD MAY
PY 2009
VL 5
IS 5
AR e1000490
DI 10.1371/journal.pgen.1000490
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA 459EH
UT WOS:000267083000012
PM 19461885
ER
PT J
AU Namekawa, SH
Lee, JT
AF Namekawa, Satoshi H.
Lee, Jeannie T.
TI XY and ZW: Is Meiotic Sex Chromosome Inactivation the Rule in Evolution?
SO PLOS GENETICS
LA English
DT Editorial Material
ID DOSAGE COMPENSATION; CHROMATIN; MEIOSIS; SPERMATOGENESIS; MAMMALS; MOUSE
C1 [Namekawa, Satoshi H.; Lee, Jeannie T.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Dept Mol Biol, Boston, MA 02114 USA.
[Namekawa, Satoshi H.; Lee, Jeannie T.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA.
RP Namekawa, SH (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Dept Mol Biol, Boston, MA 02114 USA.
EM lee@molbio.mgh.harvard.edu
FU Howard Hughes Medical Institute
NR 24
TC 21
Z9 21
U1 1
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7390
J9 PLOS GENET
JI PLoS Genet.
PD MAY
PY 2009
VL 5
IS 5
AR e1000493
DI 10.1371/journal.pgen.1000493
PG 3
WC Genetics & Heredity
SC Genetics & Heredity
GA 459EH
UT WOS:000267083000001
PM 19461890
ER
PT J
AU Lotter, H
Gonzalez-Roldan, N
Lindner, B
Winau, F
Isibasi, A
Moreno-Lafont, M
Ulmer, AJ
Holst, O
Tannich, E
Jacobs, T
AF Lotter, Hannelore
Gonzalez-Roldan, Nestor
Lindner, Buko
Winau, Florian
Isibasi, Armando
Moreno-Lafont, Martha
Ulmer, Artur J.
Holst, Otto
Tannich, Egbert
Jacobs, Thomas
TI Natural Killer T Cells Activated by a Lipopeptidophosphoglycan from
Entamoeba histolytica Are Critically Important To Control Amebic Liver
Abscess
SO PLOS PATHOGENS
LA English
DT Article
ID INNATE IMMUNE-RESPONSE; INVARIANT NKT CELLS; PHENOL-WATER METHOD;
ALPHA-GALACTOSYLCERAMIDE; INTERFERON-GAMMA; GLYCOSYLPHOSPHATIDYLINOSITOL
ANCHORS; MONOCLONAL-ANTIBODY; CD1D MOLECULES; HK-9 STRAIN;
LIPOPHOSPHOGLYCAN
AB The innate immune response is supposed to play an essential role in the control of amebic liver abscess (ALA), a severe form of invasive amoebiasis due to infection with the protozoan parasite Entamoeba histolytica. In a mouse model for the disease, we previously demonstrated that J alpha 18(-/-) mice, lacking invariant natural killer T (iNKT) cells, suffer from more severe abscess development. Here we show that the specific activation of iNKT cells using alpha-galactosylceramide (alpha-GalCer) induces a significant reduction in the sizes of ALA lesions, whereas CD1d(-/-) mice develop more severe abscesses. We identified a lipopeptidophosphoglycan from E. histolytica membranes (EhLPPG) as a possible natural NKT cell ligand and show that the purified phosphoinositol (PI) moiety of this molecule induces protective IFN-gamma but not IL-4 production in NKT cells. The main component of EhLPPG responsible for NKT cell activation is a diacylated PI, (1-O-[(28: 0)-lyso-glycero-3-phosphatidyl-]2-O(C16:0)-Ins). IFN-gamma production by NKT cells requires the presence of CD1d and simultaneously TLR receptor signalling through MyD88 and secretion of IL-12. Similar to alpha-GalCer application, EhLPPG treatment significantly reduces the severity of ALA in ameba-infected mice. Our results suggest that EhLPPG is an amebic molecule that is important for the limitation of ALA development and may explain why the majority of E. histolytica-infected individuals do not develop amebic liver abscess.
C1 [Lotter, Hannelore; Gonzalez-Roldan, Nestor; Tannich, Egbert; Jacobs, Thomas] Bernhard Nocht Inst Trop Med, Hamburg, Germany.
[Gonzalez-Roldan, Nestor; Holst, Otto] Leibniz Ctr Med & Biosci, Res Ctr Borstel, Div Struct Biochem, Borstel, Germany.
[Gonzalez-Roldan, Nestor; Isibasi, Armando] Hosp Especialidades Ctr Med Nacl Siglo XXI, Unidad Invest Med Immunoquim, IMSS, Mexico City, DF, Mexico.
[Gonzalez-Roldan, Nestor; Moreno-Lafont, Martha] Inst Politecn Nacl, Dept Inmunol, Escuela Nacl Ciencias Biol, Mexico City, DF, Mexico.
[Lindner, Buko] Leibniz Ctr Med & Biosci, Div Immunochem, Res Ctr Borstel, Borstel, Germany.
[Winau, Florian] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Winau, Florian] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA.
[Ulmer, Artur J.] Leibniz Ctr Med & Biosci, Res Ctr Borstel, Div Immunol & Cell Biol, Borstel, Germany.
RP Lotter, H (reprint author), Bernhard Nocht Inst Trop Med, Hamburg, Germany.
EM lotter@bni-hamburg.de; oholst@fz-borstel.de
RI Lindner, Buko/G-9731-2014
FU Deutsche Forschungsgemeinschaft (www.dfg.de) [TA 110/8-1]; SFB [470, LI
448/4-1]
FX We are grateful to the Deutsche Forschungsgemeinschaft (www.dfg.de) for
funding TA 110/8-1 to ET and the materials and position of HL; the
funding of SFB 470 to TJ, and materials and expertise for the
immunological parts; and for supporting the project LI 448/4-1 to BL and
providing mass and gas chromatography materials. We also thank the
Consejo Nacional de Ciencia y Tecnologica (www.conacyt.mx) for grant
50545-M to AI and the financial support to NGR. The funders had no role
in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 61
TC 42
Z9 42
U1 0
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7366
J9 PLOS PATHOG
JI PLoS Pathog.
PD MAY
PY 2009
VL 5
IS 5
AR e1000434
DI 10.1371/journal.ppat.1000434
PG 11
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 459FH
UT WOS:000267085800037
PM 19436711
ER
PT J
AU York, RM
Perell-Gerson, KL
Barr, M
Durham, J
Roper, JM
AF York, Robyn M.
Perell-Gerson, Karen L.
Barr, Michele
Durham, Jayson
Roper, Janice M.
TI Motor Learning of a Gait Pattern to Reduce Forefoot Plantar Pressures in
Individuals with Diabetic Peripheral Neuropathy
SO PM&R
LA English
DT Article
AB Objective: To examine the role of visual feedback in the reduction of plantar pressures through teaching a "new" gait pattern to diabetic peripheral neuropathy subjects. Immediate, next day, and 1-week retention were studied to determine if motor pattern changes could occur.
Design: Randomized controlled trial.
Setting: VA Urban Healthcare System.
Participants: Twenty-nine community-dwelling older adults with diabetic peripheral neuropathy volunteered.
Interventions: Subjects were randomized into feedback and no-feedback groups. All subjects received instruction and 2 days of practice and returned for a 1-week retention test. Instruction to pull the leg forward from the hip to initiate swing rather than push off the ground with the foot while walking was given to all subjects. The feedback group received visual feedback regarding peak plantar pressures after each practice trial. The no-feedback group received no feedback.
Main Outcome Measures: Peak plantar pressures in the forefoot region for immediate retention (retention 1), next day retention (retention 2), and long-term retention (1-week retention).
Results: Peak plantar pressures were significantly (P < .01) reduced from baseline to retention 2 testing at the first metatarsal area in the feedback group. The feedback group walked significantly (P < .01) slower at retention 1 and 1-week testing compared with baseline.
Conclusions: Individuals with diabetic peripheral neuropathy were unable to use a "new" strategy gait pattern to reduce peak plantar pressures long term (1 week). The use of visual feedback following the trial did not assist in the learning of a new walking pattern.
C1 [York, Robyn M.; Perell-Gerson, Karen L.; Roper, Janice M.] VA Greater Los Angeles Healthcare Syst, Dept Res, Los Angeles, CA USA.
[York, Robyn M.; Perell-Gerson, Karen L.; Barr, Michele] Calif State Univ Fullerton, Dept Kinesiol, Fullerton, CA 92634 USA.
[Durham, Jayson] Space & Naval Warfare Syst Ctr, San Diego, CA USA.
RP Perell-Gerson, KL (reprint author), VA Greater Los Angeles Healthcare Syst, Dept Res, Los Angeles, CA USA.
EM kperell@fullerton.edu
FU VA Rehabilitation Research and Development Service [A2372K, A3117R]
FX Supported by a Career Development Award (A2372K) from the VA
Rehabilitation Research and Development Service to K.L.P.-G. and a grant
(A3117R) from the VA Rehabilitation Research and Development Service to
K.L.P.-G. and J.M.R.
NR 22
TC 6
Z9 6
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1934-1482
J9 PM&R
JI PM&R
PD MAY
PY 2009
VL 1
IS 5
BP 434
EP 441
DI 10.1016/j.pmrj.2009.03.001
PG 8
WC Rehabilitation; Sport Sciences
SC Rehabilitation; Sport Sciences
GA V24LI
UT WOS:000208411500006
PM 19627930
ER
PT J
AU Goldfine, AB
Fonseca, VA
AF Goldfine, Allison B.
Fonseca, Vivian A.
TI The Use of Colesevelam HCl in Patients with Type 2 Diabetes Mellitus:
Combining Glucose- and Lipid-Lowering Effects
SO POSTGRADUATE MEDICINE
LA English
DT Article
DE bile acid sequestrant; cardiovascular; colesevelam HCl; glycemic
control; lipid lowering; type 2 diabetes mellitus
ID CORONARY HEART-DISEASE; GLYCEMIC CONTROL; DOUBLE-BLIND; BILE-ACIDS;
THERAPY; HYPERCHOLESTEROLEMIA; HYDROCHLORIDE; CHOLESTEROL; COLESTIMIDE;
EFFICACY
AB Therapy is often required to manage the hyperglycemia, hypertension, and dyslipidemia that occur in patients with type 2 diabetes mellitus (T2DM) in order to control the risk of cardiovascular (CV) events. The importance of managing these risk factors is underscored by the recommendation from the American Diabetes Association and the American Association of Clinical Endocrinologists for treatment of these CV risk factors to target levels. However, relatively few patients achieve simultaneous control of these risk factors. As such, therapy that has positive effects on more than I risk factor is of potential benefit. Initially approved as a lipid-lowering agent, the bile acid sequestrant colesevelam hydrochloride (HCl) is now also approved as an adjunct therapy to improve glycemic control in patients with T2DM. This review summarizes the major findings of clinical studies that investigated the glucose- and lipid-lowering effects of colesevelam HCl when added to stable metformin-, sulfonylurea-, or insulin-based antidiabetes therapies in patients with T2DM.
C1 [Goldfine, Allison B.] Joslin Diabet Ctr, Boston, MA 02215 USA.
[Fonseca, Vivian A.] Tulane Univ, Hlth Sci Ctr, New Orleans, LA 70118 USA.
RP Goldfine, AB (reprint author), 1 Joslin Pl, Boston, MA 02115 USA.
EM allison.goldfine@joslin.harvard.edu
FU Daiichi Sankyo, Inc
FX Acknowledgments Funding for the preparation of this manuscript was
provided by Daiichi Sankyo, Inc. Editorial assistance was provided by
Luana Atherly, PhD and Karen Stauffer, PhD.
NR 26
TC 3
Z9 3
U1 0
U2 0
PU JTE MULTIMEDIA
PI BERWYN
PA 1235 WESTLAKES DR, STE 220, BERWYN, PA 19312 USA
SN 0032-5481
J9 POSTGRAD MED
JI Postgrad. Med.
PD MAY
PY 2009
VL 121
IS 3
BP 13
EP 18
PG 6
WC Medicine, General & Internal
SC General & Internal Medicine
GA 467TN
UT WOS:000267766100003
PM 19494473
ER
PT J
AU Goldfine, AB
Fonseca, VA
AF Goldfine, Allison B.
Fonseca, Vivian A.
TI The Use of Colesevelam HCl in Patients with Type 2 Diabetes Mellitus:
Combining Glucose- and Lipid-Lowering Effects
SO POSTGRADUATE MEDICINE
LA English
DT Article
DE bile acid sequestrant; cardiovascular; colesevelam HCl; glycemic
control; lipid lowering; type 2 diabetes mellitus
ID CORONARY HEART-DISEASE; GLYCEMIC CONTROL; DOUBLE-BLIND; BILE-ACIDS;
THERAPY; HYPERCHOLESTEROLEMIA; HYDROCHLORIDE; CHOLESTEROL; COLESTIMIDE;
EFFICACY
AB Therapy is often required to manage the hyperglycemia, hypertension, and dyslipidemia that occur in patients with type 2 diabetes mellitus (T2DM) in order to control the risk of cardiovascular (CV) events. The importance of managing these risk factors is underscored by the recommendation from the American Diabetes Association and the American Association of Clinical Endocrinologists for treatment of these CV risk factors to target levels. However, relatively few patients achieve simultaneous control of these risk factors. As such, therapy that has positive effects on more than I risk factor is of potential benefit. Initially approved as a lipid-lowering agent, the bile acid sequestrant colesevelam hydrochloride (HCl) is now also approved as an adjunct therapy to improve glycemic control in patients with T2DM. This review summarizes the major findings of clinical studies that investigated the glucose- and lipid-lowering effects of colesevelam HCl when added to stable metformin-, sulfonylurea-, or insulin-based antidiabetes therapies in patients with T2DM.
C1 [Goldfine, Allison B.] Joslin Diabet Ctr, Boston, MA 02215 USA.
[Fonseca, Vivian A.] Tulane Univ, Hlth Sci Ctr, New Orleans, LA 70118 USA.
RP Goldfine, AB (reprint author), 1 Joslin Pl, Boston, MA 02115 USA.
EM allison.goldfine@joslin.harvard.edu
FU Daiichi Sankyo, Inc
FX Funding for the preparation of this manuscript was provided by Daiichi
Sankyo, Inc. Editorial assistance was provided by Luana Atherly, PhD and
Karen Stauffer, PhD.
NR 26
TC 0
Z9 0
U1 0
U2 0
PU JTE MULTIMEDIA
PI BERWYN
PA 1235 WESTLAKES DR, STE 220, BERWYN, PA 19312 USA
SN 0032-5481
J9 POSTGRAD MED
JI Postgrad. Med.
PD MAY
PY 2009
BP 13
EP 18
PG 6
WC Medicine, General & Internal
SC General & Internal Medicine
GA 493NA
UT WOS:000269742500003
ER
PT J
AU Allen, JD
Mohllajee, AP
Shelton, RC
Othus, MKD
Fontenot, HB
Hanna, R
AF Allen, Jennifer D.
Mohllajee, Anshu P.
Shelton, Rachel C.
Othus, Megan K. D.
Fontenot, Holly B.
Hanna, Richard
TI Stage of adoption of the human papillomavirus vaccine among college
women
SO PREVENTIVE MEDICINE
LA English
DT Article
DE Cervical neoplasia; Human papillomavirus vaccine; Intention; Attitudes;
Knowledge; Social norms
ID TRANSMITTED INFECTION VACCINATION; PARENTAL ATTITUDES; HPV VACCINATION;
TRANSTHEORETICAL MODEL; ADOLESCENT CHILDREN; SMOKING CESSATION; HEALTH
BEHAVIOR; UNITED-STATES; YOUNG-ADULTS; ACCEPTABILITY
AB Background. Certain types of human papillomavirus (HPV) can cause cervical and other cancers. A vaccine that protects against HPV types responsible for 70% of cervical cancers is available to females ages 9-26.
Objective. To examine correlates of stage of vaccine adoption among women ages 18-22.
Methods. In 2007, female students (n = 4774) at a New England University in the U.S. were invited to complete an on-line survey that assessed knowledge of HPV, perceived susceptibility, severity, vaccine benefits/barriers, social and subjective norms, and stage of vaccine adoption
Results. 1897 women (40%) responded; complete data were available for 1401. About half (53%) were planning to be vaccinated, 12% had received the vaccine, 15% were undecided, and 7% had decided against vaccination. HPV knowledge was low (mean 58%). In multivariate analyses, social norms was the strongest correlate of stage; each standard deviation increase in social norms score was associated with more than four times the odds of intending to be vaccinated within the next 30 days, compared with those who had decided against vaccination (OR=4.15: 95% CI 2.17-6.36).
Conclusions. Acceptance of the vaccine was high, although misconceptions about viral transmission, availability of treatment, and the role of Pap tests were common. Perceived norms were strongly associated with intentions. Interventions on college campuses should stress vaccination as a normative behavior, provide information about viral transmission, and stress the role of continued Pap screening. (C) 2008 Elsevier Inc. All rights reserved.
C1 [Allen, Jennifer D.; Mohllajee, Anshu P.; Shelton, Rachel C.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA.
[Allen, Jennifer D.; Fontenot, Holly B.; Hanna, Richard] Boston Coll, Chestnut Hill, MA 02167 USA.
[Allen, Jennifer D.; Mohllajee, Anshu P.; Shelton, Rachel C.; Othus, Megan K. D.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Hanna, Richard] Northeastern Univ, Boston, MA 02115 USA.
RP Allen, JD (reprint author), Boston Coll, William Connell Sch Nursing, 140 Commonwealth Ave, Boston, MA 02167 USA.
EM jennifer.allen.5@bc.edu
RI Hanna, Richard/A-4342-2010; Allen, Jennifer/M-2113-2015
NR 54
TC 70
Z9 70
U1 4
U2 7
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0091-7435
J9 PREV MED
JI Prev. Med.
PD MAY
PY 2009
VL 48
IS 5
BP 420
EP 425
DI 10.1016/j.ypmed.2008.12.005
PG 6
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 451LB
UT WOS:000266470600004
PM 19133288
ER
PT J
AU Wakchoure, S
Swain, TM
Hentunen, TA
Bauskin, AR
Brown, DA
Breit, SN
Vuopala, KS
Harris, KW
Selander, KS
AF Wakchoure, Savita
Swain, Telisha Millender
Hentunen, Teuvo A.
Bauskin, Asne R.
Brown, David A.
Breit, Samuel N.
Vuopala, Katri S.
Harris, Kevin W.
Selander, Katri S.
TI Expression of Macrophage Inhibitory Cytokine-1 in Prostate Cancer Bone
Metastases Induces Osteoclast Activation and Weight Loss
SO PROSTATE
LA English
DT Article
DE MIC-1; prostate cancer; bone metastases
ID TGF-BETA SUPERFAMILY; GROWTH-FACTOR-BETA; RHEUMATOID-ARTHRITIS;
GENE-EXPRESSION; TUMOR-CELLS; MAP KINASE; IN-VITRO; MIC-1; SERUM;
PROGRESSION
AB BACKGROUND. Macrophage inhibitory cytokine-1 (MIC-1) belongs to the bone morphogenic protein/transforming growth factor-beta (BMP/TGF-beta) superfamily. Serum MIC-1 concentrations are elevated in patients with advanced prostate cancer. The effects of MIC-1 on prostate cancer bone metastases are unknown.
METHODS. In vitro effects of MIC-1 on osteoblast differentiation and activity were analyzed with alkaline phosphatase and mineralization assays; osteoclast numbers were counted microscopically. MIC-1 effects on TLR9 expression were studied with Western blotting. Human Du-145 prostate cancer cells were stably transfected with a cDNA encoding for mature MIC-1 or with an empty vector. The in vivo growth characteristics of the characterized cells were studied with the intra-tibial model of bone metastasis. Tumor associated bone changes were viewed with X-rays, histology, and histomorphometry. Bone formation was assayed by measuring serum PINP.
RESULTS. MIC-1 induced osteoblast differentiation and activity and osteoclast formation in vitro. These effects were independent of TLR9 expression, which was promoted by MIC-1. Both MIC-1 and control tumors induced mixed sclerotic/lytic bone lesions, but MIC-1 increased the osteolytic component of tumors. Osteoclast formation at the tumor-bone interface was significantly higher in the MIC-1 tumors, whereas bone formation was significantly higher in the control mice. At sacrifice, the mice bearing MIC-1 tumors were significantly lighter with significantly smaller tumors.
CONCLUSIONS. MIC-1 up-regulates TLR9 expression in various cells. MIC-1 stimulates both osteoblast and osteoclast differentiation in vitro, independently of TLR9. MIC-1 over-expressing prostate cancer cells that grow in bone induce osteoclast formation and cachexia. Prostate 69: 652-661, 2009. (C) 2009 Wiley-Liss, Inc.
C1 [Selander, Katri S.] Univ Alabama, Dept Med, Div Hematol Oncol, UAB, Birmingham, AL 35294 USA.
[Hentunen, Teuvo A.] Univ Turku, Inst Biomed, Dept Anat, FIN-20520 Turku, Finland.
[Bauskin, Asne R.; Brown, David A.; Breit, Samuel N.] St Vincents Hosp, Ctr Immunol, Sydney, NSW 2010, Australia.
[Bauskin, Asne R.; Brown, David A.; Breit, Samuel N.] Univ New S Wales, Sydney, NSW, Australia.
[Vuopala, Katri S.] Lapland Cent Hosp, Rovaniemi, Finland.
[Harris, Kevin W.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA.
RP Selander, KS (reprint author), Univ Alabama, Dept Med, Div Hematol Oncol, UAB, WTI T558,1824 6th Ave S, Birmingham, AL 35294 USA.
EM katri.selander@ccc.uab.edu
FU National Health & Medical Research Council, Australia; New South Wales
Health Research and Development Infrastructure; Department of Defense
[W81XWH-05-1-0066]
FX National Health & Medical Research Council, Australia; Grant sponsor:
New South Wales Health Research and Development Infrastructure; Grant
sponsor: Department of Defense; Grant number: W81XWH-05-1-0066.
NR 52
TC 32
Z9 36
U1 0
U2 1
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0270-4137
J9 PROSTATE
JI Prostate
PD MAY 1
PY 2009
VL 69
IS 6
BP 652
EP 661
DI 10.1002/pros.20913
PG 10
WC Endocrinology & Metabolism; Urology & Nephrology
SC Endocrinology & Metabolism; Urology & Nephrology
GA 437YU
UT WOS:000265523600009
PM 19152406
ER
PT J
AU Rho, JH
Roehrl, MHA
Wang, JY
AF Rho, Jung-Hyun
Roehrl, Michael H. A.
Wang, Julia Y.
TI Glycoproteomic Analysis of Human Lung Adenocarcinomas Using Glycoarrays
and Tandem Mass Spectrometry: Differential Expression and Glycosylation
Patterns of Vimentin and Fetuin A Isoforms
SO PROTEIN JOURNAL
LA English
DT Article
DE Lung cancer; Lectin affinity; Mass spectrometry; Glycoproteins;
Vimentin; Fetuin A
ID GROWTH-FACTOR-BETA; N-GLYCANS; PROTEIN GLYCOSYLATION; COLORECTAL-CANCER;
TUMOR PROGRESSION; IMMUNE-RESPONSE; ANNEXIN-II; OLIGOSACCHARIDES;
ALPHA-2HS-GLYCOPROTEIN; ALPHA-1-ANTITRYPSIN
AB Human lung cancer is a major cause of cancer mortality worldwide. Advances in pathophysiologic understanding and novel biomarkers for diagnosis and treatment are significant tasks. We have undertaken a comprehensive glycoproteomic analysis of human lung adenocarcinoma tissues. Glycoproteins from paired lung adenocarcinoma and normal tissues were enriched by the lectins Con A, WGA, and AIL. 2-D PAGE revealed 30 differentially expressed protein spots, and 15 proteins were identified by MS/MS, including 8 up- (A1AT, ALDOA, ANXA1, CALR, ENOA, PDIA1, PSB1 and SODM) and 7 down-regulated (ANXA3, CAH2, FETUA, HBB, PRDX2, RAGE and VIME) proteins in lung cancer. By reverse-transcription PCR, nine proteins showed positive correlation between mRNA and glycoprotein expression. Vimentin and fetuin A (alpha(2)-HS-glycoprotein) were selected for further investigation. While for vimentin there was little correlation between total protein and mRNA abundance, expression of WGA-captured glycosylated vimentin protein was frequently decreased in cancer. Glycoarray analysis suggested that vimentins from normal and cancerous lung tissue differ in their contents of sialic acid and terminal GlcNAc. For fetuin A, both total protein and mRNA abundance showed concordant decrease in cancer. WGA- and AIL-binding glycosylated fetuin A was also consistently decreased in cancer. Glycoarray analysis suggested that high mannose glycan structures on fetuin A were only detectable in cancer but not normal tissue. The intriguing expression patterns of different isoforms of glycosylated vimentin and fetuin A in lung cancer illustrate the complexities and benefits of in-depth glycoproteomic analysis. In particular, the discovery of differentially glycosylated protein isoforms in lung adenocarcinoma may represent avenues towards new functional biomarkers for diagnosis, treatment guidance, and response monitoring.
C1 [Roehrl, Michael H. A.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Rho, Jung-Hyun; Wang, Julia Y.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA.
[Rho, Jung-Hyun; Roehrl, Michael H. A.; Wang, Julia Y.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
RP Roehrl, MHA (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA.
EM michael_roehrl@hms.harvard.edu
FU NIAID/NIH
FX We acknowledge financial support from the NIAID/NIH. We thank Drs. Bin
Ye, Brian Liu, and Sam Mok of Brigham and Women's Hospital for use of
proteomic equipment. We thank the Taplin Biological Mass Spectrometry
Center of Harvard Medical School for expert advice.
NR 46
TC 32
Z9 36
U1 0
U2 12
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1572-3887
J9 PROTEIN J
JI Protein J.
PD MAY
PY 2009
VL 28
IS 3-4
BP 148
EP 160
DI 10.1007/s10930-009-9177-0
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 469LE
UT WOS:000267898900005
PM 19412661
ER
PT J
AU Thomas, JJ
Vartanian, LR
Brownell, KD
AF Thomas, Jennifer J.
Vartanian, Lenny R.
Brownell, Kelly D.
TI The Relationship Between Eating Disorder Not Otherwise Specified (EDNOS)
and Officially Recognized Eating Disorders: Meta-Analysis and
Implications for DSM
SO PSYCHOLOGICAL BULLETIN
LA English
DT Review
DE eating disorder not otherwise specified (EDNOS); eating disorder
classification; DSM; Meta-analysis
ID SUBTHRESHOLD BULIMIA-NERVOSA; RANDOMIZED CONTROLLED-TRIAL;
ANOREXIA-NERVOSA; DIAGNOSTIC-CRITERIA; CHINESE PATIENTS;
PERSONALITY-DISORDERS; HONG-KONG; FOLLOW-UP; COMMUNITY SAMPLE;
SELF-REPORT
AB Eating disorder not otherwise specified (EDNOS) is the most prevalent eating disorder (ED) diagnosis. In this meta-analysis, the authors aimed to inform Diagnostic and Statistical Manual of Mental Disorders revisions by comparing the psychopathology of EDNOS with that of the officially recognized EDs: anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED). A comprehensive literature search identified 125 eligible studies (Published and unpublished) appearing in the literature from 1987 to 2007. Random effects analyses indicated that whereas EDNOS did not differ significantly from AN and BED on eating pathology or general psychopathology, BN exhibited greater eating and general psychopathology than EDNOS. Moderator analyses indicated that EDNOS groups who met all diagnostic criteria for AN except for amenorrhea did not differ significantly from full syndrome cases. Similarly, EDNOS groups who met all criteria for BN or BED except for binge frequency did not differ significantly from full syndrome cases. Results suggest that EDNOS represents a set of disorders associated with substantial psychological and physiological morbidity. Although certain EDNOS subtypes could be incorporated into existing Diagnostic and Statistical Manual of Mental Disorders (4th ed.; American Psychiatric Association, 1994) categories, others-such as purging disorder and non-fat-phobic AN-may be best conceptualized as distinct syndromes.
C1 [Thomas, Jennifer J.] Harvard Univ, McLean Hosp, Sch Med, Eating Disorders Ctr, Cambridge, MA 02138 USA.
[Thomas, Jennifer J.; Brownell, Kelly D.] Yale Univ, Dept Psychol, New Haven, CT 06520 USA.
[Vartanian, Lenny R.] Syracuse Univ, Dept Psychol, Syracuse, NY 13244 USA.
RP Thomas, JJ (reprint author), Massachusetts Gen Hosp, Eating Disorders Clin & Res Program, WAC 816D,15 Parkman St, Boston, MA 02114 USA.
EM jjthomas@partners.org
FU National Institutes of Mental Health; National Research Service
[F31MH078394]
FX We thank the National Institutes of Mental Health for their financial
support of this research project through the auspices of Ruth L.
Kirschstein National Research Service Award F31MH078394. We also
acknowledge the meticulous work of our study coders, Andres De Los
Reyes, Kate A. McLaughlin, and Jessica M. Cronce. Lastly, we thank the
investigators who contributed their in-press and unpublished studies for
inclusion in our meta-analysis.
NR 232
TC 111
Z9 114
U1 10
U2 26
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0033-2909
J9 PSYCHOL BULL
JI Psychol. Bull.
PD MAY
PY 2009
VL 135
IS 3
BP 407
EP 433
DI 10.1037/a0015326
PG 27
WC Psychology; Psychology, Multidisciplinary
SC Psychology
GA 436RW
UT WOS:000265433900006
PM 19379023
ER
PT J
AU Thomas, JJ
Roberto, CA
Brownell, KD
AF Thomas, J. J.
Roberto, C. A.
Brownell, K. D.
TI Eighty-five per cent of what? Discrepancies in the weight cut-off for
anorexia nervosa substantially affect the prevalence of underweight
SO PSYCHOLOGICAL MEDICINE
LA English
DT Article; Proceedings Paper
CT 41st Annual Meeting of the
Association-of-Behavioral-and-Cognitive-Therapies
CY NOV 17, 2007
CL Philadelphia, PA
SP Assoc Behav & Cognit Therapies
DE Anorexia nervosa; expected body weight; body mass index; DSM-IV criteria
for eating disorders; Centers for Disease Control and Prevention (CDC);
National Health and Nutrition Examination Survey (NHANES)
ID EATING DISORDER PATIENTS; CHINESE PATIENTS; CONTROLLED-TRIAL;
DOUBLE-BLIND; HONG-KONG; AMENORRHEA; CRITERION; ADOLESCENTS; FLUOXETINE;
CHILDREN
AB Background. DSM-IV cites <85% of expected body weight (EBW) as a guideline for the diagnosis of anorexia nervosa (AN) but does not require a specific method for calculating EBW. The purpose of the present Study was to determine the degree to which weight cut-off calculations vary across studies, and to evaluate whether differential cut-offs lead to discrepancies in the prevalence of individuals who are eligible for the AN diagnosis.
Method. Two coders independently recorded the EBW Calculation methods from 99 Studies that either (a) compared individuals with AN to those With subclinical eating disorders or (b) conducted AN treatment trials. Each weight Cutoff was applied to a nationally representative (n = 12001) and treatment-seeking (n = 189) sample to determine the impact of EBW calculation on the proportion who met the AN weight criterion.
Results. Coders identified 10 different EBW methods, each of which produced different weight cut-offs for the diagnosis of AN. Although only 0.23%, of the national sample met the lowest cut-off, this number increased 43-fold to 10.10% under the highest cut-off. Similarly, only 48.1% of treatment seekers met the lowest cut-off, whereas 89.4%, met the highest.
Conclusions. There is considerable variance across studies in the determination of the AN weight cut-off. Discrepancies Substantially affect the proportion of individuals who are eligible for diagnosis, treatment and insurance reimbursement. However, differences may not be fully appreciated because the ubiquitous citation of the 85%, criterion creates a sense of false consensus.
C1 [Thomas, J. J.] Massachusetts Gen Hosp, Eating Disorders Clin & Res Program, Boston, MA 02114 USA.
[Thomas, J. J.; Roberto, C. A.; Brownell, K. D.] Yale Univ, Dept Psychol, New Haven, CT 06520 USA.
[Thomas, J. J.] Harvard Univ, McLean Hosp, Klarman Eating Disorders Ctr, Sch Med, Cambridge, MA 02138 USA.
RP Thomas, JJ (reprint author), Massachusetts Gen Hosp, Eating Disorders Clin & Res Program, WAC-816D,15 Parkman St, Boston, MA 02114 USA.
EM jjthomas@partners.org
FU NIMH NIH HHS [1F31 MH078394, F31 MH078394, F31 MH078394-01, F31
MH078394-02]
NR 56
TC 12
Z9 12
U1 4
U2 7
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 0033-2917
J9 PSYCHOL MED
JI Psychol. Med.
PD MAY
PY 2009
VL 39
IS 5
BP 833
EP 843
DI 10.1017/S0033291708004327
PG 11
WC Psychology, Clinical; Psychiatry; Psychology
SC Psychology; Psychiatry
GA 438QA
UT WOS:000265569200015
PM 18775087
ER
PT J
AU Zhang, XY
Zhou, DF
Qi, LY
Chen, S
Cao, LY
Chen, DC
Xiu, MH
Wang, F
Wu, GY
Lu, L
Kosten, TA
Kosten, TR
AF Zhang, Xiang Yang
Zhou, Dong Feng
Qi, Ling Yan
Chen, Song
Cao, Lian Yuan
Chen, Da Chun
Xiu, Mei Hong
Wang, Fan
Wu, Gui Ying
Lu, Lin
Kosten, Therese A.
Kosten, Thomas R.
TI Superoxide dismutase and cytokines in chronic patients with
schizophrenia: association with psychopathology and response to
antipsychotics
SO PSYCHOPHARMACOLOGY
LA English
DT Article
DE Schizophrenia; Immune; Cytokine; Oxidative stress; Antioxidant enzymes;
Antipsychotic; Psychopathology
ID NEUROLEPTIC-FREE SCHIZOPHRENIA; ANTIOXIDANT DEFENSE SYSTEM; FREE-RADICAL
PATHOLOGY; IN-VITRO PRODUCTION; TRANSCRIPTION FACTOR; SERUM
INTERLEUKIN-6; TARDIVE-DYSKINESIA; FATTY-ACIDS; CSF LEVELS; DRUG-FREE
AB Both schizophrenia and oxidative stress have been associated with immune system abnormalities in interleukin-2 and -6 (IL-2; IL-6) and increases in superoxide dismutase (SOD) activity. These abnormalities may improve during antipsychotic drug treatment that reduces symptoms in schizophrenic patients.
Subjects included 30 healthy controls (HC) and 78 schizophrenic (SCH) in-patients who were randomly assigned to 12 weeks of double-blind treatment with risperidone 6 mg/day or haloperidol 20 mg/day. Ratings using the Positive and Negative Syndrome Scale (PANSS) were correlated with blood SOD and serum IL-2 levels.
SCH patients who were medication-free for 2 weeks had greater SOD, IL-2, and IL-6 levels than HC. At baseline, these SOD elevations were associated with higher PANSS total scores and the IL-2 elevations with lower PANSS positive symptom scores. The SOD and IL-2 levels in the SCH were also positively correlated. After treatment, PANSS positive symptoms and both SOD and IL-2 showed a significant decrease, but IL-6 showed no change. The SOD and IL-2 reductions were correlated with the reductions in PANSS total score, and SOD reductions also correlated with positive subscore reductions. Females showed these associations more strongly than males.
Our results suggest that the dysregulation in the cytokine system and oxidative stress in patients with schizophrenia is implicated in clinical symptoms and is improved at least partially with antipsychotic treatment. The stronger associations in females deserve further study and confirmation.
C1 [Zhang, Xiang Yang; Kosten, Thomas R.] Baylor Coll Med, VA Med Ctr, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA.
[Zhou, Dong Feng] Peking Univ, Inst Mental Hlth, Beijing 100083, Peoples R China.
[Zhang, Xiang Yang; Qi, Ling Yan; Chen, Song; Cao, Lian Yuan; Chen, Da Chun; Xiu, Mei Hong; Wang, Fan] Beijing HuiLongGuan Hosp, Ctr Biol Psychiat, Beijing 100096, Peoples R China.
[Lu, Lin] Peking Univ, Natl Inst Drug Dependence, Beijing 10083, Peoples R China.
RP Zhang, XY (reprint author), Baylor Coll Med, VA Med Ctr, Menninger Dept Psychiat & Behav Sci, Res Bldg 109,Room 130,2002 Holcombe Blvd, Houston, TX 77030 USA.
EM xyzhang@bcm.edu
FU Stanley Medical Institute Foundation [03T-459, 05T-726]; Mental Illness
Research, Education and Clinical Center (MIRECC); National Institute on
Drug Abuse [K05-DA0454, P50-DA18827]
FX This study was funded by the Stanley Medical Institute Foundation
(03T-459, 05T-726; XYZ), and the Department of Veterans Affairs, VISN 1,
Mental Illness Research, Education and Clinical Center (MIRECC) and
National Institute on Drug Abuse K05-DA0454 and P50-DA18827 (TRK).
NR 55
TC 43
Z9 45
U1 2
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0033-3158
J9 PSYCHOPHARMACOLOGY
JI Psychopharmacology
PD MAY
PY 2009
VL 204
IS 1
BP 177
EP 184
DI 10.1007/s00213-008-1447-6
PG 8
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 436AT
UT WOS:000265385700017
PM 19139851
ER
PT J
AU Sandt, AR
Sloan, DM
Johnson, KJ
AF Sandt, Arthur R.
Sloan, Denise M.
Johnson, Kareem J.
TI Measuring appetitive responding with the postauricular reflex
SO PSYCHOPHYSIOLOGY
LA English
DT Article
DE Emotion; Startle blink; Normal volunteers; EMG; Motivation
ID AFFECTIVE STARTLE MODULATION; FEAR-POTENTIATED STARTLE; PREPULSE
INHIBITION; EMOTION; ATTENTION; RATS; LY354740; AGONIST; PROBE
AB Recent research has provided evidence that the postauricular reflex (PAR) is potentiated while people view pleasant images relative to unpleasant and neutral images. The present study sought to extend these findings by investigating whether the PAR is more robustly modulated by the appetitive salience of the stimuli. Eyeblink startle and PAR responses of 51 participants were recorded while they viewed images that varied in valence and thematic content. Participants displayed significantly greater mean PAR magnitude during appetitive-related images (e.g., food, erotica, families) compared with non-appetitive-related pleasant images. These findings support the contention that the PAR is a useful tool for measuring appetitive responding in humans.
C1 [Sloan, Denise M.] Natl Ctr PTSD, VA Boston Healthcare Syst, Boston, MA USA.
[Sandt, Arthur R.; Johnson, Kareem J.] Temple Univ, Dept Psychol, Philadelphia, PA USA.
[Sloan, Denise M.] Boston Univ, Sch Med, Boston, MA 02118 USA.
RP Sloan, DM (reprint author), Natl Ctr PTSD 116B 2, VA Boston Healthcare Syst, 150 S Huntington Ave, Boston, MA 02130 USA.
EM Denise.Sloan@va.gov
OI Sloan, Denise/0000-0002-0962-478X
NR 29
TC 12
Z9 12
U1 1
U2 13
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0048-5772
J9 PSYCHOPHYSIOLOGY
JI Psychophysiology
PD MAY
PY 2009
VL 46
IS 3
BP 491
EP 497
DI 10.1111/j.1469-8986.2009.00797.x
PG 7
WC Psychology, Biological; Neurosciences; Physiology; Psychology;
Psychology, Experimental
SC Psychology; Neurosciences & Neurology; Physiology
GA 430SG
UT WOS:000265008200007
PM 19496218
ER
PT J
AU Chao, CP
Walker, TG
Kalva, SP
AF Chao, Christine P.
Walker, T. Gregory
Kalva, Sanjeeva P.
TI Natural History and CT Appearances of Aortic Intramural Hematoma
SO RADIOGRAPHICS
LA English
DT Article
ID MULTIDETECTOR ROW CT; THORACIC AORTA; IMAGING FEATURES; RETROPERITONEAL
FIBROSIS; ATHEROSCLEROTIC ULCER; IMPENDING RUPTURE; ASCENDING AORTA;
HELICAL CT; DISSECTION; DIAGNOSIS
AB Rupture of the vasa vasorum into the media of the aortic wall results in an aortic intramural hematoma. Characteristic findings of an aortic intramural hematoma include a crescentic hyperattenuating fluid collection at unenhanced computed tomography (CT) and a smooth, nonenhancing, thickened aortic wall at contrast material-enhanced CT. The CT appearance of untreated intramural hematomas evolves over time, and decreased attenuation is a clue to the chronicity of a hematoma. CT is particularly useful for evaluating aortic intramural hematomas because it allows their differentiation from aortic dissections, which have similar clinical manifestations, and permits an exact determination of their location-crucial information for surgical planning. On the basis of CT findings, some hematomas may be expected to resolve spontaneously, whereas others may be identified as posing a high risk for serious complications such as aortic dissection, aneurysm, and rupture. Appropriate clinical management is aided by accurate recognition of diagnostically specific CT features and awareness of their significance. (C) RSNA, 2009. radiographics.rsnajnls.org
C1 [Chao, Christine P.; Walker, T. Gregory; Kalva, Sanjeeva P.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
RP Chao, CP (reprint author), Kaiser Permanente, 99 Montecillo Rd, San Rafael, CA 94903 USA.
EM c.chao.md@gmail.com
NR 37
TC 37
Z9 43
U1 0
U2 2
PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0271-5333
J9 RADIOGRAPHICS
JI Radiographics
PD MAY-JUN
PY 2009
VL 29
IS 3
BP 791
EP 804
DI 10.1148/rg.293085122
PG 14
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 455UC
UT WOS:000266790800014
PM 19448116
ER
PT J
AU Dupuis, CS
Westra, SJ
Makris, J
Wallace, EC
AF Dupuis, Carolyn S.
Westra, Sjirk J.
Makris, Joseph
Wallace, E. Christine
TI Injuries and Conditions of the Extensor Mechanism of the Pediatric Knee
SO RADIOGRAPHICS
LA English
DT Article; Proceedings Paper
CT 93rd Scientific Assembly and Annual Meeting of the
Radiological-Society-of-North-America
CY NOV 25-30, 2007
CL Chicago, IL
SP Radiol Soc N Amer
ID AVULSION FRACTURES; SLEEVE FRACTURE; CHILDREN; PATELLA
AB The extensor mechanism of the knee is essential to ambulation and is subject to a number of traumatic, congenital, and inflammatory processes. In the pediatric population, the spectrum of pathologic conditions affecting the extensor mechanism is specific to skeletally immature patients. In addition, certain congenital and developmental disorders may further predispose the knee extensor mechanism to injury. The pathologic processes can be subdivided into categories: conditions of the attachments and insertions of the quadriceps and patellar tendons, conditions of the patella, conditions of the quadriceps muscle group, and avulsions of the superior attachments of the quadriceps. Cases of conditions affecting the extensor mechanism of the pediatric knee were collected at two large trauma centers, and the clinical and radiologic features were reviewed. Initial evaluation of these conditions is performed with radiography, but magnetic resonance imaging has evolved into a useful adjunct for assessing the soft tissues for a more precise evaluation of the true extent of an injury, thereby affecting decisions about surgical intervention and prognosis. (C) RSNA, 2009. radiographics.rsnajnls.org
C1 [Dupuis, Carolyn S.] Univ Massachusetts, Sch Med, Dept Radiol, Worcester, MA 01655 USA.
Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
RP Dupuis, CS (reprint author), Univ Massachusetts, Sch Med, Dept Radiol, 55 Lake Ave N, Worcester, MA 01655 USA.
EM dupuisc@ummhc.org
NR 17
TC 19
Z9 20
U1 0
U2 0
PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0271-5333
J9 RADIOGRAPHICS
JI Radiographics
PD MAY-JUN
PY 2009
VL 29
IS 3
BP 877
EP 886
DI 10.1148/rg.293085163
PG 10
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 455UC
UT WOS:000266790800020
PM 19448122
ER
PT J
AU Sosnovik, DE
AF Sosnovik, David E.
TI Will Molecular MR Imaging Play a Role in Identification and Treatment of
Patients with Vulnerable Atherosclerotic Plaques?
SO RADIOLOGY
LA English
DT Article
AB Although the translation of experimental molecular MR imaging agents is highly compelling, it is substantially more complex than the translation of radiolabeled imaging agents. The prognostic value, safety, and cost-effectiveness of molecular MR imaging for the detection of plaque inflammation will need to be demonstrated and will require a robust and collaborative effort among basic scientists, clinicians, epidemiologists, and industry. The well-conducted and valuable study reported by Amirbekian et al (1) in this issue of Radiology adds further momentum to this important endeavor.
C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res,Dept Radiol, Boston, MA 02129 USA.
RP Sosnovik, DE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res,Dept Radiol, 149 13th St, Boston, MA 02129 USA.
EM sosnovik@nmr.mgh.harvard.edu
NR 8
TC 2
Z9 3
U1 0
U2 2
PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0033-8419
J9 RADIOLOGY
JI Radiology
PD MAY
PY 2009
VL 251
IS 2
BP 309
EP 310
DI 10.1148/radiol.2512090268
PG 2
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 439QW
UT WOS:000265643100001
PM 19401565
ER
PT J
AU Rybak, LD
Rosenthal, DI
Wittig, JC
AF Rybak, Leon D.
Rosenthal, Daniel I.
Wittig, James C.
TI Chondroblastoma: Radiofrequency Ablation-Alternative to Surgical
Resection in Selected Cases
SO RADIOLOGY
LA English
DT Article
ID METASTASES INVOLVING BONE; OSTEOID OSTEOMA; ELECTRODE
AB Purpose: To demonstrate that radiofrequency (RF) ablation can be used safely and effectively to treat selected cases of chondroblastoma.
Materials and Methods: Approval was obtained from institutional review boards, research was in compliance with HIPAA protocol. The need to obtain informed consent was waived for retrospective review of patient records. The records of patients with biopsy-proved chondroblastoma who were treated with RF ablation at two academic centers from July 1995 to July 2007 were reviewed. RF ablation was performed with a single-tip electrode by using computed tomography for guidance. Lesion characteristics were determined from imaging studies obtained at the time of the procedure. Symptoms were assessed before and 1 day after the procedure. Longer-term follow-up was obtained from medical records.
Results: Thirteen male and four female patients were treated (mean age, 17.3 years). The lesions were located in the proximal humerus (n = 7), proximal tibia (n = 4), proximal femur (n = 3), and distal femur (n = 3). The mean volume of the lesions was 2.46 mL. All patients reported relief of symptoms on postprocedure day 1. Three patients were lost to follow-up. Of the 14 patients for whom longer-term (mean, 41.3 months; range, 4-134 months) follow-up was available, 12 had complete relief of symptoms with no need for medications and full return to all activities. The patient who had the largest lesion of the study required surgical intervention because of collapse of the articular surface in the treatment area. Residual viable tumor was found at surgery. Another patient experienced mechanical problems that were thought to be unrelated to the RF ablation and was rendered pain-free after subsequent surgical treatment.
Conclusion: Percutaneous RF ablation is an alternative to surgery for treatment of selected chondroblastomas. Larger lesions beneath weight-bearing surfaces should be approached with caution due to an increased risk of articular collapse and recurrence.
C1 [Rybak, Leon D.] NYU, Hosp Joint Dis, Dept Radiol, New York, NY 10003 USA.
[Rosenthal, Daniel I.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Wittig, James C.] Mt Sinai Med Ctr, Dept Orthoped Surg, New York, NY 10029 USA.
RP Rybak, LD (reprint author), NYU, Hosp Joint Dis, Dept Radiol, 301 E 17th St,6th Floor, New York, NY 10003 USA.
EM Leon.rybak@med.nyu.edu
OI RYBAK, Leon/0000-0003-0467-577X
NR 16
TC 35
Z9 37
U1 0
U2 0
PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0033-8419
J9 RADIOLOGY
JI Radiology
PD MAY
PY 2009
VL 251
IS 2
BP 599
EP 604
DI 10.1148/radiol.2512080500
PG 6
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 439QW
UT WOS:000265643100036
PM 19304917
ER
PT J
AU Liu, SS
Wu, CL
Ballantyne, JC
Buvanendran, A
Rathmell, JP
Warren, DT
Viscusi, ER
Ginsberg, B
Rosenquist, RW
Yadeau, JT
Liguori, GA
AF Liu, Spencer S.
Wu, Christopher L.
Ballantyne, Jane C.
Buvanendran, Asokumar
Rathmell, James P.
Warren, Daniel T.
Viscusi, Eugene R.
Ginsberg, Brian
Rosenquist, Richard W.
Yadeau, Jacques T.
Liguori, Gregory A.
TI Where in the World Is ASRA AcutePOP?
SO REGIONAL ANESTHESIA AND PAIN MEDICINE
LA English
DT Article
AB Progress continues on American Society of Regional Anesthesia (ASRA) AcutePOP Highlights include selection of data fields and creation of definitions for complications jointly accepted by clinical registries for ASRA, American Society of Anesthesiologists, Regional Anesthesia Surveillance System, Society for Obstetric Anesthesia and Perinatology, and Society for Pediatric Anesthesia. Development of a Web site and applications continues, and a demonstration is planned for the ASRA 2009 meeting.
C1 [Liu, Spencer S.; Yadeau, Jacques T.; Liguori, Gregory A.] Hosp Special Surg, Dept Anesthesiol, New York, NY 10021 USA.
[Liu, Spencer S.; Yadeau, Jacques T.; Liguori, Gregory A.] Weill Cornell Med Coll, New York, NY USA.
[Wu, Christopher L.] Johns Hopkins Univ, Dept Anesthesiol & Crit Care Med, Baltimore, MD USA.
[Ballantyne, Jane C.] Univ Penn, Dept Anesthesiol & Crit Care, Philadelphia, PA 19104 USA.
[Buvanendran, Asokumar] Rush Univ, Med Ctr, Dept Anesthesiol, Chicago, IL 60612 USA.
[Rathmell, James P.] Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA.
[Warren, Daniel T.] Virginia Mason Med Ctr, Dept Anesthesiol, Seattle, WA 98101 USA.
[Warren, Daniel T.] Univ Washington, Seattle, WA 98195 USA.
[Viscusi, Eugene R.] Thomas Jefferson Univ, Dept Anesthesiol, Philadelphia, PA 19107 USA.
[Ginsberg, Brian] Duke Univ, Dept Anesthesiol, Durham, NC USA.
[Rosenquist, Richard W.] Univ Iowa, Dept Anesthesia, Iowa City, IA 52242 USA.
RP Liu, SS (reprint author), Hosp Special Surg, Dept Anesthesiol, 535 E 70th St, New York, NY 10021 USA.
EM iusp@hss.edu
NR 2
TC 7
Z9 7
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1098-7339
J9 REGION ANESTH PAIN M
JI Region. Anesth. Pain Med.
PD MAY-JUN
PY 2009
VL 34
IS 3
BP 269
EP 274
DI 10.1097/AAP.0b013e3181a39597
PG 6
WC Anesthesiology
SC Anesthesiology
GA 444FH
UT WOS:000265965600019
PM 19591261
ER
PT J
AU Levitt, JJ
Styner, M
Niethammer, M
Bouix, S
Koo, MS
Voglmaier, MM
Dickey, CC
Niznikiewicz, MA
Kikinis, R
McCarley, RW
Shenton, ME
AF Levitt, James J.
Styner, Martin
Niethammer, Marc
Bouix, Sylvain
Koo, Min-Seong
Voglmaier, Martina M.
Dickey, Chandlee C.
Niznikiewicz, Margaret A.
Kikinis, Ron
McCarley, Robert W.
Shenton, Martha E.
TI Shape abnormalities of caudate nucleus in schizotypal personality
disorder
SO SCHIZOPHRENIA RESEARCH
LA English
DT Article
DE Schizotypal personality disorder; Caudate nucleus; Striatum; MRI; Shape;
Spherical harmonics
ID ANTERIOR CINGULATE CORTEX; MEDIAL PREFRONTAL CORTEX; BASAL GANGLIA
VOLUMES; ADULT HUMAN BRAIN; NEUROLEPTIC-NAIVE; SCHIZOPHRENIC-PATIENTS;
MORPHOMETRIC-ANALYSIS; ANTIPSYCHOTIC-DRUGS; HUMAN STRIATUM; MRI DATA
AB Background: Previously, we reported abnormal volume and global shape in the caudate nucleus in schizotypal personality disorder (SPD). Here, we use a new shape measure which importantly permits local in addition to global shape analysis, as well as local correlations with behavioral measures.
Methods: Thirty-two female and 15 male SPDs, and 29 female and 14 male normal controls (NCLs), underwent brain magnetic resonance imaging (MRI). We assessed caudate shape measures using spherical harmonic-point distribution model (SPHARM-PDM) methodology.
Results: We found more pronounced global shape differences in the right caudate in male and female SPD, compared with NCLs. Local shape differences, principally in the caudate head, survived statistical correction on the right. Also, we performed correlations between local surface deformations with clinical measures and found significant correlations between local shape deflated deformations in the anterior medial surface of the caudate with verbal learning capacity in female SPD.
Conclusions: Using SPHARM-PDM methodology, we found both global and local caudate shape abnormalities in male and female SPD, particularly right-sided, and largely restricted to limbic and cognitive anterior caudate. The most important and novel findings were bilateral statistically significant correlations between local surface deflations in the anterior medial surface of the head of the caudate and verbal learning capacity in female SPD. By extension, these local caudate correlation findings implicate the ventromedial prefrontal cortex (vmPFC), which innervates that area of the caudate, and demonstrate the utility of local shape analysis to investigate the relationship between specific subcortical and cortical brain structures in neuropsychiatric conditions. (c) 2008 Published by Elsevier B.V.
C1 [Levitt, James J.; Voglmaier, Martina M.; Dickey, Chandlee C.; Niznikiewicz, Margaret A.; McCarley, Robert W.; Shenton, Martha E.] Harvard Univ, Sch Med, Vet Affairs Boston Healthcare Syst, Dept Psychiat,Brockton Div,Lab Neurosci, Brockton, MA 02301 USA.
[Levitt, James J.; Bouix, Sylvain; Dickey, Chandlee C.; Niznikiewicz, Margaret A.; Shenton, Martha E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Psychiat,Psychiat Neuroimaging Lab, Boston, MA 02115 USA.
[Kikinis, Ron; Shenton, Martha E.] Harvard Univ, Brigham & Womens Hosp, Sch Med,Dept Radiol, Surg Planning Lab,Magnet Resonance Imaging Div, Boston, MA 02115 USA.
[Styner, Martin; Niethammer, Marc] Univ N Carolina, Dept Comp Sci, Chapel Hill, NC USA.
[Styner, Martin; Niethammer, Marc] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA.
[Koo, Min-Seong] Kwandong Univ, Coll Med, Seoul, South Korea.
[Voglmaier, Martina M.] Cambridge Hlth Alliance, Dept Psychiat, Cambridge, MA USA.
RP Levitt, JJ (reprint author), Harvard Univ, Sch Med, VA Boston Healthcare Syst, Dept Psychiat 116A, 940 Belmont St, Brockton, MA 02301 USA.
EM james_levitt@hms.harvard.edu
RI McCarley, Robert/N-5562-2014;
OI McCarley, Robert/0000-0001-5705-7495; Styner,
Martin/0000-0002-8747-5118; Bouix, Sylvain/0000-0003-1326-6054
FU National Institute of Health [K05MH070047, R01 MH50740, R01 MH 40799,
R01 MH 052807, U54 EB005149, P50MH080272]
FX This work was supported in part by Department of Veteran Affairs Awards
(Merits, JJL, MES, RWM: Research Enhancement Award Program, RWM, MES),
and National Institute of Health grants K05MH070047 and R01 MH50740
(MES) and R01 MH 40799 and R01 MH 052807 (RWM), Grant U54 EB005149 (RK,
CC, MES, MS, MR), P50MH080272 (RWM MES, MK,SB).
NR 63
TC 20
Z9 20
U1 1
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0920-9964
J9 SCHIZOPHR RES
JI Schizophr. Res.
PD MAY
PY 2009
VL 110
IS 1-3
BP 127
EP 139
DI 10.1016/j.schres.2008.11.012
PG 13
WC Psychiatry
SC Psychiatry
GA 463MZ
UT WOS:000267437600016
PM 19328654
ER
PT J
AU Niznikiewicz, MA
Spencer, KM
Dickey, C
Voglmaier, M
Seidman, LJ
Shenton, ME
McCarley, RW
AF Niznikiewicz, Margaret A.
Spencer, Kevin M.
Dickey, Chandlee
Voglmaier, Martina
Seidman, Larry J.
Shenton, Martha E.
McCarley, Robert W.
TI Abnormal pitch mismatch negativity in individuals with schizotypal
personality disorder
SO SCHIZOPHRENIA RESEARCH
LA English
DT Article
DE MMN; SPD; Schizophrenia; Auditory processing; Auditory cortex
ID AUDITORY SENSORY MEMORY; CHRONIC-SCHIZOPHRENIA; GYRUS VOLUME;
GENERATION; DEFICITS; 1ST-EPISODE; ONSET; DYSFUNCTION; POTENTIALS;
MODULATION
AB Background: The goal of the study was to examine mismatch negativity (MMN) in schizotypal personality disorder (SPD) individuals. Abnormal MMN has been a consistent finding in chronic schizophrenia and there also have been reports of reduced duration MMN in first episode schizophrenia patients [Umbricht, D., Krljes, S., Mismatch negativity in schizophrenia: a meta-analysis. Schizophrenia Research (2005); 76(1):1-23], with some studies finding no pitch MMN amplitude differences [Salisbury, D.F., Shenton, M.E., Griggs, C.B., Bonner-Jackson, A., McCarley, R.W., Mismatch negativity in chronic schizophrenia and first-episode schizophrenia. Archives of General Psychiatry (2002); 59(8):686-694.], while others reporting a modest reduction [Umbricht, D.S., Bates, J.A., Lieberman, J.A., Kane, J.M., Javitt, D.C., Electrophysiological indices of automatic and controlled auditory information processing in first-episode, recent-onset and chronic schizophrenia. Biological Psychiatry (2006); 59(8):762-772], in recent onset schizophrenia patients. To our knowledge no reports exist of MMN in SPD individuals.
Methods: Twenty six normal (14 females) control and 23 SPD (12 females) individuals were tested using the pitch MMN paradigm. Normal control (NC) and SPD individuals were recruited from the general population and assessed using DSM-IV. SPD individuals were included if they met 5 or more criteria for SPD disorder. The subjects listened to 2000 frequent 1 kHz pure tones and 100 rare 1.2 kHz pure tones while reading a magazine article. MMN was measured from a difference waveform within the latency window of 175-276 ms.
Results: Reduced MMN amplitude was found in SPD relative to NC subjects (p < 0.045).
Conclusions: These results point to potential differences between SPD and schizophrenia, where no reduction in MMN was found in most studies of first episode patients. Published by Elsevier B.V.
C1 [Niznikiewicz, Margaret A.; Spencer, Kevin M.; Dickey, Chandlee; Voglmaier, Martina; Seidman, Larry J.; Shenton, Martha E.; McCarley, Robert W.] Harvard Univ, Sch Med, Boston VA Healthcare Syst, Brockton, MA 02301 USA.
[Seidman, Larry J.] Beth Israel Deaconess Med Ctr, Boston VA Healthcare Syst, Boston, MA 02215 USA.
[Seidman, Larry J.] Massachusetts Gen Hosp, Boston VA Healthcare Syst, Boston, MA 02114 USA.
RP Niznikiewicz, MA (reprint author), Harvard Univ, Sch Med, Boston VA Healthcare Syst, Psychiat 116A,940 Belmont St, Brockton, MA 02301 USA.
EM margaret_niznikiewicz@hms.harvard.edu
RI McCarley, Robert/N-5562-2014;
OI McCarley, Robert/0000-0001-5705-7495; Spencer, Kevin/0000-0002-5500-7627
FU MAN [R01 MH 63360]; RWM [R01 MH 52807]
FX The research has been funded with grants awarded to MAN (R01 MH 63360)
and to RWM (R01 MH 52807). The NIMH had no further role in study design:
in the collection, analysis and interpretation of the data; in the
writing ofthe report: and in the decision to submit the paper for
publication.
NR 41
TC 16
Z9 16
U1 2
U2 7
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0920-9964
J9 SCHIZOPHR RES
JI Schizophr. Res.
PD MAY
PY 2009
VL 110
IS 1-3
BP 188
EP 193
DI 10.1016/j.schres.2008.10.017
PG 6
WC Psychiatry
SC Psychiatry
GA 463MZ
UT WOS:000267437600023
PM 19327968
ER
PT J
AU Livingston, DM
AF Livingston, David M.
TI Complicated Supercomplexes
SO SCIENCE
LA English
DT Editorial Material
ID CANCER SUSCEPTIBILITY GENE; BREAST-CANCER; FANCONI-ANEMIA; PALB2;
MUTATIONS; PARTNER
C1 [Livingston, David M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Genet, Boston, MA 02115 USA.
[Livingston, David M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA.
RP Livingston, DM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Genet, Boston, MA 02115 USA.
EM david_livingston@dfci.harvard.edu
NR 14
TC 12
Z9 12
U1 1
U2 3
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD MAY 1
PY 2009
VL 324
IS 5927
BP 602
EP 603
DI 10.1126/science.1174839
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 439DW
UT WOS:000265608800031
PM 19407191
ER
PT J
AU Schweitzer, MH
Zheng, WX
Organ, CL
Avci, R
Suo, ZY
Freimark, LM
Lebleu, VS
Duncan, MB
Heiden, MGV
Neveu, JM
Lane, WS
Cottrell, JS
Horner, JR
Cantley, LC
Kalluri, R
Asara, JM
AF Schweitzer, Mary H.
Zheng, Wenxia
Organ, Chris L.
Avci, Recep
Suo, Zhiyong
Freimark, Lisa M.
Lebleu, Valerie S.
Duncan, Michael B.
Heiden, Matthew G. Vander
Neveu, John M.
Lane, William S.
Cottrell, John S.
Horner, John R.
Cantley, Lewis C.
Kalluri, Raghu
Asara, John M.
TI Biomolecular Characterization and Protein Sequences of the Campanian
Hadrosaur B. canadensis
SO SCIENCE
LA English
DT Article
ID TYRANNOSAURUS-REX; SOFT-TISSUE; CELLULAR PRESERVATION;
MASS-SPECTROMETRY; IDENTIFICATION; MASTODON; BONE; OSTEOCYTE; BACTERIAL;
COLLAGEN
AB Molecular preservation in non-avian dinosaurs is controversial. We present multiple lines of evidence that endogenous proteinaceous material is preserved in bone fragments and soft tissues from an 80-million-year-old Campanian hadrosaur, Brachylophosaurus canadensis [Museum of the Rockies (MOR) 2598]. Microstructural and immunological data are consistent with preservation of multiple bone matrix and vessel proteins, and phylogenetic analyses of Brachylophosaurus collagen sequenced by mass spectrometry robustly support the bird-dinosaur clade, consistent with an endogenous source for these collagen peptides. These data complement earlier results from Tyrannosaurus rex (MOR 1125) and confirm that molecular preservation in Cretaceous dinosaurs is not a unique event.
C1 [Schweitzer, Mary H.; Zheng, Wenxia] N Carolina State Univ, Raleigh, NC 27695 USA.
[Schweitzer, Mary H.] N Carolina Museum Nat Sci, Raleigh, NC 27601 USA.
[Organ, Chris L.] Harvard Univ, Dept Organism & Evolutionary Biol, Cambridge, MA 02138 USA.
[Avci, Recep; Suo, Zhiyong] Montana State Univ, Imaging & Chem Anal Lab, Bozeman, MT 59717 USA.
[Freimark, Lisa M.; Cantley, Lewis C.; Asara, John M.] Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02115 USA.
[Lebleu, Valerie S.; Duncan, Michael B.; Kalluri, Raghu] Beth Israel Deaconess Med Ctr, Div Matrix Biol, Boston, MA 02115 USA.
[Lebleu, Valerie S.; Duncan, Michael B.; Kalluri, Raghu] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
[Heiden, Matthew G. Vander] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Neveu, John M.; Lane, William S.] Harvard Univ, Ctr Syst Biol, Fac Arts & Sci, Cambridge, MA 02138 USA.
[Cottrell, John S.] Matrix Sci Ltd, London W1U 7GB, England.
[Horner, John R.] Museum Rockies, Bozeman, MT 59717 USA.
[Cantley, Lewis C.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA.
[Kalluri, Raghu] Harvard Univ, Dept Biol Chem & Mol Pharmacol, Cambridge, MA 02139 USA.
[Kalluri, Raghu] Harvard Univ, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
[Asara, John M.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RP Schweitzer, MH (reprint author), N Carolina State Univ, Raleigh, NC 27695 USA.
EM schweitzer@ncsu.edu; jasara@bidmc.harvard.edu
RI Cantley, Lewis/D-1800-2014; LeBleu, Valerie /E-2991-2015; Kalluri,
Raghu/E-2677-2015
OI Cantley, Lewis/0000-0002-1298-7653; Kalluri, Raghu/0000-0002-2190-547X
FU NSF [EAR 0722702, EAR 0634136, EAR 0548847, EAR-0541744]; David and
Lucile Packard Foundation; United Negro College Fund Merck Postdoctoral
Science Research Fellowship; Taplin Funds for Discovery (Harvard Medical
School); NASA Expermental Project to Simulate Competitive Research
[NCC5-579]; Damon Runyon Cancer Research Foundation; NIH [DK 55001, DK
62987, AA 13913, DK 61866, CA 125550]; Department of Medicine for the
Division of Matrix Biology at the Beth Israel Deaconess Medical Center
FX We acknowledge funding from NSF [awards EAR 0722702 and EAR 0634136
(J.M.A.) and EAR 0548847 and EAR-0541744 (M.H.S.)]; the David and Lucile
Packard Foundation (M.H.S.); United Negro College Fund Merck
Postdoctoral Science Research Fellowship (M.B.D.); the Taplin Funds for
Discovery (Harvard Medical School); partial support by NASA Expermental
Project to Simulate Competitive Research under grant NCC5-579 (R.A. and
Z.S.); Damon Runyon Cancer Research Foundation (M.G.V.H.); NIH grants DK
55001, DK 62987, AA 13913, DK 61866, and CA 125550; and the Department
of Medicine for the Division of Matrix Biology at the Beth Israel
Deaconess Medical Center. Correspondence and requests for materials
should be addressed to M.H.S. for biochemical and morphological analyses
and to J.M.A. for mass spectrometry and molecular phylogenetics
analyses.
NR 24
TC 80
Z9 85
U1 3
U2 40
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD MAY 1
PY 2009
VL 324
IS 5927
BP 626
EP 631
DI 10.1126/science.1165069
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 439DW
UT WOS:000265608800039
PM 19407199
ER
PT J
AU Serneels, L
Van Biervliet, J
Craessaerts, K
Dejaegere, T
Horre, K
Van Houtvin, T
Esselmann, H
Paul, S
Schafer, MK
Berezovska, O
Hyman, BT
Sprangers, B
Sciot, R
Moons, L
Jucker, M
Yang, ZX
May, PC
Karran, E
Wiltfang, J
D'Hooge, R
De Strooper, B
AF Serneels, Lutgarde
Van Biervliet, Jerome
Craessaerts, Katleen
Dejaegere, Tim
Horre, Katrien
Van Houtvin, Tine
Esselmann, Hermann
Paul, Sabine
Schaefer, Martin K.
Berezovska, Oksana
Hyman, Bradley T.
Sprangers, Ben
Sciot, Raf
Moons, Lieve
Jucker, Mathias
Yang, Zhixiang
May, Patrick C.
Karran, Eric
Wiltfang, Jens
D'Hooge, Rudi
De Strooper, Bart
TI gamma-Secretase Heterogeneity in the Aph1 Subunit: Relevance for
Alzheimer's Disease
SO SCIENCE
LA English
DT Article
ID AMYLOID PRECURSOR PROTEIN; MODERATE REDUCTION; TRANSGENIC MODEL;
IN-VIVO; MICE; PRESENILIN-1; COMPLEXES; DEFICIENCY; EXPRESSION; CLEAVAGE
AB The gamma-secretase complex plays a role in Alzheimer's disease and cancer progression. The development of clinically useful inhibitors, however, is complicated by the role of the gamma-secretase complex in regulated intramembrane proteolysis of Notch and other essential proteins. Different gamma-secretase complexes containing different Presenilin or Aph1 protein subunits are present in various tissues. Here we show that these complexes have heterogeneous biochemical and physiological properties. Specific inactivation of the Aph1B gamma-secretase in a mouse Alzheimer's disease model led to improvements of Alzheimer's disease-relevant phenotypic features without any Notch-related side effects. The Aph1B complex contributes to total gamma-secretase activity in the human brain, and thus specific targeting of Aph1B-containing gamma-secretase complexes may help generate less toxic therapies for Alzheimer's disease.
C1 [Serneels, Lutgarde; Van Biervliet, Jerome; Craessaerts, Katleen; Dejaegere, Tim; Horre, Katrien; Van Houtvin, Tine; De Strooper, Bart] Katholieke Univ Leuven VIB, Dept Mol & Dev Genet, B-3000 Louvain, Belgium.
[Serneels, Lutgarde; Van Biervliet, Jerome; Craessaerts, Katleen; Dejaegere, Tim; Horre, Katrien; Van Houtvin, Tine; De Strooper, Bart] Katholieke Univ Leuven, Ctr Human Genet, B-3000 Louvain, Belgium.
[Esselmann, Hermann; Paul, Sabine; Wiltfang, Jens] Univ Erlangen Nurnberg, Dept Psychiat & Psychotherapy, D-91054 Erlangen, Germany.
[Esselmann, Hermann; Paul, Sabine; Wiltfang, Jens] Univ Duisburg Essen, Rhine State Hosp Essen, Dept Psychiat & Psychotherapy, D-45147 Essen, Germany.
[Schaefer, Martin K.] Univ Marburg, Inst Anat & Cell Biol, Dept Mol Neurosci, D-35032 Marburg, Germany.
[Berezovska, Oksana; Hyman, Bradley T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Disorders, Charlestown, MA 02129 USA.
[Sprangers, Ben] Katholieke Univ Leuven, Lab Expt Transplantat, B-3000 Louvain, Belgium.
[Sciot, Raf] Katholieke Univ Leuven, Lab Morphol & Mol Pathol, B-3000 Louvain, Belgium.
[Moons, Lieve] Katholieke Univ Leuven, Lab Neural Circuit Dev & Regenerat, Dept Biol, B-3000 Louvain, Belgium.
[Jucker, Mathias] Univ Tubingen, Dept Cellular Neurol, Hertie Inst Clin Brain Res, D-72076 Tubingen, Germany.
[Yang, Zhixiang; May, Patrick C.] Eli Lilly & Co, Lilly Res Labs, Neurosci Discovery Res, Indianapolis, IN 46285 USA.
[Karran, Eric] Lilly Res Ctr Ltd, Windlesham GU20 6PH, Surrey, England.
[D'Hooge, Rudi] Katholieke Univ Leuven, Dept Psychol, Lab Biol Psychol, B-3000 Louvain, Belgium.
RP De Strooper, B (reprint author), Katholieke Univ Leuven VIB, Dept Mol & Dev Genet, Herestr 49, B-3000 Louvain, Belgium.
EM bart.destrooper@med.kuleuven.be
RI De Strooper, Bart/F-6507-2012;
OI De Strooper, Bart/0000-0001-5455-5819; Wiltfang,
Jens/0000-0003-1492-5330
FU Alzheimers Association; Fund for Scientific Research Flanders; KULeuven
(Geconcerteerde onderzoeksacties); Federal Office for Scientific
Affairs, Belgium; Flemish Government [Methusalem]; MEMOSAD of the
European Union [F2-2007-200611]; NIH [P01AG015379, R01AG026593,
AG026593, AG 13579]
FX We thank C. Peeters for assistance in pathological evaluations, C.
Mathieu for FACS analysis, L. Van Aerschot for assistance with
behavioral testing, S. Terclavers and H. Schieb for technical
assistance, and A. Thathiah for proofreading the manuscript. This work
was supported by a Pioneer award from the Alzheimers Association; the
Fund for Scientific Research Flanders (to R.D. and B.D.S.); KULeuven
(Geconcerteerde onderzoeksacties); Federal Office for Scientific
Affairs, Belgium; a Methusalem grant of the Flemish Government; MEMOSAD
(F2-2007-200611) of the European Union; and NIH grants P01AG015379,
R01AG026593, and AG026593 (to B.T.H.) and NIH AG 13579 (to B.T.H. and
O.B.). B.D.S. is a paid consultant for Eli Lilly and Envivo
Pharmaceuticals; B.T.H. is a paid consultant for Elan, Genentech,
Pfizer, Takeda, Link, and Neurophage.
NR 24
TC 124
Z9 135
U1 2
U2 15
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD MAY 1
PY 2009
VL 324
IS 5927
BP 639
EP 642
DI 10.1126/science.1171176
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 439DW
UT WOS:000265608800043
PM 19299585
ER
PT J
AU Ng, AKL
Wang, JH
Shaw, PC
AF Ng, Andy Ka-Leung
Wang Jia-Huai
Shaw, Pang-Chui
TI Structure and sequence analysis of influenza A virus nucleoprotein
SO SCIENCE IN CHINA SERIES C-LIFE SCIENCES
LA English
DT Review
DE Influenza H5N1; nucleoprotein; oligomerization; RNA binding
ID RNA-BINDING; MUTATIONAL ANALYSIS; AVIAN INFLUENZA; IDENTIFICATION;
OLIGOMERIZATION; TRANSCRIPTION; REPLICATION; POLYMERASE; PANHANDLE;
COMPLEX
AB Influenza A virus nucleoprotein (NP) forms homo-oligomers and multiple copies of NP wrap around genomic RNA, along with a trimeric polymerase making up ribonucleoprotein (RNP) complex. Sequence comparison of more than 2500 influenza A NP showed that this protein contains 30.1 % of polymorphic residues. NP is composed of a head and a body domain and a tail loop/ linker region. The head domain is more conserved than the body domain, as revealed from the structure-based sequence alignment. NP oligomerization is mediated by the insertion of the non-polymorphic and structurally conserved tail loop of one NP molecule to a groove of another NP. The different form of NP oligomers is due to the flexibility of the polymorphic linkers that join the tail loop to the rest of the protein. The RNA binding property of NP is known to involve the protruding element and the flexible basic loop between the head and body domains, both having high degree of primary sequence conservation. To bind RNA, NP may first capture the RNA by the flexible basic loop and then the RNA is clamped by the protruding element.
C1 [Ng, Andy Ka-Leung; Shaw, Pang-Chui] Chinese Univ Hong Kong, Dept Biochem, Mol Biotechnol Programme, Shatin, Hong Kong, Peoples R China.
[Ng, Andy Ka-Leung; Shaw, Pang-Chui] Chinese Univ Hong Kong, Ctr Prot Sci & Crystallog, Shatin, Hong Kong, Peoples R China.
[Wang Jia-Huai] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Dana Farber Canc Inst,Dept Pediat, Boston, MA 02115 USA.
RP Shaw, PC (reprint author), Chinese Univ Hong Kong, Dept Biochem, Mol Biotechnol Programme, Shatin, Hong Kong, Peoples R China.
EM pcshaw@cuhk.edu.hk
NR 36
TC 30
Z9 35
U1 2
U2 10
PU SCIENCE PRESS
PI BEIJING
PA 16 DONGHUANGCHENGGEN NORTH ST, BEIJING 100717, PEOPLES R CHINA
SN 1006-9305
J9 SCI CHINA SER C
JI Sci. China Ser. C-Life Sci.
PD MAY
PY 2009
VL 52
IS 5
BP 439
EP 449
DI 10.1007/s11427-009-0064-x
PG 11
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA 451FW
UT WOS:000266457100006
PM 19471866
ER
PT J
AU Meeker, JD
Johnson, PI
Camann, D
Hauser, R
AF Meeker, John D.
Johnson, Paula I.
Camann, David
Hauser, Russ
TI Polybrominated diphenyl ether (PBDE) concentrations in house dust are
related to hormone levels in men
SO SCIENCE OF THE TOTAL ENVIRONMENT
LA English
DT Article
DE Endocrine disruption; Exposure; Flame retardant; Human; Male
ID BROMINATED FLAME RETARDANTS; VOLUME SURFACE SAMPLER; DEVELOPMENTAL
EXPOSURE; INDOOR AIR; MIXTURE; METABOLITES; PESTICIDES; DE-71; RATS
AB Despite documented widespread human exposure to polybrominated diphenyl ethers (PBDEs) through dietary intake and contact with or inhalation of indoor dust, along with growing laboratory evidence for altered endocrine function following exposure, human Studies of PBDE exposure and endocrine effects remain limited. We conducted a preliminary study within an ongoing study on the impact of environmental exposures on male reproductive health. We measured serum hormone levels and PBDE concentrations (BDE 47, 99 and 100) in house dust from 24 men recruited through a US infertility clinic. BDE 47 and 99 were detected in 100% of dust samples, and BDE 100 was detected in 67% of dust samples, at concentrations similar to those reported in previous US studies. In multivariable regression models adjusted for age and BMI, there was a statistically significant inverse relationship between dust PBDE concentrations and free androgen index. Dust PBDE concentrations were also strongly and inversely associated with luteinizing hormone (LH) and follicle stimulating hormone (FSH), and positively associated with inhibin B and sex hormone binding globulin (SHBG). Finally, consistent with limited recent human studies of adults, PBDEs were positively associated with free T4. In conclusion, the present study provides compelling evidence of altered hormone levels in relation to PBDE exposures estimated as concentrations in house dust, and that house dust is an important source of human PBDE exposure, but more research is urgently needed. (C) 2009 Elsevier B.V. All rights reserved.
C1 [Meeker, John D.] Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, Ann Arbor, MI 48109 USA.
[Camann, David] SW Res Inst, San Antonio, TX USA.
[Hauser, Russ] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA.
[Hauser, Russ] Massachusetts Gen Hosp, Androl Lab, Vincent Mem Obstet & Gynecol Serv, Boston, MA 02114 USA.
[Hauser, Russ] Massachusetts Gen Hosp, In Vitro Fertilizat Unit, Boston, MA 02114 USA.
RP Meeker, JD (reprint author), Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, 6635 SPH Tower,109 S Observ St, Ann Arbor, MI 48109 USA.
EM meekerj@umich.edu
RI Perez , Claudio Alejandro/F-8310-2010;
OI Perez , Claudio Alejandro/0000-0001-9688-184X; Meeker,
John/0000-0001-8357-5085
FU National Institute of Environmental Health Sciences (NIEHS) [ES009718,
ES00002]; National Institutes of Health (NIH)
FX This work was supported by grant ES009718 and ES00002 from the National
Institute of Environmental Health Sciences (NIEHS), National Institutes
of Health (NIH).
NR 39
TC 125
Z9 134
U1 6
U2 43
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0048-9697
J9 SCI TOTAL ENVIRON
JI Sci. Total Environ.
PD MAY 1
PY 2009
VL 407
IS 10
BP 3425
EP 3429
DI 10.1016/j.scitotenv.2009.01.030
PG 5
WC Environmental Sciences
SC Environmental Sciences & Ecology
GA 437VV
UT WOS:000265515900021
PM 19211133
ER
PT J
AU Khademhosseini, A
Vacanti, JP
Langer, R
AF Khademhosseini, Ali
Vacanti, Joseph P.
Langer, Robert
TI PROGRESS IN TISSUE ENGINEERING
SO SCIENTIFIC AMERICAN
LA English
DT Article
C1 [Khademhosseini, Ali] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
[Khademhosseini, Ali; Vacanti, Joseph P.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[Vacanti, Joseph P.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA.
[Langer, Robert] MIT, Cambridge, MA 02139 USA.
RP Khademhosseini, A (reprint author), Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
RI Khademhosseini, Ali/A-9435-2010
OI Khademhosseini, Ali/0000-0002-2692-1524
NR 4
TC 167
Z9 174
U1 4
U2 80
PU SCI AMERICAN INC
PI NEW YORK
PA 415 MADISON AVE, NEW YORK, NY 10017 USA
SN 0036-8733
J9 SCI AM
JI Sci.Am.
PD MAY
PY 2009
VL 300
IS 5
BP 64
EP +
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 434LO
UT WOS:000265276400035
PM 19438051
ER
PT J
AU Mount, DB
AF Mount, David B.
TI Hyponatremia: Introduction
SO SEMINARS IN NEPHROLOGY
LA English
DT Editorial Material
ID NONCARDIOGENIC PULMONARY-EDEMA; BRAIN-BARRIER DISRUPTION; INAPPROPRIATE
ANTIDIURESIS; NEPHROGENIC SYNDROME; INADVERTENT OVERCORRECTION; INDUCED
DEMYELINATION; ENCEPHALOPATHY; RATS; MICE; ASSOCIATION
C1 [Mount, David B.] Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA.
[Mount, David B.] Harvard Univ, Sch Med, Div Renal, VA Boston Healthcare Syst, Boston, MA USA.
RP Mount, DB (reprint author), Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA.
NR 27
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 0270-9295
J9 SEMIN NEPHROL
JI Semin. Nephrol.
PD MAY
PY 2009
VL 29
IS 3
BP 175
EP 177
DI 10.1016/j.semnephrol.2009.03.007
PG 3
WC Urology & Nephrology
SC Urology & Nephrology
GA 461AX
UT WOS:000267237000001
PM 19523567
ER
PT J
AU Mount, DB
AF Mount, David B.
TI The Brain in Hyponatremia: Both Culprit and Victim
SO SEMINARS IN NEPHROLOGY
LA English
DT Review
DE Vasopressin; thirst; magnocellular; TRP1; TRP4; cell volume; aquaporin;
K-Cl cotransport; osmotic demyelination; hyponatremia
ID CENTRAL PONTINE MYELINOLYSIS; HYPOTHALAMIC PARAVENTRICULAR NUCLEUS;
ESTROGEN-RECEPTOR-BETA; NONCARDIOGENIC PULMONARY-EDEMA; PLASMA
VASOPRESSIN RESPONSE; NONSELECTIVE CATION CHANNEL; CONVERTING
ENZYME-INHIBITOR; NORMAL THIRST RESPONSES; PITUITARY-ADRENAL AXIS;
CELL-VOLUME REGULATION
AB Abnormalities in thirst and vasopressin (AVP) release play key roles in the genesis of hyponatremia; both processes are under the control of osmoreceptive neurons in the central nervous system (CNS). The acute development of hyponatremia ill turn leads to profound cerebral edema, whereas treatment of chronic hyponatremia call be associated with osmotic demyelination syndrome (ODS). The brain is thus both "culprit" and "victim" in hyponatremia. This review Summarizes recent advances in the understanding of osmoreception in the brain, the CNS response to acute and chronic hyponatremia, and the pathophysiology of ODS. Semin Nephrol 29:196-215 (C) 2009 Elsevier Inc. All rights reserved.
C1 [Mount, David B.] Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA.
[Mount, David B.] Harvard Univ, Sch Med, Div Renal, VA Boston Healthcare Syst, Boston, MA USA.
RP Mount, DB (reprint author), Brigham & Womens Hosp, Div Renal, Room 540,4 Blackfan Circle, Boston, MA 02115 USA.
EM dmount@rics.bwh.harvard.edu
FU National Institutes of Health [DK57708, DK070756]; American Heart
Association; Veterans Administration
FX Supported by National Institutes of Health grants (DK57708 and
DK070756). the American Heart Association and the Veterans
Administration.
NR 134
TC 16
Z9 16
U1 1
U2 4
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0270-9295
J9 SEMIN NEPHROL
JI Semin. Nephrol.
PD MAY
PY 2009
VL 29
IS 3
BP 196
EP 215
DI 10.1016/j.semnephrol.2009.03.021
PG 20
WC Urology & Nephrology
SC Urology & Nephrology
GA 461AX
UT WOS:000267237000003
PM 19523569
ER
PT J
AU Mount, DB
Krahn, TA
AF Mount, David B.
Krahn, Thomas A.
TI Hyponatremia: Case Vignettes
SO SEMINARS IN NEPHROLOGY
LA English
DT Review
DE Beer potomania; thiazide; pregnancy; olfactory neuroblastoma;
hypopituitarism; SIADH; conivaptan; tolvaptan; DDAVP; hypertonic saline
ID ANTIDIURETIC-HORMONE SECRETION; DIURETIC-INDUCED HYPONATREMIA;
THIAZIDE-INDUCED HYPONATREMIA; CENTRAL PONTINE MYELINOLYSIS;
BEER-DRINKERS; INAPPROPRIATE ANTIDIURESIS; INADVERTENT OVERCORRECTION;
NEUROENDOCRINE CARCINOMA; OLFACTORY NEUROBLASTOMA; ADRENAL INSUFFICIENCY
AB The diagnosis and management of hyponatremia can be intimidating, for both trainees and clinicians alike. We present five clinical scenarios of patients with hyponatremia. These discussions reinforce concepts reviewed elsewhere in this issue of Seminars in Nephrology and/or emphasize specific causes and management issues. Semin Nephrol 29:300-317 (C) 2009 Elsevier Inc. All rights reserved.
C1 [Mount, David B.] Harvard Univ, Div Renal, Brigham & Womens Hosp, Sch Med, Boston, MA 02215 USA.
[Mount, David B.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02215 USA.
[Krahn, Thomas A.] Brown Univ, Div Kidney Dis & Hypertens, Warren Alpert Med Sch, Providence, RI 02912 USA.
RP Mount, DB (reprint author), Harvard Univ, Div Renal, Brigham & Womens Hosp, Sch Med, Room 540,4 Blackfan Circle, Boston, MA 02215 USA.
EM dmount@rics.bwh.harvard.edu
FU National Institutes of Health [DK57708, DK070756]; American Heart
Association; Veterans Administration
FX Supported by National Institutes of Health grants (DK57708 and
DK070756). the American Heart Association, and the Veterans
Administration.
NR 75
TC 5
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 0270-9295
J9 SEMIN NEPHROL
JI Semin. Nephrol.
PD MAY
PY 2009
VL 29
IS 3
BP 300
EP 317
DI 10.1016/j.semnephrol.2009.04.001
PG 18
WC Urology & Nephrology
SC Urology & Nephrology
GA 461AX
UT WOS:000267237000010
PM 19523576
ER
PT J
AU Platt, AB
Kuna, ST
AF Platt, Alec B.
Kuna, Samuel T.
TI To Adhere or Not to Adhere-Patients Selectively Decide
SO SLEEP
LA English
DT Editorial Material
ID POSITIVE AIRWAY PRESSURE; OBSTRUCTIVE SLEEP-APNEA; CARDIOVASCULAR
OUTCOMES; MORTALITY; THERAPY; HYPOPNEA; TRIAL; RISK; MEN
C1 [Kuna, Samuel T.] Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA.
[Platt, Alec B.] Reading Hosp Med Ctr, Reading, PA USA.
[Platt, Alec B.] Resp Specialists LTD, Wyomissing, PA USA.
[Kuna, Samuel T.] Univ Penn, Sch Med, Ctr Sleep & Resp Neurobiol, Philadelphia, PA 19104 USA.
RP Kuna, ST (reprint author), Philadelphia VA Med Ctr, 3900 Woodland Ave, Philadelphia, PA 19104 USA.
EM skuna@mail.med.upenn.edu
NR 15
TC 2
Z9 2
U1 0
U2 3
PU AMER ACAD SLEEP MEDICINE
PI WESTCHESTER
PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA
SN 0161-8105
J9 SLEEP
JI Sleep
PD MAY 1
PY 2009
VL 32
IS 5
BP 583
EP 584
PG 2
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 438FS
UT WOS:000265541900002
PM 19480222
ER
PT J
AU Rice, I
Impink, B
Niyonkuru, C
Boninger, M
AF Rice, I.
Impink, B.
Niyonkuru, C.
Boninger, M.
TI Manual wheelchair stroke characteristics during an extended period of
propulsion
SO SPINAL CORD
LA English
DT Article
DE spinal cord injury; biomechanics; propulsion; fatigue; kinetics;
wheelchair dynamometer
ID MECHANICAL EFFICIENCY; PUSHRIM FORCES; KINETICS; USERS; BIOMECHANICS;
FATIGUE; MOTION
AB Study Design: Cross-sectional study.
Objectives: The purpose of this study was to examine stroke characteristics of long-term manual wheelchair users during an extended manual wheelchair propulsion trial and the extent to which changes in propulsion biomechanics occurred.
Setting: Human Engineering Research Laboratories, VA Rehabilitation Research and Development Center, VA Pittsburgh Healthcare Systems, Pittsburgh, PA, USA.
Methods: Kinetic data were recorded from 21 subjects with paraplegia at four time points over the course of a 10-min propulsion trial at a steady state speed of 1.4 ms(-1). Upper extremity kinetic parameters were recorded using Smartwheels, force and torque sensing pushrims.
Results: Subjects for propulsion biomechanics changed from early to late during the 10-min trial. Individuals displayed decreased maximum rate of rise of resultant force (P=0.0045) with a simultaneous increase in push time (P=0.043) and stroke time (P=0.023), whereas stroke frequency remained static. In addition, there was a decrease in out of plane moment application (P=0.032).
Conclusion: Individuals seemed to naturally accommodate their propulsive stroke, using less injurious propulsion biomechanics over the course of a 10-minute trial on a dynamometer. The findings may have occurred as a result of both biomechanical compensations to a challenging propulsion trial and accommodation to propelling on a dynamometer. These results suggest that subjects may be capable of independently incorporating favorable biomechanical strategies to meet the demands of a challenging propulsion scenario. Spinal Cord (2009) 47, 413 - 417; doi:10.1038/sc.2008.139; published online 11 November 2008
C1 [Rice, I.] Univ Pittsburgh, Rehabil Sci Human Engn Res Lab, VA Pittsburgh Healthcare Syst, VA Rehabil Res & Dev Ctr,Human Engn Res Labs, Pittsburgh, PA 15206 USA.
[Rice, I.; Boninger, M.] Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA 15206 USA.
[Impink, B.] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA 15206 USA.
[Boninger, M.] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA 15206 USA.
RP Rice, I (reprint author), Univ Pittsburgh, Rehabil Sci Human Engn Res Lab, VA Pittsburgh Healthcare Syst, VA Rehabil Res & Dev Ctr,Human Engn Res Labs, VA Pittsburgh 7180 Highland Dr 151R-1, Pittsburgh, PA 15206 USA.
EM ricei@herlpitt.org
OI Boninger, Michael/0000-0001-6966-919X
FU Office of Research and Development; Rehabilitation Research and
Development Service; Department of Veterans Affairs [B3142C]
FX This study was supported by the Office of Research and Development,
Rehabilitation Research and Development Service, Department of Veterans
Affairs, Grant# B3142C'.
NR 18
TC 9
Z9 9
U1 1
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1362-4393
J9 SPINAL CORD
JI Spinal Cord
PD MAY
PY 2009
VL 47
IS 5
BP 413
EP 417
DI 10.1038/sc.2008.139
PG 5
WC Clinical Neurology; Rehabilitation
SC Neurosciences & Neurology; Rehabilitation
GA 443DM
UT WOS:000265890400012
PM 19002155
ER
PT J
AU Chou, R
Loeser, JD
Owens, DK
Rosenquist, RW
Atlas, SJ
Baisden, J
Carragee, EJ
Grabois, M
Murphy, DR
Resnick, DK
Stanos, SP
Shaffer, WO
Wall, EM
AF Chou, Roger
Loeser, John D.
Owens, Douglas K.
Rosenquist, Richard W.
Atlas, Steven J.
Baisden, Jamie
Carragee, Eugene J.
Grabois, Martin
Murphy, Donald R.
Resnick, Daniel K.
Stanos, Steven P.
Shaffer, William O.
Wall, Eric M.
CA Amer Pain Soc Low Back Pain Guidel
TI Interventional Therapies, Surgery, and Interdisciplinary Rehabilitation
for Low Back Pain An Evidence-Based Clinical Practice Guideline From the
American Pain Society
SO SPINE
LA English
DT Review
DE low back pain; guideline; evidence-based; surgery; fusion; laminectomy;
discectomy; injection; radiofrequency denervation; intradiscal
electrothermal therapy; botulinum toxin; interdisciplinary therapy;
multidisciplinary therapy; spinal cord stimulation
ID RANDOMIZED CONTROLLED-TRIAL; SPINAL-CORD STIMULATION; LUMBAR-DISK
HERNIATION; EXTRADURAL CORTICOSTEROID INJECTION; EPIDURAL STEROID
INJECTION; INTERACTIVE VIDEO PROGRAM; DOUBLE-BLIND EVALUATION; NERVE
ROOT COMPRESSION; UNITED-STATES TRENDS; PROVOCATIVE DISCOGRAPHY
AB Study Design. Clinical practice guideline. Objective. To develop evidence-based recommendations on use of interventional diagnostic tests and therapies, surgeries, and interdisciplinary rehabilitation for low back pain of any duration, with or without leg pain.
Summary of Background Data. Management of patients with persistent and disabling low back pain remains a clinical challenge. A number of interventional diagnostic tests and therapies and surgery are available and their use is increasing, but in some cases their utility remains uncertain or controversial. Interdisciplinary rehabilitation has also been proposed as a potentially effective noninvasive intervention for persistent and disabling low back pain.
Methods. A multidisciplinary panel was convened by the American Pain Society. Its recommendations were based on a systematic review that focused on evidence from randomized controlled trials. Recommendations were graded using methods adapted from the US Preventive Services Task Force and the Grading of Recommendations, Assessment, Development, and Evaluation Working Group.
Results. Investigators reviewed 3348 abstracts. A total of 161 randomized trials were deemed relevant to the recommendations in this guideline. The panel developed a total of 8 recommendations.
Conclusion. Recommendations on use of interventional diagnostic tests and therapies, surgery, and interdisciplinary rehabilitation are presented. Due to important trade-offs between potential benefits, harms, costs, and burdens of alternative therapies, shared decision-making is an important component of a number of the recommendations.
C1 [Chou, Roger] Oregon Hlth & Sci Univ, Dept Med, Oregon Evidence Based Practice Ctr, Portland, OR 97201 USA.
[Loeser, John D.] Univ Washington, Dept Neurol Surg, Seattle, WA 98195 USA.
[Owens, Douglas K.] Vet Affairs Med Ctr, Palo Alto, CA 94304 USA.
[Carragee, Eugene J.] Stanford Univ, Dept Orthoped Surg, Stanford, CA 94305 USA.
[Rosenquist, Richard W.] Univ Iowa, Dept Anesthesiol, Iowa City, IA USA.
[Atlas, Steven J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Med Serv,Gen Med Div, Boston, MA USA.
[Baisden, Jamie] Med Coll Wisconsin, Dept Neurosurg, Milwaukee, WI 53226 USA.
[Grabois, Martin] Baylor Coll Med, Inst Rehabil & Res, Dept Phys Med & Rehabil, Houston, TX 77030 USA.
[Murphy, Donald R.] Brown Univ, Alpert Med Sch, Rhode Isl Spine Ctr, Dept Community Hlth, Pawtucket, RI USA.
[Resnick, Daniel K.] Univ Wisconsin, Dept Neurosurg, Madison, WI USA.
[Stanos, Steven P.] Northwestern Univ, Dept Phys Med & Rehabil, Chicago, IL 60611 USA.
[Shaffer, William O.] Univ Kentucky, Dept Orthopaed, Lexington, KY USA.
[Wall, Eric M.] Qualis Hlth, Seattle, WA USA.
RP Chou, R (reprint author), 3181 SW Sam Jackson Pk Rd,Mail Code BICC, Portland, OR 97239 USA.
EM chour@ohsu.edu
FU American Pain Society (APS)
FX Supported by the American Pain Society (APS).
NR 143
TC 205
Z9 214
U1 6
U2 38
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0362-2436
J9 SPINE
JI SPINE
PD MAY 1
PY 2009
VL 34
IS 10
BP 1066
EP 1077
DI 10.1097/BRS.0b013e3181a1390d
PG 12
WC Clinical Neurology; Orthopedics
SC Neurosciences & Neurology; Orthopedics
GA 440DB
UT WOS:000265677900013
PM 19363457
ER
PT J
AU Latorre, JGS
Chou, SHY
Nogueira, RG
Singhal, AB
Carter, BS
Ogilvy, CS
Rordorf, GA
AF Latorre, Julius Gene S.
Chou, Sherry Hsiang-Yi
Nogueira, Raul Gomes
Singhal, Aneesh B.
Carter, Bob S.
Ogilvy, Christopher S.
Rordorf, Guy A.
TI Effective Glycemic Control With Aggressive Hyperglycemia Management Is
Associated With Improved Outcome in Aneurysmal Subarachnoid Hemorrhage
SO STROKE
LA English
DT Article
DE critical care; hyperglycemia; intracranial aneurysm; outcome;
subarachnoid hemorrhage
ID INTENSIVE INSULIN THERAPY; TRAUMATIC BRAIN-INJURY; CRITICALLY-ILL;
CEREBRAL GLUCOSE; MICRODIALYSIS; IMPACT; LACTATE; STROKE; RATES
AB Background and Purpose-Hyperglycemia strongly predicts poor outcome in patients with aneurysmal subarachnoid hemorrhage, but the effect of hyperglycemia management on outcome is unclear. We studied the impact of glycemic control on outcome of patients with aneurysmal subarachnoid hemorrhage.
Methods-A prospective intensive care unit database was used to identify 332 patients with hyperglycemic aneurysmal subarachnoid hemorrhage admitted between January 2000 and December 2006. Patients treated with an aggressive hyperglycemia management (AHM) protocol after 2003 (N = 166) were compared with 166 patients treated using a standard hyperglycemia management before 2003. Within the AHM group, outcome was compared between patients who achieved good (mean glucose burden <1.1 mmol/L) and poor (mean glucose burden <1.1 mmol/L) glycemic control. Poor outcome was defined as modified Rankin scale >= 4 at 3 to 6 months. Multivariable logistic regression models correcting for temporal trend were used to quantify the effect of AHM on poor outcome.
Results-Poor outcome in AHM-treated patients was lower (28.31% versus 40.36%) but was not statistically significant after correcting for temporal trend. However, good glycemic control significantly reduced the incidence of poor outcome (OR, 0.25; 95% CI, 0.08 to 0.80; P=0.02) compared with patients with poor glycemic control within the AHM group. No difference in the rate of clinical vasospasm or the development of delayed ischemic neurological deficit was seen before and after AHM protocol implementation.
Conclusion-AHM results in good glucose control and significantly reduces the odds for poor outcome after aneurysmal subarachnoid hemorrhage in glucose-controlled patients. Further studies are needed to confirm these results. (Stroke. 2009; 40: 1644-1652.)
C1 [Latorre, Julius Gene S.] SUNY Upstate Med Univ, Dept Neurol, Syracuse, NY 13210 USA.
[Chou, Sherry Hsiang-Yi] Harvard Univ, Brigham & Womens Hosp, Dept Neurol, Sch Med, Boston, MA 02115 USA.
[Nogueira, Raul Gomes] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol & Intervent Neuroradiol, Boston, MA USA.
[Carter, Bob S.; Ogilvy, Christopher S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA USA.
[Singhal, Aneesh B.; Rordorf, Guy A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA.
RP Latorre, JGS (reprint author), SUNY Upstate Med Univ, Dept Neurol, 7134UH,750 E Adams St, Syracuse, NY 13210 USA.
EM latorrej@upstate.edu
RI Chou, Sherry/G-5779-2015
FU National Institutes of Health [NCRR K30-RR022292-07]
FX We express gratitude to National Institutes of Health for NCRR
K30-RR022292-07 grant support to S.H.-Y.C.
NR 27
TC 28
Z9 32
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
J9 STROKE
JI Stroke
PD MAY
PY 2009
VL 40
IS 5
BP 1644
EP 1652
DI 10.1161/STROKEAHA.108.535534
PG 9
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 438UB
UT WOS:000265579800019
PM 19286596
ER
PT J
AU Earnshaw, SR
Jackson, D
Farkouh, R
Schwamm, L
AF Earnshaw, Stephanie R.
Jackson, Dan
Farkouh, Ray
Schwamm, Lee
TI Cost-Effectiveness of Patient Selection Using Penumbral-Based MRI for
Intravenous Thrombolysis
SO STROKE
LA English
DT Article
DE ischemic stroke; MRI; cost-effectiveness analysis; economics; stroke
management
ID ACUTE ISCHEMIC-STROKE; TISSUE-PLASMINOGEN ACTIVATOR; INTRACEREBRAL
HEMORRHAGE; RANDOMIZED-TRIAL; UNITED-STATES; 3 H; THERAPY; DIFFUSION;
EMERGENCY; MODEL
AB Background and Purpose-Better selection of patients for intravenous recombinant tissue plasminogen activator (IV tPA) treatment may improve clinical outcomes. We examined the cost-effectiveness of adding penumbral-based MRI to usual computed tomography (CT)-based methods to identify patients for IV tPA treatment.
Methods-A decision-analytic model estimated the lifetime costs and outcomes associated with penumbral-based MRI selection in a patient population similar to that enrolled in the IV tPA clinical trials. Inputs were obtained from published literature, clinical trial data, claims databases, and expert opinion. Outcomes included cost per life-year saved and cost per quality-adjusted life-year (QALY) gained. Costs and outcomes were discounted at 3% annually. Sensitivity analyses were conducted.
Results-The addition of penumbral-based MRI selection increased total cost by $103 over the patient's remaining lifetime. Penumbral-based MRI selection resulted in favorable outcomes (modified Rankin Scale <= 1) more often than CT-based selection (36.66% versus 35.06%) with an incremental cost per life year of $1840 and an incremental cost per QALY of $1004. Multivariate sensitivity analysis predicted cost-effectiveness (<=$50 000 per QALY) in 99.7% of simulation runs.
Conclusions-Selecting ischemic stroke patients for IV tPA treatment using penumbral-based MRI after routine CT may increase overall acute care costs, but the benefit is large enough to make this highly cost-effective. This economic analysis lends further support to the consideration of a paradigm shift in acute stroke evaluation. (Stroke. 2009; 40: 1710-1720.)
C1 [Earnshaw, Stephanie R.; Farkouh, Ray] RTI Hlth Solut, Res Triangle Pk, NC 27709 USA.
[Jackson, Dan] GE Healthcare, Chalfont St Giles, Bucks, England.
[Schwamm, Lee] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02115 USA.
RP Earnshaw, SR (reprint author), RTI Hlth Solut, POB 12194,Res Triangle Pk, Res Triangle Pk, NC 27709 USA.
EM searnshaw@rti.org
OI Schwamm, Lee/0000-0003-0592-9145
FU GE Healthcare
FX This work was supported by GE Healthcare.
NR 43
TC 28
Z9 28
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
J9 STROKE
JI Stroke
PD MAY
PY 2009
VL 40
IS 5
BP 1710
EP 1720
DI 10.1161/STROKEAHA.108.540138
PG 11
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 438UB
UT WOS:000265579800030
PM 19286581
ER
PT J
AU Gropen, T
Magdon-Ismail, Z
Day, D
Melluzzo, S
Schwamm, LH
AF Gropen, Toby
Magdon-Ismail, Zainab
Day, David
Melluzzo, Shannon
Schwamm, Lee H.
CA NECC Advisory Grp
TI Regional Implementation of the Stroke Systems of Care Model
Recommendations of the Northeast Cerebrovascular Consortium
SO STROKE
LA English
DT Article
DE regional implementation; stroke; stroke systems
ID INTERNATIONAL EXPERIENCE; REGISTRIES
AB Background and Purpose-The Northeast Cerebrovascular Consortium was established to examine regional disparities and recommend strategies to improve stroke care based on the Stroke Systems of Care Model.
Methods-An annual summit was first held in 2006, bringing together public health officials, researchers, physicians, nurses, health professionals, state legislators, and advocacy organizations. Best practices and evidence-based interventions within each of the Stroke Systems of Care Model components were presented. Six writing groups were tasked with cataloging each state's current activities and identifying goals for the region.
Results-There were significant variations in the delivery of stroke care, particularly in urban versus rural areas, as evidenced by the availability of designated stroke centers and neurologists, and stroke-related death rates. Recommendations to address variations in care delivery included the use of a common stroke data collection system, unified community education criteria, improvements to emergency medical services dispatch and training, adoption of prehospital care measures, creation of a web-based central repository of acute stroke protocols and order sets, a regional atlas of stroke resources and capabilities, a stroke patient "report card" to promote adherence to secondary prevention strategies, and explicit standards for rehabilitation services.
Conclusions-Significant disparities in the delivery of stroke care across the 8 state-region have been identified. Northeast Cerebrovascular Consortium demonstrates that multistate regional collaboration is a viable process for developing specific regional recommendations to address those disparities. Northeast Cerebrovascular Consortium is assessing the usefulness of the Stroke Systems of Care Model as a framework for implementing a regional approach to stroke across the continuum of care. (Stroke. 2009; 40: 1793-1802.)
C1 [Gropen, Toby] Long Isl Coll Hosp, Dept Neurol, Brooklyn, NY 11201 USA.
[Magdon-Ismail, Zainab; Day, David; Melluzzo, Shannon] Amer Stroke Assoc, Dallas, TX USA.
[Schwamm, Lee H.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Gropen, T (reprint author), Long Isl Coll Hosp, Dept Neurol, 339 Hicks St, Brooklyn, NY 11201 USA.
EM tgropen@chpnet.org
OI Schwamm, Lee/0000-0003-0592-9145
FU NCCDPHP CDC HHS [5 U13 DP001176-02]
NR 20
TC 35
Z9 35
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
J9 STROKE
JI Stroke
PD MAY
PY 2009
VL 40
IS 5
BP 1793
EP 1802
DI 10.1161/STROKEAHA.108.531053
PG 10
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 438UB
UT WOS:000265579800041
PM 19299641
ER
PT J
AU Ross, JS
Halm, EA
Bravata, DM
AF Ross, Joseph S.
Halm, Ethan A.
Bravata, Dawn M.
TI Use of Stroke Secondary Prevention Services Are There Disparities in
Care?
SO STROKE
LA English
DT Article
DE health care; prevention; women and minorities; quality of care
ID TRANSIENT ISCHEMIC ATTACK; PHYSICAL-ACTIVITY; RISK-FACTORS; HEALTH;
BEHAVIORS; MORTALITY; OUTCOMES; DISEASE; CANCER
AB Background and Purpose-The purpose of this study was to examine whether there are disparities in use of stroke secondary prevention services because disparities in stroke outcomes have been found among older adults, women, racial minorities, and within Stroke Belt states.
Methods-Using the nationally-representative 2005 Behavior Risk Factor Surveillance System, we examined self-reported use of 11 stroke secondary prevention services queried in the survey. We used multivariable logistic regression to examine the association between service use and age, sex, race, and Stroke Belt state residence, controlling for other socio-demographic and health care access characteristics.
Results-Among 11 862 adults with a history of stroke, 16% were 80 or older, 54% were women, 13% were non-Hispanic black, and 23% lived within a Stroke Belt state. Overall service use varied: 31% reported poststroke outpatient rehabilitation, 57% regular exercise, 66% smoking cessation counseling, and 91% current use of antihypertensive medications. Age 80 or older was not associated with lower use of any of the 11 services. Women were less likely to report poststroke outpatient rehabilitation and regular exercise when compared with men (probability values <= 0.005); there were no sex-based differences in use of the 9 other services. Blacks were less likely to report pneumococcal vaccination when compared with whites, but were more likely to report poststroke outpatient rehabilitation (probability values <= 0.005); there were no race-based differences in use of the 9 other services. Stroke Belt state residence was not associated with lower use of any of the 11 services.
Conclusions-Use of many stroke secondary prevention services was suboptimal. We did not find consistent age, sex, racial, or Stroke Belt state residence disparities in care. (Stroke. 2009; 40: 1811-1819.)
C1 [Ross, Joseph S.] Mt Sinai Sch Med, Dept Geriatr & Adult Dev, Bronx, NY USA.
James J Peter VA Med Ctr, HSR&D Res Enhancement Award Program, Bronx, NY USA.
James J Peter VA Med Ctr, Ctr Geriatr Res Educ & Clin, Bronx, NY USA.
[Halm, Ethan A.] Univ Texas SW Med Ctr Dallas, Dept Med, Dallas, TX 75390 USA.
[Bravata, Dawn M.] Indiana Univ, Sch Med, Dept Med, Indianapolis, IN USA.
Richard L Roudebush Vet Adm Med Ctr, HSR&D Ctr Excellence, Indianapolis, IN 46202 USA.
RP Ross, JS (reprint author), Mt Sinai Sch Med, 1 Gustave L Levy Pl,Box 1070, New York, NY 10029 USA.
EM joseph.ross@mssm.edu
FU NINDS NIH HHS [R01 NS056028-02, R01 NS056028-04, R01 NS056028-03, R01
NS056028-01A1, R01 NS056028]
NR 26
TC 14
Z9 14
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
J9 STROKE
JI Stroke
PD MAY
PY 2009
VL 40
IS 5
BP 1811
EP 1819
DI 10.1161/STROKEAHA.108.539619
PG 9
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 438UB
UT WOS:000265579800043
PM 19265044
ER
PT J
AU Romero, JM
Babiarz, LS
Forero, NP
Murphy, EK
Schaefer, PW
Gonzalez, RG
Lev, MH
AF Romero, Javier M.
Babiarz, Lukasz S.
Forero, N. Paola
Murphy, Erin K.
Schaefer, Pamela W.
Gonzalez, R. Gilberto
Lev, Michael H.
TI Arterial Wall Enhancement Overlying Carotid Plaque on CT Angiography
Correlates With Symptoms in Patients With High Grade Stenosis
SO STROKE
LA English
DT Article
DE cerebrovascular disease; CT; risk factors; carotid artery
ID COMPUTED-TOMOGRAPHY; VASA VASORUM; ATHEROSCLEROSIS
AB Background and Purpose-The degree of internal carotid artery (ICA) stenosis is an established primary risk factor for embolic stroke. Recent publications suggest that inflammatory features may also play an important role. Our purpose was to correlate acute neurological symptoms with either carotid artery wall enhancement or plaque calcification, on axial CT angiographic source images (CTA-SI) of patients with severe (>= 70%) ICA stenosis.
Methods-75 consecutive patients with >= 70% ICA stenosis on CTA-SI were identified. Each case was classified as symptomatic (n=37) or asymptomatic (n=38), and as having either calcified or noncalcified plaque. The latter group was stratified into those with versus without arterial wall enhancement, measured in absolute and relative Hounsfield Units (HU).
Results-Calcified plaque was present in 39% (15/38) of the symptomatic patients and in 62% (23/37) of the asymptomatic patients (P=0.065). Of the 37 patients without calcified plaque, carotid wall enhancement was observed in 83% (19/23) of the symptomatic, but only in 57% (8/14) of the asymptomatic patients (P=0.041). When the "calcified plaque" and "no carotid wall enhancement" groups were pooled, versus the "carotid wall enhancement" group, enhancement was more likely in symptomatic patients (OR 3.625, CI 95% 1.3229 to 9.93, P=0.01 Fisher Exact test).
Conclusions-In patients with severe ICA stenosis, additional stratification of stroke risk may be possible based on the presence of carotid wall enhancement on CTA-SI. Patients with carotid wall enhancement are more likely to be symptomatic, compared to those with either calcified plaque or no enhancement. (Stroke. 2009; 40: 1894-1896.)
C1 [Romero, Javier M.; Babiarz, Lukasz S.; Forero, N. Paola; Murphy, Erin K.; Schaefer, Pamela W.; Gonzalez, R. Gilberto; Lev, Michael H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA.
RP Romero, JM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA.
EM jmromero@partners.org
NR 9
TC 20
Z9 20
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
J9 STROKE
JI Stroke
PD MAY
PY 2009
VL 40
IS 5
BP 1894
EP 1896
DI 10.1161/STROKEAHA.108.529008
PG 3
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 438UB
UT WOS:000265579800055
PM 19182087
ER
PT J
AU Heiss, WD
Sorensen, AG
AF Heiss, Wolf-Dieter
Sorensen, A. Gregory
TI Advances in Imaging
SO STROKE
LA English
DT Editorial Material
DE imaging; advances
ID ACUTE ISCHEMIC-STROKE; PERFUSION-DIFFUSION MISMATCH; MAGNETIC-RESONANCE;
CT-ANGIOGRAPHY; PENUMBRA; THROMBOLYSIS; OXYGEN; BRAIN; RISK; MRI
C1 [Heiss, Wolf-Dieter] Max Planck Inst Neurol Res, D-50931 Cologne, Germany.
[Sorensen, A. Gregory] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Sorensen, A. Gregory] Harvard Univ, Sch Med, Boston, MA USA.
RP Heiss, WD (reprint author), Max Planck Inst Neurol Res, Gleueler Str 50, D-50931 Cologne, Germany.
EM wdh@nf.mpg.de
NR 30
TC 1
Z9 1
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
J9 STROKE
JI Stroke
PD MAY
PY 2009
VL 40
IS 5
BP E313
EP E314
DI 10.1161/STROKEAHA.108.545434
PG 2
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 438UB
UT WOS:000265579800079
PM 19359627
ER
PT J
AU Regenbogen, SE
Greenberg, CC
Resch, SC
Kollengode, A
Cima, RR
Zinner, MJ
Gawande, AA
AF Regenbogen, Scott E.
Greenberg, Caprice C.
Resch, Stephen C.
Kollengode, Anantha
Cima, Robert R.
Zinner, Michael J.
Gawande, Atul A.
TI Prevention of retained surgical sponges: A decision-analytic model
predicting relative cost-effectiveness
SO SURGERY
LA English
DT Article
ID FOREIGN-BODIES; PATIENT SAFETY; OPERATING-ROOM; SURGERY; INSTRUMENTS;
TECHNOLOGY; IMPACT
AB Background. New technologies are available to reduce or prevent retained surgical sponges (RSS), but their relative cost effectiveness are unknown. We developed an empirically calibrated decision-analytic model comparing standard. counting against alternative strategies: universal or selective x-ray, bar-coded sponges (BCS), and radiofrequency-tagged (RF) sponges.
Methods. Key model parameters were obtained front field observations during a randomized-controlled BCS trial (n = 298), an observational study of RSS (n = 191,168), and clinical experience with BCS (n similar to 60,000). Because no comparable data exist for RF, we modeled its performance under 2 alternative assumptions. Only incremental sponge tracking costs, excluding those common to all strategies, were considered. Main outcomes were RSS incidence and cost-effectiveness ratios for each strategy, front the institutional decision maker's perspective.
Results. Standard counting detects 82% of RSS. Bar coding prevents >= 97.5% for an additional $95,000 per RSS averted. If RF were as effective as bar coding, it would cost $720,000 per additional RSS averted (versus standard counting). Universal and selective x-rays for high-risk operations are more costly, but less effective than BCS-$1.1 to 1.4 million per RSS event prevented. In sensitivity analyses, results were robust over the plausible range of effectiveness assumptions, but sensitive to cost.
Conclusion. Using currently available data, this analysis provides a useful model for comparing the relative cost effectiveness of existing sponge tracking strategies. Selecting the best method for an institution depends on its priorities: ease of use, cost reduction., or ensuring RSS are truly "never events." Given medical and liability costs of >$200,000 per incident, novel technologies can substantially reduce the incidence of RSS at an acceptable cost. (Surgery 2009;145:527-35.)
C1 [Regenbogen, Scott E.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Regenbogen, Scott E.; Gawande, Atul A.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA.
[Greenberg, Caprice C.; Zinner, Michael J.; Gawande, Atul A.] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA 02115 USA.
[Resch, Stephen C.] ABT Associates Inc, Cambridge, MA 02138 USA.
[Kollengode, Anantha] Mayo Clin, Off Qual Management, Rochester, MN USA.
[Cima, Robert R.] Mayo Clin, Dept Surg, Rochester, MN USA.
RP Regenbogen, SE (reprint author), Massachusetts Gen Hosp, Dept Surg, 55 Fruit St,GRB 425, Boston, MA 02114 USA.
EM sregenbogen@partners.org
OI Gawande, Atul/0000-0002-1824-9176
FU Agency for Healthcare Research and Quality [T32-HS000020]; SurgiCount
Medical, Temecula, CA
FX S.E.R. was supported by Kirschstein National Research Service Award
T32-HS000020 from the Agency for Healthcare Research and Quality. Drs
Greenberg and Gawande have received research grant support from
SurgiCount Medical, Temecula, CA. The funding agencies were not involved
in the conduct, analysis, or composition of this study, and were not
given the opportunity to approve or edit the manuscript before
submission. Accepted for publication January 28, 2009.
NR 38
TC 36
Z9 36
U1 0
U2 6
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 MAY
PY 2009
VL 145
IS 5
BP 527
EP 535
DI 10.1016/j.surg.2009.01.011
PG 9
WC Surgery
SC Surgery
GA 439VK
UT WOS:000265655300011
PM 19375612
ER
PT J
AU Levine, A
Ramos, A
Escalona, A
Rodriguez, L
Greve, JW
Janssen, I
Rothstein, R
Nepomnayshy, D
Gersin, KS
Melanson, D
Lamport, R
Fishman, E
Malomo, K
Kaplan, LM
Neto, MG
AF Levine, Andy
Ramos, Almino
Escalona, Alex
Rodriguez, Leonardo
Greve, Jan Willem
Janssen, Ignace
Rothstein, Richard
Nepomnayshy, Dmitry
Gersin, Keith S.
Melanson, David
Lamport, Ronald
Fishman, Ezra
Malomo, Kenneth
Kaplan, Lee M.
Galvao Neto, Manoel
TI Radiographic appearance of endoscopic duodenal-jejunal bypass liner for
treatment of obesity and type 2 diabetes
SO SURGERY FOR OBESITY AND RELATED DISEASES
LA English
DT Editorial Material
DE Bariatric; Endoluminal; Radiographic; Obesity; Duodenum; Diabetes
ID SLEEVE; EXPERIENCE; SURGERY
C1 [Levine, Andy; Melanson, David; Lamport, Ronald; Fishman, Ezra; Malomo, Kenneth] GI Dynam Inc, Lexington 02421, MA USA.
[Ramos, Almino; Galvao Neto, Manoel] Gastro Obeso Ctr, Sao Paulo, Brazil.
[Escalona, Alex] Pontificia Univ Catolica Chile, Hosp Univ Catolica, Santiago, Chile.
[Rodriguez, Leonardo] Hosp DIPRECA, Ctr Cirugia Obesidad, Santiago, Chile.
[Greve, Jan Willem] Univ Hosp, Maastricht, Netherlands.
[Janssen, Ignace] Ziekenluis Rijnstate, Arnhem, Netherlands.
[Rothstein, Richard] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA.
[Nepomnayshy, Dmitry] Lahey Clin Med Ctr, Burlington, MA 01803 USA.
[Gersin, Keith S.] Carolinas Med Ctr, Charlotte, NC 28203 USA.
[Kaplan, Lee M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Levine, A (reprint author), GI Dynam Inc, 1 Maguire Rd, Lexington 02421, MA USA.
EM alevine@gidynamics.com
NR 6
TC 8
Z9 8
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1550-7289
J9 SURG OBES RELAT DIS
JI Surg. Obes. Relat. Dis.
PD MAY-JUN
PY 2009
VL 5
IS 3
BP 371
EP 374
DI 10.1016/j.soard.2009.02.010
PG 4
WC Surgery
SC Surgery
GA 454GO
UT WOS:000266670600014
PM 19460677
ER
PT J
AU Tarazi, FI
Choi, YK
Gardner, M
Wong, EHF
Henry, B
Shahid, M
AF Tarazi, Frank I.
Choi, Yong Kee
Gardner, Matthew
Wong, Erik H. F.
Henry, Brian
Shahid, Mohammed
TI Asenapine Exerts Distinctive Regional Effects on Ionotropic Glutamate
Receptor Subtypes in Rat Brain
SO SYNAPSE
LA English
DT Article
DE asenapine; caudate putamen; frontal cortex; hippocampus; glutamate
receptor
ID MEDIAL PREFRONTAL CORTEX; ANTIPSYCHOTIC-DRUGS; NEGATIVE SYMPTOMS;
EMERGING ROLE; D-SERINE; SCHIZOPHRENIA; EXPRESSION; RISPERIDONE;
DOPAMINE; HALOPERIDOL
AB Asenapine, a new pyschopharmacologic agent being developed for the treatment of schizophrenia and bipolar disorder, has a unique human receptor binding signature with strong affinity for dopaminergic, alpha-adrenergic, and, in particular, serotonergic receptors raising the possibility of interactions with glutamatergic receptors. Changes in ionotropic glutamate (Glu) N-methyl-D-aspartic acid (NMDA) receptors and 2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propionic acid (AMPA) receptors in rat forebrain regions were quantified after repeated administration of multiple doses of asenapine (0.03, 0.1, or 0.3 mg/kg, subcutaneous, twice/day) or vehicle for 4 weeks. Brain sections were collected from the medial prefrontal cortex (mPFC), dorsolateral frontal cortex, caudate putamen (CPu), nucleus accumbens (NAc), and hippocampus (HIP), and processed for in vitro receptor autoradiography. Four weeks of treatment with 0.03, 0.1, or 0.3 mg/kg of asenapine significantly (P < 0.01) decreased binding of [(3)H]MK-801 to NMDA/MK-801 modulatory sites in NAc (by 27%, 29%, and 26%, respectively), medial CPu (by 25%, 28%, and 24%), and lateral CPu (by 24%, 31%, and 26%). In contrast, the same doses of asenapine did not alter binding of [(3)H]glycine to NMDA/glycine modulatory sites in any of the brain regions examined. [(3)H]AMPA binding to AMPA receptors was selectively and significantly (P < 0.001) elevated in hippocampal CA(1) (41%) and CA(3) (40%) regions but only at the highest dose tested. These results indicate that chronic treatment with asenapine has region-specific and dose-dependent effects on ionotropic Glu-receptor subtypes in rat forebrain, which might contribute to the unique psychopharmacologic properties of asenapine. Synapse 63:413-420, 2009. (C) 2009 Wiley-Liss, Inc.
C1 [Tarazi, Frank I.; Choi, Yong Kee; Gardner, Matthew] Massachusetts Gen Hosp, McLean Div, Mailman Res Ctr, Belmont, MA USA.
[Tarazi, Frank I.; Choi, Yong Kee] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
[Tarazi, Frank I.; Choi, Yong Kee] Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA.
[Wong, Erik H. F.] Pfizer Global R&D, Ann Arbor, MI USA.
[Henry, Brian; Shahid, Mohammed] Schering Plough Corp, Newhouse, Lanark, Scotland.
RP Tarazi, FI (reprint author), Harvard Univ, Sch Med, McLean Hosp, Lab Psychiat Neurosci, 115 Mill St, Belmont, MA 02478 USA.
EM ftarazi@hms.harvard.edu
FU NICHD [HD-052752]; Schering-Plough
FX NICHD; Contract grant number: HD-052752; Contract grant sponsor:
Schering-Plough.
NR 45
TC 23
Z9 23
U1 0
U2 0
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0887-4476
J9 SYNAPSE
JI Synapse
PD MAY
PY 2009
VL 63
IS 5
BP 413
EP 420
DI 10.1002/syn.20618
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA 424NZ
UT WOS:000264574700006
PM 19177511
ER
PT J
AU Yeung, A
Johnson, DP
Trinh, NH
Weng, WCC
Kvedar, J
Fava, M
AF Yeung, Albert
Johnson, Daniel P.
Trinh, Nhi-Ha
Weng, Wan-Chen Claire
Kvedar, Joseph
Fava, Maurizio
TI Feasibility and Effectiveness of Telepsychiatry Services for Chinese
Immigrants in a Nursing Home
SO TELEMEDICINE JOURNAL AND E-HEALTH
LA English
DT Article
DE nursing home; telemedicine; psychiatric consultation; Chinese immigrants
ID CARE
AB This study investigates the feasibility and effectiveness of providing telepsychiatry services to Chinese immigrants in a nursing home. The psychiatrist interviewed patients face-to-face for the initial consultation, and encouraged them to participate in this study to receive telepsychiatry-based follow-up visits. The feasibility and outcomes of telepsychiatry visits and satisfaction of the subjects, their families, and the nursing home staff were assessed. Nine monolingual Chinese immigrants, 8 women and 1 man, ranging from 54 to 88 years of age, were enrolled. The main reasons for psychiatric consultation were mood and behavioral problems. Eight of the 9 (88.9%) subjects participated in videoconference follow-up visits, and 1 subject (11.1%) declined. Among the 8 subjects, 6 were referred for psychiatric intervention, 1 for differential diagnosis, and 1 for suicide assessment. At the end of the study, all 6 subjects referred for intervention had greatly improved; the subjects, their families, and the nursing staff were highly satisfied with the telepsychiatry service. It is feasible to provide psychiatry consultations to ethnic immigrants in a nursing home despite the fact that many of them are unfamiliar with the technology and suffer from dementia and psychotic symptoms. Telepsychiatry provides an efficient way for ethnic elders in nursing homes to connect with mental health professionals with the appropriate language and cultural background, regardless of location. Telepsychiatry may decrease the disparities in treatment of mental illnesses among ethnic immigrants in nursing homes.
C1 [Yeung, Albert; Johnson, Daniel P.; Trinh, Nhi-Ha; Fava, Maurizio] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA.
[Weng, Wan-Chen Claire] Boston Coll, Boston, MA USA.
[Kvedar, Joseph] Ctr Connected Hlth, Boston, MA USA.
RP Yeung, A (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 50 Staniford St,Suite 401, Boston, MA 02114 USA.
EM ayeung@partners.org
FU Center of Connected Health, Partners HealthCare System, Boston,
Massachusetts
FX Research was funded by the Center of Connected Health, Partners
HealthCare System, Boston, Massachusetts.
NR 14
TC 18
Z9 18
U1 0
U2 4
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1530-5627
EI 1556-3669
J9 TELEMED J E-HEALTH
JI Telemed. J. e-Health
PD MAY
PY 2009
VL 15
IS 4
BP 336
EP 341
DI 10.1089/tmj.2008.0138
PG 6
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA 446GN
UT WOS:000266110200005
PM 19441951
ER
PT J
AU Zhou, J
Liu, SC
Ma, M
Hou, JX
Yu, HJ
Lu, CF
Gilbert, GE
Shi, JL
AF Zhou, Jin
Liu, Shuchuan
Ma, Ming
Hou, Jinxiao
Yu, Hongjuan
Lu, Chengfang
Gilbert, Gary E.
Shi, Jialan
TI Procoagulant activity and phosphatidylserine of amniotic fluid cells
SO THROMBOSIS AND HAEMOSTASIS
LA English
DT Article
DE Amniotic fluid cells; phosphatidylserine; procoagulant activity;
lactadherin
ID TISSUE FACTOR PATHWAY; BLOOD-COAGULATION; MEMBRANE-SURFACE;
BINDING-SITE; FACTOR-VIII; PROTEIN-C; FACTOR VA; L-SERINE; EMBOLISM;
INHIBITOR
AB Amniotic fluid (AF) may induce disseminated intravascular coagulation (DIC) when it enters maternal circulation by breaching the placental-maternal circulation barrier. The precise mechanism of the procoagulant activity of AF is unclear, but tissue factor (TF) has been proposed to be the main cause. As one constituent of AF, AF cells accumulate and undergo apoptosis continuously. Therefore, we speculate that AF cells have procoagulant activity due to the externalisation of phosphatidylserine (PS). The present study aims to demonstrate that, in addition to TF, the PS that is externalised on AF cells is important for the procoagulant activity of AF. Ten AF samples from parturient women were analysed using lactadherin as the probe for PS. Anti-TF antibody also was used to identify TF and its associated coagulation functions in AF cells. Normal platelets, neutrophils, and lymphocytes were harvested as controls. Confocal microscopy and flow cytometry was used to assess PS expression on AF cells. The procoagulant activity of AF cells was demonstrated by a plasma coagulation assay and further confirmed by factor Xase/prothrombinase assays. PS and TF were present on most AF cells, providing substantial procoagulant activity. Furthermore, factor Xase and prothrombinase assays showed that AF cells substantially enforced the activation of factor X and prothrombin. PS on AF cells is an important procoagulant source for AF. Lactadherin is an ideal anticoagulant for inhibiting the procoagulant activity of AF cells.
C1 [Zhou, Jin; Liu, Shuchuan; Ma, Ming; Hou, Jinxiao; Yu, Hongjuan; Lu, Chengfang; Shi, Jialan] Haibin Med Univ, Affiliated Hosp 1, Dept Hematol, Harbin 150001, Peoples R China.
[Gilbert, Gary E.; Shi, Jialan] Harvard Univ, Sch Med, Boston, MA USA.
[Gilbert, Gary E.; Shi, Jialan] Brigham & Womens Hosp, Dept Med, VA Boston Hlth Care Syst, Boston, MA 02115 USA.
RP Shi, JL (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, VA Boston Healthcare Syst, W Roxbury, MA 02132 USA.
EM jinzhouh85@163.com; jialan_shi@hms.harvard.edu
NR 30
TC 17
Z9 19
U1 1
U2 5
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 MAY
PY 2009
VL 101
IS 5
BP 845
EP 851
DI 10.1160/TH08-08-0531
PG 7
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 446VA
UT WOS:000266148300012
PM 19404537
ER
PT J
AU Delaney, M
Cutler, CS
Haspel, RL
Yeap, BY
McAfee, SL
Dey, BR
Attar, E
Kao, G
Alyea, EP
Koreth, J
Ho, VT
Saidman, S
Liney, D
Sese, D
Soiffer, RJ
Spitzer, TR
Antin, JH
Ballen, KK
AF Delaney, Meghan
Cutler, Corey S.
Haspel, Richard L.
Yeap, Beow Y.
McAfee, Steven L.
Dey, Bimalangshu R.
Attar, Eyal
Kao, Grace
Alyea, Edwin P.
Koreth, John
Ho, Vincent T.
Saidman, Susan
Liney, Deborah
Sese, Doreen
Soiffer, Robert J.
Spitzer, Thomas R.
Antin, Joseph H.
Ballen, Karen K.
TI High-resolution HLA matching in double-umbilical-cord-blood
reduced-intensity transplantation in adults
SO TRANSFUSION
LA English
DT Article
ID HEMATOPOIETIC-CELL TRANSPLANTATION; MARROW-TRANSPLANTATION; CLASS-I;
DONOR; OUTCOMES; RECONSTITUTION; RECIPIENT; IMPACT
AB Double-cord-blood transplantation (DCBT) offers an option for patients receiving reduced-intensity transplants. These unique transplants have two donors, both of whom are usually HLA mismatched at one to two loci.
Fifty-three patients were recipients of a reduced-intensity DCBT. Cords were at least 4/6 allele-level HLA-A, -B, and -DR match with the patient and each other with a minimum combined cell dose of more than 3.7 x 10(7) total nucleated cells per kg. Twenty-one patients received cyclosporine/mycophenolate mofetil and 32 patients received sirolimus/tacrolimus (SIR/TAC) for graft-versus-host disease prophylaxis. The effect of allele level HLA typing on clinical endpoints of overall survival (OS), disease-free survival (DFS), engraftment, and acute graft-versus-host disease (aGVHD) were assessed.
Neutrophil (p = 0.001) engraftment and platelet engraftment (p = 0.027) were significantly faster in patients who have closer Class I (HLA-A, -B, -C) matching. Neutrophil engraftment was faster in patients who had closer HLA-B matching to their combined cords (p = 0.007). There was a low incidence of aGVHD overall, especially in the SIR/TAC group. Class I HLA matching had no effect on aGVHD. HLA-DR and -DQ had no effect on engraftment or aGVHD.
Class I allele matching, and HLA-B matching specifically, were associated with faster neutrophil engraftment. High-resolution HLA matching did not affect OS or DFS.
C1 [Delaney, Meghan] Puget Sound Blood Ctr, Seattle, WA 98104 USA.
Massachusetts Gen Hosp, Div Hematol Oncol, Dept Med, Boston, MA 02114 USA.
Massachusetts Gen Hosp, Histocompatibil Lab, Boston, MA 02114 USA.
Dana Farber Canc Inst, Boston, MA USA.
Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA USA.
Brigham & Womens Hosp, Tissue Typing Lab, Boston, MA 02115 USA.
RP Delaney, M (reprint author), Puget Sound Blood Ctr, 921 Terry Ave, Seattle, WA 98104 USA.
EM meghand@psbc.org
FU NHLBI NIH HHS [P01 HL070149, U54 HL081030-01, U54 HL081030, HL070149]
NR 24
TC 23
Z9 24
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0041-1132
EI 1537-2995
J9 TRANSFUSION
JI Transfusion
PD MAY
PY 2009
VL 49
IS 5
BP 995
EP 1002
DI 10.1111/j.1537-2995.2008.02077.x
PG 8
WC Hematology
SC Hematology
GA 436JQ
UT WOS:000265410800026
PM 19159415
ER
PT J
AU McClatchey, AI
Fehon, RG
AF McClatchey, Andrea I.
Fehon, Richard G.
TI Merlin and the ERM proteins - regulators of receptor distribution and
signaling at the cell cortex
SO TRENDS IN CELL BIOLOGY
LA English
DT Review
ID NF2 TUMOR-SUPPRESSOR; MEMBRANE-CYTOSKELETON ADHESION; GROWTH-FACTOR;
ADHERENS JUNCTIONS; ACTIN CYTOSKELETON; FERM DOMAIN; NEUROFIBROMATOSIS
TYPE-2; INTERCELLULAR-ADHESION; IMMUNOLOGICAL SYNAPSE; CONTACT
INHIBITION
AB Recent studies highlight the importance of the distribution of membrane receptors in controlling receptor output and in contributing to complex biological processes. The cortical cytoskeleton is known to affect membrane protein distribution but the molecular basis of this is largely unknown. Here, we discuss the functions of Merlin and the ERM proteins both in linking membrane proteins to the underlying cortical cytoskeleton and in controlling the distribution of and signaling from membrane receptors. We also propose a model that could account for the intricacies of Merlin function across model organisms.
C1 [McClatchey, Andrea I.] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA 02129 USA.
[McClatchey, Andrea I.] Harvard Univ, Sch Med, Dept Pathol, Charlestown, MA 02129 USA.
[Fehon, Richard G.] Univ Chicago, Dept Mol Genet & Cell Biol, Chicago, IL 60637 USA.
RP McClatchey, AI (reprint author), Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA 02129 USA.
EM mcclatch@helix.mgh.harvard.edu
FU NIH [RO1 CA113733, RO1 NS034738]; DOD [W81XWH-05-1-0189]
FX The authors would like to thank the members of the McClatchey and Fehon
laboratories for helpful comments and discussions. This work was
supported by NIH RO1 CA113733 and DOD W81XWH-05-1-0189 to A.I.M. and NIH
RO1 NS034738 to R.G.F.
NR 92
TC 93
Z9 94
U1 0
U2 5
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0962-8924
J9 TRENDS CELL BIOL
JI Trends Cell Biol.
PD MAY
PY 2009
VL 19
IS 5
BP 198
EP 206
DI 10.1016/j.tcb.2009.02.006
PG 9
WC Cell Biology
SC Cell Biology
GA 453PN
UT WOS:000266623500002
PM 19345106
ER
PT J
AU Yoo, SD
Cho, YH
Sheen, J
AF Yoo, Sang-Dong
Cho, Younghee
Sheen, Jen
TI Emerging connections in the ethylene signaling network
SO TRENDS IN PLANT SCIENCE
LA English
DT Review
ID HISTIDINE KINASE-ACTIVITY; F-BOX PROTEINS; RECEPTOR FAMILY-MEMBERS;
RAF-LIKE KINASE; ARABIDOPSIS-THALIANA; RESPONSE PATHWAY; AUXIN
BIOSYNTHESIS; GENE FAMILY; ENDOPLASMIC-RETICULUM; TRANSCRIPTION FACTOR
AB The gaseous plant hormone ethylene acts as a pivotal mediator to respond to and coordinate internal and external cues in modulating plant growth dynamics and developmental programs. Genetic analysis of Arabidopsis thaliana has been used to identify key components and to build a linear ethylene-signaling pathway from the receptors through to the nuclear transcription factors. Studies applying integrative approaches have revealed new regulators, molecular connections and mechanisms in ethylene signaling and unexpected links to other plant hormones. Here, we review and discuss recent discoveries about the functional mode of ethylene receptor complexes, dual mitogen-activated protein kinase cascade signaling, stability control of the master nuclear transcription activator ETHYLENE INSENSITIVE 3 (EIN3), and the contextual relationships between ethylene and other plant hormones, such as auxin and gibberellins, in organ-specific growth regulation.
C1 [Yoo, Sang-Dong; Cho, Younghee; Sheen, Jen] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol,Dept Genet, Boston, MA 02114 USA.
[Yoo, Sang-Dong] Sungkyunkwan Univ, Dept Biol Sci, Suwon, South Korea.
RP Sheen, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol,Dept Genet, Boston, MA 02114 USA.
EM sheen@molbio.mgh.harvard.edu
RI allasia, valerie/B-4214-2009
FU US National Science Foundation; National Institutes of Health;
SungKyunKwan University
FX We apologize to authors whose work could not be cited here because of
space constraints. We thank C. Chang, S. Zhang and W.H. Cheng for
sharing information before publication. This work was supported by
grants from the US National Science Foundation and the National
Institutes of Health (J.S.) and SungKyunKwan University (S.D.Y.).
NR 90
TC 101
Z9 109
U1 1
U2 54
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 1360-1385
J9 TRENDS PLANT SCI
JI Trends Plant Sci.
PD MAY
PY 2009
VL 14
IS 5
BP 270
EP 279
DI 10.1016/j.tplants.2009.02.007
PG 10
WC Plant Sciences
SC Plant Sciences
GA 449YR
UT WOS:000266367600006
PM 19375376
ER
PT J
AU Gee, MS
Harisinghani, MG
Tabatabaei, S
AF Gee, Michael S.
Harisinghani, Mukesh G.
Tabatabaei, Shahin
TI Molecular Imaging in Urologic Surgery
SO UROLOGIC CLINICS OF NORTH AMERICA
LA English
DT Article
DE Radiology; MRI; Optical imaging
ID POSITRON-EMISSION-TOMOGRAPHY; OPTICAL COHERENCE TOMOGRAPHY;
SUPERPARAMAGNETIC IRON-OXIDE; URINARY-BLADDER CANCER; LYMPH-NODE
DISSECTION; GERM-CELL TUMORS; PROSTATE-CANCER; CONTRAST AGENTS; MR;
FLUORESCENCE
AB Recently, advances in imaging technology have made possible the ability to image noninvasively specific molecular pathways in vivo that are involved in disease processes. Molecular imaging evaluates changes in cellular physiology and function rather than anatomy, which are likely to be earlier and more sensitive manifestations of disease. In addition, as newer drugs to treat disease become increasingly molecule specific, molecular imaging has become necessary to provide noninvasive determination of patients likely to benefit from treatment and early therapy response. This article reviews current and emerging molecular imaging technologies relevant to urologic surgery.
C1 [Gee, Michael S.; Harisinghani, Mukesh G.; Tabatabaei, Shahin] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Tabatabaei, S (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA.
EM stabatabaei@partners.org
NR 41
TC 3
Z9 3
U1 0
U2 2
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0094-0143
J9 UROL CLIN N AM
JI Urol. Clin. N. Am.
PD MAY
PY 2009
VL 36
IS 2
BP 125
EP +
DI 10.1016/j.ucl.2009.02.007
PG 9
WC Urology & Nephrology
SC Urology & Nephrology
GA 452YR
UT WOS:000266577600003
PM 19406314
ER
PT J
AU Kupelian, V
McVary, KT
Barry, MJ
Link, CL
Rosen, RC
Aiyer, LP
Mollon, P
McKinlay, JB
AF Kupelian, Varant
McVary, Kevin T.
Barry, Michael J.
Link, Carol L.
Rosen, Raymond C.
Aiyer, Lalitha Padmanabhan
Mollon, Patrick
McKinlay, John B.
TI Association of C-reactive Protein and Lower Urinary Tract Symptoms in
Men and Women: Results From Boston Area Community Health Survey
SO UROLOGY
LA English
DT Article
ID BENIGN PROSTATIC HYPERPLASIA; QUALITY-OF-LIFE; BACH SURVEY; PREVALENCE;
INDEX; INFLAMMATION; GENDER; SAMPLE; SCALE
AB OBJECTIVES: To determine whether an association exists between C reactive protein (CRP) levels and lower urinary tract symptoms (LUTS) as assessed by the American Urological Association Symptom Index (AUA-SI) among both men and women, and to determine the association of CRP levels with the individual urologic symptoms comprising the AUA-SI among both men and women.
METHODS: The Boston Area Community Health survey used a multistage stratified design to recruit a random sample of 5502 adults aged 30-79 years. Blood samples were obtained from 3752 participants. The analyses were conducted on 1898 men and 1854 women with complete data on CRP levels. Overall LUTS was defined as an AUA-SI of >= 8 (moderate to severe LUTS). The urologic symptoms comprising the AUA-SI were included in the analysis as reports of fairly often to almost always vs non/rarely/a few times.
RESULTS: A statistically significant association was observed between the CRP levels and overall LUTS among both men and women. The pattern of associations between the individual symptoms and CRP levels varied by sex. Nocturia and straining were associated with greater CRP levels among men, and incomplete emptying and weak stream were associated with greater CRP levels among women.
CONCLUSIONS: The results of this study have demonstrated an association between CRP levels and LUTS in both men and women. The dose-response relationship between increased CRP levels and an increased odds of LUTS supports the hypothesized role of inflammatory processes in the etiology of LUTS. UROLOGY 73: 950-957, 2009. (C) 2009 Elsevier Inc.
C1 [McKinlay, John B.] New England Res Inst, Watertown, MA 02472 USA.
Northwestern Univ, Sch Med, Dept Urol, Chicago, IL 60611 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
Pfizer Inc, New York, NY USA.
Pfizer Ltd, Sandwich CT13 9NJ, Kent, England.
RP McKinlay, JB (reprint author), New England Res Inst, 9 Galen St, Watertown, MA 02472 USA.
EM bach@neriscience.com
FU NIDDK NIH HHS [R01 DK056842, U01 DK056842, DK 56842]
NR 31
TC 46
Z9 48
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0090-4295
J9 UROLOGY
JI Urology
PD MAY
PY 2009
VL 73
IS 5
BP 950
EP 957
DI 10.1016/j.urology.2008.12.012
PG 8
WC Urology & Nephrology
SC Urology & Nephrology
GA 443PU
UT WOS:000265923100009
PM 19394490
ER
PT J
AU Buchanan, J
Fleischmann, R
Genovese, MC
Kay, J
Hsia, EC
Doyle, MK
Rahman, MU
Han, C
Parasuraman, S
AF Buchanan, J.
Fleischmann, R.
Genovese, M. C.
Kay, J.
Hsia, E. C.
Doyle, M. K.
Rahman, M. U.
Han, C.
Parasuraman, S.
TI GOLIMUMAB, A HUMAN ANTI-TNF-ALPHA MONOCLONAL ANTIBODY, SIGNIFICANTLY
IMPROVES SELF-REPORTED PRODUCTIVITY IN PATIENTS WITH RHEUMATOID
ARTHRITIS: RESULTS FROM THREE PHASE 3 STUDIES
SO VALUE IN HEALTH
LA English
DT Meeting Abstract
C1 [Buchanan, J.; Han, C.; Parasuraman, S.] Johnson & Johnson Pharmaceut Serv LLC, Malvern, PA USA.
[Fleischmann, R.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Genovese, M. C.] Stanford Univ, Palo Alto, CA 94304 USA.
[Kay, J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
[Hsia, E. C.; Doyle, M. K.; Rahman, M. U.] U Penn Med Sch, Centocor Res & Dev Inc, Malvern, PA USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1098-3015
J9 VALUE HEALTH
JI Value Health
PD MAY
PY 2009
VL 12
IS 3
BP A72
EP A72
DI 10.1016/S1098-3015(10)73423-9
PG 1
WC Economics; Health Care Sciences & Services; Health Policy & Services
SC Business & Economics; Health Care Sciences & Services
GA 433WO
UT WOS:000265236700355
ER
PT J
AU Parikh, NM
Shah, DH
Deswal, A
Ashton, CM
Agarwal, SJ
Chen, H
Johnson, M
AF Parikh, N. M.
Shah, D. H.
Deswal, A.
Ashton, C. M.
Agarwal, S. J.
Chen, H.
Johnson, M.
TI THE ASSOCIATION OF ASPIRIN USE ON RISK OF HOSPITALIZATION IN CHF
PATIENTS TAKING ACE INHIBITORS: A RETROSPECTIVE ANALYSIS OF A NATIONAL
COHORT OF VETERANS
SO VALUE IN HEALTH
LA English
DT Meeting Abstract
C1 [Parikh, N. M.] Anal Grp Inc, Boston, MA USA.
[Shah, D. H.] Abt Bio Pharma Solut Inc, Waltham, MA USA.
[Deswal, A.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA.
[Ashton, C. M.] Methodist Inst Technol Innovat & Educ, Houston, TX USA.
[Agarwal, S. J.; Chen, H.; Johnson, M.] Univ Houston, Houston, TX USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1098-3015
J9 VALUE HEALTH
JI Value Health
PD MAY
PY 2009
VL 12
IS 3
BP A146
EP A146
DI 10.1016/S1098-3015(10)73792-X
PG 1
WC Economics; Health Care Sciences & Services; Health Policy & Services
SC Business & Economics; Health Care Sciences & Services
GA 433WO
UT WOS:000265236700724
ER
PT J
AU Toy, EL
Porter, CL
Books, P
Vekeman, F
Barghout, V
Duh, M
Skarin, AT
AF Toy, E. L.
Porter, C. L.
Books, P.
Vekeman, F.
Barghout, V
Duh, M.
Skarin, A. T.
TI BUDGET IMPACT ANALYSIS OF SARGRAMOSTIM USE IN PATIENTS WITH
CHEMOTHERAPY-INDUCED NEUTROPENIA
SO VALUE IN HEALTH
LA English
DT Meeting Abstract
C1 [Toy, E. L.; Porter, C. L.; Books, P.] Anal Grp Inc, Lakewood, CO USA.
[Vekeman, F.] Grp Analyse Ltee, Montreal, PQ, Canada.
[Barghout, V] Bayer HealthCare Pharmaceut Inc, Wayne, NJ USA.
[Duh, M.] Anal Grp Inc, Boston, MA USA.
[Skarin, A. T.] Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1098-3015
J9 VALUE HEALTH
JI Value Health
PD MAY
PY 2009
VL 12
IS 3
BP A39
EP A39
DI 10.1016/S1098-3015(10)73256-3
PG 1
WC Economics; Health Care Sciences & Services; Health Policy & Services
SC Business & Economics; Health Care Sciences & Services
GA 433WO
UT WOS:000265236700188
ER
PT J
AU Vekeman, F
Laliberte, F
Afonja, O
Lafeuille, MH
Barghout, V
Duh, MS
Skarin, AT
AF Vekeman, F.
Laliberte, F.
Afonja, O.
Lafeuille, M. H.
Barghout, V
Duh, M. S.
Skarin, A. T.
TI PATTERN OF UTILIZATION OF PEGFILGRASTIM IN PATIENTS WITH
CHEMOTHERAPY-INDUCED NEUTROPENIA: A RETROSPECTIVE ANALYSIS OF
ADMINISTRATIVE CLAIMS DATA
SO VALUE IN HEALTH
LA English
DT Meeting Abstract
C1 [Vekeman, F.; Laliberte, F.; Lafeuille, M. H.] Grpe Analyse Ltee, Montreal, PQ, Canada.
[Afonja, O.; Barghout, V] Bayer HealthCare Pharmaceut Inc, Wayne, NJ USA.
[Duh, M. S.] Anal Grp Inc, Boston, MA USA.
[Skarin, A. T.] Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1098-3015
J9 VALUE HEALTH
JI Value Health
PD MAY
PY 2009
VL 12
IS 3
BP A3
EP A3
DI 10.1016/S1098-3015(10)73079-5
PG 1
WC Economics; Health Care Sciences & Services; Health Policy & Services
SC Business & Economics; Health Care Sciences & Services
GA 433WO
UT WOS:000265236700011
ER
PT J
AU Yeh, SY
Doupis, J
Rahangdale, S
Horr, S
Malhotra, A
Veves, A
AF Yeh, Susie Yim
Doupis, John
Rahangdale, Shilpa
Horr, Samuel
Malhotra, Atul
Veves, Aristidis
TI Total serum bilirubin does not affect vascular reactivity in patients
with diabetes
SO VASCULAR MEDICINE
LA English
DT Article
DE bilirubin; diabetes; endothelial function
ID FLOW-MEDIATED VASODILATION; ENDOTHELIAL DYSFUNCTION; CARDIOVASCULAR
EVENTS; HEART-DISEASE; RISK; HEALTH; ATHEROSCLEROSIS; ASSOCIATION;
ADULTS
AB Bilirubin may have a major role in the prevention of cardiovascular disease based on recent data regarding its anti-oxidant properties. We determined the relationship between total serum bilirubin and vascular reactivity in a large cohort of individuals with diabetes, a disease associated with known oxidant stress. We studied 302 individuals: 52 controls, 37 with type 1 diabetes, 213 with type 2 diabetes. High-resolution ultrasound was used to measure flow-mediated dilation (FMD; endotheliumdependent) and nitroglycerin-induced dilation (NID, endothelium-independent) of the brachial artery. Laser Doppler perfusion imaging was used to measure microvascular reactivity in the forearm skin before and after iontophoresis of acetylcholine (endothelium-dependent) and sodium nitroprusside (endothelium- independent). Bilirubin levels were higher in the type 2 diabetes group (0.71 +/- 0.34 mg/dl) compared to controls (0.56 +/- 0.26 mg/dl, p < 0.0001). A weak inverse correlation was observed between bilirubin and FMD (r = -0.125, p = 0.032) and skin endothelium- dependent vasodilation (r = -0.157, p = 0.019). In multivariate analyses, however, these correlations were not statistically significant. There is no association between bilirubin levels and vascular reactivity in the macro- and microcirculation of individuals with diabetes. Bilirubin, therefore, does not correlate with predictors of cardiovascular risk in the diabetic population.
C1 [Horr, Samuel; Veves, Aristidis] Harvard Univ, Sch Med, Microcirculat Lab, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Yeh, Susie Yim; Rahangdale, Shilpa; Malhotra, Atul] Harvard Univ, Sch Med, Sleep Disorders Program, Brigham & Womens Hosp, Cambridge, MA 02138 USA.
[Doupis, John] Joslin Diabet Ctr, Boston, MA USA.
RP Veves, A (reprint author), Harvard Univ, Sch Med, Microcirculat Lab, Beth Israel Deaconess Med Ctr, Palmer 317,1 Deaconess Rd, Boston, MA 02215 USA.
EM aveves@caregroup.harvard.edu
FU NCRR NIH HHS [M01 RR001032, RR 01032]; NHLBI NIH HHS [K24 HL093218, R01
HL073146, R01 HL073146-04, R01 HL075678, R01 HL75678, R01-HL73146]; NIA
NIH HHS [K23 AG024837, K23 AG024837-04]
NR 24
TC 10
Z9 10
U1 1
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 MAY
PY 2009
VL 14
IS 2
BP 129
EP 136
DI 10.1177/1358863X08098273
PG 8
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 433PR
UT WOS:000265218500005
PM 19366819
ER
PT J
AU Gul, KM
Ahmadi, N
Wang, ZY
Jamieson, C
Nasir, K
Metcalfe, R
Hecht, HS
Hartley, CJ
Naghavi, M
AF Gul, Khawar M.
Ahmadi, Naser
Wang, Zhiying
Jamieson, Craig
Nasir, Khurram
Metcalfe, Ralph
Hecht, Harvey S.
Hartley, Craig J.
Naghavi, Morteza
TI Digital thermal monitoring of vascular function: a novel tool to improve
cardiovascular risk assessment
SO VASCULAR MEDICINE
LA English
DT Article
DE coronary heart disease; digital thermal monitoring; endothelial
function; Framingham risk score; reactive hyperemia; vascular reactivity
ID REACTIVE HYPEREMIA; MICROVASCULAR FUNCTION; ATHEROSCLEROSIS; DISEASE;
FLOW; SKIN
AB Digital thermal monitoring (DTM) of vascular function during cuff-occlusive reactive hyperemia relies on the premise that changes in fingertip temperature during and after an ischemic stimulus reflect changes in blood flow. To determine its utility in individuals with and without known coronary heart disease (CHD), 133 consecutive individuals (age 54 +/- 10 years, 50% male, 19 with known CHD) underwent DTM during and after 2 minutes of supra-systolic arm cuff inflation. Fingertip temperatures of the occluded and non-occluded fingertips were measured simultaneously. Post-cuff deflation temperature rebound (TR) was lower in the CHD patients and in those with an increased Framingham risk score (FRS) compared to the normal group. After adjustment for age, sex, and cardiac risk factors, TR was significantly lower in those with CHD compared to those without CHD (p < 0.05). This study demonstrates that vascular dysfunction measured by DTM is associated with CHD and an increased FRS, and could potentially be used to identify high-risk patients.
C1 [Gul, Khawar M.; Ahmadi, Naser] Harbor UCLA Med Ctr, Torrance, CA USA.
[Wang, Zhiying] Univ Texas Houston Hlth Sci Ctr, Houston, TX USA.
[Nasir, Khurram] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac MRI PET CT Program, Cambridge, MA 02138 USA.
[Metcalfe, Ralph] Univ Houston, Houston, TX 77004 USA.
[Hartley, Craig J.] Baylor Coll Med, Houston, TX 77030 USA.
RP Naghavi, M (reprint author), 8275 El Rio,Suite 100, Houston, TX 77054 USA.
EM mn@vp.org
FU NHLBI NIH HHS [R01 HL022512]
NR 16
TC 20
Z9 23
U1 1
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 MAY
PY 2009
VL 14
IS 2
BP 143
EP 148
DI 10.1177/1358863X08098850
PG 6
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 433PR
UT WOS:000265218500007
PM 19366821
ER
PT J
AU Isayama, T
England, SLM
Crouch, RK
Zimmerman, AL
Makino, CL
AF Isayama, Tomoki
England, S. L. McCabe
Crouch, R. K.
Zimmerman, A. L.
Makino, C. L.
TI beta-ionone activates and bleaches visual pigment in salamander
photoreceptors
SO VISUAL NEUROSCIENCE
LA English
DT Article
DE Retinoids; Phototransduction; Rhodopsin; Cyclic nucleotide-gated
channel; Neurophysiology
ID PROTEIN-COUPLED RECEPTORS; ROD OUTER SEGMENT; RETINAL CONES;
BINDING-SITE; ALLOSTERIC MODULATION; OPSIN; RHODOPSIN; ADAPTATION;
CHANNELS; PHOTOTRANSDUCTION
AB Vision begins with photoisomerization of 11-cis retinal to the all-trans conformation within the chromophore-binding pocket of opsin, leading to activation of a biochemical cascade. Release of all-trans retinal from the binding pocket curtails but does not fully quench file ability of opsin to activate transducin. All-trans retinal and some other analogs, Such as beta-ionone, enhance opsin's activity, presumably oil binding the empty chromophore-binding pocket. By recording from isolated salamander photoreceptors and from patches of rod outer segment membrane, we now show that high concentrations of beta-ionone suppressed circulating current in dark-adapted green-sensitive rods by inhibiting the cyclic nucleotide-gated channels. There were also decreases in circulating current and flash sensitivity, and accelerated flash response kinetics in dark-adapted blue-sensitive (BS) rods and cones. and in Ultraviolet-sensitive cones, at concentrations too low to inhibit the channels. These effects persisted in BS rods even after incubation with 9-cis retinal to ensure complete regeneration of their visual pigment, After long exposures to high concentrations of beta-ionone. recovery was incomplete unless 9-cis retinal was given, indicating that visual pigment had been bleached. Therefore, we propose that beta-ionone activates and bleaches some types of visual pigments, mimicking the effects of light.
C1 [Isayama, Tomoki; Makino, C. L.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA.
[England, S. L. McCabe; Zimmerman, A. L.] Brown Univ, Dept Mol Pharmacol Physiol & Biotechnol, Providence, RI 02912 USA.
[Crouch, R. K.] Med Univ S Carolina, Dept Ophthalmol, Storm Eye Res Inst, Charleston, SC 29425 USA.
RP Isayama, T (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA.
EM tomoki_isayama@meei.harvard.edu
OI Makino, Clint/0000-0002-6005-9069
FU Medical University of South Carolina (MUSC); [NEI EY11358]; [EY12944];
[EY07774]; [EY04939]; [EY014793]; [EY014104]
FX We thank William N. Zagotta for the CNGA1 clone, Michael Varnum tor the
CNGA3 clone. and V. Ketalov and M.C. Cornwall for helpful discussions.
This work was supported by NEI EY11358, EY12944, EY07774, EY04939,
EY014793, EY014104, and an unrestricted grant to Medical University of
South Carolina (MUSC) flour Research to Prevent Blindness, Inc. R.K.C.
is an Research to Prevent Blindness Senior Scientific Investigator.
NR 43
TC 3
Z9 3
U1 1
U2 4
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 0952-5238
J9 VISUAL NEUROSCI
JI Visual Neurosci.
PD MAY-JUN
PY 2009
VL 26
IS 3
BP 267
EP 274
DI 10.1017/S0952523809090105
PG 8
WC Neurosciences; Ophthalmology
SC Neurosciences & Neurology; Ophthalmology
GA 485DV
UT WOS:000269102000002
PM 19500430
ER
PT J
AU Chatterjee, S
Rath, ME
Spiro, A
Eisen, S
Sloan, KL
Rosen, AK
AF Chatterjee, Sharmila
Rath, Maria E.
Spiro, Avron, III
Eisen, Susan
Sloan, Kevin L.
Rosen, Amy K.
TI GENDER DIFFERENCES IN VETERANS HEALTH ADMINISTRATION MENTAL HEALTH
SERVICE USE Effects of Age and Psychiatric Diagnosis
SO WOMENS HEALTH ISSUES
LA English
DT Article
ID POSTTRAUMATIC-STRESS-DISORDER; NATIONAL COMORBIDITY SURVEY; GULF-WAR
VETERANS; WOMEN VETERANS; FEMALE VETERANS; SEXUAL ASSAULT;
UNITED-STATES; CARE UTILIZATION; SUBSTANCE-ABUSE; IN-SERVICE
AB Purpose. The objective of this study was to compare gender differences in mental health disease burden and outpatient mental health utilization among veterans utilizing Veterans Health Administration (VHA) mental health services in fiscal year 1999 (FY99), after the first Gulf War and significant restructuring of VHA services.
Methods. We used logistic regression to examine the relationships among gender, age, diagnostic groups, and utilization of mental health and specialty mental health services in a national sample of veterans. The sample included 782,789 veterans with at least 1 outpatient visit in the VHA in FY99 associated with a mental health or substance abuse (SA) diagnosis. Subgroup analyses were performed for 4 diagnostic categories: 1) posttraumatic stress disorder (PTSD), 2) SA disorders, 3) bipolar and psychotic disorders, and 4) mood and anxiety disorders.
Main Findings. Younger women veterans (<35 years old) were significantly less likely and older women (>= 35) more likely to use any mental health services in comparison with their male counterparts. Similar findings were observed for younger women diagnosed with SA or mood and anxiety disorders, but not among veterans with PTSD or bipolar and psychotic disorders, among whom no there were no gender or age differences. In the case of specialized services for SA or PTSD, women younger than 55 with SA or PTSD were significantly less likely to use services than men.
Conclusion. Women veterans underutilized specialty mental health services in relation to men but receipt of mental health care overall in FY99 varied by age and diagnosis. Examining gender differences alone, without taking other factors into account, may not provide an adequate picture of women veterans' current mental health service needs.
C1 [Chatterjee, Sharmila] Bedford VAMC 152, Ctr Hlth Qual Outcomes & Econ Res, Dept Hlth Policy & Management, Bedford, MA 01730 USA.
[Chatterjee, Sharmila; Eisen, Susan; Rosen, Amy K.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA.
[Rath, Maria E.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Spiro, Avron, III] Boston VA Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA.
[Spiro, Avron, III] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Sloan, Kevin L.] VA Puget Sound Healthcare Syst, Seattle, WA USA.
[Sloan, Kevin L.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
RP Chatterjee, S (reprint author), Bedford VAMC 152, Ctr Hlth Qual Outcomes & Econ Res, Dept Hlth Policy & Management, Bedford, MA 01730 USA.
EM sharmcha@bu.edu
OI Spiro III, Avron/0000-0003-4080-8621
NR 53
TC 11
Z9 11
U1 3
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1049-3867
J9 WOMEN HEALTH ISS
JI Womens Health Iss.
PD MAY-JUN
PY 2009
VL 19
IS 3
BP 176
EP 184
DI 10.1016/j.whi.2009.03.002
PG 9
WC Public, Environmental & Occupational Health; Women's Studies
SC Public, Environmental & Occupational Health; Women's Studies
GA 454RH
UT WOS:000266699700003
PM 19447322
ER
PT J
AU Letai, A
AF Letai, Anthony
TI Hiding from ABT-737 in lymph nodes
SO BLOOD
LA English
DT Editorial Material
ID CHRONIC LYMPHOCYTIC-LEUKEMIA; SURVIVAL
C1 Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Letai, A (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 5
TC 2
Z9 2
U1 0
U2 0
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD APR 30
PY 2009
VL 113
IS 18
BP 4132
EP 4133
DI 10.1182/blood-2008-12-192831
PG 4
WC Hematology
SC Hematology
GA 442MW
UT WOS:000265846300004
PM 19406997
ER
PT J
AU Morel, P
Duhamel, A
Gobbi, P
Dimopoulos, MA
Dhodapkar, MV
McCoy, J
Crowley, J
Ocio, EM
Garcia-Sanz, R
Treon, SP
Leblond, V
Kyle, RA
Barlogie, B
Merlini, G
AF Morel, Pierre
Duhamel, Alain
Gobbi, Paolo
Dimopoulos, Meletios A.
Dhodapkar, Madhav V.
McCoy, Jason
Crowley, John
Ocio, Enrique M.
Garcia-Sanz, Ramon
Treon, Steven P.
Leblond, Veronique
Kyle, Robert A.
Barlogie, Bart
Merlini, Giampaolo
TI International prognostic scoring system for Waldenstrom
macroglobulinemia
SO BLOOD
LA English
DT Article; Proceedings Paper
CT 48th Annual Meeting of the American-Society-of-Hematology
CY DEC 09-12, 2006
CL Orlando, FL
SP Amer Soc Hematol
ID CONSENSUS PANEL RECOMMENDATIONS; CHRONIC LYMPHOCYTIC-LEUKEMIA;
MULTIPLE-MYELOMA; MODEL; RITUXIMAB; WORKSHOP; SURVIVAL; THERAPY;
CLASSIFICATION; VALIDATION
AB Recently, many new drugs have been developed for the treatment of Waldenstrom macroglobulinemia (WM). To optimize the treatment according to the prognosis and to facilitate the comparison of trials, we developed an International Prognostic Scoring System for WM in a series of 587 patients with clearly defined criteria for diagnosis and for initiation of treatment. The median survival after treatment initiation was 87 months. Five adverse covariates were identified: advanced age (> 65 years), hemoglobin less than or equal to 11.5 g/dL, platelet count less than or equal to 100 x 10(9)/L, beta 2-microglobulin more than 3 mg/L, and serum monoclonal protein concentration more than 7.0 g/dL. Low-risk patients (27%) presented with no or 1 of the adverse characteristics and advanced age, intermediate-risk patients (38%) with 2 adverse characteristics or only advanced age, and high-risk patients (35%) with more than 2 adverse characteristics. Five-year survival rates were 87%, 68%, and 36%, respectively (P<.001). The ISSWM retained its prognostic significance in subgroups defined by age, treatment with alkylating agent, and purine analog. Thus, the ISSWM may provide a means to design risk-adapted studies. However, independent validation and new biologic markers may enhance its significance. (Blood. 2009; 113: 4163-4170)
C1 [Morel, Pierre] Hop Schaffner, Lens, France.
[Morel, Pierre; Leblond, Veronique] French Cooperat Grp Chron Lymphocyt Leukaemia Wal, Paris, France.
[Duhamel, Alain] Fac Med Lille, F-59045 Lille, France.
[Gobbi, Paolo; Merlini, Giampaolo] Univ Pavia, Fdn IRCCS, Policlin San Matteo, I-27100 Pavia, Italy.
[Dimopoulos, Meletios A.] Univ Athens, Sch Med, GR-11527 Athens, Greece.
[Dhodapkar, Madhav V.] Rockefeller Univ, New York, NY 10021 USA.
[McCoy, Jason; Crowley, John] SW Oncol Grp, Seattle, WA USA.
[Ocio, Enrique M.; Garcia-Sanz, Ramon] Spanish Grp Study Waldenstrom Macroglobulinaemia, Salamanca, Spain.
[Treon, Steven P.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Leblond, Veronique] Univ Paris 06, Hop Pitie Salpetriere, Paris, France.
[Kyle, Robert A.] Mayo Clin, Rochester, MN USA.
[Barlogie, Bart] Univ Arkansas Med Sci, Little Rock, AR 72205 USA.
RP Morel, P (reprint author), Ctr Hosp Schaffner, Serv Hematol Clin, 99 Route Bassee, F-62300 Lens, France.
EM pmorel@ch-lens.fr
RI Duhamel, Alain/B-8624-2011; 2009, Secribsal/A-1266-2012; Duhamel,
Alain/A-4899-2013; Garcia-Sanz, Ramon/B-7986-2017;
OI Garcia-Sanz, Ramon/0000-0003-4120-2787; Merlini,
Giampaolo/0000-0001-7680-3254
NR 34
TC 121
Z9 129
U1 1
U2 11
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD APR 30
PY 2009
VL 113
IS 18
BP 4163
EP 4170
DI 10.1182/blood-2008-08-174961
PG 8
WC Hematology
SC Hematology
GA 442MW
UT WOS:000265846300011
PM 19196866
ER
PT J
AU Azab, AK
Runnels, JM
Pitsillides, C
Moreau, AS
Azab, F
Leleu, X
Jia, X
Wright, R
Ospina, B
Carlson, AL
Alt, C
Burwick, N
Roccaro, AM
Ngo, HT
Farag, M
Melhem, MR
Sacco, A
Munshi, NC
Hideshima, T
Rollins, BJ
Anderson, KC
Kung, AL
Lin, CP
Ghobrial, IM
AF Azab, Abdel Kareem
Runnels, Judith M.
Pitsillides, Costas
Moreau, Anne-Sophie
Azab, Feda
Leleu, Xavier
Jia, Xiaoying
Wright, Renee
Ospina, Beatriz
Carlson, Alicia L.
Alt, Clemens
Burwick, Nicholas
Roccaro, Aldo M.
Ngo, Hai T.
Farag, Mena
Melhem, Molly R.
Sacco, Antonio
Munshi, Nikhil C.
Hideshima, Teru
Rollins, Barrett J.
Anderson, Kenneth C.
Kung, Andrew L.
Lin, Charles P.
Ghobrial, Irene M.
TI CXCR4 inhibitor AMD3100 disrupts the interaction of multiple myeloma
cells with the bone marrow microenvironment and enhances their
sensitivity to therapy
SO BLOOD
LA English
DT Article
ID MEDIATED DRUG-RESISTANCE; NON-HODGKINS-LYMPHOMA; STEM-CELLS;
MOBILIZATION; MECHANISMS; BORTEZOMIB; ADHESION; GROWTH; FACTOR-1-ALPHA;
INVOLVEMENT
AB The interaction of multiple myeloma (MM) cells with their microenvironment in the bone marrow (BM) provides a protective environment and resistance to therapeutic agents. We hypothesized that disruption of the interaction of MM cells with their BM milieu would lead to their sensitization to therapeutic agents such as bortezomib, melphalan, doxorubicin, and dexamethasone. We report that the CXCR4 inhibitor AMD3100 induces disruption of the interaction of MM cells with the BM reflected by mobilization of MM cells into the circulation in vivo, with kinetics that differed from that of hematopoietic stem cells. AMD3100 enhanced sensitivity of MM cell to multiple therapeutic agents in vitro by disrupting adhesion of MM cells to bone marrow stromal cells (BMSCs). Moreover, AMD3100 increased mobilization of MM cells to the circulation in vivo, increased the ratio of apoptotic circulating MM cells, and enhanced the tumor reduction induced by bortezomib. Mechanistically, AMD3100 significantly inhibited Akt phosphorylation and enhanced poly(ADP-ribose) polymerase (PARP) cleavage as a result of bortezomib, in the presence of BMSCs in coculture. These experiments provide a proof of concept for the use of agents that disrupt interaction with the microenvironment for enhancement of efficacy of cytotoxic agents in cancer therapy. (Blood. 2009; 113: 4341-4351)
C1 [Azab, Abdel Kareem; Runnels, Judith M.; Pitsillides, Costas; Carlson, Alicia L.; Alt, Clemens; Lin, Charles P.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.
[Azab, Abdel Kareem; Runnels, Judith M.; Pitsillides, Costas; Carlson, Alicia L.; Alt, Clemens; Lin, Charles P.] Massachusetts Gen Hosp, Adv Microscopy Program, Ctr Syst Biol, Boston, MA 02114 USA.
[Azab, Abdel Kareem; Runnels, Judith M.; Moreau, Anne-Sophie; Azab, Feda; Leleu, Xavier; Jia, Xiaoying; Wright, Renee; Ospina, Beatriz; Burwick, Nicholas; Roccaro, Aldo M.; Ngo, Hai T.; Farag, Mena; Melhem, Molly R.; Sacco, Antonio; Munshi, Nikhil C.; Hideshima, Teru; Rollins, Barrett J.; Anderson, Kenneth C.; Kung, Andrew L.; Ghobrial, Irene M.] Harvard Univ, Sch Med, Boston, MA USA.
[Azab, Abdel Kareem; Runnels, Judith M.; Moreau, Anne-Sophie; Azab, Feda; Leleu, Xavier; Jia, Xiaoying; Wright, Renee; Ospina, Beatriz; Burwick, Nicholas; Roccaro, Aldo M.; Ngo, Hai T.; Farag, Mena; Melhem, Molly R.; Sacco, Antonio; Munshi, Nikhil C.; Hideshima, Teru; Rollins, Barrett J.; Anderson, Kenneth C.; Ghobrial, Irene M.] Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Lin, CP (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.
EM lin@helix.mgh.harvard.edu; Irene_ghobrial@dfci.harvard.edu
RI Sacco, Antonio/K-4681-2016;
OI Sacco, Antonio/0000-0003-2945-9416; Roccaro, Aldo/0000-0002-1872-5128;
Kung, Andrew/0000-0002-9091-488X
FU National Institutes of Health (NIH, Bethesda, MD) [R01CA125690,
EB000664]; Leukemia & Lymphoma Society (White Plains, NY); Multiple
Myeloma Research Foundation (MMRF, Nowalk, CT)
FX This work was supported in part by R01CA125690, National Institutes of
Health (NIH, Bethesda, MD) EB000664, the Leukemia & Lymphoma Society
(White Plains, NY), and Multiple Myeloma Research Foundation (MMRF,
Nowalk, CT).
NR 41
TC 211
Z9 215
U1 5
U2 22
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD APR 30
PY 2009
VL 113
IS 18
BP 4341
EP 4351
DI 10.1182/blood-2008-10-186668
PG 11
WC Hematology
SC Hematology
GA 442MW
UT WOS:000265846300030
PM 19139079
ER
PT J
AU Roccaro, AM
Sacco, A
Chen, CZ
Runnels, J
Leleu, X
Azab, F
Azab, AK
Jia, XY
Ngo, HT
Melhem, MR
Burwick, N
Varticovski, L
Novina, CD
Rollins, BJ
Anderson, KC
Ghobrial, IM
AF Roccaro, Aldo M.
Sacco, Antonio
Chen, Changzhong
Runnels, Judith
Leleu, Xavier
Azab, Feda
Azab, Abdel Kareem
Jia, Xiaoying
Ngo, Hai T.
Melhem, Molly R.
Burwick, Nicholas
Varticovski, Lyuba
Novina, Carl D.
Rollins, Barrett J.
Anderson, Kenneth C.
Ghobrial, Irene M.
TI microRNA expression in the biology, prognosis, and therapy of
Waldenstrom macroglobulinemia
SO BLOOD
LA English
DT Article
ID NF-KAPPA-B; MULTIPLE-MYELOMA; CELL LYMPHOMAS; TARGET; REVEALS; MIR-155;
PATHWAY; PROTEIN; KINASE; CANCER
AB Multilevel genetic characterization of Waldenstrom macroglobulinemia (WM) is required to improve our understanding of the underlying molecular changes that lead to the initiation and progression of this disease. We performed microRNA-expression profiling of bone marrow-derived CD19(+) WM cells, compared with their normal cellular counterparts and validated data by quantitative reverse-transcription-polymerase chain reaction (qRT-PCR). We identified a WM-specific microRNA signature characterized by increased expression of microRNA-363*/-206/-494/-155/-184/-542-3p, and decreased expression of microRNA-9* (ANOVA; P < .01). We found that microRNA-155 regulates proliferation and growth of WM cells in vitro and in vivo, by inhibiting MAPK/ERK, PI3/AKT, and NF-kappa B pathways. Potential microRNA-155 target genes were identified using gene-expression profiling and included genes involved in cell-cycle progression, adhesion, and migration. Importantly, increased expression of the 6 miRNAs significantly correlated with a poorer outcome predicted by the International Prognostic Staging System for WM. We further demonstrated that therapeutic agents commonly used in WM alter the levels of the major miRNAs identified, by inducing downmodulation of 5 increased miRNAs and up-modulation of patient-downexpressed miRNA-9*. These data indicate that microRNAs play a pivotal role in the biology of WM; represent important prognostic marker; and provide the basis for the development of new microRNA-based targeted therapies in WM. (Blood. 2009; 113: 4391-4402)
C1 [Ghobrial, Irene M.] Dana Farber Canc Inst, Kirsch Lab Waldenstrom Macroglobulinemia, Dept Med Oncol, Boston, MA 02115 USA.
[Roccaro, Aldo M.; Sacco, Antonio; Chen, Changzhong; Runnels, Judith; Leleu, Xavier; Azab, Feda; Azab, Abdel Kareem; Jia, Xiaoying; Ngo, Hai T.; Melhem, Molly R.; Burwick, Nicholas; Novina, Carl D.; Rollins, Barrett J.; Anderson, Kenneth C.; Ghobrial, Irene M.] Harvard Univ, Sch Med, Boston, MA USA.
[Roccaro, Aldo M.] Univ Bari, Dept Internal Med & Clin Oncol, Sch Med, Bari, Italy.
[Roccaro, Aldo M.] Univ Brescia, Sch Med, Unit Blood Dis & Cell Therapies, Brescia, Italy.
[Varticovski, Lyuba] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Ghobrial, IM (reprint author), Dana Farber Canc Inst, Kirsch Lab Waldenstrom Macroglobulinemia, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA.
EM irene_ghobrial@dfci.harvard.edu
RI Sacco, Antonio/K-4681-2016;
OI Sacco, Antonio/0000-0003-2945-9416; Roccaro, Aldo/0000-0002-1872-5128
FU NIH [R21 1R21CA126119-01]; International Waldenstrom Macroglobulinemia
Foundation (IWMF); Kirsch Laboratory for Waldenstrom Macroglobulinemia;
Italian Association for Cancer Research; Berlucchi Foundation
FX This work was supported in part by NIH (Washington, DC) grant R21
1R21CA126119-01, International Waldenstrom Macroglobulinemia Foundation
(IWMF), Kirsch Laboratory for Waldenstrom Macroglobulinemia, Italian
Association for Cancer Research (A. M. R.), and Berlucchi Foundation (A.
M. R.).
NR 42
TC 62
Z9 66
U1 0
U2 8
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD APR 30
PY 2009
VL 113
IS 18
BP 4391
EP 4402
DI 10.1182/blood-2008-09-178228
PG 12
WC Hematology
SC Hematology
GA 442MW
UT WOS:000265846300035
PM 19074725
ER
PT J
AU Romeo, HE
Tio, DL
Taylor, AN
AF Romeo, Horacio E.
Tio, Delia L.
Taylor, Anna N.
TI Effects of superior cervical ganglionectomy on body temperature and on
the lipopolysaccharide-induced febrile response in rats
SO JOURNAL OF NEUROIMMUNOLOGY
LA English
DT Article
DE Fever; Superior cervical ganglionectomy; Biotelemetry;
Lipopolysaccharide; Sprague-Dawley rat
ID CORTICOTROPIN-RELEASING HORMONE; SUBMAXILLARY LYMPH-NODES; BROWN
ADIPOSE-TISSUE; SYMPATHETIC NEURONS; BRAIN COMMUNICATION;
LOCUS-COERULEUS; PITUITARY-GLAND; PREOPTIC AREA; NEUROENDOCRINE;
HYPOTHALAMUS
AB The involvement of the cervical sympathetic ganglia (SCG) on body temperature and during the occurrence of the induced febrile response was investigated in rats. Bilateral superior cervical gaglionectomy (SCGx) attenuated the daily dark-phase temperature compared to that of the sham-operated rats during the first 2 days post surgery. Body temperatures returned to pre-surgery levels by Day-3. Ten days after surgery, a febrile response was induced by lipopolysaccharide (LPS) immune challenge. SCGx significantly blunted the LPS-induced febrile response. These data suggest that obliteration of the cervical sympathetic peripheral innervation impairs the capability to produce an induced febrile response. (C) 2009 Elsevier B.V. All rights reserved.
C1 [Romeo, Horacio E.] Univ Buenos Aires, Fac Med, Dept Fisiol, RA-2155 Buenos Aires, DF, Argentina.
[Romeo, Horacio E.; Tio, Delia L.; Taylor, Anna N.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA.
[Tio, Delia L.; Taylor, Anna N.] W Los Angeles Healthcare Ctr, Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA.
RP Romeo, HE (reprint author), Univ Buenos Aires, Fac Med, Dept Fisiol, 1121BA, RA-2155 Buenos Aires, DF, Argentina.
EM hromeo@fmed.uba.ar
FU National Institute of Dental and Craniofacial Research [DE016063-01]
FX This work is supported by The National Institute of Dental and
Craniofacial Research; Grant number: DE016063-01 (H.E. Romeo).
NR 56
TC 3
Z9 3
U1 0
U2 7
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-5728
J9 J NEUROIMMUNOL
JI J. Neuroimmunol.
PD APR 30
PY 2009
VL 209
IS 1-2
BP 81
EP 86
DI 10.1016/j.jneuroim.2009.01.027
PG 6
WC Immunology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA 448ZG
UT WOS:000266299900009
PM 19251325
ER
PT J
AU Liu, HS
Agam, Y
Madsen, JR
Kreiman, G
AF Liu, Hesheng
Agam, Yigal
Madsen, Joseph R.
Kreiman, Gabriel
TI Timing, Timing, Timing: Fast Decoding of Object Information from
Intracranial Field Potentials in Human Visual Cortex
SO NEURON
LA English
DT Article
ID INFERIOR TEMPORAL NEURONS; SINGLE NEURONS; INFEROTEMPORAL CORTEX;
PREFRONTAL CORTEX; FACE PERCEPTION; HUMAN BRAIN; RECOGNITION; MEMORY;
RESPONSES; CATEGORY
AB The difficulty of visual recognition stems from the need to achieve high selectivity while maintaining robustness to object transformations within hundreds of milliseconds. Theories of visual recognition differ in whether the neuronal circuits invoke recurrent feedback connections or not. The timing of neurophysiological responses in visual cortex plays a key role in distinguishing between bottom-up and top-down theories. Here, we quantified at millisecond resolution the amount of visual information conveyed by intracranial field potentials from 912 electrodes in 11 human subjects. We could decode object category information from human visual cortex in single trials as early as 100 ms poststimulus. Decoding performance was robust to depth rotation and scale changes. The results suggest that physiological activity in the temporal lobe can account for key properties of visual recognition. The fast decoding in single trials is compatible with feedforward theories and provides strong constraints for computational models of human vision.
C1 [Liu, Hesheng; Agam, Yigal; Kreiman, Gabriel] Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Neurosci & Ophthalmol, Boston, MA 02115 USA.
[Liu, Hesheng] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02115 USA.
[Madsen, Joseph R.] Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Neurosurg, Boston, MA 02129 USA.
[Kreiman, Gabriel] Harvard Univ, Ctr Brain Sci, Boston, MA 02115 USA.
[Kreiman, Gabriel] Harvard Univ, Swartz Ctr Theoret Neurosci, Boston, MA 02115 USA.
RP Kreiman, G (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Neurosci & Ophthalmol, Boston, MA 02115 USA.
EM gabriel.kreiman@tch.harvard.edu
OI Liu, Hesheng/0000-0002-7233-1509
FU Epilepsy Foundation; Whitehall Foundation; Klingenstein Fund; Children's
Hospital Boston Ophthalmology Foundation
FX We would like to thank the patients for their cooperation in these
studies. We also thank Margaret Livingstone, Ethan Meyers, and Thomas
Serre for comments on the manuscript, and Calin Buia, Sheryl Manganaro,
Paul Dionne, and Malena Espanol for technical assistance. We also
acknowledge the financial support from the Epilepsy Foundation, the
Whitehall Foundation, the Klingenstein Fund, and Children's Hospital
Boston Ophthalmology Foundation.
NR 56
TC 179
Z9 180
U1 1
U2 21
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0896-6273
J9 NEURON
JI Neuron
PD APR 30
PY 2009
VL 62
IS 2
BP 281
EP 290
DI 10.1016/j.neuron.2009.02.025
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 441MU
UT WOS:000265774100015
PM 19409272
ER
PT J
AU Gaissert, HA
Piyavisetpat, N
Mark, EJ
AF Gaissert, Henning A.
Piyavisetpat, Nitra
Mark, Eugene J.
TI A Man with Chest Pain, Dysphagia, and Pleural and Mediastinal
Calcifications Diffuse malignant mesothelioma, with extensive osseous
differentiation, involving the pleura, chest wall, lung, mediastinum,
esophagus, and pericardium. Acute myocardial infarction
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID FIBRODYSPLASIA OSSIFICANS PROGRESSIVA; ASBESTOS EXPOSURE; CARTILAGINOUS
DIFFERENTIATION; TUMOR; OSTEOSARCOMA; HYPERPLASIA; MORTALITY; DIAGNOSIS;
FEATURES; BRITAIN
C1 [Gaissert, Henning A.] Massachusetts Gen Hosp, Dept Thorac Surg, Boston, MA 02114 USA.
[Piyavisetpat, Nitra] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Mark, Eugene J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Gaissert, Henning A.] Harvard Univ, Sch Med, Dept Surg, Cambridge, MA 02138 USA.
[Piyavisetpat, Nitra] Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA.
[Mark, Eugene J.] Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA.
RP Gaissert, HA (reprint author), Massachusetts Gen Hosp, Dept Thorac Surg, Boston, MA 02114 USA.
NR 36
TC 2
Z9 2
U1 0
U2 3
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD APR 30
PY 2009
VL 360
IS 18
BP 1886
EP 1895
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 438MU
UT WOS:000265560300012
PM 19403907
ER
PT J
AU Kaufman, RE
Ostacher, MJ
Marks, EH
Simon, NM
Sachs, GS
Jensen, JE
Renshaw, PF
Pollack, MH
AF Kaufman, Rebecca E.
Ostacher, Michael J.
Marks, Elizabeth H.
Simon, Naomi M.
Sachs, Gary S.
Jensen, J. Eric
Renshaw, Perry F.
Pollack, Mark H.
TI Brain GABA levels in patients with bipolar disorder
SO PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
LA English
DT Review
DE Anxiety; Bipolar disorder; GABA; Glutamate; Magnetic resonance
spectroscopy; Neuroimaging
ID MAGNETIC-RESONANCE-SPECTROSCOPY; ANTERIOR CINGULATE CORTEX;
AMINOBUTYRIC-ACID CONCENTRATIONS; DORSOLATERAL PREFRONTAL CORTEX; MOOD
DISORDERS; ELECTROCONVULSIVE-THERAPY; SCHIZOPHRENIC-PATIENTS;
DEPRESSED-PATIENTS; GABAERGIC NEURONS; ANXIETY DISORDERS
AB Purpose: A growing body of research supports an important role for GABA in the pathophysiology of bipolar and other mood disorders. The purpose of the current study was to directly examine brain GABA levels in a clinical sample of bipolar patients.
General methods: We used magnetic resonance spectroscopy (MRS) to examine whole brain and regional GABA, glutamate and glutamine in 13 patients with bipolar disorder compared to a matched group of 11 healthy controls.
Findings: There were no significant differences in GABA, glutamate or glutamine between patients and controls.
Conclusions: Further research is needed to better characterize the GABAergic and glutamatergic effects of pharmacotherapy, anxiety comorbidity and clinical state in bipolar disorder. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Pollack, Mark H.] Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Dept Psychiat, Boston, MA 02114 USA.
[Jensen, J. Eric; Renshaw, Perry F.] McLean Hosp, Dept Psychiat, Belmont, MA 02478 USA.
RP Pollack, MH (reprint author), Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Dept Psychiat, Simches Res Bldg,2nd Floor,185 Cambridge St, Boston, MA 02114 USA.
EM mpollack@partners.org
OI Ostacher, Michael/0000-0003-0353-7535; Sripada,
Rebecca/0000-0002-2844-3458
FU NARSAD Independent Investigator Grant
FX This study was funded by a NARSAD Independent Investigator Grant.
NR 49
TC 27
Z9 27
U1 2
U2 10
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0278-5846
J9 PROG NEURO-PSYCHOPH
JI Prog. Neuro-Psychopharmacol. Biol. Psychiatry
PD APR 30
PY 2009
VL 33
IS 3
BP 427
EP 434
DI 10.1016/j.pnpbp.2008.12.025
PG 8
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 437EY
UT WOS:000265470500007
PM 19171176
ER
PT J
AU Healy, BC
Engler, D
AF Healy, Brian C.
Engler, David
TI Modeling disease-state transition heterogeneity through Bayesian
variable selection
SO STATISTICS IN MEDICINE
LA English
DT Article
DE Bayesian variable selection; Markov transition models; multinomial logit
models; Multiple sclerosis
ID MULTIPLE-SCLEROSIS; PROGRESSION; DISABILITY; TIME
AB In many diseases, Markov transition models are useful in describing transitions between discrete disease states. Often the probability of transitioning from one state to another varies widely across subjects. This heterogeneity is driven, in part, by a possibly unknown number of previous disease states and by potentially complex relationships between clinical data and these states. We propose use of Bayesian variable selection in Markov transition models to allow estimation of subject-specific transition probabilities. Our approach simultaneously estimates the order of the Markov process and the transition-specific covariate effects. The methods are assessed using Simulation studies and applied to model disease-state transition on the expanded disability status scale (EDSS) in multiple sclerosis (MS) patients from the Partners MS Center in Boston, MA. The proposed methodology is shown to accurately identify complex covariate-transition relationships in simulations and identifies a clinically significant interaction between relapse history and EDSS history in MS patients. Copyright (C) 2009 John Wiley & Sons, Ltd.
C1 [Healy, Brian C.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurol,Partners MS Ctr, Boston, MA 02115 USA.
[Healy, Brian C.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA.
[Engler, David] Brigham Young Univ, Dept Stat, Provo, UT 84602 USA.
RP Engler, D (reprint author), 223 TMCB, Provo, UT 84602 USA.
EM engler@byu.edu
FU Partners MS Center
FX We would like to thank Micha Mandel and the reviewers for helpful
comments, and the Partners MS Center for access to the data and funding
this research.
NR 24
TC 3
Z9 3
U1 1
U2 3
PU JOHN WILEY & SONS LTD
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND
SN 0277-6715
J9 STAT MED
JI Stat. Med.
PD APR 30
PY 2009
VL 28
IS 9
BP 1353
EP 1368
DI 10.1002/sim.3545
PG 16
WC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Medicine, Research &
Experimental; Statistics & Probability
SC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Research & Experimental
Medicine; Mathematics
GA 434YG
UT WOS:000265309600003
PM 19206077
ER
PT J
AU Smith, MJ
Culhane, AC
Donovan, M
Coffey, JC
Barry, BD
Kelly, MA
Higgins, DG
Wang, JH
Kirwan, WO
Cotter, TG
Redmond, HP
AF Smith, M. J.
Culhane, A. C.
Donovan, M.
Coffey, J. C.
Barry, B. D.
Kelly, M. A.
Higgins, D. G.
Wang, J. H.
Kirwan, W. O.
Cotter, T. G.
Redmond, H. P.
TI Analysis of differential gene expression in colorectal cancer and stroma
using fluorescence-activated cell sorting purification
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE colorectal cancer; fluorescence-activated cell sorting; gene expression
microarray analysis; humans
ID BREAST-CANCER; MICROARRAY DATA; HEPATOCELLULAR-CARCINOMA;
CLINICAL-APPLICATION; SIGNATURE; PROFILES; MICRODISSECTION; PREDICTION;
TUMORS; RECURRENCE
AB Tumour stroma gene expression in biopsy specimens may obscure the expression of tumour parenchyma, hampering the predictive power of microarrays. We aimed to assess the utility of fluorescence-activated cell sorting (FACS) for generating cell populations for gene expression analysis and to compare the gene expression of FACS-purified tumour parenchyma to that of whole tumour biopsies. Single cell suspensions were generated from colorectal tumour biopsies and tumour parenchyma was separated using FACS. Fluorescence-activated cell sorting allowed reliable estimation and purification of cell populations, generating parenchymal purity above 90%. RNA from FACS-purified and corresponding whole tumour biopsies was hybridised to Affymetrix oligonucleotide microarrays. Whole tumour and parenchymal samples demonstrated differential gene expression, with 289 genes significantly overexpressed in the whole tumour, many of which were consistent with stromal gene expression (e. g., COL6A3, COL1A2, POSTN, TIMP2). Genes characteristic of colorectal carcinoma were overexpressed in the FACS- purified cells (e. g., HOX2D and RHOB). We found FACS to be a robust method for generating samples for gene expression analysis, allowing simultaneous assessment of parenchymal and stromal compartments. Gross stromal contamination may affect the interpretation of cancer gene expression microarray experiments, with implications for hypotheses generation and the stability of expression signatures used for predicting clinical outcomes.
C1 [Smith, M. J.; Coffey, J. C.; Barry, B. D.; Kelly, M. A.; Wang, J. H.; Kirwan, W. O.; Redmond, H. P.] Natl Univ Ireland Univ Coll Cork, Acad Dept Surg, Cork, Ireland.
[Smith, M. J.; Donovan, M.; Cotter, T. G.] Natl Univ Ireland Univ Coll Cork, Dept Biochem, Cork, Ireland.
[Culhane, A. C.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Culhane, A. C.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Higgins, D. G.] Univ Coll Dublin, Conway Inst, Dublin 2, Ireland.
RP Redmond, HP (reprint author), Natl Univ Ireland Univ Coll Cork, Cork Univ Hosp, Acad Dept Surg, Cork, Ireland.
EM Henry.Redmond@hse.ie
RI Smith, Myles/B-7803-2009; Higgins, des/J-6314-2012;
OI Smith, Myles/0000-0002-3254-4817; Higgins, Des/0000-0002-3952-3285
NR 55
TC 19
Z9 19
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0007-0920
J9 BRIT J CANCER
JI Br. J. Cancer
PD APR 28
PY 2009
VL 100
IS 9
BP 1452
EP 1464
DI 10.1038/sj.bjc.6604931
PG 13
WC Oncology
SC Oncology
GA 438SH
UT WOS:000265575200013
PM 19401702
ER
PT J
AU Thangaroopan, M
Truong, QA
Kalra, MK
Yared, K
Abbara, S
AF Thangaroopan, Molly
Truong, Quynh A.
Kalra, Mannudeep K.
Yared, Kibar
Abbara, Suhny
TI Rare Case of an Unroofed Coronary Sinus Diagnosis by Multidetector
Computed Tomography
SO CIRCULATION
LA English
DT Editorial Material
C1 [Truong, Quynh A.] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Div Cardiol, Boston, MA 02114 USA.
[Thangaroopan, Molly; Kalra, Mannudeep K.; Abbara, Suhny] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Dept Radiol, Boston, MA 02114 USA.
RP Truong, QA (reprint author), Massachusetts Gen Hosp, Cardiac MR PET CT Program, Div Cardiol, 165 Cambridge St,Suite 400, Boston, MA 02114 USA.
EM qtruong@partners.org
FU NHLBI NIH HHS [T32 HL076136-05, K23 HL098370, L30 HL093806, L30
HL093806-01, T32 HL076136]
NR 2
TC 17
Z9 18
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD APR 28
PY 2009
VL 119
IS 16
BP E518
EP E520
DI 10.1161/CIRCULATIONAHA.107.707018
PG 3
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 438UG
UT WOS:000265580300019
PM 19398672
ER
PT J
AU Friedrich, MG
Sechtem, U
Schulz-Menger, J
Holmvang, G
Alakija, P
Cooper, LT
White, JA
Abdel-Aty, H
Gutberlet, M
Prasad, S
Aletras, A
Laissy, JP
Paterson, I
Filipchuk, NG
Kumar, A
Pauschinger, M
Liu, P
AF Friedrich, Matthias G.
Sechtem, Udo
Schulz-Menger, Jeanette
Holmvang, Godtfred
Alakija, Pauline
Cooper, Leslie T.
White, James A.
Abdel-Aty, Hassan
Gutberlet, Matthias
Prasad, Sanjay
Aletras, Anthony
Laissy, Jean-Pierre
Paterson, Ian
Filipchuk, Neil G.
Kumar, Andreas
Pauschinger, Matthias
Liu, Peter
CA Int Consensus Grp Cardiovasc Magne
TI Cardiovascular Magnetic Resonance in Myocarditis: A JACC White Paper
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
DE cardiovascular magnetic resonance; myocarditis; consensus
ID SUDDEN CARDIAC DEATH; AMERICAN-HEART-ASSOCIATION; ENDOMYOCARDIAL BIOPSY;
ECHOCARDIOGRAPHIC FINDINGS; SUSPECTED MYOCARDITIS; DELAYED ENHANCEMENT;
VIRAL MYOCARDITIS; GADOLINIUM-DTPA; ENZYME-RELEASE; CHEST-PAIN
AB Cardiovascular magnetic resonance (CMR) has become the primary tool for noninvasive assessment of myocardial inflammation in patients with suspected myocarditis. The International Consensus Group on CMR Diagnosis of Myocarditis was founded in 2006 to achieve consensus among CMR experts and develop recommendations on the current state-of-the-art use of CMR for myocarditis. The recommendations include indications for CMR in patients with suspected myocarditis, CMR protocol standards, terminology for reporting CMR findings, and diagnostic CMR criteria for myocarditis (i.e., "Lake Louise Criteria").
C1 [Friedrich, Matthias G.; Filipchuk, Neil G.; Kumar, Andreas] Univ Calgary, Stephenson Cardiovasc MR Ctr, Libin Cardiovasc Inst Alberta, Dept Cardiac Sci & Radiol, Calgary, AB T2N 2T9, Canada.
[Alakija, Pauline] Univ Calgary, Dept Pathol, Calgary, AB T2N 2T9, Canada.
[Sechtem, Udo] Robert Bosch Krankenhaus, Dept Cardiol, Stuttgart, Germany.
[Schulz-Menger, Jeanette; Abdel-Aty, Hassan] Charite Univ Med Berlin, HELIOS Klinikum Berlin Buch, Franz Volhard Klin, Berlin, Germany.
[Holmvang, Godtfred] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Cooper, Leslie T.] Mayo Clin, Coll Med, Rochester, MN USA.
[White, James A.] London Hlth Sci Ctr, London, ON, Canada.
[Gutberlet, Matthias] Univ Leipzig, Dept Diagnost & Intervent Radiol, Leipzig, Germany.
[Prasad, Sanjay] Royal Brompton Hosp, London SW3 6LY, England.
[Aletras, Anthony] NHLBI, NIH, Bethesda, MD 20892 USA.
[Laissy, Jean-Pierre] Hop Bichat Claude Bernard, Dept Radiol, F-75877 Paris, France.
[Paterson, Ian] Univ Alberta, Div Cardiol, Edmonton, AB, Canada.
[Pauschinger, Matthias] Klinikum Nurnberg Sud, Dept Cardiol, Nurnberg, Germany.
[Liu, Peter] Toronto Gen Hosp, Max Bell Res Ctr, Toronto, ON, Canada.
RP Friedrich, MG (reprint author), Univ Calgary, Stephenson Cardiovasc MR Ctr, Libin Cardiovasc Inst Alberta, Dept Cardiac Sci & Radiol, 1403 29th St NW, Calgary, AB T2N 2T9, Canada.
EM matthias.friedrich@ucalgary.ca
OI Aletras, Anthony/0000-0002-3786-3817
FU Intramural NIH HHS [Z99 HL999999]
NR 65
TC 538
Z9 571
U1 2
U2 15
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 28
PY 2009
VL 53
IS 17
BP 1475
EP 1487
DI 10.1016/j.jacc.2009.02.007
PG 13
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 437VN
UT WOS:000265515100001
PM 19389557
ER
PT J
AU Wilson, SR
Scirica, BM
Braunwald, E
Murphy, SA
Karwatowska-Prokopczuk, E
Buros, JL
Chaitman, BR
Morrow, DA
AF Wilson, Sean R.
Scirica, Benjamin M.
Braunwald, Eugene
Murphy, Sabina A.
Karwatowska-Prokopczuk, Ewa
Buros, Jacqueline L.
Chaitman, Bernard R.
Morrow, David A.
TI Efficacy of Ranolazine in Patients With Chronic Angina Observations From
the Randomized, Double-Blind, Placebo-Controlled MERLIN-TIMI (Metabolic
Efficiency With Ranolazine for Less Ischemia in Non-ST-Segment Elevation
Acute Coronary Syndromes) 36 Trial
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
DE angina; exercise tolerance; ranolazine; recurrent ischemia
ID MYOCARDIAL-INFARCTION; HEART-DISEASE; AMLODIPINE; PREVENTION; COMMITTEE;
PECTORIS; UPDATE; 1-YEAR
AB Objectives We aimed to evaluate the efficacy and safety of ranolazine in a larger and more diverse group of patients with angina than previously studied.
Background Ranolazine is an antianginal shown to reduce angina and improve exercise performance in selected patients with early-positive exercise testing and those with frequent angina.
Methods We investigated the antianginal effects of ranolazine in the subgroup of patients with prior chronic angina (n = 3,565, 54%) enrolled in the randomized, double-blind, placebo-controlled MERLIN-TIMI (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST Elevation Acute Coronary Syndromes) 36 trial of patients with acute coronary syndrome. Follow-up was a median of 350 days.
Results Patients with prior angina received evidence-based therapy (95% aspirin, 78% statins, 89% beta-blockers, average 2.9 antianginal agents). The primary end point (cardiovascular death, myocardial infarction, recurrent ischemia) was less frequent with ranolazine (hazard ratio [HR]: 0.86; 95% confidence interval [CI]: 0.75 to 0.97; p = 0.017), due entirely to a significant reduction in recurrent ischemia (HR: 0.78; 95% CI: 0.67 to 0.91; p = 0.002). Ranolazine also reduced worsening angina (HR: 0.77; 95% CI: 0.59 to 1.00; p = 0.048) and intensification of antianginal therapy (HR: 0.77; 95% CI: 0.64 to 0.92, p = 0.005). Exercise duration at 8 months was greater with ranolazine (514 s vs. 482 s, p = 0.002). Cardiovascular death or myocardial infarction did not differ between treatment groups (HR: 0.97; 95% CI: 0.80 to 1.16; p = 0.71). Symptomatic documented arrhythmias (2.9% vs. 2.9%, p = 0.92) and total mortality (6.2% vs. 6.4%, p = 0.96) were similar with ranolazine or placebo.
Conclusions In this largest study of ranolazine in patients with established coronary artery disease, ranolazine was effective in reducing angina with favorable safety in a substantially broader group of patients with angina than previously studied. (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST Elevation Acute Coronary Syndromes; NCT00099788) (J Am Coll Cardiol 2009;53:1510-6) (C) 2009 by the American College of Cardiology Foundation
C1 [Morrow, David A.] Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Dept Med, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Boston, MA USA.
[Karwatowska-Prokopczuk, Ewa] CV Therapeut, Palo Alto, CA USA.
[Chaitman, Bernard R.] St Louis Univ, Sch Med, St Louis, MO USA.
RP Morrow, DA (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Dept Med, 75 Francis St, Boston, MA 02115 USA.
EM dmorrow@partners.org
FU CV Therapeutics (CVT) (Palo Alto, California)
FX The MERLIN-TIMI 36 trial was supported by CV Therapeutics (CVT) (Palo
Alto, California). Dr. Scirica has received research funding and
honoraria for educational presentations and consulting for CVT. Dr.
Braunwald received research grant support from CVT for the MERLIN-TIMI
36 trial.
NR 24
TC 74
Z9 78
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 28
PY 2009
VL 53
IS 17
BP 1510
EP 1516
DI 10.1016/j.jacc.2009.01.037
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 437VN
UT WOS:000265515100005
PM 19389561
ER
PT J
AU Weyman, AE
AF Weyman, Arthur E.
TI The Year in Echocardiography
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
DE echocardiography; year; 2008
ID CARDIAC-RESYNCHRONIZATION THERAPY; VENTRICULAR FILLING PATTERN; RADIAL
2-DIMENSIONAL STRAIN; PATENT FORAMEN OVALE; HEART-FAILURE; ORIFICE AREA;
TRACKING; TORSION; NEOVASCULARIZATION; DYSSYNCHRONY
C1 Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA.
RP Weyman, AE (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Yawkey 5E, Boston, MA 02114 USA.
EM aweyman@partners.org
NR 34
TC 4
Z9 4
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 28
PY 2009
VL 53
IS 17
BP 1558
EP 1567
DI 10.1016/j.jacc.2009.01.042
PG 10
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 437VN
UT WOS:000265515100013
PM 19389569
ER
PT J
AU Lentz, MR
Kim, WK
Lee, V
Bazner, S
Halpern, EF
Venna, N
Williams, K
Rosenberg, ES
Gonzalez, RG
AF Lentz, M. R.
Kim, W. K.
Lee, V.
Bazner, S.
Halpern, E. F.
Venna, N.
Williams, K.
Rosenberg, E. S.
Gonzalez, R. G.
TI Changes in MRS neuronal markers and T cell phenotypes observed during
early HIV infection
SO NEUROLOGY
LA English
DT Article
ID SIMIAN IMMUNODEFICIENCY VIRUS; CENTRAL-NERVOUS-SYSTEM; AIDS DEMENTIA
COMPLEX; MAGNETIC-RESONANCE-SPECTROSCOPY; CEREBROSPINAL-FLUID;
METABOLITE ABNORMALITIES; ANTIRETROVIRAL THERAPY; IMMUNE-RESPONSES; H-1
MRS; BRAIN
AB Objective: To determine if changes in brain metabolites are observed during early HIV infection and correlate these changes with immunologic alterations.
Methods: Eight subjects with early HIV infection, 9 HIV-seronegative controls, and 10 chronically HIV-infected subjects without neurologic impairment underwent (1)H magnetic resonance spectroscopy. Subjects with early stage infection were identified near the time of HIV seroconversion and imaged within 60 days of an evolving Western blot, while still having detectable plasma virus. Subjects had blood drawn for viral RNA and T cell quantification.
Results: Both N-acetylaspartate (NAA) and Glx (glutamate + glutamine) were decreased in the frontal cortical gray matter of seropositive subjects. NAA levels were found to be decreased in the centrum semiovale white matter of chronically HIV-infected subjects, but not in those with early infection. Both HIV-infected cohorts demonstrated a lower number of CD4(+) T lymphocytes and a higher number of CD8(+) T lymphocytes in their blood. Lower NAA levels in the frontal cortex of subjects with early infection were associated with an expansion of CD8(+) T cells, especially effector CD8(+) T cells.
Conclusions: These results verify metabolism changes occurring in the brain early during HIV infection. Lower NAA and Glx levels in the cortical gray matter suggests that HIV causes neuronal dysfunction soon after infection, which correlates to the expansion of CD8(+) T cells, specifically to an activated phenotype. Utilizing magnetic resonance spectroscopy to track NAA levels may provide important information on brain metabolic health while allowing better understanding of the virus-host interactions involved in CNS functional deficits. Neurology (R) 2009; 72: 1465-1472
C1 [Lentz, M. R.; Lee, V.; Halpern, E. F.; Gonzalez, R. G.] Massachusetts Gen Hosp, Dept Neuroradiol, AA Martinos Ctr Biomed Imaging, Boston, MA 02114 USA.
[Venna, N.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Bazner, S.; Rosenberg, E. S.] Massachusetts Gen Hosp, Partners AIDS Res Ctr, Dept Med, Boston, MA 02114 USA.
[Bazner, S.; Rosenberg, E. S.] Massachusetts Gen Hosp, Partners AIDS Res Ctr, Dept Pathol, Boston, MA 02114 USA.
[Williams, K.] Boston Coll, Dept Biol, Boston, MA USA.
[Kim, W. K.] Eastern Virginia Med Sch, Dept Microbiol & Mol Cell Biol, Norfolk, VA 23501 USA.
RP Lentz, MR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Bldg 149,13th St,Rm 2301, Charlestown, MA 02129 USA.
EM mlentz@nmr.mgh.harvard.edu
FU NIH [NS040237, NS037654, U19MH81835, NS050041, AI040873]; National
Center for Research Resources [P41 RR14075]; Mental Illness and
Neuroscience Discovery (MIND) Institute
FX Supported by NIH grants NS051129 (M.R.L.), NS040237 (K.W.), NS037654 and
U19MH81835 (K.W.), NS050041 (R.G.G.), AI040873 (E.S.R.), the National
Center for Research Resources (P41 RR14075), and the Mental Illness and
Neuroscience Discovery (MIND) Institute.
NR 40
TC 55
Z9 57
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD APR 28
PY 2009
VL 72
IS 17
BP 1465
EP 1472
DI 10.1212/WNL.0b013e3181a2e90a
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA 438UD
UT WOS:000265580000004
PM 19398702
ER
PT J
AU Wua, M
Jung, L
Cooper, AB
Fleet, C
Chen, LH
Breault, L
Clark, K
Cai, ZH
Vincent, S
Bottega, S
Shen, Q
Richardson, A
Bosenburg, M
Naber, SP
DePinho, RA
Kuperwasserf, C
Robinson, MO
AF Wua, Min
Jung, Lina
Cooper, Adrian B.
Fleet, Christina
Chen, Lihao
Breault, Lyne
Clark, Kimberly
Cai, Zuhua
Vincent, Sylvie
Bottega, Steve
Shen, Qiong
Richardson, Andrea
Bosenburg, Marcus
Naber, Stephen P.
DePinho, Ronald A.
Kuperwasserf, Charlotte
Robinson, Murray O.
TI Dissecting genetic requirements of human breast tumorigenesis in a
tissue transgenic model of human breast cancer in mice
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE cancer model; human in mouse; tissue reconstitution
ID EXPRESSION; CELLS; TRANSFORMATION; APOPTOSIS; MUTATION; MOUSE
AB Breast cancer development is a complex pathobiological process involving sequential genetic alterations in normal epithelial cells that results in uncontrolled growth in a permissive microenvironment. Accordingly, physiologically relevant models of human breast cancer that recapitulate these events are needed to study cancer biology and evaluate therapeutic agents. Here, we report the generation and utilization of the human breast cancer in mouse (HIM) model, which is composed of genetically engineered primary human breast epithelial organoids and activated human breast stromal cells. By using this approach, we have defined key genetic events required to drive the development of human preneoplastic lesions as well as invasive adenocarcinomas that are histologically similar to those in patients. Tumor development in the HIM model proceeds through defined histological stages of hyperplasia, DCIS to invasive carcinoma. Moreover, HIM tumors display characteristic responses to targeted therapies, such as HER2 inhibitors, further validating the utility of these models in preclinical compound testing. The HIM model is an experimentally tractable human in vivo system that holds great potential for advancing our basic understanding of cancer biology and for the discovery and testing of targeted therapies.
C1 [Kuperwasserf, Charlotte] Tufts Univ, Sch Med, Dept Anat & Cellular Biol, Boston, MA 02111 USA.
[Wua, Min; Jung, Lina; Cooper, Adrian B.; Fleet, Christina; Chen, Lihao; Breault, Lyne; Clark, Kimberly; Cai, Zuhua; Vincent, Sylvie; Bottega, Steve; Shen, Qiong; Robinson, Murray O.] Aveo Pharmaceut Inc, Cambridge, MA 02139 USA.
[Richardson, Andrea] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Richardson, Andrea] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Bosenburg, Marcus] Yale Univ, Sch Med, Dept Dermatol, New Haven, CT 06520 USA.
[Naber, Stephen P.] Tufts Univ New England Med Ctr, Dept Pathol, Boston, MA 02111 USA.
[DePinho, Ronald A.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
[DePinho, Ronald A.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[DePinho, Ronald A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Appl Canc Sci, Boston, MA 02115 USA.
[DePinho, Ronald A.] Harvard Univ, Sch Med, Dept Med Oncol, Boston, MA 02115 USA.
RP Kuperwasserf, C (reprint author), Tufts Univ, Sch Med, Dept Anat & Cellular Biol, Boston, MA 02111 USA.
EM Charlotte.Kuperwasser@tufts.edu; mrobinson@aveopharma.com
OI Robinson, Murray/0000-0003-4462-0685
NR 23
TC 0
Z9 0
U1 0
U2 0
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD APR 28
PY 2009
VL 106
IS 17
BP 7022
EP 7027
DI 10.1073/pnas.0811785106
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 438VS
UT WOS:000265584500029
ER
PT J
AU Muller, MR
Sasaki, Y
Stevanovic, I
Lamperti, ED
Ghosh, S
Sharma, S
Gelinas, C
Rossi, DJ
Pipkin, ME
Rajewsky, K
Hogan, PG
Rao, A
AF Mueller, Martin R.
Sasaki, Yoshiteru
Stevanovic, Irena
Lamperti, Edward D.
Ghosh, Srimoyee
Sharma, Sonia
Gelinas, Curtis
Rossi, Derrick J.
Pipkin, Matthew E.
Rajewsky, Klaus
Hogan, Patrick G.
Rao, Anjana
TI Requirement for balanced Ca/NFAT signaling in hematopoietic and
embryonic development
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID DEPENDENT TRANSCRIPTIONAL PATHWAY; PATERNAL X-CHROMOSOME; EARLY MOUSE
EMBRYOS; T-CELL DEVELOPMENT; NF-ATC; MYELOID DIFFERENTIATION;
NUCLEAR-LOCALIZATION; CD34(+) CELLS; FACTOR NFAT1; CALCINEURIN
AB NFAT transcription factors are highly phosphorylated proteins residing in the cytoplasm of resting cells. Upon dephosphorylation by the phosphatase calcineurin, NFAT proteins translocate to the nucleus, where they orchestrate developmental and activation programs in diverse cell types. NFAT is rephosphorylated and inactivated through the concerted action of at least 3 different kinases: CK1, GSK-3, and DYRK. The major docking sites for calcineurin and CK1 are strongly conserved throughout vertebrate evolution, and conversion of either the calcineurin docking site to a high-affinity version or the CK1 docking site to a low-affinity version results in generation of hyperactivable NFAT proteins that are still fully responsive to stimulation. In this study, we generated transgenic mice expressing hyperactivable versions of NFAT1 from the ROSA26 locus. We show that hyperactivable NFAT increases the expression of NFAT-dependent cytokines by differentiated T cells as expected, but exerts unexpected signal-dependent effects during T cell differentiation in the thymus, and is progressively deleterious for the development of B cells from hematopoietic stem cells. Moreover, progressively hyperactivable versions of NFAT1 are increasingly deleterious for embryonic development, particularly when normal embryos are also present in utero. Forced expression of hyperactivable NFAT1 in the developing embryo leads to mosaic expression in many tissues, and the hyperactivable proteins are barely tolerated in organs such as brain, and cardiac and skeletal muscle. Our results highlight the need for balanced Ca/NFAT signaling in hematopoietic stem cells and progenitor cells of the developing embryo, and emphasize the evolutionary importance of kinase and phosphatase docking sites in preventing inappropriate activation of NFAT.
C1 [Rao, Anjana] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA.
RP Rao, A (reprint author), Harvard Univ, Sch Med, Dept Pathol, 200 Longwood Ave, Boston, MA 02115 USA.
EM arao@idi.harvard.edu
FU National Institutes of Health; Deutsche Krebshilfe postdoctoral
fellowship; Cancer Research Institute postdoctoral fellowship; Canadian
Institutes of Health Research postdoctoral fellowship
FX We thank D. Ghitza for help with blastocyst injections of ES cells and
K. Ketman for help with cell sorting. This study was supported by grants
(to K. R. and A. R.); a T32 training grant (to S. G.), a Deutsche
Krebshilfe postdoctoral fellowship (to M. R. M.), a Cancer Research
Institute postdoctoral fellowship (to M. R. M.), a Canadian Institutes
of Health Research postdoctoral fellowship (to S. S.), and a (to S. S.).
NR 45
TC 28
Z9 29
U1 0
U2 2
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD APR 28
PY 2009
VL 106
IS 17
BP 7034
EP 7039
DI 10.1073/pnas.0813296106
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 438VS
UT WOS:000265584500031
PM 19351896
ER
PT J
AU Schnipper, JL
Hamann, C
Ndumele, CD
Liang, CL
Carty, MG
Karson, AS
Bhan, I
Coley, CM
Poon, E
Turchin, A
Labonville, SA
Diedrichsen, EK
Lipsitz, S
Broverman, CA
McCarthy, P
Gandhi, TK
AF Schnipper, Jeffrey L.
Hamann, Claus
Ndumele, Chima D.
Liang, Catherine L.
Carty, Marcy G.
Karson, Andrew S.
Bhan, Ishir
Coley, Christopher M.
Poon, Eric
Turchin, Alexander
Labonville, Stephanie A.
Diedrichsen, Ellen K.
Lipsitz, Stuart
Broverman, Carol A.
McCarthy, Patricia
Gandhi, Tejal K.
TI Effect of an Electronic Medication Reconciliation Application and
Process Redesign on Potential Adverse Drug Events A Cluster-Randomized
Trial
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Article; Proceedings Paper
CT Summer Meeting of the American-Society-of-Health-System-Pharmacists
CY JUN 25-26, 2007
CL San Francisco, CA
SP Amer Soc Hlth Syst Pharmacists
ID HOSPITAL ADMISSION; ERRORS; DISCREPANCIES; SYSTEM; PREVENTION
AB Background: Medication reconciliation at transitions in care is a national patient safety goal, but its effects on important patient outcomes require further evaluation. We sought to measure the impact of an information technology -based medication reconciliation intervention on medication discrepancies with potential for harm (potential adverse drug events [PADEs]).
Methods: We performed a controlled trial, randomized by medical team, on general medical inpatient units at 2 academic hospitals from May to June 2006. We enrolled 322 patients admitted to 14 medical teams, for whom amedication history could be obtained before discharge. The intervention was a computerized medication reconciliation tool and process redesign involving physicians, nurses, and pharmacists. The main outcome was unintentional discrepancies between preadmission medications and admission or discharge medications that had potential for harm (PADEs).
Results: Among 160 control patients, there were 230 PADEs (1.44 per patient), while among 162 intervention patients there were 170 PADEs (1.05 per patient) (adjusted relative risk [ARR], 0.72; 95% confidence interval [CI], 0.52-0.99). A significant benefit was found at hospital 1 (ARR, 0.60; 95% CI, 0.38-0.97) but not at hospital 2 (ARR, 0.87; 95% CI, 0.57-1.32) (P=.32 for test of effect modification). Hospitals differed in the extent of integration of the medication reconciliation tool into computerized provider order entry applications at discharge.
Conclusions: A computerized medication reconciliation tool and process redesign were associated with a decrease in unintentional medication discrepancies with potential for patient harm. Software integration issues are likely important for successful implementation of computerized medication reconciliation tools.
Trial Registration: clinicaltrials. gov Identifier: NCT00296426
C1 [Schnipper, Jeffrey L.] Brigham & Womens Hosp, Div Gen Med, Brigham & Womens Acad Hosp Serv, Boston, MA 02120 USA.
[McCarthy, Patricia; Gandhi, Tejal K.] Brigham & Womens Hosp, Ctr Clin Excellence, Boston, MA 02120 USA.
[Labonville, Stephanie A.; Diedrichsen, Ellen K.] Brigham & Womens Hosp, Serv Pharm, Boston, MA 02120 USA.
[Hamann, Claus; Karson, Andrew S.; Bhan, Ishir; Coley, Christopher M.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Hamann, Claus] Massachusetts Gen Hosp, Geriatr Med Unit, Boston, MA 02114 USA.
[Karson, Andrew S.; McCarthy, Patricia] Massachusetts Gen Hosp, Ctr Qual & Safety, Boston, MA 02114 USA.
[Poon, Eric; Turchin, Alexander; Broverman, Carol A.] Partners Informat Syst Clin Informat Res & Dev, Boston, MA USA.
[Schnipper, Jeffrey L.; Hamann, Claus; Carty, Marcy G.; Karson, Andrew S.; Bhan, Ishir; Coley, Christopher M.; Poon, Eric; Turchin, Alexander; Lipsitz, Stuart; Gandhi, Tejal K.] Harvard Univ, Sch Med, Boston, MA USA.
[Diedrichsen, Ellen K.] Massachusetts Gen Hosp, Serv Pharm, Boston, MA 02114 USA.
RP Schnipper, JL (reprint author), Brigham & Womens Hosp, Div Gen Med, Brigham & Womens Acad Hosp Serv, 1620 Tremont St, Boston, MA 02120 USA.
EM jschnipper@partners.org
RI Tao, Youyou/D-2367-2014; Vila, Vanessa/B-4982-2014
FU NHLBI NIH HHS [K08 HL072806]
NR 36
TC 107
Z9 107
U1 1
U2 23
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0003-9926
J9 ARCH INTERN MED
JI Arch. Intern. Med.
PD APR 27
PY 2009
VL 169
IS 8
BP 771
EP 780
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 438FE
UT WOS:000265540500007
PM 19398689
ER
PT J
AU Linder, JA
Rigotti, NA
Schneider, LI
Kelley, JHK
Brawarsky, P
Haas, JS
AF Linder, Jeffrey A.
Rigotti, Nancy A.
Schneider, Louise I.
Kelley, Jennifer H. K.
Brawarsky, Phyllis
Haas, Jennifer S.
TI An Electronic Health Record-Based Intervention to Improve Tobacco
Treatment in Primary Care A Cluster-Randomized Controlled Trial
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Article; Proceedings Paper
CT 31st Annual Meeting of the Society-of-General-Internal-Medicine
CY APR 09-12, 2008
CL Pittsburgh, PA
SP Soc Gen Internal Med
ID CLINICAL DECISION-SUPPORT; SMOKING-CESSATION; MEDICAL-RECORD; TREATMENT
GUIDELINES; QUALITY IMPROVEMENT; AMBULATORY-CARE; UNITED-STATES;
SMOKERS; PHYSICIANS; PATIENT
AB Background: To improve the documentation and treatment of tobacco use in primary care, we developed and implemented a 3-part electronic health record enhancement: (1) smoking status icons, (2) tobacco treatment reminders, and (3) a Tobacco Smart Form that facilitated the ordering of medication and fax and e-mail counseling referrals.
Methods: We performed a cluster-randomized controlled trial of the enhancement in 26 primary care practices between December 19, 2006, and September 30, 2007. The primary outcome was the proportion of documented smokers who made contact with a smoking cessation counselor. Secondary outcomes included coded smoking status documentation and medication prescribing.
Results: During the 9-month study period, 132 630 patients made 315 962 visits to study practices. Coded documentation of smoking status increased from 37% of patients to 54% (+ 17%) in intervention practices and from 35% of patients to 46% (+ 11%) in control practices (P <. 001 for the difference in differences). Among the 9589 patients who were documented smokers at the start of the study, more patients in the intervention practices were recorded as nonsmokers by the end of the study (5.3% vs 1.9% in control practices; P <. 001). Among 12 207 documented smokers, more patients in the intervention practices made contact with a cessation counselor(3.9% vs 0.3% in control practices; P <. 001). Smokers in the intervention practices were no more likely to be prescribed smoking cessation medication (2% vs 2% in control practices; P=.40).
Conclusion: This electronic health record-based intervention improved smoking status documentation and increased counseling assistance to smokers but not the prescription of cessation medication.
Trial Registration: clinicaltrials. gov Identifier: NCT00383461
C1 [Linder, Jeffrey A.; Schneider, Louise I.; Kelley, Jennifer H. K.; Brawarsky, Phyllis; Haas, Jennifer S.] Brigham & Womens Hosp, Div Gen Med & Primary Care, Boston, MA 02120 USA.
[Rigotti, Nancy A.] Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA.
[Rigotti, Nancy A.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA.
[Linder, Jeffrey A.; Rigotti, Nancy A.; Schneider, Louise I.; Haas, Jennifer S.] Harvard Univ, Sch Med, Boston, MA USA.
RP Linder, JA (reprint author), Brigham & Womens Hosp, Div Gen Med & Primary Care, 1620 Tremont St,BC 3-2X, Boston, MA 02120 USA.
EM jlinder@partners.org
FU AHRQ HHS [K08 HS014563]; NCI NIH HHS [R21 CA121906, R21 CA121906-02];
NHLBI NIH HHS [K24 HL04440, K24 HL004440-09, K24 HL004440]
NR 38
TC 33
Z9 33
U1 2
U2 7
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0003-9926
J9 ARCH INTERN MED
JI Arch. Intern. Med.
PD APR 27
PY 2009
VL 169
IS 8
BP 781
EP 787
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 438FE
UT WOS:000265540500008
PM 19398690
ER
PT J
AU Obeso, EG
Murphy, E
Brugge, W
Deshpande, V
AF Obeso, Elvira Gonzalez
Murphy, Erin
Brugge, William
Deshpande, Vikram
TI Pseudocyst of the Pancreas The Role of Cytology and Special Stains for
Mucin
SO CANCER CYTOPATHOLOGY
LA English
DT Article
DE Alcian blue; mucicarmine; intraductal; papillary-mucinous neoplasms;
pseudocyst
ID NEEDLE-ASPIRATION-CYTOLOGY; CYSTIC NEOPLASMS; CLINICOPATHOLOGICAL
CHARACTERISTICS; SYMPTOMATIC PATIENTS; DIAGNOSIS; LESIONS; BIOPSY
AB BACKGROUND: Currently, the preoperative diagnosis of a pancreatic cyst is based on clinical and imaging findings, frequently in conjunction with chemical analysis of cyst fluid and cytologic evaluation. The purpose of these diagnostic tests is to distinguish benign from malignant cysts of the pancreas. Accordingly, it is imperative to distinguish pancreatic pseudocysts from their mimics. In this study, the authors explored the cytomorphologic features of pseudocyst of the pancreas and evaluated the role of Alcian blue and mucicarmine stains in the cytologic evaluation of pancreatic cysts, METHODS: Forty-two patients were identified who had an eventual diagnosis of pancreatic pseudocyst and had an endoscopic ultrasoundguided fine-needle aspirate available. Clinical and imaging findings and chemical analyses of cyst fluid were recorded. The cytologic preparations were evaluated for gastrointestinal contamination, inflammatory cells, mucin, and pigmented material. The cytomorphologic features of 110 neoplastic mucinous cysts (intraductal papillary-mucinous neoplasms/mucinous cystic neoplasms of the pancreas) were evaluated and compared with the pseudocysts. RESULTS: The majority of patients (95%) had a prior episode of pancreatitis. On imaging, the pseudocysts were unilocular (92%). In 69% of cases, the endosonographic diagnosis was that of a pseudocyst. The mean carcinoembryonic antigen level was 41 ng/mL. In contrast, the cytopathologist rendered a definitive diagnosis of pseudocyst in only 10% of cases. The majority of smears (75%) revealed neutrophils and/or histiocytes. Atypical epithelial clusters were identified in 3 cases, I of which was diagnosed as suspicious for carcinoma. Yellow pigmented material, which was identified in 13 pseudocysts (31%), was not observed in neoplastic mucinous cysts. Alcian blue- and mucicarmine-positive material was identified in 64% and 40% of pseudocysts, respectively, and in 57% and 38% of neoplastic mucinous cysts, respectively. CONCLUSIONS: The diagnosis of a pseudocyst depended primarily on clinical and imaging findings and on chemical analysis of cyst fluid. The cytologic features frequently were nonspecific. The presence of yellow pigmented material served as a surrogate marker of a pseudocyst. Special stains for mucin did not distinguish pseudocysts from neoplastic mucinous cysts. Cancer (Cancer Cytopathol) 2009;117:101-7. (C) 2009 American Cancer Society.
C1 [Deshpande, Vikram] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,James Homer Wright Pathol Labs, Boston, MA 02114 USA.
[Brugge, William] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA.
RP Deshpande, V (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,James Homer Wright Pathol Labs, Warren 2,55 Fruit St, Boston, MA 02114 USA.
EM vdeshpande@partners.org
NR 15
TC 14
Z9 15
U1 1
U2 3
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1934-662X
J9 CANCER CYTOPATHOL
JI Cancer Cytopathol.
PD APR 25
PY 2009
VL 117
IS 2
BP 101
EP 107
DI 10.1002/cncy.20000
PG 7
WC Oncology; Pathology
SC Oncology; Pathology
GA 430RJ
UT WOS:000265005900004
ER
PT J
AU Awazawa, M
Ueki, K
Inabe, K
Yamauchi, T
Kaneko, K
Okazaki, Y
Bardeesy, N
Ohnishi, S
Nagai, R
Kadowaki, T
AF Awazawa, Motoharu
Ueki, Kohjiro
Inabe, Kazunori
Yamauchi, Toshimasa
Kaneko, Kazuma
Okazaki, Yukiko
Bardeesy, Nabeel
Ohnishi, Shin
Nagai, Ryozo
Kadowaki, Takashi
TI Adiponectin suppresses hepatic SREBP1c expression in an
AdipoR1/LKB1/AMPK dependent pathway
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE Diabetes mellitus; Adipocytokine; Adiponectin; SREBP1c; Fatty acid
synthesis; AMPK
ID ACTIVATED PROTEIN-KINASE; ADIPOSE-SPECIFIC PROTEIN; INSULIN-SENSITIVITY;
FATTY LIVERS; MICE; RECEPTOR; GLUCOSE; BINDING; RESISTANCE; GENE
AB Adiponectin, one of the insulin-sensitizing adipokines, has been shown to activate fatty acid oxidation in liver and skeletal muscle, thus maintaining insulin sensitivity. However, the precise roles of adiponectin in fatty acid synthesis are poorly understood. Here we show that adiponectin administration acutely suppresses expression of sterol regulatory element-binding protein (SREBP) I c, the master regulator which controls and upregulates the enzymes involved in fatty acid synthesis, in the liver of +Lepr(db)/+Lep(db) (db/db) mouse as well as in Cultured hepatocytes. We also show that adiponectin suppresses SREBP1c by AdipoR1, one of the functional receptors for adiponetin, and furthermore that suppressing either AMP-activated protein kinase (AMPK) via its upstream kinase LKB1 deletion cancels the negative effect of adiponectin on SREBP1c expression. These data show that adiponectin suppresses SREBP1c through the AdipoR1/LKB1/AMPK pathway, and suggest a possible role for adiponectin in the regulation of hepatic fatty acid synthesis. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Awazawa, Motoharu; Ueki, Kohjiro; Yamauchi, Toshimasa; Kaneko, Kazuma; Okazaki, Yukiko; Kadowaki, Takashi] Univ Tokyo, Grad Sch Med, Dept Metab Dis, Bunkyo Ku, Tokyo 1138655, Japan.
[Awazawa, Motoharu; Kadowaki, Takashi] Natl Inst Hlth & Nutr, Sinjuku Ku, Tokyo 1628636, Japan.
[Inabe, Kazunori] Astellas Pharma Inc, Drug Discovery Res, Tsukuba, Ibaraki 3058585, Japan.
[Bardeesy, Nabeel] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp Canc Ctr, Boston, MA 02114 USA.
[Ohnishi, Shin] Univ Tokyo, Dept Gastroenterol, Grad Sch Med, Tokyo 1138655, Japan.
[Nagai, Ryozo] Univ Tokyo, Dept Cardiovasc Dis, Grad Sch Med, Tokyo 1138655, Japan.
RP Kadowaki, T (reprint author), Univ Tokyo, Grad Sch Med, Dept Metab Dis, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138655, Japan.
EM kadowaki-3im@h.u-tokyo.ac.jp
FU Japan Society for the Promotion of Science [10NP0201]; juvenile Diabetes
Foundation International [1-2003-746]; Ministry of Education, Culture,
Sports, Science and Technology of Japan; Ministry of Health and Welfare;
Takeda Science Foundation
FX We thank Dr. H. Shimano for the reporter plasmid used for the
measurement of SREBP1c promoter activity, and F. Takahashi and H.
Chiyonobu for their excellent technical assistance. This work was
supported by a Grant-in-Aid for Creative Scientific Research from the
Japan Society for the Promotion of Science (10NP0201) (to T.K.), a grant
from Special Coordination Funds for Promoting Science and Technology, a
grant from the juvenile Diabetes Foundation International (1-2003-746)
(to T.K.), a Grant-in-Aid for the Development of Innovative Technology
from the Ministry of Education, Culture, Sports, Science and Technology
of Japan (to T.K. and K.U.), Health Science Research grants (Research on
Human Genome and Gene Therapy) from the Ministry of Health and Welfare,
a grant from Takeda Science Foundation (to K.U.).
NR 27
TC 68
Z9 74
U1 0
U2 7
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0006-291X
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD APR 24
PY 2009
VL 382
IS 1
BP 51
EP 56
DI 10.1016/j.bbrc.2009.02.131
PG 6
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 432HO
UT WOS:000265124300011
PM 19254698
ER
PT J
AU Avruch, J
Xavier, R
Bardeesy, N
Zhang, XF
Praskova, M
Zhou, D
Xia, F
AF Avruch, Joseph
Xavier, Ramnik
Bardeesy, Nabeel
Zhang, Xian-Feng
Praskova, Maria
Zhou, Dawang
Xia, Fan
TI Rassf Family of Tumor Suppressor Polypeptides
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Review
ID ORGAN SIZE CONTROL; MICROTUBULE STABILITY; BIOCHEMICAL-ANALYSIS; HIPPO
PATHWAY; KINASE MST1; APOPTOSIS; PROTEIN; ACTIVATION; DOMAINS; NORE1
AB The Rassf1-6 polypeptides each contain a Ras/Rap association domain, which enables binding to several GTP-charged Ras-like GTPases, at least in vitro or when overexpressed. The Ras/Rap association domains are followed by SARAH domains, which mediate Rassf heterodimerization with the Mst1/2 protein kinases. Rassf1A is unequivocally a tumor suppressor, and all Rassf proteins behave like tumor suppressors, exhibiting epigenetic silencing of expression in many human cancers and proapoptotic and/or anti-proliferative effects when re-expressed in tumor cell lines. Herein, we review the binding of the Rassf polypeptides to Ras-like GTPases and the Mst1/2 kinases and their role in Rassf function.
C1 [Avruch, Joseph; Zhang, Xian-Feng; Praskova, Maria; Zhou, Dawang; Xia, Fan] Harvard Univ, Sch Med, Dept Mol Biol, Boston, MA 02114 USA.
[Bardeesy, Nabeel] Harvard Univ, Sch Med, Ctr Canc, Boston, MA 02114 USA.
[Xavier, Ramnik] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA.
[Avruch, Joseph; Zhang, Xian-Feng; Praskova, Maria; Zhou, Dawang; Xia, Fan] Harvard Univ, Sch Med, Diabet Unit, Med Serv, Boston, MA 02114 USA.
[Xavier, Ramnik] Harvard Univ, Sch Med, Gastrointestinal Unit, Med Serv, Boston, MA 02114 USA.
[Avruch, Joseph; Xavier, Ramnik; Bardeesy, Nabeel; Zhang, Xian-Feng; Praskova, Maria; Zhou, Dawang; Xia, Fan] Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA.
RP Avruch, J (reprint author), Harvard Univ, Sch Med, Dept Mol Biol, Boston, MA 02114 USA.
EM avruch@molbio.mgh.harvard.edu
OI Zhou, Dawang/0000-0002-9053-5249
FU National Institutes of Health [DK17776, P30 DK57521, HL088297, DK043351,
T32 DK007028]
FX This work was supported, in whole or in part, by National Institutes of
Health Grants DK17776 and P30 DK57521 (to J. A.), HL088297 and DK043351
(to R. X.), and T32 DK007028 (to D. Z.). This is the second article of
three in the Thematic Minireview Series on Novel Ras Effectors. This
minireview will be reprinted in the 2009 Minireview Compendium, which
will be available in January, 2010.
NR 40
TC 62
Z9 65
U1 1
U2 9
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD APR 24
PY 2009
VL 284
IS 17
BP 11001
EP 11005
DI 10.1074/jbc.R800073200
PG 5
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 437NP
UT WOS:000265494500003
PM 19091744
ER
PT J
AU Gobert, RP
van den Eijnden, M
Szyndralewiez, C
Jorand-Lebrun, C
Swinnen, D
Chen, LF
Gillieron, C
Pixley, F
Juillard, P
Gerber, P
Johnson-Leger, C
Halazy, S
Camps, M
Bombrun, A
Shipp, M
Vitte, PA
Ardissone, V
Ferrandi, C
Perrin, D
Rommel, C
van Huijsduijnen, RH
AF Gobert, Rosanna Pescini
van den Eijnden, Monique
Szyndralewiez, Cedric
Jorand-Lebrun, Catherine
Swinnen, Dominique
Chen, Linfeng
Gillieron, Corine
Pixley, Fiona
Juillard, Pierre
Gerber, Patrick
Johnson-Leger, Caroline
Halazy, Serge
Camps, Montserrat
Bombrun, Agnes
Shipp, Margaret
Vitte, Pierre-Alain
Ardissone, Vittoria
Ferrandi, Chiara
Perrin, Dominique
Rommel, Christian
van Huijsduijnen, Rob Hooft
TI GLEPP1/Protein-tyrosine Phosphatase phi Inhibitors Block Chemotaxis in
Vitro and in Vivo and Improve Murine Ulcerative Colitis
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID PROTEIN-TYROSINE-PHOSPHATASE; RECEPTOR-TYPE-O; GROWTH-HORMONE RECEPTOR;
MOLECULAR-CLONING; IMMUNE-RESPONSE; PTP-OC; EXPRESSION; IDENTIFICATION;
SYK; PROMOTER
AB We describe novel, cell-permeable, and bioavailable salicylic acid derivatives that are potent and selective inhibitors of GLEPP1/protein-tyrosine phosphatase phi. Two previously described GLEPP1 substrates, paxillin and Syk, are both required for cytoskeletal rearrangement and cellular motility of leukocytes in chemotaxis. We show here that GLEPP1 inhibitors prevent dephosphorylation of Syk1 and paxillin in resting cells and block primary human monocyte and mouse bone marrow-derived macrophage chemotaxis in a gradient of monocyte chemotactic protein-1. In mice, the GLEPP1 inhibitors also reduce thioglycolate-induced peritoneal chemotaxis of neutrophils, lymphocytes, and macrophages. In murine disease models, the GLEPP1 inhibitors significantly reduce severity of contact hypersensitivity, a model for allergic dermatitis, and dextran sulfate sodium-induced ulcerative colitis, a model for inflammatory bowel disease. Taken together, our data provide confirmation that GLEPP1 plays an important role in controlling chemotaxis of multiple types of leukocytes and that pharmacological inhibition of this phosphatase may have therapeutic use.
C1 [Gobert, Rosanna Pescini; van den Eijnden, Monique; Szyndralewiez, Cedric; Jorand-Lebrun, Catherine; Swinnen, Dominique; Gillieron, Corine; Juillard, Pierre; Gerber, Patrick; Johnson-Leger, Caroline; Halazy, Serge; Camps, Montserrat; Bombrun, Agnes; Vitte, Pierre-Alain; Perrin, Dominique; Rommel, Christian; van Huijsduijnen, Rob Hooft] Merck Serono Int, CH-1211 Geneva, Switzerland.
[Chen, Linfeng; Shipp, Margaret] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Pixley, Fiona] Univ Western Australia, Sch Med & Pharmacol, Nedlands, WA 6009, Australia.
[Ardissone, Vittoria; Ferrandi, Chiara] Merck Serono Ist Ric Biomed Antoine Marxer, I-10010 Colleretto Giacosa, TO, Italy.
RP van Huijsduijnen, RH (reprint author), Merck Serono Int, 9 Chemin Mines, CH-1211 Geneva, Switzerland.
EM rob.hooft@merckserono.net
FU European Union Research Training Network [MRTN-CT-2006-035830]
FX Supported by European Union Research Training Network Grant
MRTN-CT-2006-035830.
NR 53
TC 7
Z9 8
U1 0
U2 3
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD APR 24
PY 2009
VL 284
IS 17
BP 11385
EP 11395
DI 10.1074/jbc.M807241200
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 437NP
UT WOS:000265494500043
PM 19233845
ER
PT J
AU Neel, BG
Cross, FR
Pellman, D
AF Neel, Benjamin G.
Cross, Frederick R.
Pellman, David
TI Hidesaburo Hanafusa 1929-2009 Obituary
SO MOLECULAR CELL
LA English
DT Biographical-Item
C1 [Neel, Benjamin G.] Univ Toronto, Ontario Canc Inst, Toronto, ON M4W 2V1, Canada.
[Cross, Frederick R.] Rockefeller Univ, New York, NY 10065 USA.
[Pellman, David] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Neel, BG (reprint author), Univ Toronto, Ontario Canc Inst, Toronto, ON M4W 2V1, Canada.
EM bneel@uhnresearch.ca; fcross@rockefeller.edu;
david_pellman@dfci.harvard.edu
NR 0
TC 0
Z9 0
U1 1
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1097-2765
J9 MOL CELL
JI Mol. Cell
PD APR 24
PY 2009
VL 34
IS 2
BP 141
EP 143
DI 10.1016/j.molcel.2009.04.005
PG 3
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 437XX
UT WOS:000265521300005
ER
PT J
AU Zhu, J
Luo, BH
Barth, P
Schonbrun, J
Baker, D
Springer, TA
AF Zhu, Jieqing
Luo, Bing-Hao
Barth, Patrick
Schonbrun, Jack
Baker, David
Springer, Timothy A.
TI The Structure of a Receptor with Two Associating Transmembrane Domains
on the Cell Surface: Integrin alpha(IIb)beta(3)
SO MOLECULAR CELL
LA English
DT Article
ID GROWTH-FACTOR RECEPTOR; CYTOPLASMIC DOMAINS; PROTEIN STRUCTURES; SPATIAL
STRUCTURE; HELIX PACKING; GLYCOPHORIN-A; RESTING STATE; ACTIVATION;
PREDICTION; MECHANISM
AB Structures of intact receptors with single-pass transmembrane domains are essential to understand how extracellular and cytoplasmic domains regulate association and signaling through transmembrane domains. A chemical and computational method to determine structures of the membrane regions of such receptors on the cell surface is developed here and validated with glycophorin A. An integrin heterodimer structure reveals association over most of the lengths of the alpha and beta transmembrane domains and shows that the principles governing association of hetero and homo transmembrane dimers differ. A turn at the Gly of the juxtamembrane GFFKR motif caps the alpha TM helix and brings the two Phe of GFFKR into the alpha/beta interface. A juxtamembrane Lys residue in beta also has an important role in the interface. The structure shows how transmembrane association/dissociation regulates integrin signaling. A joint ectodomain and membrane structure shows that substantial flexibility between the extracellular and TM domains is compatible with TM signaling.
C1 [Zhu, Jieqing; Luo, Bing-Hao; Springer, Timothy A.] Harvard Univ, Sch Med, Childrens Hosp, Immune Dis Inst, Boston, MA 02115 USA.
[Zhu, Jieqing; Luo, Bing-Hao; Springer, Timothy A.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Barth, Patrick; Schonbrun, Jack; Baker, David] Univ Washington, Dept Biochem, Seattle, WA 98195 USA.
[Barth, Patrick; Schonbrun, Jack; Baker, David] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA.
RP Springer, TA (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Immune Dis Inst, 3 Blackfan Circle, Boston, MA 02115 USA.
EM springeroffice@idi.harvard.edu
RI Baker, David/K-8941-2012
OI Baker, David/0000-0001-7896-6217
FU NIH [HL-48675]; HHMI
FX We thank Junichi Takagi and Guo-hui Li for early help with the project,
This work was supported by NIH grant HL-48675 and HHMI.
NR 40
TC 87
Z9 89
U1 1
U2 6
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1097-2765
J9 MOL CELL
JI Mol. Cell
PD APR 24
PY 2009
VL 34
IS 2
BP 234
EP 249
DI 10.1016/j.molcel.2009.02.022
PG 16
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 437XX
UT WOS:000265521300014
PM 19394300
ER
PT J
AU Coleman, JJ
Mylonakis, E
AF Coleman, Jeffrey J.
Mylonakis, Eleftherios
TI The Tangled Web of Signaling in Innate Immunity
SO CELL HOST & MICROBE
LA English
DT Editorial Material
ID KINASE-C-DELTA; CAENORHABDITIS-ELEGANS
AB Similarities in innate immune signaling exist between mammals and the nematode Caenorhabditis elegans. Now, Ziegler et al. (2009) and Ren et al. (2009) demonstrate that a protein kinase C 8 homolog in C. elegans is involved in innate immunity, providing evidence that the conservation of immune signaling networks extends further than previously thought.
C1 [Coleman, Jeffrey J.; Mylonakis, Eleftherios] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
RP Mylonakis, E (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
EM emylonakis@partners.org
RI Coleman, Jeffrey/E-2981-2015;
OI Coleman, Jeffrey/0000-0001-8579-1996
FU NIAID NIH HHS [R01 AI075286, T32 AI007061]
NR 12
TC 4
Z9 4
U1 0
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1931-3128
J9 CELL HOST MICROBE
JI Cell Host Microbe
PD APR 23
PY 2009
VL 5
IS 4
BP 313
EP 315
DI 10.1016/j.chom.2009.04.002
PG 3
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 438QX
UT WOS:000265571600003
PM 19380109
ER
PT J
AU Sin, MLY
Gau, V
Liao, JC
Haake, DA
Wong, PK
AF Sin, Mandy L. Y.
Gau, Vincent
Liao, Joseph C.
Haake, David A.
Wong, Pak Kin
TI Active Manipulation of Quantum Dots using AC Electrokinetics
SO JOURNAL OF PHYSICAL CHEMISTRY C
LA English
DT Article
ID ELECTRIC-FIELDS; FLUID-FLOW; DNA; MICROELECTRODES; DIELECTROPHORESIS;
NANOPARTICLES; ELECTROLYTES; BIOMOLECULES; NANOTUBES; BIOSENSOR
AB The superior optical and electrical properties of quantum dot (QD) nanoparticles are being applied in a new generation of QD devices for microelectronic, nanophotonic, and biomedical systems. Research on integrated QD-based systems has been focused on passive manipulation of QDs including template-guided self-assembly, molecular scaffold-based assembly, and microbead-based assembly. However, little effort has been devoted to development of methods for active manipulation, such as positioning and concentration, of QDs. In this study, we show that 20 nm colloidal QDs can be effectively positioned and concentrated using a combination of dielectrophoresis (DEP) and AC electro-osmosis (ACEO). The long-range fluid motion generated by ACEO entrains QDs to the area near the electrode surface, which facilitates the trapping of QDs by DEP. A systematic investigation was performed to examine electrokinetic processes at different applied frequencies and voltages using a concentric electrode configuration. We demonstrate that QDs can be dynamically positioned with an electric field strength as small as 10 kV/m and define the operating parameters for increasing the concentration of colloidal QDs by 2 orders of magnitude within one minute.
C1 [Sin, Mandy L. Y.; Wong, Pak Kin] Univ Arizona, Dept Aerosp & Mech Engn, Tucson, AZ 85721 USA.
[Gau, Vincent] Genefluidics Inc, Monterey Pk, CA 91754 USA.
[Liao, Joseph C.] Stanford Univ, Dept Urol, Stanford, CA 94305 USA.
[Liao, Joseph C.] Stanford Univ, Bio X Program, Stanford, CA 94305 USA.
[Haake, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA.
[Haake, David A.] Vet Affairs Greater Los Angeles Healthcare Syst, Div Infect Dis, Los Angeles, CA 90095 USA.
[Wong, Pak Kin] Univ Arizona, Biomed Engn Interdisciplinary Program, Tucson, AZ 85721 USA.
[Wong, Pak Kin] Univ Arizona, Inst Bio5, Tucson, AZ 85721 USA.
RP Wong, PK (reprint author), Univ Arizona, Dept Aerosp & Mech Engn, Tucson, AZ 85721 USA.
EM pak@email.arizona.edu
RI Wong, Pak Kin/A-7974-2012; Liao, Joseph/J-5874-2015
OI Wong, Pak Kin/0000-0001-7388-2110;
FU American Chemical Society Petroleum Research Fund [47507-G7]; Arizona
Biomedical Research Commission; Arizona Research Laboratories Center for
Insect Science [AI075565]; National Institute of Allergy and Infectious
Disease [1U01AI082457-01]; Veterans Affairs RRD Merit Review [4872]
FX The authors thank V. Constantino, C. S. Chen, and M. Junkin for
technical assistance. This work was supported by the American Chemical
Society Petroleum Research Fund (47507-G7), Arizona Biomedical Research
Commission, Arizona Research Laboratories Center for Insect Science,
Cooperative Agreement Award AI075565 (to D.A.H.) from the National
Institute of Allergy and Infectious Disease (1U01AI082457-01), and
Veterans Affairs RR&D Merit Review 4872 (to J.C.L.).
NR 39
TC 22
Z9 22
U1 1
U2 14
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1932-7447
J9 J PHYS CHEM C
JI J. Phys. Chem. C
PD APR 23
PY 2009
VL 113
IS 16
BP 6561
EP 6565
DI 10.1021/jp9004423
PG 5
WC Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science,
Multidisciplinary
SC Chemistry; Science & Technology - Other Topics; Materials Science
GA 435ZV
UT WOS:000265383300032
ER
PT J
AU Canto, C
Gerhart-Hines, Z
Feige, JN
Lagouge, M
Noriega, L
Milne, JC
Elliott, PJ
Puigserver, P
Auwerx, J
AF Canto, Carles
Gerhart-Hines, Zachary
Feige, Jerome N.
Lagouge, Marie
Noriega, Lilia
Milne, Jill C.
Elliott, Peter J.
Puigserver, Pere
Auwerx, Johan
TI AMPK regulates energy expenditure by modulating NAD(+) metabolism and
SIRT1 activity
SO NATURE
LA English
DT Article
ID ACTIVATED PROTEIN-KINASE; GENE-EXPRESSION; NICOTINAMIDE
PHOSPHORIBOSYLTRANSFERASE; MITOCHONDRIAL-FUNCTION; GLUCOSE-HOMEOSTASIS;
SKELETAL-MUSCLE; RECEPTOR-GAMMA; PGC-1-ALPHA; MECHANISM; OXIDATION
AB AMP-activated protein kinase (AMPK) is a metabolic fuel gauge conserved along the evolutionary scale in eukaryotes that senses changes in the intracellular AMP/ATP ratio(1). Recent evidence indicated an important role for AMPK in the therapeutic benefits of metformin(2,3), thiazolidinediones(4) and exercise(5), which form the cornerstones of the clinical management of type 2 diabetes and associated metabolic disorders. In general, activation of AMPK acts to maintain cellular energy stores, switching on catabolic pathways that produce ATP, mostly by enhancing oxidative metabolism and mitochondrial biogenesis, while switching off anabolic pathways that consume ATP(1). This regulation can take place acutely, through the regulation of fast post-translational events, but also by transcriptionally reprogramming the cell to meet energetic needs. Here we demonstrate that AMPK controls the expression of genes involved in energy metabolism in mouse skeletal muscle by acting in coordination with another metabolic sensor, the NAD(+)-dependent type III deacetylase SIRT1. AMPK enhances SIRT1 activity by increasing cellular NAD(+) levels, resulting in the deacetylation and modulation of the activity of downstream SIRT1 targets that include the peroxisome proliferator-activated receptor-gamma coactivator 1 alpha and the forkhead box O1 (FOXO1) and O3 (FOXO3a) transcription factors. The AMPK-induced SIRT1-mediated deacetylation of these targets explains many of the convergent biological effects of AMPK and SIRT1 on energy metabolism.
C1 [Canto, Carles; Feige, Jerome N.; Lagouge, Marie; Noriega, Lilia; Auwerx, Johan] CNRS INSERM ULP, Inst Genet & Biol Mol & Cellulaire, F-67404 Illkirch Graffenstaden, France.
[Canto, Carles; Noriega, Lilia; Auwerx, Johan] Ecole Polytech Fed Lausanne, CH-1015 Lausanne, Switzerland.
[Gerhart-Hines, Zachary; Puigserver, Pere] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Gerhart-Hines, Zachary; Puigserver, Pere] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
[Milne, Jill C.; Elliott, Peter J.] Sirtris Pharmaceut Inc, Cambridge, MA 02139 USA.
[Auwerx, Johan] Inst Clin Souris, F-67404 Illkirch Graffenstaden, France.
RP Auwerx, J (reprint author), CNRS INSERM ULP, Inst Genet & Biol Mol & Cellulaire, F-67404 Illkirch Graffenstaden, France.
EM admin.auwerx@epfl.ch
OI Canto, Carles/0000-0002-5167-7922
FU CNRS; Ecole Polytechnique Federale de Lausanne; INSERM; ULP; NIH
[DK59820, DK069966]; EU [LSHM-CT-2004-512013, ERC-2008-AdG-23118];
Fondation de la Recherche Medicale (FRM); EMBO; FEBS
FX This work was supported by grants of CNRS, Ecole Polytechnique Federale
de Lausanne, INSERM, ULP, NIH (DK59820 and DK069966), EU FP6 (EUGENE2;
LSHM-CT-2004-512013) and EU Ideas programme (sirtuins;
ERC-2008-AdG-23118). C. C. has been supported by grants of Fondation de
la Recherche Medicale (FRM) and EMBO. J. N. F. was supported by a FEBS
grant. The authors thank F. Foufelle and P. Ferre, B. Spiegelman, D. P.
Kelly, S.-i. Imai, G. Hardie, C. Ammann (Topotarget) and F. Alt for
providing materials, and members of the Auwerx and Puigserver
laboratories for discussion.
NR 33
TC 1089
Z9 1135
U1 36
U2 217
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD APR 23
PY 2009
VL 458
IS 7241
BP 1056
EP U140
DI 10.1038/nature07813
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 436KL
UT WOS:000265412900049
PM 19262508
ER
PT J
AU Weinblatt, ME
Abbott, GF
Koreishi, AF
AF Weinblatt, Michael E.
Abbott, Gerald F.
Koreishi, Aashiyana F.
TI A Woman with Respiratory Failure and a Cavitary Lesion in the Lung
Invasive group A beta-hemolytic streptococcal infection, with acute
necrotizing bronchopneumonia with cavitation and with evidence of the
toxic shock syndrome, in a patient treated with anti-TNF antibody.
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
ID NECROSIS-FACTOR-ALPHA; SERIOUS BACTERIAL-INFECTIONS;
RHEUMATOID-ARTHRITIS; PNEUMOCOCCAL PNEUMONIA; FACTOR ANTAGONISTS;
DEFICIENT MICE; THERAPY; RISK; TUBERCULOSIS; ETANERCEPT
C1 [Weinblatt, Michael E.] Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA.
[Abbott, Gerald F.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Koreishi, Aashiyana F.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Weinblatt, Michael E.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Abbott, Gerald F.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA.
[Koreishi, Aashiyana F.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RP Weinblatt, ME (reprint author), Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, 75 Francis St, Boston, MA 02115 USA.
NR 29
TC 6
Z9 6
U1 0
U2 2
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD APR 23
PY 2009
VL 360
IS 17
BP 1770
EP 1779
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 435XY
UT WOS:000265377800013
PM 19387019
ER
PT J
AU Bakirtzi, K
Belfort, G
Lopez-Coviella, I
Kuruppu, D
Cao, L
Abel, ED
Brownell, AL
Kandror, KV
AF Bakirtzi, Kyriaki
Belfort, Gabriel
Lopez-Coviella, Ignacio
Kuruppu, Darshini
Cao, Lei
Abel, E. Dale
Brownell, Anna-Liisa
Kandror, Konstantin V.
TI Cerebellar Neurons Possess a Vesicular Compartment Structurally and
Functionally Similar to Glut4-Storage Vesicles from Peripheral
Insulin-Sensitive Tissues
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID GLUCOSE-TRANSPORTER GLUT4; CENTRAL-NERVOUS-SYSTEM; REGULATED MEMBRANE
AMINOPEPTIDASE; SKELETAL-MUSCLE; GLUT4-CONTAINING VESICLES;
SUBCELLULAR-LOCALIZATION; RAT ADIPOCYTES; PC12 CELLS; RESPONSIVE
AMINOPEPTIDASE; STIMULATED TRANSLOCATION
AB The insulin-sensitive isoform of the glucose transporting protein, Glut4, is expressed in fat as well as in skeletal and cardiac muscle and is responsible for the effect of insulin on blood glucose clearance. Recent studies have revealed that Glut4 is also expressed in the brain, although the intracellular compartmentalization and regulation of Glut4 in neurons remains unknown. Using sucrose gradient centrifugation, immunoadsorption and immunofluorescence staining, we have shown that Glut4 in the cerebellum is localized in intracellular vesicles that have the sedimentation coefficient, the buoyant density, and the protein composition similar to the insulin-responsive Glut4-storage vesicles from fat and skeletal muscle cells. In cultured cerebellar neurons, insulin stimulates glucose uptake and causes translocation of Glut4 to the cell surface. Using (18)FDG ((18)fluoro-2-deoxyglucose) positron emission tomography, we found that physical exercise acutely increases glucose uptake in the cerebellum in vivo. Prolonged physical exercise increases expression of the Glut4 protein in the cerebellum. Our results suggest that neurons have a novel type of translocation-competent vesicular compartment which is regulated by insulin and physical exercise similar to Glut4-storage vesicles in peripheral insulin target tissues.
C1 [Bakirtzi, Kyriaki; Belfort, Gabriel; Kandror, Konstantin V.] Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA.
[Lopez-Coviella, Ignacio] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA.
[Kuruppu, Darshini; Cao, Lei; Brownell, Anna-Liisa] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Abel, E. Dale] Univ Utah, Div Endocrinol Diabet & Metab, Salt Lake City, UT 84112 USA.
[Abel, E. Dale] Univ Utah, Program Human Mol Biol & Genet, Salt Lake City, UT 84112 USA.
RP Kandror, KV (reprint author), Boston Univ, Sch Med, Dept Biochem, K124D,715 Albany St, Boston, MA 02118 USA.
EM kandror@biochem.bumc.bu.edu
RI Cao, Lei/B-3254-2012;
OI Cao, Lei/0000-0003-4018-9496; Kandror, Konstantin/0000-0002-8601-9313
FU National Institutes of Health [EB001850, DK52057, DK56736]; American
Diabetes Association
FX This work was supported by research grants from the National Institutes
of Health [Grants EB001850 (A.L.B.) and DK52057 and DK56736 (K.V.K.)],
and by an Innovation Award from the American Diabetes Association (K.V.
K.). We are grateful to Dr. Paul Toselli, Dr. Daniela Pellegrino, Dr.
Aijun Zhu, and Mark Jedrychowski for help with some experiments.
NR 67
TC 22
Z9 22
U1 1
U2 7
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD APR 22
PY 2009
VL 29
IS 16
BP 5193
EP 5201
DI 10.1523/JNEUROSCI.0858-09.2009
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA 436XV
UT WOS:000265450300017
PM 19386915
ER
PT J
AU Zhu, TF
Szostak, JW
AF Zhu, Ting F.
Szostak, Jack W.
TI Coupled Growth and Division of Model Protocell Membranes
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID FATTY-ACID VESICLES; MURCHISON CARBONACEOUS CHONDRITE; MONOCARBOXYLIC
ACIDS; SELF-REPRODUCTION; TRANSFORMATION; COMPETITION; COMPONENTS;
PARTICLES; LIPOSOMES; NETWORKS
AB The generation of synthetic forms of cellular life requires solutions to the problem of how biological processes such as cyclic growth and division could emerge from purely physical and chemical systems. Small unilamellar fatty acid vesicles grow when fed with fatty acid micelles and can be forced to divide by extrusion, but this artificial division process results in significant loss of protocell contents during each division cycle. Here we describe a simple and efficient pathway for model protocell membrane growth and division. The growth of large multilamellar fatty acid vesicles fed with fatty acid micelles, in a solution where solute permeation across the membranes is slow, results in the transformation of initially spherical vesicles into long thread-like vesicles, a process driven by the transient imbalance between surface area and volume growth. Modest shear forces are then sufficient to cause the thread-like vesicles to divide into multiple daughter vesicles without loss of internal contents. In an environment of gentle shear, protocell growth and division are thus coupled processes. We show that model protocells can proceed through multiple cycles of reproduction. Encapsulated RNA molecules, representing a primitive genome, are distributed to the daughter vesicles. Our observations bring us closer to the laboratory synthesis of a complete protocell consisting of a self-replicating genome and a self-replicating membrane compartment. In addition, the robustness and simplicity of this pathway suggests that similar processes might have occurred under the prebiotic conditions of the early Earth.
C1 [Zhu, Ting F.; Szostak, Jack W.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA.
[Zhu, Ting F.; Szostak, Jack W.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
[Zhu, Ting F.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
RP Szostak, JW (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA.
EM szostak@molbio.mgh.harvard.edu
FU NASA [EXB020031-0018]
FX We thank R. Bruckner, I. Chen, S. Chung, M. Elenko, R. Irwin, P. L.
Luisi, A. Luptak, S. Mansy, D. Treco, C. Wong, and S. Zhou for helpful
discussions and comments on the manuscript. This work was supported in
part by grant EXB020031-0018 from the NASA Exobiology Program. J.W.S. is
an Investigator of the Howard Hughes Medical Institute.
NR 38
TC 128
Z9 134
U1 66
U2 128
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0002-7863
J9 J AM CHEM SOC
JI J. Am. Chem. Soc.
PD APR 22
PY 2009
VL 131
IS 15
BP 5705
EP 5713
DI 10.1021/ja900919c
PG 9
WC Chemistry, Multidisciplinary
SC Chemistry
GA 434IJ
UT WOS:000265268100055
PM 19323552
ER
PT J
AU Shekelle, PG
AF Shekelle, Paul G.
TI Supplementation with vitamin E or vitamin C did not differ from placebo
for major cardiovascular events and mortality
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Editorial Material
ID PREVENTION; DISEASE; METAANALYSIS
C1 W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA.
RP Shekelle, PG (reprint author), W Los Angeles Vet Affairs Med Ctr, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA.
NR 4
TC 0
Z9 0
U1 0
U2 2
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD APR 21
PY 2009
VL 150
IS 8
AR JC4-12
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 437AD
UT WOS:000265457000027
PM 19391226
ER
PT J
AU Winkler, DD
Schuermann, JP
Cao, XH
Holloway, SP
Borchelt, DR
Carroll, MC
Proescher, JB
Culotta, VC
Hart, PJ
AF Winkler, Duane D.
Schuermann, Jonathan P.
Cao, Xiaohang
Holloway, Stephen P.
Borchelt, David R.
Carroll, Mark C.
Proescher, Jody B.
Culotta, Valeria C.
Hart, P. John
TI Structural and Biophysical Properties of the Pathogenic SOD1 Variant
H46R/H48Q
SO BIOCHEMISTRY
LA English
DT Article
ID AMYOTROPHIC-LATERAL-SCLEROSIS; ZINC SUPEROXIDE-DISMUTASE; MOTOR-NEURON
DEGENERATION; COPPER CHAPERONE CCS; CU,ZN-SUPEROXIDE DISMUTASE;
TRANSGENIC MICE; BINDING-SITE; FAMILIAL ALS; IN-VITRO; DISULFIDE
AB Over 100 mutations in the gene encoding human copper-zinc superoxide dismutase (SOD1) cause an inherited form of the fatal neurodegenerative disease amyotrophic lateral sclerosis (ALS). Two pathogenic SOD1 mutations, His46Arg (H46R) and His48Gln (H48Q), affect residues that act as copper ligands in the wild type enzyme. Transgenic mice expressing a human SOD1 variant containing both mutations develop paralytic disease akin to ALS. Here we show that H46R/H48Q SOD1 possesses multiple characteristics that distinguish it from the wild type. These properties include the following: (1) an ablated copper-binding site, (2) a substantially weakened affinity for zinc, (3) a binding site for a calcium ion, (4) the ability to form stable heterocomplexes with the copper chaperone for SOD1 (CCS), and (5) compromised CCS-mediated oxidation of the intrasubunit disulfide bond in vivo. The results presented here, together with data on pathogenic SOD1 proteins coming from cell culture and transgenic mice, suggest that incomplete posttranslational modification of nascent SOD1 polypeptides via CCS may be a characteristic shared by familial ALS SOD1 mutants, leading to a population of destabilized, off-pathway folding intermediates that are toxic to motor neurons.
C1 [Winkler, Duane D.; Schuermann, Jonathan P.; Cao, Xiaohang; Holloway, Stephen P.; Hart, P. John] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA.
[Winkler, Duane D.; Schuermann, Jonathan P.; Cao, Xiaohang; Holloway, Stephen P.; Hart, P. John] Univ Texas Hlth Sci Ctr San Antonio, Xray Crystallog Core Lab, San Antonio, TX 78229 USA.
[Hart, P. John] S Texas Vet Hlth Care Syst, Dept Vet Affairs, Audie Murphy Div, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78229 USA.
[Borchelt, David R.] Univ Florida, Dept Neurosci, McKnight Brain Inst, Gainesville, FL 32610 USA.
[Carroll, Mark C.; Proescher, Jody B.; Culotta, Valeria C.] Johns Hopkins Univ, Dept Environm Hlth Sci, Bloomberg Sch Publ Hlth, Baltimore, MD 21218 USA.
RP Hart, PJ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA.
EM pjhart@biochem.uthscsa.edu
FU NIH-NINDS [R01-NS39112, P01-NS04913]; NIHGMS [GM50016]; JHU NIEHS
center; American Foundation for Aging Research (AFAR).; NIH
[T32AG021890-03]; NIEHS [ES 07141]; William and Ella Owens Medical
Research Foundation; Judith and Jean Pape Adams Charitable Foundation
FX This work was supported by grants NIH-NINDS R01-NS39112 (P.J.H.),
P01-NS04913 (Joan S. Valentine, D.R.B., and P.J.H.), NIHGMS GM50016
(V.C.C.), and the JHU NIEHS center (V.C.C.). D.D.W. was supported in
part by the American Foundation for Aging Research (AFAR). J.P.S. was
supported by NIH T32AG021890-03. J.B.P. was supported by NIEHS training
grant ES 07141. X.C. was supported in part by the William and Ella Owens
Medical Research Foundation and the Judith and Jean Pape Adams
Charitable Foundation. Support for the X-ray Crystallography Core
Laboratory and the Center for Analytical Ultracentrifugation of
Macromolecular Assemblies by the UTHSCSA Executive Research Committee
and the San Antonio Cancer Institute is also gratefully acknowledged.
NR 58
TC 18
Z9 18
U1 0
U2 2
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD APR 21
PY 2009
VL 48
IS 15
BP 3436
EP 3447
DI 10.1021/bi8021735
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 432YL
UT WOS:000265170200020
PM 19227972
ER
PT J
AU Scirica, BM
Morrow, DA
Budaj, A
Dalby, AJ
Mohanavelu, S
Aroesty, J
Hedgepeth, CM
Stone, PH
Braunwald, E
AF Scirica, Benjamin M.
Morrow, David A.
Budaj, Andrzej
Dalby, Anthony J.
Mohanavelu, Satishkumar
Aroesty, Julian
Hedgepeth, Chester M.
Stone, Peter H.
Braunwald, Eugene
TI Ischemia Detected on Continuous Electrocardiography After Acute Coronary
Syndrome Observations From the MERLIN-TIMI 36 (Metabolic Efficiency With
Ranolazine for Less Ischemia in Non-ST-Elevation Acute Coronary
Syndrome-Thrombolysis In Myocardial Infarction 36) Trial
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
DE acute coronary syndrome; ischemia; electrocardiography; Holter;
ranolazine
ID UNSTABLE ANGINA; CARDIOVASCULAR EVENTS; RECURRENT ISCHEMIA;
RANDOMIZED-TRIAL; PROGNOSTIC VALUE; ARTERY-DISEASE; HEART-FAILURE;
HIGH-RISK; AMLODIPINE; BIOMARKERS
AB Objectives The purpose of this study was to assess the relationship between ischemia detected on continuous electrocardiographic (cECG) recording and cardiovascular outcomes after acute coronary syndrome (ACS).
Background The small size of prior studies evaluating cECG prevented full evaluation of the risk associated with ischemia across subpopulations and compared with other methods of risk stratification. Ranolazine, a new antianginal agent, reduces ischemic symptoms in patients with chronic angina and after ACS but the anti-ischemic effect, as detected by cECG, is not known.
Methods In all, 6,560 patients hospitalized with non-ST-segment elevation ACS were randomly assigned to ranolazine or placebo in the MERLIN-TIMI 36 (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST-Elevation Acute Coronary Syndrome-Thrombolysis In Myocardial Infarction 36) trial. The cECG was performed for 7 days after randomization. Outcomes were followed for a median of 348 days. Clinical events that occurred during cECG recording were excluded from analysis.
Results A total of 6,355 (97%) patients had cECG recordings evaluable for ischemia analysis. Patients with >= 1 episode of ischemia on cECG (n = 1,271, 20%) were at increased risk of cardiovascular death ( 7.7% vs. 2.7%, p < 0.001), MI (9.4% vs. 5.0%, p < 0.001), and recurrent ischemia (17.5% vs. 12.3%, p < 0.001). The relationship with cardiovascular death was independent of baseline characteristics or elevated biomarkers ( adjusted hazard ratio: 2.46, p < 0.001). Ischemia on cECG was associated with significantly worse outcomes in several subgroups. Ranolazine did not reduce the rate of ischemia detected on cECG (19.9% vs. 21.0%, hazard ratio: 0.93, p = 0.21).
Conclusions In more than 6,300 patients with ACS, ischemia detected on cECG occurred frequently and was strongly and independently associated with poor cardiovascular outcomes, including cardiovascular death. Continuous ECG monitoring to detect ischemia after ACS may help to identify patients at increased risk. (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST Elevation Acute Coronary Syndromes [MERLIN]; NCT00099788) (J Am Coll Cardiol 2009; 53: 1411-21) (C) 2009 by the American College of Cardiology Foundation
C1 [Scirica, Benjamin M.] Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Dept Med, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Boston, MA USA.
[Budaj, Andrzej] Grochowski Hosp, Postgrad Med Sch, Warsaw, Poland.
[Dalby, Anthony J.] Milpark Hosp, Johannesburg, South Africa.
RP Scirica, BM (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Dept Med, 75 Francis St, Boston, MA 02115 USA.
EM bscirica@partners.org
FU CV Therapeutics; Accumetrics; Amgen; AstraZeneca; Bayer Healthcare;
Beckman Coulter; Biosite; Bristol-Myers Squibb; Eli Lilly; Michael
Lerner
FX The MERLIN-TIMI 36 study was supported by CV Therapeutics. The TIMI
Study Group reports receiving significant research grant support from
Accumetrics, Amgen, AstraZeneca, Bayer Healthcare, Beckman Coulter,
Biosite, Bristol-Myers Squibb, CV Therapeutics, Eli Lilly,
GlaxoSmithKline, Inotek Pharmaceuticals, Integrated Therapeutics, Merck
& Co., Merck-Schering Plough Joint Venture, Millennium Pharmaceuticals,
Novartis Pharmaceuticals, Nuvelo, OrthoClinical Diagnostics, Pfizer,
Roche Diagnostics, Sanofi-Aventis, Sanofi-Synthelabo, and
Schering-Plough. Dr. Scirica receives honoraria for consulting and
educational presentations from CV Therapeutics, and is supported in part
by an unrestricted research grant from Michael Lerner. Dr. Morrow
receives honoraria for educational presentations from CV Therapeutics
and Sanofi-Aventis, serves as a consultant for GlaxoSmithKline and
Sanofi-Aventis, and is on the advisory board for Genentech. Dr. Budaj
receives honoraria from CV Therapeutics, AstraZeneca, GlaxoSmithKline,
Boehringer Ingelheim, and Sanofi-Aventis, and serves as a consultant to
GlaxoSmithKline and Sanofi-Aventis. Dr. Aroesty serves as a consultant
to Fibrogen, which has no commercial products and is conducting no
research that could bear any relationship to this paper. Dr. Stone
receives a research grant from CV Therapeutics. Dr. Braunwald receives
honoraria from and serves as a consultant to AstraZeneca, Bayer AG, CV
Therapeutics, Daichii Sankyo, Merck, Pfizer, and Schering-Plough.
NR 25
TC 23
Z9 26
U1 1
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 21
PY 2009
VL 53
IS 16
BP 1411
EP 1421
DI 10.1016/j.jacc.2008.12.053
PG 11
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 432UR
UT WOS:000265160200003
PM 19371824
ER
PT J
AU Arsava, EM
Rahman, R
Rosand, J
Lu, J
Smith, EE
Rost, NS
Singhal, AB
Lev, MH
Furie, KL
Koroshetz, WJ
Sorensen, AG
Ay, H
AF Arsava, E. M.
Rahman, R.
Rosand, J.
Lu, J.
Smith, E. E.
Rost, N. S.
Singhal, A. B.
Lev, M. H.
Furie, K. L.
Koroshetz, W. J.
Sorensen, A. G.
Ay, H.
TI Severity of leukoaraiosis correlates with clinical outcome after
ischemic stroke
SO NEUROLOGY
LA English
DT Article
ID WHITE-MATTER CHANGES; SCALE SCORE; MRI; AGE; LESIONS; BRAIN; CT;
REHABILITATION; ENCEPHALOPATHY; CONNECTIVITY
AB Background: Leukoaraiosis (LA) is closely associated with aging, a major determinant of clinical outcome after ischemic stroke. In this study we sought to identify whether LA, independent of advancing age, affects outcome after acute ischemic stroke.
Methods: LA volume was quantified in 240 patients with ischemic stroke and MRI within 24 hours of symptom onset. We explored the relationship between LA volume at admission and clinical outcome at 6 months, as assessed by the modified Rankin Scale (mRS). An ordinal logistic regression model was developed to analyze the independent effect of LA volume on clinical outcome.
Results: Bivariate analyses showed a significant correlation between LA volume and mRS at 6 months (r = 0.19, p = 0.003). Mean mRS was 1.7 +/- 1.8 among those in the lowest (<= 1.2 mL) and 2.5 +/- 1.9 in the highest (>9.9 mL) quartiles of LA volume (p = 0.01). The unfavorable prognostic effect of LA volume on clinical outcome was retained in the multivariable model (p = 0.002), which included age, gender, stroke risk factors (hypertension, diabetes mellitus, atrial fibrillation), previous history of brain infarction, admission plasma glucose level, admission NIH Stroke Scale score, IV rtPA treatment, and acute infarct volume on MRI as covariates.
Conclusions: The volume of leukoaraiosis is a predictor of clinical outcome after ischemic stroke and this relationship persists after adjustment for important prognostic factors including age, initial stroke severity, and infarct volume. Neurology(R) 2009; 72: 1403-1410
C1 [Arsava, E. M.; Lu, J.; Lev, M. H.; Sorensen, A. G.; Ay, H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging,Dept Radiol, Boston, MA 02129 USA.
[Rahman, R.; Rosand, J.; Smith, E. E.; Rost, N. S.; Singhal, A. B.; Furie, K. L.; Ay, H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke Serv,Dept Neurol, Boston, MA 02129 USA.
[Rahman, R.; Rosand, J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02129 USA.
[Rahman, R.; Rosand, J.; Rost, N. S.] MIT & Harvard, Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
[Koroshetz, W. J.] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA.
RP Ay, H (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging,Dept Radiol, 149 13th St,Room 2301, Boston, MA 02129 USA.
EM hay@partners.org
RI Arsava, Ethem Murat/I-9197-2013;
OI Arsava, Ethem Murat/0000-0002-6527-4139; Smith, Eric/0000-0003-3956-1668
FU NIH [R01-NS059727, R01-NS051412, P50-NS051343, R01-HS011392,
R01-NS038477]
FX Supported by NIH grants R01-NS059727 (J.R.), R01-NS051412 and
P50-NS051343 ( A. B. S.), P50-NS051343 ( M. H. L.), R01-HS011392 and
P50-NS051343 ( K. L. F.), and R01-NS038477 ( A. G. S.).
NR 39
TC 79
Z9 84
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD APR 21
PY 2009
VL 72
IS 16
BP 1403
EP 1410
DI 10.1212/WNL.0b013e3181a18823
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA 436DV
UT WOS:000265393700007
PM 19380699
ER
PT J
AU Bohnen, NI
Muller, MLTM
Kuwabara, H
Constantine, GM
Studenski, SA
AF Bohnen, N. I.
Mueller, M. L. T. M.
Kuwabara, H.
Constantine, G. M.
Studenski, S. A.
TI Age-associated leukoaraiosis and cortical cholinergic deafferentation
SO NEUROLOGY
LA English
DT Article
ID WHITE-MATTER HYPERINTENSITIES; HUMAN-BRAIN; ACETYLCHOLINESTERASE
ACTIVITY; PARKINSONS-DISEASE; ALZHEIMER-DISEASE; RATING-SCALE; IN-VIVO;
DENERVATION; PATHWAYS; PERFORMANCE
AB Objective: To investigate the relationship between age-associated MRI leukoaraiosis or white matter hyperintensities (WMH) and cortical acetylcholinesterase (AChE) activity.
Background: One possible mechanism of cognitive decline in elderly individuals with leukoaraiosis is disruption of cholinergic fibers by strategically located white matter lesions. Periventricular lesions may have a higher chance of disrupting cholinergic projections compared with more superficial nonperiventricular white matter lesions because of anatomic proximity to the major cholinergic axonal projection bundles that originate from the basal forebrain.
Methods: Community-dwelling, middle-aged and elderly subjects without dementia (mean age 71.0 +/- 9.2 years; 55-84 years; n = 18) underwent brain MRI and AChE PET imaging. The severity of periventricular and nonperiventricular WMH on fluid-attenuated inversion recovery MRI images was scored using the semiquantitative rating scale of Scheltens et al. [(11)C] methyl-4-piperidinyl propionate AChE PET imaging was used to assess cortical AChE activity. Age-corrected Spearman partial rank correlation coefficients were calculated.
Results: The severity of periventricular (R = -0.52, p = 0.04) but not nonperiventricular (R = -0.20, not significant) WMH was inversely related to global cortical AChE activity. Regional cortical cholinergic effects of periventricular WMH were most significant for the occipital lobe (R = -0.58, p = 0.02).
Conclusions: The presence of periventricular but not nonperiventricular white matter hyperintensities (WMH) is significantly associated with lower cortical cholinergic activity. These findings support a regionally specific disruption of cholinergic projection fibers by WMH. Neurology(R) 2009; 72: 1411-1416
C1 [Bohnen, N. I.; Mueller, M. L. T. M.] Univ Michigan, Funct Neuroimaging Cognit & Mobil Lab, Dept Radiol, Ann Arbor, MI 48105 USA.
[Bohnen, N. I.; Mueller, M. L. T. M.] Univ Michigan, Funct Neuroimaging Cognit & Mobil Lab, Dept Neurol, Ann Arbor, MI 48105 USA.
[Bohnen, N. I.] GRECC, VA Ann Arbor Healthcare Syst, Ann Arbor, MI USA.
[Kuwabara, H.] Johns Hopkins Univ, Dept Radiol, Baltimore, MD USA.
[Constantine, G. M.] Univ Pittsburgh, Dept Math & Stat, Pittsburgh, PA 15260 USA.
[Studenski, S. A.] GRECC, VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA.
[Studenski, S. A.] Univ Pittsburgh, Sch Med, Div Geriatr Med, Dept Med, Pittsburgh, PA 15260 USA.
RP Bohnen, NI (reprint author), Univ Michigan, Funct Neuroimaging Cognit & Mobil Lab, Dept Radiol, 24 Frank Lloyd Wright Dr,Box 362, Ann Arbor, MI 48105 USA.
EM nbohnen@umich.edu
RI Muller, Martijn/A-7205-2010
FU Department of Veterans Affairs and National Institute on Aging
[AG023641, AG024827]
FX Supported by the Department of Veterans Affairs and National Institute
on Aging grants AG023641 and AG024827.
NR 31
TC 13
Z9 19
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD APR 21
PY 2009
VL 72
IS 16
BP 1411
EP 1416
DI 10.1212/WNL.0b013e3181a187c6
PG 6
WC Clinical Neurology
SC Neurosciences & Neurology
GA 436DV
UT WOS:000265393700008
PM 19380700
ER
PT J
AU Yi, CR
Goldberg, MB
AF Yi, Chae-ryun
Goldberg, Marcia B.
TI Enterohemorrhagic Escherichia coli raises the I-BAR
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Editorial Material
ID ESPF(U); EFFECTOR; PROTEIN; TIR; MEMBRANES; MECHANISM; WASP
C1 [Yi, Chae-ryun; Goldberg, Marcia B.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Cambridge, MA 02139 USA.
RP Goldberg, MB (reprint author), Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Cambridge, MA 02139 USA.
EM mgoldberg1@partners.org
FU NIAID NIH HHS [R01 AI081724]
NR 12
TC 3
Z9 3
U1 0
U2 1
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD APR 21
PY 2009
VL 106
IS 16
BP 6431
EP 6432
DI 10.1073/pnas.0902773106
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 437SI
UT WOS:000265506800003
PM 19380713
ER
PT J
AU Letai, A
AF Letai, Anthony
TI Puma strikes Bax
SO JOURNAL OF CELL BIOLOGY
LA English
DT Editorial Material
ID MITOCHONDRIAL-MEMBRANE PERMEABILIZATION; BCL-2 FAMILY-MEMBERS;
ACTIVATION; APOPTOSIS; DEATH; P53; LIGAND
AB The commitment to programmed cell death via apoptosis is largely made upon activation of the proapoptotic mitochondrial proteins Bax or Bak. In this issue, Gallenne et al. (Gallenne, T., F. Gautier, L. Oliver, E. Hervouet, B. Noel, J.A. Hickman, O. Geneste, P.-F. Cartron, F.M. Vallette, S. Manon, and P. Juin. 2009. J. Cell Biol. 185: 279-290) provide evidence that the p53 up-regulated modulator of apoptosis (Puma) protein can directly activate Bax.
C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
RP Letai, A (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
EM anthony_letai@dfci.harvard.edu
NR 19
TC 21
Z9 23
U1 0
U2 1
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0021-9525
J9 J CELL BIOL
JI J. Cell Biol.
PD APR 20
PY 2009
VL 185
IS 2
BP 189
EP 191
DI 10.1083/jcb.200903134
PG 3
WC Cell Biology
SC Cell Biology
GA 439AR
UT WOS:000265599200005
PM 19380876
ER
PT J
AU Kilbridge, KL
Fraser, G
Krahn, M
Nelson, EM
Conaway, M
Bashore, R
Wolf, A
Barry, MJ
Gong, DA
Nease, RF
Connors, AF
AF Kilbridge, Kerry L.
Fraser, Gertrude
Krahn, Murray
Nelson, Elizabeth M.
Conaway, Mark
Bashore, Randall
Wolf, Andrew
Barry, Michael J.
Gong, Debra A.
Nease, Robert F., Jr.
Connors, Alfred F.
TI Lack of Comprehension of Common Prostate Cancer Terms in an Underserved
Population
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article; Proceedings Paper
CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology
CY JUN 02-06, 2006
CL Atlanta, GA
SP Amer Soc Clin Oncol
ID QUALITY-OF-LIFE; DECISION-ANALYSIS; INFORMED-CONSENT; RADICAL
PROSTATECTOMY; HEALTH LITERACY; MEDICARE SURVEY; PATIENT; OUTCOMES;
ANTIGEN; MEN
AB Purpose
To assess the comprehension of common medical terms used in prostate cancer in patient education materials to obtain informed consent, and to measure outcomes after prostate cancer treatment. We address this issue among underserved, African-American men because of the increased cancer incidence and mortality observed in this population.
Patients and Methods
We reviewed patient education materials and prostate-specific quality-of-life instruments to identify technical terms describing sexual, urinary, and bowel function. Understanding of these terms was assessed in face-to-face interviews of 105, mostly African-American men, age >= 40, from two low-income clinics. Comprehension was evaluated using semiqualitative methods coded by two independent investigators. Demographics were collected and literacy was measured.
Results
Fewer than 50% of patients understood the terms "erection" or "impotent." Only 5% of patients understood the term "incontinence" and 25% understood the term "bowel habits." More patients recognized word roots than related terms or compound words (eg, "rectum" v "rectal urgency," "intercourse" v "vaginal intercourse"). Comprehension of terms from all domains was statistically significantly correlated with reading level (P < .001). Median literacy level was fourth to sixth grade. Prostate cancer knowledge was poor. Many patients had difficulty locating key anatomic structures.
Conclusion
Limited comprehension of prostate cancer terms and low literacy create barriers to obtaining informed consent for treatment and to measuring prostate cancer outcomes accurately in our study population. In addition, the level of prostate cancer knowledge was poor. These results highlight the need for prostate cancer education efforts and outcomes measurements that consider literacy and use nonmedical language. J Clin Oncol 27: 2015-2021. (C) 2009 by American Society of Clinical Oncology
C1 [Kilbridge, Kerry L.] Massachusetts Gen Hosp, Gen Med Unit, Boston, MA 02114 USA.
Univ Toronto, Toronto, ON, Canada.
MetroHlth Med Ctr, Cleveland, OH USA.
Express Scripts, St Louis, MO USA.
Washington Univ, St Louis, MO USA.
Jesse Brown Vet Adm Med Ctr, Chicago, IL USA.
Cent Virginia Community Hlth Ctr, Class 2007, Sch Publ Hlth, New Canton, VA USA.
Univ Virginia, Charlottesville, VA USA.
Univ N Carolina, Chapel Hill, NC USA.
RP Kilbridge, KL (reprint author), Massachusetts Gen Hosp, Gen Med Unit, 50 Staniford St,9th Floor 955, Boston, MA 02114 USA.
EM kkilbridge@partners.org
OI Krahn, Murray/0000-0001-5836-397X
FU NCI NIH HHS [K07 CA085754, KO7CA085754]
NR 69
TC 32
Z9 33
U1 2
U2 5
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD APR 20
PY 2009
VL 27
IS 12
BP 2015
EP 2021
DI 10.1200/JCO.2008.17.3468
PG 7
WC Oncology
SC Oncology
GA 447MH
UT WOS:000266194700017
PM 19307512
ER
PT J
AU Egede, LE
Frueh, CB
Richardson, LK
Acierno, R
Mauldin, PD
Knapp, RG
Lejuez, C
AF Egede, Leonard E.
Frueh, Christopher B.
Richardson, Lisa K.
Acierno, Ronald
Mauldin, Patrick D.
Knapp, Rebecca G.
Lejuez, Carl
TI Rationale and design: telepsychology service delivery for depressed
elderly veterans
SO TRIALS
LA English
DT Article
ID BEHAVIORAL ACTIVATION TREATMENT; POSTTRAUMATIC-STRESS-DISORDER;
LONGITUDINAL PSYCHIATRIC DATA; RANDOM REGRESSION-MODELS; SAMPLE-SIZE
FORMULAS; QUALITY-OF-LIFE; ESTABLISH EQUIVALENCE; RANDOMIZED-TRIAL;
CLINICAL-TRIALS; NULL HYPOTHESIS
AB Background: Older adults who live in rural areas experience significant disparities in health status and access to mental health care. "Telepsychology," (also referred to as " telepsychiatry," or " telemental health") represents a potential strategy towards addressing this longstanding problem. Older adults may benefit from telepsychology due to its: (1) utility to address existing problematic access to care for rural residents; (2) capacity to reduce stigma associated with traditional mental health care; and (3) utility to overcome significant age-related problems in ambulation and transportation. Moreover, preliminary evidence indicates that telepsychiatry programs are often less expensive for patients, and reduce travel time, travel costs, and time off from work. Thus, telepsychology may provide a cost-efficient solution to access-to-care problems in rural areas.
Methods: We describe an ongoing four-year prospective, randomized clinical trial comparing the effectiveness of an empirically supported treatment for major depressive disorder, Behavioral Activation, delivered either via in-home videoconferencing technology ("Telepsychology") or traditional face-to-face services ("Same-Room"). Our hypothesis is that inhomeTelepsychology service delivery will be equally effective as the traditional mode (Same-Room). Two-hundred twenty-four (224) male and female elderly participants will be administered protocol-driven individual Behavioral Activation therapy for depression over an 8-week period; and subjects will be followed for 12-months to ascertain longer-term effects of the treatment on three outcomes domains: (1) clinical outcomes (symptom severity, social functioning); (2) process variables (patient satisfaction, treatment credibility, attendance, adherence, dropout); and (3) economic outcomes (cost and resource use).
Discussion: Results from the proposed study will provide important insight into whether telepsychology service delivery is as effective as the traditional mode of service delivery, defined in terms of clinical, process, and economic outcomes, for elderly patients with depression residing in rural areas without adequate access to mental health services.
Trial registration: National Institutes of Health Clinical Trials Registry (ClinicalTrials.gov identifier# NCT00324701).
C1 [Egede, Leonard E.; Frueh, Christopher B.; Acierno, Ronald; Mauldin, Patrick D.; Knapp, Rebecca G.; Lejuez, Carl] Ralph H Johnson VAMC, Ctr Dis Prevent & Hlth Intervent Div Populat, Charleston, SC USA.
[Egede, Leonard E.] Med Univ S Carolina, Div Gen Internal Med & Geriatr, Charleston, SC 29425 USA.
[Egede, Leonard E.; Mauldin, Patrick D.] Med Univ S Carolina, Ctr Hlth Dispar Res, Charleston, SC 29425 USA.
[Frueh, Christopher B.] Baylor Coll Med, Menninger Clin, Houston, TX 77030 USA.
[Frueh, Christopher B.] Baylor Coll Med, Dept Psychiat, Houston, TX 77030 USA.
[Frueh, Christopher B.; Richardson, Lisa K.; Acierno, Ronald] Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA.
[Richardson, Lisa K.] Murdoch Univ, Sch Psychol, Perth, WA, Australia.
[Mauldin, Patrick D.] Med Univ S Carolina, Dept Clin Pharm & Outcome Sci, Charleston, SC 29425 USA.
[Knapp, Rebecca G.] Med Univ S Carolina, Dept Biostat Bioinformat & Epidemiol, Charleston, SC 29425 USA.
[Lejuez, Carl] Univ Maryland, Dept Psychol, College Pk, MD 20742 USA.
RP Egede, LE (reprint author), Ralph H Johnson VAMC, Ctr Dis Prevent & Hlth Intervent Div Populat, Charleston, SC USA.
EM egedel@musc.edu; frueh@bcm.edu; l.richardson@murdoch.edu.au;
acierno@musc.edu; mauldinp@musc.edu; knappr@musc.edu;
clejuez@psyc.umd.edu
FU Veterans Health Administration Health Services Research and Development
program [IIR 04-421]
FX The study was funded by grant # IIR 04-421 from the Veterans Health
Administration Health Services Research and Development program.
NR 89
TC 19
Z9 19
U1 3
U2 18
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1745-6215
J9 TRIALS
JI Trials
PD APR 20
PY 2009
VL 10
AR 22
DI 10.1186/1745-6215-10-22
PG 14
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 452HS
UT WOS:000266531600001
PM 19379517
ER
PT J
AU Mar, JC
Kimura, Y
Schroder, K
Irvine, KM
Hayashizaki, Y
Suzuki, H
Hume, D
Quackenbush, J
AF Mar, Jessica C.
Kimura, Yasumasa
Schroder, Kate
Irvine, Katharine M.
Hayashizaki, Yoshihide
Suzuki, Harukazu
Hume, David
Quackenbush, John
TI Data-driven normalization strategies for high-throughput quantitative
RT-PCR
SO BMC BIOINFORMATICS
LA English
DT Article
ID REAL-TIME; GENE-EXPRESSION; IDENTIFICATION; VALIDATION; ARRAY
AB Background: High-throughput real-time quantitative reverse transcriptase polymerase chain reaction (qPCR) is a widely used technique in experiments where expression patterns of genes are to be profiled. Current stage technology allows the acquisition of profiles for a moderate number of genes (50 to a few thousand), and this number continues to grow. The use of appropriate normalization algorithms for qPCR-based data is therefore a highly important aspect of the data preprocessing pipeline.
Results: We present and evaluate two data-driven normalization methods that directly correct for technical variation and represent robust alternatives to standard housekeeping gene-based approaches. We evaluated the performance of these methods against a single gene housekeeping gene method and our results suggest that quantile normalization performs best. These methods are implemented in freely-available software as an R package qpcrNorm distributed through the Bioconductor project.
Conclusion: The utility of the approaches that we describe can be demonstrated most clearly in situations where standard housekeeping genes are regulated by some experimental condition. For large qPCR-based data sets, our approaches represent robust, data-driven strategies for normalization.
C1 [Mar, Jessica C.; Quackenbush, John] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Kimura, Yasumasa; Hayashizaki, Yoshihide; Suzuki, Harukazu] Yokohama Inst, Omics Sci Ctr, RIKEN, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan.
[Schroder, Kate; Irvine, Katharine M.] Univ Queensland, Inst Mol Biosci, St Lucia, Qld 4072, Australia.
[Hume, David] Univ Edinburgh, Roslin Inst, Roslin EH25 9PS, Midlothian, Scotland.
[Quackenbush, John] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Quackenbush, John] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
RP Quackenbush, J (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 677 Huntington Ave, Boston, MA 02115 USA.
EM jess@jimmy.harvard.edu; y-kimura@gsc.riken.jp; k.schroder@imb.uq.edu.au;
k.irvine@imb.uq.edu.au; yoshihide@gsc.riken.jp; harukazu@gsc.riken.jp;
David.Hume@roslin.ed.ac.uk; johnq@jimmy.harvard.edu
RI Irvine, Katharine/A-5559-2011; Schroder, Kate/C-6132-2008; Kimura,
Yasumasa/M-9720-2013; Suzuki, Harukazu/N-9553-2015
OI Schroder, Kate/0000-0001-9261-3805; Suzuki, Harukazu/0000-0002-8087-0836
FU Ministry of Education, Culture, Sports, Science and Technology of the
Japanese Government; Ministry of Education, Culture, Sports, Science and
Technology, Japan; National Human Genome Research Institute of the US
National Institutes of Health [1P50 HG004233]
FX We gratefully acknowledge the contribution of Kayoko Murakami for
generating the qPCR data. We also acknowledge the support of a research
grant for the RIKEN Omics Science Center from the Ministry of Education,
Culture, Sports, Science and Technology of the Japanese Government and a
grant of the Genome Network Project from the Ministry of Education,
Culture, Sports, Science and Technology, Japan. We also thank Dr Tom
Chittenden and Renee Rubio for helpful discussion and valuable feedback;
and Dr Razvan Sultana for technical help. We also thank the referees for
useful feedback and suggestions that have improved both the method and
our presentation. JCM and JQ were supported by a grant from the National
Human Genome Research Institute of the US National Institutes of Health
(1P50 HG004233).
NR 20
TC 47
Z9 47
U1 1
U2 14
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2105
J9 BMC BIOINFORMATICS
JI BMC Bioinformatics
PD APR 19
PY 2009
VL 10
AR 110
DI 10.1186/1471-2105-10-110
PG 9
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
GA 453IU
UT WOS:000266604900001
PM 19374774
ER
PT J
AU Neel, BG
Cross, FR
Pellman, D
AF Neel, Benjamin G.
Cross, Frederick R.
Pellman, David
TI Hidesaburo Hanafusa 1929-2009 Obituary
SO CELL
LA English
DT Biographical-Item
C1 [Neel, Benjamin G.] Univ Toronto, Ontario Canc Inst, Toronto, ON M4W 2V1, Canada.
[Cross, Frederick R.] Rockefeller Univ, New York, NY 10065 USA.
[Pellman, David] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Neel, BG (reprint author), Univ Toronto, Ontario Canc Inst, Toronto, ON M4W 2V1, Canada.
EM bneel@uhnresearch.ca; fcross@rockefeller.edu;
david_pellman@dfci.harvard.edu
NR 0
TC 0
Z9 0
U1 0
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD APR 17
PY 2009
VL 137
IS 2
BP 197
EP 199
DI 10.1016/j.cell.2009.04.004
PG 3
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 437AB
UT WOS:000265456800007
ER
PT J
AU Ng, SYM
Yoshida, T
Zhang, JW
Georgopoulos, K
AF Ng, Samuel Yao-Ming
Yoshida, Toshimi
Zhang, Jiangwen
Georgopoulos, Katia
TI Genome-wide Lineage-Specific Transcriptional Networks Underscore
Ikaros-Dependent Lymphoid Priming in Hematopoietic Stem Cells
SO IMMUNITY
LA English
DT Article
ID CHROMATIN REMODELER MI-2-BETA; ACUTE LYMPHOBLASTIC-LEUKEMIA;
BONE-MARROW; PROGENITOR CELLS; MULTIPOTENT PROGENITORS; GENE-EXPRESSION;
SELF-RENEWAL; COMMITMENT; RECEPTOR; PROTEINS
AB The mechanisms regulating lineage potential during early hematopoiesis were investigated. First, a cascade of lineage-affiliated gene expression signatures, primed in hematopoietic stem cells (HSCs) and differentially propagated in lineage-restricted progenitors, was identified. Lymphoid transcripts were primed as early as the HSC, together with myeloid and erythroid transcripts. Although this multilineage priming was resolved upon subsequent lineage restrictions, an unexpected cosegregation of lymphoid and myeloid gene expression and potential past a nominal myeloid restriction point was identified. Finally, we demonstrated that whereas the zinc finger DNA-binding factor Ikaros was required for induction of lymphoid lineage priming in the HSC, it was also necessary for repression of genetic programs compatible with self-renewal and multipotency downstream of the HSC. Taken together, our studies provide new insight into the priming and restriction of lineage potentials during early hematopoiesis and identify Ikaros as a key bivalent regulator of this process.
C1 [Ng, Samuel Yao-Ming; Yoshida, Toshimi; Georgopoulos, Katia] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA.
[Zhang, Jiangwen] Harvard Univ, FAS Ctr Syst Biol, Cambridge, MA 02138 USA.
RP Georgopoulos, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA.
EM katia.georgopoulos@cbrc2.mgh.harvard.edu
RI Zhang, Jiangwen/A-7654-2013
FU National Institutes of Health [NIH-R37-AI33062-16, NIH-R01-AI42254-11]
FX This work was supported by National Institutes of Health grants
NIH-R37-AI33062-16 and NIH-R01-AI42254-11 to K.G. We thank Bob Czyzewski
for mouse husbandry, and we thank the K.G. lab and Bruce Morgan for a
critical review of the manuscript.
NR 56
TC 128
Z9 128
U1 1
U2 10
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-7613
J9 IMMUNITY
JI Immunity
PD APR 17
PY 2009
VL 30
IS 4
BP 493
EP 507
DI 10.1016/j.immuni.2009.01.014
PG 15
WC Immunology
SC Immunology
GA 435BT
UT WOS:000265319000007
PM 19345118
ER
PT J
AU Savina, A
Peres, A
Cebrian, I
Carmo, N
Moita, C
Hacohen, N
Moita, LF
Amigorena, S
AF Savina, Ariel
Peres, Audrey
Cebrian, Ignacio
Carmo, Nuno
Moita, Catarina
Hacohen, Nir
Moita, Luis F.
Amigorena, Sebastian
TI The Small GTPase Rac2 Controls Phagosomal Alkalinization and Antigen
Crosspresentation Selectively in CD8(+) Dendritic Cells
SO IMMUNITY
LA English
DT Article
ID NUCLEOTIDE EXCHANGE FACTOR; PHAGOCYTE NADPH OXIDASE; IN-VIVO;
CROSS-PRESENTATION; PRESENTING CELLS; RHO-GTPASES; MURINE MACROPHAGES;
CATHEPSIN-S; ACTIVATION; LOCALIZATION
AB A unique subpopulation of spleen dendritic cells (DCs) that express the CD8 surface marker efficiently present phagocytosed antigens to CD8(+) T lymphocytes in a process called "crosspresentation," which initiates cytotoxic immune responses. We now show that the small GTPase Rac2 plays a critical role in antigen crosspresentation selectively in this DC subpopulation. In CD8(+) DCs, Rac2 determines the subcellular assembly of the NADPH oxidase complex (NOX2) to phagosomes, whereas in CD8(-) DCs, Rac1 mediates the assembly of NOX2 at the plasma membrane. In the absence of Rac2, the production of reactive oxygen species (ROS) in DC-phagosomes was abolished, the phagosomal pH dropped, and the efficiency of antigen crosspresentation was reduced. We conclude that the activity of Racl and 2 control crosspresentation in DC subpopulations through the regulation of phagosomal oxidation and pH.
C1 [Savina, Ariel; Peres, Audrey; Cebrian, Ignacio; Amigorena, Sebastian] Inst Curie, INSERM U653, F-75248 Paris 05, France.
[Carmo, Nuno; Moita, Catarina; Moita, Luis F.] Univ Lisbon, Fac Med, Inst Mol Med, Cell Biol Immune Syst Unit, P-1649028 Lisbon, Portugal.
[Hacohen, Nir] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA.
[Hacohen, Nir] Broad Inst Harvard, Cambridge, MA 02142 USA.
[Hacohen, Nir] MIT, Cambridge, MA USA.
RP Savina, A (reprint author), Inst Curie, INSERM U653, 26 Rue Ulm, F-75248 Paris 05, France.
EM ariel.savina@curie.fr; sebastian.amigorena@curie.fr
RI Moita, Luis/L-1296-2013;
OI Moita, Luis/0000-0003-0707-315X; Ferreira Moita,
Catarina/0000-0002-9910-2343
FU Institut National de la Sainte et de la Recherche Medicale (INSERM);
Ligue National de Lutte contre le Cancer (LLNC); Institut Curie; Contrat
CEE DC-Thera [LSBH-CT-2004-512074, LSHC-CT-2006-518234]; Fondation
Bettencourt and Association de Recherche contre le Cancer; Fundacao,
Luso-Americana para o Desenvolvimento and Fundacao para a Ciencia e a
Tecnologia [PTDC/SAU-MII/69280/2006, PTDC/SAU-MII/78333/2006]
FX We are grateful to J. Villadangos and P. Schnorrer (Melbourne
University) for help with the DC sorting protocols. We also specially
thank A. Boissonnas, C. Hivroz, S. Dogniaux, S. Krumeich, and K. Chemin
for experimental help and reagents and A. Lennon for comments on the
manuscript. This work was supported by Institut National de la Sainte et
de la Recherche Medicale (INSERM), Ligue National de Lutte contre le
Cancer (LLNC), the Institut Curie, Contrat CEE DC-Thera No
LSBH-CT-2004-512074 "Dendritic Cells for novel immunotherapies" and
Contrat CEE CancerImmunotherapy LSHC-CT-2006-518234 "Cancer Immunology
and Immunotherapy," Fondation Bettencourt and Association de Recherche
contre le Cancer (prix L. Griffuel), and Fundacao, Luso-Americana para o
Desenvolvimento and Fundacao para a Ciencia e a Tecnologia
(PTDC/SAU-MII/69280/2006 and PTDC/SAU-MII/78333/2006). A.S. was
supported by INSERM; A.P. by LLNC.
NR 44
TC 121
Z9 124
U1 3
U2 10
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-7613
J9 IMMUNITY
JI Immunity
PD APR 17
PY 2009
VL 30
IS 4
BP 544
EP 555
DI 10.1016/j.immuni.2009.01.013
PG 12
WC Immunology
SC Immunology
GA 435BT
UT WOS:000265319000011
PM 19328020
ER
PT J
AU Menze, MA
Boswell, L
Toner, M
Hand, SC
AF Menze, Michael A.
Boswell, Leaf
Toner, Mehmet
Hand, Steven C.
TI Occurrence of Mitochondria-targeted Late Embryogenesis Abundant (LEA)
Gene in Animals Increases Organelle Resistance to Water Stress
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID ARTEMIA-FRANCISCANA EMBRYOS; SHOCK/ALPHA-CRYSTALLIN PROTEIN;
MAMMALIAN-CELLS; INTRACELLULAR TREHALOSE; DESICCATION TOLERANCE;
ENHANCED PROTECTION; MEMBRANE INTEGRITY; DIVALENT-CATIONS; IMPORT
MACHINERY; IN-VITRO
AB Anhydrobiotic animals survive virtually complete loss of cellular water. The mechanisms that explain this phenomenon are not fully understood but often include the accumulation of low molecular weight solutes such as trehalose and macromolecules like Late Embryogenesis Abundant (LEA) proteins. Here we report for the first time the occurrence of a mitochondria-targeted LEA gene (Afrlea3m) product in an animal species. The deduced molecular mass of the 307-amino acid polypeptide from the brine shrimp Artemia franciscana is 34 kDa. Bioinformatic analyses reveal features typical of a Group 3 LEA protein, and subcellular localization programs predict targeting of the mature peptide to the mitochondrial matrix, based on an N-terminal, amphipathic presequence. Real-time quantitative PCR shows that Afralea3m mRNA is expressed manyfold higher in desiccation-tolerant embryonic stages when compared with intolerant nauplius larvae. Mitochondrial localization of the protein was confirmed by transfection of human hepatoma cells (HepG2/C3A) with a nucleotide construct encoding the first 70 N-terminal amino acids of AfrLEA3m in-frame with the nucleotide sequence for green fluorescence protein. The chimeric protein was readily incorporated into mitochondria of these cells. Successful targeting of a protein to human mitochondria by use of an arthropod signaling sequence clearly reveals the highly conserved nature of such presequences, as well as of the import machinery. Finally, mitochondria isolated from A. franciscana embryos, which naturally contain AfrLEA3m and trehalose, exhibit resistance to water stress (freezing) as evidenced by an unchanged capacity for oxidative phosphorylation on succinate + rotenone, a resistance that is absent in mammalian mitochondria lacking AfrLEA3m.
C1 [Menze, Michael A.; Boswell, Leaf; Hand, Steven C.] Louisiana State Univ, Dept Biol Sci, Div Cellular Dev & Integrat Biol, Baton Rouge, LA 70803 USA.
[Toner, Mehmet] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med & Surg Serv, Charlestown, MA 02129 USA.
RP Menze, MA (reprint author), Louisiana State Univ, Dept Biol Sci, Div Cellular Dev & Integrat Biol, 202 Life Sci Bldg, Baton Rouge, LA 70803 USA.
EM menze@lsu.edu
OI Menze, Michael/0000-0003-1072-5462
FU National Institutes of Health [2 RO1 DK046270-14A1]
FX This work was supported, in whole or in part, by National Institutes of
Health Grant 2 RO1 DK046270-14A1.
NR 59
TC 35
Z9 38
U1 2
U2 10
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD APR 17
PY 2009
VL 284
IS 16
BP 10714
EP 10719
DI 10.1074/jbc.C900001200
PG 6
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 431ZZ
UT WOS:000265104600045
PM 19228698
ER
PT J
AU Kitagaki, H
Cowart, LA
Matmati, N
Montefusco, D
Gandy, J
de Avalos, SV
Novgorodo, SA
Zheng, J
Obeid, LM
Hannun, YA
AF Kitagaki, Hiroshi
Cowart, L. Ashley
Matmati, Nabil
Montefusco, David
Gandy, Jason
de Avalos, Silvia Vaena
Novgorodo, Sergei A.
Zheng, Jim
Obeid, Lina M.
Hannun, Yusuf A.
TI ISC1-dependent Metabolic Adaptation Reveals an Indispensable Role for
Mitochondria in Induction of Nuclear Genes during the Diauxic Shift in
Saccharomyces cerevisiae
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID PHOSPHOSPHINGOLIPID-PHOSPHOLIPASE-C; SPHINGOLIPID BIOSYNTHESIS;
RETROGRADE RESPONSE; LINKS METABOLISM; GENOME STABILITY; YEAST
LONGEVITY; RTG2 PROTEIN; EXPRESSION; ACTIVATION; KINASE
AB Growth of Saccharomyces cerevisiae following glucose depletion ( the diauxic shift) depends on a profound metabolic adaptation accompanied by a global reprogramming of gene expression. In this study, we provide evidence for a heretofore unsuspected role for Isc1p in mediating this reprogramming. Initial studies revealed that yeast cells deleted in ISC1, the gene encoding inositol sphingolipid phospholipase C, which resides in mitochondria in the post-diauxic phase, showed defective aerobic respiration in the post-diauxic phase but retained normal intrinsic mitochondrial functions, including intact mitochondrial DNA, normal oxygen consumption, and normal mitochondrial polarization. Microarray analysis revealed that the Delta isc1 strain failed to up-regulate genes required for nonfermentable carbon source metabolism during the diauxic shift, thus suggesting a mechanism for the defective supply of respiratory substrates into mitochondria in the post-diauxic phase. This defect in regulating nuclear gene induction in response to a defect in a mitochondrial enzyme raised the possibility that mitochondria may initiate diauxic shift-associated regulation of nucleus-encoded genes. This was established by demonstrating that in respiratory-deficient petite cells these genes failed to be upregulated across the diauxic shift in a manner similar to the Delta isc1 strain. Isc1p- and mitochondrial function-dependent genes significantly overlapped with Adr1p-, Snf1p-, and Cat8p-dependent genes, suggesting some functional link among these factors. However, the retrograde response was not activated in Delta isc1, suggesting that the response of Delta isc1 cannot be simply attributed to mitochondrial dysfunction. These results suggest a novel role for Isc1p in allowing the reprogramming of gene expression during the transition from anaerobic to aerobic metabolism.
C1 [Kitagaki, Hiroshi; Cowart, L. Ashley; Matmati, Nabil; Montefusco, David; Gandy, Jason; de Avalos, Silvia Vaena; Zheng, Jim; Hannun, Yusuf A.] Med Univ S Carolina, Dept Biochem, Charleston, SC 29425 USA.
[Kitagaki, Hiroshi; Cowart, L. Ashley; Matmati, Nabil; Montefusco, David; Gandy, Jason; de Avalos, Silvia Vaena; Zheng, Jim; Hannun, Yusuf A.] Med Univ S Carolina, Dept Mol Biol, Charleston, SC 29425 USA.
[Novgorodo, Sergei A.; Obeid, Lina M.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA.
[Cowart, L. Ashley; Obeid, Lina M.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA.
[Kitagaki, Hiroshi] Saga Univ, Fac Agr, Saga 8408502, Japan.
RP Hannun, YA (reprint author), Med Univ S Carolina, Dept Biochem, 173 Ashley Ave,POB 250509, Charleston, SC 29425 USA.
EM hannun@musc.edu
OI obeid, lina/0000-0002-0734-0847
FU National Institutes of Health [GM43825, R01 AG016583]; Veterans Affairs
Merit Award; Merit Review Entry Program Award; Department of Veterans
Affairs, Office of Research and Development; Noda Institute for
Scientific Research
FX This work was supported, in whole or in part, by National Institutes of
Health Grant GM43825 ( to Y. A. H.) and Grant R01 AG016583 ( to L. M.
O.). This work was also supported by a Veterans Affairs Merit Award ( to
L. M. O.), a Merit Review Entry Program Award ( to L. A. C.) from the
Department of Veterans Affairs, Office of Research and Development, and
in part by an NISR research grant from the Noda Institute for Scientific
Research ( to H. K.). The costs of publication of this article were
defrayed in part by the payment of page charges. This article must
therefore be hereby marked " advertisement" in accordance with 18 U. S.
C. Section 1734 solely to indicate this fact.
NR 45
TC 40
Z9 40
U1 0
U2 5
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD APR 17
PY 2009
VL 284
IS 16
BP 10818
EP 10830
DI 10.1074/jbc.M805029200
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 431ZZ
UT WOS:000265104600056
PM 19179331
ER
PT J
AU Butt, MU
Zacharias, N
Velmahos, GC
AF Butt, Muhammad U.
Zacharias, Nikolaos
Velmahos, George C.
TI Penetrating abdominal injuries: management controversies
SO SCANDINAVIAN JOURNAL OF TRAUMA RESUSCITATION & EMERGENCY MEDICINE
LA English
DT Review
ID SELECTIVE NONOPERATIVE MANAGEMENT; GUNSHOT WOUNDS; STAB WOUNDS;
COMPUTED-TOMOGRAPHY; ROUTINE LAPAROTOMY; TRAUMA; ABDOMEN; DIAPHRAGM;
DURATION; BACK
AB Penetrating abdominal injuries have been traditionally managed by routine laparotomy. New understanding of trajectories, potential for organ injury, and correlation with advanced radiographic imaging has allowed a shift towards non-operative management of appropriate cases. Although a selective approach has been established for stab wounds, the management of abdominal gunshot wounds remains a matter of controversy. In this chapter we describe the rationale and methodology of selecting patients for non-operative management. We also discuss additional controversial issues, as related to antibiotic prophylaxis, management of asymptomatic thoracoabdominal injuries, and the use of colostomy vs. primary repair for colon injuries.
C1 [Velmahos, George C.] Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Velmahos, GC (reprint author), Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA.
EM umarbutt177@gmail.com; nzacharias@partners.org; gvelmahos@partners.org
NR 31
TC 18
Z9 18
U1 1
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1757-7241
J9 SCAND J TRAUMA RESUS
JI Scand. J. Trauma Resusc. Emerg. Med.
PD APR 17
PY 2009
VL 17
AR 19
DI 10.1186/1757-7241-17-19
PG 7
WC Emergency Medicine
SC Emergency Medicine
GA 665HU
UT WOS:000283026800002
PM 19374761
ER
PT J
AU Treon, SP
Branagan, AR
Ioakimidis, L
Soumerai, JD
Patterson, CJ
Turnbull, B
Wasi, P
Emmanouilides, C
Frankel, SR
Lister, A
Morel, P
Matous, J
Gregory, SA
Kimby, E
AF Treon, Steven P.
Branagan, Andrew R.
Ioakimidis, Leukothea
Soumerai, Jacob D.
Patterson, Christopher J.
Turnbull, Barry
Wasi, Parveen
Emmanouilides, Christos
Frankel, Stanley R.
Lister, Andrew
Morel, Pierre
Matous, Jeffrey
Gregory, Stephanie A.
Kimby, Eva
TI Long-term outcomes to fludarabine and rituximab in Waldenstrom
macroglobulinemia
SO BLOOD
LA English
DT Article
ID CHRONIC LYMPHOCYTIC-LEUKEMIA; 3RD INTERNATIONAL WORKSHOP;
COOPERATIVE-ONCOLOGY-GROUP; MANTLE-CELL LYMPHOMA; MULTIPLE-MYELOMA;
PHASE-II; TREATMENT RECOMMENDATIONS; FOLLICULAR LYMPHOMA; PROGNOSTIC
FACTORS; LOW-GRADE
AB We report the long-term outcome of a multicenter, prospective study examining fludarabine and rituximab in Waldenstrom macroglobulinemia (WM). WM patients with less than 2 prior therapies were eligible. Intended therapy consisted of 6 cycles (25 mg/m(2) per day for 5 days) of fludarabine and 8 infusions (375 mg/m(2) per week) of rituximab. A total of 43 patients were enrolled. Responses were: complete response (n = 2), very good partial response (n = 14), partial response (n = 21), and minor response (n = 4), for overall and major response rates of 95.3% and 86.0%, respectively. Median time to progression for all patients was 51.2 months and was longer for untreated patients (P = .017) and those achieving at least a very good partial response (P = .049). Grade 3 or higher toxicities included neutropenia (n = 27), thrombocytopenia (n = 7), and pneumonia (n = 6), including 2 patients who died of non-Pneumocystis carinii pneumonia. With a median follow-up of 40.3 months, we observed 3 cases of transformation to aggressive lymphoma and 3 cases of myelodysplastic syndrome/acute myeloid leukemia. The results of this study demonstrate that fludarabine and rituximab are highly active in WM, although short- and long-term toxicities need to be carefully weighed against other available treatment options. This study is registered at clinicaltrials.gov as NCT00020800. (Blood. 2009; 113: 3673-3678)
C1 [Treon, Steven P.; Branagan, Andrew R.; Ioakimidis, Leukothea; Soumerai, Jacob D.; Patterson, Christopher J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, Boston, MA 02115 USA.
[Wasi, Parveen] McMaster Univ, Med Ctr, Hamilton, ON, Canada.
[Turnbull, Barry] BioBridges, Boston, MA USA.
[Emmanouilides, Christos] Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA.
[Frankel, Stanley R.] Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA.
[Lister, Andrew] St Bartholomews Hosp & Canc Res, London, England.
[Morel, Pierre] Ctr Hosp Schaffner, Lens, France.
[Matous, Jeffrey] Rocky Mt Canc Ctr, Denver, CO USA.
[Gregory, Stephanie A.] Rush Univ, Med Ctr, Chicago, IL 60612 USA.
[Kimby, Eva] Huddinge Univ Hosp, Karolinska Inst, Stockholm, Sweden.
RP Treon, SP (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, M547,44 Binney St, Boston, MA 02115 USA.
EM steven_treon@dfci.harvard.edu
FU Dana-Farber Cancer Institute; Berlex Pharmaceuticals; Genentech; Biogen
IDEC; Bing Fund for Waldenstrom macroglobulinemia; National Institutes
of Health Career Development Award [K23CA087977-03]
FX This work was supported by the Research Fund for Waldenstrom's at the
Dana-Farber Cancer Institute, Berlex Pharmaceuticals, Genentech, Biogen
IDEC, the Bing Fund for Waldenstrom macroglobulinemia, and a National
Institutes of Health Career Development Award (K23CA087977-03) (S.P.T.).
NR 40
TC 69
Z9 71
U1 0
U2 1
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD APR 16
PY 2009
VL 113
IS 16
BP 3673
EP 3678
DI 10.1182/blood-2008-09-177329
PG 6
WC Hematology
SC Hematology
GA 436WD
UT WOS:000265445900006
PM 19015393
ER
PT J
AU Ali, N
Karlsson, C
Aspling, M
Hu, G
Hacohen, N
Scadden, DT
Larsson, J
AF Ali, Nicole
Karlsson, Christine
Aspling, Marie
Hu, Guang
Hacohen, Nir
Scadden, David T.
Larsson, Jonas
TI Forward RNAi screens in primary human hematopoietic stem/progenitor
cells
SO BLOOD
LA English
DT Article
ID NOD/SCID REPOPULATING CELLS; CULTURE-INITIATING CELLS; VECTOR
TRANSDUCTION; GENETIC SCREEN; SECONDARY
AB The mechanisms regulating key fate decisions such as self-renewal and differentiation in hematopoietic stem and progenitor cells (HSPC) remain poorly understood. We report here a screening strategy developed to assess modulators of human hematopoiesis using a lentiviral short hairpin RNA (shRNA) library transduced into cord blood-derived stem/progenitor cells. To screen for modifiers of self-renewal/differentiation, we used the limited persistence of HSPCs under ex vivo culture conditions as a baseline for functional selection of shRNAs conferring enhanced maintenance or expansion of the stem/progenitor potential. This approach enables complex, pooled screens in large numbers of cells. Functional selection identified novel specific gene targets (exostoses 1) or shRNA constructs capable of altering human hematopoietic progenitor differentiation or stem cell expansion, respectively, thereby demonstrating the potential of this forward screening approach in primary human stem cell populations. (Blood. 2009; 113: 3690-3695)
C1 [Ali, Nicole; Aspling, Marie; Scadden, David T.; Larsson, Jonas] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA.
[Ali, Nicole; Aspling, Marie; Scadden, David T.; Larsson, Jonas] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
[Karlsson, Christine; Larsson, Jonas] Lund Univ, Lund Stem Cell Ctr, Lund, Sweden.
[Hu, Guang] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Genet,Ctr Genet & Genom, Boston, MA 02114 USA.
[Hu, Guang] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02114 USA.
[Hacohen, Nir] Broad Inst Massachusetts Inst Technol, Cambridge, MA USA.
[Hacohen, Nir] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Cambridge, MA 02138 USA.
[Scadden, David T.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
RP Scadden, DT (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Regenerat Med, 185 Cambridge St,CPZN 4265A, Boston, MA 02114 USA.
EM scadden.david@mgh.harvard.edu; jonas.larsson@med.lu.se
RI Hu, Guang/E-7474-2016
OI Hu, Guang/0000-0003-0437-4723
FU National Institutes of Health (Bethesda, MD); Swedish Cancer Foundation
(Stockholm, Sweden); Swedish Childhood Cancer Foundation (Stockholm,
Sweden)
FX This work was supported by National Institutes of Health (Bethesda, MD)
grants to D.T.S. and grants from the Swedish Cancer Foundation
(Stockholm, Sweden) and the Swedish Childhood Cancer Foundation
(Stockholm, Sweden) to J.L.
NR 14
TC 19
Z9 20
U1 0
U2 0
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD APR 16
PY 2009
VL 113
IS 16
BP 3690
EP 3695
DI 10.1182/blood-2008-10-176396
PG 6
WC Hematology
SC Hematology
GA 436WD
UT WOS:000265445900009
PM 19188664
ER
PT J
AU Sarantopoulos, S
Stevenson, KE
Kim, HT
Cutler, CS
Bhuiya, NS
Schowalter, M
Ho, VT
Alyea, EP
Koreth, J
Blazar, BR
Soiffer, RJ
Antin, JH
Ritz, J
AF Sarantopoulos, Stefanie
Stevenson, Kristen E.
Kim, Haesook T.
Cutler, Corey S.
Bhuiya, Nazmim S.
Schowalter, Michael
Ho, Vincent T.
Alyea, Edwin P.
Koreth, John
Blazar, Bruce R.
Soiffer, Robert J.
Antin, Joseph H.
Ritz, Jerome
TI Altered B-cell homeostasis and excess BAFF in human chronic
graft-versus-host disease
SO BLOOD
LA English
DT Article
ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; MINOR HISTOCOMPATIBILITY ANTIGENS;
BONE-MARROW TRANSPLANTATION; SJOGRENS-SYNDROME; CUTTING EDGE; LYMPHOCYTE
STIMULATOR; TOLERANCE CHECKPOINTS; ACTIVATING FACTOR; CHRONIC GVHD;
AUTOANTIBODIES
AB Chronic graft-versus-host disease (cGVHD) causes significant morbidity and mortality in patients otherwise cured of malignancy after hematopoietic stem cell transplantation (HSCT). The presence of alloantibodies and high plasma B cell activating factor (BAFF) levels in patients with cGVHD suggest that B cells play a role in disease pathogenesis. We performed detailed phenotypic and functional analyses of peripheral B cells in 82 patients after HSCT. Patients with cGVHD had significantly higher BAFF/B-cell ratios compared with patients without cGVHD or healthy donors. In cGVHD, increasing BAFF concentrations correlated with increased numbers of circulating pre-germinal center (GC) B cells and post-GC "plasmablast-like" cells, suggesting in vivo BAFF dependence of these 2 CD27(+) B-cell subsets. Circulating CD27(+) B cells in cGVHD comprised in vivo activated B cells capable of IgG production without requiring additional antigen stimulation. Serial studies revealed that patients who subsequently developed cGVHD had delayed reconstitution of naive B cells despite persistent BAFF elevation as well as proportional increase in CD27(+) B cells in the first year after HSCT. These studies delineate specific abnormalities of B-cell homeostasis in patients with cGVHD and suggest that BAFF targeting agents may be useful in this disease. (Blood. 2009; 113: 3865-3874)
C1 [Sarantopoulos, Stefanie; Cutler, Corey S.; Bhuiya, Nazmim S.; Schowalter, Michael; Ho, Vincent T.; Alyea, Edwin P.; Koreth, John; Soiffer, Robert J.; Antin, Joseph H.; Ritz, Jerome] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA.
[Sarantopoulos, Stefanie; Cutler, Corey S.; Bhuiya, Nazmim S.; Schowalter, Michael; Ho, Vincent T.; Alyea, Edwin P.; Koreth, John; Soiffer, Robert J.; Antin, Joseph H.; Ritz, Jerome] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Stevenson, Kristen E.; Kim, Haesook T.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Blazar, Bruce R.] Univ Minnesota, Dept Pediat, Div Bone Marrow Transplantat, Minneapolis, MN 55455 USA.
[Blazar, Bruce R.] Univ Minnesota, Ctr Canc, Minneapolis, MN 55455 USA.
[Ritz, Jerome] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA.
[Ritz, Jerome] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Boston, MA USA.
RP Sarantopoulos, S (reprint author), Dana Farber Canc Inst, Div Hematol Malignancies, 44 Binney St,M530, Boston, MA 02115 USA.
EM stefanie_sarantopoulos@dfci.harvard.edu
OI Ritz, Jerome/0000-0001-5526-4669
FU Leukemia & Lymphoma Society; Jock and Bunny Adams Research and Education
Endowment; Ted and Eileen Pasquarello Research Fund; National Institutes
of Health [AI29530, HL70149, K12CA087723]
FX This study was supported by the Leukemia & Lymphoma Society (White
Plains, NY), Jock and Bunny Adams Research and Education Endowment
(Boston, MA), Ted and Eileen Pasquarello Research Fund (Boston, MA), and
National Institutes of Health (Bethesda, MD) grants AI29530, HL70149,
and K12CA087723.
NR 63
TC 139
Z9 143
U1 1
U2 4
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD APR 16
PY 2009
VL 113
IS 16
BP 3865
EP 3874
DI 10.1182/blood-2008-09-177840
PG 10
WC Hematology
SC Hematology
GA 436WD
UT WOS:000265445900029
PM 19168788
ER
PT J
AU Wang, SB
Xia, Q
Passias, P
Wood, K
Li, GA
AF Wang, Shaobai
Xia, Qun
Passias, Peter
Wood, Kirkham
Li, Guoan
TI Measurement of geometric deformation of lumbar intervertebral discs
under in-vivo weightbearing condition
SO JOURNAL OF BIOMECHANICS
LA English
DT Article
DE Lumbar spine; Spine kinematics; Disc deformation; In-vivo weightbearing;
Fluoroscopic and MR imaging
ID CREEP RESPONSE ANALYSIS; IMAGE MATCHING METHOD; AXIAL-COMPRESSION;
MOTION SEGMENT; SHEAR STRAIN; KINEMATICS; ELEMENT; DEGENERATION;
HEALTHY; SYSTEM
AB Quantitative data of spinal intervertebral disc deformation is instrumental for investigation of spinal disc pathology. In this study, we employed a combined dual fluoroscopic imaging system and the MR imaging technique to determine the lumbar disc deformation in living human subjects. Discs at L2-3, L3-4 and L4-5 levels were investigated in 8 normal subjects. The geometric deformation of the discs under full body weight loading condition (upright standing) was determined using the supine, non-weightbearing condition as a reference. The average maximum tensile deformation was -21% in compression and 24% in tension, and maximum shear deformation on the disc surface reached 26%. The data indicated that different portions of the disc are under different tensile and shear deformation. Further, discs of L2-3, L3-4 and L4-5 have different deformation behavior under the physiological weightbearing condition. In general, the higher level discs have higher deformation values. The technique used in this Study can be used to investigate the deformation behaviors of diseased discs as well as the efficacy of different surgical modalities at restoring normal disc deformation patterns. (C) 2009 Elsevier Ltd. All rights reserved.
C1 [Wang, Shaobai; Xia, Qun; Passias, Peter; Wood, Kirkham; Li, Guoan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg,Bioengn Lab, Boston, MA 02114 USA.
[Wang, Shaobai] MIT, Dept Mech Engn, Cambridge, MA 02139 USA.
RP Li, GA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg,Bioengn Lab, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA.
EM gli1@partners.org
FU NASS; Department of Orthopaedic Surgery, Massachusetts General
Hospital/Harvard Medical School
FX Support from the NASS grant and the Department of Orthopaedic Surgery,
Massachusetts General Hospital/Harvard Medical School was greatly
appreciated.
NR 25
TC 18
Z9 23
U1 0
U2 1
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0021-9290
J9 J BIOMECH
JI J. Biomech.
PD APR 16
PY 2009
VL 42
IS 6
BP 705
EP 711
DI 10.1016/j.jbiomech.2009.01.004
PG 7
WC Biophysics; Engineering, Biomedical
SC Biophysics; Engineering
GA 436WS
UT WOS:000265447400006
PM 19268946
ER
PT J
AU Chen, CC
Kennedy, RD
Sidi, S
Look, AT
D'Andrea, A
AF Chen, Clark C.
Kennedy, Richard D.
Sidi, Samuel
Look, A. Thomas
D'Andrea, Alan
TI CHK1 inhibition as a strategy for targeting fanconi anemia (FA) DNA
repair pathway deficient tumors
SO MOLECULAR CANCER
LA English
DT Article
ID DEPENDENT KINASE INHIBITOR; CELL-CYCLE CHECKPOINTS; ADVANCED SOLID
TUMORS; PHASE-I TRIAL; DAMAGE CHECKPOINT; BRCA PATHWAY; PROTEIN; CANCER;
COMBINATION; UCN-01
AB Background: DNA repair deficient tumor cells have been shown to accumulate high levels of DNA damage. Consequently, these cells become hyper-dependent on DNA damage response pathways, including the CHK1-kinase-mediated response. These observations suggest that DNA repair deficient tumors should exhibit increased sensitivity to CHK1 inhibition. Here we offer experimental evidence in support of this hypothesis.
Results: Using isogenic pairs of cell lines differing only in the Fanconi Anemia ( FA) DNA repair pathway, we showed that FA deficient cell lines were hypersensitive to CHK1 silencing by independent siRNAs as well as CHK1 pharmacologic inhibition by Go6976 and UCN-01. In parallel, an siRNA screen designed to identify gene silencings synthetically lethal with CHK1 inhibition identified genes required for FA pathway function. To confirm these findings in vivo, we demonstrated that whole zebrafish embryos, depleted for FANCD2 by a morpholino approach, were hypersensitive to Go6976. Silencing of FA genes led to hyper-activation of CHK1 and vice versa. Furthermore, inactivation of CHK1 in FA deficient cell lines caused increased accumulation of DNA strand and chromosomal breakages. These results suggest that the functions subserved by CHK1 and the FA pathway mutually compensate in maintaining genome integrity. As CHK1 inhibition has been under clinical trial in combination with cisplatin, we showed that the FA specific tumoricidal effect of CHK1 inhibition and cisplatin was synergistic.
Conclusion: Taken together, these results suggest CHK1 inhibition as a strategy for targeting FA deficient tumors.
C1 [Chen, Clark C.; Kennedy, Richard D.; D'Andrea, Alan] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA.
[Chen, Clark C.] Harvard Univ, Sch Med, Beth Israel Hosp, Dept Neurosurg, Boston, MA 02115 USA.
[Sidi, Samuel; Look, A. Thomas] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
RP D'Andrea, A (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA.
EM cchen1@partners.org; richard_kennedy@dfci.harvard.edu;
samuel_sidi@dfci.harvard.edu; thomas_look@dfci.harvard.edu;
Alan_Dandrea@dfci.harvard.edu
RI Kennedy, Richard/J-3489-2012; Chen, Clark/C-8714-2013
OI Kennedy, Richard/0000-0003-4737-6163; Chen, Clark/0000-0001-6258-9277
FU NCI NIH HHS [P50CA105009-01]; NHLBI NIH HHS [R01HL52725, P01HL54785, R37
HL052725]; NIDDK NIH HHS [R01DK43889, R01 DK043889]; PHS HHS
[(U19A1067751, P01150654]
NR 44
TC 52
Z9 54
U1 1
U2 8
PU BIOMED CENTRAL LTD
PI LONDON
PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T
4LB, ENGLAND
SN 1476-4598
J9 MOL CANCER
JI Mol. Cancer
PD APR 16
PY 2009
VL 8
AR 24
DI 10.1186/1476-4598-8-24
PG 16
WC Biochemistry & Molecular Biology; Oncology
SC Biochemistry & Molecular Biology; Oncology
GA 449IA
UT WOS:000266322900001
PM 19371427
ER
PT J
AU Devore, S
Ihlefeld, A
Hancock, K
Shinn-Cunningham, B
Delgutte, B
AF Devore, Sasha
Ihlefeld, Antje
Hancock, Kenneth
Shinn-Cunningham, Barbara
Delgutte, Bertrand
TI Accurate Sound Localization in Reverberant Environments Is Mediated by
Robust Encoding of Spatial Cues in the Auditory Midbrain
SO NEURON
LA English
DT Article
ID INTERAURAL TIME DIFFERENCES; AMPLITUDE-MODULATED TONES; INFERIOR
COLLICULUS NEURONS; SUPERIOR OLIVARY COMPLEX; LOW-FREQUENCY CELLS;
SPEECH-INTELLIGIBILITY; UNANESTHETIZED RABBIT; BINAURAL INTERACTION;
RESPONSE PROPERTIES; NEURAL MECHANISMS
AB In reverberant environments, acoustic reflections interfere with the direct sound arriving at a listener's ears, distorting the spatial cues for sound localization. Yet, human listeners have little difficulty localizing sounds in most settings. Because reverberant energy builds up overtime, the source location is represented relatively faithfully during the early portion of a sound, but this representation becomes increasingly degraded later in the stimulus. We show that the directional sensitivity of single neurons in the auditory midbrain of anesthetized cats follows a similar time course, although onset dominance in temporal response patterns results in more robust directional sensitivity than expected, suggesting a simple mechanism for improving directional sensitivity in reverberation. In parallel behavioral experiments, we demonstrate that human lateralization judgments are consistent with predictions from a population rate model decoding the observed midbrain responses, suggesting a subcortical origin for robust sound localization in reverberant environments.
C1 [Devore, Sasha; Hancock, Kenneth; Delgutte, Bertrand] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA.
[Devore, Sasha; Shinn-Cunningham, Barbara; Delgutte, Bertrand] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
[Ihlefeld, Antje; Shinn-Cunningham, Barbara] Boston Univ, Hearing Res Ctr, Boston, MA 02108 USA.
[Delgutte, Bertrand] MIT, Elect Res Lab, Cambridge, MA 02139 USA.
RP Devore, S (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA.
EM sashad@alum.mit.edu
OI , /0000-0003-1349-9608; Ihlefeld, Antje/0000-0001-7185-5848
FU National Institutes of Health (NIH) [R01 DC002258, R01 DC05778-02, P30
DC005209, T32 DC00038]
FX This work was supported by National Institutes of Health (NIH) Grants
R01 DC002258 (B.D.), R01 DC05778-02 (B.S.-C.), and core grant P30
DC005209 to Eaton Peabody Laboratory. S.D. was partially supported by
NIH Grant T32 DC00038. We thank Connie Miller for surgical assistance
and Lorraine Delhorne and Eric Larson for assistance with the behavioral
experiments. Dr. Adrian K.C. Lee provided the ILD-pointer software and
Dr. Jay Desloges provided the BRIR-simulation software. We additionally
thank three anonymous reviewers who helped us to improve this
manuscript.
NR 86
TC 42
Z9 44
U1 0
U2 6
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0896-6273
J9 NEURON
JI Neuron
PD APR 16
PY 2009
VL 62
IS 1
BP 123
EP 134
DI 10.1016/j.neuron.2009.02.018
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA 435LZ
UT WOS:000265346700014
PM 19376072
ER
PT J
AU Viel, KR
Ameri, A
Abshire, TC
Iyer, RV
Watts, RG
Lutcher, C
Channell, C
Cole, SA
Fernstrom, KM
Nakaya, S
Kasper, CK
Thompson, AR
Almasy, L
Howard, TE
AF Viel, Kevin R.
Ameri, Afshin
Abshire, Thomas C.
Iyer, Rathi V.
Watts, Raymond G.
Lutcher, Charles
Channell, Cynthia
Cole, Shelley A.
Fernstrom, Karl M.
Nakaya, Shelley
Kasper, Carol K.
Thompson, Arthur R.
Almasy, Laura
Howard, Tom E.
TI Inhibitors of Factor VIII in Black Patients with Hemophilia
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article; Proceedings Paper
CT 48th Annual Meeting of the American-Society-of-Hematology
CY DEC 09-12, 2006
CL Orlando, FL
SP Amer Soc Hematol
ID PREVIOUSLY UNTREATED PATIENTS; RECOMBINANT FACTOR-VIII; FACTOR-IX;
GENETIC ASSOCIATION; AFRICAN-AMERICANS; UNITED-STATES; F8 GENE;
MUTATIONS; RISK; INVERSION
AB BACKGROUND
Black patients with hemophilia A (factor VIII deficiency) are twice as likely as white patients to produce inhibitors against factor VIII proteins given as replacement therapy. There are six wild-type factor VIII proteins, designated H1 through H6, but only two (H1 and H2) match the recombinant factor VIII products used clinically. H1 and H2 are found in all racial groups and are the only factor VIII proteins found in the white population to date. H3, H4, and H5 have been found only in blacks. We hypothesized that mismatched factor VIII transfusions contribute to the high incidence of inhibitors among black patients.
METHODS
We sequenced the factor VIII gene (F8) in black patients with hemophilia A to identify causative mutations and the background haplotypes on which they reside. Results from previous Bethesda assays and information on the baseline severity of hemophilia, age at enrollment, and biologic relationships among study patients were obtained from review of the patients' medical charts. We used multivariable logistic regression to control for these potential confounders while testing for associations between F8 haplotype and the development of inhibitors.
RESULTS
Of the 78 black patients with hemophilia enrolled, 24% had an H3 or H4 background haplotype. The prevalence of inhibitors was higher among patients with either of these haplotypes than among patients with haplotype H1 or H2 (odds ratio, 3.6; 95% confidence interval, 1.1 to 12.3; P = 0.04), despite a similar spectrum of hemophilic mutations and degree of severity of illness in these two subgroups.
CONCLUSIONS
These preliminary results suggest that mismatched factor VIII replacement therapy may be a risk factor for the development of anti-factor VIII alloantibodies.
C1 [Viel, Kevin R.; Cole, Shelley A.; Almasy, Laura] SW Fdn Biomed Res, San Antonio, TX 78284 USA.
[Ameri, Afshin; Lutcher, Charles] Med Coll Georgia, Augusta, GA 30912 USA.
[Abshire, Thomas C.; Channell, Cynthia; Fernstrom, Karl M.] Emory Univ, Atlanta, GA 30322 USA.
[Iyer, Rathi V.] Univ Mississippi, Med Ctr, Jackson, MS USA.
[Watts, Raymond G.] Univ Alabama, Birmingham, AL USA.
[Nakaya, Shelley; Thompson, Arthur R.] Univ Washington, Seattle, WA 98195 USA.
[Kasper, Carol K.; Howard, Tom E.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA.
[Kasper, Carol K.] Orthoped Hosp, Los Angeles, CA USA.
[Howard, Tom E.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Howard, Tom E.] Greater Los Angeles Vet Affairs Hosp, Los Angeles, CA USA.
RP Howard, TE (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Dept Pathol & Lab Med, 11301 Wilshire Blvd,Bldg 500,Rm 12S4, Los Angeles, CA 90073 USA.
EM tom.howard@va.gov
FU NHLBI NIH HHS [HL-07109, HL-70751, HL-71130, HL-72533, K08 HL071130, K08
HL071130-06, R01 HL070751, R01 HL070751-07, R01 HL072533, R01
HL072533-05]
NR 53
TC 106
Z9 111
U1 0
U2 6
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD APR 16
PY 2009
VL 360
IS 16
BP 1618
EP 1627
DI 10.1056/NEJMoa075760
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 433BH
UT WOS:000265178000006
PM 19369668
ER
PT J
AU Jha, AK
DesRoches, CM
Campbell, EG
Donelan, K
Rao, SR
Ferris, TG
Shields, A
Rosenbaum, S
Blumenthal, D
AF Jha, Ashish K.
DesRoches, Catherine M.
Campbell, Eric G.
Donelan, Karen
Rao, Sowmya R.
Ferris, Timothy G.
Shields, Alexandra
Rosenbaum, Sara
Blumenthal, David
TI Use of Electronic Health Records in U. S. Hospitals
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID PHYSICIAN ORDER ENTRY; INFORMATION-TECHNOLOGY; UNITED-STATES; CARE;
QUALITY; ADOPTION; ORGANIZATIONS; SYSTEMS
AB BACKGROUND
Despite a consensus that the use of health information technology should lead to more efficient, safer, and higher-quality care, there are no reliable estimates of the prevalence of adoption of electronic health records in U. S. hospitals.
METHODS
We surveyed all acute care hospitals that are members of the American Hospital Association for the presence of specific electronic-record functionalities. Using a definition of electronic health records based on expert consensus, we determined the proportion of hospitals that had such systems in their clinical areas. We also examined the relationship of adoption of electronic health records to specific hospital characteristics and factors that were reported to be barriers to or facilitators of adoption.
RESULTS
On the basis of responses from 63.1% of hospitals surveyed, only 1.5% of U. S. hospitals have a comprehensive electronic-records system (i.e., present in all clinical units), and an additional 7.6% have a basic system (i.e., present in at least one clinical unit). Computerized provider-order entry for medications has been implemented in only 17% of hospitals. Larger hospitals, those located in urban areas, and teaching hospitals were more likely to have electronic-records systems. Respondents cited capital requirements and high maintenance costs as the primary barriers to implementation, although hospitals with electronic-records systems were less likely to cite these barriers than hospitals without such systems.
CONCLUSIONS
The very low levels of adoption of electronic health records in U. S. hospitals suggest that policymakers face substantial obstacles to the achievement of health care performance goals that depend on health information technology. A policy strategy focused on financial support, interoperability, and training of technical support staff may be necessary to spur adoption of electronic-records systems in U. S. hospitals.
C1 [Jha, Ashish K.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA.
[Jha, Ashish K.] Brigham & Womens Hosp, Div Gen Med, Boston, MA 02115 USA.
[Jha, Ashish K.] Vet Affairs Boston Healthcare Syst, Boston, MA USA.
[DesRoches, Catherine M.; Campbell, Eric G.; Donelan, Karen; Rao, Sowmya R.; Ferris, Timothy G.; Shields, Alexandra; Blumenthal, David] Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA.
[Rao, Sowmya R.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA.
[Rosenbaum, Sara] George Washington Univ, Dept Hlth Policy, Washington, DC USA.
RP Jha, AK (reprint author), Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, 677 Huntington Ave, Boston, MA 02115 USA.
EM ajha@hsph.harvard.edu
RI Tao, Youyou/D-2367-2014
FU Office of the National Coordinator for Health Information Technology in
the Department of Health and Human Services; Robert Wood Johnson
Foundation
FX Supported by grants from the Office of the National Coordinator for
Health Information Technology in the Department of Health and Human
Services and the Robert Wood Johnson Foundation.
NR 24
TC 574
Z9 581
U1 10
U2 67
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD APR 16
PY 2009
VL 360
IS 16
BP 1628
EP 1638
DI 10.1056/NEJMsa0900592
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA 433BH
UT WOS:000265178000007
PM 19321858
ER
PT J
AU Berkowitz, RS
Goldstein, DP
AF Berkowitz, Ross S.
Goldstein, Donald P.
TI Molar Pregnancy
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID GESTATIONAL TROPHOBLASTIC DISEASE; COMPLETE HYDATIDIFORM MOLE;
UNDETECTABLE HCG LEVELS; FOLLOW-UP; ORAL-CONTRACEPTIVES;
NATURAL-HISTORY; LOW-RISK; DIAGNOSIS; NEOPLASIA; MANAGEMENT
AB A healthy 37-year-old woman presents at 10 weeks of pregnancy with vaginal bleeding. Physical examination shows that the uterine size is appropriate for gestational age. The level of serum human chorionic gonadotropin (hCG) is 22,000 mIU per milliliter. Ultrasonography does not show an identifiable fetal heartbeat. After receiving a clinical diagnosis of missed abortion, the patient undergoes evacuation of the uterus; pathological examination indicates a complete molar pregnancy. How should this case be managed?
C1 [Berkowitz, Ross S.] Brigham & Womens Hosp, Div Gynecol Oncol, Dept Obstet & Gynecol, Boston, MA 02115 USA.
Trophoblast Tumor Registry, New England Trophoblast Dis Ctr, Boston, MA USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Berkowitz, RS (reprint author), Brigham & Womens Hosp, Div Gynecol Oncol, Dept Obstet & Gynecol, 75 Francis St, Boston, MA 02115 USA.
EM rberkowitz@partners.org
NR 56
TC 70
Z9 79
U1 1
U2 4
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD APR 16
PY 2009
VL 360
IS 16
BP 1639
EP 1645
DI 10.1056/NEJMcp0900696
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 433BH
UT WOS:000265178000008
PM 19369669
ER
PT J
AU Brass, SD
Smith, EE
Arboleda-Velasquez, JF
Copen, WA
Frosch, MP
AF Brass, Steven D.
Smith, Eric E.
Arboleda-Velasquez, Joseph F.
Copen, William A.
Frosch, Matthew P.
TI A Man with Migraine, Aphasia, and Hemiparesis and Similarly Affected
Family Members Cerebral autosomal dominant arteriopathy with subcortical
infarcts and leukoencephalopathy (CADASIL)
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID SMALL-VESSEL DISEASE; MULTIPLE-SCLEROSIS; NOTCH3 MUTATIONS;
DIFFERENTIAL-DIAGNOSIS; HEREDITARY; STROKE; DEMENTIA; SPECTRUM; BINDING;
MUSCLE
C1 [Brass, Steven D.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Copen, William A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Frosch, Matthew P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Smith, Eric E.] Foothills Prov Gen Hosp, Dept Neurol, Calgary, AB T2N 2T9, Canada.
[Smith, Eric E.] Univ Calgary, Dept Clin Neurosci, Calgary, AB, Canada.
[Brass, Steven D.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA.
[Arboleda-Velasquez, Joseph F.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA.
[Copen, William A.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA.
[Frosch, Matthew P.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RP Brass, SD (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
RI Smith, Eric/C-5443-2012
OI Smith, Eric/0000-0003-3956-1668
NR 40
TC 9
Z9 9
U1 0
U2 1
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD APR 16
PY 2009
VL 360
IS 16
BP 1656
EP 1665
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 433BH
UT WOS:000265178000012
PM 19369672
ER
PT J
AU Spiegel, BMR
Farid, M
Van Oijen, MGH
Laine, L
Howden, CW
Esrailian, E
AF Spiegel, B. M. R.
Farid, M.
Van Oijen, M. G. H.
Laine, L.
Howden, C. W.
Esrailian, E.
TI Adherence to best practice guidelines in dyspepsia: a survey comparing
dyspepsia experts, community gastroenterologists and primary-care
providers
SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS
LA English
DT Article
ID HELICOBACTER-PYLORI INFECTION; PROTON PUMP INHIBITORS; PHYSICIANS
PERCEPTIONS; NATIONAL-SURVEY; QUALITY; RISK; MANAGEMENT; DISORDERS;
ENDOSCOPY; THERAPY
AB Although 'best practice' guidelines for dyspepsia management have been disseminated, it remains unclear whether providers adhere to these guidelines.
To compare adherence to 'best practice' guidelines among dyspepsia experts, community gastroenterologists and primary-care providers (PCPs).
We administered a vignette survey to elicit knowledge and beliefs about dyspepsia including a set of 16 best practices, to three groups: (i) dyspepsia experts; (ii) community gastroenterologists and (iii) PCPs.
The expert, community gastroenterologist and PCP groups endorsed 75%, 73% and 57% of best practices respectively. Gastroenterologists were more likely to adhere with guidelines than PCPs (P < 0.0001). PCPs were more likely to define dyspepsia incorrectly, overuse radiographic testing, delay endoscopy, treat empirically for Helciobacter pylori without confirmatory testing and avoid first-line proton pump inhibitors (PPIs). PCPs had more concerns about adverse events with PPIs [e.g. osteoporosis (P = 0.04), community-acquired pneumonia (P = 0.01)] and higher level of concern predicted lower guideline adherence (P = 0.04).
Gastroenterologists are more likely than PCPs to comply with best practices in dyspepsia, although compliance remains incomplete in both groups. PCPs harbour more concerns regarding long-term PPI use and these concerns may affect therapeutic decision making. This suggests that best practices have not been uniformly adopted and persistent guideline-practice disconnects should be addressed.
C1 [Spiegel, B. M. R.; Farid, M.; Esrailian, E.] Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Los Angeles, CA 90095 USA.
[Spiegel, B. M. R.; Farid, M.] VA Greater Los Angeles Healthcare Syst, Dept Gastroenterol, Los Angeles, CA USA.
[Spiegel, B. M. R.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90024 USA.
[Spiegel, B. M. R.; Van Oijen, M. G. H.; Esrailian, E.] UCLA VA Ctr Outcomes Res & Educ, Los Angels, CA USA.
[Van Oijen, M. G. H.] Radboud Univ Nijmegen, Med Ctr, Dept Gastroenterol & Hepatol, NL-6525 ED Nijmegen, Netherlands.
[Laine, L.] Univ So Calif, Dept Gastroenterol, Keck Sch Med, Los Angels, CA USA.
[Howden, C. W.] Northwestern Univ, Div Gastroenterol, Feinberg Sch Med, Chicago, IL 60611 USA.
RP Spiegel, BMR (reprint author), 11301 Wilshire Blvd,Bldg 115,Room 215, Los Angeles, CA 90073 USA.
EM bspiegel@mednet.ulca.edu
FU Veteran's Affairs Health Services Research and Development (HSR&D)
Career Development Transition Award [RCD 03-179-2]; AstraZeneca;
Novartis; Amgen; Procter Gamble; TAP; Takeda; CURE Digestive Disease
Research Center [NIH 2P30 DK 041301-17]; Nycomed
FX Declaration of personal and funding interests: Dr Spiegel is supported
by a Veteran's Affairs Health Services Research and Development (HSR&D)
Career Development Transition Award (RCD 03-179-2). Dr Spiegel has
served as a consultant to TAP Pharmaceutical Products Inc, Takeda
Pharmaceuticals of North America, Novartis, and AstraZeneca. He has
received research funding from AstraZeneca, Novartis, Amgen, Procter &
Gamble, TAP, Takeda, and AstraZeneca. Drs Esrailian and Spiegel are
supported by the CURE Digestive Disease Research Center (NIH 2P30 DK
041301-17). Dr Howden has served as a consultant to TAP Pharmaceutical
Products Inc., Takeda Pharmaceuticals of North America, Santarus,
Otsuka, Novartis, Biovail, Extera Partners and KV Pharmaceuticals, as a
speaker for AstraZeneca, Santarus and Otsuka, and has received research
funding from AstraZeneca. Dr Laine has acted as a consultant for
AstraZeneca, Eisai, Santarus, Horizon and Pozen, and has received
research support from Takeda Pharmaceuticals and GSK. M. G. H. van Oijen
is a consultant and has received grant support from AstraZeneca and
Nycomed. The authors had complete authority over all aspects of the
study, including development of the hypotheses and analysis plan,
development of data collection instruments, collection of data, analysis
and interpretation of data, and writing of the manuscript.
NR 27
TC 15
Z9 15
U1 1
U2 3
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0269-2813
J9 ALIMENT PHARM THER
JI Aliment. Pharmacol. Ther.
PD APR 15
PY 2009
VL 29
IS 8
BP 871
EP 881
DI 10.1111/j.1365-2036.2009.03935.x
PG 11
WC Gastroenterology & Hepatology; Pharmacology & Pharmacy
SC Gastroenterology & Hepatology; Pharmacology & Pharmacy
GA 421QC
UT WOS:000264372400009
PM 19183152
ER
PT J
AU Tung, P
Wiviott, SD
Cannon, CP
Murphy, SA
McCabe, CH
Gibson, CM
AF Tung, Patricia
Wiviott, Stephen D.
Cannon, Christopher P.
Murphy, Sabina A.
McCabe, Carolyn H.
Gibson, C. Michael
TI Seasonal Variation in Lipids in Patients Following Acute Coronary
Syndrome on Fixed Doses of Pravastatin (40 mg) or Atorvastatin (80 mg)
(from the Pravastatin or Atorvastatin Evaluation and Infection
Therapy-Thrombolysis In Myocardial Infarction 22 [PROVE IT-TIMI 22]
Study)
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID TRIAL PLACEBO GROUP; SERUM-LIPIDS; CHOLESTEROL; STATINS
AB Previous studies have shown seasonal variation in lipids. To understand whether this variation exists in patients with acute coronary syndromes receiving statins, we examined data from the PROVE IT-TIMI 22 Study. At baseline, no significant difference in low-density lipoprotein (LDL) cholesterol was observed when stratified by season. However, a statistically significant difference in high-density lipoprotein cholesterol between winter (37 mg/dl) and summer (39 mg/dl) was observed (p <0.001) at baseline. On treatment, median LDL cholesterol was 102 mg/dl in winter versus 96 mg/dl in summer (p <0.001) for the pravastatin group and 68 mg/dl in winter versus 62 mg/dl in summer (p <0.001) for the atorvastatin group. Median high-density lipoprotein cholesterol was 43 mg/dl in summer versus 41 mg/dl in winter in the pravastatin group and 42 mg/dl in summer versus 39 mg/dl in winter in the atorvastatin group (p <0.001). More patients achieved LDL cholesterol <100 mg/dl in summer at 56% versus 47% in winter in the pravastatin group (p <0.001) and 89% versus 87% in winter for the atorvastatin group (p = 0.11). Achievement of LDL cholesterol <70 mg/dl was also higher in summer than winter. In conclusion, this was the first evidence of seasonal variability in cholesterol in patients with acute coronary syndromes treated with statins. This variability affected achievement of National Cholesterol Education Program goals and may affect management decisions based on season of collection. (C) 2009 Elsevier Inc. (Am J Cardiol 2009;103:1056-1060)
C1 [Tung, Patricia; Wiviott, Stephen D.; Cannon, Christopher P.; Murphy, Sabina A.; McCabe, Carolyn H.; Gibson, C. Michael] Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA.
[Tung, Patricia; Wiviott, Stephen D.; Cannon, Christopher P.; Murphy, Sabina A.; McCabe, Carolyn H.; Gibson, C. Michael] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
RP Wiviott, SD (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA.
EM swiviott@partners.org
NR 13
TC 20
Z9 21
U1 0
U2 0
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9149
J9 AM J CARDIOL
JI Am. J. Cardiol.
PD APR 15
PY 2009
VL 103
IS 8
BP 1056
EP 1060
DI 10.1016/j.amjcard.2008.12.034
PG 5
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 436RR
UT WOS:000265433300003
PM 19361589
ER
PT J
AU Parashar, S
Katz, R
Smith, NL
Arnold, AM
Vaccarino, V
Wenger, NK
Gottdiener, JS
AF Parashar, Susmita
Katz, Ronit
Smith, Nicholas L.
Arnold, Alice M.
Vaccarino, Viola
Wenger, Nanette K.
Gottdiener, John S.
TI Race, Gender, and Mortality in Adults >= 65 Years of Age With Incident
Heart Failure (from the Cardiovascular Health Study)
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID ACUTE MYOCARDIAL-INFARCTION; RACIAL-DIFFERENCES; UNITED-STATES;
ELDERLY-PATIENTS; SEX-DIFFERENCES; HOSPITALIZATION; POPULATION;
SURVIVAL; OUTCOMES; EPIDEMIOLOGY
AB In patients with heart failure (HF), mortality is lower in women versus men. However, it is unknown whether the survival advantage in women compared with men is present in both whites and African Americans with HF. The inception cohort consisted of adults >= 65 years with incident HF after enrollment in the CHS, a prospective population-based study of cardiovascular disease. Of 5,888 CHS subjects, 1,264 developed new HF and were followed up for 3 years. Subjects were categorized into 4 race-gender groups, and Cox proportional hazard regression models were used to examine whether 3-year total and cardiovascular mortality differed among the 4 groups after adjusting for sociodemographic factors, co-morbidities, and treatment. A gender-race interaction was also tested for each outcome. In subjects with incident HF, African Americans had more hypertension and diabetes than whites, and white men had more coronary heart disease than other gender-race groups. Receipt of cardiovascular treatments among the 4 groups was similar. Mortality rates after HF were lower in women compared with men (for white women, African-American women, African-American men, and white men, total mortality was 35.5, 33.6, 44.4, and 40.5/100 person-years, and cardiovascular mortality was 18.4, 19.5, 20.2, and 22.7/100 person-years, respectively). After adjusting for covariates, women had a 15% to 20% lower risk of total and cardiovascular mortality compared with men, but there was no significant difference in outcome by race. The gender-race interaction for either outcome was not significant. In conclusion, in older adults with HF, women had significantly better survival than men irrespective of race, suggesting that gender-based survival differences may be more important than race-based differences. (C) 2009 Elsevier Inc. (Am J Cardiol 2009;103:1120-1127)
C1 [Parashar, Susmita; Vaccarino, Viola; Wenger, Nanette K.] Emory Univ, Sch Med, Dept Med, Atlanta, GA 30322 USA.
[Katz, Ronit; Smith, Nicholas L.; Arnold, Alice M.] Univ Washington, Dept Epidemiol, Seattle Epidemiol Res & Informat Ctr, Seattle, WA 98195 USA.
[Smith, Nicholas L.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA.
[Gottdiener, John S.] Univ Maryland, Div Cardiol, Baltimore, MD 21201 USA.
RP Parashar, S (reprint author), Emory Univ, Sch Med, Dept Med, Atlanta, GA 30322 USA.
EM susmita.parashar@emory.edu
FU National Heart, Lung, and Blood Institute, Bethesda, Maryland
[N01-HC-35129, N01-HC45133, N01-HC-75150, N01-HC-85079, N01-HC-85086,
N01 HC15103, N01 HC-55222, U01 HL080295]; National Institute of
Neurological Disorders and Stroke. Bethesda, Maryland; American Heart
Association, Dallas, Texas [0630084N]; National Center for Research
Resources/ National Institutes of Health [1K23RR023171]
FX This work was supported by contracts N01-HC-35129, N01-HC45133,
N01-HC-75150. N01-HC-85079 through N01-HC-85086, N01 HC15103, N01
HC-55222, and U01 HL080295 from the National Heart, Lung, and Blood
Institute, Bethesda, Maryland, with additional contribution from the
National Institute of Neurological Disorders and Stroke. Bethesda,
Maryland. Dr. Parashar was supported by Scientist Development Award
0630084N from the American Heart Association, Dallas, Texas, and
Mentored Clinical Scientist Development Award 1K23RR023171 from the
National Center for Research Resources/ National Institutes of Health.
NR 30
TC 26
Z9 26
U1 0
U2 3
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9149
J9 AM J CARDIOL
JI Am. J. Cardiol.
PD APR 15
PY 2009
VL 103
IS 8
BP 1120
EP 1127
DI 10.1016/j.amjcard.2008.12.043
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 436RR
UT WOS:000265433300014
PM 19361600
ER
PT J
AU Blankstein, R
Shah, A
Pale, R
Abbara, S
Bezerra, H
Bolen, M
Mamuya, WS
Hoffmann, U
Brady, TJ
Cury, RC
AF Blankstein, Ron
Shah, Amar
Pale, Rodrigo
Abbara, Suhny
Bezerra, Hiram
Bolen, Michael
Mamuya, Wilfred S.
Hoffmann, Udo
Brady, Thomas J.
Cury, Ricardo C.
TI Radiation Dose and Image Quality of Prospective Triggering With
Dual-Source Cardiac Computed Tomography
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID CORONARY CT ANGIOGRAPHY
AB Prospectively triggered (PT) cardiac computed tomography (CT), whereby radiation is administered only at a predefined phase of the cardiac cycle, has been shown to substantially decrease radiation dose. The aim of our study was to assess the use of this technique in a clinical population using dual-source cardiac CT. Of 312 consecutive patients referred for a dual-source cardiac computed tomographic examination, PT was used in 42 patients for whom, based on physician judgment, it was decided to minimize radiation, whereas retrospective gating was used for 188 patients (coronary artery bypass grafting and pulmonary vein studies were excluded). Kilovolt and milliampere per second were chosen for each patient based on assessment of body habitus and effective radiation dose was calculated. Analysis of nonevaluable vessels was based on clinical readings. For each study, image quality (IQ) was rated on a subjective IQ score and contrast-to-noise and signal-to-noise ratios were calculated. Of the 42 PT examinations (mean age 44.3 years, body mass index 27.8 kg/m(2), 62% men), 28 were referred for coronary evaluation, 11 for aortic disease with/without coronaries, and 3 for other reasons (i.e., suspected mass and congenital disease). Average heart rate was 64.5 beats/min. Average radiation dose of all 42 PT scans was 3.2 +/- 1.6 vs 13.4 +/- 7.8 mSv for the 188 non-PT scans. There was no significant difference in IQ score and contrast-to-noise and signal-to-noise ratios between the 2 groups. Furthermore, the incidence of limited right coronary artery evaluation and of limitations related to right coronary artery motion did not differ between PT and non-PT scans. In conclusion, in selected patients, prospective triggering. with dual-source cardiac CT is feasible and results in a dramatic decrease of radiation dose without compromising IQ. Future advances in cardiac CT may further improve this technique, thus allowing for wider use. (C) 2009 Elsevier Inc. All rights reserved. (Am J Cardiol 2009;103:1168-1173)
C1 [Blankstein, Ron; Shah, Amar; Pale, Rodrigo; Abbara, Suhny; Bezerra, Hiram; Bolen, Michael; Mamuya, Wilfred S.; Hoffmann, Udo; Brady, Thomas J.; Cury, Ricardo C.] Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET CT Program, Boston, MA 02114 USA.
[Blankstein, Ron; Shah, Amar; Pale, Rodrigo; Abbara, Suhny; Bezerra, Hiram; Bolen, Michael; Mamuya, Wilfred S.; Hoffmann, Udo; Brady, Thomas J.; Cury, Ricardo C.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Blankstein, Ron; Shah, Amar; Pale, Rodrigo; Abbara, Suhny; Bezerra, Hiram; Bolen, Michael; Mamuya, Wilfred S.; Hoffmann, Udo; Brady, Thomas J.; Cury, Ricardo C.] Harvard Univ, Sch Med, Boston, MA USA.
[Blankstein, Ron] Brigham & Womens Hosp, Dept Med & Radiol, Noninvas Cardiovasc Imaging Program, Boston, MA 02115 USA.
[Cury, Ricardo C.] Baptist Cardiac & Vasc Inst, Miami, FL USA.
RP Blankstein, R (reprint author), Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET CT Program, Boston, MA 02114 USA.
EM rblankstein@partners.org
FU NHLBI NIH HHS [1T32 HL076136]
NR 6
TC 40
Z9 49
U1 0
U2 2
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9149
J9 AM J CARDIOL
JI Am. J. Cardiol.
PD APR 15
PY 2009
VL 103
IS 8
BP 1168
EP 1173
DI 10.1016/j.amjcard.2008.12.045
PG 6
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 436RR
UT WOS:000265433300023
PM 19361609
ER
PT J
AU Wilson, KM
Mucci, LA
Cho, E
Hunter, DJ
Chen, WY
Willett, WC
AF Wilson, Kathryn M.
Mucci, Lorelei A.
Cho, Eunyoung
Hunter, David J.
Chen, Wendy Y.
Willett, Walter C.
TI Dietary Acrylamide Intake and Risk of Premenopausal Breast Cancer
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE acrylamide; breast neoplasms; diet
ID ONCOGENICITY; EXPOSURE; WOMEN; RATS; FOOD
AB Acrylamide, a probable human carcinogen, is formed during high-temperature cooking of many commonly consumed foods. It is widespread; approximately 30% of calories consumed in the United States are from foods containing acrylamide. In animal studies, acrylamide causes mammary tumors, but it is unknown whether the level of acrylamide in foods affects human breast cancer risk. The authors studied the association between acrylamide intake and breast cancer risk among 90,628 premenopausal women in the Nurses' Health Study II. They calculated acrylamide intake from food frequency questionnaires in 1991, 1995, 1999, and 2003. From 1991 through 2005, they documented 1,179 cases of invasive breast cancer. They used Cox proportional hazards models to assess the association between acrylamide and breast cancer risk. The multivariable-adjusted relative risk of premenopausal breast cancer was 0.92 (95% confidence interval: 0.76, 1.11) for the highest versus the lowest quintile of acrylamide intake (P(trend) = 0.61). Results were similar regardless of smoking status or estrogen and progesterone receptor status of the tumors. The authors found no associations between intakes of foods high in acrylamide, including French fries, coffee, cereal, potato chips, potatoes, and baked goods, and breast cancer risk. They found no evidence that acrylamide intake, within the range of US diets, is associated with increased risk of premenopausal breast cancer.
C1 [Wilson, Kathryn M.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA.
[Wilson, Kathryn M.; Mucci, Lorelei A.; Hunter, David J.; Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Wilson, Kathryn M.; Cho, Eunyoung; Hunter, David J.; Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Mucci, Lorelei A.; Cho, Eunyoung; Hunter, David J.; Chen, Wendy Y.; Willett, Walter C.] Harvard Univ, Sch Med, Channing Lab, Dept Med, Boston, MA 02115 USA.
[Chen, Wendy Y.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
RP Wilson, KM (reprint author), Brigham & Womens Hosp, Channing Lab, 181 Longwood Ave,3rd Floor, Boston, MA 02115 USA.
EM kwilson@hsph.harvard.edu
FU National Cancer Institute [CA050385]; National Cancer Institute/National
Institutes of Health training grant [T32 CA09001]
FX This work was supported by a grant from the National Cancer Institute
(CA050385) and by a National Cancer Institute/National Institutes of
Health training grant (T32 CA09001 to K. M. W.)
NR 18
TC 31
Z9 35
U1 1
U2 4
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD APR 15
PY 2009
VL 169
IS 8
BP 954
EP 961
DI 10.1093/aje/kwn421
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 425KH
UT WOS:000264634900005
PM 19224978
ER
PT J
AU McCarthy, JF
Valenstein, M
Kim, HM
Ilgen, M
Zivin, K
Blow, FC
AF McCarthy, John F.
Valenstein, Marcia
Kim, H. Myra
Ilgen, Mark
Zivin, Kara
Blow, Frederic C.
TI Suicide Mortality Among Patients Receiving Care in the Veterans Health
Administration Health System
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE military medicine; mortality; suicide; veterans
ID POSTTRAUMATIC-STRESS-DISORDER; VIETNAM VETERANS; WAR VETERANS; US
VETERANS; GULF-WAR; AFFAIRS; RISK; WOMEN; OUTPATIENTS; DEPRESSION
AB Understanding and reducing mortality from suicide among veterans is a national priority, particularly for individuals receiving care from the US Veterans Health Administration (VHA). This report examines suicide rates among VHA patients and compares them with rates in the general population. Suicide mortality was assessed in fiscal year 2001 for patients alive at the start of that fiscal year and with VHA use in fiscal years 2000-2001 (n = 4,692,034). Deaths from suicide were identified by using National Death Index data. General population rates were identified by use of the Web-based Injury Statistics Query and Reporting System. VHA rates were 43.13/100,000 person-years for men and 10.41/100,000 person-years for women. For male patients, the age-adjusted standardized mortality ratio was 1.66; for females, it was 1.87. Male patients aged 30-79 years had increased risks relative to men in the general population; standardized mortality ratios ranged from 2.56 (ages 30-39 years) to 1.33 (ages 70-79 years). Female patients aged 40-59 years had greater risks than did women in the general population, with standardized mortality ratios of 2.15 (ages 40-49 years) and 2.36 (ages 50-59 years). Findings offer heretofore unavailable comparison points for health systems. Prior to the conflicts in Afghanistan and Iraq and before recent VHA initiatives, rates were higher among VHA patients than in the general population. Female patients had particularly high relative risks.
C1 [McCarthy, John F.; Valenstein, Marcia; Ilgen, Mark; Zivin, Kara; Blow, Frederic C.] Serious Mental Illness Treatment Res & Evaluat Ct, US Dept Vet Affairs, Ann Arbor, MI 48113 USA.
[McCarthy, John F.; Valenstein, Marcia; Kim, H. Myra; Ilgen, Mark; Zivin, Kara; Blow, Frederic C.] Ctr Clin Management Res, US Dept Vet Affairs, Ann Arbor, MI USA.
[McCarthy, John F.; Valenstein, Marcia; Kim, H. Myra; Ilgen, Mark; Zivin, Kara; Blow, Frederic C.] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA.
RP McCarthy, JF (reprint author), Serious Mental Illness Treatment Res & Evaluat Ct, US Dept Vet Affairs, POB 13017, Ann Arbor, MI 48113 USA.
EM john.mccarthy2@va.gov
NR 37
TC 116
Z9 116
U1 1
U2 5
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD APR 15
PY 2009
VL 169
IS 8
BP 1033
EP 1038
DI 10.1093/aje/kwp010
PG 6
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 425KH
UT WOS:000264634900014
PM 19251753
ER
PT J
AU Lott, JP
Iwashyna, TJ
Christie, JD
Asch, DA
Kramer, AA
Kahn, JM
AF Lott, Jason P.
Iwashyna, Theodore J.
Christie, Jason D.
Asch, David A.
Kramer, Andrew A.
Kahn, Jeremy M.
TI Critical Illness Outcomes in Specialty versus General Intensive Care
Units
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Article
DE critical care; health services; organization; intensive care unit;
hospital mortality
ID EVALUATION APACHE IV; EMERGENCY-DEPARTMENT; ILL PATIENTS; MECHANICAL
VENTILATION; PATIENT OUTCOMES; BURNOUT SYNDROME; ACUTE PHYSIOLOGY;
IMPACT; SERVICES; STATES
AB Rationale: General intensive care units (ICUs) provide care across a wide range of diagnoses, whereas specialty ICUs provide diagnosis-specific care. Risk-adjusted outcome differences across such units are unknown.
Objectives: To determine the association between specialty ICU care and the outcome of critical illness.
Methods: We conducted a retrospective cohort study design analyzing patients admitted to 124 ICUs participating in the Acute Physiology and Chronic Health Evaluation IV from January 2002 to December 2005. We examined 84,182 patients admitted to specialty and general ICUs with an admitting diagnosis or procedure of acute coronary syndrome, ischemic stroke, intracranial hemorrhage, pneumonia, abdominal surgery, or coronary-artery bypass graft surgery. ICU type determined by a local data coordinator at each site. Patients were classified by admission to a general ICU, a diagnosis-appropriate ("ideal") specialty ICU, or a diagnosis-inappropriate ("non-ideal") specialty ICU. The primary outcomes were in-hospital mortality and ICU length of stay.
Measurements and Main Results: After adjusting for important con-founders, there were no significant differences in risk-adjusted mortality between general versus ideal specialty ICUs for all conditions other than pneumonia. Risk-adjusted mortality was significantly greater for patients admitted to non-ideal specialty ICUs. There was no consistent effect of specialization on length of stay for all patients or for ICU survivors.
Conclusions: Ideal specialty ICU care appears to offer no survival benefit over general ICU care for select common diagnoses. Non-ideal specialty ICU care (i.e., "boarding") is associated with increased risk-adjusted mortality.
C1 [Christie, Jason D.; Kahn, Jeremy M.] Univ Penn, Sch Med, Div Pulm Allergy & Crit Care, Philadelphia, PA 19104 USA.
[Christie, Jason D.; Kahn, Jeremy M.] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[Iwashyna, Theodore J.] Univ Michigan, Sch Med, Div Pulm & Crit Care Med, Ann Arbor, MI USA.
[Iwashyna, Theodore J.; Asch, David A.; Kahn, Jeremy M.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA.
[Asch, David A.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equity Res & Promot, Philadelphia, PA USA.
[Kramer, Andrew A.] Cerner Corp, Vienna, VA USA.
RP Kahn, JM (reprint author), Univ Penn, Sch Med, Div Pulm Allergy & Crit Care, 723 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA.
EM jmkahn@mail.med.upenn.edu
OI Kramer, Andrew/0000-0002-5681-5781; Asch, David/0000-0002-7970-286X;
Lott, Jason/0000-0002-4097-7225; Iwashyna, Theodore/0000-0002-4226-9310
NR 38
TC 40
Z9 41
U1 0
U2 5
PU AMER THORACIC SOC
PI NEW YORK
PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA
SN 1073-449X
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PD APR 15
PY 2009
VL 179
IS 8
BP 676
EP 683
DI 10.1164/rccm.200808-1281OC
PG 8
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 434BZ
UT WOS:000265251500008
PM 19201923
ER
PT J
AU Collier, DS
Kay, J
Estey, G
Surrao, D
Chueh, HC
Grant, RW
AF Collier, Deborah S.
Kay, Jonathan
Estey, Greg
Surrao, Dominic
Chueh, Henry C.
Grant, Richard W.
TI A Rheumatology-Specific Informatics-Based Application With a Disease
Activity Calculator
SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH
LA English
DT Article
ID CONTROLLED-TRIAL; ACTIVITY SCORE; ACTIVITY INDEX; ARTHRITIS; VALIDATION;
OUTCOMES; STRATEGY
AB Objective. To design a rheumatology-specific tool with a disease activity calculator integrated into the electronic medical records (EMRs) at our institution and assess physicians' attitudes toward the use of this tool.
Methods. The Rheumatology OnCall (ROC) application culls rheumatology-pertinent data from our institution's laboratory, microbiology, pathology, radiology, and pharmacy information systems. Attending rheumatologists and rheumatology fellows accessed the ROC and disease activity calculator during outpatient visits at the time of the clinical encounter.
Results. During the 12-week study period, 15 physicians used the ROC application and the disease activity calculator during 474 and 429 outpatient clinic visits, respectively. In weekly survey responses, physicians reported that use of the ROC interface improved patient care in 140 (78%) of 179 visits, and that the Disease Activity Score in 28 joints (DAS28) results at the time of the visit would not have changed patient management in 157 (88%) of these, although seeing a trend in DAS28 was useful in 149 (96%) of 156 visits. At the study's conclusion, most physicians reported that the ROC application was useful (11 of 12 physicians) and that seeing a trend in DAS28 improved daily patient care (12 of 13 physicians).
Conclusion. The ROC application is useful in daily rheumatologic care, and the disease activity calculator facilitates management of patients with rheumatoid arthritis. However, widespread acceptance and use of such tools depend upon the general acceptance of and access to EMRs in the clinical setting. The utility of the disease activity calculator may be limited by the lack of available acute-phase reactant results at the time of the clinical encounter.
C1 [Collier, Deborah S.] Massachusetts Gen Hosp, Yawkey Ctr, Boston, MA 02114 USA.
[Collier, Deborah S.; Kay, Jonathan; Chueh, Henry C.; Grant, Richard W.] Harvard Univ, Sch Med, Boston, MA USA.
RP Collier, DS (reprint author), Massachusetts Gen Hosp, Yawkey Ctr, Suite 2C-2100,55 Fruit St, Boston, MA 02114 USA.
EM dscollier@partners.org
OI Grant, Richard/0000-0002-6164-8025; Kay, Jonathan/0000-0002-8970-4260
FU Centocor; Pfizer
FX Dr. Collier's work was supported by an unrestricted educational grant
from Centocor. Dr. Kay's work was supported by an unrestricted
educational grant from Pfizer.
NR 15
TC 9
Z9 10
U1 0
U2 0
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0004-3591
J9 ARTHRIT RHEUM-ARTHR
JI Arthritis Rheum-Arthritis Care Res.
PD APR 15
PY 2009
VL 61
IS 4
BP 488
EP 494
DI 10.1002/art.24345
PG 7
WC Rheumatology
SC Rheumatology
GA 431AL
UT WOS:000265033600012
PM 19333976
ER
PT J
AU Collier, DS
Grant, RW
Estey, G
Surrao, D
Chueh, HC
Kay, J
AF Collier, Deborah S.
Grant, Richard W.
Estey, Greg
Surrao, Dominic
Chueh, Henry C.
Kay, Jonathan
TI Physician Ability to Assess Rheumatoid Arthritis Disease Activity Using
an Electronic Medical Record-Based Disease Activity Calculator
SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH
LA English
DT Article
ID COLLEGE-OF-RHEUMATOLOGY; RANDOMIZED CONTROLLED-TRIAL; ACTIVITY SCORE;
CLINICAL-PRACTICE; IMPROVEMENT CRITERIA; ACTIVITY INDEX; JOINT COUNTS;
VALIDATION; METHOTREXATE; COMBINATION
AB Objective. To assess physicians' concordance with Disease Activity Score in 28 joints (DAS28) categories calculated by an electronic medical record (EMR)-embedded disease activity calculator, as well as attitudes toward this application.
Methods. Fifteen rheumatologists used the EMR-embedded disease activity calculator to predict a rheumatoid arthritis (RA) DAS28 disease activity category at the time of each clinical encounter.
Results. physician-predicted DAS28 disease activity categories ranged from high (> 5.1, 15% of cohort, 66 of 429 patient visits) to moderate (>3.2-5.1, 21% of cohort, 90 of 429 patient visits) to low (2.6-3.2, 29% of cohort, 123 of 429 patient visits) to remission (<2.6, 35% of cohort, 150 of 429 patient visits). Overall concordance between calculated DAS28 results and physician-predicted RA disease activity was 64%. Using either the physician-predicted or the calculated DAS28 category as the gold standard, accuracy was greatest for patients in remission (75% and 88% accuracy, respectively) and those with high disease activity (68% and 79% accuracy, respectively), and less for patients with moderate (48% and 62% accuracy, respectively) or low disease activity (62% and 31% accuracy, respectively).
Conclusion. Accurate physician prediction of DAS28 remission and high disease activity categories, even without immediate availability of the erythrocyte sedimentation rate or the C-reactive protein level at the time of the visit, may be used to guide quantitatively driven outpatient RA management.
C1 [Collier, Deborah S.] Massachusetts Gen Hosp, Yawkey Ctr, Boston, MA 02114 USA.
[Collier, Deborah S.; Grant, Richard W.; Chueh, Henry C.; Kay, Jonathan] Harvard Univ, Sch Med, Boston, MA USA.
RP Collier, DS (reprint author), Massachusetts Gen Hosp, Yawkey Ctr, Suite 2C-2100,55 Fruit St, Boston, MA 02114 USA.
EM dscollier@partners.org
OI Grant, Richard/0000-0002-6164-8025; Kay, Jonathan/0000-0002-8970-4260
FU Centocor; Pfizer
FX Dr. Collier's work was supported by an unrestricted educational grant
from Centocor. Dr. Kay's work was supported by an unrestricted
educational grant from Pfizer.
NR 20
TC 8
Z9 8
U1 0
U2 0
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0004-3591
J9 ARTHRIT RHEUM-ARTHR
JI Arthritis Rheum-Arthritis Care Res.
PD APR 15
PY 2009
VL 61
IS 4
BP 495
EP 500
DI 10.1002/art.24335
PG 6
WC Rheumatology
SC Rheumatology
GA 431AL
UT WOS:000265033600013
PM 19333984
ER
PT J
AU Taylor, WJ
Shewchuk, R
Saag, KG
Schumacher, HR
Singh, JA
Grainger, R
Edwards, NL
Bardin, T
Waltrip, RW
Simon, LS
Burgos-Vargas, R
AF Taylor, W. J.
Shewchuk, R.
Saag, K. G.
Schumacher, H. R., Jr.
Singh, J. A.
Grainger, R.
Edwards, N. L.
Bardin, T.
Waltrip, R. W.
Simon, L. S.
Burgos-Vargas, R.
TI Toward a Valid Definition of Gout Flare: Results of Consensus Exercises
Using Delphi Methodology and Cognitive Mapping
SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH
LA English
DT Article
ID CONTROLLED-TRIAL; TRIAMCINOLONE ACETONIDE; DOUBLE-BLIND; ARTHRITIS;
INDOMETHACIN; ATTACKS; ETORICOXIB; HYPERURICEMIA; EFFICACY; THERAPY
AB Objective. To identify, in people known to have gout, the testable, key components of a standard definition of gout flare for use in clinical research.
Methods. Consensus methodology was used to identify key elements of a gout flare. Two Delphi exercises were conducted among different groups of rheumatologists. A cognitive mapping technique among 9 gout experts with hierarchical cluster analysis provided a framework to guide the panel discussion, which identified the final set of items that should be tested empirically.
Results. From the Delphi exercises, 21 items were presented to the expert panel. Cluster analysis and multidimensional scaling showed that: these items clustered into 5 concepts (joint inflammation, severity of symptoms, stereotypical nature, pain, and gout archetype) distributed along 2 dimensions (objective to subjective features and general features to specific features of gout). Using this analysis, expert panel discussion generated a short list of potential features: joint swelling, joint tenderness, joint warmth, severity of pain, patient global assessment, time to maximum pain, time to complete resolution of pain, an acute-phase marker, and functional impact of the episode.
Conclusion. A short list of features has been identified and now requires validation against a patient and physician-defined gout flare in order to determine the best combination of features.
C1 [Taylor, W. J.] Univ Otago, Wellington Sch Med & Hlth Sci, Dept Med, Wellington 6242, New Zealand.
[Taylor, W. J.; Grainger, R.] Hutt Valley Dist Hlth Board, Wellington Reg Rheumatol Unit, Wellington, New Zealand.
[Shewchuk, R.] Univ Alabama, Birmingham, AL USA.
[Schumacher, H. R., Jr.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
[Schumacher, H. R., Jr.] Vet Affairs Med Ctr, Philadelphia, PA USA.
[Singh, J. A.] Univ Minnesota, Minneapolis, MN USA.
[Singh, J. A.] Minneapolis VA Med Ctr, Minneapolis, MN USA.
[Grainger, R.] Malaghan Inst Med Res, Wellington, New Zealand.
[Edwards, N. L.] Univ Florida, Gainesville, FL USA.
[Bardin, T.] Hop Lariboisiere, F-75475 Paris, France.
[Waltrip, R. W.] Savient Pharmaceut, E Brunswick, NJ USA.
[Simon, L. S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA.
[Burgos-Vargas, R.] Univ Nacl Autonoma Mexico, Hosp Gen Mexico, Mexico City 04510, DF, Mexico.
RP Taylor, WJ (reprint author), Univ Otago, Wellington Sch Med & Hlth Sci, Dept Med, POB 7343, Wellington 6242, New Zealand.
EM will.taylor@otago.ac.nz
RI Grainger, Rebecca/I-1866-2012;
OI singh, jasvinder/0000-0003-3485-0006
FU American College of Rheumatology/European League Against Rheumatism;
TAP; Savient
FX Supported in part by an American College of Rheumatology/European League
Against Rheumatism grant. Dr. Singh is recipient of
investigator-initiated research grants from TAP and Savient for a
different project.
NR 25
TC 14
Z9 14
U1 0
U2 1
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0004-3591
J9 ARTHRIT RHEUM-ARTHR
JI Arthritis Rheum-Arthritis Care Res.
PD APR 15
PY 2009
VL 61
IS 4
BP 535
EP 543
DI 10.1002/art.24166
PG 9
WC Rheumatology
SC Rheumatology
GA 431AL
UT WOS:000265033600018
PM 19333981
ER
PT J
AU New, AS
Hazlett, E
aan het Rot, M
Liu, X
Lazarus, S
Goodman, M
Zipursky, E
Koenigsberg, HW
Siever, LJ
AF New, Antonia S.
Hazlett, Erin
aan het Rot, Marije
Liu, Xun
Lazarus, Sophie
Goodman, Marianne
Zipursky, Emma
Koenigsberg, Harold W.
Siever, Larry J.
TI The Neuroscience of Alexithymia in Borderline Personality Disorder
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
CT 64th Annual Convention of the Society-of-Biological-Psychiatry
CY MAY 14-16, 2009
CL Vancouver, CANADA
SP Soc Biol Psychiat
C1 [New, Antonia S.; Hazlett, Erin; aan het Rot, Marije; Liu, Xun; Lazarus, Sophie; Goodman, Marianne; Zipursky, Emma; Koenigsberg, Harold W.; Siever, Larry J.] Mt Sinai Sch Med, New York, NY USA.
[New, Antonia S.; Goodman, Marianne; Koenigsberg, Harold W.] James J Peters VA Med Ctr, Mental Hlth Care Ctr, Bronx, NY USA.
RI Liu, Xun/C-2400-2009
OI Liu, Xun/0000-0003-1366-8926
NR 0
TC 0
Z9 0
U1 0
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD APR 15
PY 2009
VL 65
IS 8
MA 13
BP 4S
EP 4S
PG 1
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 432OS
UT WOS:000265144200014
ER
PT J
AU Mathalon, DH
Ford, JM
Guglielmino, R
Roach, BJ
Gueorguieva, R
Clapp, WC
Teyler, TJ
Cavus, I
AF Mathalon, Daniel H.
Ford, Judith M.
Guglielmino, Robert
Roach, Brian J.
Gueorguieva, Ralitza
Clapp, Wesley C.
Teyler, Timothy J.
Cavus, Idil
TI Long-Term Potentiation of Visual Evoked Potentials is Impaired in
Schizophrenia
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
CT 64th Annual Convention of the Society-of-Biological-Psychiatry
CY MAY 14-16, 2009
CL Vancouver, CANADA
SP Soc Biol Psychiat
C1 [Mathalon, Daniel H.; Ford, Judith M.; Roach, Brian J.; Gueorguieva, Ralitza] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Mathalon, Daniel H.; Ford, Judith M.] San Francisco VA Med Ctr, Mental Hlth Serv, San Francisco, CA USA.
[Guglielmino, Robert; Clapp, Wesley C.; Cavus, Idil] Yale Univ, New Haven, CT USA.
[Roach, Brian J.] No Calif Inst Res & Educ, San Francisco, CA USA.
[Teyler, Timothy J.] Univ Idaho, Moscow, ID 83843 USA.
[Teyler, Timothy J.] Washington State Univ, Vcapp, Pullman, WA 99164 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD APR 15
PY 2009
VL 65
IS 8
MA 41
BP 13S
EP 13S
PG 1
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 432OS
UT WOS:000265144200036
ER
PT J
AU Evans, KC
AF Evans, Karleyton C.
TI The Cortico-Limbic Neural Response to Air Hunger Shares Temporal
Dynamics with Subjective Interoception: A Proof of Concept fMRI Study
for Panic Disorder
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
CT 64th Annual Convention of the Society-of-Biological-Psychiatry
CY MAY 14-16, 2009
CL Vancouver, CANADA
SP Soc Biol Psychiat
C1 [Evans, Karleyton C.] Massachusetts Gen Hosp, Charlestown, MA USA.
NR 0
TC 2
Z9 2
U1 1
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD APR 15
PY 2009
VL 65
IS 8
MA 101
BP 31S
EP 31S
PG 1
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 432OS
UT WOS:000265144200096
ER
PT J
AU Wynn, JK
Crosby, S
Nori, P
Green, MF
AF Wynn, Jonathan K.
Crosby, Shelly
Nori, Poorang
Green, Michael F.
TI Association Between Mismatch Negativity Deficits, Social Cognition and
Functional Outcome in Schizoprhenia
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
CT 64th Annual Convention of the Society-of-Biological-Psychiatry
CY MAY 14-16, 2009
CL Vancouver, CANADA
SP Soc Biol Psychiat
C1 [Wynn, Jonathan K.] VA Greater Los Angeles Healthcare Syst, Res & Dev, Los Angeles, CA USA.
[Crosby, Shelly; Nori, Poorang; Green, Michael F.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA.
RI Wynn, Jonathan/H-3749-2014
OI Wynn, Jonathan/0000-0002-1763-8540
NR 0
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 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD APR 15
PY 2009
VL 65
IS 8
MA 176
BP 54S
EP 54S
PG 1
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 432OS
UT WOS:000265144200171
ER
PT J
AU Yao, J
Dougherty, GG
Keshavan, MS
Montrose, DM
Matson, WR
McEvoy, J
Kaddurah-Daouk, R
Condray, R
Reddy, RD
AF Yao, Jeffrey
Dougherty, George G.
Keshavan, Matched S.
Montrose, Debra M.
Matson, Wayne R.
McEvoy, Joseph
Kaddurah-Daouk, Rima
Condray, Ruth
Reddy, Ravinder D.
TI Homeostatic Imbalance of Purine Catabolism in First-Episode
Neuroleptic-Naive Patients with Schizophrenia
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
CT 64th Annual Convention of the Society-of-Biological-Psychiatry
CY MAY 14-16, 2009
CL Vancouver, CANADA
SP Soc Biol Psychiat
C1 [Yao, Jeffrey; Dougherty, George G.; Condray, Ruth] VA Pittsburgh Healthcare Syst, Med Res Serv, Pittsburgh, PA USA.
[Yao, Jeffrey; Dougherty, George G.; Keshavan, Matched S.; Montrose, Debra M.; Condray, Ruth; Reddy, Ravinder D.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA.
[Keshavan, Matched S.] Wayne State Univ, Dept Psychiat, Detroit, MI USA.
[Matson, Wayne R.] Bedford VA Med Ctr, Med Res Serv, Bedford, MA USA.
[McEvoy, Joseph; Kaddurah-Daouk, Rima] Duke Univ, Med Ctr, Dept Psychiat, Durham, NC 27710 USA.
NR 0
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 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD APR 15
PY 2009
VL 65
IS 8
MA 211
BP 65S
EP 65S
PG 1
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 432OS
UT WOS:000265144200205
ER
PT J
AU Sklar, P
Ferreira, MAR
Craddock, N
Meng, Y
Ruderfer, D
Fran, J
Daly, MJ
Holmans, P
O'Donovan, M
Scolnick, EM
Corvin, AP
Blackwood, DH
Gurling, HM
Purcell, SM
AF Sklar, Pamela
Ferreira, M. A. R.
Craddock, N.
Meng, Y.
Ruderfer, D.
Fran, J.
Daly, M. J.
Holmans, P.
O'Donovan, M.
Scolnick, E. M.
Corvin, A. P.
Blackwood, D. H.
Gurling, H. M.
Purcell, S. M.
TI Collaborative Genome-Wide Analysis Supports a Role for ANK3 and CACNA1C
in Bipolar Disorder
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
CT 64th Annual Convention of the Society-of-Biological-Psychiatry
CY MAY 14-16, 2009
CL Vancouver, CANADA
SP Soc Biol Psychiat
C1 [Sklar, Pamela; Ferreira, M. A. R.; Meng, Y.; Ruderfer, D.; Fran, J.; Daly, M. J.; Purcell, S. M.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Sklar, Pamela; Ferreira, M. A. R.; Meng, Y.; Ruderfer, D.; Fran, J.; Daly, M. J.; Scolnick, E. M.; Purcell, S. M.] Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Boston, MA USA.
[Craddock, N.; Holmans, P.; O'Donovan, M.] Cardiff Univ, Dept Psychol Med, Cardiff, S Glam, Wales.
[Corvin, A. P.] Univ Dublin Trinity Coll, Trinity Ctr Hlth Sci, Dublin 2, Ireland.
[Blackwood, D. H.] Univ Edinburgh, Royal Edinburgh Hosp, Div Psychiat, Edinburgh, Midlothian, Scotland.
[Gurling, H. M.] Univ Coll London, Dept Mental Hlth Sci, Windeyer Inst Med Sci, Mol Psychiat Lab, Edinburgh, Midlothian, Scotland.
RI Gurling, Hugh/A-5029-2010; Holmans, Peter/F-4518-2015; Ruderfer,
Douglas/M-5795-2016
OI Holmans, Peter/0000-0003-0870-9412; Ruderfer,
Douglas/0000-0002-2365-386X
NR 0
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 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD APR 15
PY 2009
VL 65
IS 8
MA 318
BP 95S
EP 96S
PG 2
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 432OS
UT WOS:000265144200306
ER
PT J
AU Britton, JC
Stewart, SE
Price, LM
Killgore, WDS
Jenike, MA
Rauch, SL
AF Britton, Jennifer C.
Stewart, S. Evelyn
Price, Lauren M.
Killgore, William D. S.
Jenike, Michael A.
Rauch, Scott L.
TI The Neural Correlates of Negative Priming in Pediatric Obsessive
Compulsive Disorder.
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
CT 64th Annual Convention of the Society-of-Biological-Psychiatry
CY MAY 14-16, 2009
CL Vancouver, CANADA
SP Soc Biol Psychiat
C1 [Britton, Jennifer C.; Price, Lauren M.; Killgore, William D. S.; Rauch, Scott L.] McLean Hosp, Belmont, MA 02178 USA.
[Stewart, S. Evelyn; Jenike, Michael A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RI Britton, Jennifer/J-4501-2013; Stewart, Evelyn/K-6961-2014
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD APR 15
PY 2009
VL 65
IS 8
MA 344
BP 103S
EP 103S
PG 1
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 432OS
UT WOS:000265144200333
ER
PT J
AU Koenigsberg, HW
AF Koenigsberg, Harold W.
TI Neural Network Sensitization and Habituation and Emotional Reactivity in
Borderline and Avoidant Personality Disorders
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
CT 64th Annual Convention of the Society-of-Biological-Psychiatry
CY MAY 14-16, 2009
CL Vancouver, CANADA
SP Soc Biol Psychiat
C1 [Koenigsberg, Harold W.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA.
[Koenigsberg, Harold W.] James J Peters VA Med Ctr, Bronx, NY USA.
NR 0
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 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD APR 15
PY 2009
VL 65
IS 8
MA 347
BP 104S
EP 104S
PG 1
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 432OS
UT WOS:000265144200336
ER
PT J
AU Hoelzel, BK
Carmody, J
Evans, KC
Hoge, EA
Dusek, JA
Morgan, L
Pitman, RK
Lazar, SW
AF Hoelzel, Britta K.
Carmody, James
Evans, Karleyton C.
Hoge, Elizabeth A.
Dusek, Jeffery A.
Morgan, Lucas
Pitman, Roger K.
Lazar, Sara W.
TI Stress Reduction Correlates with Changes in Gray Matter Concentration in
the Right Amygdala
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
CT 64th Annual Convention of the Society-of-Biological-Psychiatry
CY MAY 14-16, 2009
CL Vancouver, CANADA
SP Soc Biol Psychiat
C1 [Hoelzel, Britta K.; Evans, Karleyton C.; Morgan, Lucas; Pitman, Roger K.; Lazar, Sara W.] Massachusetts Gen Hosp, Charlestown, MA USA.
[Carmody, James] Univ Massachusetts, Sch Med, Ctr Mindfulness, Worcester, MA USA.
[Hoge, Elizabeth A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Dusek, Jeffery A.] Abbott NW Hosp, Penny George Inst Hlth & Healing, Minneapolis, MN 55407 USA.
NR 0
TC 0
Z9 0
U1 1
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD APR 15
PY 2009
VL 65
IS 8
MA 361
BP 108S
EP 108S
PG 1
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 432OS
UT WOS:000265144200350
ER
PT J
AU Hezel, DM
Jenike, EA
Sampaio, A
Egan-Stack, D
Stewart, SE
AF Hezel, Dianne M.
Jenike, Eric A.
Sampaio, Aline
Egan-Stack, Denise
Stewart, S. Evelyn
TI Gender as a Mediator of Intensive Residential Treatment Response in OCD
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
CT 64th Annual Convention of the Society-of-Biological-Psychiatry
CY MAY 14-16, 2009
CL Vancouver, CANADA
SP Soc Biol Psychiat
C1 [Hezel, Dianne M.; Sampaio, Aline; Stewart, S. Evelyn] McLean Hosp, Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA USA.
[Egan-Stack, Denise] McLean Hosp, Obsess Compuls Disorder Inst, Belmont, MA 02178 USA.
RI Stewart, Evelyn/K-6961-2014
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD APR 15
PY 2009
VL 65
IS 8
MA 396
BP 119S
EP 119S
PG 1
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 432OS
UT WOS:000265144200385
ER
PT J
AU Sallee, F
Spencer, T
Connor, D
Lopez, F
Lyne, A
Tremblay, G
AF Sallee, Floyd
Spencer, Thomas
Connor, Daniel
Lopez, Frank
Lyne, Andrew
Tremblay, Gerald
TI Effects of Guanfacine Extended Release on Secondary Measures in Children
With Attention-Deficit/Hyperactivity Disorder and Oppositional Symptoms
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
CT 64th Annual Convention of the Society-of-Biological-Psychiatry
CY MAY 14-16, 2009
CL Vancouver, CANADA
SP Soc Biol Psychiat
C1 [Sallee, Floyd] Univ Cincinnati, Coll Med, Dept Psychiat, Cincinnati, OH USA.
[Spencer, Thomas] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Clin & Res Program Pediat Psychopharmacol, Boston, MA USA.
[Connor, Daniel] Univ Connecticut, Sch Med, Farmington, CT USA.
[Lopez, Frank] Childrens Dev Ctr, Winter Pk, FL USA.
[Lyne, Andrew] Shire Pharmaceut Dev Ltd, Global Biomet, Basingstoke, Hants, England.
[Tremblay, Gerald] Shire Dev Inc, Neurosci, Wayne, PA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD APR 15
PY 2009
VL 65
IS 8
MA 488
BP 149S
EP 149S
PG 1
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 432OS
UT WOS:000265144200477
ER
PT J
AU Levitt, JJ
Alvarado, JL
Kubicki, M
Nestor, PG
McCarley, RW
Shenton, ME
AF Levitt, James J.
Alvarado, Jorge L.
Kubicki, Marek
Nestor, Paul G.
McCarley, Robert W.
Shenton, Martha E.
TI Decreased Fractional Anisotropy in the Anterior Limb of the Internal
Capsule in Schizophrenia and its Cognitive Correlates
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
CT 64th Annual Convention of the Society-of-Biological-Psychiatry
CY MAY 14-16, 2009
CL Vancouver, CANADA
SP Soc Biol Psychiat
C1 [Levitt, James J.; Nestor, Paul G.; McCarley, Robert W.; Shenton, Martha E.] Harvard Univ, Sch Med, VA Boston Hlth Care Syst, Brockton, MA 02401 USA.
[Levitt, James J.; Alvarado, Jorge L.; Kubicki, Marek; Shenton, Martha E.] Harvard Univ, Brigham & Womens Hosp, Psychiat Neuroimaging Lab, Sch Med, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD APR 15
PY 2009
VL 65
IS 8
MA 520
BP 159S
EP 160S
PG 2
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 432OS
UT WOS:000265144200509
ER
PT J
AU Schwartz, CE
Blackford, JU
Zald, DH
Kalin, N
AF Schwartz, Carl E.
Blackford, Jennifer Urbano
Zald, David H.
Kalin, Ned
TI Neural Substrates of Developmental Risk for Psychiatric Disorders:
Research Methods
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
CT 64th Annual Convention of the Society-of-Biological-Psychiatry
CY MAY 14-16, 2009
CL Vancouver, CANADA
SP Soc Biol Psychiat
C1 [Schwartz, Carl E.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Blackford, Jennifer Urbano; Zald, David H.] Vanderbilt Univ, Nashville, TN USA.
[Kalin, Ned] Univ Wisconsin, Dept Psychiat, Madison, WI 53706 USA.
NR 0
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 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD APR 15
PY 2009
VL 65
IS 8
MA 532
BP 163S
EP 163S
PG 1
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 432OS
UT WOS:000265144200520
ER
PT J
AU Vinogradov, S
Deicken, R
Ellman, LM
Kern, DM
Genevsky, A
Poole, JH
Kremen, W
Schaefer, C
Brown, AS
AF Vinogradov, Sophia
Deicken, Ray
Ellman, Lauren M.
Kern, David M.
Genevsky, Alex
Poole, John H.
Kremen, William
Schaefer, Catherine
Brown, Alan S.
TI The Interaction of Fetal Hypoxia and Prenatal infection in
Schizophrenia: Investigating Effects of Concomitant Obstetric
Complications
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
CT 64th Annual Convention of the Society-of-Biological-Psychiatry
CY MAY 14-16, 2009
CL Vancouver, CANADA
SP Soc Biol Psychiat
C1 [Vinogradov, Sophia; Deicken, Ray] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Ellman, Lauren M.; Kern, David M.; Brown, Alan S.] Columbia Univ, New York, NY USA.
[Genevsky, Alex] San Francisco VA Med Ctr, San Francisco, CA USA.
[Poole, John H.] Palo Alto VA, Palo Alto, CA USA.
[Kremen, William] Univ Calif San Diego, San Diego, CA 92103 USA.
[Kremen, William] Kaiser Permanente, Div Res, Res, Oakland, CA USA.
NR 0
TC 0
Z9 0
U1 4
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD APR 15
PY 2009
VL 65
IS 8
SU S
MA 629
BP 191S
EP 192S
PG 2
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 432OS
UT WOS:000265144200608
ER
PT J
AU Vinogradov, S
Deicken, R
Ellman, LM
Kern, DM
Cook, CL
Poole, JH
Kremen, W
Schaefer, C
Brown, AS
AF Vinogradov, Sophia
Deicken, Ray
Ellman, Lauren M.
Kern, David M.
Cook, Colleen L.
Poole, John H.
Kremen, William
Schaefer, Catherine
Brown, Alan S.
TI Fetal Hypoxia and Schizophrenia: A Longitudinal Case-Control Study of
Cognitive and Brain Volumetric Outcomes
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
CT 64th Annual Convention of the Society-of-Biological-Psychiatry
CY MAY 14-16, 2009
CL Vancouver, CANADA
SP Soc Biol Psychiat
C1 [Vinogradov, Sophia; Deicken, Ray] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Ellman, Lauren M.; Kern, David M.; Brown, Alan S.] Columbia Univ, New York, NY USA.
[Cook, Colleen L.] San Francisco VA Med Ctr, San Francisco, CA USA.
[Poole, John H.] Palo Alto VA, Palo Alto, CA USA.
[Kremen, William] Univ Calif San Diego, San Diego, CA 92103 USA.
[Schaefer, Catherine] Kaiser Permanente, Div Res, Res, Oakland, CA USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD APR 15
PY 2009
VL 65
IS 8
SU S
MA 628
BP 191S
EP 191S
PG 1
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 432OS
UT WOS:000265144200607
ER
PT J
AU Levitt, JJ
Bobrow, LH
Lucia, DM
Smith, KM
McCarley, RW
Shenton, ME
AF Levitt, James J.
Bobrow, Laurel H.
Lucia, Diandra M.
Smith, Katherine M.
McCarley, Robert W.
Shenton, Martha E.
TI An MRI Study of Anterior Cingulate Gyrus Subregions in Schizophrenia
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
CT 64th Annual Convention of the Society-of-Biological-Psychiatry
CY MAY 14-16, 2009
CL Vancouver, CANADA
SP Soc Biol Psychiat
C1 [Levitt, James J.; McCarley, Robert W.; Shenton, Martha E.] Harvard Univ, Sch Med, VA Boston Hlth Care Syst, Brockton, MA 02401 USA.
[Levitt, James J.; Bobrow, Laurel H.; Lucia, Diandra M.; Smith, Katherine M.; Shenton, Martha E.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Psychiat Neuroimaging Lab, Brockton, MA 02401 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD APR 15
PY 2009
VL 65
IS 8
MA 638
BP 194S
EP 194S
PG 1
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 432OS
UT WOS:000265144200616
ER
PT J
AU Pendergrass, JC
Weiss, AR
Heckers, S
AF Pendergrass, Jo Cara
Weiss, Anthony R.
Heckers, Stephan
TI Abnormal Cortical-Thalamic-Cerebellar Recruitment During Successful
Memory Retrieval in Schizophrenia
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
CT 64th Annual Convention of the Society-of-Biological-Psychiatry
CY MAY 14-16, 2009
CL Vancouver, CANADA
SP Soc Biol Psychiat
C1 [Pendergrass, Jo Cara; Heckers, Stephan] Vanderbilt Univ, Med Ctr, Nashville, TN USA.
[Weiss, Anthony R.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RI Heckers, Stephan/F-3051-2010
OI Heckers, Stephan/0000-0003-3601-9910
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD APR 15
PY 2009
VL 65
IS 8
MA 640
BP 195S
EP 195S
PG 1
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 432OS
UT WOS:000265144200618
ER
PT J
AU Melonakos, ED
Shenton, M
Rathi, Y
Bouix, S
Kubicki, M
AF Melonakos, Eric D.
Shenton, Martha
Rathi, Yogesh
Bouix, Sylvain
Kubicki, Marek
TI Can Whole Brain Voxel-Based Morphometry Studies Applied to DTI Data
Localize White Matter Changes in Schizophrenia?
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
CT 64th Annual Convention of the Society-of-Biological-Psychiatry
CY MAY 14-16, 2009
CL Vancouver, CANADA
SP Soc Biol Psychiat
C1 [Melonakos, Eric D.; Shenton, Martha; Rathi, Yogesh; Bouix, Sylvain; Kubicki, Marek] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Psychiat,Psychiat Neuroimaging Lab, Boston, MA 02115 USA.
[Shenton, Martha] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA.
[Shenton, Martha; Kubicki, Marek] Harvard Univ, Sch Med, Dept Psychiat, VA Boston Healthcare Syst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD APR 15
PY 2009
VL 65
IS 8
SU S
MA 673
BP 204S
EP 205S
PG 2
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 432OS
UT WOS:000265144200649
ER
PT J
AU Melonakos, ED
Shenton, ME
Markant, D
Alvarado, J
Westin, CF
Kubicki, M
AF Melonakos, Eric D.
Shenton, Martha E.
Markant, Doug
Alvarado, Jorge
Westin, Carl-Fredrik
Kubicki, Marek
TI White Matter Properties of Orbitofrontal Connections in Schizophrenia
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
CT 64th Annual Convention of the Society-of-Biological-Psychiatry
CY MAY 14-16, 2009
CL Vancouver, CANADA
SP Soc Biol Psychiat
C1 [Melonakos, Eric D.; Shenton, Martha E.; Markant, Doug; Alvarado, Jorge; Kubicki, Marek] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Psychiat,Psychiat Neuroimaging Lab, Boston, MA 02115 USA.
[Shenton, Martha E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA.
[Shenton, Martha E.; Kubicki, Marek] Harvard Univ, Sch Med, Dept Psychiat, VA Boston Healthcare Syst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD APR 15
PY 2009
VL 65
IS 8
SU S
MA 672
BP 204S
EP 204S
PG 1
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 432OS
UT WOS:000265144200648
ER
PT J
AU Daly, EJ
Trivedi, MH
Fava, M
Shelton, R
Wisniewski, SR
Morris, DW
Stegman, D
Preskorn, SH
Rush, AJ
AF Daly, Ella J.
Trivedi, Madhukar H.
Fava, Maurizio
Shelton, Richard
Wisniewski, Stephen R.
Morris, David W.
Stegman, Diane
Preskorn, Sheldon H.
Rush, A. J.
TI The Relationship Between Adverse Events During SSRI Treatment for MDD
and Nonremission - Report from the Suicide Assessment Methodology Study
(SAMS)
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
CT 64th Annual Convention of the Society-of-Biological-Psychiatry
CY MAY 14-16, 2009
CL Vancouver, CANADA
SP Soc Biol Psychiat
C1 [Daly, Ella J.; Trivedi, Madhukar H.; Morris, David W.; Stegman, Diane; Rush, A. J.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Daly, Ella J.] Johnson & Johnson Pharmaceut Res & Dev, Titusville, NJ USA.
[Fava, Maurizio; Shelton, Richard] Massachusetts Gen Hosp, Clin Psychopharmacol Unit, Boston, MA 02114 USA.
[Wisniewski, Stephen R.] Vanderbilt Univ, Nashville, TN USA.
[Preskorn, Sheldon H.] Univ Kansas, Sch Med, Wichita, KS 67214 USA.
[Rush, A. J.] Duke Natl Univ Singapore, Singapore, Singapore.
RI Preskorn, Sheldon/L-9839-2016
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD APR 15
PY 2009
VL 65
IS 8
MA 715
BP 217S
EP 217S
PG 1
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 432OS
UT WOS:000265144200689
ER
PT J
AU Nguyen, VT
Eskandari, F
Duan, ZG
Wright, E
Cizza, G
AF Nguyen, Vi T.
Eskandari, Farideh
Duan, Zhigang
Wright, Elizabeth
Cizza, Giovanni
TI Premenopausal Women with Major Depressive Disorder (MDD) have Lower
24-hour Adiponectin Levels with Preserved Circadian Rhythm and Higher
ACTH vs. Cortisol Correlation: Implications for Greater Metabolic and
Cardiovascular Risk
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
CT 64th Annual Convention of the Society-of-Biological-Psychiatry
CY MAY 14-16, 2009
CL Vancouver, CANADA
SP Soc Biol Psychiat
C1 [Nguyen, Vi T.; Cizza, Giovanni] NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD USA.
[Nguyen, Vi T.] Massachusetts Gen Hosp, Pediat Endocrine Unit, Boston, MA 02114 USA.
[Eskandari, Farideh] NIMH, Sect Neuroendocrine Immunol & Behav, Integrat Neural Immune Program, NIH, Bethesda, MD 20892 USA.
[Duan, Zhigang; Wright, Elizabeth] NIDDK, Off Director, NIH, Bethesda, MD USA.
NR 0
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 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD APR 15
PY 2009
VL 65
IS 8
MA 753
BP 230S
EP 230S
PG 1
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 432OS
UT WOS:000265144200727
ER
PT J
AU Perlis, RH
Houston, JR
Adams, DH
Heinloth, AN
Fijal, B
AF Perlis, Roy H.
Houston, John R.
Adams, David H.
Heinloth, Alexandra N.
Fijal, Bonnie
TI Failure To Replicate Prior Genetic Associations Of SNPs in Candidate
Genes With Antidepressant Treatment Response in Patients Treated With
Duloxetine
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
CT 64th Annual Convention of the Society-of-Biological-Psychiatry
CY MAY 14-16, 2009
CL Vancouver, CANADA
SP Soc Biol Psychiat
C1 [Perlis, Roy H.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Houston, John R.; Adams, David H.; Fijal, Bonnie] Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA.
[Heinloth, Alexandra N.] I3Statprobe, UnitedHlth Grp, Ann Arbor, MI USA.
NR 0
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 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD APR 15
PY 2009
VL 65
IS 8
MA 754
BP 230S
EP 230S
PG 1
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 432OS
UT WOS:000265144200728
ER
PT J
AU Crabbe, JC
Metten, P
Rhodes, JS
Yu, CH
Brown, LL
Phillips, TJ
Finn, DA
AF Crabbe, John C.
Metten, Pamela
Rhodes, Justin S.
Yu, Chia-Hua
Brown, Lauren Lyon
Phillips, Tamara J.
Finn, Deborah A.
TI A Line of Mice Selected for High Blood Ethanol Concentrations Shows
Drinking in the Dark to Intoxication
SO BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE DID; ethanol consumption; genetic animal models; HDID; intoxication;
mouse; pharmacogenetics; selective breeding
ID VOLUNTARY ALCOHOL-CONSUMPTION; C57BL/6J MICE; STRAIN DIFFERENCES;
SCHEDULED ACCESS; LATERAL SEPTUM; ANIMAL-MODELS; GENETICS; RAT;
SUSCEPTIBILITY; PERCEPTION
AB Background: Many animal models of alcoholism have targeted aspects of excessive alcohol intake (abuse) and dependence. In the rodent, models aimed at increasing alcohol self-ad ministration have used genetic or environmental manipulations, or their combination. Strictly genetic manipulations (e.g., comparison of inbred strains or targeted mutants, selective breeding) have not yielded rat or mouse genotypes that will regularly and voluntarily drink alcohol to the point of intoxication. Although some behavioral manipulations (e.g., scheduling or limiting access to alcohol, adding a sweetener)will induce mice or rats to drink enough alcohol to become intoxicated, these typically require significant food or water restriction or a long time to develop. We report progress toward the development of a new genetic animal model for high levels of alcohol drinking.
Methods: High Drinking in the Dark (HDID-1) mice have been selectively bred for high blood ethanol concentrations (BEC, ideally exceeding 100 mg%) resulting from the ingestion of a 20% alcohol solution.
Results: After 11 generations of selection, more than 56% of the population now exceeds this BEC after a 4-hour drinking session in which a single bottle containing 20% ethanol is available. The dose of ethanol consumed also produced quantifiable signs of intoxication.
Conclusions: These mice will be useful for mechanistic studies of the biological and genetic contributions to excessive drinking.
C1 [Crabbe, John C.; Metten, Pamela; Yu, Chia-Hua; Brown, Lauren Lyon; Phillips, Tamara J.; Finn, Deborah A.] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland Alcohol Res Ctr, Portland, OR 97201 USA.
[Crabbe, John C.; Metten, Pamela; Yu, Chia-Hua; Brown, Lauren Lyon; Phillips, Tamara J.; Finn, Deborah A.] VA Med Ctr, Portland, OR USA.
[Rhodes, Justin S.] Univ Illinois, Beckman Inst, Dept Psychol, Urbana, IL USA.
RP Crabbe, JC (reprint author), Portland VA Med Ctr, R&D 12,3710 SW Vet Hosp Rd, Portland, OR 97239 USA.
EM crabbe@ohsu.edu
FU National Institutes of Health and by the Department of Veterans Affairs
[AA010760, AA013478, AA013519]
FX These studies were conducted as part of the Integrative Neuroscience
Initiative on Alcoholism of the National Institute on Alcohol Abuse and
Alcoholism and were supported by Grant Nos. AA010760, AA013478, and
AA013519 from the National Institutes of Health and by the Department of
Veterans Affairs. We thank Andy Jade Cameron, Alex Henry, Katie
Mordarski, Jason Schlumbohm, Michelle Sorensen, and Stephanie Spence for
expert technical assistance.
NR 36
TC 70
Z9 70
U1 1
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD APR 15
PY 2009
VL 65
IS 8
BP 662
EP 670
DI 10.1016/j.biopsych.2008.11.002
PG 9
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 428OG
UT WOS:000264857400005
PM 19095222
ER
PT J
AU Sos, ML
Koker, M
Weir, BA
Heynck, S
Rabinovsky, R
Zander, T
Seeger, JM
Weiss, J
Fischer, F
Frommolt, P
Michel, K
Peifer, M
Mermel, C
Girard, L
Peyton, M
Gazdar, AF
Minna, JD
Garraway, LA
Kashkar, H
Pao, W
Meyerson, M
Thomas, RK
AF Sos, Martin L.
Koker, Miriam
Weir, Barbara A.
Heynck, Stefanie
Rabinovsky, Rosalia
Zander, Thomas
Seeger, Jens M.
Weiss, Jonathan
Fischer, Florian
Frommolt, Peter
Michel, Kathrin
Peifer, Martin
Mermel, Craig
Girard, Luc
Peyton, Michael
Gazdar, Adi F.
Minna, John D.
Garraway, Levi A.
Kashkar, Hamid
Pao, William
Meyerson, Matthew
Thomas, Roman K.
TI PTEN Loss Contributes to Erlotinib Resistance in EGFR-Mutant Lung Cancer
by Activation of Akt and EGFR
SO CANCER RESEARCH
LA English
DT Article
ID TYROSINE KINASE INHIBITORS; ACQUIRED-RESISTANCE; ADENOCARCINOMA;
SENSITIVITY; MUTATIONS; SURVIVAL; PATHWAY; EXPRESSION; GEFITINIB; CELLS
AB Clinical resistance to epidermal growth factor receptor (EGFR) inhibition in lung cancer has been linked to the emergence of the EGFR T790M resistance mutation or amplification of MET. Additional mechanisms contributing to EGFR inhibitor resistance remain elusive. By applying combined analyses of gene expression, copy number, and biochemical analyses of EGFR inhibitor responsiveness, we identified homozygous loss of PTEN to segregate EGFR-dependent and EGFR-independent cells. We show that in EGFR-dependent cells, PTEN loss partially uncouples mutant EGFR from downstream signaling and activates EGFR, thereby contributing to erlotinib resistance. The clinical relevance of our findings is supported by the observation of PTEN loss in I out of 24 primary EGFR-mutant non-small cell lung cancer (NSCLC) tumors. These results suggest a novel resistance mechanism in EGFR-mutant NSCLC involving PTEN loss. [Cancer Res 2009;69(8):3256-61]
C1 [Thomas, Roman K.] Max Planck Soc, Chem Genom Ctr, Dortmund, Germany.
[Pao, William] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10021 USA.
[Minna, John D.] Univ Texas SW Med Ctr Dallas, Dept Internal Med & Pharmacol, Dallas, TX 75390 USA.
[Gazdar, Adi F.] Univ Texas SW Med Ctr Dallas, Dept Pathol, Dallas, TX 75390 USA.
[Girard, Luc; Peyton, Michael; Gazdar, Adi F.; Minna, John D.] Univ Texas SW Med Ctr Dallas, Hamon Ctr Therapeut Oncol Res, Dallas, TX 75390 USA.
[Meyerson, Matthew] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Garraway, Levi A.; Meyerson, Matthew] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA.
[Rabinovsky, Rosalia; Mermel, Craig; Garraway, Levi A.; Meyerson, Matthew] Harvard Univ, Sch Med, Dept Med Oncol, Boston, MA 02115 USA.
[Weir, Barbara A.; Mermel, Craig; Garraway, Levi A.; Meyerson, Matthew] Broad Inst Harvard, Cambridge, MA USA.
[Weir, Barbara A.; Mermel, Craig; Garraway, Levi A.; Meyerson, Matthew] MIT, Cambridge, MA 02139 USA.
[Frommolt, Peter] Inst Med Stat Informat & Epidemiol, Cologne, Germany.
[Seeger, Jens M.; Kashkar, Hamid] Inst Med Microbiol Immunol & Hyg, Cologne, Germany.
[Sos, Martin L.; Koker, Miriam; Heynck, Stefanie; Weiss, Jonathan; Fischer, Florian; Michel, Kathrin; Peifer, Martin; Thomas, Roman K.] Max Planck Soc, Max Planck Inst Neurol Res, Klaus Joachim Zulch Labs, D-50931 Cologne, Germany.
[Sos, Martin L.; Koker, Miriam; Heynck, Stefanie; Weiss, Jonathan; Fischer, Florian; Michel, Kathrin; Peifer, Martin; Thomas, Roman K.] Univ Cologne, Fac Med, Cologne, Germany.
[Zander, Thomas; Thomas, Roman K.] Univ Cologne, Ctr Integrated Oncol, Cologne, Germany.
[Zander, Thomas; Thomas, Roman K.] Univ Cologne, Dept Internal Med 1, Cologne, Germany.
RP Thomas, RK (reprint author), Max Planck Soc, Max Planck Inst Neurol Res, Klaus Joachim Zulch Labs, Gleueler Str 50, D-50931 Cologne, Germany.
EM nini@nf.mpg.de
RI Peyton, Michael/A-8728-2008; Meyerson, Matthew/E-7123-2012; Frommolt,
Peter/L-9656-2016
OI Frommolt, Peter/0000-0002-1966-8014
FU International Association for the Study of Lung Cancer; Deutsche
Krebshilfe [107954]; Fritz-Thyssen-Stiftung [10.08.2.175]; NGFN-Plus
Program of the German Ministry of Science and Education [01GS08100];
Specialized Programs of Research Excellence [P50CA70907]; DOD PROSPECT;
Longenbaugh Foundation
FX R.K. Thomas is a fellow of the International Association for the Study
of Lung Cancer: and is supported by the Deutsche Krebshilfe (107954),
the Fritz-Thyssen-Stiftung (10.08.2.175), and the NGFN-Plus Program of
the German Ministry of Science and Education (BMBF, 01GS08100). J.D.
Minna is supported by grants from the Specialized Programs of Research
Excellence P50CA70907, DOD PROSPECT, and the Longenbaugh Foundation.
NR 21
TC 233
Z9 254
U1 3
U2 14
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2009
VL 69
IS 8
BP 3256
EP 3261
DI 10.1158/0008-5472.CAN-08-4055
PG 6
WC Oncology
SC Oncology
GA 435AF
UT WOS:000265314900004
PM 19351834
ER
PT J
AU Sun, T
Wang, QB
Balk, S
Brown, M
Lee, GSM
Kantoff, P
AF Sun, Tong
Wang, Qianben
Balk, Steven
Brown, Myles
Lee, Gwo-Shu Mary
Kantoff, Philip
TI The Role of microRNA-221 and microRNA-222 in Androgen-Independent
Prostate Cancer Cell Lines
SO CANCER RESEARCH
LA English
DT Article
ID LUNG-CANCER; EXPRESSION; CARCINOMA; RECEPTOR; GROWTH; PROLIFERATION;
PROGRESSION; P27(KIP1); MIR-221; SIGNATURES
AB Androgen-dependent prostate cancer typically progresses to castration-resistant prostate cancer (CRPC) after the androgen deprivation therapy. MicroRNAs (mill) are noncoding small RNAs (19-25nt) that play an important role in the regulation of gene expression. Recent studies have shown that mill expression patterns are significantly different in normal and neoplastic prostate epithelial cells. However, the importance of mills in the development of CRPC has not yet been explored. By performing genome-wide expression profiling of mills, we found that expression levels of several mills, in particular miR-221 and miR-222, were significantly increased, in CRPC cells (the LNCaP-derived cell line LNCaP-Abl) compared with those in the androgen-dependent prostate cancer cell line (LNCaP). Overexpression of miR-221 or miR-222 in LNCaP or another androgen-dependent cell line, LAPC-4, significantly reduced the level of the dihydrotestosterone (DHT) induced up-regulation of prostate-specific antigen (PSA) expression and increased androgen-independent growth of LNCaP cells. Knocking down the expression level of miR-221 and miR-222 with antagonist mills in the LNCaP-Abl cell line restored the response to the DHT induction of PSA transcription and also increased the growth response of the LNCaP-Abl cells to the androgen treatment. Changing the expression level of p27/kip1, a known target of miR-221 and miR-222, alone in LNCaP cells affected the DHT-independent cell growth but did not significantly influence the response of PSA transcription to the DHT treatment. In conclusion, our data suggest the involvement of miR-221 and miR-222 in the development or maintenance of the CRPC phenotype. [Cancer Res 2009;69(8):3356-63]
C1 [Sun, Tong; Wang, Qianben; Brown, Myles; Lee, Gwo-Shu Mary; Kantoff, Philip] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Sun, Tong; Wang, Qianben; Balk, Steven; Brown, Myles; Lee, Gwo-Shu Mary; Kantoff, Philip] Harvard Univ, Sch Med, Boston, MA USA.
[Balk, Steven] Beth Israel Deaconess Med Ctr, Dept Med, Canc Biol Program, Boston, MA 02215 USA.
RP Lee, GSM (reprint author), Dana Farber Canc Inst, Dept Med Oncol, D710B,44 Binney St, Boston, MA 02115 USA.
EM gwo-shu_lee@dfci.harvard.edu
RI Wang, Qianben/E-4267-2011;
OI Brown, Myles/0000-0002-8213-1658
FU NCI NIH HHS [2 P50 CA090381-06, P50 CA090381-06, P50 CA090381]
NR 35
TC 145
Z9 157
U1 0
U2 4
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2009
VL 69
IS 8
BP 3356
EP 3363
DI 10.1158/0008-5472.CAN-08-4112
PG 8
WC Oncology
SC Oncology
GA 435AF
UT WOS:000265314900018
PM 19351832
ER
PT J
AU Ohashi, E
Kogai, T
Kagechika, H
Brent, GA
AF Ohashi, Emi
Kogai, Takahiko
Kagechika, Hiroyuki
Brent, Gregory A.
TI Activation of the PI3 Kinase Pathway By Retinoic Acid Mediates
Sodium/Iodide Symporter Induction and Iodide Transport in MCF-7 Breast
Cancer Cells
SO CANCER RESEARCH
LA English
DT Article
ID RADIOIODIDE UPTAKE; NONGENOMIC ACTIONS; SIGNALING PATHWAY;
ESTROGEN-RECEPTOR; GENE-EXPRESSION; PROTEIN; NUCLEAR; DIFFERENTIATION;
3-KINASE; TARGET
AB Iodide uptake in the thyroid and breast is mediated by the sodium/iodide symporter (NIS). NIS activation is used for radioiodide imaging and therapeutic ablation of thyroid carcinoma. NIS is expressed in >70% of breast cancers but at a level insufficient for radioiodine treatment. All-traps retinoic acid (tRA) induces NIS gene expression and functional iodide uptake in human breast cancer cell lines and mouse breast cancer models. tRA usually regulates gene expression by direct interaction of RA receptor (RAR) with a target gene, but it can also act through nongenomic pathways. We report a direct influence of tRA treatment on the phosphoinositide 3-kinase (PI3K) signal transduction pathway that mediates tRA-induced NIS expression in MCF-7 breast cancer cells. MCF-7 cells express all three RAR isoforms, alpha, beta, and gamma, and RXR alpha. We previously identified RAR beta and RXR alpha as important for NIS induction by tRA. Treatment with LY294002, the PI3K inhibitor, or p85 alpha knockdown with siRNA abolished tRA-induced NIS expression. Immunoprecipitation experiments and glutathione S-transferase pull-down assay showed a direct interaction between RAR beta 2, RXR alpha, and p85 alpha. RA also induced rapid activation of Akt in MCF-7 cells. Treatment with an Akt inhibitor or Akt knockdown with siRNA reduced NIS expression. These findings indicate that RA induction of NIS in MCF-7 cells is mediated, by rapid activation of the PI3K pathway and involves direct interaction with RAR and retinoid X receptor. Defining these mechanisms should lead to methods to further enhance NIS expression, as well as retinoid targets that influence growth and differentiation of breast cancer. [Cancer Res 2009;69(8):3443-50]
C1 [Ohashi, Emi; Kogai, Takahiko; Brent, Gregory A.] Univ Calif Los Angeles, Mol Endocrinol Lab, VA Greater Los Angeles Healthcare Syst, David Geffen Sch Med,Dept Med, Los Angeles, CA 90073 USA.
[Ohashi, Emi; Kogai, Takahiko; Brent, Gregory A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90073 USA.
[Kagechika, Hiroyuki] Tokyo Med & Dent Univ, Sch Biomed Sci, Chiyoda Ku, Tokyo, Japan.
RP Brent, GA (reprint author), Univ Calif Los Angeles, Mol Endocrinol Lab, VA Greater Los Angeles Healthcare Syst, David Geffen Sch Med,Dept Med, Bldg 114,Room 230,11301 Wilshire Blvd, Los Angeles, CA 90073 USA.
EM gbrent@ucla.edu
FU NIH [RO1 CA089364]
FX Grant support: NIH RO1 CA089364 (GA Brent).
NR 37
TC 32
Z9 34
U1 0
U2 6
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2009
VL 69
IS 8
BP 3443
EP 3450
DI 10.1158/0008-5472.CAN-08-3234
PG 8
WC Oncology
SC Oncology
GA 435AF
UT WOS:000265314900028
PM 19351850
ER
PT J
AU Wakimoto, H
Kesari, S
Farrell, CJ
Curry, WT
Zaupa, C
Aghi, M
Kuroda, T
Stemmer-Rachamimov, A
Shah, K
Liu, TC
Jeyaretna, DS
Debasitis, J
Pruszak, J
Martuza, RL
Rabkin, SD
AF Wakimoto, Hiroaki
Kesari, Santosh
Farrell, Christopher J.
Curry, William T., Jr.
Zaupa, Cecile
Aghi, Manish
Kuroda, Toshihiko
Stemmer-Rachamimov, Anat
Shah, Khalid
Liu, Ta-Chiang
Jeyaretna, Deva S.
Debasitis, Jason
Pruszak, Jan
Martuza, Robert L.
Rabkin, Samuel D.
TI Human Glioblastoma-Derived Cancer Stem Cells: Establishment of Invasive
Glioma Models and Treatment with Oncolytic Herpes Simplex Virus Vectors
SO CANCER RESEARCH
LA English
DT Article
ID MALIGNANT GLIOMA; DOPAMINERGIC-NEURONS; NEURAL PRECURSORS; EXPRESSION;
TUMORS; GROWTH; THERAPY; VIROTHERAPY; IDENTIFICATION; ANGIOGENESIS
AB Glioblastoma, the most malignant type of primary brain tumor, is one of the solid cancers where cancer stem cells have been isolated, and studies have suggested resistance of those cells to chemotherapy and radiotherapy. Here, we report the establishment of CSC-enriched cultures derived from human glioblastoma specimens. They grew as neurospheres in serum-free medium with epidermal growth factor and fibroblast growth factor 2, varied in the level of CD133 expression and very efficiently formed highly invasive and/or vascular tumors upon intracerebral implantation into immunodeficient mice. As a novel therapeutic strategy for glioblastoma-derived cancer stem-like cells (GBM-SC), we have tested oncolytic herpes simplex virus (oHSV) vectors. We show that although ICP6 (UL39)-deleted mutants kill GBM-SCs as efficiently as wild-type HSV, the deletion of gamma 34.5 significantly attenuated the vectors due to poor replication. However, this was significantly reversed by the additional deletion of alpha 47. Infection with oHSV G47 Delta (ICP6(-), gamma 34.5(-), alpha 47(-)) not only killed GBM-SCs but also inhibited their self-renewal as evidenced by the inability of viable cells to form secondary tumor spheres. Importantly, despite the highly invasive nature of the intracerebral tumors generated by GBM-SCs, intratumoral injection of 6470 significantly prolonged survival. These results for the first time show the efficacy of oHSV against human GBM-SCs, and correlate this cytotoxic property with specific oHSV mutations. This is important for designing new oHSV vectors and clinical trials. Moreover, the new glioma models described in this study provide powerful tools for testing experimental therapeutics and studying invasion and angiogenesis. [Cancer Res 2009;69(8):3472-81]
C1 [Wakimoto, Hiroaki; Farrell, Christopher J.; Curry, William T., Jr.; Zaupa, Cecile; Aghi, Manish; Kuroda, Toshihiko; Liu, Ta-Chiang; Jeyaretna, Deva S.; Debasitis, Jason; Martuza, Robert L.; Rabkin, Samuel D.] Massachusetts Gen Hosp, Brain Tumor Res Ctr, Mol Neurosurg Lab, Dept Neurosurg, Boston, MA 02114 USA.
[Stemmer-Rachamimov, Anat] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Shah, Khalid] Massachusetts Gen Hosp, Mol Neurotherapy & Imaging Lab, Ctr Mol Imaging Res, Dept Radiol,Dept Neurol, Boston, MA 02114 USA.
[Kesari, Santosh] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol & Med Oncol,Dept Neurol,Brigham &, Boston, MA 02115 USA.
[Pruszak, Jan] Harvard Univ, McLean Hosp, Sch Med, Ctr Neurogenerat Res, Belmont, MA 02178 USA.
RP Wakimoto, H (reprint author), Massachusetts Gen Hosp, Brain Tumor Res Ctr, Mol Neurosurg Lab, Dept Neurosurg, CPZN-3800,185 Cambridge St, Boston, MA 02114 USA.
EM hwakimoto@partners.org
RI rabkin, samuel/C-2443-2012; Kesari, Santosh/E-8461-2013; Pruszak,
Jan/G-6972-2015;
OI rabkin, samuel/0000-0003-2344-2795; Pruszak, Jan/0000-0003-4297-4009;
Kuroda, Toshihiko/0000-0001-6660-8930
FU NIH [NS-032677, K08 CA124804]; Department of Defense [W81XWH-07-1-0359];
Sontag Foundation Distinguished Scientist Grant
FX NIH grant NS-032677 (R.L. Martuza), Department of Defense grant
W81XWH-07-1-0359 (S.D. Rabkin), and NIH grant K08 CA124804 and a Sontag
Foundation Distinguished Scientist Grant (S. Kesari).
NR 50
TC 138
Z9 143
U1 4
U2 18
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2009
VL 69
IS 8
BP 3472
EP 3481
DI 10.1158/0008-5472.CAN-08-3886
PG 10
WC Oncology
SC Oncology
GA 435AF
UT WOS:000265314900032
PM 19351838
ER
PT J
AU Braggio, E
Keats, JJ
Leleu, X
Van Wier, S
Jimenez-Zepeda, VH
Valdez, R
Schop, RFJ
Price-Troska, T
Henderson, K
Sacco, A
Azab, F
Greipp, P
Gertz, M
Hayman, S
Rajkumar, SV
Carpten, J
Chesi, M
Barrett, M
Stewart, AK
Dogan, A
Bergsagel, L
Ghobrial, IM
Fonseca, R
AF Braggio, Esteban
Keats, Jonathan J.
Leleu, Xavier
Van Wier, Scott
Jimenez-Zepeda, Victor H.
Valdez, Riccardo
Schop, Roelandt F. J.
Price-Troska, Tammy
Henderson, Kimberly
Sacco, Antonio
Azab, Feda
Greipp, Philip
Gertz, Morie
Hayman, Suzanne
Rajkumar, S. Vincent
Carpten, John
Chesi, Marta
Barrett, Michael
Stewart, A. Keith
Dogan, Ahmet
Bergsagel, Leif
Ghobrial, Irene M.
Fonseca, Rafael
TI Identification of Copy Number Abnormalities and Inactivating Mutations
in Two Negative Regulators of Nuclear Factor-kappa B Signaling Pathways
in Waldenstrom's Macroglobulinemia
SO CANCER RESEARCH
LA English
DT Article
ID CHRONIC LYMPHOCYTIC-LEUKEMIA; RECEPTOR-ASSOCIATED FACTOR-3;
MULTIPLE-MYELOMA; CELL LYMPHOMA; CHROMOSOMAL TRANSLOCATION; MALT
LYMPHOMA; 6Q DELETIONS; TARGET GENES; ACTIVATION; BORTEZOMIB
AB Waldenstrom's macroglobulinemia (WM) is a distinct clinicobiological entity defined as a B-cell neoplasm characterized by a lymphoplasmacytic infiltrate in bone marrow (BM) and IgM paraprotein production. Cytogenetic analyses were historically limited by difficulty in obtaining tumor metaphases, and the genetic basis of the disease remains poorly defined. Here, we performed a comprehensive analysis in 42 WM patients by using a high-resolution, array-based comparative genomic hybridization approach to unravel the genetic mechanisms associated with WM pathogenesis. Overall, 83% of cases have chromosomal abnormalities, with a median of three abnormalities per patient. Gain of 61) was the second most common abnormality (17%), and its presence was always concomitant with 6q loss. A minimal deleted region, including MIRN15A and MIRN16-1, was delineated on 13q14 in 10% of patients. Of interest, we reported biallelic deletions and/or inactivating mutations with uniparental disomy in tumor necrosis factor (TNF) receptor-associated factor 3 and TNF alpha-induced protein 3, two negative regulators of the nuclear factor-kappa B (NF-kappa B) signaling pathway. Furthermore, we confirmed the association between TRAF3 inactivation and increased transcriptional activity of NF-kappa B target genes. Mutational activation of the NF-kappa B pathway, which is normally activated by ligand receptor interactions within the BM microenvironment, highlights its biological importance, and suggests a therapeutic role for inhibitors of NF-kappa B pathway activation in the treatment of WM. [Cancer Res 2009;69(8):3579-88]
C1 [Braggio, Esteban; Keats, Jonathan J.; Van Wier, Scott; Jimenez-Zepeda, Victor H.; Valdez, Riccardo; Schop, Roelandt F. J.; Chesi, Marta; Stewart, A. Keith; Bergsagel, Leif; Fonseca, Rafael] Mayo Clin, Ctr Canc, Scottsdale, AZ 85259 USA.
[Leleu, Xavier; Sacco, Antonio; Azab, Feda; Ghobrial, Irene M.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Price-Troska, Tammy; Henderson, Kimberly; Greipp, Philip; Gertz, Morie; Hayman, Suzanne; Rajkumar, S. Vincent; Dogan, Ahmet] Mayo Clin, Rochester, MI USA.
[Carpten, John; Barrett, Michael] Translat Genom, Phoenix, AZ USA.
RP Fonseca, R (reprint author), Mayo Clin, Ctr Canc, 13400 E Shea Blvd,Collaborat Res Bldg 3-006, Scottsdale, AZ 85259 USA.
EM fonseca.rafael@mayo.edu
RI Bergsagel, Peter/A-7842-2011; Sacco, Antonio/K-4681-2016
OI Bergsagel, Peter/0000-0003-1523-7388; Fonseca,
Rafael/0000-0002-5938-3769; Sacco, Antonio/0000-0003-2945-9416
FU IWMF 2S; MMRF Fellowship; Mary-Lou Kurtz Fellowship [R01-AG020686,
CA83724-01, SPORE P50-CA100707-01]; National Cancer Institute
[P01-CA62242]; Donaldson Charitable Trust Fund; International
Waldenstrom Macroglobulinemia Foundation; Damon Runyon Cancer Research
Fund
FX IWMF 2S grant (E. Braggio). MMRF Fellowship and Gene and Mary-Lou Kurtz
Fellowship (J.J. Keats), grants R01-AG020686 and SPORE P50-CA100707-01
(P.L. Bergsagel), grant R01-CA83724-01, SPORE P50-CA100707-01 and
P01-CA62242 from the National Cancer Institute, and the Donaldson
Charitable Trust Fund (R. Fonseca), and the International Waldenstrom
Macroglobulinemia Foundation. R. Fonseca is a clinical investigator of
the Damon Runyon Cancer Research Fund.
NR 49
TC 68
Z9 70
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2009
VL 69
IS 8
BP 3579
EP 3588
DI 10.1158/0008-5472.CAN-08-3701
PG 10
WC Oncology
SC Oncology
GA 435AF
UT WOS:000265314900044
PM 19351844
ER
PT J
AU Sakamoto, KM
Frank, DA
AF Sakamoto, Kathleen M.
Frank, David A.
TI CREB in the Pathophysiology of Cancer: Implications for Targeting
Transcription Factors for Cancer Therapy
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID COLONY-STIMULATING FACTOR; ELEMENT-BINDING-PROTEIN; CHRONIC
MYELOID-LEUKEMIA; MULTIPLE SIGNALING PATHWAYS; GRANULOCYTE-MACROPHAGE;
FACTOR-RECEPTOR; POLYCYTHEMIA-VERA; LUNG-CANCER; CELL-LINE; PROGENITOR
CELLS
AB Transcription factors are key regulators of the pattern of gene expression in a cell and directly control central processes such as proliferation, survival, self-renewal, and invasion. Given this critical role, the function of transcription factors is normally regulated closely, often through transient phosphorylation. Although transcription factors are not often directly modified by mutations in cancer cells, they frequently become activated constitutively through mutations affecting "upstream" pathways. By continually driving the expression of key target genes, these oncogenic transcription factors play a central role in tumor pathogenesis. One such transcription factor is the cAMP-regulatory element-binding protein (CREB), which can be activated through phosphorylation by a number of kinases, including Akt, p90Rsk, protein kinase A, and calcium/calmodulin-dependent kinases and regulates genes whose deregulated expression promotes oncogenesis, including cyclins, Bcl-2 family members, and Egr-1. CREB is overexpressed and constitutively phosphorylated in a number of forms of human cancer, including acute myeloid leukemia (AML) and non-small cell lung cancer, and appears to play a direct role in disease pathogenesis and prognosis. Although transcription factors have not been a central focus of drug development, recent advances suggest that CREB and other such proteins may be worthwhile targets for cancer therapy.
C1 [Frank, David A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Sakamoto, Kathleen M.] Univ Calif Los Angeles, Mattel Childrens Hosp, Jonsson Comprehens Canc Ctr, Gwynne Hazen Cherry Mem Labs,Div Hematol Oncol, Los Angeles, CA USA.
[Sakamoto, Kathleen M.] David Geffen Sch Med, Dept Pathol & Lab Med, Brooklyn, NY USA.
[Sakamoto, Kathleen M.] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90024 USA.
[Sakamoto, Kathleen M.] CALTECH, Div Biol, Pasadena, CA 91125 USA.
[Frank, David A.] Harvard Univ, Sch Med, Boston, MA USA.
[Frank, David A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
RP Frank, DA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,Mayer 522B, Boston, MA 02115 USA.
EM david_frank@dfci.harvard.edu
FU National Institutes of Health [HL75826, HL83077]; American Cancer
Society [RSG-99-081-01-LIB]; Department of Defense [CM050077]; Leukemia
and Lymphoma Society Translational Research [6019-07]
FX Grant support: National Institutes of Health grants HL75826 and HL83077,
American Cancer Society grant RSG-99-081-01-LIB, the Department of
Defense (CM050077), and the Leukemia and Lymphoma Society Translational
Research Grant 6019-07 (K.M. Sakamoto).
NR 46
TC 107
Z9 111
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 APR 15
PY 2009
VL 15
IS 8
BP 2583
EP 2587
DI 10.1158/1078-0432.CCR-08-1137
PG 5
WC Oncology
SC Oncology
GA 435AC
UT WOS:000265314600002
PM 19351775
ER
PT J
AU Kuang, Y
Rogers, A
Yeap, BY
Wang, L
Makrigiorgos, M
Vetrand, K
Thiede, S
Distel, RJ
Janne, PA
AF Kuang, Yanan
Rogers, Andrew
Yeap, Beow Y.
Wang, Lilin
Makrigiorgos, Mike
Vetrand, Kristi
Thiede, Sara
Distel, Robert J.
Jaenne, Pasi A.
TI Noninvasive Detection of EGFR T790M in Gefitinib or Erlotinib Resistant
Non-Small Cell Lung Cancer
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID GROWTH-FACTOR-RECEPTOR; CHEMOTHERAPY-NAIVE PATIENTS; PROSPECTIVE
PHASE-II; ACQUIRED-RESISTANCE; CIRCULATING DNA; GENE-MUTATIONS;
AMPLIFICATION; PLASMA; TRIAL; PREDICTOR
AB Purpose: Tumors from 50% of epidermal growth factor receptor (EGFR) mutant non - small cell lung cancer patients that develop resistance to gefitinib or erlotinib will contain a secondary EGFR T790M mutation. As most patients do not undergo repeated tumor biopsies we evaluated whether EGFR T790M could be detected using plasma DNA.
Experimental Design: DNA from plasma of 54 patients with known clinical response to gefitinib or erlotinib was extracted and used to detect both EGFR-activating and EGFR T790M mutations. Forty-three (80%) of patients had tumor EGFR sequencing (EGFR mutant/wild type: 30/13) and seven patients also had EGFR T790M gefitinib/erlotinib-resistant tumors. EGFR mutations were detected using two methods, the Scorpion Amplification Refractory Mutation System and the WAVE/Surveyor, combined with whole genome amplification.
Results: Both EGFR-activating and EGFR T790M were identified in 70% of patients with known tumor EGFR-activating (21 of 30) or T790M (5 of 7) mutations. EGFR T790M was identified from plasma DNA in 54% (15 of 28) of patients with prior clinical response to gefitinib/erlotinib, 29% (4 of 14) with prior stable disease, and in 0% (0 of 12) that had primary progressive disease or were untreated with gefitinib/erlotinib.
Conclusions: EGFR T790M can be detected using plasma DNA from gefitinib- or erlotinib-resistant patients. This noninvasive method may aid in monitoring drug resistance and in directing the course of subsequent therapy.
C1 [Vetrand, Kristi; Thiede, Sara; Jaenne, Pasi A.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA.
[Kuang, Yanan; Rogers, Andrew; Distel, Robert J.; Jaenne, Pasi A.] Dana Farber Canc Inst, Ctr Clin & Translat Res, Translat Res Lab, Boston, MA 02115 USA.
[Wang, Lilin] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA.
[Vetrand, Kristi; Thiede, Sara; Jaenne, Pasi A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Yeap, Beow Y.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Jaenne, Pasi A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Yeap, Beow Y.; Jaenne, Pasi A.] Harvard Univ, Sch Med, Boston, MA USA.
RP Janne, PA (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, D820,44 Binney St, Boston, MA 02115 USA.
EM pjanne@partners.org
FU NIH [RO1CA114465-03]; National Cancer Institute Lung SPORE
[P50CA090578]; Hazel and Samuel Bellin research fund; Department of
Defense [W81 XOSH06-1-0303]
FX NIH RO1CA114465-03 (P.A. Janne, B.Y. Yeap), National Cancer Institute
Lung SPORE P50CA090578 (P.A. Janne, BY Yeap), the Hazel and Samuel
Bellin research fund (P.A. Janne), and Department of Defense W81
XOSH06-1-0303 (P.A. Janne).
NR 26
TC 123
Z9 127
U1 1
U2 13
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD APR 15
PY 2009
VL 15
IS 8
BP 2630
EP 2636
DI 10.1158/1078-0432.CCR-08-2592
PG 7
WC Oncology
SC Oncology
GA 435AC
UT WOS:000265314600008
PM 19351754
ER
PT J
AU Lun, XQ
Jang, JH
Tang, N
Deng, H
Head, R
Bell, JC
Stojdl, DF
Nutt, CL
Senger, DL
Forsyth, PA
McCart, JA
AF Lun, Xue Qing
Jang, Ji-Hyun
Tang, Nan
Deng, Helen
Head, Renee
Bell, John C.
Stojdl, David F.
Nutt, Catherine L.
Senger, Donna L.
Forsyth, Peter A.
McCart, J. Andrea
TI Efficacy of Systemically Administered Oncolytic Vaccinia Virotherapy for
Malignant Gliomas Is Enhanced by Combination Therapy with Rapamycin or
Cyclophosphamide
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID PHASE-I TRIAL; BLOOD-BRAIN-BARRIER; REGULATORY T-CELLS; MYXOMA-VIRUS;
ANTITUMOR-ACTIVITY; TUMOR; PATHWAY; CANCER; MUTANT; GLIOBLASTOMA
AB Purpose: The oncolytic effects of a systemically delivered, replicating, double-deleted vaccinia virus has been previously shown for the treatment of many cancers, including colon, ovarian, and others. The purpose of this study was to investigate the oncolytic potential of double-deleted vaccinia virus alone or in combination with rapamycin or cyclophosphamide to treat malignant gliomas in vitro and in vivo.
Experimental Design: Rat (RG2, F98, C6) and human (A172, U87MG, U118) glioma cell lines were cultured in vitro and treated with live or UV-inactivated vaccinia virus. Viral gene [enhanced green fluorescent protein (EGFP)] expression by fluorescence-activated cell sorting, relative cell viability by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), and assays for cytopathic effects were examined. S.c. murine tumor xenografts (U87MG, U118, C6) and i.c. (RG2, F98) tumor models in immunocompetent rats were treated with systemic administration of EGFP-expressing vaccinia virus (vvDD-EGFP), alone or in combination with rapamycin or cyclophosphamide, or controls. Tumor size, viral biodistribution, and animal survival were assessed. Lastly, the oncolytic effects of vvDD-EGFP on human malignant glioma explants were evaluated.
Results: vvDD-EGFP was able to infect and kill glioma cells in vitro. A single systemic dose of vvDD-EGFP significantly inhibited the growth of xenografts in athymic mice. Systemic delivery of vvDD-EGFP alone was able to target solitary and multifocal i.c. tumors and prolong survival of immunocompetent rats, whereas combination therapy with rapamycin or cyclophosphamide enhanced viral replication and further prolonged survival. Finally, vvDD-EGFP was able to infect and kill ex vivo primary human malignant gliomas.
Conclusions: These results suggest that vvDD-EGFP is a promising novel agent for human malignant glioma therapy, and in combination with immunosuppressive agents, may lead to prolonged survival from this disease.
C1 [Jang, Ji-Hyun; Tang, Nan; Deng, Helen; Head, Renee; McCart, J. Andrea] Toronto Gen Res Inst, Div Expt Therapeut, Toronto, ON, Canada.
[Lun, Xue Qing; Senger, Donna L.; Forsyth, Peter A.] Univ Calgary, Clark H Smith Brain Tumor Ctr, Calgary, AB T2N 1N4, Canada.
[Lun, Xue Qing; Senger, Donna L.; Forsyth, Peter A.] Univ Calgary, Tom Baker Canc Ctr, Dept Oncol, Calgary, AB T2N 1N4, Canada.
[Lun, Xue Qing; Senger, Donna L.; Forsyth, Peter A.] Univ Calgary, Tom Baker Canc Ctr, Dept Clin Neurosci, Calgary, AB T2N 1N4, Canada.
[Lun, Xue Qing; Senger, Donna L.; Forsyth, Peter A.] Univ Calgary, Tom Baker Canc Ctr, Dept Biochem & Mol Biol, Calgary, AB T2N 1N4, Canada.
[McCart, J. Andrea] Mt Sinai Hosp, Dept Surg, Toronto, ON, Canada.
[McCart, J. Andrea] Univ Toronto, Toronto, ON M5S 1A1, Canada.
[Bell, John C.] Ottawa Hlth Res Inst, Ctr Canc Therapeut, Ottawa, ON, Canada.
[Stojdl, David F.] Childrens Hosp Eastern Ontario, Apoptosis Res Ctr, Ottawa, ON K1H 8L1, Canada.
[Nutt, Catherine L.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Nutt, Catherine L.] Harvard Univ, Sch Med, Boston, MA USA.
RP McCart, JA (reprint author), Toronto Gen Res Inst, Div Expt Therapeut, Room 4-408,67 Coll St, Toronto, ON, Canada.
EM amccart@uhnres.utoronto.ca
RI Nutt, Catherine/K-8794-2012
FU National Cancer Institute of Canada; Terry Fox Foundation; Clark Smith
Brain Tumor Center; Faculty of Medicine, University of Toronto; Jennerex
FX National Cancer Institute of Canada with funds raised by the Canadian
Cancer Society (P.A. Forsyth and D.L. Senger); a Program Project Grant
from the Terry Fox Foundation (P.A. Forsyth, D.L. Senger, J.C. Bell, and
D.F. Stojdl); the Clark Smith Brain Tumor Center (P.A. Forsyth); a Grant
Miller Cancer Research Grant from the Faculty of Medicine, University of
Toronto (J.A. McCart); and commercial support from Jennerex (D.F. Stojdl
and J.C. Bell).
NR 48
TC 64
Z9 65
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 APR 15
PY 2009
VL 15
IS 8
BP 2777
EP 2788
DI 10.1158/1078-0432.CCR-08-2342
PG 12
WC Oncology
SC Oncology
GA 435AC
UT WOS:000265314600024
PM 19351762
ER
PT J
AU Huang, JM
Levitsky, LL
Rhoads, DB
AF Huang, Jianmin
Levitsky, Lynne L.
Rhoads, David B.
TI Novel P2 promoter-derived HNF4 alpha isoforms with different N-terminus
generated by alternate exon insertion
SO EXPERIMENTAL CELL RESEARCH
LA English
DT Article
DE Alternative splicing; Diabetes; HNF4 alpha; Transcription factor;
Variant/isoform; P2 promoter; HNF4 alpha 10/alpha 11/alpha 12;
Evolutionary conservation; Exon 1E
ID HEPATOCYTE NUCLEAR FACTOR-4-ALPHA; PANCREATIC BETA-CELLS; TRANSCRIPTION
FACTOR HNF-4; FACTOR 4-ALPHA ISOFORMS; LIVER DEVELOPMENT;
HEPATOCYTE-NUCLEAR-FACTOR-4-ALPHA HNF4A; COMMON VARIANTS;
GENE-EXPRESSION; YOUNG GENES; P1 PROMOTER
AB Hepatocyte nuclear factor 4 alpha (HNF4 alpha) is a critical transcription factor for pancreas and liver development and functions in islet beta cells to maintain glucose homeostasis. Mutations in the human HNF4A gene lead to maturity onset diabetes of the young (MODY1) and polymorphisms are associated with increased risk for type 2 diabetes mellitus (T2DM). Expression of six HNF4 alpha variants, three each from two developmentally regulated promoters, has been firmly established. We have now detected a new set of HNF4 alpha variants designated HNF4 alpha 10-12 expressed from distal promoter P2. These variants, generated by inclusion of previously undetected exon 1E (human =222 nt, rodent =136 nt) following exon 1D have an altered N-terminus but identical remaining reading frame. HNF4 alpha 10-alpha 12 are expressed in pancreatic islets (and liver) and exhibit transactivation potentials similar to the corresponding alpha 7-alpha 9 isoforms. DNA-binding analyses implied much higher protein levels of HNF4 alpha 10-alpha 12 in liver than expected from the RT-PCR data. Our results provide evidence for a more complex expression pattern of HNF4 alpha than previously appreciated. We recommend inclusion of exon 1E and nearby DNA sequences in screening for HNF4 alpha mutations and polymorphisms in genetic analyses of MODY1 and T2DM. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Huang, Jianmin] MassGen Hosp Children, Pediat Endocrine Unit, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Huang, JM (reprint author), MassGen Hosp Children, Pediat Endocrine Unit, Boston, MA 02114 USA.
EM jmhuang@partners.org; rhoads@helix.mgh.harvard.edu
FU American Diabetes Association Research [7-05-RA-121]; Diabetes Action
Research & Education Foundation [204]; William F. Milton Fund of Harvard
University (DBR); Nicholas Dulong Diabetes Research Fund
FX We thank Dr. Yin Xia (MassGeneral Hospital) for comments on the
manuscript and assistance in real-time qRT-PCR, and Dr. Sheng Xiao
(Brigham and Women's Hospital) for comments on the manuscript. We are
grateful to the Islet Cell Resource Centers of the University of
Alabama, the University of Miami, and the University of Minnesota. This
study was supported by American Diabetes Association Research Grant
7-05-RA-121 (DBR), Diabetes Action Research & Education Foundation Grant
#204 (DBR), The William F. Milton Fund of Harvard University (DBR), and
the Nicholas Dulong Diabetes Research Fund (LLL).
NR 53
TC 10
Z9 11
U1 0
U2 4
PU ELSEVIER INC
PI SAN DIEGO
PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0014-4827
J9 EXP CELL RES
JI Exp. Cell Res.
PD APR 15
PY 2009
VL 315
IS 7
BP 1200
EP 1211
DI 10.1016/j.yexcr.2009.01.004
PG 12
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 432IO
UT WOS:000265126900011
PM 19353766
ER
PT J
AU Zhang, XP
Huang, X
Olumi, AF
AF Zhang, Xiaoping
Huang, Xu
Olumi, Aria F.
TI Repression of NF-kappa B and activation of AP-1 enhance apoptosis in
prostate cancer cells
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE apoptosis; TRAIL; TNF-alpha; mechanisms of resistance
ID TRAIL-INDUCED APOPTOSIS; DEATH DOMAIN KINASE; MEDIATED APOPTOSIS; C-FOS;
RECEPTOR; EXPRESSION; CASPASE-8; ALPHA; INHIBITION; INDUCTION
AB TNF alpha and TRAIL, 2 members of the tumor necrosis factor family, share many common signaling pathways to induce apoptosis. Although many cancer cells are sensitive to these proapoptotic agents, some develop resistance. Recently, we have demonstrated that upregulation of c-Fos/AP-1 is necessary, but insufficient for cancer cells to undergo TRAIL-induced apoptosis. Here we present a prostate cancer model with differential sensitivity to TNF alpha and TRAIL. We show that inhibition of NF-kappa B or activation of AP-1 can only partially sensitize resistant prostate cancer cells to proapoptotic effects of TNFa or TRAIL. Inhibition of NF-kappa B by silencing TRAF2, by silencing RIP or by ectopic expression Of I kappa B partially sensitized resistant prostate cancer. Similarly, activation of c-Fos/AP-1 only partially sensitized resistant cancer cells to proapoptotic effects of TNFa or TRAIL. However, concomitant repression of NF-kappa B and activation of c-Fos/AP-1 significantly enhanced the proapoptotic effects of TNF alpha and TRAIL in resistant prostate cancer cells. Therefore, multiple molecular pathways may need to be modified, to overcome cancers that are resistant to proapoptotic therapies. (c) 2008 Wiley-Liss, Inc.
C1 [Zhang, Xiaoping; Huang, Xu; Olumi, Aria F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA 02114 USA.
[Zhang, Xiaoping] Huazhong Univ Sci & Technol, Tongji Med Sch, Union Hosp, Dept Urol, Wuhan 430074, Peoples R China.
RP Olumi, AF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Yawkey Bldg,Suite 7E, Boston, MA 02114 USA.
EM aolumi@partners.org
FU Howard Hughes Medical Institute/SPORE; National Natural Science
Foundation of China (NSFC)
FX Financial support from Howard Hughes Medical Institute/SPORE grant to
the Biomedical Research Support Program at Harvard Medical School to AFO
and the National Natural Science Foundation of China (NSFC) to XZ is
acknowledged.
NR 46
TC 12
Z9 14
U1 0
U2 2
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD APR 15
PY 2009
VL 124
IS 8
BP 1980
EP 1989
DI 10.1002/ijc.24139
PG 10
WC Oncology
SC Oncology
GA 422UH
UT WOS:000264452700029
PM 19123467
ER
PT J
AU Kahn, SE
AF Kahn, Steven E.
TI Glucose Control in Type 2 Diabetes Still Worthwhile and Worth Pursuing
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
ID CARDIOVASCULAR-DISEASE; AUTONOMIC NEUROPATHY; COMPLICATIONS; MELLITUS;
HYPOGLYCEMIA; OUTCOMES
C1 [Kahn, Steven E.] VA Puget Sound Hlth Care Syst, Div Metab Endocrinol & Nutr, Dept Med, Seattle, WA USA.
[Kahn, Steven E.] Univ Washington, Seattle, WA 98195 USA.
RP Kahn, SE (reprint author), VA Puget Sound Hlth Care Syst 151, 1660 S Columbian Way, Seattle, WA 98108 USA.
EM skahn@u.washington.edu
OI Kahn, Steven/0000-0001-7307-9002
NR 15
TC 9
Z9 9
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0098-7484
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD APR 15
PY 2009
VL 301
IS 15
BP 1590
EP 1592
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 432MH
UT WOS:000265137900031
PM 19366780
ER
PT J
AU Nathan, DM
AF Nathan, David M.
TI Progress in Diabetes Research-What's Next
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
ID LONG-TERM COMPLICATIONS; BLOOD-GLUCOSE CONTROL; INTENSIVE THERAPY;
MELLITUS
C1 [Nathan, David M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Diabet, Boston, MA USA.
RP Nathan, DM (reprint author), MGH Diabet Ctr, 50 Staniford St,Ste 340, Boston, MA 02114 USA.
EM dnathan@partners.org
NR 23
TC 5
Z9 5
U1 2
U2 3
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0098-7484
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD APR 15
PY 2009
VL 301
IS 15
BP 1599
EP 1601
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 432MH
UT WOS:000265137900034
PM 19366783
ER
PT J
AU Castriotta, RJ
Atanasov, S
Wilde, MC
Masel, BE
Lai, JM
Kuna, ST
AF Castriotta, Richard J.
Atanasov, Strahil
Wilde, Mark C.
Masel, Brent E.
Lai, Jenny M.
Kuna, Samuel T.
TI Treatment of Sleep Disorders after Traumatic Brain Injury
SO JOURNAL OF CLINICAL SLEEP MEDICINE
LA English
DT Article
DE Trauma; brain injury; hypersomnia; sleep apnea; narcolepsy; sleep
disorders; MSLT; continuous positive airway pressure
ID EXCESSIVE DAYTIME SLEEPINESS; POSITIVE AIRWAY PRESSURE; APNEA-HYPOPNEA
SYNDROME; MILD HEAD-INJURY; QUALITY-OF-LIFE; CPAP TREATMENT; RESIDUAL
SLEEPINESS; DOUBLE-BLIND; MODAFINIL; PLACEBO
AB Study Objectives: Determine whether treatment of sleep disorders identified in brain injured adults would result in resolution of those sleep disorders and improvement of symptoms and daytime function.
Methods: Prospective evaluation of unselected traumatic brain injury patients with nocturnal polysomnography (NPSG), multiple sleep latency test (MSLT), Epworth Sleepiness Scale (ESS), and neuropsychological testing including Psychomotor Vigilance Test (PVT), Profile of Mood States (POMS), and Functional Outcome of Sleep Questionnaire (FOSQ) before and after treatment with continuous positive airway pressure (CPAP) for obstructive sleep apnea (OSA), modafinil (200 mg) for narcolepsy and posttraumatic hypersomnia (PTH), or pramipexole (0.375 mg) for periodic limb movements in sleep (PLMS).
Setting: Three academic medical centers.
Participants: Fifty-seven (57) adults >= 3 months post traumatic brain injury (TBI).
Measurements And Results: Abnormal sleep studies were found in 22 subjects (39%), of whom 13 (23%) had OSA, 2 (3%) had PTH, 3 (5%) had narcolepsy, 4 (7%) had PLMS, and 12 had objective excessive daytime sleepiness with MSLT score < 10 minutes. Apneas, hypopneas, and snoring were eliminated by CPAP in OSA subjects, but there was no significant change in MSLT scores. Periodic limb movements were eliminated with pramipexole. One of 3 narcolepsy subjects and 1 of 2 PTH subjects had resolution of hypersomnia with modafinil. There was no significant change in FOSQ, POMS, or PVT results after treatment.
Conclusions: Treatment of sleep disorders after TBI may result in polysomnographic resolution without change in sleepiness or neuropsychological function.
C1 [Castriotta, Richard J.] Univ Texas Hlth Sci Ctr Houston, Div Pulm Crit Care & Sleep Med, Houston, TX 77030 USA.
[Castriotta, Richard J.; Wilde, Mark C.; Lai, Jenny M.] Mem Hermann Hosp Sleep Disorders Ctr, Houston, TX USA.
[Atanasov, Strahil] Univ Texas Med Branch Galveston, Galveston, TX USA.
[Masel, Brent E.] Transit Learning Ctr, Galveston, TX USA.
[Kuna, Samuel T.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
[Kuna, Samuel T.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA.
RP Castriotta, RJ (reprint author), Univ Texas Hlth Sci Ctr Houston, Div Pulm Crit Care & Sleep Med, 6431 Fannin St,MSB 1-274, Houston, TX 77030 USA.
EM Richard.J.Castriotta@uth.tmc.edu
RI Sanguansri, Luz/B-6630-2011;
OI Sanguansri, Luz/0000-0003-1908-7604; Castriotta,
Richard/0000-0003-3502-4558
NR 48
TC 40
Z9 40
U1 0
U2 7
PU AMER ACAD SLEEP MEDICINE
PI WESTCHESTER
PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA
SN 1550-9389
J9 J CLIN SLEEP MED
JI J. Clin. Sleep Med.
PD APR 15
PY 2009
VL 5
IS 2
BP 137
EP 144
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA 499YN
UT WOS:000270262900009
PM 19968047
ER
PT J
AU Huett, A
Ng, A
Cao, ZF
Kuballa, P
Komatsu, M
Daly, MJ
Podolsky, DK
Xavier, RJ
AF Huett, Alan
Ng, Aylwin
Cao, Zhifang
Kuballa, Petrie
Komatsu, Masaaki
Daly, Mark J.
Podolsky, Daniel K.
Xavier, Ramnik J.
TI A Novel Hybrid Yeast-Human Network Analysis Reveals an Essential Role
for FNBP1L in Antibacterial Autophagy
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID SALMONELLA-CONTAINING VACUOLE; PLASMA-MEMBRANE INVAGINATION;
PROTEIN-PROTEIN INTERACTIONS; GENOME-WIDE ASSOCIATION; PHOSPHOLIPID
SCRAMBLASE-1; SACCHAROMYCES-CEREVISIAE; ACTIN CYTOSKELETON;
CROHNS-DISEASE; MACHINERY; CELLS
AB Autophagy is a conserved cellular process required for the removal of defective organelles, protein aggregates, and intracellular pathogens. We used a network analysis strategy to identify novel human autophagy components based upon the yeast interactome centered on the core yeast autophagy proteins. This revealed the potential involvement of 14 novel mammalian genes in autophagy, several of which have known or predicted roles in membrane organization or dynamics. We selected one of these membrane interactors, FNBP1L (formin binding protein 1-like), an F-BAR-containing protein (also termed Toca-1), for further study based upon a predicted interaction with ATG3. We confirmed the FNBP1L/ATG3 interaction biochemically and mapped the FNBP1L domains responsible. Using a functional RNA interference approach, we determined that FNBP1L is essential for autophagy of the intracellular pathogen Salmonella enterica serovar Typhimurium and show that the autophagy process serves to restrict the growth of intracellular bacteria. However, FNBP1L appears dispensable for other forms of autophagy induced by serum starvation or rapamycin. We present a model where FNBP1L is essential for autophagy of intracellular pathogens and identify FNBP1L as a differentially used molecule in specific autophagic contexts. By using network biology to derive functional biological information, we demonstrate the utility of integrated genomics to novel molecule discovery in autophagy. The Journal of Immunology, 2009, 182: 4917-4930.
C1 [Xavier, Ramnik J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Computat & Integrat Biol,Richard B Simches Re, Boston, MA 02114 USA.
[Huett, Alan; Ng, Aylwin; Cao, Zhifang; Kuballa, Petrie; Podolsky, Daniel K.; Xavier, Ramnik J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit,Ctr Inflammatory Bowel Dis, Boston, MA 02114 USA.
[Daly, Mark J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Komatsu, Masaaki] Tokyo Metropolitan Inst Med Sci, Lab Frontier Sci, Tokyo 113, Japan.
[Komatsu, Masaaki] Juntendo Univ, Sch Med, Dept Biochem, Tokyo 113, Japan.
[Daly, Mark J.; Xavier, Ramnik J.] Broad Inst Massachussetts Inst Technol & Harvard, Cambridge, MA 02142 USA.
[Podolsky, Daniel K.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
RP Xavier, RJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Computat & Integrat Biol,Richard B Simches Re, 185 Cambridge St,7th Floor, Boston, MA 02114 USA.
EM Xavier@molbio.mgh.harvard.edu
FU National Institutes of Health [A1062773, DK83756, DK043351, DK060049];
Crohn's and Colitis Foundation of America
FX This work was supported National Institutes of Health Grants A1062773,
DK83756, and DK043351 (to R.J.X., M.J.D., and A.H.) and DK060049 and
DK043351 (to D.K.P.). A.N, is supported by a Crohn's and Colitis
Foundation of America fellowship.
NR 64
TC 31
Z9 33
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 APR 15
PY 2009
VL 182
IS 8
BP 4917
EP 4930
DI 10.4049/jimmunol.0803050
PG 14
WC Immunology
SC Immunology
GA 430QX
UT WOS:000265004700054
PM 19342671
ER
PT J
AU Tai, AW
Chung, RT
AF Tai, Andrew W.
Chung, Raymond T.
TI Racial Differences in Response to Interferon-Based Antiviral Therapy for
Hepatitis C Virus Infection: A Hardwiring Issue?
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Editorial Material
ID CAUCASIAN AMERICAN PATIENTS; AFRICAN-AMERICAN; CONTROLLED TRIAL;
PEGINTERFERON; RIBAVIRIN; GENOTYPE-1; EXPRESSION; CYTOKINE-SIGNALING-3;
SUPPRESSOR; ALFA
C1 [Tai, Andrew W.; Chung, Raymond T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
RP Chung, RT (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, WRN 1007,55 Fruit St, Boston, MA 02114 USA.
EM rtchung@partners.org
OI Tai, Andrew/0000-0002-6877-450X
FU NIAID NIH HHS [F32 AI080122]
NR 15
TC 2
Z9 2
U1 0
U2 0
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD APR 15
PY 2009
VL 199
IS 8
BP 1101
EP 1103
DI 10.1086/597385
PG 3
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 422EB
UT WOS:000264409000001
PM 19284288
ER
PT J
AU Schneidewind, A
Brumme, ZL
Brumme, CJ
Power, KA
Reyor, LL
O'Sullivan, K
Gladden, A
Hempel, U
Kuntzen, T
Wang, YYE
Oniangue-Ndza, C
Jessen, H
Markowitz, M
Rosenberg, ES
Sekaly, RP
Kelleher, AD
Walker, BD
Allen, TM
AF Schneidewind, Arne
Brumme, Zabrina L.
Brumme, Chanson J.
Power, Karen A.
Reyor, Laura L.
O'Sullivan, Kristin
Gladden, Adrianne
Hempel, Ursula
Kuntzen, Thomas
Wang, Yaoyu E.
Oniangue-Ndza, Cesar
Jessen, Heiko
Markowitz, Martin
Rosenberg, Eric S.
Sekaly, Rafick-Pierre
Kelleher, Anthony D.
Walker, Bruce D.
Allen, Todd M.
TI Transmission and Long-Term Stability of Compensated CD8 Escape Mutations
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; T-CELL RESPONSES; ACUTE/EARLY HIV-1
INFECTION; VIRAL LOAD; LYMPHOCYTE RESPONSE; CYCLOPHILIN-A; GAG PROTEIN;
EVOLUTION; REVERSION; ASSOCIATION
AB Human immunodeficiency virus effectively evades CD8(+) T-cell responses through the development of CD8 escape mutations. Recent reports documenting reversion of transmitted mutations and the impact of specific escape mutations upon viral replication suggest that complex forces limit the accumulation of CD8 escape mutations at the population level. However, the presence of compensatory mutations capable of alleviating the impact of CD8 escape mutations on replication capacity may enable their persistence in an HLA-mismatched host. Herein, we illustrate the long-term stability of stereotypic escape mutations in the immunodominant HLA-B27-restricted epitope KK10 in p24/Gag following transmission when accompanied by a specific compensatory mutation.
C1 [Allen, Todd M.] Massachusetts Gen Hosp, Div Infect Dis, Partners AIDS Res Ctr, Charlestown, MA 02129 USA.
[Schneidewind, Arne] Univ Klinikum Regensburg, Innere Med Klin 1, Regensburg, Germany.
[Jessen, Heiko] Jessen Praxis, Berlin, Germany.
[Markowitz, Martin] Aaron Diamond AIDS Res Ctr, New York, NY USA.
[Sekaly, Rafick-Pierre] Univ Montreal, Montreal, PQ, Canada.
[Kelleher, Anthony D.] Univ New S Wales, Sydney, NSW, Australia.
RP Allen, TM (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Partners AIDS Res Ctr, Bldg 149,13th St,Rm 6625, Charlestown, MA 02129 USA.
EM tallen2@partners.org
RI Allen, Todd/F-5473-2011;
OI Brumme, Chanson/0000-0003-2722-5288
FU National Institutes of Health [R01-AI054178]; Bill & Melinda Gates
Foundation; NHMRC of Australia
FX This study was supported by the National Institutes of Health, grant
R01-AI054178 (T. M. A.), and a grant from the Bill & Melinda Gates
Foundation (B. D. W. and T. M. A.). A. D. K. is supported by a
Practitioner grant from the NHMRC of Australia.
NR 35
TC 40
Z9 40
U1 0
U2 1
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD APR 15
PY 2009
VL 83
IS 8
BP 3993
EP 3997
DI 10.1128/JVI.01108-08
PG 5
WC Virology
SC Virology
GA 420ZI
UT WOS:000264327300055
PM 19091871
ER
PT J
AU Ikeda, S
He, AB
Kong, SW
Lu, J
Bejar, R
Bodyak, N
Lee, KH
Ma, Q
Kang, PM
Golub, TR
Pu, WT
AF Ikeda, Sadakatsu
He, Aibin
Kong, Sek Won
Lu, Jun
Bejar, Rafael
Bodyak, Natalya
Lee, Kyu-Ho
Ma, Qing
Kang, Peter M.
Golub, Todd R.
Pu, William T.
TI MicroRNA-1 Negatively Regulates Expression of the Hypertrophy-Associated
Calmodulin and Mef2a Genes
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID MUSCLE-SPECIFIC MICRORNA; INDUCED HEART-FAILURE; CARDIAC-HYPERTROPHY;
IN-VIVO; TRANSCRIPTION FACTORS; PRESSURE-OVERLOAD; TARGETS; GATA4;
DIFFERENTIATION; OVEREXPRESSION
AB Calcium signaling is a central regulator of cardiomyocyte growth and function. Calmodulin is a critical mediator of calcium signals. Because the amount of calmodulin within cardiomyocytes is limiting, the precise control of calmodulin expression is important for the regulation of calcium signaling. In this study, we show for the first time that calmodulin levels are regulated posttranscriptionally in heart failure. The cardiomyocyte-restricted microRNA miR-1 inhibited the translation of calmodulin-encoding mRNAs via highly conserved target sites within their 3' untranslated regions. In keeping with its effect on calmodulin expression, miR-1 downregulated calcium-calmodulin signaling through calcineurin to NFAT. miR-1 also negatively regulated the expression of Mef2a and Gata4, key transcription factors that mediate calcium-dependent changes in gene expression. Consistent with the downregulation of these hypertrophy-associated genes, miR-1 attenuated cardiomyocyte hypertrophy in cultured neonatal rat cardiomyocytes and in the intact adult heart. Our data indicate that miR-1 regulates cardiomyocyte growth responses by negatively regulating the calcium signaling components calmodulin, Mef2a, and Gata4.
C1 [Ikeda, Sadakatsu; He, Aibin; Kong, Sek Won; Lee, Kyu-Ho; Ma, Qing; Pu, William T.] Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Cardiol, Boston, MA 02115 USA.
[Ikeda, Sadakatsu; He, Aibin; Kong, Sek Won; Lee, Kyu-Ho; Ma, Qing; Pu, William T.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Lu, Jun; Golub, Todd R.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Lu, Jun; Golub, Todd R.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA.
[Bejar, Rafael] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Bodyak, Natalya; Kang, Peter M.] Beth Israel Deaconess Med Ctr, Div Cardiovasc, Boston, MA 02115 USA.
[Golub, Todd R.] Childrens Hosp Boston, Dept Med, Boston, MA 02115 USA.
[Golub, Todd R.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
[Pu, William T.] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
RP Pu, WT (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Cardiol, Enders 1254,300 Longwood Ave, Boston, MA 02115 USA.
EM wpu@enderstch.harvard.edu
FU AHA; NIH [PO1 HL074734]
FX I. was supported by an AHA fellowship. This work was supported by NIH
grant PO1 HL074734 and by a charitable donation from Edward P. Marram
and Karen K. Carpenter.
NR 46
TC 207
Z9 237
U1 2
U2 7
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0270-7306
J9 MOL CELL BIOL
JI Mol. Cell. Biol.
PD APR 15
PY 2009
VL 29
IS 8
BP 2193
EP 2204
DI 10.1128/MCB.01222-08
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 424HS
UT WOS:000264558400018
PM 19188439
ER
PT J
AU Zhang, Q
Strangman, GE
Ganis, G
AF Zhang, Quan
Strangman, Gary E.
Ganis, Giorgio
TI Adaptive filtering to reduce global interference in non-invasive NIRS
measures of brain activation: How well and when does it work?
SO NEUROIMAGE
LA English
DT Article
DE Near infrared; Brain; Visual cortex; Vision; Hemodynamics; Adaptive
filter; Interference; Cancellation; Physiological noise
ID NEAR-INFRARED SPECTROSCOPY; DIFFUSE OPTICAL TOMOGRAPHY; VISUAL-CORTEX;
HUMAN ADULTS; HEMODYNAMICS; OXYGENATION; METABOLISM; ARTIFACT; REMOVAL;
INFANTS
AB In previous work we introduced a novel method for reducing global interference, based on adaptive filtering, to improve the contrast to noise ratio (CNR) of evoked hemodynamic responses measured non-invasively with near infrared spectroscopy (NIRS). Here, we address the issue of how to generally apply the proposed adaptive filtering method. A total of 156 evoked visual response measurements, collected from 15 individuals, were analyzed. The similarity (correlation) between measurements with far and near source-detector separations collected during the rest period before visual stimulation was used as indicator of global interference dominance. A detailed analysis of CNR improvement in oxy-hemoglobin (O(2)Hb) and deoxyhemoglobin (HHb), as a function of the rest period correlation coefficient, is presented. Results show that for O2Hb measurements, 66% exhibited substantial global interference. For this dataset, dominated by global interference, 71% of the measurements revealed CNR improvements after adaptive filtering, with a mean CNR improvement of 60%. No CNR improvement was observed for HHb. This study corroborates our previous finding that adaptive filtering provides an effective method to increase CNR when there is strong global interference, and also provides a practical way for determining when and where to apply this technique. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Strangman, Gary E.; Ganis, Giorgio] Massachusetts Gen Hosp, Athinoula Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
[Zhang, Quan; Strangman, Gary E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA.
[Ganis, Giorgio] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02114 USA.
[Ganis, Giorgio] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA.
RP Ganis, G (reprint author), Massachusetts Gen Hosp, Athinoula Martinos Ctr Biomed Imaging, Bldg 149,13th St, Charlestown, MA 02129 USA.
EM ganis@nmr.mgh.harvard.edu
OI Ganis, Giorgio/0000-0001-6175-2618
FU NIMH [R21-MH068610]; NSF [BCS-0322611]; NIBIB [R01-EB006589]; National
Space Biomedical Research Institute [NCC 9-58]
FX We would like to thank Christina Supelana for technical support. This
effort was supported primarily by the NIMH (R21-MH068610 to GG), with
contributions from the NSF (BCS-0322611), the NIBIB (R01-EB006589), and
the National Space Biomedical Research Institute through NASA
Cooperative Agreement NCC 9-58.
NR 37
TC 77
Z9 83
U1 3
U2 8
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD APR 15
PY 2009
VL 45
IS 3
BP 788
EP 794
DI 10.1016/j.neuroimage.2008.12.048
PG 7
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 421SK
UT WOS:000264378400016
PM 19166945
ER
PT J
AU Kong, J
Kaptchuk, TJ
Polich, G
Kirsch, I
Vangel, M
Zyloney, C
Rosen, B
Gollub, R
AF Kong, Jian
Kaptchuk, Ted J.
Polich, Ginger
Kirsch, Irving
Vangel, Mark
Zyloney, Carolyn
Rosen, Bruce
Gollub, Randy
TI Expectancy and treatment interactions: A dissociation between
acupuncture analgesia and expectancy evoked placebo analgesia
SO NEUROIMAGE
LA English
DT Review
DE Acupuncture; Acupuncture analgesia; Placebo; Placebo analgesia;
Expectancy; Expectancy manipulation; Conditioning; Pain; Sham
acupuncture needle
ID RANDOMIZED CONTROLLED-TRIAL; LOW-BACK-PAIN; CARPAL-TUNNEL-SYNDROME;
CONNECTIVE-TISSUE; HUMAN BRAIN; ACUPOINT STIMULATION;
PARKINSONS-DISEASE; NEURAL MECHANISMS; OPIOID ACTIVITY; RATIO SCALES
AB Recent advances in placebo research have demonstrated the mind's power to alter physiology. In this study, we combined an expectancy manipulation model with both verum and sham acupuncture treatments to address: 1) how and to what extent treatment and expectancy effects - including both subjective pain intensity levels (pain sensory ratings) and objective physiological activations (fMRI) - interact; and 2) if the underlying mechanism of expectancy remains the same whether placebo treatment is given alone or in conjunction with active treatment. The results indicate that although verum acupuncture+high expectation and sham acupuncture+high expectation induced subjective reports of analgesia of equal magnitude, fMRI analysis showed that verum acupuncture produced greater fMRI signal decrease in pain related brain regions during application of calibrated heat pain stimuli on the right arm. We believe our study provides brain imaging evidence for the existence of different mechanisms underlying acupuncture analgesia and expectancy evoked placebo analgesia. Our results also suggest that the brain network involved in expectancy may vary under different treatment situations (verum and sham acupuncture treatment). (c) 2008 Elsevier Inc. All rights reserved.
C1 [Kong, Jian; Polich, Ginger; Zyloney, Carolyn; Gollub, Randy] Massachusetts Gen Hosp, Dept Psychiat, Bldg 149,13th St,Suite 2661, Charlestown, MA 02129 USA.
[Kong, Jian; Vangel, Mark; Rosen, Bruce; Gollub, Randy] MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA USA.
[Kaptchuk, Ted J.; Gollub, Randy] Harvard Univ, Sch Med, Osher Res Ctr, Boston, MA USA.
[Kirsch, Irving] Univ Hull, Kingston Upon Hull HU6 7RX, N Humberside, England.
[Vangel, Mark] MGH CRC Biomed Imaging Core, Charlestown, MA USA.
RP Kong, J (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Bldg 149,13th St,Suite 2661, Charlestown, MA 02129 USA.
EM kongj@nmr.mgh.harvard.edu
OI Gollub, Randy L./0000-0002-9434-4044
FU National Center for Complimentary and Alternative Medicine (NCCAM)
[PO1-AT002048]; NCCAM [R21AT00949, KO1AT003883, K24AT004095,
M01-RR-01066]; National Center for Research Resources (NCRR) [UL1
RR025758-01]; NCRR [P41RR14075]; MIND Institute
FX This work was supported by PO1-AT002048 to Bruce Rosen from National
Center for Complimentary and Alternative Medicine (NCCAM), R21AT00949 to
Randy Gollub from NCCAM, KO1AT003883 to Jian Kong from NCCAM,
K24AT004095 to Ted Kaptchuk from NCCAM, M01-RR-01066 and UL1 RR025758-01
for Clinical Research Center Biomedical Imaging Core from National
Center for Research Resources (NCRR), P41RR14075 for Center for
Functional Neuroimaging Technologies from NCRR and the MIND Institute.
NR 104
TC 69
Z9 80
U1 1
U2 29
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
EI 1095-9572
J9 NEUROIMAGE
JI Neuroimage
PD APR 15
PY 2009
VL 45
IS 3
BP 940
EP 949
DI 10.1016/j.neuroimage.2008.12.025
PG 10
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 421SK
UT WOS:000264378400029
PM 19159691
ER
PT J
AU Timbie, JW
Shahian, DM
Newhouse, JP
Rosenthal, MB
Normand, SLT
AF Timbie, Justin W.
Shahian, David M.
Newhouse, Joseph P.
Rosenthal, Meredith B.
Normand, Sharon-Lise T.
TI Composite measures for hospital quality using quality-adjusted life
years
SO STATISTICS IN MEDICINE
LA English
DT Article
DE quality of care; quality-adjusted life years; provider profiling;
cardiac bypass graft surgery; hierarchical model
ID LONG-TERM-SURVIVAL; BYPASS GRAFT-SURGERY; ADULT CARDIAC-SURGERY;
UNINTENDED CONSEQUENCES; MYOCARDIAL-INFARCTION; PERFORMANCE-MEASURES;
COST-EFFECTIVENESS; RISK-FACTORS; OF-LIFE; OUTCOMES
AB Developing clinically meaningful summary measures of health-care quality is key to inferring quality of care. Current summary measures use a number of different approaches to weight their individual measures but rarely use weights based on clinical 'importance'. Such an approach would help to focus quality improvement efforts on areas likely to have the largest impact On health outcomes. Using coronary artery bypass graft (CABG) surgery as a case study, we weight and combine 11 process, complication, and survival measures to summarize differences in quality-adjusted life expectancy 1 year following surgery for a sample of hospitals. We use a fully Bayesian analysis to estimate 1-year survival outcomes using a hierarchical exponential survival model. We then estimate the expected utility of the year following surgery for each patient using complication probabilities fitted from hierarchical models and utility values from the literature. We estimate quality-adjusted life years (QALYs) for each hospital as the utility-weighted average 1-year survival probability and then estimate 'incremental QALYs' by taking the difference in QALYs for each hospital relative to a comparison group that reflects the average performance of all hospitals in the state. We illustrate our framework by estimating incremental QALYs for 14 hospitals performing CABG surgery in Massachusetts in 2003 and find that a composite measure based on QALYs can change the classification of quality outliers relative to conventional mortality measures. Copyright (C) 2009 John Wiley & Sons, Ltd.
C1 [Timbie, Justin W.] VA Ann Arbor Healthcare Syst, HSR&D Ctr Clin Management Res, Ann Arbor, MI 48105 USA.
[Shahian, David M.] Massachusetts Gen Hosp, Dept Surg, Ctr Qual & Safety, Boston, MA 02114 USA.
[Newhouse, Joseph P.; Normand, Sharon-Lise T.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
[Newhouse, Joseph P.; Rosenthal, Meredith B.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA.
[Newhouse, Joseph P.] Harvard Univ, John F Kennedy Sch Govt, Cambridge, MA 02138 USA.
[Normand, Sharon-Lise T.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
RP Timbie, JW (reprint author), VA Ann Arbor Healthcare Syst, HSR&D Ctr Clin Management Res, 2215 Fuller Rd, Ann Arbor, MI 48105 USA.
EM justinti@med.umich.edu
OI Rosenthal, Meredith/0000-0003-3410-0184
FU Alfred P. Sloan Foundation
FX Contract/grant sponsor: Alfred P. Sloan Foundation
NR 48
TC 5
Z9 5
U1 0
U2 2
PU JOHN WILEY & SONS LTD
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND
SN 0277-6715
J9 STAT MED
JI Stat. Med.
PD APR 15
PY 2009
VL 28
IS 8
BP 1238
EP 1254
DI 10.1002/sim.3539
PG 17
WC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Medicine, Research &
Experimental; Statistics & Probability
SC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Research & Experimental
Medicine; Mathematics
GA 425NW
UT WOS:000264645400003
PM 19184974
ER
PT J
AU Bonetti, M
Zahrieh, D
Cole, BF
Gelber, RD
AF Bonetti, Marco
Zahrieh, David
Cole, Bernard F.
Gelber, Richard D.
TI A small sample study of the STEPP approach to assessing
treatment-covariate interactions in survival data
SO STATISTICS IN MEDICINE
LA English
DT Article
DE treatment-covariate interaction; clinical trials; permutation-based
inference; survival analysis
ID NEGATIVE BREAST-CANCER; CLINICAL-TRIALS; ENDOCRINE RESPONSIVENESS;
ADJUVANT CHEMOTHERAPY; RANDOMIZED-TRIAL; SUBSETS; THERAPY; WOMEN; CMF
AB A new, intuitive method has recently been proposed to explore treatment-covariate interactions in survival data arising from two treatment arms of a clinical trial. The method is based on constructing overlapping subpopulations of patients with respect to one (or more) covariates of interest and in observing the pattern of the treatment effects estimated across the subpopulations. A plot of these treatment effects is called a subpopulation treatment effect pattern plot. Here, we explore the small sample characteristics of the asymptotic results associated with the method and develop an alternative permutation distribution-based approach to inference that should be preferred for smaller sample sizes. We then describe an extension of the method to the case in which the pattern of estimated quantiles of survivor functions is of interest. Copyright (C) 2009 John Wiley & Sons, Ltd.
C1 [Bonetti, Marco] Bocconi Univ, Dept Decis Sci, I-20136 Milan, Italy.
[Zahrieh, David; Gelber, Richard D.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Cole, Bernard F.] Univ Vermont, Dept Math & Stat, Burlington, VT 05401 USA.
[Gelber, Richard D.] Harvard Univ, Dept Biostat, Sch Publ Hlth, Boston, MA 02115 USA.
RP Bonetti, M (reprint author), Bocconi Univ, Dept Decis Sci, Via Rontgen 1, I-20136 Milan, Italy.
EM marco.bonetti@unibocconi.it
OI Bonetti, Marco/0000-0003-2304-4180
FU The United States National Cancer Institute [CA-75362]; The Italian
Ministry for Research (MIUR) protocol [2007AYHZWC]
FX Contract/grant sponsor: The Italian Ministry for Research (MIUR)
protocol; contract/grant number: 2007AYHZWC
NR 11
TC 18
Z9 18
U1 0
U2 7
PU JOHN WILEY & SONS LTD
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND
SN 0277-6715
J9 STAT MED
JI Stat. Med.
PD APR 15
PY 2009
VL 28
IS 8
BP 1255
EP 1268
DI 10.1002/sim.3524
PG 14
WC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Medicine, Research &
Experimental; Statistics & Probability
SC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Research & Experimental
Medicine; Mathematics
GA 425NW
UT WOS:000264645400004
PM 19170050
ER
PT J
AU Heher, EC
Spitzer, TR
Goes, NB
AF Heher, Eliot C.
Spitzer, Thomas R.
Goes, Nelson B.
TI Light Chains: Heavy Burden in Kidney Transplantation
SO TRANSPLANTATION
LA English
DT Review
DE Plasma cell dyscrasia; Multiple myeloma; Monoclonal gammopathy of
uncertain significance; Light chain deposition disease; Monoclonal
immunoglobulin deposition disease
ID STEM-CELL TRANSPLANTATION; DIAGNOSED MULTIPLE-MYELOMA;
ACUTE-RENAL-FAILURE; MONOCLONAL GAMMOPATHY; DEPOSITION DISEASE;
UNDETERMINED SIGNIFICANCE; PLASMA-EXCHANGE; PLUS DEXAMETHASONE;
FOLLOW-UP; IN-VITRO
AB Plasma cell dyscrasias are frequently encountered malignancies which are often associated with kidney disease through the production of monoclonal immunoglobulin (Ig). Recent advances in the field include the availability of an assay for free light chains, the introduction of new agents which more effectively target malignant plasma cells, and refinements in the application of stem-cell transplantation. Well-selected patients with plasma cell dyscrasias whose monoclonal Ig is well controlled may be candidates for kidney transplantation. Kidney transplant patients with allograft dysfunction from recurrent or de novo monoclonal Ig deposition can be successfully identified and treated with these new approaches.
C1 [Heher, Eliot C.; Goes, Nelson B.] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA.
[Heher, Eliot C.; Spitzer, Thomas R.; Goes, Nelson B.] Massachusetts Gen Hosp, Transplantat Ctr, Boston, MA 02114 USA.
[Spitzer, Thomas R.] Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA.
RP Heher, EC (reprint author), MGH GRB 1003,55 Fruit St, Boston, MA 02114 USA.
EM eheher@partners.org
NR 55
TC 5
Z9 5
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0041-1337
J9 TRANSPLANTATION
JI Transplantation
PD APR 15
PY 2009
VL 87
IS 7
BP 947
EP 952
DI 10.1097/TP.0b013e31819b9977
PG 6
WC Immunology; Surgery; Transplantation
SC Immunology; Surgery; Transplantation
GA 433DQ
UT WOS:000265184900001
PM 19352111
ER
PT J
AU Christen, T
Nahrendorf, M
Wildgruber, M
Swirski, FK
Aikawa, E
Waterman, P
Shimizu, K
Weissleder, R
Libby, P
AF Christen, Thomas
Nahrendorf, Matthias
Wildgruber, Moritz
Swirski, Filip K.
Aikawa, Elena
Waterman, Peter
Shimizu, Koichi
Weissleder, Ralph
Libby, Peter
TI Molecular Imaging of Innate Immune Cell Function in Transplant Rejection
SO CIRCULATION
LA English
DT Article
DE imaging; inflammation; leukocytes; rejection; transplantation
ID CARDIAC ALLOGRAFT VASCULOPATHY; IRON-OXIDE PARTICLES; IN-VIVO; PROTEASE
ACTIVITY; CONTRAST AGENT; ATHEROSCLEROSIS; ACCUMULATION; INFILTRATION;
REPERFUSION; MACROPHAGES
AB Background-Clinical detection of transplant rejection by repeated endomyocardial biopsy requires catheterization and entails risks. Recently developed molecular and cellular imaging techniques that visualize macrophage host responses could provide a noninvasive alternative. Yet, which macrophage functions may provide useful markers for detecting parenchymal rejection remains uncertain.
Methods and Results-We transplanted isografts from B6 mice and allografts from Balb/c mice heterotopically into B6 recipients. In this allograft across major histocompatability barriers, the transplanted heart undergoes predictable progressive rejection, leading to graft failure after 1 week. During rejection, crucial macrophage functions, including phagocytosis and release of proteases, render these abundant innate immune cells attractive imaging targets. Two or 6 days after transplantation, we injected either a fluorescent protease sensor or a magnetofluorescent phagocytosis marker. Histological and flow cytometric analyses established that macrophages function as the major cellular signal source. In vivo, we obtained a 3-dimensional functional map of macrophages showing higher phagocytic uptake of magnetofluorescent nanoparticles during rejection using magnetic resonance imaging and higher protease activity in allografts than in isografts using tomographic fluorescence. We further assessed the sensitivity of imaging to detect the degree of rejection. In vivo imaging of macrophage response correlated closely with gradually increasing allograft rejection and attenuated rejection in recipients with a genetically impaired immune response resulting from a deficiency in recombinase-1 (RAG-1(-/-)).
Conclusions-Molecular imaging reporters of either phagocytosis or protease activity can detect cardiac allograft rejection noninvasively, promise to enhance the search for novel tolerance-inducing strategies, and have translational potential. (Circulation. 2009;119:1925-1932.)
C1 [Christen, Thomas; Shimizu, Koichi; Libby, Peter] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA.
[Nahrendorf, Matthias; Swirski, Filip K.; Waterman, Peter; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA.
[Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA.
[Nahrendorf, Matthias; Wildgruber, Moritz; Swirski, Filip K.; Aikawa, Elena; Waterman, Peter; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA USA.
[Nahrendorf, Matthias; Wildgruber, Moritz; Swirski, Filip K.; Aikawa, Elena; Waterman, Peter; Weissleder, Ralph] Harvard Univ, Sch Med, Charlestown, MA USA.
RP Libby, P (reprint author), Brigham & Womens Hosp, Dept Med, Div Cardiovasc, NRB 741,77 Ave Louis Pasteur, Boston, MA 02115 USA.
EM plibby@rics.bwh.harvard.edu
FU Donald W. Reynolds Foundation [U01HL080731]; American Heart Association
Scientist Development [0630010N]; American Society of Transplantation
Basic Science
FX This work was funded in part by the Donald W. Reynolds Foundation,
Translational Program of Excellence in Nanotechnology grant U01HL080731,
American Heart Association Scientist Development grant 0630010N (to Dr
Shimizu), and American Society of Transplantation Basic Science Faculty
Development grant (to Dr Shimizu).
NR 26
TC 39
Z9 40
U1 2
U2 11
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD APR 14
PY 2009
VL 119
IS 14
BP 1925
EP 1932
DI 10.1161/CIRCULATIONAHA.108.796888
PG 8
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 432BW
UT WOS:000265109500011
PM 19332470
ER
PT J
AU Desai, NR
Mega, JL
Jiang, ST
Cannon, CP
Sabatine, MS
AF Desai, Nihar R.
Mega, Jessica L.
Jiang, Songtao
Cannon, Christopher P.
Sabatine, Marc S.
TI Interaction Between Cigarette Smoking and Clinical Benefit of
Clopidogrel
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
DE clopidogrel; cytochrome P450; smoking
ID ST-SEGMENT ELEVATION; PLATELET REACTIVITY; MYOCARDIAL-INFARCTION;
RESPONSE VARIABILITY; STENT IMPLANTATION; ASPIRIN; EVENTS; TRIAL;
AGGREGATION; INHIBITION
AB Objectives The aim of this study was to examine the interaction between cigarette smoking and the clinical efficacy of clopidogrel in ST-segment elevation myocardial infarction (STEMI).
Background Cigarette smoking induces cytochrome P450 (CYP)1A2, which converts clopidogrel into its active metabolite, and prior studies suggest greater inhibition of platelet aggregation by clopidogrel in smokers of >= 10 cigarettes/day.
Methods The effect of clopidogrel compared with placebo on angiographic and clinical outcomes was examined in 3,429 STEMI patients in the CLARITY-TIMI 28 (Clopidogrel as Adjunctive Reperfusion Therapy-Thrombolysis In Myocardial Infarction 28) randomized trial stratified by smoking intensity as follows: not current smokers (n = 1,732), and smokers of 1 to 9 (n = 206), 10 to 19 (n = 354), 20 to 29 (n = 715), and >= 30 cigarettes/day (n = 422). Logistic regression was used to adjust for other baseline characteristics and interaction terms to test for effect modification.
Results Although clopidogrel reduced the rate of the primary end point of a closed infarct-related artery or death/myocardial infarction before angiography in the CLARITY-TIMI 28 trial, the benefit was especially marked among those who smoked >= 10 cigarettes/day (adjusted odds ratio [OR]: 0.49, 95% confidence interval [CI]: 0.37 to 0.66; p < 0.0001) compared with those who did not (adjusted OR: 0.72, 95% CI: 0.57 to 0.91; p = 0.006; p(interaction) = 0.04). Similarly, clopidogrel was significantly more effective at reducing the rate of cardiovascular death, myocardial infarction, or urgent revascularization through 30 days among those who smoked >= 10 cigarettes/ day (adjusted OR: 0.54, 95% CI: 0.38 to 0.76; p = 0.0004) compared with those who did not (adjusted OR: 0.98; 95% CI: 0.75 to 1.28; p = 0.87; p(interaction) = 0.006).
Conclusions Cigarette smoking seems to positively modify the beneficial effect of clopidogrel on angiographic and clinical outcomes. This study demonstrates that common clinical factors that influence the metabolism of clopidogrel might impact its clinical effectiveness. (J Am Coll Cardiol 2009; 53: 1273-8) (c) 2009 by the American College of Cardiology Foundation
C1 [Mega, Jessica L.; Cannon, Christopher P.; Sabatine, Marc S.] Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA.
[Desai, Nihar R.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Mega, Jessica L.; Cannon, Christopher P.; Sabatine, Marc S.] Harvard Univ, Sch Med, Boston, MA USA.
[Jiang, Songtao] Harvard Clin Res Inst, Boston, MA USA.
RP Sabatine, MS (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA.
EM msabatine@partners.org
FU Bristol-Myers Squibb; AstraZeneca; Bayer Healthcare; Beckman Coulter;
Biosite; CV Therapeutics; Eli Lilly; Genentech; GlaxoSmithKline;
Integrated Therapeutics Group; Johnson Johnson; Merck; Nanosphere;
Novartis; Pfizer; Roche Diagnostics; Sanofi-Aventis; Schering-Plough;
Siemens Medical Solutions; Accumetrics; Bristol Myers Squibb/Sanofi
Pharmaceuticals Partnership; Merck/Schering-Plough Partnership;
Sanofi-Aventis and Schering-Plough
FX From the *Department of Medicine and dagger TIMI Study Group,
Cardiovascular Division, Brigham and Women's Hospital, and Harvard
Medical School, Boston, Massachusetts; and the Harvard Clinical Research
Institute, Boston, Massachusetts. The CLARITY-TIMI 28 trial was funded
by Bristol-Myers Squibb. The TIMI Study Group reports receiving
significant research grant support from AstraZeneca, Bayer Healthcare,
Beckman Coulter, Biosite, Bristol-Myers Squibb, CV Therapeutics, Eli
Lilly, Genentech, GlaxoSmithKline, Integrated Therapeutics Group,
Johnson & Johnson, Merck, Nanosphere, Novartis, Pfizer, Roche
Diagnostics, Sanofi-Aventis, Schering-Plough, Siemens Medical Solutions,
and Singulex. Dr. Mega receives research grant support from
Schering-Plough. Dr. Cannon receives research grant support from
Accumetrics, AstraZeneca, Bristol Myers Squibb/Sanofi Pharmaceuticals
Partnership, GlaxoSmithKline, Merck, and Merck/Schering-Plough
Partnership and holds equity in Automedics Medical Systems. Dr. Sabatine
reports receiving research grant support from Sanofi-Aventis and
Schering-Plough and honoraria from Bristol- Myers Squibb and
Sanofi-Aventis.
NR 28
TC 71
Z9 73
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD APR 14
PY 2009
VL 53
IS 15
BP 1273
EP 1278
DI 10.1016/j.jacc.2008.12.044
PG 6
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 430TV
UT WOS:000265012600003
PM 19358940
ER
PT J
AU Kernan, WN
Viscoli, CM
DeMarco, D
Mendes, B
Shrauger, K
Schindler, JL
McVeety, JC
Sicklick, A
Moalli, D
Greco, P
Bravata, DM
Eisen, S
Resor, L
Sena, K
Story, D
Brass, LM
Furie, KL
Gutmann, L
Hinnau, E
Gorman, M
Lovejoy, AM
Inzucchi, SE
Young, LH
Horwitz, RI
AF Kernan, W. N.
Viscoli, C. M.
DeMarco, D.
Mendes, B.
Shrauger, K.
Schindler, J. L.
McVeety, J. C.
Sicklick, A.
Moalli, D.
Greco, P.
Bravata, D. M.
Eisen, S.
Resor, L.
Sena, K.
Story, D.
Brass, L. M.
Furie, K. L.
Gutmann, L.
Hinnau, E.
Gorman, M.
Lovejoy, A. M.
Inzucchi, S. E.
Young, L. H.
Horwitz, R. I.
CA IRIS Trial Investigators
TI Boosting enrollment in neurology trials with Local Identification and
Outreach Networks (LIONs)
SO NEUROLOGY
LA English
DT Article
ID CLINICAL-TRIAL; RECRUITMENT; STROKE
AB Objective: Our purpose was to develop a geographically localized, multi-institution strategy for improving enrolment in a trial of secondary stroke prevention.
Methods: We invited 11 Connecticut hospitals to participate in a project named the Local Identification and Outreach Network (LION). Each hospital provided the names of patients with stroke or TIA, identified from electronic admission or discharge logs, to researchers at a central coordinating center. After obtaining permission from personal physicians, researchers contacted each patient to describe the study, screen for eligibility, and set up a home visit for consent. Researchers traveled throughout the state to enroll and follow participants. Outside the LION, investigators identified trial participants using conventional recruitment strategies. We compared recruitment success for the LION and other sites using data from January 1, 2005, through June 30, 2007.
Results: The average monthly randomization rate from the LION was 4.0 participants, compared with 0.46 at 104 other Insulin Resistance Intervention after Stroke (IRIS) sites. The LION randomized on average 1.52/1,000 beds/month, compared with 0.76/1,000 beds/month at other IRIS sites (p = 0.03). The average cost to randomize and follow one participant was $8,697 for the LION, compared with $7,198 for other sites.
Conclusion: A geographically based network of institutions, served by a central coordinating center, randomized substantially more patients per month compared with sites outside of the network. The high enrollment rate was a result of surveillance at multiple institutions and greater productivity at each institution. Although the cost per patient was higher for the network, compared with nonnetwork sites, cost savings could result from more rapid completion of research. Neurology (R) 2009; 72: 1345-1351
C1 [Kernan, W. N.; Viscoli, C. M.; DeMarco, D.; Mendes, B.; Shrauger, K.; Hinnau, E.; Lovejoy, A. M.; Inzucchi, S. E.; Young, L. H.] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA.
[Schindler, J. L.; McVeety, J. C.; Story, D.; Brass, L. M.] Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06510 USA.
[Sicklick, A.] Yale Univ, Sch Med, Dept Orthopaed & Rehabil, New Haven, CT 06510 USA.
[Horwitz, R. I.] Stanford Univ, Sch Med, Dept Med, Palo Alto, CA 94304 USA.
[Bravata, D. M.] Indiana Univ, Sch Med, Richard L Roudebush VAMC, Indianapolis, IN USA.
[Gorman, M.] Univ Vermont, Dept Neurol, Burlington, VT USA.
[Furie, K. L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA.
[Moalli, D.] Lawrence Mem Hosp, Groton, CT USA.
[Greco, P.] St Marys Hosp, Waterbury, CT USA.
[Eisen, S.] Waterbury Hosp & Hlth Ctr, Waterbury, CT USA.
[Resor, L.] Stamford Hosp, Stamford, CT USA.
[Shrauger, K.] Bridgeport Hosp, Bridgeport, CT USA.
[Gutmann, L.] NINDS, NIH, Bethesda, MD 20892 USA.
RP Kernan, WN (reprint author), Suite 515,2 Church St S, New Haven, CT 06519 USA.
EM walter.kernan@yale.edu
RI Tanne, David/F-2560-2010; Spence, J. David/K-6396-2013
OI Tanne, David/0000-0002-6699-2220; Spence, J. David/0000-0001-7478-1098
FU National Institute of Neurological Disorders and Stroke [U01 NS044876];
Takeda Pharmaceuticals North America, Inc
FX Supported by the National Institute of Neurological Disorders and Stroke
(U01 NS044876) and by a grant from Takeda Pharmaceuticals North America,
Inc.
NR 8
TC 5
Z9 5
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD APR 14
PY 2009
VL 72
IS 15
BP 1345
EP 1351
DI 10.1212/WNL.0b013e3181a0fda3
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA 432AZ
UT WOS:000265107200010
PM 19365056
ER
PT J
AU Gorgun, G
Ramsay, AG
Holderried, TAW
Zahrieh, D
Le Dieu, R
Liu, F
Quackenbush, J
Croce, CM
Gribben, JG
AF Gorgun, Gullu
Ramsay, Alan G.
Holderried, Tobias A. W.
Zahrieh, David
Le Dieu, Rifca
Liu, Fenglong
Quackenbush, John
Croce, Carlo M.
Gribben, John G.
TI E mu-TCL1 mice represent a model for immunotherapeutic reversal of
chronic lymphocytic leukemia-induced T-cell dysfunction
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID IMMUNOLOGICAL SYNAPSE; EXPRESSION; LENALIDOMIDE; PEPTIDES; THERAPY;
MOUSE; DRUG; CD28; CD4
AB Preclinical animal models have largely ignored the immune-suppressive mechanisms that are important in human cancers. The identification and use of such models should allow better predictions of successful human responses to immunotherapy. As a model for changes induced in nonmalignant cells by cancer, we examined T-cell function in the chronic lymphocytic leukemia (CLL) E mu-TCL1 transgenic mouse model. With development of leukemia, E mu-TCL1 transgenic mice developed functional T-cell defects and alteration of gene and protein expression closely resembling changes seen in CLL human patients. Furthermore, infusion of CLL cells into young E mu-TCL1 mice induced defects comparable to those seen in mice with developed leukemia, demonstrating a causal relationship between leukemia and the T-cell defects. Altered pathways involved genes regulating actin remodeling, and T cells exhibited dysfunctional immunological synapse formation and T-cell signaling, which was reversed by the immunomodulatory drug lenalidomide. These results further demonstrate the utility of this animal model of CLL and define a versatile model to investigate both the molecular mechanisms of cancer-induced immune suppression and immunotherapeutic repair strategies.
C1 [Ramsay, Alan G.; Le Dieu, Rifca; Gribben, John G.] Univ London, Barts & London Sch Med, Inst Canc, London EC1M 6BQ, England.
[Gorgun, Gullu; Holderried, Tobias A. W.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Zahrieh, David; Liu, Fenglong; Quackenbush, John] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Croce, Carlo M.] Ohio State Univ, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA.
RP Gribben, JG (reprint author), Univ London, Barts & London Sch Med, Inst Canc, London EC1M 6BQ, England.
EM john.gribben@cancer.org.uk
RI Ramsay, Alan/A-8374-2015
OI Ramsay, Alan/0000-0002-0452-0420
FU CLL Research Consortium [81538]; National Cancer Institute; CLL Global
Research Foundation
FX We thank Peter Varney for editorial assistance, Dr. Edward Alvin Fox and
the Staff of the Dana- Farber Cancer Institute Microarray Core Facility.
This work was supported by the CLL Research Consortium Grant PO1 CA
81538 from the National Cancer Institute ( to J. G. G. and C. M. C.) and
by grants from the CLL Global Research Foundation.
NR 26
TC 68
Z9 68
U1 0
U2 4
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD APR 14
PY 2009
VL 106
IS 15
BP 6250
EP 6255
DI 10.1073/pnas.0901166106
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 433AB
UT WOS:000265174600041
PM 19332800
ER
PT J
AU Ford, AC
Chey, WD
Talley, NJ
Malhotra, A
Spiegel, BMR
Moayyedi, P
AF Ford, Alexander C.
Chey, William D.
Talley, Nicholas J.
Malhotra, Ashish
Spiegel, Brennan M. R.
Moayyedi, Paul
TI Yield of Diagnostic Tests for Celiac Disease in Individuals With
Symptoms Suggestive of Irritable Bowel Syndrome Systematic Review and
Meta-analysis
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Review
ID ROME-II CRITERIA; COST-EFFECTIVENESS ANALYSIS; POPULATION-BASED COHORT;
HEALTH-CARE SEEKING; GLUTEN-FREE DIET; GENERAL-POPULATION; SECONDARY
CARE; PREVALENCE; DYSPEPSIA; RISK
AB Background: Individuals with irritable bowel syndrome (IBS) report abdominal pain, bloating, and diarrhea, symptoms similar to those in celiac disease. Studies suggest that the prevalence of celiac disease is increased in individuals with IBS; however, evidence is conflicting, and current guidelines do not always recommend screening for celiac disease in these individuals.
Methods: We conducted a systematic review and meta-analysis to estimate prevalence of celiac disease in unselected adults who met diagnostic criteria for IBS. MEDLINE (1950 to May 31, 2008) and EMBASE (1980 to May 31, 2008) were searched. Case series and case-control studies that used serologic tests for celiac disease were eligible for inclusion. Prevalence of positive serologic indications of celiac disease and biopsy-proved celiac disease were extracted and pooled for all studies and were compared between cases and controls using an odds ratio and 95% confidence interval.
Results: Fourteen studies were identified comprising 4204 individuals, of whom 2278 (54%) met diagnostic criteria for IBS. Pooled prevalence of positive IgA-class antigliadin antibodies, either positive endomysial antibodies or tissue transglutaminase, and biopsy-proved celiac disease were 4.0% (95% confidence interval, 1.7-7.2), 1.63% (0.7-3.0), and 4.1% (1.9-7.0), respectively. Pooled odds ratios (95% confidence intervals) for positive IgA-class antigliadin antibodies, either positive endomysial antibodies or tissue transglutaminase, and biopsy-proved celiac disease in cases meeting diagnostic criteria for IBS compared with controls without IBS were 3.40 (1.62-7.13), 2.94 (1.36-6.35), and 4.34 (1.78-10.6).
Conclusion: Prevalence of biopsy-proved celiac disease in cases meeting diagnostic criteria for IBS was more than 4-fold that in controls without IBS.
C1 [Ford, Alexander C.; Moayyedi, Paul] McMaster Univ, Hlth Sci Ctr, Div Gastroenterol, Hamilton, ON L8N 3Z5, Canada.
[Chey, William D.] Univ Michigan, Med Ctr, Dept Med, Div Gastroenterol, Ann Arbor, MI 48109 USA.
[Talley, Nicholas J.] Mayo Clin Florida, Dept Med, Jacksonville, FL USA.
[Malhotra, Ashish] Mayo Clin Rochester, Div Gastroenterol & Hepatol, Rochester, MN USA.
[Spiegel, Brennan M. R.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
[Spiegel, Brennan M. R.] Univ Calif Los Angeles, David Geffen Sch Med, Sch Publ Hlth, VA Ctr Outcomes Res & Educ, Los Angeles, CA 90095 USA.
RP Ford, AC (reprint author), McMaster Univ, Hlth Sci Ctr, Div Gastroenterol, 1200 Main St W, Hamilton, ON L8N 3Z5, Canada.
EM alexf12399@yahoo.com
RI Ford, Alexander/K-5491-2012; Talley, nicholas/D-5399-2013
OI Ford, Alexander/0000-0001-6371-4359; Talley,
nicholas/0000-0003-2537-3092
FU American College of Gastroenterology
FX This study was funded by the American College of Gastroenterology (Dr
Moayyedi).
NR 56
TC 124
Z9 127
U1 2
U2 10
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0003-9926
J9 ARCH INTERN MED
JI Arch. Intern. Med.
PD APR 13
PY 2009
VL 169
IS 7
BP 651
EP 658
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 432AK
UT WOS:000265105700002
PM 19364994
ER
PT J
AU Kalogeropoulos, A
Georgiopoulou, V
Kritchevsky, SB
Psaty, BM
Smith, NL
Newman, AB
Rodondi, N
Satterfield, S
Bauer, DC
Bibbins-Domingo, K
Smith, AL
Wilson, PWF
Vasan, RS
Harris, TB
Butler, J
AF Kalogeropoulos, Andreas
Georgiopoulou, Vasiliki
Kritchevsky, Stephen B.
Psaty, Bruce M.
Smith, Nicholas L.
Newman, Anne B.
Rodondi, Nicolas
Satterfield, Suzanne
Bauer, Douglas C.
Bibbins-Domingo, Kirsten
Smith, Andrew L.
Wilson, Peter W. F.
Vasan, Ramachandran S.
Harris, Tamara B.
Butler, Javed
TI Epidemiology of Incident Heart Failure in a Contemporary Elderly Cohort
The Health, Aging, and Body Composition Study
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Article
ID RISK-FACTORS; SURVIVAL; POPULATION; PREVALENCE; PROGNOSIS; ASSOCIATION;
COMMUNITY; TRENDS; ADULTS; DEATH
AB Background: The race- and sex-specific epidemiology of incident heart failure (HF) among a contemporary elderly cohort are not well described.
Methods: We studied 2934 participants without HF enrolled in the Health, Aging, and Body Composition Study (mean [SD] age, 73.6 [2.9] years; 47.9% men; 58.6% white; and 41.4% black) and assessed the incidence of HF, population-attributable risk (PAR) of independent risk factors for HF, and outcomes of incident HF.
Results: During a median follow-up of 7.1 years, 258 participants (8.8%) developed HF (13.6 cases per 1000 person-years; 95% confidence interval, 12.1-15.4). Men and black participants were more likely to develop HF. No significant sex-based differences were observed in risk factors. Coronary heart disease (PAR, 23.9% for white participants and 29.5% for black participants) and uncontrolled blood pressure (PAR, 21.3% for white participants and 30.1% for black participants) carried the highest PAR in both races. Among black participants, 6 of 8 risk factors assessed (smoking, increased heart rate, coronary heart disease, left ventricular hypertrophy, uncontrolled blood pressure, and reduced glomerular filtration rate) had more than 5% higher PAR compared with that among white participants, leading to a higher overall proportion of HF attributable to modifiable risk factors in black participants vs white participants (67.8% vs 48.9%). Participants who developed HF had higher annual mortality (18.0% vs 2.7%). No racial difference in survival after HF was noted; however, rehospitalization rates were higher among black participants (62.1 vs 30.3 hospitalizations per 100 person-years, P <.001).
Conclusions: Incident HF is common in older persons; a large proportion of HF risk is attributed to modifiable risk factors. Racial differences in risk factors for HF and in hospitalization rates after HF need to be considered in prevention and treatment efforts.
C1 [Kalogeropoulos, Andreas; Georgiopoulou, Vasiliki; Smith, Nicholas L.; Wilson, Peter W. F.; Butler, Javed] Emory Univ, Dept Med, Atlanta, GA 30322 USA.
[Kritchevsky, Stephen B.] Wake Forest Univ, Winston Salem, NC 27109 USA.
[Psaty, Bruce M.] Univ Washington, Dept Med, Seattle, WA USA.
[Smith, Nicholas L.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Smith, Nicholas L.] VA Puget Sound Hlth Care Syst, Seattle VA Epidemiol Res & Informat Ctr, Seattle, WA USA.
[Newman, Anne B.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA.
[Rodondi, Nicolas] Univ Lausanne, Dept Ambulatory Care & Community Med, Lausanne, Switzerland.
[Satterfield, Suzanne] Univ Memphis, Dept Prevent Med, Memphis, TN 38152 USA.
[Bauer, Douglas C.; Bibbins-Domingo, Kirsten] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Vasan, Ramachandran S.] Boston Univ, Dept Med, Boston, MA 02215 USA.
[Harris, Tamara B.] NIA, Geriatr Epidemiol Sect, NIH, Bethesda, MD 20892 USA.
RP Butler, J (reprint author), Emory Univ, Emory Univ Hosp, Div Cardiol, 1365 Clifton Rd NE,Ste AT430, Atlanta, GA 30322 USA.
EM javed.butler@emory.edu
RI Kalogeropoulos, Andreas/A-9494-2009; Newman, Anne/C-6408-2013;
OI Kalogeropoulos, Andreas/0000-0002-1284-429X; Newman,
Anne/0000-0002-0106-1150; Ramachandran, Vasan/0000-0001-7357-5970
FU National Institute on Aging [N01-AG-6-2101, N01-AG-6-2103,
N01-AG-6-2106]; National Institutes of Health
FX This study was supported in part by the Intramural Research Program of
the National Institute on Aging and by grants N01-AG-6-2101,
N01-AG-6-2103, and N01-AG-6-2106 from the National Institute on Aging,
National Institutes of Health.
NR 36
TC 78
Z9 82
U1 0
U2 3
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0003-9926
J9 ARCH INTERN MED
JI Arch. Intern. Med.
PD APR 13
PY 2009
VL 169
IS 7
BP 708
EP 715
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 432AK
UT WOS:000265105700010
PM 19365001
ER
PT J
AU Soto-Nieves, N
Puga, I
Abe, BT
Bandyopadhyay, S
Baine, I
Rao, A
Macian, F
AF Soto-Nieves, Noemi
Puga, Irene
Abe, Brian T.
Bandyopadhyay, Sanmay
Baine, Ian
Rao, Anjana
Macian, Fernando
TI Transcriptional complexes formed by NFAT dimers regulate the induction
of T cell tolerance
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID E3 UBIQUITIN LIGASE; KAPPA-B COMPLEX; GENE-TRANSCRIPTION; HISTONE
ACETYLATION; SIGNALING PROTEINS; IN-VIVO; ANERGY; ACTIVATION;
DIFFERENTIATION; CALCINEURIN
AB T cells, anergy can be induced after T cell receptor engagement in the absence of costimulation. Under these conditions, the expression of a specific set of anergy-associated genes is activated. Several lines of evidence suggest that nuclear factor of activated T cells (NFAT) proteins may regulate the expression of many of those genes; however, the nature of the complexes responsible for the induction of this new program of gene expression is unknown. Here, we show that transcriptional complexes formed by NFAT homodimers are directly responsible for the activation of at least two anergy-inducing genes, Grail and Caspase3. Our data shows that Grail expression is activated by direct binding of NFAT dimers to the Grail promoter at two different sites. Consequently, a mutant NFAT protein with impaired ability to dimerize is not able to induce an unresponsive state in T cells. Our results not only identify a new biological function for NFAT dimers but also reveal the different nature of NFAT-containing complexes that induce anergy versus those that are activated during a productive immune response. These data also establish a basis for the design of immunomodulatory strategies that specifically target each type of complex.
C1 [Soto-Nieves, Noemi; Puga, Irene; Abe, Brian T.; Bandyopadhyay, Sanmay; Baine, Ian; Macian, Fernando] Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10461 USA.
[Rao, Anjana] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA.
[Rao, Anjana] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RP Macian, F (reprint author), Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10461 USA.
EM fmacianj@aecom.yu.edu
OI Baine, Ian/0000-0002-0419-0054; Puga, Irene/0000-0003-2208-3196; Macian,
Fernando/0000-0003-2666-035X
FU National Institutes of Health (NIH) [AI059738, CA42471, AI48213,
GM007288]; Irene Diamond Foundation
FX This work was supported by National Institutes of Health (NIH) grants
AI059738 (F. Macian), CA42471 (A. Rao), and AI48213 (A. Rao); NIH
training grants GM007288 (N. Soto-Nieves) and GM007288 (B. T. Abe and I.
Baine); and the Irene Diamond Foundation (F. Macian).
NR 57
TC 39
Z9 41
U1 0
U2 2
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1007
J9 J EXP MED
JI J. Exp. Med.
PD APR 13
PY 2009
VL 206
IS 4
BP 867
EP 876
DI 10.1084/jem.20082731
PG 10
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 444VX
UT WOS:000266009600013
PM 19307325
ER
PT J
AU Maldonado, RA
Soriano, MA
Perdomo, LC
Sigrist, K
Irvine, DJ
Decker, T
Glimcher, LH
AF Maldonado, Roberto A.
Soriano, Michelle A.
Perdomo, L. Carolina
Sigrist, Kirsten
Irvine, Darrell J.
Decker, Thomas
Glimcher, Laurie H.
TI Control of T helper cell differentiation through cytokine receptor
inclusion in the immunological synapse
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID INTERFERON-GAMMA-RECEPTOR; STAT1 TRANSACTIVATION DOMAIN; NFAT
FAMILY-MEMBERS; IFN-GAMMA; SIGNAL-TRANSDUCTION; IN-VIVO; SERINE
PHOSPHORYLATION; GENE-EXPRESSION; DENDRITIC CELLS; BETA CHAIN
AB The antigen recognition interface formed by T helper precursors (Thps) and antigen-presenting cells (APCs), called the immunological synapse (IS), includes receptors and signaling molecules necessary for Thp activation and differentiation. We have recently shown that recruitment of the interferon-gamma receptor (IFNGR) into the IS correlates with the capacity of Thps to differentiate into Th1 effector cells, an event regulated by signaling through the functionally opposing receptor to interleukin-4 (IL4R). Here, we show that, similar to IFN-gamma ligation, TCR stimuli induce the translocation of signal transducer and activator of transcription 1 (STAT1) to IFNGR1-rich regions of the membrane. Unexpectedly, STAT1 is preferentially expressed, is constitutively serine (727) phosphorylated in Thp, and is recruited to the IS and the nucleus upon TCR signaling. IL4R engagement controls this process by interfering with both STAT1 recruitment and nuclear translocation. We also show that in cells with deficient Th1 or constitutive Th2 differentiation, the IL4R is recruited to the IS. This observation suggest that the IL4R is retained outside the IS, similar to the exclusion of IFNGR from the IS during IL4R signaling. This study provides new mechanistic cues for the regulation of lineage commitment by mutual immobilization of functionally antagonistic membrane receptors.
C1 [Maldonado, Roberto A.; Soriano, Michelle A.; Sigrist, Kirsten; Glimcher, Laurie H.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA.
[Perdomo, L. Carolina] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA.
[Glimcher, Laurie H.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
[Irvine, Darrell J.] MIT, Dept Mat Sci & Engn, Biol Engn Div, Cambridge, MA 02139 USA.
[Decker, Thomas] Univ Vienna, Dept Microbiol & Immunobiol, Max F Perutz Labs, A-1030 Vienna, Austria.
RP Glimcher, LH (reprint author), Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, 665 Huntington Ave, Boston, MA 02115 USA.
EM lglimche@hsph.harvard.edu
FU National Institutes of Health [P01 NS038037]; Kelli and Gerald Ford
Irvington Institute Postdoctoral; Austrian Science Foundation (FWF)
[SFB28]
FX We thank Drs. Michael Grusby, Wendy Garrett, and Marc Wein for
thoughtful review of the manuscript, Drs. H. Cantor and R. Schreiber for
sharing animals and antibodies and Landy Kangaloo for valuable technical
help. This work was supported by National Institutes of Health grant P01
NS038037 (LHG). R. M. is a recipient of the Kelli and Gerald Ford
Irvington Institute Postdoctoral Fellowship. TD is supported by the
Austrian Science Foundation (FWF) through grant SFB28. LHG is a member
of the Board of Directors of and holds equity in the Bristol Myers
Squibb Corporation. The authors have no conflicting financial interests.
NR 80
TC 31
Z9 31
U1 0
U2 2
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1007
J9 J EXP MED
JI J. Exp. Med.
PD APR 13
PY 2009
VL 206
IS 4
BP 877
EP 892
DI 10.1084/jem.20082900
PG 16
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 444VX
UT WOS:000266009600014
PM 19349465
ER
PT J
AU Crawford, H
Lumm, W
Leslie, A
Schaefer, M
Boeras, D
Prado, JG
Tang, JM
Farmer, P
Ndung'u, T
Lakhi, S
Gilmour, J
Goepfert, P
Walker, BD
Kaslow, R
Mulenga, J
Allen, S
Goulder, PJR
Hunter, E
AF Crawford, Hayley
Lumm, Wendy
Leslie, Alasdair
Schaefer, Malinda
Boeras, Debrah
Prado, Julia G.
Tang, Jianming
Farmer, Paul
Ndung'u, Thumbi
Lakhi, Shabir
Gilmour, Jill
Goepfert, Paul
Walker, Bruce D.
Kaslow, Richard
Mulenga, Joseph
Allen, Susan
Goulder, Philip J. R.
Hunter, Eric
TI Evolution of HLA-B*5703 HIV-1 escape mutations in HLA-B*5703-positive
individuals and their transmission recipients
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; LYMPHOCYTE-BASED CONTROL; DISCORDANT
COUPLES; HLA-B; RHESUS MACAQUES; VACCINE TRIAL; VIRAL LOAD; INFECTION;
AIDS; GAG
AB HLA-B*57 is the class I allele most consistently associated with control of human immunodeficiency virus (HIV) replication, which may be linked to the specific HIV peptides that this allele presents to cytotoxic T lymphocytes (CTLs), and the resulting efficacy of these cellular immune responses. In two HIV C clade-infected populations in South Africa and Zambia, we sought to elucidate the role of HLA-B*5703 in HIV disease outcome. HLA-B*5703 restricted CTL responses select for escape mutations in three Gag p24 epitopes, in a predictable order. We show that the accumulation of these mutations sequentially reduces viral replicative capacity in vitro. Despite this, in vivo data demonstrate that there is ultimately an increase in viral load concomitant with evasion of all three HLA-B*5703-restricted CTL responses. In HLA-B*5703-mismatched recipients, the previously described early benefit of transmitted HLA-B*5703-associated escape mutations is abrogated by the increase in viral load coincident with reversion. Rapid disease progression is observed in HLA-matched recipients to whom mutated virus is transmitted. These data demonstrate that, although costly escape from CTL responses can progressively attenuate the virus, high viral loads develop in the absence of adequate, continued CTL responses. These data underline the need for a CTL vaccine against multiple conserved epitopes.
C1 [Lumm, Wendy; Schaefer, Malinda; Boeras, Debrah; Farmer, Paul; Allen, Susan; Hunter, Eric] Emory Univ, Yerkes Natl Primate Res Ctr, Emory Vaccine Ctr, Atlanta, GA 30329 USA.
[Crawford, Hayley; Leslie, Alasdair; Prado, Julia G.; Goulder, Philip J. R.] Univ Oxford, Dept Pediat, Oxford OX1 3SY, England.
[Lumm, Wendy; Schaefer, Malinda; Boeras, Debrah; Farmer, Paul; Allen, Susan; Hunter, Eric] Emory Univ, Dept Pathol & Lab Med, Atlanta, GA 30329 USA.
[Tang, Jianming; Kaslow, Richard] Univ Alabama, Dept Med, Birmingham, AL 35294 USA.
[Tang, Jianming; Kaslow, Richard] Univ Alabama, Dept Epidemiol, Birmingham, AL 35294 USA.
[Ndung'u, Thumbi; Walker, Bruce D.; Goulder, Philip J. R.] Univ KwaZulu Natal, Doris Duke Med Res Inst, HIV Pathogenesis Programme, ZA-4013 Durban, South Africa.
[Ndung'u, Thumbi; Walker, Bruce D.; Goulder, Philip J. R.] Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02129 USA.
[Lakhi, Shabir; Mulenga, Joseph; Allen, Susan; Hunter, Eric] Zambia Emory HIV Res Project, Lusaka, Zambia.
[Gilmour, Jill] Chelsea & Westminster Hosp, Core Lab, Int AIDS Vaccine Initiat, London SW10 9NH, England.
[Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
[Mulenga, Joseph] Zambia Blood Transfus Serv, Lusaka, Zambia.
RP Hunter, E (reprint author), Emory Univ, Yerkes Natl Primate Res Ctr, Emory Vaccine Ctr, Atlanta, GA 30329 USA.
EM eric.hunter2@emory.edu
OI Tang, Jianming/0000-0003-0137-7486; Ndung'u, Thumbi/0000-0003-2962-3992
FU National Institutes of Health [AI-64060, AI-46995, AI-067073]; Bill &
Melinda Gates Foundation [37874]; Wellcome Trust; Department for
International Development and the Commonwealth Scholarship Commission;
International AIDS Vaccine Initiative; Elizabeth Glaser Pediatric AIDS
Foundation
FX This work was supported by the National Institutes of Health (grant
AI-64060 to E. Hunter, grant AI-46995 to P. J. R. Goulder, and grant
AI-067073 B. D. Walker), the Bill & Melinda Gates Foundation Grand
Challenges Program (grant 37874 to E. Hunter), the Wellcome Trust (P. J.
R. Goulder and A. Leslie), the Department for International Development
and the Commonwealth Scholarship Commission (H. Crawford), and the
International AIDS Vaccine Initiative (S. Allen, B. D. Walker, and E.
Hunter). E. Hunter is a Georgia Research Alliance Eminent Scholar, P. J.
R. Goulder is an Elizabeth Glaser Pediatric AIDS Foundation Scientist,
and T. Ndung'u holds the South African Research Chair in Systems Biology
of HIV/AIDS.
NR 41
TC 117
Z9 122
U1 0
U2 2
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1007
J9 J EXP MED
JI J. Exp. Med.
PD APR 13
PY 2009
VL 206
IS 4
BP 909
EP 921
DI 10.1084/jem.20081984
PG 13
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 444VX
UT WOS:000266009600016
PM 19307327
ER
PT J
AU Wrighton, KH
Lin, X
Yu, PB
Feng, XH
AF Wrighton, Katharine H.
Lin, Xia
Yu, Paul B.
Feng, Xin-Hua
TI Transforming Growth Factor beta Can Stimulate Smad1 Phosphorylation
Independently of Bone Morphogenic Protein Receptors
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID TGF-BETA; SIGNAL-TRANSDUCTION; FUNCTIONAL-CHARACTERIZATION; SPECIFICITY;
ACTIVATION; ALK5; LOOP
AB Transforming growth factor-beta (TGF beta) superfamily ligands control a diverse set of cellular processes by activating type I and type II serine-threonine receptor kinases. Canonical TGF beta signaling is mediated via the T beta RI/ALK5 type I receptor that phosphorylates Smad2 and Smad3 in their SXS motif to facilitate their activation and subsequent role in transcriptional regulation. Canonical bone morphogenic protein (BMP) signaling is mediated via the ALK1/2/3/6 type I receptors that phosphorylate Smad1, Smad5, and Smad8 in their SXS motif. However, studies in endothelial cells have shown that TGF beta can also lead to the phosphorylation of Smad1, dependent on ALK1 receptor activity. Here we present data showing that TGF beta can significantly induce Smad1 phosphorylation in several non-endothelial cell lineages. Additionally, by using chemical inhibitors specific for the TGF beta/activin/nodal (ALK4/5/7) and BMP (ALK1/2/3/6) type I receptors, we show that in some cell types TGF beta induces Smad1 phosphorylation independently of the BMP type I receptors. Thus, TGF beta-mediated Smad1 phosphorylation appears to occur via different receptor complexes in a cell type-specific manner.
C1 [Wrighton, Katharine H.; Feng, Xin-Hua] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA.
[Wrighton, Katharine H.; Lin, Xia; Feng, Xin-Hua] Baylor Coll Med, Michael E DeBakey Dept Surg, Houston, TX 77030 USA.
[Yu, Paul B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr,Dept Med, Boston, MA 02114 USA.
[Yu, Paul B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol,Dept Med, Boston, MA 02114 USA.
RP Feng, XH (reprint author), Baylor Coll Med, Dept Mol & Cellular Biol, 1 Baylor Plaza,Rm 137D, Houston, TX 77030 USA.
EM xfeng@bcm.edu
OI Yu, Paul/0000-0003-2145-4944
FU National Institutes of Health [R01DK073932, R01CA108454, R01AR053591,
P50HL083794]
FX This work was supported, in whole or in part, by National Institutes of
Health Grants R01DK073932 ( to X. L.) and R01CA108454, R01AR053591, and
P50HL083794 ( X.- H. F.).
NR 20
TC 80
Z9 82
U1 0
U2 4
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD APR 10
PY 2009
VL 284
IS 15
BP 9755
EP 9763
DI 10.1074/jbc.M809223200
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 429AJ
UT WOS:000264892900015
PM 19224917
ER
PT J
AU Schrag, D
AF Schrag, Deborah
TI Evaluating the Impact of Organizational Changes in Health Care Delivery:
Challenges in Study Design
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Editorial Material
ID TRIALS
C1 Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Schrag, D (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 6
TC 1
Z9 1
U1 1
U2 2
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD APR 10
PY 2009
VL 27
IS 11
BP 1744
EP 1745
DI 10.1200/JCO.2008.19.7756
PG 2
WC Oncology
SC Oncology
GA 447ME
UT WOS:000266194400005
PM 19273700
ER
PT J
AU Bertagnolli, MM
Niedzwiecki, D
Compton, CC
Hahn, HP
Hall, M
Damas, B
Jewell, SD
Mayer, RJ
Goldberg, RM
Saltz, LB
Warren, RS
Redston, M
AF Bertagnolli, Monica M.
Niedzwiecki, Donna
Compton, Carolyn C.
Hahn, Hejin P.
Hall, Margaret
Damas, Beatrice
Jewell, Scott D.
Mayer, Robert J.
Goldberg, Richard M.
Saltz, Leonard B.
Warren, Robert S.
Redston, Mark
TI Microsatellite Instability Predicts Improved Response to Adjuvant
Therapy With Irinotecan, Fluorouracil, and Leucovorin in Stage III Colon
Cancer: Cancer and Leukemia Group B Protocol 89803
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID COLORECTAL-CANCER; FRAMESHIFT MUTATIONS; MUTATOR PHENOTYPE; GENE; CELLS;
MECHANISM; CPT-11; HMLH1; CARCINOGENESIS; CAMPTOTHECIN
AB Purpose
Colon cancers exhibiting DNA mismatch repair (MMR) defects demonstrate distinct clinical and pathologic features, including better prognosis and reduced response to fluorouracil (FU) - based chemotherapy. This prospective study investigated adjuvant chemotherapy containing FU and irinotecan in patients with MMR deficient (MMR-D) colon cancers.
Patients and Methods
Cancer and Leukemia Group B 89803 randomly assigned 1,264 patients with stage III colon cancer to postoperative weekly bolus FU/leucovorin (LV) or weekly bolus irinotecan, FU, and LV (IFL). The primary end point was overall survival; disease-free survival (DFS) was a secondary end point. Tumor expression of the MMR proteins, MLH1 and MSH2, was determined by immunohistochemistry (IHC). DNA microsatellite instability was also assessed using a panel of mono-and dinucleotide markers. Tumors with MMR defects were those demonstrating loss of MMR protein expression (MMR-D) and/or microsatellite instability high (MSI-H) genotype.
Results
Of 723 tumor cases examined by genotyping and IHC, 96 (13.3%) were MMR-D/MSI-H. Genotyping results were consistent with IHC in 702 cases (97.1%). IFL-treated patients with MMR-D/MSI-H tumors showed improved 5-year DFS as compared with those with mismatch repair intact tumors (0.76; 95% CI, 0.64 to 0.88 v 0.59; 95% CI, 0.53 to 0.64; P = .03). This relationship was not observed among patients treated with FU/LV. A trend toward longer DFS was observed in IFL-treated patients with MMR-D/MSI-H tumors as compared with those receiving FU/LV (0.57; 95% CI, 0.42 to 0.71 v 0.76; 95% CI, 0.64 to 0.88; P = .07; hazard ratio interaction between tumor status and treatment, 0.51; likelihood ratio P = .117).
Conclusion
Loss of tumor MMR function may predict improved outcome in patients treated with the IFL regimen as compared with those receiving FU/LV. J Clin Oncol 27: 1814-1821. (C) 2009 by American Society of Clinical Oncology
C1 [Bertagnolli, Monica M.] Brigham & Womens Hosp, Boston, MA 02115 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Duke Univ, Canc & Leukemia Grp Stat Ctr B, Med Ctr, Durham, NC 27706 USA.
Univ N Carolina, Chapel Hill, NC USA.
NCI, Bethesda, MD 20892 USA.
Ohio State Univ, Columbus, OH 43210 USA.
Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
Univ Calif San Francisco, San Francisco, CA 94143 USA.
RP Bertagnolli, MM (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.
EM mbertagnolli@partners.org
RI Goldberg , Richard/M-1311-2013;
OI Saltz, Leonard/0000-0001-8353-4670
FU NCI NIH HHS [CA31946, CA33601, U10 CA031946, U10 CA033601]
NR 35
TC 201
Z9 208
U1 0
U2 9
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD APR 10
PY 2009
VL 27
IS 11
BP 1814
EP 1821
DI 10.1200/JCO.2008.18.2071
PG 8
WC Oncology
SC Oncology
GA 447ME
UT WOS:000266194400016
PM 19273709
ER
PT J
AU Lohoff, FW
Bloch, PJ
Ferraro, TN
Berrettini, WH
Pettinati, HM
Dackis, CA
O'Brien, CP
Kampman, KM
Oslin, DW
AF Lohoff, Falk W.
Bloch, Paul J.
Ferraro, Thomas N.
Berrettini, Wade H.
Pettinati, Helen M.
Dackis, Charles A.
O'Brien, Charles P.
Kampman, Kyle M.
Oslin, David W.
TI Association analysis between polymorphisms in the conserved dopamine
neurotrophic factor (CDNF) gene and cocaine dependence
SO NEUROSCIENCE LETTERS
LA English
DT Article
DE Addiction; Association study; Cocaine; Neurotrophic factor; Genetics;
Substance abuse; ARMETL1
ID POPULATION-BASED SAMPLE; RECEPTOR GENE; TYROSINE-HYDROXYLASE; LINKAGE
DISEQUILIBRIUM; AFRICAN-AMERICANS; ADMIXED POPULATIONS; ADMIXTURE
DYNAMICS; GENOMIC CONTROL; DRUG-ADDICTION; NO ASSOCIATION
AB Cocaine-induced neuroplasticity changes in the mesocorticolimbic dopamine systems are thought to be involved in the pathophysiology of cocaine dependence. Since neurotrophic factors have been observed to prevent/reverse and mimic cocaine-induced neurobiological changes in the brain, related genes are plausible candidates for susceptibility to cocaine dependence. The novel conserved dopamine neurotrophic factor protein (CDNF) promotes the survival, growth, and function of dopamine-specific neurons and is expressed in brain regions that undergo cocaine-induced neuroplasticity. In this study, we hypothesize that polymorphisms in the CDNF gene (CDNF/ARMETL1) contribute to increased risk for cocaine dependence. Cocaine dependent individuals (n = 351) and unaffected controls (n = 257) of African descent were ere genotyped for four single nucleotide polymorphisms (SNPs) in the CDNF gene (rs11259365, rs7094179, rs7900873. rs2278871). We observed no significant differences in allele, genotype, or haplotype frequencies between cases and controls for any of the tested SNPs. Our study suggests that there is no association between variants in the CDNF gene and cocaine dependence. However, additional studies using larger sample sizes, comprehensive SNP coverage, and clinically homogenous populations are necessary before confidently excluding CDNF as a significant genetic risk factor for cocaine dependence. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
C1 [Lohoff, Falk W.] Univ Penn, Sch Med, Dept Psychiat, Ctr Neurobiol & Behav,Translat Res Labs, Philadelphia, PA 19104 USA.
[Pettinati, Helen M.; Dackis, Charles A.; O'Brien, Charles P.; Kampman, Kyle M.; Oslin, David W.] Univ Penn, Sch Med, Dept Psychiat, Treatment Res Ctr, Philadelphia, PA 19104 USA.
[Oslin, David W.] VISN 4 MIRECC, Vet Affairs Med Ctr, Philadelphia, PA USA.
RP Lohoff, FW (reprint author), Univ Penn, Sch Med, Dept Psychiat, Ctr Neurobiol & Behav,Translat Res Labs, 125 S 31st St, Philadelphia, PA 19104 USA.
EM lohoff@mail.med.upenn.edu
RI Lohoff, Falk/M-7951-2016
FU Center for Neurobiology and Behavior; Department of Psychiatry,
University of Pennsylvania; National Institutes of Health [K08MH080372];
NIDA [P60-051186]; Veterans Affairs Administration [P50-12756]; Tzedakah
Foundation; Philip and Marcia Cohen
FX This work was supported by the Center for Neurobiology and Behavior,
Department of Psychiatry, University of Pennsylvania. Financial support
is gratefully acknowledged from National Institutes of Health grants
K08MH080372 (F.W.L.), NIDA grants P60-051186 (C.P.O.) and P50-12756
(H.M.P), the VISN4 Mental Illness Research and Clinical Center grant
from the Veterans Affairs Administration (D.W.O.), a grant from the
Tzedakah Foundation (W.H.B.) and a grant from Philip and Marcia Cohen
(W.H.B.). Most importantly, we thank the subjects who have participated
in and contributed to these studies.
NR 54
TC 2
Z9 2
U1 0
U2 1
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0304-3940
J9 NEUROSCI LETT
JI Neurosci. Lett.
PD APR 10
PY 2009
VL 453
IS 3
BP 199
EP 203
DI 10.1016/j.neulet.2009.02.026
PG 5
WC Neurosciences
SC Neurosciences & Neurology
GA 429UW
UT WOS:000264946600016
PM 19429035
ER
PT J
AU Gekas, C
Rhodes, KE
Gereige, LM
Helgadottir, H
Ferrari, R
Kurdistani, SK
Montecino-Rodriguez, E
Bassel-Duby, R
Olson, E
Krivtsov, AV
Armstrong, S
Orkin, SH
Pellegrini, M
Mikkola, HKA
AF Gekas, Christos
Rhodes, Katrin E.
Gereige, Laurraine M.
Helgadottir, Hildur
Ferrari, Roberto
Kurdistani, Siavash K.
Montecino-Rodriguez, Encarnacion
Bassel-Duby, Rhonda
Olson, Eric
Krivtsov, Andrei V.
Armstrong, Scott
Orkin, Stuart H.
Pellegrini, Matteo
Mikkola, Hanna K. A.
TI Mef2C is a lineage-restricted target of Scl/Tal1 and regulates
megakaryopoiesis and B-cell homeostasis
SO BLOOD
LA English
DT Article
ID TRANSCRIPTION FACTOR MEF2C; HEMATOPOIETIC STEM-CELLS; SKELETAL-MUSCLE
DEVELOPMENT; HELIX-LOOP-HELIX; VASCULAR DEVELOPMENT; GENE-EXPRESSION;
MYOGENIC BHLH; LEUKEMIA GENE; BONE-MARROW; FACTOR SCL
AB The basic helix-loop-helix transcription factor stem cell leukemia gene (Scl) is a master regulator for hematopoiesis essential for hematopoietic specification and proper differentiation of the erythroid and megakaryocyte lineages. However, the critical downstream targets of Scl remain undefined. Here, we identified a novel Scl target gene, transcription factor myocyte enhancer factor 2 C (Mef2C) from Scl(fl/fl) fetal liver progenitor cell lines. Analysis of Mef2C(-/-) embryos showed that Mef2C, in contrast to Scl, is not essential for specification into primitive or definitive hematopoietic lineages. However, adult VavCre(+)Mef2C(fl/fl) mice exhibited platelet defects similar to those observed in Scl-deficient mice. The platelet counts were reduced, whereas platelet size was increased and the platelet shape and granularity were altered. Furthermore, megakaryopoiesis was severely impaired in vitro. Chromatin immunoprecipitation microarray hybridization analysis revealed that Mef2C is directly regulated by Scl in megakaryocytic cells, but not in erythroid cells. In addition, an Scl-independent requirement for Mef2C in B-lymphoid homeostasis was observed in Mef2C-deficient mice, characterized as severe age-dependent reduction of specific B-cell progenitor populations reminiscent of premature aging. In summary, this work identifies Mef2C as an integral member of hematopoietic transcription factors with distinct upstream regulatory mechanisms and functional requirements in megakaryocyte and B-lymphoid lineages. (Blood. 2009; 113: 3461-3471)
C1 [Gekas, Christos; Rhodes, Katrin E.; Gereige, Laurraine M.; Pellegrini, Matteo; Mikkola, Hanna K. A.] Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA.
[Helgadottir, Hildur; Armstrong, Scott; Orkin, Stuart H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Ferrari, Roberto; Kurdistani, Siavash K.] Univ Calif Los Angeles, Dept Biol Chem, Los Angeles, CA 90095 USA.
[Montecino-Rodriguez, Encarnacion] Univ Calif Los Angeles, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA.
[Bassel-Duby, Rhonda; Olson, Eric] Univ Texas SW Med Ctr Dallas, Dept Mol Biol, Dallas, TX 75390 USA.
[Krivtsov, Andrei V.; Armstrong, Scott; Orkin, Stuart H.] Harvard Univ, Sch Med, Childrens Hosp Boston, Div Hematol Oncol, Cambridge, MA 02138 USA.
[Orkin, Stuart H.] Howard Hughes Med Inst, Boston, MA 02115 USA.
[Orkin, Stuart H.] Harvard Stem Cell Inst, Boston, MA USA.
[Pellegrini, Matteo; Mikkola, Hanna K. A.] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA.
[Mikkola, Hanna K. A.] Univ Calif Los Angeles, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, Los Angeles, CA 90095 USA.
[Mikkola, Hanna K. A.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA.
RP Mikkola, HKA (reprint author), Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, 621 Charles E Young Dr S,LSB 2204, Los Angeles, CA 90095 USA.
EM hmikkola@mcdb.ucla.edu
RI Gekas, Christos/M-3209-2015;
OI Gekas, Christos/0000-0002-3429-4145; Kurdistani,
Siavash/0000-0003-3295-3511
FU Cancer Research Coordinating Committee (Davis, CA); Stop Cancer
Foundation (Los Angeles, CA); V Foundation for Cancer Research (Cary,
NC); California Institute for Regenerative Medicine (San Francisco, CA);
Ruth L. Kirschstein National Research Service Award [GM07185]
FX The authors thank Suvi Aivio, Mattias Magnusson, and Yanling Wang for
excellent technical assistance, the staff at University of
California-Los Angeles Division of Laboratory Animal Medicine laboratory
for blood analysis, Marianne Cilluffo and Alicia Thompson for their
expertise in electron microscopy, the University of California-Los
Angeles Flow Cytometry Core for FACS sorting, and Kenneth Dorshkind for
critical reading of the manuscript.; This work was supported by grants
from the Cancer Research Coordinating Committee (Davis, CA), the Stop
Cancer Foundation (Los Angeles, CA), the V Foundation for Cancer
Research (Cary, NC) and the California Institute for Regenerative
Medicine (San Francisco, CA) to H. K. A. M.), and a Ruth L. Kirschstein
National Research Service Award at University of California-Los Angeles
(Bethesda, MD; GM07185, to K. E. R).
NR 49
TC 25
Z9 27
U1 0
U2 2
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD APR 9
PY 2009
VL 113
IS 15
BP 3461
EP 3471
DI 10.1182/blood-2008-07-167577
PG 11
WC Hematology
SC Hematology
GA 431HN
UT WOS:000265052300011
PM 19211936
ER
PT J
AU Kurtz, J
Raval, F
Vallot, C
Der, J
Sykes, M
AF Kurtz, Josef
Raval, Forum
Vallot, Casey
Der, Jayden
Sykes, Megan
TI CTLA-4 on alloreactive CD4 T cells interacts with recipient CD80/86 to
promote tolerance
SO BLOOD
LA English
DT Article
ID BONE-MARROW-TRANSPLANTATION; DONOR-SPECIFIC TRANSFUSION;
LYMPHOCYTE-ASSOCIATED ANTIGEN-4; CARDIAC ALLOGRAFT-REJECTION;
VERSUS-HOST-DISEASE; GROWTH-FACTOR-BETA; IN-VIVO; MIXED CHIMERISM;
CUTTING EDGE; HEMATOPOIETIC CHIMERISM
AB Although the inhibitory receptor CTLA-4 (CD152) has been implicated in peripheral CD4 T-cell tolerance, its mechanism of action remains poorly defined. We analyzed mechanisms of CD4 cell tolerance in a model of tolerance induction involving establishment of mixed hematopoietic chimerism in recipients of fully MHC-mismatched allogeneic bone marrow cells with anti-CD154 mAb. Animals lacking CD80 and CD86 failed to achieve chimerism. We detected no T cell-intrinsic requirement for CD28 for chimerism induction. However, a CD4 T cell-intrinsic signal through CTLA-4 was shown to be essential within the first 48 hours of exposure to alloantigen for the establishment of tolerance and mixed chimerism. This signal must be provided by a recipient CD80/86(+) non-T-cell population. Donor CD80/86 expression was insufficient to achieve tolerance. Together, our findings demonstrate a surprising role for interactions of CTLA-4 expressed by alloreactive peripheral CD4 T cells with CD80/86 on recipient antigen-presenting cells (APCs) in the induction of early tolerance, suggesting a 3-cell tolerance model involving directly alloreactive CD4 cells, donor antigen-expressing bone marrow cells, and recipient antigen-presenting cells. This tolerance is independent of regulatory T cells and culminates in the deletion of directly alloreactive CD4 T cells. (Blood. 2009; 113: 3475-3484)
C1 [Kurtz, Josef; Raval, Forum; Vallot, Casey; Der, Jayden; Sykes, Megan] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Bone Marrow Transplantat Sect,Transplantat Biol R, Boston, MA 02129 USA.
[Kurtz, Josef; Raval, Forum; Vallot, Casey] Univ Cambridge Emmanuel Coll, Dept Biol, Boston, MA USA.
RP Sykes, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Bone Marrow Transplantat Sect,Transplantat Biol R, MGH E Bldg 149-5102,13th St, Boston, MA 02129 USA.
EM megan.sykes@tbrc.mgh.harvard.edu
FU NIH [R01HL49915]
FX We thank Dr Thomas Wekerle and Dr Emmanuel Zorn for critical review of
the paper, Joia Spinelli for assistance with DKO/TKO experiments, and Ms
KellyWalsh for assistance in paper preparation.; This work was supported
by NIH grant R01HL49915.
NR 75
TC 25
Z9 25
U1 0
U2 0
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD APR 9
PY 2009
VL 113
IS 15
BP 3475
EP 3484
DI 10.1182/blood-2008-01-133736
PG 10
WC Hematology
SC Hematology
GA 431HN
UT WOS:000265052300013
PM 19179471
ER
PT J
AU Wang, H
Asavaroengchai, W
Yeap, BY
Wang, MG
Wang, SM
Sykes, M
Yang, YG
AF Wang, Hui
Asavaroengchai, Wannee
Yeap, Beow Yong
Wang, Min-Guang
Wang, Shumei
Sykes, Megan
Yang, Yong-Guang
TI Paradoxical effects of IFN-gamma in graft-versus-host disease reflect
promotion of lymphohematopoietic graft-versus-host reactions and
inhibition of epithelial tissue injury
SO BLOOD
LA English
DT Article
ID BONE-MARROW-TRANSPLANTATION; CD8 T-CELLS; REFRACTORY HEMATOLOGIC
MALIGNANCIES; IDIOPATHIC PNEUMONIA SYNDROME; CYTOKINE GENE-EXPRESSION;
ANTIGEN-PRESENTING CELLS; MURINE RENAL-CANCER; INTERFERON-GAMMA; ALPHA;
MICE
AB Interferon-gamma (IFN-gamma) inhibits graft-versus-host disease (GVHD) in lethally irradiated mice receiving allogeneic hematopoietic cell transplantation (allo-HCT) but promotes lethality in unirradiated and sublethally irradiated recipients. We investigated the role of IFN-gamma in GVHD in sublethally irradiated B6D2F1 recipients of B6 allo-HCT. B6D2F1 mice receiving wild-type B6 splenocytes alone died rapidly, whereas those receiving wild-type B6 splenocytes plus marrow survived long-term. Mice in both groups showed rapid elimination of host hematopoietic cells but minimal parenchymal tissue injury. However, mice receiving allo-HCT from IFN-gamma-deficient donors died rapidly regardless of whether donor marrow was given, and they exhibited severe parenchymal injury but prolonged survival of host hematopoietic cells. IFN-gamma plays a similar role in another model involving delayed B6 donor leukocyte infusion (DLI) to established mixed allogeneic (B6 -> BALB/c) chimeras. IFN-gamma promotes DLI-mediated conversion from mixed to full donor chimerism while attenuating GVHD. Importantly, IFN-gamma enhances graft-versus-leukemia (GVL) effects in both models. Our data indicate that previously reported IFN-gamma-induced early mortality in allo-HCT recipients is due to augmentation of lymphohematopoietic graft-versus-host reaction (LGVHR) and can be avoided by providing an adequate source of donor hematopoietic stem/progenitor cells. Furthermore, the magnitude of GVL is correlated with the strength of LGVHR, and IFN-gamma reduces the potential of this allo-reactivity to cause epithelial tissue GVHD. (Blood. 2009; 113: 3612-3619)
C1 [Wang, Hui; Asavaroengchai, Wannee; Wang, Shumei; Sykes, Megan; Yang, Yong-Guang] Harvard Univ, Transplantat Biol Res Ctr, Massachusetts Gen Hosp, Sch Med,Bone Marrow Transplantat Sect, Boston, MA 02129 USA.
[Yeap, Beow Yong] Harvard Univ, Dept Med, Massachusetts Gen Hosp, Sch Med, Boston, MA 02129 USA.
[Wang, Min-Guang] Lower Columbia Pathologists, Longview, WA USA.
RP Yang, YG (reprint author), Harvard Univ, Transplantat Biol Res Ctr, Massachusetts Gen Hosp, Sch Med,Bone Marrow Transplantat Sect, MGH E,Bldg 149-5102,13th St, Boston, MA 02129 USA.
EM yongguang.yang@tbrc.mgh.harvard.edu
FU National Institutes of Health (Bethesda, MD) [5P01CA111519-020002];
American Cancer Society (Atlanta, GA) [RSG-03-227-01-LIB]
FX The authors thank Drs Christene Huang and Giovanna Andreola for critical
review of this manuscript, Mr Orlando Moreno for outstanding animal
husbandry, and Ms Kelly Walsh for expert assistance with the
manuscript.; This work was supported by grants from National Institutes
of Health (Bethesda, MD; 5P01CA111519-020002) and American Cancer
Society (Atlanta, GA; RSG-03-227-01-LIB).
NR 46
TC 27
Z9 31
U1 0
U2 0
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD APR 9
PY 2009
VL 113
IS 15
BP 3612
EP 3619
DI 10.1182/blood-2008-07-168419
PG 8
WC Hematology
SC Hematology
GA 431HN
UT WOS:000265052300030
PM 19211507
ER
PT J
AU Saenz, J
Toner, M
Risco, R
AF Saenz, Jaime
Toner, Mehmet
Risco, Ramon
TI Comparison between Ideal and Nonideal Solution Models for Single-Cell
Cryopreservation Protocols
SO JOURNAL OF PHYSICAL CHEMISTRY B
LA English
DT Article
ID AQUEOUS-SOLUTIONS; STRONG ELECTROLYTES; PERMEABILITY; SPERMATOZOA;
TRANSPORT; DIMETHYL; HUCKEL; VOLUME; DEBYE
AB Models for cell dehydration during a cryopreservation protocol are usually based on the hypothesis of id a dilute solution. The strong electrolyte character of NaCl makes us revisit these models. The case of nonideal solution is analyzed by computing the dehydration curves without this additional hypothesis. The conclusion is that, in general, while the application of the ideal dilute solution hypothesis is convenient in many cases, for some specific cooling rates there exist important differences in the degree of dehydration predicted by these two models in the studied cases of mouse sperm and hepatocyte. It is shown how this finding has relevant implications for the design and optimization of cryopreservation protocols.
C1 [Saenz, Jaime; Risco, Ramon] Univ Seville, Escuela Super Ingn, Seville 41092, Spain.
[Toner, Mehmet] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA.
RP Risco, R (reprint author), Univ Seville, Escuela Super Ingn, Seville 41092, Spain.
EM ramon@us.es
OI Risco Delgado, Ramon/0000-0001-5995-6590
NR 40
TC 6
Z9 6
U1 1
U2 2
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1520-6106
J9 J PHYS CHEM B
JI J. Phys. Chem. B
PD APR 9
PY 2009
VL 113
IS 14
BP 4853
EP 4864
DI 10.1021/jp807274z
PG 12
WC Chemistry, Physical
SC Chemistry
GA 427UW
UT WOS:000264805600048
PM 19338369
ER
PT J
AU Blumenthal, D
AF Blumenthal, David
TI Stimulating the Adoption of Health Information Technology.
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
C1 [Blumenthal, David] Massachusetts Gen Hosp Partners Healthcare Syst, Inst Hlth Policy, Boston, MA 02114 USA.
[Blumenthal, David] Harvard Univ, Sch Med, Boston, MA USA.
RP Blumenthal, D (reprint author), Massachusetts Gen Hosp Partners Healthcare Syst, Inst Hlth Policy, Boston, MA 02114 USA.
RI Tao, Youyou/D-2367-2014
NR 0
TC 316
Z9 318
U1 0
U2 18
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD APR 9
PY 2009
VL 360
IS 15
BP 1477
EP 1479
DI 10.1056/NEJMp0901592
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 430GL
UT WOS:000264976800001
PM 19321856
ER
PT J
AU Campbell, EG
AF Campbell, Eric G.
TI The Future of Research Funding in Academic Medicine.
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
C1 [Campbell, Eric G.] Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA.
[Campbell, Eric G.] Harvard Univ, Sch Med, Boston, MA USA.
RP Campbell, EG (reprint author), Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA.
NR 4
TC 18
Z9 19
U1 0
U2 0
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD APR 9
PY 2009
VL 360
IS 15
BP 1482
EP 1483
DI 10.1056/NEJMp0900132
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 430GL
UT WOS:000264976800003
PM 19357403
ER
PT J
AU Cypess, AM
Lehman, S
Williams, G
Tal, I
Rodman, D
Goldfine, AB
Kuo, FC
Palmer, EL
Tseng, Y
Doria, A
Kolodny, GM
Kahn, CR
AF Cypess, Aaron M.
Lehman, Sanaz
Williams, Gethin
Tal, Ilan
Rodman, Dean
Goldfine, Allison B.
Kuo, Frank C.
Palmer, Edwin L.
Tseng, Yu-Hua
Doria, Alessandro
Kolodny, Gerald M.
Kahn, C. Ronald
TI Identification and Importance of Brown Adipose Tissue in Adult Humans.
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID POSITRON-EMISSION-TOMOGRAPHY; DIET-INDUCED THERMOGENESIS; F-18-FDG
PET/CT; FDG-UPTAKE; USA-FAT; OBESITY; TEMPERATURE; PATIENT; MUSCLE;
SCANS
AB Background: Obesity results from an imbalance between energy intake and expenditure. In rodents and newborn humans, brown adipose tissue helps regulate energy expenditure by thermogenesis mediated by the expression of uncoupling protein 1 (UCP1), but brown adipose tissue has been considered to have no physiologic relevance in adult humans.
Methods: We analyzed 3640 consecutive (sup 18)F-fluorodeoxyglucose ((sup 18)F-FDG) positron-emission tomographic and computed tomographic (PET-CT) scans performed for various diagnostic reasons in 1972 patients for the presence of substantial depots of putative brown adipose tissue. Such depots were defined as collections of tissue that were more than 4 mm in diameter, had the density of adipose tissue according to CT, and had maximal standardized uptake values of (sup 18)F-FDG of at least 2.0 g per milliliter, indicating high metabolic activity. Clinical indexes were recorded and compared with those of date-matched controls. Immunostaining for UCP1 was performed on biopsy specimens from the neck and supraclavicular regions in patients undergoing surgery.
Results: Substantial depots of brown adipose tissue were identified by PET-CT in a region extending from the anterior neck to the thorax. Tissue from this region had UCP1-immunopositive, multilocular adipocytes indicating brown adipose tissue. Positive scans were seen in 76 of 1013 women (7.5%) and 30 of 959 men (3.1%), corresponding to a female:male ratio greater than 2:1 (P<0.001). Women also had a greater mass of brown adipose tissue and higher (sup 18)F-FDG uptake activity. The probability of the detection of brown adipose tissue was inversely correlated with years of age (P<0.001), outdoor temperature at the time of the scan (P=0.02), beta-blocker use (P<0.001), and among older patients, body-mass index (P=0.007).
Conclusions: Defined regions of functionally active brown adipose tissue are present in adult humans, are more frequent in women than in men, and may be quantified noninvasively with the use of (sup 18)F-FDG PET-CT. Most important, the amount of brown adipose tissue is inversely correlated with body-mass index, especially in older people, suggesting a potential role of brown adipose tissue in adult human metabolism.
N Engl J Med 2009;360:1509-17.
C1 [Kahn, C. Ronald] Joslin Diabet Ctr, Sect Obes & Hormone Act, Div Res, Boston, MA 02215 USA.
[Lehman, Sanaz; Williams, Gethin; Tal, Ilan; Rodman, Dean; Kolodny, Gerald M.] Beth Israel Deaconess Med Ctr, Div Nucl Med, Boston, MA 02215 USA.
[Kuo, Frank C.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Palmer, Edwin L.] Massachusetts Gen Hosp, Div Nucl Med, Boston, MA 02114 USA.
[Cypess, Aaron M.; Lehman, Sanaz; Williams, Gethin; Tal, Ilan; Rodman, Dean; Goldfine, Allison B.; Kuo, Frank C.; Palmer, Edwin L.; Tseng, Yu-Hua; Doria, Alessandro; Kolodny, Gerald M.; Kahn, C. Ronald] Harvard Univ, Sch Med, Boston, MA USA.
RP Kahn, CR (reprint author), Joslin Diabet Ctr, Sect Obes & Hormone Act, Div Res, 1 Joslin Pl, Boston, MA 02215 USA.
EM c.ronald.kahn@joslin.harvard.edu
FU National Institutes of Health [DK070722, P30 DK46200, DK33201, DK55545,
DK046200-16]; Eli Lilly Foundation
FX Supported by the Clinical Investigator Training Program, Beth Israel
Deaconess Medical Center-Harvard/MIT Health Sciences and Technology, in
collaboration with Pfizer and Merck; grants from the National Institutes
of Health (DK070722 and P30 DK46200 [to Dr. Tseng], DK33201 and DK55545
[to Dr. Kahn], and DK046200-16 [to Dr. Cypess]); and the Eli Lilly
Foundation.
NR 41
TC 1391
Z9 1448
U1 32
U2 169
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD APR 9
PY 2009
VL 360
IS 15
BP 1509
EP 1517
DI 10.1056/NEJMoa0810780
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 430GL
UT WOS:000264976800007
PM 19357406
ER
PT J
AU Bell, SK
Rosenberg, ES
AF Bell, Sigall K.
Rosenberg, Eric S.
TI A Man with Fever, Headache, Rash, and Vomiting Acute HIV-1 infection
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS-INFECTION; ACTIVE ANTIRETROVIRAL THERAPY; T-CELL
RESPONSES; UNITED-STATES; ASEPTIC-MENINGITIS; TYPE-1 INFECTION;
TRANSMISSION; DISEASE; LYMPHOCYTES; RESISTANCE
C1 [Bell, Sigall K.] Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA.
[Rosenberg, Eric S.] Massachusetts Gen Hosp, Infect Dis Unit, Dept Pathol, Boston, MA 02114 USA.
[Bell, Sigall K.; Rosenberg, Eric S.] Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA.
[Rosenberg, Eric S.] Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA.
RP Bell, SK (reprint author), Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA.
NR 38
TC 1
Z9 1
U1 0
U2 0
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD APR 9
PY 2009
VL 360
IS 15
BP 1541
EP 1549
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 430GL
UT WOS:000264976800012
ER
PT J
AU Miclea, RL
Karperien, M
Bosch, CA
van der Horst, G
van der Valk, MA
Kobayashi, T
Kronenberg, HM
Rawadi, G
Akcakaya, P
Lowik, CWGM
Fodde, R
Wit, JM
Robanus-Maandag, EC
AF Miclea, Razvan L.
Karperien, Marcel
Bosch, Cathy A. J.
van der Horst, Geertje
van der Valk, Martin A.
Kobayashi, Tatsuya
Kronenberg, Henry M.
Rawadi, Georges
Akcakaya, Pinar
Lowik, Clemens W. G. M.
Fodde, Riccardo
Wit, Jan Maarten
Robanus-Maandag, Els C.
TI Adenomatous polyposis coli-mediated control of beta-catenin is essential
for both chondrogenic and osteogenic differentiation of skeletal
precursors
SO BMC DEVELOPMENTAL BIOLOGY
LA English
DT Article
ID CHONDROCYTE DIFFERENTIATION; ENDOCHONDRAL OSSIFICATION; ARTICULAR
CHONDROCYTES; BONE-FORMATION; NASAL-SEPTUM; GROWTH-PLATE; MOUSE;
EXPRESSION; OSTEOBLAST; MICE
AB Background: During skeletogenesis, protein levels of beta-catenin in the canonical Wnt signaling pathway determine lineage commitment of skeletal precursor cells to osteoblasts and chondrocytes. Adenomatous polyposis coli (Apc) is a key controller of beta-catenin turnover by down-regulating intracellular levels of beta-catenin.
Results: To investigate whether Apc is involved in lineage commitment of skeletal precursor cells, we generated conditional knockout mice lacking functional Apc in Col2a1-expressing cells. In contrast to other models in which an oncogenic variant of beta-catenin was used, our approach resulted in the accumulation of wild type beta-catenin protein due to functional loss of Apc. Conditional homozygous Apc mutant mice died perinatally showing greatly impaired skeletogenesis. All endochondral bones were misshaped and lacked structural integrity. Lack of functional Apc resulted in a pleiotropic skeletal cell phenotype. The majority of the precursor cells lacking Apc failed to differentiate into chondrocytes or osteoblasts. However, skeletal precursor cells in the proximal ribs were able to escape the noxious effect of functional loss of Apc resulting in formation of highly active osteoblasts. Inactivation of Apc in chondrocytes was associated with dedifferentiation of these cells.
Conclusion: Our data indicate that a tight Apc-mediated control of beta-catenin levels is essential for differentiation of skeletal precursors as well as for the maintenance of a chondrocytic phenotype in a spatio-temporal regulated manner.
C1 [Karperien, Marcel] Univ Twente, Inst Biomed Technol, Dept Tissue Regenerat, NL-7500 AE Enschede, Netherlands.
[Miclea, Razvan L.; Wit, Jan Maarten] Leiden Univ, Med Ctr, Dept Pediat, Leiden, Netherlands.
[Bosch, Cathy A. J.; Akcakaya, Pinar; Robanus-Maandag, Els C.] LUMC, Dept Human Genet, Leiden, Netherlands.
[van der Horst, Geertje] Leiden Univ, Med Ctr, Dept Urol, Leiden, Netherlands.
[van der Valk, Martin A.] Netherlands Canc Inst, Dept Anim Pathol, Amsterdam, Netherlands.
[Kobayashi, Tatsuya; Kronenberg, Henry M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit,Dept Med, Boston, MA USA.
[Rawadi, Georges] Galapagos, F-93230 Romainville, France.
[Lowik, Clemens W. G. M.] Leiden Univ, Med Ctr, Dept Endocrinol & Metab Dis, Leiden, Netherlands.
[Fodde, Riccardo] Erasmus MC, Josephine Nefkens Inst, Dept Pathol, Rotterdam, Netherlands.
RP Karperien, M (reprint author), Univ Twente, Inst Biomed Technol, Dept Tissue Regenerat, POB 217, NL-7500 AE Enschede, Netherlands.
EM r.l.miclea@lumc.nl; h.b.j.karperien@tnw.utwente.nl; c.a.j.bosch@lumc.nl;
g.van_der_horst@lumc.nl; ma.vd.valk@nki.ni;
kobayash@HELIX.MGH.HARVARD.EDU; hkronenberg@partners.org;
georges.rawadi@glpg.com; pinarakcakaya@gmail.com; c.w.g.m.lowik@lumc.nl;
r.fodde@erasmusmc.nl; j.m.wit@lumc.nl; e.c.robanus@lumc.nl
OI Akcakaya, Pinar/0000-0001-5868-7069; Fodde, Riccardo/0000-0001-9839-4324
FU European Society for Pediatric Endocrinology (RLM)
FX This work was financially supported by a short-term research fellowship
from the European Society for Pediatric Endocrinology (RLM), an
unrestricted educational grant from IPSEN FARMACEUTICA BV (RLM), a
research grant from The Human Growth Foundation (MK), and a research
grant from the Association for International Cancer Research (CAJB).
NR 50
TC 28
Z9 30
U1 0
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T
4LB, ENGLAND
SN 1471-213X
J9 BMC DEV BIOL
JI BMC Dev. Biol.
PD APR 8
PY 2009
VL 9
AR 26
DI 10.1186/1471-213X-9-26
PG 14
WC Developmental Biology
SC Developmental Biology
GA 454BS
UT WOS:000266657200001
PM 19356224
ER
PT J
AU Kawamori, D
Kurpad, AJ
Hu, J
Liew, CW
Shih, JL
Ford, EL
Herrera, PL
Polonsky, KS
McGuinness, OP
Kulkarni, RN
AF Kawamori, Dan
Kurpad, Amarnath J.
Hu, Jiang
Liew, Chong Wee
Shih, Judy L.
Ford, Eric L.
Herrera, Pedro L.
Polonsky, Kenneth S.
McGuinness, Owen P.
Kulkarni, Rohit N.
TI Insulin Signaling in alpha Cells Modulates Glucagon Secretion In Vivo
SO CELL METABOLISM
LA English
DT Article
ID RECURRENTLY HYPOGLYCEMIC RATS; SENSITIVE K+ CHANNELS; SWITCH-OFF
HYPOTHESIS; BETA-CELL; ENDOCRINE PANCREAS; DIABETES-MELLITUS; RECEPTOR
EXPRESSION; GENE-TRANSCRIPTION; A-CELL; GLUCOSE
AB Glucagon plays an important role in glucose homeostasis by regulating hepatic glucose output in both normo- and hypoglycemic conditions. In, this study, we created and characterized alpha cell-specific insulin receptor knockout (alpha IRKO) mice to directly explore the role of insulin signaling in the regulation of glucagon secretion in vivo. Adult male alpha IRKO mice exhibited mild glucose intolerance, hyperglycemia, and hyperglucagonemia in the fed state and enhanced glucagon secretion in response to L-arginine stimulation. Hyperinsulinemic-hypoglycemic clamp studies revealed an enhanced glucagon secretory response and an abnormal norepinephrine response to hypoglycemia in alpha IRKO mice. The mutants also exhibited an age-dependent increase in 0 cell mass. Furthermore, siRNA-mediated knockdown of insulin receptor in glucagon-secreting InR1G cells promoted enhanced glucagon secretion and complemented our in vivo findings. Together, these data indicate a significant role for intraislet insulin signaling in the regulation of alpha cell function in both normo- and hypoglycemic conditions.
C1 [Kawamori, Dan; Kurpad, Amarnath J.; Hu, Jiang; Liew, Chong Wee; Shih, Judy L.; Kulkarni, Rohit N.] Harvard Univ, Sch Med, Dept Cellular & Mol Physiol, Joslin Diabet Ctr, Boston, MA 02215 USA.
[Kawamori, Dan; Kurpad, Amarnath J.; Hu, Jiang; Liew, Chong Wee; Shih, Judy L.; Kulkarni, Rohit N.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA.
[Ford, Eric L.; Polonsky, Kenneth S.] Washington Univ, Sch Med, Div Metab, Dept Internal Med, St Louis, MO 63110 USA.
[Herrera, Pedro L.] Univ Geneva, Sch Med, Dept Genet Med & Dev, CH-1211 Geneva, Switzerland.
[McGuinness, Owen P.] Vanderbilt Univ, Sch Med, Dept Mol Physiol & Biophys, Nashville, TN 37240 USA.
RP Kulkarni, RN (reprint author), Harvard Univ, Sch Med, Dept Cellular & Mol Physiol, Joslin Diabet Ctr, Boston, MA 02215 USA.
EM rohit.kulkarni@joslin.harvard.edu
OI /0000-0003-0771-9504
FU Research Fellowship (Manpei Suzuki Diabetes Foundation, Japan); JDRF
Postdoctoral Fellowship; American Diabetes Association Research
[7-04-RA-55]; NIH [DK67536, 5P30DK36836, DK31842, DK56341]; Swiss
National Science Foundation; the European Union; Washington University
CTSA [UL1RR024992]; (Vanderbilt MMPC) [DK59637]; (Vanderbilt DRTC)
[DK20593]
FX We thank Dr. C. Ronald Kahn (Joslin) for insulin receptor floxed mice;
Dr. Jacques Philippe (Geneva, Switzerland) for InR1G cells; Dr. K.C.
Hayes (Brandeis University, MA) for housing of mice; Drs. Pierre
Lefebvre (University of Liege, Belgium), Rory McCrimmon (Yale
University, CT), and Ryo Suzuki (Joslin) for discussions; Dr. Susan
Bonner-Weir (Joslin) for discussions regarding phloridzin experiments;
Drs. Wataru Nishimura and Arun J. Sharma (Joslin) for neonatal pancreas
sections; Hui Li (Specialized Assay Core, DERC, Joslin) for assays; and
Lindsay Huse for excellent assistance with manuscript preparation. We
especially acknowledge the valued and continued support of Cathy and
Stan Bernstein for research work in the Kulkarni lab. D.K. is the
recipient of a Research Fellowship (Manpei Suzuki Diabetes Foundation,
Japan) and a JDRF Postdoctoral Fellowship. This work was supported, in
part, by an American Diabetes Association Research Grant 7-04-RA-55
(R.N.K.), NIH DK67536 (R.N.K.), 5P30DK36836 (Joslin DERC Specialized
Assay and Advanced Microscopy Cores), the Swiss National Science
Foundation (P.L.H.), the NIH/NIDDK (Beta Cell Biology Consortium)
(P.L.H.), JDRF (P.L.H.), the European Union (6th F.P.) (P.L.H.), NIH
DK31842 and DK56341 (Washington University DRTC) (K.S.P.), UL1RR024992
(Washington University CTSA) (K.S.P.), DK59637 (Vanderbilt MMPC)
(O.P.M.), and DK20593 (Vanderbilt DRTC) (O.P.M.). K.S.P. is an advisory
board member for Pfizer Inc.
NR 63
TC 122
Z9 127
U1 3
U2 15
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1550-4131
J9 CELL METAB
JI Cell Metab.
PD APR 8
PY 2009
VL 9
IS 4
BP 350
EP 361
DI 10.1016/j.cmet.2009.02.007
PG 12
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA 430YN
UT WOS:000265028600008
PM 19356716
ER
PT J
AU Arai, K
Lo, EH
AF Arai, Ken
Lo, Eng H.
TI An Oligovascular Niche: Cerebral Endothelial Cells Promote the Survival
and Proliferation of Oligodendrocyte Precursor Cells
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID PROJECTION NEURONS; TROPHIC SUPPORT; BRAIN; IDENTIFICATION;
NEUROGENESIS; ANGIOGENESIS; DISEASE; CNS
AB We show that cerebral endothelial cells secrete trophic factors that support the survival and proliferation of rat oligodendrocyte precursor cells (OPCs). This OPC-supportive phenomenon was mediated by Akt and Src signaling pathways. Noncytotoxic levels of oxidative stress downregulate trophic factor production and disrupt the ability of cerebral endothelial cells to support OPCs. These data suggest that a novel oligovascular niche may be important for sustaining oligodendrocyte renewal and homeostasis in mammalian brain.
C1 [Arai, Ken] Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Radiol, Charlestown, MA 02129 USA.
Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Neurol, Charlestown, MA 02129 USA.
Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
RP Arai, K (reprint author), Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Radiol, MGH E 149-2401, Charlestown, MA 02129 USA.
EM karai@partners.org; lo@helix.mgh.harvard.edu
FU Deane Foundation; American Heart Association; National Institutes of
Health [R37-NS37074, R01-NS48422, R01-NS53560, P50-NS10828, P01-NS55104]
FX This work was supported in part by the Deane Foundation, American Heart
Association, and National Institutes of Health Grants R37-NS37074,
R01-NS48422, R01-NS53560, P50-NS10828, and P01-NS55104. We thank Drs.
Paul Rosenberg, Xiaoying Wang, Klaus van Leyen, Shuzhen Guo, Guang Jin,
Jianfeng Xu, and Josephine Lok for many helpful discussions.
NR 17
TC 77
Z9 77
U1 0
U2 6
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD APR 8
PY 2009
VL 29
IS 14
BP 4351
EP 4355
DI 10.1523/JNEUROSCI.0035-09.2009
PG 5
WC Neurosciences
SC Neurosciences & Neurology
GA 430ST
UT WOS:000265009600004
PM 19357263
ER
PT J
AU Kutchukian, PS
Yang, JS
Verdine, GL
Shakhnovich, EI
AF Kutchukian, Peter S.
Yang, Jae Shick
Verdine, Gregory L.
Shakhnovich, Eugene I.
TI All-Atom Model for Stabilization of alpha-Helical Structure in Peptides
by Hydrocarbon Staples
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID RING-CLOSING METATHESIS; FREE-ENERGY SURFACES; FOLDING PROBLEM;
AMINO-ACIDS; PHOTOSWITCHABLE PEPTIDE; EMPIRICAL PARAMETERS; DISULFIDE
BONDS; CROSS-LINKS; NISIN-Z; PROTEIN
AB Recent work has shown that the incorporation of an all-hydrocarbon "staple" into peptides can greatly increase their alpha-helix propensity, leading to an improvement in pharmaceutical properties such as proteolytic stability, receptor affinity, and cell permeability. Stapled peptides thus show promise as a new class of drugs capable of accessing intractable targets such as those that engage in intracellular protein-protein interactions. The extent of alpha-helix stabilization provided by stapling has proven to be substantially context dependent, requiring cumbersome screening to identify the optimal site for staple incorporation. In certain cases, a staple encompassing one turn of the helix (attached at residues i and i+4) furnishes greater helix stabilization than one encompassing two turns (i,i+7 staple), which runs counter to expectation based on polymer theory. These findings highlight the need for a more thorough understanding of the forces that underlie helix stabilization by hydrocarbon staples. Here we report all-atom Monte Carlo folding simulations comparing unmodified peptides derived from RNase A and BID BH3 with various i,i+4 and i,i+7 stapled versions thereof. The results of these simulations were found to be in quantitative agreement with experimentally determined helix propensities. We also discovered that staples can stabilize quasi-stable decoy conformations, and that the removal of these states plays a major role in determining the helix stability of stapled peptides. Finally, we critically investigate why our method works, exposing the underlying physical forces that stabilize stapled peptides.
C1 [Kutchukian, Peter S.; Yang, Jae Shick; Verdine, Gregory L.; Shakhnovich, Eugene I.] Harvard Univ, Dept Chem & Biol Chem, Cambridge, MA 02138 USA.
[Verdine, Gregory L.; Shakhnovich, Eugene I.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA.
[Kutchukian, Peter S.; Verdine, Gregory L.] Dana Farber Canc Inst, Program Canc Chem Biol, Boston, MA 02115 USA.
RP Shakhnovich, EI (reprint author), Harvard Univ, Dept Chem & Biol Chem, 12 Oxford St, Cambridge, MA 02138 USA.
EM eugene@belok.harvard.edu
RI Kutchukian, Peter/A-9826-2016
OI Kutchukian, Peter/0000-0002-5684-1971
FU NSF; NIH [GM52126]
FX This work was supported by an NSF fellowship (to P.S.K.) and NIH grant
GM52126 (to E.I.S.). We thank Stefan Wallin for helpful discussions.
NR 58
TC 60
Z9 61
U1 2
U2 32
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0002-7863
J9 J AM CHEM SOC
JI J. Am. Chem. Soc.
PD APR 8
PY 2009
VL 131
IS 13
BP 4622
EP 4627
DI 10.1021/ja805037p
PG 6
WC Chemistry, Multidisciplinary
SC Chemistry
GA 427VD
UT WOS:000264806300033
PM 19334772
ER
PT J
AU di Tomaso, E
London, N
Fuja, D
Logie, J
Tyrrell, JA
Kamoun, W
Munn, LL
Jain, RK
AF di Tomaso, Emmanuelle
London, Nyall
Fuja, Daniel
Logie, James
Tyrrell, James A.
Kamoun, Walid
Munn, Lance L.
Jain, Rakesh K.
TI PDGF-C Induces Maturation of Blood Vessels in a Model of Glioblastoma
and Attenuates the Response to Anti-VEGF Treatment
SO PLOS ONE
LA English
DT Article
ID PROTEASE-ACTIVATED LIGAND; GROWTH-FACTOR; BETA-RECEPTOR; KINASE
INHIBITOR; ALPHA-RECEPTOR; STROMAL CELLS; BRAIN-TUMORS; IN-VIVO;
EXPRESSION; ANGIOGENESIS
AB Background: Recent clinical trials of VEGF inhibitors have shown promise in the treatment of recurrent glioblastomas (GBM). However, the survival benefit is usually short-lived as tumors escape anti-VEGF therapies. Here we tested the hypothesis that Platelet Derived Growth Factor-C (PDGF-C), an isoform of the PDGF family, affects GBM progression independent of VEGF pathway and hinders anti-VEGF therapy.
Principal Findings: We first showed that PDGF-C is present in human GBMs. Then, we overexpressed or downregulated PDGF-C in a human GBM cell line, U87MG, and grew them in cranial windows in nude mice to assess vessel structure and function using intravital microscopy. PDGF-C overexpressing tumors had smaller vessel diameters and lower vascular permeability compared to the parental or siRNA-transfected tumors. Furthermore, vessels in PDGF-C overexpressing tumors had more extensive coverage with NG2 positive perivascular cells and a thicker collagen IV basement membrane than the controls. Treatment with DC101, an anti-VEGFR-2 antibody, induced decreases in vessel density in the parental tumors, but had no effect on the PDGF-C overexpressing tumors.
Conclusion: These results suggest that PDGF-C plays an important role in glioma vessel maturation and stabilization, and that it can attenuate the response to anti-VEGF therapy, potentially contributing to escape from vascular normalization.
RP di Tomaso, E (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, EL Steele Lab Tumor Biol, Boston, MA 02114 USA.
EM munn@steele.mgh.harvard.edu; jain@steele.mgh.harvard.edu
RI Tyrrell, James/A-6359-2010; Munn, Lance/L-3950-2016
OI Munn, Lance/0000-0003-0698-7232
FU NCI NIH HHS [P01 CA080124, P01-CA80124]
NR 43
TC 56
Z9 57
U1 1
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD APR 8
PY 2009
VL 4
IS 4
AR e5123
DI 10.1371/journal.pone.0005123
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 437RX
UT WOS:000265505700019
PM 19352490
ER
PT J
AU Walter, LC
Lindquist, K
Nugent, S
Schult, T
Lee, SJ
Casadei, MA
Partin, MR
AF Walter, Louise C.
Lindquist, Karla
Nugent, Sean
Schult, Tammy
Lee, Sei J.
Casadei, Michele A.
Partin, Melissa R.
TI Impact of Age and Comorbidity on Colorectal Cancer Screening Among Older
Veterans
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Article
ID FECAL-OCCULT-BLOOD; SERVICES TASK-FORCE; HEALTH-CARE-SYSTEM; PREVENTIVE
SERVICES; MEDICARE BENEFICIARIES; ELDERLY-PATIENTS; UNITED-STATES;
PROSTATE; AFFAIRS; QUALITY
AB Background: The Veterans Health Administration, the American Cancer Society, and the American Geriatrics Society recommend colorectal cancer screening for older adults unless they are unlikely to live 5 years or have significant comorbidity that would preclude treatment.
Objective: To determine whether colorectal cancer screening is targeted to healthy older patients and is avoided in older patients with severe comorbidity who have life expectancies of 5 years or less.
Design: Cohort study.
Setting: Veterans Affairs (VA) medical centers in Minneapolis, Minnesota; Durham, North Carolina; Portland, Oregon; and West Los Angeles, California, with linked national VA and Medicare administrative claims.
Patients: 27 068 patients 70 years or older who had an outpatient visit at 1 of 4 VA medical centers in 2001 or 2002 and were due for screening.
Measurements: The main outcome was receipt of fecal occult blood testing (FOBT), colonoscopy, sigmoidoscopy, or barium enema in 2001 or 2002, on the basis of national VA and Medicare claims. Charlson-Deyo comorbidity scores at the start of 2001 were used to stratify patients into 3 groups ranging from no comorbidity (score of 0) to severe comorbidity (score >= 4), and 5-year mortality was determined for each group.
Results: 46% of patients were screened from 2001 through 2002. Only 47% of patients with no comorbidity were screened despite having life expectancies greater than 5 years (5-year mortality, 19%). Although the incidence of screening decreased with age and worsening comorbidity, it was still 41% for patients with severe comorbidity who had life expectancies less than 5 years (5-year mortality, 55%). The number of VA outpatient visits predicted screening independent of comorbidity, such that patients with severe comorbidity and 4 or more visits had screening rates similar to or higher than those of healthier patients with fewer visits.
Limitations: Some tests may have been performed for nonscreening reasons. The generalizability of findings to persons who do not use the VA system is uncertain.
Conclusion: Advancing age was inversely associated with colorectal cancer screening, whereas comorbidity was a weaker predictor. More attention to comorbidity is needed to better target screening to older patients with substantial life expectancies and avoid screening older patients with limited life expectancies.
C1 San Francisco VA Med Ctr, San Francisco, CA USA.
Univ Calif San Francisco, San Francisco, CA 94143 USA.
Minneapolis Vet Affairs Med Ctr, Minneapolis, MN USA.
RP Walter, LC (reprint author), Vet Affairs Med Ctr 181G, 4150 Clement St, San Francisco, CA 94121 USA.
EM louise.walter@ucsf.edu
FU VA Health Services Research and Development [IIR-04-427]; Robert Wood
Johnson Physician Faculty Scholar
FX Grant Support: Dr. Walter is supported by VA Health Services Research
and Development grant IIR-04-427 and is a Robert Wood Johnson Physician
Faculty Scholar. Dr. Lee is a Hartford Geriatrics Health Outcomes
Research Scholar.
NR 54
TC 89
Z9 89
U1 2
U2 7
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD APR 7
PY 2009
VL 150
IS 7
BP 465
EP +
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 432EZ
UT WOS:000265117600004
PM 19349631
ER
PT J
AU Rigotti, NA
AF Rigotti, Nancy A.
TI The Future of Tobacco Treatment in the Health Care System
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Editorial Material
ID UNITED-STATES; CESSATION; SMOKING; DEPENDENCE
C1 [Rigotti, Nancy A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Rigotti, NA (reprint author), Massachusetts Gen Hosp, 50 Staniford St, Boston, MA 02114 USA.
EM nrigotti@partners.org
NR 14
TC 5
Z9 7
U1 0
U2 0
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD APR 7
PY 2009
VL 150
IS 7
BP 496
EP 497
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 432EZ
UT WOS:000265117600009
PM 19349633
ER
PT J
AU Spuentrup, E
Ruhl, KM
Botnar, RM
Wiethoff, AJ
Buhl, A
Jacques, V
Greenfield, MT
Krombach, GA
Gunther, RW
Vangel, MG
Caravan, P
AF Spuentrup, Elmar
Ruhl, Karl M.
Botnar, Rene M.
Wiethoff, Andrea J.
Buhl, Alexandra
Jacques, Vincent
Greenfield, Matthew T.
Krombach, Gabriele A.
Guenther, Rolf W.
Vangel, Mark G.
Caravan, Peter
TI Molecular Magnetic Resonance Imaging of Myocardial Perfusion With
EP-3600, a Collagen-Specific Contrast Agent Initial Feasibility Study in
a Swine Model
SO CIRCULATION
LA English
DT Article
DE contrast media; coronary disease; ischemia; magnetic resonance imaging;
perfusion
ID CORONARY-ARTERY STENOSIS; ISCHEMIC-HEART; DISEASE; STRESS; MATRIX;
VOLUME; DTPA
AB Background-Cardiac magnetic resonance (MR) perfusion imaging during the first pass after intravenous administration of extracellular contrast agents is hampered by the spatial and temporal resolution achievable and by the artifacts seen in ultrafast MR imaging. Furthermore, time-consuming quantitative data analysis is often added. The use of molecular MR imaging with a target-specific contrast agent with perfusion-dependent binding to myocardium may enable prolonged visualization of perfusion defects and thus may help to overcome limitations of currently used first-pass extracellular MR imaging. EP-3600 is a new gadolinium-containing molecular contrast agent that binds reversibly to myocardial collagen.
Methods and Results-A significant but nonocclusive coronary artery stenosis was modeled in 7 domestic swine with an undersized MR-compatible balloon positioned in the left anterior descending artery as verified by x-ray angiography. Two animals died before contrast injection as a result of arrhythmias. In 5 swine, high-spatial-resolution gradient echo imaging (approximate to 1 x 1 mm(2) in-plane resolution) was performed before and 5, 20, 40, and 60 minutes after intravenous administration of 12.3 mu mol/kg EP-3600. Contrast was administered during stress induced by an infusion of mu 250 . mol (.) kg(-1) . min(-1) adenosine. Yb-DTPA was administered simultaneously for comparison of myocardium-to-plasma ratios. Images were assessed subjectively by 2 investigators, and signal-to-noise and contrast-to-noise ratios over time were calculated. Normal myocardium showed a significant signal-to-noise ratio increase during the entire examination time. In all animals (n = 5), the perfusion defect in the left anterior descending artery territory could be visualized with a high contrast-to-noise ratio for at least 20 minutes after contrast injection. A significantly higher myocardium-to-plasma ratio was found for EP-3600 compared with the control agent Yb-DTPA (0.85 +/- 0.26 versus 0.22 +/- 0.08, respectively; P < 0.01).
Conclusion-EP-3600 is a new molecular MR imaging contrast agent that binds to the myocardium and enables prolonged, high-contrast, high-spatial-resolution visualization of myocardial perfusion defects. (Circulation. 2009; 119: 1768-1775.)
C1 [Spuentrup, Elmar] Univ Cologne, Univ Hosp, Dept Radiol, D-50924 Cologne, Germany.
[Spuentrup, Elmar; Ruhl, Karl M.; Buhl, Alexandra; Krombach, Gabriele A.; Guenther, Rolf W.] Rhein Westfal TH Aachen, Univ Hosp, Dept Diagnost Radiol, Aachen, Germany.
[Botnar, Rene M.] Tech Univ Munich, Dept Nucl Med, Munich, Germany.
[Wiethoff, Andrea J.] Philips Med Syst, Best, Netherlands.
[Jacques, Vincent; Greenfield, Matthew T.] EPIX Pharmaceut, Lexington, MA USA.
[Vangel, Mark G.; Caravan, Peter] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA.
RP Spuentrup, E (reprint author), Univ Cologne, Univ Hosp, Dept Radiol, Kerpener Str 62, D-50924 Cologne, Germany.
EM spuenti@rad.rwth-aachen.de
RI Botnar, Rene/E-6875-2012
OI Botnar, Rene/0000-0003-2811-2509
FU EPIX Pharmaceuticals, Lexington Mass,; German Research Council
[SP634/2-1]
FX This work was supported in part by EPIX Pharmaceuticals, Lexington,
Mass, and the German Research Council (SP634/2-1).
NR 27
TC 28
Z9 29
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD APR 7
PY 2009
VL 119
IS 13
BP 1768
EP 1775
DI 10.1161/CIRCULATIONAHA.108.826388
PG 8
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 429OA
UT WOS:000264928800011
PM 19307474
ER
PT J
AU Aikawa, E
Aikawa, M
Libby, P
Figueiredo, JL
Rusanescu, G
Iwamoto, Y
Fukuda, D
Kohler, RH
Shi, GP
Jaffer, FA
Weissleder, R
AF Aikawa, Elena
Aikawa, Masanori
Libby, Peter
Figueiredo, Jose-Luiz
Rusanescu, Gabriel
Iwamoto, Yoshiko
Fukuda, Daiju
Kohler, Rainer H.
Shi, Guo-Ping
Jaffer, Farouc A.
Weissleder, Ralph
TI Arterial and Aortic Valve Calcification Abolished by Elastolytic
Cathepsin S Deficiency in Chronic Renal Disease
SO CIRCULATION
LA English
DT Article
DE calcification; aortic valve; atherosclerosis; kidney failure, chronic;
elastin
ID CHRONIC KIDNEY-DISEASE; SMOOTH-MUSCLE-CELLS; VASCULAR CALCIFICATION;
CYSTATIN-C; ATHEROSCLEROTIC PLAQUES; POTENTIAL MECHANISM; VULNERABLE
PLAQUE; ELASTIN PEPTIDES; IN-VIVO; FAILURE
AB Background-Clinical studies have demonstrated that 50% of individuals with chronic renal disease (CRD) die of cardiovascular causes, including advanced calcific arterial and valvular disease; however, the mechanisms of accelerated calcification in CRD remain obscure, and no therapies can prevent disease progression. We recently demonstrated in vivo that inflammation triggers cardiovascular calcification. In vitro evidence also indicates that elastin degradation products may promote osteogenesis. Here, we used genetically modified mice and molecular imaging to test the hypothesis in vivo that cathepsin S (catS), a potent elastolytic proteinase, accelerates calcification in atherosclerotic mice with CRD induced by 5/6 nephrectomy.
Methods and Results-Apolipoprotein- deficient (apoE(-/-))/catS(+/+) (n = 24) and apoE(-/-) / catS(+/+) (n = 24) mice were assigned to CRD and control groups. CRD mice had significantly higher serum phosphate, creatinine, and cystatin C levels than those without CRD. To visualize catS activity and osteogenesis in vivo, we coadministered catS-activatable and calcification-targeted molecular imaging agents 10 weeks after nephrectomy. Imaging coregistered increased catS and osteogenic activities in the CRD apoE(-/-) / catS(+/+) cohort, whereas CRD apoE (/) / catS (/) mice exhibited less calcification. Quantitative histology demonstrated greater catS-associated elastin fragmentation and calcification in CRD apoE(-/-) / catS(+/+) than CRD apoE(-/-) / catS(+/+) aortas and aortic valves. Notably, catS deletion did not cause compensatory increases in RNA levels of other elastolytic cathepsins or matrix metalloproteinases. Elastin peptide and recombinant catS significantly increased calcification in smooth muscle cells in vitro, a process further amplified in phosphate-enriched culture medium.
Conclusions-The present study provides direct in vivo evidence that catS-induced elastolysis accelerates arterial and aortic valve calcification in CRD, providing new insight into the pathophysiology of cardiovascular calcification. (Circulation. 2009; 119: 1785-1794.)
C1 [Aikawa, Elena; Figueiredo, Jose-Luiz; Rusanescu, Gabriel; Iwamoto, Yoshiko; Kohler, Rainer H.; Weissleder, Ralph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA USA.
[Aikawa, Elena; Aikawa, Masanori; Libby, Peter; Jaffer, Farouc A.; Weissleder, Ralph] Harvard Univ, Sch Med, Donald W Reynolds Cardiovasc Clin Res Ctr Atheros, Boston, MA USA.
[Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA.
[Aikawa, Masanori; Libby, Peter; Fukuda, Daiju; Shi, Guo-Ping] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc,Dept Med, Boston, MA 02115 USA.
RP Aikawa, E (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, 149 13th St,Room 5420, Charlestown, MA 02129 USA.
EM eaikawa@mgh.harvard.edu
OI Jaffer, Farouc/0000-0001-7980-384X
FU Translational Program of Excellence in Nanotechnology; Donald W.
Reynolds Foundation; Leducq Foundation [07CVD04]; American Heart
Association [0835460N]
FX This study was supported in part by the Donald W. Reynolds Foundation
(Drs Libby and Weissleder), the Translational Program of Excellence in
Nanotechnology ( Drs Weissleder and Aikawa), the Leducq Foundation
(07CVD04; Dr Aikawa), and the American Heart Association ( 0835460N; Dr
Aikawa).
NR 48
TC 135
Z9 141
U1 1
U2 19
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD APR 7
PY 2009
VL 119
IS 13
BP 1785
EP U162
DI 10.1161/CIRCULATIONAHA.108.827972
PG 19
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 429OA
UT WOS:000264928800013
PM 19307473
ER
PT J
AU Kimberly, WT
Gilson, A
Rost, NS
Rosand, J
Viswanathan, A
Smith, EE
Greenberg, SM
AF Kimberly, W. T.
Gilson, A.
Rost, N. S.
Rosand, J.
Viswanathan, A.
Smith, E. E.
Greenberg, S. M.
TI Silent ischemic infarcts are associated with hemorrhage burden in
cerebral amyloid angiopathy
SO NEUROLOGY
LA English
DT Article
ID WHITE-MATTER LESIONS; LOBAR INTRACEREBRAL HEMORRHAGE;
CLINICAL-DIAGNOSIS; ALZHEIMERS-DISEASE; DEMENTIA; RISK; LEUKOARAIOSIS;
VALIDATION; COGNITION; AD
AB Background: Neuropathologic studies suggest an association between cerebral amyloid angiopathy (CAA) and small ischemic infarctions as well as hemorrhages. We examined the prevalence and associated risk factors for infarcts detected by diffusion-weighted imaging (DWI).
Methods: We performed retrospective analysis of MR images from 78 subjects with a diagnosis of probable CAA and a similar aged group of 55 subjects with Alzheimer disease or mild cognitive impairment (AD/MCI) for comparison. DWI and apparent diffusion coefficient (ADC) maps were inspected for acute or subacute infarcts. We also examined the association between DWI lesions and demographic variables, conventional vascular risk factors, and radiographic markers of CAA severity such as number of hemorrhages on gradient-echo MRI and volume of T2-hyperintense white matter lesions.
Results: Twelve of 78 subjects with CAA (15%) had a total of 17 DWI-hyperintense lesions consistent with subacute cerebral infarctions vs 0 of 55 subjects with AD/MCI (p = 0.001). The DWI lesions were located primarily in cortex and subcortical white matter. CAA subjects with DWI lesions had a higher median number of total hemorrhages ( 22 vs 4, p = 0.025) and no difference in white matter hyperintensity volume or conventional vascular risk factors compared to subjects with CAA without lesions.
Conclusions: MRI evidence of small subacute infarcts is present in a substantial proportion of living patients with advanced cerebral amyloid angiopathy ( CAA). The presence of these lesions is associated with a higher burden of hemorrhages, but not with conventional vascular risk factors. This suggests that advanced CAA predisposes to ischemic infarction as well as intracerebral hemorrhage. Neurology(R) 2009; 72: 1230-1235
C1 [Greenberg, S. M.] Massachusetts Gen Hosp, JP Kistler Stroke Res Ctr, Dept Neurol, Hemorrhag Stroke Res Program, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Greenberg, SM (reprint author), Massachusetts Gen Hosp, JP Kistler Stroke Res Ctr, Dept Neurol, Hemorrhag Stroke Res Program, 175 Cambridge St, Boston, MA 02114 USA.
EM sgreenberg@partners.org
OI Smith, Eric/0000-0003-3956-1668
FU NIH [RO1 AG026484, K24 NS056207]
FX Supported by NIH grants RO1 AG026484 and K24 NS056207.
NR 30
TC 98
Z9 102
U1 0
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD APR 7
PY 2009
VL 72
IS 14
BP 1230
EP 1235
DI 10.1212/01.wnl.0000345666.83318.03
PG 6
WC Clinical Neurology
SC Neurosciences & Neurology
GA 429OV
UT WOS:000264930900008
PM 19349602
ER
PT J
AU Gao, X
Schwarzschild, MA
Wang, H
Ascherio, A
AF Gao, Xiang
Schwarzschild, Michael A.
Wang, Hao
Ascherio, Alberto
TI Obesity and restless legs syndrome in men and women
SO NEUROLOGY
LA English
DT Article
ID PARKINSONS-DISEASE; GENERAL-POPULATION; RISK; PREVALENCE; SLEEP;
DOPAMINE; HEALTH; RLS; PATHOPHYSIOLOGY; EPIDEMIOLOGY
AB Background: Obesity and restless legs syndrome (RLS) are both associated with hypofunction of dopamine in the CNS. We therefore examined whether individuals who are obese have an increased risk of RLS in two ongoing US cohorts, the Nurses' Health Study II and the Health Professional Follow-up Study.
Methods: We included 65,554 women and 23,119 men free of diabetes, arthritis, and pregnancy in the current analyses. Information on RLS was assessed using a set of standardized questions. Participants were considered to have RLS if they met four RLS diagnostic criteria recommended by the International RLS Study Group and had restless legs >= 5 times/month. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed using logistic regression models adjusting for age, smoking, use of antidepressant, phobic anxiety score, and other covariates. Log ORs from the two cohorts were pooled by a fixed-effects model.
Results: There were 6.4% of women and 4.1% of men who were considered to have RLS. Multivariate adjusted ORs for RLS were 1.42 (95% CI: 1.3, 1.6; p trend < 0.0001) for participants with body mass index (BMI) > 30 vs < 23 kg/m(2) and 1.60 (95% CI: 1.5, 1.8; p trend < 0.0001) for highest vs lowest waist circumference quintiles. Greater BMI in early adulthood ( age 18-21 years) and weight gain were also associated with a higher prevalence of RLS (p trend < 0.01 for both).
Conclusions: Both overall and abdominal adiposity are associated with increased likelihoods of having restless legs syndrome ( RLS). Further prospective studies are warranted to clarify causative association between obesity and risk of developing RLS. Neurology(R) 2009; 72: 1255-1261
C1 [Gao, Xiang; Ascherio, Alberto] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA.
[Gao, Xiang; Ascherio, Alberto] Harvard Univ, Sch Med, Boston, MA USA.
[Gao, Xiang; Wang, Hao; Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Schwarzschild, Michael A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
RP Gao, X (reprint author), Brigham & Womens Hosp, Dept Med, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA.
EM xiang.gao@channing.harvard.edu
FU NIH/NINDS [R01 NS048517]
FX Supported by NIH/NINDS grant R01 NS048517.
NR 30
TC 61
Z9 63
U1 0
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD APR 7
PY 2009
VL 72
IS 14
BP 1255
EP 1261
DI 10.1212/01.wnl.0000345673.35676.1c
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA 429OV
UT WOS:000264930900012
PM 19349606
ER
PT J
AU Costello, DJ
Sims, KB
AF Costello, Daniel J.
Sims, Katherine B.
TI EFFICACY OF LAMOTRIGINE IN DISABLING MYOCLONUS IN A PATIENT WITH AN
mtDNA A3243G MUTATION
SO NEUROLOGY
LA English
DT Editorial Material
C1 [Costello, Daniel J.] Massachusetts Gen Hosp, Dept Neurol, Epilepsy Serv, Boston, MA 02114 USA.
[Sims, Katherine B.] Massachusetts Gen Hosp, Dept Neurol, Neurogenet Serv, Boston, MA 02114 USA.
[Sims, Katherine B.] Massachusetts Gen Hosp, Dept Neurol, Ctr Human Genet Res, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Costello, DJ (reprint author), Massachusetts Gen Hosp, Dept Neurol, Epilepsy Serv, ACC 835,55 Fruit St, Boston, MA 02114 USA.
EM djcostello@partners.org
NR 3
TC 3
Z9 3
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD APR 7
PY 2009
VL 72
IS 14
BP 1279
EP 1280
DI 10.1212/01.wnl.0000345663.71421.1d
PG 2
WC Clinical Neurology
SC Neurosciences & Neurology
GA 429OV
UT WOS:000264930900016
PM 19349610
ER
PT J
AU Bassett, EK
Slocum, AH
Masiakos, PT
Pryor, HI
Farokhzad, OC
Karp, JM
AF Bassett, Erik K.
Slocum, Alexander H.
Masiakos, Peter T.
Pryor, Howard I., II
Farokhzad, Omid C.
Karp, Jeffery M.
TI Design of a mechanical clutch-based needle-insertion device
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE catheter; helical-buckling; trocar
ID WELLS
AB Insertion of trocars, needles, and catheters into unintended tissues or tissue compartments results in hundreds of thousands of complications annually. Current methods for blood vessel cannulation or epidural, chest tube, and initial trocar placement often involve the blind pass of a needle through several layers of tissue and generally rely on distinguishable anatomic landmarks and a high degree of clinical skill. To address this simply and without the use of electronics, a purely mechanical clutch system was developed for use in medical devices that access tissue and tissue compartments. This clutch utilizes the surface contact of a buckled filament inside an S-shaped tube to transmit force from the filament (catheter/guide wire) to the tube (needle). Upon encountering sufficient resistance at the tip, such as dense tissue, the catheter buckles and locks within the tube, causing the filament and needle to advance as one. When the needle reaches the target tissue or fluid-filled cavity, the filament unlocks and slides freely into the target region while the needle remains stationary. A similar locking phenomenon has long been observed in drill strings inside drill shafts used by the oil-drilling industry, and oil industry models were adapted to describe the motion of this clutch system. A predictive analytical model was generated and validated with empirical data and used to develop prototypes of a complete device then tested in vitro on muscle tissue and in vivo on a porcine laparoscopic model with promising results.
C1 [Bassett, Erik K.; Pryor, Howard I., II] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA.
[Bassett, Erik K.; Slocum, Alexander H.] Brigham & Womens Hosp, Dept Mech Engn, Ctr Biomed Engn, Cambridge, MA 02139 USA.
[Karp, Jeffery M.] Brigham & Womens Hosp, Harvard Mit Div Hlth Sci & Technol, Ctr Biomed Engn, Cambridge, MA 02139 USA.
[Karp, Jeffery M.] Brigham & Womens Hosp, Ctr Biomed Engn, MIT, Cambridge, MA 02139 USA.
[Masiakos, Peter T.; Pryor, Howard I., II; Farokhzad, Omid C.; Karp, Jeffery M.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Farokhzad, Omid C.] Brigham & Womens Hosp, Dept Anesthesia, Boston, MA 02115 USA.
[Masiakos, Peter T.] Massachusetts Gen Hosp, Dept Pediat Surg, Boston, MA 02114 USA.
RP Bassett, EK (reprint author), Massachusetts Gen Hosp, Ctr Regenerat Med, 55 Fruit St, Boston, MA 02114 USA.
EM ebassett1@partners.org; jkarp@rics.bwh.harvard.edu
FU Deshpande Center for Technological Innovation; Center for Integration of
Medicine and Innovative Technology
FX We thank Terrance Norchi for providing advice regarding translational
considerations, Demos Pafitis at Schlumberger for directing us to
appropriate oil industry references, Dr. Denise Gee for technical
laparoscopic assistance, and Dr. Douglas Shook for providing operating
room access to observe catheterization procedures. This work was
supported by the Deshpande Center for Technological Innovation at the
Massachusetts Institute of Technology and the Center for Integration of
Medicine and Innovative Technology.
NR 11
TC 8
Z9 9
U1 0
U2 9
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD APR 7
PY 2009
VL 106
IS 14
BP 5540
EP 5545
DI 10.1073/pnas.0808274106
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 430CX
UT WOS:000264967500018
PM 19307560
ER
PT J
AU Pitroda, SP
Khodarev, NN
Beckett, MA
Kufe, DW
Weichselbaum, RR
AF Pitroda, Sean P.
Khodarev, Nikolai N.
Beckett, Michael A.
Kufe, Donald W.
Weichselbaum, Ralph R.
TI MUC1-induced alterations in a lipid metabolic gene network predict
response of human breast cancers to tamoxifen treatment
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE breast cancer; expression profiling; lipid metabolism; cholesterol
biosynthesis; risk factors
ID CARCINOMA-ASSOCIATED ANTIGEN; 2-GENE EXPRESSION RATIO;
ESTROGEN-RECEPTOR; IONIZING-RADIATION; BETA-CATENIN; MUC1 GENE;
ONCOPROTEIN; CELLS; SIGNATURE; RECURRENCE
AB The mucin 1 (MUC1) oncoprotein is aberrantly overexpressed in human breast cancers. Although MUC1 modulates the activity of estrogen receptor alpha (ER), there is no information regarding the effects of MUC1 on global gene expression patterns and the potential role of MUC1-induced genes in predicting outcome for breast cancer patients. We have developed an experimental model of MUC1-induced transformation that has identified the activation of genes involved in cholesterol and fatty acid metabolism. A 38-gene set of experimentally derived MUC1-induced genes associated with lipid metabolism was applied to the analysis of ER(+) breast cancer patients treated with tamoxifen. The results obtained from 2 independent databases demonstrate that patients overexpressing MUC1 and the lipid metabolic pathways are at significantly higher risk for death and recurrence/distant metastasis. By contrast, these genes were not predictive in untreated patients. Furthermore, a positive correlation was found between expression of the 38-gene set and the ER signaling pathway. These findings indicate that (i) MUC1 regulates cholesterol and fatty acid metabolism, and (ii) activation of these pathways in ER(+) breast cancers predicts failure to tamoxifen treatment.
C1 [Pitroda, Sean P.; Khodarev, Nikolai N.; Beckett, Michael A.; Weichselbaum, Ralph R.] Univ Chicago, Dept Radiat & Cellular Oncol, Chicago, IL 60637 USA.
[Kufe, Donald W.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Weichselbaum, RR (reprint author), Univ Chicago, Dept Radiat & Cellular Oncol, Chicago, IL 60637 USA.
EM rrw@radonc.bsd.uchicago.edu
FU Lung Cancer Foundation; National Cancer Institute [CA71933, CA78766,
CA97098]
FX We thank Dr. Samuel Hellman for helpful discussion of the manuscript.
These studies were supported by grants from the Lung Cancer Foundation
and by National Cancer Institute Grants CA71933, CA78766, and CA97098.
NR 41
TC 54
Z9 54
U1 1
U2 5
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD APR 7
PY 2009
VL 106
IS 14
BP 5837
EP 5841
DI 10.1073/pnas.0812029106
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 430CX
UT WOS:000264967500069
PM 19289846
ER
PT J
AU Soe-Lin, S
Apte, SS
Andriopoulos, B
Andrews, MC
Schranzhofer, M
Kahawita, T
Garcia-Santos, D
Ponka, P
AF Soe-Lin, Shan
Apte, Sameer S.
Andriopoulos, Billy, Jr.
Andrews, Marc C.
Schranzhofer, Matthias
Kahawita, Tanya
Garcia-Santos, Daniel
Ponka, Prem
TI Nramp1 promotes efficient macrophage recycling of iron following
erythrophagocytosis in vivo
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE hemolytic anemia; iron overload; iron homeostasis; hepcidin; ferroportin
ID ANTIMICROBIAL PEPTIDE HEPCIDIN; NATURAL-RESISTANCE; MOUSE-LIVER;
INTRACELLULAR PARASITES; FERROPORTIN DISEASE; MICROCYTIC ANEMIA;
MOLECULAR CONTROL; KNOCKOUT MICE; GENE; ERYTHROPOIESIS
AB Natural resistance-associated macrophage protein 1 (Nramp1) is a divalent metal transporter expressed exclusively in phagocytic cells. We hypothesized that macrophage Nramp1 may participate in the recycling of iron acquired from phagocytosed senescent erythrocytes. To evaluate the role of Nramp1 in vivo, the iron parameters of WT and KO mice were analyzed after acute and chronic induction of hemolytic anemia. We found that untreated KO mice exhibited greater serum transferrin saturation and splenic iron content with higher duodenal ferroportin (Fpn) and divalent metal transporter 1 (DMT1) expression. Furthermore, hepatocyte iron content and hepcidin mRNA levels were dramatically lower in KO mice, indicating that hepcidin levels can be regulated by low-hepatocyte iron stores despite increased transferrin saturation. After acute treatment with the hemolytic agent phenylhydrazine (Phz), KO mice experienced a significant decrease in transferrin saturation and hematocrit, whereas WT mice were relatively unaffected. After a month-long Phz regimen, KO mice retained markedly increased quantities of iron within the liver and spleen and exhibited more pronounced splenomegaly and reticulocytosis than WT mice. After injection of (59)Fe-labeled heat-damaged reticulocytes, KO animals accumulated erythrophagocytosed (59)Fe within their liver and spleen, whereas WT animals efficiently recycled phagocytosed (59)Fe to the marrow and erythrocytes. These data imply that without Nramp1, iron accumulates within the liver and spleen during erythrophagocytosis and hemolytic anemia, supporting our hypothesis that Nramp1 promotes efficient hemoglobin iron recycling in macrophages. Our observations suggest that mutations in Nramp1 could result in a novel form of human hereditary iron overload.
C1 [Schranzhofer, Matthias; Kahawita, Tanya; Ponka, Prem] McGill Univ, Dept Physiol, Montreal, PQ H3A 2T5, Canada.
[Soe-Lin, Shan; Ponka, Prem] McGill Univ, Div Expt Med, Montreal, PQ H3A 2T5, Canada.
[Soe-Lin, Shan; Apte, Sameer S.; Schranzhofer, Matthias; Kahawita, Tanya; Garcia-Santos, Daniel; Ponka, Prem] Jewish Gen Hosp, Lady Davis Inst Med Res, Montreal, PQ H3T 1E2, Canada.
[Andrews, Marc C.] Inst Rech Clin Montreal, Dept Mol Genet & Dev, Montreal, PQ H2W 1R7, Canada.
[Andriopoulos, Billy, Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Membrane Biol,Div Nephrol,Ctr Syst Biol, Boston, MA 02114 USA.
RP Ponka, P (reprint author), Sir Mortimer B Davis Jewish Hosp, Lady Davis Inst Med Res, 3755 Cote Ste Catherine Rd, Montreal, PQ H3T 1E2, Canada.
EM prem.ponka@mcgill.ca
RI Ponka, Prem/A-4123-2011;
OI Garcia dos Santos, Daniel/0000-0003-3894-427X
FU Canadian Institutes of Health Research
FX The authors thank Drs. Tomas Ganz, Antonello Pietrangelo, and Mitchell
Knutson for their illuminating suggestions and advice; Dr. Philippe Gros
(McGill University, Montreal) for his kind gift of mice and antibodies;
and Ms. Jing Zhao for her assistance with erythropoietin measurements.
This research was funded by grants from the Canadian Institutes of
Health Research.
NR 63
TC 71
Z9 79
U1 1
U2 10
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD APR 7
PY 2009
VL 106
IS 14
BP 5960
EP 5965
DI 10.1073/pnas.0900808106
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 430CX
UT WOS:000264967500090
PM 19321419
ER
PT J
AU Zhu, TF
Szostak, JW
AF Zhu, Ting F.
Szostak, Jack W.
TI Preparation of Large Monodisperse Vesicles
SO PLOS ONE
LA English
DT Article
AB Preparation of monodisperse vesicles is important both for research purposes and for practical applications. While the extrusion of vesicles through small pores (similar to 100 nm in diameter) results in relatively uniform populations of vesicles, extrusion to larger sizes results in very heterogeneous populations of vesicles. Here we report a simple method for preparing large monodisperse multilamellar vesicles through a combination of extrusion and large-pore dialysis. For example, extrusion of polydisperse vesicles through 5-mu m-diameter pores eliminates vesicles larger than 5 mu m in diameter. Dialysis of extruded vesicles against 3-mu m-pore-size polycarbonate membranes eliminates vesicles smaller than 3 mu m in diameter, leaving behind a population of monodisperse vesicles with a mean diameter of 4 mu m. The simplicity of this method makes it an effective tool for laboratory vesicle preparation with potential applications in preparing large monodisperse liposomes for drug delivery.
C1 [Zhu, Ting F.; Szostak, Jack W.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA.
[Zhu, Ting F.; Szostak, Jack W.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
[Zhu, Ting F.] Harvard Univ, Massachusetts Inst Technol, Div Hlth Sci & Technol, Cambridge, MA USA.
RP Zhu, TF (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA.
EM szostak@molbio.mgh.harvard.edu
FU NASA Exobiology Program [EXB02-0031-0018]; Howard Hughes Medical
Institute
FX This work was supported in part by grant EXB02-0031-0018 from the NASA
Exobiology Program. JWS is an Investigator of the Howard Hughes Medical
Institute. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 23
TC 35
Z9 35
U1 3
U2 32
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD APR 6
PY 2009
VL 4
IS 4
AR e5009
DI 10.1371/journal.pone.0005009
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 437RS
UT WOS:000265505200001
PM 19347043
ER
PT J
AU Brocklebank, D
Gayan, J
Andresen, JM
Roberts, SA
Young, AB
Snodgrass, SR
Penney, JB
Ramos-Arroyo, MA
Cha, JJ
Rosas, HD
Hersch, SM
Feigin, A
Cherny, SS
Wexler, NS
Housman, DE
Cardon, LR
AF Brocklebank, D.
Gayan, J.
Andresen, J. M.
Roberts, S. A.
Young, A. B.
Snodgrass, S. R.
Penney, J. B.
Ramos-Arroyo, M. A.
Cha, J. J.
Rosas, H. D.
Hersch, S. M.
Feigin, A.
Cherny, S. S.
Wexler, N. S.
Housman, D. E.
Cardon, L. R.
CA Int-Venezuela Collaborative
TI Repeat Instability in the 27-39 CAG Range of the HD Gene in the
Venezuelan Kindreds: Counseling Implications
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS
LA English
DT Article
DE trinucleotide repeat; Huntington's disease; genetic counseling
ID HUNTINGTONS-DISEASE; INTERMEDIATE ALLELES; MUTATIONS
AB The instability of the CAG repeat size of the HD gene when transmitted intergenerationally has critical implications for genetic counseling practices. In particular, CAG repeats between 27 and 35 have been the subject of debate based on small samples. To address this issue, we analyzed allelic instability in the Venezuelan HD kindreds, the largest and most informative families ascertained for HD. We identified 647 transmissions. Our results indicate that repeats in the 27-35 CAG range are highly stable. Out of 69 transmitted alleles in this range, none expand into any penetrant ranges. Contrastingly, 14% of alleles transmitted from the incompletely penetrant range (36-39 CAGs) expand into the completely penetrant range, characterized by alleles with 40 or more CAG repeats. At least 12 of the 534 transmissions from the completely penetrant range contract into the incompletely penetrant range of 36-39 CAG repeats. In these kindreds, none of the individuals with 27-39 CAGs were symptomatic, even though they ranged in age from I I to 82 years. We expect these findings to be helpful in updating genetic counseling practices. (C) 2008 Wiley-Liss, Inc.
C1 [Brocklebank, D.; Gayan, J.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
[Gayan, J.] Neocodex, Seville, Spain.
[Andresen, J. M.; Housman, D. E.] MIT, Cambridge, MA 02139 USA.
[Roberts, S. A.; Wexler, N. S.] Hereditary Dis Fdn, New York, NY USA.
[Roberts, S. A.; Wexler, N. S.] Columbia Univ, New York, NY USA.
[Young, A. B.; Cha, J. J.; Rosas, H. D.; Hersch, S. M.] Massachusetts Gen Hosp, Charlestown, MA USA.
[Snodgrass, S. R.] Childrens Hosp, Los Angeles, CA 90027 USA.
[Ramos-Arroyo, M. A.] Hosp Virgen Camino, Pamplona, Iruna, Spain.
[Feigin, A.] N Shore Univ Hosp, Manhasset, NY USA.
[Cherny, S. S.] Univ Hong Kong, Genome Res Ctr, Dept Psychiat, Hong Kong, Hong Kong, Peoples R China.
[Cherny, S. S.] Univ Hong Kong, Li Ka Shing Fac Med, State Key Lab Brain & Cognit Sci, Hong Kong, Hong Kong, Peoples R China.
[Cardon, L. R.] GlaxoSmithKline Inc, King Of Prussia, PA USA.
RP Brocklebank, D (reprint author), Univ Oxford, Wellcome Trust Ctr, Roosevelt Dr, Oxford OX3 7BN, England.
EM deniseb@well.ox.ac.uk
RI Cherny, Stacey/B-3315-2008
OI Cherny, Stacey/0000-0002-0269-3352
FU Hereditary Disease Foundation; NINDS; NIH; W.M. Keck Foundation;
Wellcome Trust; [NS22031-15]; [EY-12562]
FX We are indebted to the Venezuelan families who have participated in this
project throughout all these years. Their generous collaboration has
been critical to the success of this project and many others. We also
acknowledge support from the Hereditary Disease Foundation, NINDS, NIH,
grant numbers: NS22031-15, EY-12562, W.M. Keck Foundation and the
Wellcome Trust.
NR 13
TC 16
Z9 16
U1 0
U2 1
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1552-4841
J9 AM J MED GENET B
JI Am. J. Med. Genet. B
PD APR 5
PY 2009
VL 150B
IS 3
BP 425
EP 429
DI 10.1002/ajmg.b.30826
PG 5
WC Genetics & Heredity; Psychiatry
SC Genetics & Heredity; Psychiatry
GA 425YZ
UT WOS:000264675500017
PM 18712713
ER
PT J
AU Fan, BJ
Wang, DY
Cheng, CY
Ko, WC
Lam, SC
Pang, CP
AF Fan, Bao Jian
Wang, Dan Yi
Cheng, Ching-Yu
Ko, Wendy Charles
Lam, Shun Chiu
Pang, Chi Pui
TI Different WDR36 mutation pattern in Chinese patients with primary
open-angle glaucoma
SO MOLECULAR VISION
LA English
DT Article
ID DNA-SEQUENCE VARIANTS; P53 CODON-72 POLYMORPHISM; WIDE SCAN MAPS; LOXL1
GENE; INTRAOCULAR-PRESSURE; GERMAN PATIENTS; ASSOCIATION;
PSEUDOEXFOLIATION; IDENTIFICATION; OPTINEURIN
AB Purpose: To determine the distribution of WD repeat domain 36 (WDR36) sequence variants in Chinese patients with primary open-angle glaucoma (POAG).
Methods: One hundred and thirty-five unrelated POAG patients (82 high tension glaucoma [HTG], 42 normal tension glaucoma [NTG], and 11 juvenile-onset POAG [JOAG] patients) and 77 unrelated controls were recruited. All 23 coding exons and splicing junctions of WDR36 were sequenced using BigDye(R) Terminator v3.1 cycle sequencing kit. Single nucleotide polymorphism (SNP) and haplotype associations were analyzed using PLINK (version 1.04).
Results: Nineteen sequence alterations were identified, and eight of them were novel including two novel nonsynonymous SNPs (L240V and I713V). Except the common I264V polymorphism, no other previously reported disease-causing or disease-susceptibility mutations were found. The novel I713V mutation was observed in three (3.7%) patients with HTG. One intronic SNP, IVS5+30C>T (rs10038177), showed significantly higher frequency of minor allele T in HTG patients (16.5%) than in controls (1.3%; Odds ratio [OR]=15.0, p=7.9x10(-7), Bonferroni corrected p=1.5x10(-5)). Haplotype GTA, which is composed of rs13153937, rs10038177, and rs11241095, was significantly associated with HTG (OR=22.5, p=0.002, Bonferroni corrected p=0.013). Neither the individual SNPs nor haplotypes of WDR36 were associated with NTG or JOAG (Bonferroni corrected p>0.05).
Conclusions: Findings in this study suggest WDR36 to be associated with sporadic HTG but not with NTG or JOAG. Our results also suggest a different mutation pattern of WDR36 in the Chinese population from other ethnic populations.
C1 [Fan, Bao Jian; Wang, Dan Yi; Ko, Wendy Charles; Lam, Shun Chiu; Pang, Chi Pui] Chinese Univ Hong Kong, Dept Ophthalmol & Visual Sci, Kowloon, Hong Kong, Peoples R China.
[Cheng, Ching-Yu] Natl Yang Ming Univ, Sch Med, Dept Ophthalmol, Taipei 112, Taiwan.
[Cheng, Ching-Yu] Taipei Vet Gen Hosp, Taipei, Taiwan.
[Fan, Bao Jian; Wang, Dan Yi] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA USA.
RP Pang, CP (reprint author), Chinese Univ Hong Kong, Hong Kong Eye Hosp, Dept Ophthalmol & Visual Sci, 147K Argyle St, Kowloon, Hong Kong, Peoples R China.
EM cppang@cuhk.edu.hk
RI Cheng, Ching-Yu/K-7017-2013; Pang, Chi/I-5388-2014;
OI Cheng, Ching-Yu/0000-0003-0655-885X; Fan, Baojian/0000-0002-6851-2737
FU University Grants Committee, Hong Kong; Medical Panel at the Chinese
University of Hong Kong [2040997]
FX This work was supported in part by a block grant from the University
Grants Committee, Hong Kong, and by a direct grant (2040997) from the
Medical Panel at the Chinese University of Hong Kong. The authors thank
Dr. Catherine C. J. Liu (Department of Ophthalmology, National Yang Ming
University and Taipei Veterans General Hospital, Taiwan) for her help in
collecting the clinical data of the glaucoma patients in the present
study.
NR 41
TC 20
Z9 20
U1 0
U2 1
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD APR 3
PY 2009
VL 15
IS 65-70
BP 646
EP 653
PG 8
WC Biochemistry & Molecular Biology; Ophthalmology
SC Biochemistry & Molecular Biology; Ophthalmology
GA 450OC
UT WOS:000266409700002
PM 19347049
ER
PT J
AU Jeong, H
Then, F
Melia, TJ
Mazzulli, JR
Cui, L
Savas, JN
Voisine, C
Paganetti, P
Tanese, N
Hart, AC
Yamamoto, A
Krainc, D
AF Jeong, Hyunkyung
Then, Florian
Melia, Thomas J., Jr.
Mazzulli, Joseph R.
Cui, Libin
Savas, Jeffrey N.
Voisine, Cindy
Paganetti, Paolo
Tanese, Naoko
Hart, Anne C.
Yamamoto, Ai
Krainc, Dimitri
TI Acetylation Targets Mutant Huntingtin to Autophagosomes for Degradation
SO CELL
LA English
DT Article
ID INCLUSION-BODY FORMATION; KNOCK-IN MOUSE; CAENORHABDITIS-ELEGANS;
NEURODEGENERATIVE DISEASES; TRANSCRIPTIONAL REPRESSION; POLYGLUTAMINE
EXPANSIONS; CELLULAR TOXICITY; SENSORY NEURON; DYSFUNCTION; PROTEIN
AB Huntington's disease (HD) is an incurable neurodegenerative disease caused by neuronal accumulation of the mutant protein huntingtin. Improving clearance of the mutant protein is expected to prevent cellular dysfunction and neurodegeneration in HD. We report here that such clearance can be achieved by posttranslational modification of the mutant Huntingtin (Htt) by acetylation at lysine residue 444 (K444). Increased acetylation at K444 facilitates trafficking of mutant Htt into autophagosomes, significantly improves clearance of the mutant protein by macroautophagy, and reverses the toxic effects of mutant huntingtin in primary striatal and cortical neurons and in a transgenic C. elegans model of HD. In contrast, mutant Htt that is rendered resistant to acetylation dramatically accumulates and leads to neurodegeneration in cultured neurons and in mouse brain. These studies identify acetylation as a mechanism for removing accumulated protein in HD, and more broadly for actively targeting proteins for degradation by autophagy.
C1 [Jeong, Hyunkyung; Then, Florian; Mazzulli, Joseph R.; Cui, Libin; Krainc, Dimitri] Harvard Univ, Sch Med, Massachusetts Gen Hosp, MassGen Inst Neurodegenerat,Dept Neurol, Charlestown, MA 02129 USA.
[Voisine, Cindy; Hart, Anne C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, MassGen Inst Neurodegenerat,Ctr Canc Res, Charlestown, MA 02129 USA.
[Melia, Thomas J., Jr.] Yale Univ, Dept Cell Biol, New Haven, CT 06519 USA.
[Savas, Jeffrey N.; Tanese, Naoko] New York Univ, Sch Med, Dept Microbiol, New York, NY 10016 USA.
[Savas, Jeffrey N.] New York Univ, Sch Med, NYU & NIH Grad Partnership Program Struct Biol, New York, NY 10016 USA.
[Paganetti, Paolo] Novartis Pharma AG, NIBR Basel, Neurosci Dis, CH-4002 Basel, Switzerland.
[Yamamoto, Ai] Columbia Univ, Coll Phys & Surg, Dept Neurol, New York, NY 10032 USA.
RP Krainc, D (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, MassGen Inst Neurodegenerat,Dept Neurol, Charlestown, MA 02129 USA.
EM krainc@helix.mgh.harvard.edu
RI Yamamoto, Ai/D-1100-2011;
OI Tanese, Naoko/0000-0002-1946-3211
FU DFG; [R01NS050352]; [R01 NS051303]; [R01 NS050199]
FX We are grateful to Drs. K. Kegel, M. DiFiglia, C. D. Allis, A. Basu, H.
Park, and A.B. Young and members of the Krainc laboratory for helpful
suggestions and comments on the manuscript. We also thank Drs. D.
Sarracino, B. Krastins, J. Kowalak, S. Markey, and A. Makusky for help
with mass spectrometry; B. Hyman, W. Stoothoff, and C. Lill for help
with live-cell imaging; E. Regulier for help with lentiviral
transductions; A. Weiss and A. Roscic for help with HN10 cells; H.
Ischiropoulos for use of HPLC system; N. Mizushima for Atg5-deficient
cells; A. Kazantsev for CBP and CBP Delta Q constructs; Y. Yoshimori for
GFP-LC3; G.A. Fitzgerald for p300 and P/CAF; P.W. Faber for
osm::Htt564-150Q; and the New York Structural Biology Center for the EM
facilities. This work was supported by R01NS050352 and R01 NS051303 (to
D.K.) and R01 NS050199 (to A.Y.). F.T. is a fellow of the DFG. Author
contributions: H.J. and F.T. contributed equally to this work.
NR 48
TC 196
Z9 201
U1 5
U2 20
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD APR 2
PY 2009
VL 137
IS 1
BP 60
EP 72
DI 10.1016/j.cell.2009.03.018
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 427XV
UT WOS:000264813300014
PM 19345187
ER
PT J
AU Francis, NJ
Follmer, NE
Simon, MD
Aghia, G
Butler, JD
AF Francis, Nicole J.
Follmer, Nicole E.
Simon, Matthew D.
Aghia, George
Butler, Jeffrey D.
TI Polycomb Proteins Remain Bound to Chromatin and DNA during DNA
Replication In Vitro
SO CELL
LA English
DT Article
ID GENOME-WIDE ANALYSIS; SIMIAN VIRUS-40 DNA; EARLY MOUSE EMBRYOS; HISTONE
H3; TRANSCRIBING POLYMERASE; DROSOPHILA-MELANOGASTER; POLYTENE
CHROMOSOMES; H2A UBIQUITYLATION; REPRESSIVE COMPLEX; CELLS
AB The transcriptional status of a gene can be maintained through multiple rounds of cell division during development. This epigenetic effect is believed to reflect heritable changes in chromatin folding and histone modifications or variants at target genes, but little is known about how these chromatin features are inherited through cell division. A particular challenge for maintaining transcription states is DNA replication, which disrupts or dilutes chromatin-associated proteins and histone modifications. PRC1-class Polycomb group protein complexes are essential for development and are thought to heritably silence transcription by altering chromatin folding and histone modifications. It is not known whether these complexes and their effects are maintained during DNA replication or subsequently re-established. We find that when PRC1-class Polycomb complex-bound chromatin or DNA is replicated in vitro, Polycomb complexes remain bound to replicated templates. Retention of Polycomb proteins through DNA replication may contribute to maintenance of transcriptional silencing through cell division.
C1 [Francis, Nicole J.; Follmer, Nicole E.; Aghia, George; Butler, Jeffrey D.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA.
[Simon, Matthew D.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
[Simon, Matthew D.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA.
RP Francis, NJ (reprint author), Harvard Univ, Dept Mol & Cellular Biol, 7 Divin Ave, Cambridge, MA 02138 USA.
EM francis@mcb.harvard.edu
FU National Institutes of Health [GM078456-01]; Searle Scholar award; March
of Dimes Basil O'Connor Scholar award; Helen Hay Whitney fellowship
FX We thank R. Kingston, T. Maniatis, W. M. Michael, N. Kleckner, A.
Murray, A. Mazo, L. Kobrossy, B. Lengsfeld, and S. Lo for advice and
support throughout the project and J. Muller, R. Jones, B. Stillman, and
W. M. Michael for reagents. This work was supported by the National
Institutes of Health (GM078456-01), a Searle Scholar award and a March
of Dimes Basil O'Connor Scholar award to N.J.F., and a Helen Hay Whitney
fellowship to M.D.S.
NR 71
TC 103
Z9 103
U1 1
U2 9
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD APR 2
PY 2009
VL 137
IS 1
BP 110
EP 122
DI 10.1016/j.cell.2009.02.017
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 427XV
UT WOS:000264813300018
PM 19303136
ER
PT J
AU Kawashima, Y
Pfafferott, K
Frater, J
Matthews, P
Payne, R
Addo, M
Gatanaga, H
Fujiwara, M
Hachiya, A
Koizumi, H
Kuse, N
Oka, S
Duda, A
Prendergast, A
Crawford, H
Leslie, A
Brumme, Z
Brumme, C
Allen, T
Brander, C
Kaslow, R
Tang, J
Hunter, E
Allen, S
Mulenga, J
Branch, S
Roach, T
John, M
Mallal, S
Ogwu, A
Shapiro, R
Prado, JG
Fidler, S
Weber, J
Pybus, OG
Klenerman, P
Ndung'u, T
Phillips, R
Heckerman, D
Harrigan, PR
Walker, BD
Takiguchi, M
Goulder, P
AF Kawashima, Yuka
Pfafferott, Katja
Frater, John
Matthews, Philippa
Payne, Rebecca
Addo, Marylyn
Gatanaga, Hiroyuki
Fujiwara, Mamoru
Hachiya, Atsuko
Koizumi, Hirokazu
Kuse, Nozomi
Oka, Shinichi
Duda, Anna
Prendergast, Andrew
Crawford, Hayley
Leslie, Alasdair
Brumme, Zabrina
Brumme, Chanson
Allen, Todd
Brander, Christian
Kaslow, Richard
Tang, James
Hunter, Eric
Allen, Susan
Mulenga, Joseph
Branch, Songee
Roach, Tim
John, Mina
Mallal, Simon
Ogwu, Anthony
Shapiro, Roger
Prado, Julia G.
Fidler, Sarah
Weber, Jonathan
Pybus, Oliver G.
Klenerman, Paul
Ndung'u, Thumbi
Phillips, Rodney
Heckerman, David
Harrigan, P. Richard
Walker, Bruce D.
Takiguchi, Masafumi
Goulder, Philip
TI Adaptation of HIV-1 to human leukocyte antigen class I
SO NATURE
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; T-LYMPHOCYTE RESPONSE; MHC-CLASS-I;
ESCAPE MUTATIONS; VIRAL LOAD; CELL RESPONSES; HLA-B; INFECTION; GAG;
TRANSMISSION
AB The rapid and extensive spread of the human immunodeficiency virus (HIV) epidemic provides a rare opportunity to witness host-pathogen co-evolution involving humans. A focal point is the interaction between genes encoding human leukocyte antigen (HLA) and those encoding HIV proteins. HLA molecules present fragments (epitopes) of HIV proteins on the surface of infected cells to enable immune recognition and killing by CD8(+) T cells; particular HLA molecules, such as HLA-B*57, HLA-B*27 and HLA-B*51, are more likely to mediate successful control of HIV infection(1). Mutation within these epitopes can allow viral escape from CD8(+) T-cell recognition. Here we analysed viral sequences and HLA alleles from. 2,800 subjects, drawn from 9 distinct study cohorts spanning 5 continents. Initial analysis of the HLA-B*51-restricted epitope, TAFTIPSI (reverse transcriptase residues 128135), showed a strong correlation between the frequency of the escape mutation I135X and HLA-B*51 prevalence in the 9 study cohorts (P=0.0001). Extending these analyses to incorporate other well-defined CD8(+) T-cell epitopes, including those restricted by HLA-B*57 and HLA-B*27, showed that the frequency of these epitope variants (n=14) was consistently correlated with the prevalence of the restricting HLA allele in the different cohorts (together, P < 0.0001), demonstrating strong evidence of HIV adaptation to HLA at a population level. This process of viral adaptation may dismantle the well-established HLA associations with control of HIV infection that are linked to the availability of key epitopes, and highlights the challenge for a vaccine to keep pace with the changing immunological landscape presented by HIV.
C1 [Pfafferott, Katja; Matthews, Philippa; Payne, Rebecca; Prendergast, Andrew; Crawford, Hayley; Leslie, Alasdair; Prado, Julia G.; Goulder, Philip] Dept Paediat, Oxford OX1 3SY, England.
[Frater, John; Duda, Anna; Klenerman, Paul; Phillips, Rodney] Nuffield Dept Clin Med, Oxford OX1 3SY, England.
[Frater, John; Duda, Anna; Klenerman, Paul; Phillips, Rodney] James Martin 21st Century Sch, Oxford OX1 3SY, England.
[Kawashima, Yuka; Fujiwara, Mamoru; Hachiya, Atsuko; Koizumi, Hirokazu; Kuse, Nozomi; Takiguchi, Masafumi] Kumamoto Univ, Div Viral Immunol, Kumamoto 8600811, Japan.
[Gatanaga, Hiroyuki; Oka, Shinichi] Kumamoto Univ, Div Infect Dis, Ctr AIDS Res, Kumamoto 8600811, Japan.
[Pfafferott, Katja; John, Mina; Mallal, Simon; Goulder, Philip] Royal Perth Hosp, Ctr Clin Immunol & Biomed Stat, Perth, WA 6000, Australia.
[Pfafferott, Katja; John, Mina; Mallal, Simon; Goulder, Philip] Murdoch Univ, Murdoch, WA 6000, Australia.
[Addo, Marylyn; Brumme, Zabrina; Brumme, Chanson; Allen, Todd; Brander, Christian; Walker, Bruce D.] Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02129 USA.
[Gatanaga, Hiroyuki; Hachiya, Atsuko; Oka, Shinichi] Int Med Ctr Japan, AIDS Clin Ctr, Shinjuku Ku, Tokyo 1628655, Japan.
[Brander, Christian] Hosp Badalona Germans Trias & Pujol, Fundacio IrsiCaixa HIVACAT, Badalona, Spain.
[Brander, Christian] ICREA, Barcelona 08916, Spain.
[Kaslow, Richard; Tang, James] Univ Alabama Birmingham, Birmingham, AL 35294 USA.
[Hunter, Eric] Emory Univ, Vaccine Ctr, Atlanta, GA 30329 USA.
[Hunter, Eric] Yerkes Natl Primate Res Ctr, Atlanta, GA 30329 USA.
[Allen, Susan; Mulenga, Joseph] Zambia Emory HIV Res Project, Lusaka, Zambia.
[Allen, Susan; Mulenga, Joseph] Zambia Blood Transfus Serv, Lusaka, Zambia.
[Branch, Songee; Roach, Tim] Univ W Indies, Ladymeade Reference Unit, BB-11156 Bridgetown, Barbados.
[Ogwu, Anthony; Shapiro, Roger] Botswana Harvard Sch Publ Hlth, AIDS Initiat Partnership, Gaborone, Botswana.
[Fidler, Sarah; Weber, Jonathan] Univ London Imperial Coll Sci Technol & Med, St Marys Hosp, Wright Fleming Inst, Div Med, London W2 1PG, England.
[Pybus, Oliver G.] Univ Oxford, Dept Zool, Oxford OX1 3SY, England.
[Ndung'u, Thumbi; Walker, Bruce D.; Goulder, Philip] Univ KwaZulu Natal, Doris Duke Med Res Inst, HIV Pathogenesis Programme, ZA-4013 Durban, South Africa.
[Harrigan, P. Richard] Miscrosoft Res, Redmond, WA USA.
[Heckerman, David] BC Ctr Excellence HIV AIDS, Vancouver, BC V6Z 1Y6, Canada.
[Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD 20185 USA.
RP Goulder, P (reprint author), Dept Paediat, Peter Medawar Bldg Pathogen Res,S Parks Rd, Oxford OX1 3SY, England.
EM philip.goulder@paediatrics.ox.ac.uk
RI pybus, oliver/B-2640-2012; Takiguchi, Masafumi/E-7468-2013; Kumamoto
University, CAIDS/G-8446-2013; Publications, Remarkable/I-1756-2013;
Allen, Todd/F-5473-2011;
OI Matthews, Philippa/0000-0002-4036-4269; Pybus,
Oliver/0000-0002-8797-2667; Brander, Christian/0000-0002-0548-5778;
Ndung'u, Thumbi/0000-0003-2962-3992
FU National Institutes of Health [RO1AI46995, 1 R01 AI067073, R01AI64060];
Wellcome Trust; UK Medical Research Council; Mark and Lisa Schwartz
Foundation; Ministry of Health, Labour and Welfare [012]; Ministry of
Education, Science, Sports and Culture [18390141]; NIHR Biomedical
Research Centre Programme; Elizabeth Glaser Pediatric AIDS Foundation
Scientist; Marie Curie Fellow [IEF-041811]
FX This work is funded by grants from the National Institutes of Health
(RO1AI46995 ( P. G.), 1 R01 AI067073 ( B. D. W.), R01AI64060 ( E. H.)),
the Wellcome Trust ( P. G., P. K.), the UK Medical Research Council
(J.F., A. P. and P. M.), and the Mark and Lisa Schwartz Foundation, the
Ministry of Health, Labour and Welfare (Health and Labour HIV/AIDS
Research Grants 012), the NIHR Biomedical Research Centre Programme and
the Ministry of Education, Science, Sports and Culture ( number
18390141), Japan ( M. T.). P. G. is an Elizabeth Glaser Pediatric AIDS
Foundation Scientist; J.G.P. is a Marie Curie Fellow (contract number
IEF-041811). The authors are also grateful to A. McLean and H. Fryer for
discussions of the manuscript.
NR 30
TC 257
Z9 271
U1 4
U2 40
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD APR 2
PY 2009
VL 458
IS 7238
BP 641
EP U108
DI 10.1038/nature07746
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 427RK
UT WOS:000264796200043
PM 19242411
ER
PT J
AU Granziera, C
Schmahmann, JD
Hadjikhani, N
Meyer, H
Meuli, R
Wedeen, V
Krueger, G
AF Granziera, Cristina
Schmahmann, Jeremy Dan
Hadjikhani, Nouchine
Meyer, Heiko
Meuli, Reto
Wedeen, Van
Krueger, Gunnar
TI Diffusion Spectrum Imaging Shows the Structural Basis of Functional
Cerebellar Circuits in the Human Cerebellum In Vivo
SO PLOS ONE
LA English
DT Article
AB Background: The cerebellum is a complex structure that can be affected by several congenital and acquired diseases leading to alteration of its function and neuronal circuits. Identifying the structural bases of cerebellar neuronal networks in humans in vivo may provide biomarkers for diagnosis and management of cerebellar diseases.
Objectives: To define the anatomy of intrinsic and extrinsic cerebellar circuits using high-angular resolution diffusion spectrum imaging (DSI).
Methods: We acquired high-resolution structural MRI and DSI of the cerebellum in four healthy female subjects at 3T. DSI tractography based on a streamline algorithm was performed to identify the circuits connecting the cerebellar cortex with the deep cerebellar nuclei, selected brainstem nuclei, and the thalamus. Results: Using in-vivo DSI in humans we were able to demonstrate the structure of the following cerebellar neuronal circuits: (1) connections of the inferior olivary nucleus with the cerebellar cortex, and with the deep cerebellar nuclei (2) connections between the cerebellar cortex and the deep cerebellar nuclei, (3) connections of the deep cerebellar nuclei conveyed in the superior (SCP), middle (MCP) and inferior (ICP) cerebellar peduncles, (4) complex intersections of fibers in the SCP, MCP and ICP, and (5) connections between the deep cerebellar nuclei and the red nucleus and the thalamus.
Conclusion: For the first time, we show that DSI tractography in humans in vivo is capable of revealing the structural bases of complex cerebellar networks. DSI thus appears to be a promising imaging method for characterizing anatomical disruptions that occur in cerebellar diseases, and for monitoring response to therapeutic interventions.
C1 [Granziera, Cristina] CHU Vaudois, Dept Neurol, Lausanne, Switzerland.
[Schmahmann, Jeremy Dan] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA.
[Hadjikhani, Nouchine; Wedeen, Van] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imag, Charlestown, MA USA.
[Hadjikhani, Nouchine] Ecole Polytechn Fed, Brain Mind Inst, Lausanne, Switzerland.
[Meyer, Heiko] Siemens AG, Erlangen, Germany.
[Meuli, Reto] CHU Vaudois, Dept Radiol, Lausanne, Switzerland.
[Krueger, Gunnar] Siemens Schweiz AG, Healthcare Sector IM&WS S, Renens, Switzerland.
RP Granziera, C (reprint author), CHU Vaudois, Dept Neurol, Lausanne, Switzerland.
EM Cristina.Granziera@chuv.ch
RI Hadjikhani, Nouchine/C-2018-2008; Centre d'imagerie Biomedicale,
CIBM/B-5740-2012;
OI Hadjikhani, Nouchine/0000-0003-4075-3106; Granziera,
Cristina/0000-0002-4917-8761
FU Center for Biomedical Imaging (CIBM) of Geneva - Lausanne; University of
Geneva; University of Lasuanne; Ecole Polytechnique Federale de Lausanne
(EPFL); Leenaards foundation; Louis-Jeantet Foundation; Siemens AG
(Erlangen) Foundation; NIH [5PO1NS 35611]
FX The work was supported by the Center for Biomedical Imaging (CIBM) of
Geneva - Lausanne, the Universities of Geneva and Lasuanne as welll as
the Ecole Polytechnique Federale de Lausanne (EPFL), the foundations
Leenaards and Louis-Jeantet and Siemens AG (Erlangen). NH was also
supported by NIH 5PO1NS 35611.The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 41
TC 57
Z9 60
U1 0
U2 9
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD APR 2
PY 2009
VL 4
IS 4
AR e5101
DI 10.1371/journal.pone.0005101
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 437PZ
UT WOS:000265500700014
PM 19340289
ER
PT J
AU Thatte, HS
He, XD
Goyal, RK
AF Thatte, Hemant S.
He, Xue D.
Goyal, Raj K.
TI Imaging of Nitric Oxide in Nitrergic Neuromuscular Neurotransmission in
the Gut
SO PLOS ONE
LA English
DT Article
AB Background: Numerous functional studies have shown that nitrergic neurotransmission plays a central role in peristalsis and sphincter relaxation throughout the gut and impaired nitrergic neurotransmission has been implicated in clinical disorders of all parts of the gut. However, the role of nitric oxide (NO) as a neurotransmitter continues to be controversial because: 1) the cellular site of production during neurotransmission is not well established; 2) NO may interacts with other inhibitory neurotransmitter candidates, making it difficult to understand its precise role.
Methodology/Principal Findings: Imaging NO can help resolve many of the controversies regarding the role of NO in nitrergic neurotransmission. Imaging of NO and its cellular site of production is now possible. NO forms quantifiable fluorescent compound with diaminofluorescein (DAF) and allows imaging of NO with good specificity and sensitivity in living cells. In this report we describe visualization and regulation of NO and calcium (Ca(2+)) in the myenteric nerve varicosities during neurotransmission using multiphoton microscopy. Our results in mice gastric muscle strips provide visual proof that NO is produced de novo in the nitrergic nerve varicosities upon nonadrenergic noncholinergic (NANC) nerve stimulation. These studies show that NO is a neurotransmitter rather than a mediator. Changes in NO production in response to various pharmacological treatments correlated well with changes in slow inhibitory junction potential of smooth muscles.
Conclusions/Significance: Dual imaging and electrophysiologic studies provide visual proof that during nitrergic neurotransmission NO is produced in the nerve terminals. Such studies may help define whether NO production or its signaling pathway is responsible for impaired nitrergic neurotransmission in pathological states.
C1 [Thatte, Hemant S.] VA Boston Hlth Care Syst, Cardiothorac Div, Dept Surg, Boston, MA USA.
[Thatte, Hemant S.; He, Xue D.; Goyal, Raj K.] Harvard Univ, Sch Med, Boston, MA USA.
[He, Xue D.; Goyal, Raj K.] VA Boston Hlth Care Syst, Ctr Swallow & Motil Disorders, Dept Med, Boston, MA USA.
RP Thatte, HS (reprint author), VA Boston Hlth Care Syst, Cardiothorac Div, Dept Surg, Boston, MA USA.
EM Raj_Goyal@hms.harvard.edu
FU NIDDK [DK 062867]; Office of Research and Development, Medical Research
Service, Department of Veterans Affairs [VA Merit Review Award]
FX Supported in parts by a research grant DK 062867 from the NIDDK and a VA
Merit Review Award from the Office of Research and Development, Medical
Research Service, Department of Veterans Affairs. The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 24
TC 7
Z9 7
U1 1
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD APR 2
PY 2009
VL 4
IS 4
AR e4990
DI 10.1371/journal.pone.0004990
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 437PZ
UT WOS:000265500700005
PM 19340298
ER
PT J
AU Wingo, SN
Gallardo, TD
Akbay, EA
Liang, MC
Contreras, CM
Boren, T
Shimamura, T
Miller, DS
Sharpless, NE
Bardeesy, N
Kwiatkowski, DJ
Schorge, JO
Wong, KK
Castrillon, DH
AF Wingo, Shana N.
Gallardo, Teresa D.
Akbay, Esra A.
Liang, Mei-Chi
Contreras, Cristina M.
Boren, Todd
Shimamura, Takeshi
Miller, David S.
Sharpless, Norman E.
Bardeesy, Nabeel
Kwiatkowski, David J.
Schorge, John O.
Wong, Kwok-Kin
Castrillon, Diego H.
TI Somatic LKB1 Mutations Promote Cervical Cancer Progression
SO PLOS ONE
LA English
DT Article
AB Human Papilloma Virus (HPV) is the etiologic agent for cervical cancer. Yet, infection with HPV is not sufficient to cause cervical cancer, because most infected women develop transient epithelial dysplasias that spontaneously regress. Progression to invasive cancer has been attributed to diverse host factors such as immune or hormonal status, as no recurrent genetic alterations have been identified in cervical cancers. Thus, the pressing question as to the biological basis of cervical cancer progression has remained unresolved, hampering the development of novel therapies and prognostic tests. Here we show that at least 20% of cervical cancers harbor somatically-acquired mutations in the LKB1 tumor suppressor. Approximately one-half of tumors with mutations harbored single nucleotide substitutions or microdeletions identifiable by exon sequencing, while the other half harbored larger monoallelic or biallelic deletions detectable by multiplex ligation probe amplification (MLPA). Biallelic mutations were identified in most cervical cancer cell lines; HeLa, the first human cell line, harbors a homozygous 25 kb deletion that occurred in vivo. LKB1 inactivation in primary tumors was associated with accelerated disease progression. Median survival was only 13 months for patients with LKB1-deficient tumors, but.100 months for patients with LKB1-wild type tumors (P = 0.015, log rank test; hazard ratio = 0.25, 95% CI = 0.083 to 0.77). LKB1 is thus a major cervical tumor suppressor, demonstrating that acquired genetic alterations drive progression of HPV-induced dysplasias to invasive, lethal cancers. Furthermore, LKB1 status can be exploited clinically to predict disease recurrence.
C1 [Wingo, Shana N.; Boren, Todd] Univ Texas SW Med Ctr Dallas, Div Gynecol Oncol, Dallas, TX 75390 USA.
[Gallardo, Teresa D.; Akbay, Esra A.; Contreras, Cristina M.; Miller, David S.; Castrillon, Diego H.] Univ Texas SW, Simmons Comprehensive Canc Ctr, Dept Pathol, Dallas, TX 75390 USA.
[Liang, Mei-Chi; Shimamura, Takeshi; Wong, Kwok-Kin] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA.
[Sharpless, Norman E.] Univ N Carolina, Sch Med, Lineberger Comprehensive Canc Ctr, Dept Med & Genet, Chapel Hill, NC USA.
[Bardeesy, Nabeel] Massachusetts Gen Hosp, Canc Ctr, Boston, MA USA.
[Kwiatkowski, David J.] Brigham and Womens Hosp, Dept Med, Boston, MA USA.
[Schorge, John O.] Massachusetts Gen Hosp, Div Gynecol Oncol, Boston, MA USA.
RP Wingo, SN (reprint author), Univ Texas SW Med Ctr Dallas, Div Gynecol Oncol, Dallas, TX 75390 USA.
EM diego.castrillon@utsouthwestern.edu
RI Miller, David/H-4604-2011;
OI Miller, David/0000-0002-8215-5887; wong, kwok kin/0000-0001-6323-235X
FU Sidney Kimmel Translational Science Awards; NIH NRSA [fellowship];
American Cancer Society/UT Southwestern Simmons Comprehensive Cancer
Center [Young Investigator Award]; National Center for Research
Resources [K26RR024196]
FX This work was funded through Sidney Kimmel Translational Science Awards
to D.H.C., K.K.W., N.B., and N.E.S., an NIH NRSA F31 fellowship to
C.M.C., a Young Investigator Award from the American Cancer Society/UT
Southwestern Simmons Comprehensive Cancer Center to D.H.C, and the
National Center for Research Resources (K26RR024196) (D.H.C.). The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 32
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U1 2
U2 8
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD APR 2
PY 2009
VL 4
IS 4
AR e5137
DI 10.1371/journal.pone.0005137
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 437PZ
UT WOS:000265500700022
PM 19340305
ER
PT J
AU Kabrhel, C
Courtney, DM
Camargo, CA
Moore, CL
Richman, PB
Plewa, MC
Nordenholtz, KE
Smithline, HA
Beam, DM
Brown, MD
Kline, JA
AF Kabrhel, Christopher
Courtney, D. Mark
Camargo, Carlos A.
Moore, Christopher L.
Richman, Peter B.
Plewa, Michael C.
Nordenholtz, Kristen E.
Smithline, Howard A.
Beam, Daren M.
Brown, Michael D.
Kline, Jeffrey A.
TI Potential Impact of Adjusting the Threshold of the Quantitative D-dimer
Based on Pretest Probability of Acute Pulmonary Embolism
SO ACADEMIC EMERGENCY MEDICINE
LA English
DT Article; Proceedings Paper
CT Annual Meeting of the Society-for-Academic-Emergency-Medicine Research
Forum
CY JUN 02, 2008
CL Washington, DC
SP Soc Acad Emergency Med
DE D-dimer; emergency department; venous thromboembolism; decision-making
ID VENOUS THROMBOEMBOLISM; COMPUTED-TOMOGRAPHY; CLINICAL-MODEL; DIAGNOSIS;
OUTPATIENTS; MANAGEMENT; METAANALYSIS; SCORE; RULE
AB The utility of D-dimer testing for suspected pulmonary embolism (PE) can be limited by test specificity. The authors tested if the threshold of the quantitative D-dimer can be varied according to pretest probability (PTP) of PE to increase specificity while maintaining a negative predictive value (NPV) of > 99%.
This was a prospective, observational multicenter study of emergency department (ED) patients in the United States. Eligible patients had a diagnostic study ordered to evaluate possible PE. PTP was determined by the clinician's unstructured estimate and the Wells score. Five different D-dimer assays were used. D-dimer test performance was measured using 1) standard thresholds and 2) variable threshold values: twice (for low PTP patients), equal (intermediate PTP patients), or half (high PTP patients) of standard threshold. Venous thromboembolism (VTE) within 45 days required positive imaging plus decision to treat.
The authors enrolled 7,940 patients tested for PE, and clinicians ordered a quantitative D-dimer for 4,357 (55%) patients who had PTPs distributed as follows: low (74%), moderate (21%), or high (4%). At standard cutoffs, across all PTP strata, quantitative D-dimer testing had a test sensitivity of 94% (95% confidence interval [CI] = 91% to 97%), specificity of 58% (95% CI = 56% to 60%), and NPV of 99.5% (95% CI = 99.1% to 99.7%). If variable cutoffs had been used the overall sensitivity would have been 88% (95% CI = 83% to 92%), specificity 75% (95% CI = 74% to 76%), and NPV 99.1% (95% CI = 98.7% to 99.4%).
This large multicenter observational sample demonstrates that emergency medicine clinicians currently order a D-dimer in the majority of patients tested for PE, including a large proportion with intermediate PTP and high PTP. Varying the D-dimer's cutoff according to PTP can increase specificity with no measurable decrease in NPV.
C1 [Kabrhel, Christopher; Camargo, Carlos A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Serv, Boston, MA 02115 USA.
[Courtney, D. Mark] Northwestern Univ, Med Ctr, Dept Emergency Med, Chicago, IL 60611 USA.
[Moore, Christopher L.] Yale Univ, Med Ctr, Dept Emergency Med, New Haven, CT USA.
[Richman, Peter B.] Mayo Clin, Dept Emergency Med, Scottsdale, AZ USA.
[Plewa, Michael C.] Med Coll Ohio, Dept Surg, St Vincent Mercy Med Ctr, Toledo, OH 43699 USA.
[Nordenholtz, Kristen E.] Univ Colorado, Dept Surg, Div Emergency Med, Denver, CO 80202 USA.
[Smithline, Howard A.] Baystate Med Ctr, Dept Emergency Med, Springfield, MA USA.
[Beam, Daren M.] E Carolina Univ, Sch Med, Pitt Cty Mem Hosp, Greenville, NC USA.
[Brown, Michael D.] Michigan State Univ, Dept Emergency Med, Grand Rapids, MI USA.
[Kline, Jeffrey A.] Carolinas Med Ctr, Dept Emergency Med, Charlotte, NC 28203 USA.
RP Kline, JA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Serv, Boston, MA 02115 USA.
EM Jeffery.kline@carolinashealthcare.org
OI Kabrhel, Christopher/0000-0002-8699-7176
NR 21
TC 20
Z9 20
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1069-6563
J9 ACAD EMERG MED
JI Acad. Emerg. Med.
PD APR
PY 2009
VL 16
IS 4
BP 325
EP 332
DI 10.1111/j.1553-2712.2009.00368.x
PG 8
WC Emergency Medicine
SC Emergency Medicine
GA 429XL
UT WOS:000264953300007
PM 19298619
ER
PT J
AU Goldhamer, MEJ
Cohen, AP
Bates, DW
Cook, EF
Davis, RB
Singer, DE
Simon, SR
AF Goldhamer, Mary Ellen J.
Cohen, Amy P.
Bates, David W.
Cook, E. Francis
Davis, Roger B.
Singer, Daniel E.
Simon, Steven R.
TI Protecting an Endangered Species: Training Physicians to Conduct
Clinical Research
SO ACADEMIC MEDICINE
LA English
DT Article
ID MEDICAL-STUDENTS; BIOMEDICAL-RESEARCH; INTERNAL-MEDICINE; PROGRAM;
SCIENTISTS; CARE; INVESTIGATORS; PERSPECTIVES; CHALLENGES; OBSTACLES
AB Purpose
The Program in Clinical Effectiveness (PCE) at Harvard School of Public Health is a postgraduate program emphasizing clinical research. The authors sought to evaluate the research careers of physician graduates and to determine correlates of National Institutes of Health (NIH) grant funding.
Method
In 2006, all 1,489 graduates from 19862005 were sent a 48-item survey that collected information on demographics, program experience, chosen career path, grant awards, and research pursued postprogram. Reported NIH grants were verified on the NIH Computer Retrieval of Information on Scientific Projects Web site. Cox proportional hazard regression was used to determine participant and program features associated with NIH grant funding.
Results
Overall, 994 of the 1,365 located graduates (73%) responded to the survey. Graduates pursued research in the following areas: 437 respondents (44%) pursued clinical trials, 537 (54%) pursued epidemiology, and 408 (41%) pursued health services research. A total of 156 respondents (24%) were principal investigators on an NIH grant. Correlates of receiving NIH grant funding included age less than 40 years at time of program enrollment (hazard ratio [HR] 1.87, CI 1.03, 3.41), generalist status (HR 1.57, CI 1.14, 2.16), and publishing research begun as course projects (HR 1.65, CI 1.19, 2.31). Gender, academic status at enrollment, ethnicity, tuition sponsorship, and earning an advanced degree were not associated with receipt of NIH grant funding.
Conclusions
Physicians who enrolled in the PCE at an early age and generalist physicians were particularly successful in establishing careers as clinician-investigators. Programs such as the PCE can help to sustain the workforce of physician-investigators.
C1 [Goldhamer, Mary Ellen J.; Singer, Daniel E.] Massachusetts Gen Hosp, Bulfinch Med Grp, Div Gen Med, Clin Epidemiol Unit, Boston, MA 02114 USA.
[Simon, Steven R.] Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA.
[Cohen, Amy P.] Harvard Univ, Sch Publ Hlth, Dept Informat Technol, Boston, MA 02115 USA.
[Cook, E. Francis] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Bates, David W.] Brigham & Womens Hosp, Div Gen Med, Boston, MA 02115 USA.
[Davis, Roger B.] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA.
[Simon, Steven R.] Harvard Pilgrim Hlth Care, Boston, MA USA.
RP Goldhamer, MEJ (reprint author), Massachusetts Gen Hosp, Bulfinch Med Grp, Div Gen Med, Clin Epidemiol Unit, Wang Bldg,5th Floor,Suite 535, Boston, MA 02114 USA.
EM mgoldhamer@partners.org
FU institutional National Research Service Award [5 T32HP1100119]
FX Dr. Goldhamer was supported on an institutional National Research
Service Award 5 T32HP1100119. The Program in Clinical Effectiveness
provided funds for programming the Internet survey and research
assistants who assisted in locating all graduates' addresses and in
verifying NIH grants on CRISP.
NR 39
TC 20
Z9 21
U1 1
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1040-2446
J9 ACAD MED
JI Acad. Med.
PD APR
PY 2009
VL 84
IS 4
BP 439
EP 445
PG 7
WC Education, Scientific Disciplines; Health Care Sciences & Services
SC Education & Educational Research; Health Care Sciences & Services
GA 466IQ
UT WOS:000267655200013
PM 19318774
ER
PT J
AU Vogeli, C
Koski, G
Campbell, EG
AF Vogeli, Christine
Koski, Greg
Campbell, Eric G.
TI Policies and Management of Conflicts of Interest Within Medical Research
Institutional Review Boards: Results of a National Study
SO ACADEMIC MEDICINE
LA English
DT Article
ID INDUSTRY
AB Purpose
To examine institutional review board (IRB) policies and practices with regard to conflicts of interest (COIs) among IRB members who review and approve research protocols and to assess IRB policies and procedures in light of federal policies and guidance.
Method
An anonymous survey of IRB chairs serving the most research-intensive medical institutions in the United States was conducted in fall 2005. The survey collected information about the chairs, the IRBs, and the processes IRBs had in place to manage member relationships and COIs.
Results
Two hundred eleven out of 296 eligible chairs responded (71.7%). One third of IRBs in the nation's medical schools and major academic medical centers did not require voting members to disclose relationships with industry. In practice, IRB member industry relationships were disclosed to the entire IRB (75.9%), the IRB chair (62.1%), and/or a group or entity separate from the IRB but within the institution it serves (52.5%). One in five chairs of IRBs did not feel confident that their IRB's policies and procedures ensured appropriate disclosure of industry relationships in every case. Finally, one in four IRBs did not have written policies defining appropriate actions when IRB member COIs were identified.
Conclusions
The relatively high proportion of IRBs without a requirement that voting members disclose industry relationships is inconsistent with current guidance, and likely results in lapses in awareness of when members with conflicts vote on protocols. There was no clear consensus on where oversight responsibility for member-industry relationships should lie.
C1 [Vogeli, Christine; Campbell, Eric G.] Massachusetts Gen Hosp, Dept Med, Inst Hlth Policy, Boston, MA 02038 USA.
[Koski, Greg] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA USA.
RP Vogeli, C (reprint author), Massachusetts Gen Hosp, Dept Med, Inst Hlth Policy, 50 Staniford St 9th Floor, Boston, MA 02038 USA.
EM cvogeli@partners.org
FU NCI NIH HHS [R01 CA095400]
NR 13
TC 7
Z9 7
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1040-2446
J9 ACAD MED
JI Acad. Med.
PD APR
PY 2009
VL 84
IS 4
BP 488
EP 494
PG 7
WC Education, Scientific Disciplines; Health Care Sciences & Services
SC Education & Educational Research; Health Care Sciences & Services
GA 466IQ
UT WOS:000267655200022
PM 19318786
ER
PT J
AU Eikermann, M
Rasmussen, LS
AF Eikermann, M.
Rasmussen, L. S.
TI Improving the prediction of a neuromuscular block
SO ACTA ANAESTHESIOLOGICA SCANDINAVICA
LA English
DT Editorial Material
ID MORBIDITY; IMPACT
C1 [Eikermann, M.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA.
[Eikermann, M.] Univ Klinikum Essen, Essen, Germany.
[Rasmussen, L. S.] Rigshosp, Copenhagen Univ Hosp, Ctr Head & Orthopaed, Dept Anaesthesia, DK-2100 Copenhagen, Denmark.
[Eikermann, M.] Harvard Univ, Sch Med, Boston, MA USA.
RP Eikermann, M (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA.
EM meikermann@partners.org
NR 9
TC 5
Z9 5
U1 0
U2 1
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0001-5172
J9 ACTA ANAESTH SCAND
JI Acta Anaesthesiol. Scand.
PD APR
PY 2009
VL 53
IS 4
BP 423
EP 424
DI 10.1111/j.1399-6576.2009.01941.x
PG 2
WC Anesthesiology
SC Anesthesiology
GA 418QD
UT WOS:000264162400002
PM 19317860
ER
PT J
AU Byne, W
Hazlett, EA
Buchsbaum, MS
Kemether, E
AF Byne, William
Hazlett, Erin A.
Buchsbaum, Monte S.
Kemether, Eileen
TI The thalamus and schizophrenia: current status of research
SO ACTA NEUROPATHOLOGICA
LA English
DT Review
DE Thalamus; Schizophrenia; Mediodorsal nucleus; Pulvinar; Anterior
nucleus; Centromedian nucleus
ID NEVER-MEDICATED SCHIZOPHRENICS; DOPAMINE-D-2 RECEPTOR-BINDING; LATERAL
GENICULATE-NUCLEUS; POOR-OUTCOME SCHIZOPHRENIA; MEDIAL PREFRONTAL
CORTEX; STROOP TASK-PERFORMANCE; VOXEL-BASED MORPHOMETRY; TOTAL NEURON
NUMBER; ATAXIA TYPE-3 SCA3; MEDIODORSAL NUCLEUS
AB The thalamus provides a nodal link for multiple functional circuits that are impaired in schizophrenia (SZ). Despite inconsistencies in the literature, a meta analysis suggests that the volume of the thalamus relative to that of the brain is decreased in SZ. Morphometric neuroimaging studies employing deformation, voxel-based and region of interest methodologies suggest that the volume deficit preferentially affects the thalamic regions containing the anterior and mediodorsal nuclei, and the pulvinar. Postmortem design-based stereological studies have produced mixed results regarding volume and neuronal deficits in these nuclei. This review examines those aspects of thalamic circuitry and function that suggest salience to SZ. Evidence for anomalies of thalamic structure and function obtained from postmortem and neuroimaging studies is then examined and directions for further research proposed.
C1 [Byne, William] James J Peters VA Med Ctr, Dept Psychiat, Bronx, NY 10468 USA.
[Byne, William; Hazlett, Erin A.; Buchsbaum, Monte S.; Kemether, Eileen] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA.
RP Byne, W (reprint author), James J Peters VA Med Ctr, Dept Psychiat, Res Bldg,Room 2F39, Bronx, NY 10468 USA.
EM william.byne@mssm.edu
FU veterans affairs VISN3 MI-RECC; VA merit award [MH66998, MH073911,
MH60023]; Charles A. Dana Foundation (
FX Supported by the veterans affairs VISN3 MI-RECC, VA merit award (WB),
MH66998 (WB), MH073911 (EAH), MH60023 (MSB) and a grant from the Charles
A. Dana Foundation (MSB).
NR 194
TC 83
Z9 85
U1 4
U2 11
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0001-6322
J9 ACTA NEUROPATHOL
JI Acta Neuropathol.
PD APR
PY 2009
VL 117
IS 4
BP 347
EP 368
DI 10.1007/s00401-008-0404-0
PG 22
WC Clinical Neurology; Neurosciences; Pathology
SC Neurosciences & Neurology; Pathology
GA 418UF
UT WOS:000264174200002
PM 18604544
ER
PT J
AU Perlis, RH
Fava, M
Trivedi, MH
Alpert, J
Luther, JF
Wisniewski, SR
Rush, AJ
AF Perlis, R. H.
Fava, M.
Trivedi, M. H.
Alpert, J.
Luther, J. F.
Wisniewski, S. R.
Rush, A. John
TI Irritability is associated with anxiety and greater severity, but not
bipolar spectrum features, in major depressive disorder
SO ACTA PSYCHIATRICA SCANDINAVICA
LA English
DT Article
DE major depressive disorder; bipolar disorder; diagnosis; irritability;
anger; suicide
ID STAR-ASTERISK-D; SEQUENCED TREATMENT ALTERNATIVES;
CORONARY-HEART-DISEASE; ILLNESS RATING-SCALE; ANGER ATTACKS; RELIEVE
DEPRESSION; PSYCHIATRIC OUTPATIENTS; ATHEROSCLEROSIS RISK; SUICIDE
ATTEMPTERS; CLINICAL-FEATURES
AB Irritability is common during major depressive episodes, but its clinical significance and overlap with symptoms of anxiety or bipolar disorder remains unclear. We examined clinical correlates of irritability in a confirmatory cohort of Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study participants with major depressive disorder (MDD).
Logistic regression was used to identify features associated with presence of irritability on the clinician-rated Inventory of Depressive Symptomatology.
Of 2307 study participants, 1067(46%) reported irritability at least half the time during the preceding week; they were more likely to be female, to be younger, to experience greater depression severity and anxiety, and to report poorer quality of life, prior suicide attempts and suicidal ideation. Bipolar spectrum features were not more common among those with irritability.
Irritable depression is not a distinct subtype of MDD, but irritability is associated with greater overall severity, anxiety comorbidity and suicidality.
C1 [Perlis, R. H.; Fava, M.; Alpert, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Trivedi, M. H.; Rush, A. John] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Luther, J. F.; Wisniewski, S. R.] Univ Pittsburgh, Pittsburgh, PA USA.
[Perlis, R. H.; Fava, M.; Alpert, J.] Harvard Univ, Sch Med, Boston, MA USA.
RP Perlis, RH (reprint author), Massachusetts Gen Hosp, 15 Parkman St,WACC 812, Boston, MA 02114 USA.
EM rperlis@partners.org
OI Wisniewski, Stephen/0000-0002-3877-9860; Alpert,
Jonathan/0000-0002-4332-908X; Rush, Augustus/0000-0003-2004-2382
FU NIMH [N01 MH-90003, K23MH67060]; Bowman Family Foundation award; NARSAD
Young Investigator/Sidney R. Baer, Jr. Foundation award.
FX We would like to thank all the STAR*D investigators for all the help in
making this large and complex multicenter study possible and for
generating the data for this report, and acknowledge the editorial
support of Jon Kilner, MS, MA, and the secretarial support of Fast Word
Information Processing Inc. (Dallas, Texas).
NR 47
TC 33
Z9 33
U1 3
U2 7
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0001-690X
J9 ACTA PSYCHIAT SCAND
JI Acta Psychiatr. Scand.
PD APR
PY 2009
VL 119
IS 4
BP 282
EP 289
DI 10.1111/j.1600-0447.2008.01298.x
PG 8
WC Psychiatry
SC Psychiatry
GA 414HW
UT WOS:000263855500005
PM 19207123
ER
PT J
AU Bech, P
Wilson, P
Wessel, T
Lunde, M
Fava, M
AF Bech, P.
Wilson, P.
Wessel, T.
Lunde, M.
Fava, M.
TI A validation analysis of two self-reported HAM-D-6 versions
SO ACTA PSYCHIATRICA SCANDINAVICA
LA English
DT Article
DE HAM-D17; paper-and-pencil self-reported HAM-D6;
interactive-voice-recording HAM-D6; Mokken's item response theory-model;
unidimensionality; validation analysis
ID DEPRESSION RATING-SCALE; MAJOR DEPRESSION; SENSITIVITY; CITALOPRAM;
INVENTORY; SEVERITY; DISORDER
AB The six items of the clinician-administrated Hamilton Depression Scale (HAM-D-6) cover the core items of depressive states reflecting the antidepressive effect of medication. In this study, the two self-reported versions of the HAM-D-6 have been psychometrically validated to ensure the unidimensionality of this administration form in patients with mild-to-moderate depression.
The item response theory analysis of Mokken was used to test the unidimensionality of both the Interactive Voice Recording System (IVRS) version of the HAM-D-6 and a paper-and-pencil self-reported version (S-HAM-D-6). Patients with typical major depression and with seasonal affective disorder were included.
The Mokken analysis showed that the two self-reported versions of the HAM-D-6 obtained coefficients of homogeneity above 0.40, similar to the clinician-rated HAM-D-6 and thus implying unidimensionality. By contrast, the full HAM-D-17 versions (self-reported as well as clinician-rated) obtained coefficients of homogeneity below 0.40, implying that the HAM-D-17 is a multidimensional scale.
The analysis show that both the IVRS version and the S-HAM-D-6 version are unidimensional self-rating scales for the measurement of depressive states.
C1 [Bech, P.; Lunde, M.] Copenhagen Univ Hosp, Frederiksborg Gen Hosp, Psychiat Res Unit, DK-3400 Hillerod, Denmark.
[Wilson, P.; Wessel, T.] Sepracor Inc, Clin Res, Marlborough, MA USA.
[Fava, M.] Massachusetts Gen Hosp, Depress Clin, Boston, MA 02114 USA.
[Fava, M.] Massachusetts Gen Hosp, Res Program, Boston, MA 02114 USA.
RP Bech, P (reprint author), Copenhagen Univ Hosp, Frederiksborg Gen Hosp, Psychiat Res Unit, Dyrehavevej 48, DK-3400 Hillerod, Denmark.
EM pebe@noh.regionh.dk
NR 37
TC 14
Z9 15
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0001-690X
J9 ACTA PSYCHIAT SCAND
JI Acta Psychiatr. Scand.
PD APR
PY 2009
VL 119
IS 4
BP 298
EP 303
DI 10.1111/j.1600-0447.2008.01289.x
PG 6
WC Psychiatry
SC Psychiatry
GA 414HW
UT WOS:000263855500007
PM 19032701
ER
PT J
AU James, S
Akerblom, A
Cannon, CP
Emanuelsson, H
Husted, S
Katus, H
Skene, A
Steg, PG
Storey, RF
Harrington, R
Becker, R
Wallentin, L
AF James, Stefan
Akerblom, Axel
Cannon, Christopher P.
Emanuelsson, Hakan
Husted, Steen
Katus, Hugo
Skene, Allan
Steg, Philippe Gabriel
Storey, Robert F.
Harrington, Robert
Becker, Richard
Wallentin, Lars
TI Comparison of ticagrelor, the first reversible oral P2Y(12) receptor
antagonist, with clopidogrel in patients with acute coronary syndromes:
Rationale, design, and baseline characteristics of the PLATelet
inhibition and patient Outcomes (PLATO) trial
SO AMERICAN HEART JOURNAL
LA English
DT Article
ID ST-SEGMENT ELEVATION; PRASUGREL ACHIEVES GREATER; ASPIRIN-TREATED
PATIENTS; MYOCARDIAL-INFARCTION; EUROPEAN-SOCIETY; ARTERY-DISEASE;
TASK-FORCE; AZD6140; PHARMACOKINETICS; PHARMACODYNAMICS
AB Background Antiplatelet therapy is essential treatment for acute coronary syndromes (ACS). Current therapies, however, have important limitations affecting their clinical success. Ticagrelor, the first reversible oral P2Y(12) receptor antagonist, provides faster, greater, and more consistent adenosine diphosphate-receptor inhibition than clopidogrel. The phase III PLATelet inhibition and patient Outcomes (PLATO) trial is designed to test the hypothesis that ticagrelor compared with clopidogrel will result in a lower risk of recurrent thrombotic events in a broad patient population with ACS.
Methods PLATO is an international, randomized, double-blind, event-driven trial involving >18,000 patients hospitalized for ST-elevation ACS with scheduled primary percutoneous coronary intervention or for non-ST-elevation ACS. After loading doses of ticagrelor 180 mg or clopidogrel 300 mg in a double-blind, double-dummy fashion (with provision for additional 300 mg clopidogrel at percutaneous coronary intervention), patients will receive ticagrelor 90 mg twice daily or clopidogrel 75 mg once daily for 6 to 12 months on top of acetylsalicylic acid. The primary efficacy end point is time to first occurrence of death from vascular causes, myocardial infarction, or stroke. The primary safety variable is PLATO-defined major bleeding. An extensive substudy program will explore the pathophysiology of ACS, indicators of prognosis and response to treatment, mechanisms of effect and safety of the study medications, health economics, and quality of life.
Conclusion The PLATO study will provide a pivotal comparison of the efficacy and safety of ticagrelor with those of clopidogrel in ACS patients, together with extensive information on treatment outcomes in different subsets of ACS in a broad patient population. (Am Heart J 2009; 157:599-605.)
C1 [Wallentin, Lars] Univ Uppsala Hosp, Uppsala Clin Res Ctr, S-75185 Uppsala, Sweden.
[Cannon, Christopher P.] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA.
[Emanuelsson, Hakan] AstraZeneca R&D, Molndal, Sweden.
[Husted, Steen] Arhus Univ Hosp, Dept Cardiol, Aarhus, Denmark.
[Katus, Hugo] Univ Klinikum Heidelberg, Med Klin, Heidelberg, Germany.
[Skene, Allan] Nottingham Clin Res Ltd, Nottingham, England.
[Steg, Philippe Gabriel] Univ Paris, F-75252 Paris, France.
[Steg, Philippe Gabriel] AP HP, INSERM, U 698, F-75252 Paris, France.
[Storey, Robert F.] Univ Sheffield, Cardiovasc Res Unit, Sheffield, S Yorkshire, England.
[Harrington, Robert; Becker, Richard] Duke Clin Res Inst, Durham, NC USA.
RP Wallentin, L (reprint author), Univ Uppsala Hosp, Uppsala Clin Res Ctr, S-75185 Uppsala, Sweden.
EM lars.wallentin@ucr.uu.se
RI Katus, Hugo/P-1712-2016
NR 20
TC 174
Z9 190
U1 4
U2 23
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-8703
J9 AM HEART J
JI Am. Heart J.
PD APR
PY 2009
VL 157
IS 4
BP 599
EP 605
DI 10.1016/j.ahj.2009.01.003
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 432CC
UT WOS:000265110100002
PM 19332184
ER
PT J
AU Mak, KH
Bhatt, DL
Shao, MY
Hankey, GJ
Easton, JD
Fox, KAA
Topol, EJ
AF Mak, Koon-Hou
Bhatt, Deepak L.
Shao, Mingyuan
Hankey, Graeme J.
Easton, J. Donald
Fox, Keith A. A.
Topol, Eric J.
TI Ethnic variation in adverse cardiovascular outcomes and bleeding
complications in the Clopidogrel for High Atherothrombotic Risk and
Ischemic Stabilization, Management, and Avoidance (CHARISMA) study
SO AMERICAN HEART JOURNAL
LA English
DT Article
ID ACUTE MYOCARDIAL-INFARCTION; THROMBOLYTIC THERAPY; MORTALITY; DISEASE;
TRIAL; CALCIFICATION; METAANALYSIS; OUTPATIENTS; DISPARITIES; STROKE
AB Background Atherothrombosis is a common condition affecting individuals worldwide. Its impact on different ethnic groups receiving evidence-based therapy is unclear. We aimed to determine if ethnicity is an independent predictor for cardiovascular events and bleeding complications in a contemporary clinical trial on antiplatelet therapy.
Methods This was a prospective observational study of 15,603 patients enrolled in the CHARISMA trial followed up every 6 months for a median of 28 months. The primary efficacy end point was the first occurrence of cardiovascular death, myocardial infarction, or stroke. The primary safety end point was bleeding.
Results The cohort comprised 12,502 (80.1%) white, 486 (3.1%) black, 775 (5.0%) Asian, and 1,613(10.3%) Hispanic patients. There was no difference in the occurrence of the primary composite end point among the 4 ethnic groups. Compared with Asians, cardiovascular and all-cause mortality occurred more frequently among black (adjusted hazard 2.19 and 2.04) and Hispanic (adjusted hazard, 1.83 and 1.69) patients. Although the occurrence of severe bleeding was similarly low among the 4 ethnic groups, Asian (adjusted hazard, 2.21) and black (adjusted hazard, 3.06) patients were more likely to have moderate bleeding complications than Hispanic patients..
Conclusion In this trial of individuals at risk of vascular events, ethnicity was not a significant, independent predictor of the primary composite cardiovascular event. However, ethnicity was a significant, independent predictor of the secondary outcomes, cardiovascular and all-cause mortality (blacks and Hispanics), and moderate bleeding complications (blacks and Asians). (Am Heart J 2009;157:658-65.)
C1 [Mak, Koon-Hou] Gleneagles Med Ctr, Singapore 258499, Singapore.
[Bhatt, Deepak L.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Bhatt, Deepak L.] VA Boston Healthcare Syst, Boston, MA USA.
[Shao, Mingyuan] Cleveland Clin, Cleveland, OH 44106 USA.
[Hankey, Graeme J.] Univ Western Australia, Sch Med & Pharmacol, Perth, WA 6009, Australia.
[Hankey, Graeme J.] Univ Western Australia, Royal Perth Hosp, Dept Neurol, Perth, WA 6009, Australia.
[Easton, J. Donald] Brown Univ, Providence, RI 02912 USA.
[Easton, J. Donald] Rhode Isl Hosp, Dept Neurol, Providence, RI USA.
[Fox, Keith A. A.] Univ & Royal Infirm Edinburgh, Edinburgh, Midlothian, Scotland.
[Topol, Eric J.] Scripps Translat Res Inst, La Jolla, CA USA.
RP Mak, KH (reprint author), Gleneagles Med Ctr, 6 Napier Rd 08-13, Singapore 258499, Singapore.
EM makheart@gmail.com
RI Hankey, Graeme /H-4968-2014;
OI Hankey, Graeme /0000-0002-6044-7328; Topol, Eric/0000-0002-1478-4729
NR 22
TC 46
Z9 46
U1 1
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-8703
J9 AM HEART J
JI Am. Heart J.
PD APR
PY 2009
VL 157
IS 4
BP 658
EP 665
DI 10.1016/j.ahj.2008.08.031
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 432CC
UT WOS:000265110100011
PM 19332192
ER
PT J
AU Truong, QA
Cannon, CP
Zakai, NA
Rogers, IS
Giugliano, RP
Wiviott, SD
McCabe, CH
Morrow, DA
Braunwald, E
AF Truong, Quynh A.
Cannon, Christopher P.
Zakai, Neil A.
Rogers, Ian S.
Giugliano, Robert P.
Wiviott, Stephen D.
McCabe, Carolyn H.
Morrow, David A.
Braunwald, Eugene
TI Thrombolysis in Myocardial Infarction (TIMI) Risk Index predicts
long-term mortality and heart failure in patients with ST-elevation
myocardial infarction in the TIMI 2 clinical trial
SO AMERICAN HEART JOURNAL
LA English
DT Article
ID ACUTE CORONARY SYNDROME; NATIONAL REGISTRY; II TRIAL; THERAPY; SCORE
AB Background TIMI (Thrombolysis in Myocardial Infarction) Risk Index (TRI) is a simple bedside score that predicts 30-day mortality in patients with ST-elevation myocardial infarction (MI). We sought to evaluate whether TRI was predictive of long-term mortality and clinical events.
Methods In the TIMI 2 trial, 3,153 patients (Mean age 57 10 years, 82% men) were randomized to invasive (n = 1,583) versus conservative In = 1,570) strategy postfibrinolysis with median follow-up of 3 years. TIMI Risk Index was divided into 5 groups. The primary end point was all-cause mortality. Secondary analyses included recurrent MI, congestive heart failure (CHF), and combined end points.
Results When compared with group 1, mortality in group 5 was more than 5-fold higher (hazard ratio [HR] 5.83, P < .0001) and was also increased in group 4 (HR 2.80, P < .0001) and group 3 (HR 1.96, P = .002) (c statistic 0.69). No difference was seen between groups 1 and 2 (P = .74). A similar increasing gradient effect was seen across TRI strata with group 5 having the highest risk for CHF (HR 4.13, P < .0001) and the highest risk for composite death/CHF (HR 4.35, P < .0001) over group 1. There was no difference in recurrent MI between the groups (P = .22). After controlling for other risk indicators, the relationship between TRI and mortality remained significant: group 5, HR 4.11, P < .0001; group 4, HR 2.14, P = .0009; group 3, HR 1.69, P = .02. When stratified by TRI groups, no differences in mortality or composite death/MI were found between treatment strategies.
Conclusions The simple TRI can predict increased long-term mortality, CHF, and composite death/CHF. (Am Heart J 2009; 157:673-79.)
C1 [Cannon, Christopher P.; Giugliano, Robert P.; Wiviott, Stephen D.; McCabe, Carolyn H.; Morrow, David A.; Braunwald, Eugene] Harvard Univ, Sch Med, Brigham & Womens Hosp, TIMI Study Grp,Div Cardiovasc, Boston, MA 02115 USA.
[Truong, Quynh A.; Rogers, Ian S.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02115 USA.
[Truong, Quynh A.; Rogers, Ian S.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02115 USA.
[Zakai, Neil A.] Univ Vermont, Coll Med, Dept Med, Burlington, VT 05405 USA.
[Zakai, Neil A.] Univ Vermont, Coll Med, Dept Pathol, Burlington, VT 05405 USA.
RP Cannon, CP (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, TIMI Study Grp,Div Cardiovasc, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA.
EM cpcannon@partners.org
FU National Heart, Lung, and Blood Institute (Bethesda, MD); National
Institutes of Health (Bethesda, MD) [L30HL093896, T32HL076136]
FX The TIMI 2 trial was supported by research contracts from the National
Heart, Lung, and Blood Institute (Bethesda, MD). Drs Truong and Rogers
received support from National Institutes of Health (Bethesda, MD) grant
L30HL093896 and T32HL076136.
NR 19
TC 9
Z9 11
U1 0
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-8703
J9 AM HEART J
JI Am. Heart J.
PD APR
PY 2009
VL 157
IS 4
BP 673
EP 679
DI 10.1016/j.ahj.2008.12.010
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 432CC
UT WOS:000265110100013
PM 19332194
ER
PT J
AU Gilon, D
Mehta, RH
Oh, JK
Januzzi, JL
Bossone, E
Cooper, JV
Smith, DE
Fang, JM
Nienaber, CA
Eagle, KA
Isselbacher, EM
AF Gilon, Dan
Mehta, Rajendra H.
Oh, Jae K.
Januzzi, James L., Jr.
Bossone, Eduardo
Cooper, Jeanna V.
Smith, Dean E.
Fang, Jianming
Nienaber, Christoph A.
Eagle, Kim A.
Isselbacher, Eric M.
CA Int Registry Acute Aortic Dissecti
TI Characteristics and In-Hospital Outcomes of Patients With Cardiac
Tamponade Complicating Type A Acute Aortic Dissection
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID HEMODYNAMIC COLLAPSE; RELIEF
AB Cardiac tamponade (TMP) is a life-threatening complication of acute type A aortic dissection (AAD). The purpose of this study was to assess the clinical characteristics and in-hospital outcomes of TMP in the setting of AAD on the basis of the findings in the large cohort of the International Registry of Acute Aortic Dissection (IRAD). Six hundred seventy-four patients (mean age 61.8 +/- 14.2 years) with AAD in IRAD were studied. TMP was suspected on clinical grounds and confirmed by diagnostic imaging. Univariate testing was followed by multivariate logistic regression analysis to determine the association of TMP. TMP was detected in 126 patients with AAD (18.7%). Age did not differ between patients with and without TMP. Those with TMP less often had previous cardiac surgery (7.0% vs 17.1%, p = 0.007). Syncope (37.8% vs 13.7%, p <0.0001) and altered mental status (31.2% vs 10.6%, p <0.0001) were more common in patients with AAD with TMP than without TMP. Patients with TMP were more likely to have widened mediastina on chest x-ray (72.6% vs 60.3%, p = 0.02) and to have periaortic hematomas (44.7% vs 21.2%, p <0.0001). In-hospital outcomes were significantly worse in patients with TMP. The mortality of patients with TMP remained significantly higher, even after adjustment for baseline clinical characteristics (p <0.001). On logistic regression, altered mental status, hypotension, and early mortality were identified as independent correlates of TMP. In conclusion, TMP is not uncommon in patients with AAD. Syncope, altered mental status, and a widened mediastinum on chest x-ray on presentation suggest TMP, the presence of which warrants urgent operative therapy to improve outcome. (C) 2009 Published by Elsevier Inc. (Am J Cardiol 2009;103:1029-1031)
C1 [Gilon, Dan] Hadassah Hebrew Univ, Med Ctr, Jerusalem, Israel.
[Mehta, Rajendra H.; Cooper, Jeanna V.; Smith, Dean E.; Eagle, Kim A.] Univ Michigan, Ann Arbor, MI 48109 USA.
[Oh, Jae K.] Mayo Clin, Rochester, MN USA.
[Januzzi, James L., Jr.; Fang, Jianming; Isselbacher, Eric M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Bossone, Eduardo] CNR, Lecce, Italy.
[Nienaber, Christoph A.] Univ Klinikum Rostock, Rostock, Germany.
RP Gilon, D (reprint author), Hadassah Hebrew Univ, Med Ctr, Jerusalem, Israel.
EM gilond@cc.huji.ac.il
FU University of Michigan Health System, Ann Arbor, Michigan; Varbedian
Fund for Aortic Research, Ann Arbor, Michigan
FX The International Registry of Acute Aortic Dissection is supported by
grants from the University of Michigan Health System, Ann Arbor,
Michigan, and the Varbedian Fund for Aortic Research, Ann Arbor,
Michigan.
NR 12
TC 34
Z9 37
U1 2
U2 4
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9149
J9 AM J CARDIOL
JI Am. J. Cardiol.
PD APR 1
PY 2009
VL 103
IS 7
BP 1029
EP 1031
DI 10.1016/j.amjcard.2008.12.013
PG 3
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 428AA
UT WOS:000264819000025
PM 19327436
ER
PT J
AU Smith, SM
Gardner, KK
Locke, J
Zwart, SR
AF Smith, Scott M.
Gardner, Keri K.
Locke, James
Zwart, Sara R.
TI Vitamin D supplementation during Antarctic winter
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID CELL-MEDIATED-IMMUNITY; SERUM-LEVELS; OLDER-ADULTS; D DEFICIENCY;
25-HYDROXYVITAMIN-D; DISEASE; OSTEOPOROSIS; POPULATION; PREVALENCE;
WOMEN
AB Background: Persons with limited exposure to ultraviolet B light, including space travelers, may not receive enough vitamin D. Recent studies indicate that optimal serum 25-hydroxyvitamin D [25(OH) D] should be >= 80 nmol/L.
Objective: This study was designed to evaluate the effectiveness of 3 doses of vitamin D to raise and maintain 25(OH) D to a concentration.80 nmol/L in persons with limited ultraviolet B light exposure.
Design: This was a 5-mo, prospective, randomized, double-blind study of vitamin D supplementation. It was conducted during winter in Antarctica at the McMurdo Station, when ultraviolet B radiation levels are essentially zero. The 55 subjects were randomly divided into 3 groups for vitamin D supplementation: 2000 IU/d (n = 18), 1000 IU/d (n = 19), and 400 IU/d (n = 18). An additional 7 subjects did not take supplements or took supplements of their own choosing. Blood samples were collected about every 2 mo during the winter.
Results: About 5 mo after supplementation started, 25(OH)D increased to 71 +/- 23 nmol/L in the 2000-IU/d group, 63 +/- 25 nmol/L in the 1000-IU/d group, and 57 +/- 15 nmol/L in the 400-IU/d group and decreased to 34 +/- 12 nmol/L in the group not taking supplements.
Conclusions: These data will enable us to provide space crews with evidence-based recommendations for vitamin D supplementation. The findings also have implications for other persons with limited ultraviolet light exposure, including polar workers and the elderly. Am J Clin Nutr 2009; 89:1092-8.
C1 [Smith, Scott M.; Locke, James] NASA, Lyndon B Johnson Space Ctr, Space Life Sci Directorate, Houston, TX 77058 USA.
[Gardner, Keri K.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA.
[Gardner, Keri K.] VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA.
[Zwart, Sara R.] Univ Space Res Assoc, Houston, TX USA.
RP Smith, SM (reprint author), NASA, Lyndon B Johnson Space Ctr, Space Life Sci Directorate, Mail Code SK3,2101 NASA Pkwy, Houston, TX 77058 USA.
EM scott.m.smith@nasa.gov
FU NASA; National Science Foundation
FX Supported by the NASA Human Research Program and made possible by the
National Science Foundation.
NR 46
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Z9 44
U1 0
U2 6
PU AMER SOC CLINICAL NUTRITION
PI BETHESDA
PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998
USA
SN 0002-9165
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD APR 1
PY 2009
VL 89
IS 4
BP 1092
EP 1098
DI 10.3945/ajcn.2008.27189
PG 7
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 420WF
UT WOS:000264319200016
PM 19225122
ER
PT J
AU Schnur, J
Nguyen, S
Divino, C
Heimann, T
Vidal, C
AF Schnur, Jessica
Nguyen, Scott
Divino, Celia
Heimann, Tomas
Vidal, Claudia
TI Coexisting Rectal and Urachal Carcinoma: A Case Report
SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS
LA English
DT Article
DE adenocarcinoma; rectal carcinoma; urachal carcinoma; urachus
C1 [Schnur, Jessica; Nguyen, Scott; Divino, Celia; Heimann, Tomas; Vidal, Claudia] Mt Sinai Hosp, Dept Surg, New York, NY 10029 USA.
[Schnur, Jessica; Nguyen, Scott; Divino, Celia; Heimann, Tomas; Vidal, Claudia] Mt Sinai Hosp, Dept Pathol, New York, NY 10029 USA.
[Schnur, Jessica; Nguyen, Scott; Divino, Celia; Heimann, Tomas; Vidal, Claudia] Bronx Vet Affairs Med Ctr, Bronx, NY USA.
RP Schnur, J (reprint author), Mt Sinai Hosp, Dept Surg, New York, NY 10029 USA.
EM jessica.schnur@mssm.edu
NR 3
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0277-3732
J9 AM J CLIN ONCOL-CANC
JI Am. J. Clin. Oncol.-Cancer Clin. Trials
PD APR
PY 2009
VL 32
IS 2
BP 220
EP 221
DI 10.1097/01.coc.0000230170.25322.cd
PG 2
WC Oncology
SC Oncology
GA 431JF
UT WOS:000265056900020
PM 19346817
ER
PT J
AU Shen, J
Pinkus, GS
Deshpande, V
Cibas, ES
AF Shen, Jian
Pinkus, Geraldine S.
Deshpande, Vikram
Cibas, Edmund S.
TI Usefulness of EMA, GLUT-1, and XIAP for the Cytologic Diagnosis of
Malignant Mesothelioma in Body Cavity Fluids
SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY
LA English
DT Article
DE Malignant mesothelioma; Cytology; Benign effusion; Epithelial membrane
antigen; EMA; Glucose transporter-1; GLUT-1; X-linked inhibitor of
apoptosis; XIAP
ID EPITHELIAL MEMBRANE ANTIGEN; NEEDLE-ASPIRATION DIAGNOSIS; CYSTIC
SQUAMOUS LESIONS; GROWTH-FACTOR-RECEPTOR; CELL BLOCKS; NONNEOPLASTIC
MESOTHELIUM; GLUCOSE TRANSPORTERS; SEROUS EFFUSIONS; BENIGN; EXPRESSION
AB We compared the effectiveness of epithelial membrane antigen (EAM)with 2 newly described markers, X-linked inhibitor of apoptosis protein (XIAP) and an isoform of glucose transporter (GLUT-1), in the distinction between malignant mesothelioma (MM) and benign effusion (BE) in body cavity fluids. Immunohistochemical studies were performed on cell block sections from, 35 cases of histologically confirmed MM and 38 BEs, using antibodies to EMA, XIAP, GLUT-1 (GLUT-1m, monoclonal; GLUT-1p, polyclonal). Results were graded based on the percentage of cells staining: negative (0016), 1+ (<25%), 2+ (25%-49%), 3+ (50%-74%), and4+ (75%-100%). The performance of each marker was compared using receiver operating characteristic curve analysis. EMA demonstrated the best accuracy, with an area under the curve of 0.91 as compared with XIAP (0.6 7), GLUT-1 in (0.74), and GLUT-1p (0.80). Based on these findings, EMA is a better marker than XIAP or GLUT-1 for the diagnosis of MM.
C1 [Shen, Jian; Deshpande, Vikram] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pathol Serv,James Homer Wright Pathol Labs, Boston, MA 02114 USA.
[Shen, Jian; Pinkus, Geraldine S.; Cibas, Edmund S.] Harvard Univ, Sch Med, Dept Pathol, Brigham & Womens Hosp, Boston, MA 02114 USA.
RP Shen, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pathol Serv,James Homer Wright Pathol Labs, 55 Fruit St, Boston, MA 02114 USA.
NR 39
TC 38
Z9 38
U1 0
U2 1
PU AMER SOC CLINICAL PATHOLOGY
PI CHICAGO
PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA
SN 0002-9173
J9 AM J CLIN PATHOL
JI Am. J. Clin. Pathol.
PD APR
PY 2009
VL 131
IS 4
BP 516
EP 523
DI 10.1309/AJCPWFW7O1FVFLKT
PG 8
WC Pathology
SC Pathology
GA 421TO
UT WOS:000264381400008
PM 19289587
ER
PT J
AU Peerschke, EIB
Castellone, DD
Ledford-Kraemer, M
Van Cott, EM
Meijer, P
AF Peerschke, Ellinor I. B.
Castellone, Donna D.
Ledford-Kraemer, Marlies
Van Cott, Elizabeth M.
Meijer, Piet
CA NASCOLA Proficiency Testing Comm
TI Laboratory Assessment of Factor VIII Inhibitor Titer The North American
Specialized Coagulation Laboratory Association Experience
SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY
LA English
DT Article
DE Coagulation; Factor VIII inhibitor titer; Hemophilia; Proficiency
testing; North American Specialized Coagulation Laboratory Association;
NASCOLA; ECAT
ID PREVIOUSLY UNTREATED PATIENTS; IMMUNE TOLERANCE INDUCTION; HEMOPHILIA-A;
BETHESDA ASSAY; NIJMEGEN MODIFICATION; C INHIBITORS; FACTOR-IX;
ANTIBODIES; ELISA; SPECIFICITY
AB Quantification of inhibitory antibodies against infused factor VIII (FVIII) has an important role in the management of patients with hemophilia A. This article summarizes results from the largest North American FVIII inhibitor proficiency testing challenge conducted to date. Test samples, 4 negative and 4 positive (1-3 Bethesda units [BU]/mL), were distributed by the ECAT Foundation in conjunction with the North American Specialized Coagulation Laboratory Association and analyzed by 38 to 42 laboratories in 2006 and 2007.
Whereas laboratories were able to distinguish between the absence and presence of low-titer FVIII inhibitors, the intralaboratory coefficient of variation was high (30%-42%) for inhibitor positive samples, and the definition of lower detection limits of the assay was variable (0-1 BU/mL). Most laboratories performed the Bethesda assay with commercially supplied buffered normal pooled plasma in a 1:1 mix patient plasma. These data provide information for the development of consensus guidelines to improve FVIII inhibitor quantification.
C1 [Peerschke, Ellinor I. B.; Castellone, Donna D.] Mt Sinai Sch Med, Dept Pathol, New York, NY 10029 USA.
[Van Cott, Elizabeth M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Ledford-Kraemer, Marlies] CLOT ED, Islamorada, FL USA.
[Meijer, Piet] ECAT Fdn, Leiden, Netherlands.
RP Peerschke, EIB (reprint author), Mt Sinai Sch Med, Dept Pathol, Leahn Bldg,1425 Madison Ave,Room 8-02 A, New York, NY 10029 USA.
NR 21
TC 25
Z9 25
U1 2
U2 3
PU AMER SOC CLINICAL PATHOLOGY
PI CHICAGO
PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA
SN 0002-9173
J9 AM J CLIN PATHOL
JI Am. J. Clin. Pathol.
PD APR
PY 2009
VL 131
IS 4
BP 552
EP 558
DI 10.1309/AJCPMKP94CODILWS
PG 7
WC Pathology
SC Pathology
GA 421TO
UT WOS:000264381400012
PM 19289591
ER
PT J
AU Kane, B
Karren, J
Garcia-Godoy, C
Garcia-Godoy, F
AF Kane, Barbara
Karren, Jordan
Garcia-Godoy, Cristina
Garcia-Godoy, Franklin
TI Sealant adaptation and penetration into occlusal fissures
SO AMERICAN JOURNAL OF DENTISTRY
LA English
DT Article
ID PERFORMANCE; CARIES; PIT
AB Purpose: To evaluate the adaptation and penetration into occlusal fissures of two different types of fissure sealants. Methods: Extracted third molars (n=10) with evident occlusal fissures were cleaned with a pumice/water Slurry and randomly divided into two groups and sealed following the manufacturers' directions as follows: Group 1 - Embrace fissure sealant (Pulpdent). Surfaces were cleaned and dried, then etched for 15 seconds. Excess water was removed leaving C, the surface slightly moist. Sealant was applied from cusp to cusp without covering marginal ridges and light cured for 20 seconds using a halogen light at 500 mW/cm(2). Group 2 - ClinPro (3M Espe). Surfaces were cleaned and dried then etched for 15 seconds. The etched surface was rinsed and thoroughly dried. Dried surfaces appeared frosty white. Sealant was placed making sure not to go beyond etched area, and light cured for 20 seconds. Teeth were thermocycled (500x) and sectioned with an Isomet in a mesio-distal direction (4 slices per tooth). The sections were examined under the SEM. The marginal adaptation of the sealants was evaluated under the SEM using the following criteria: 1 = Smooth adaptation. Sealant flows with enamel. No ledges 2 = Sealant is not well adapted. Ledge may be present. The penetration ability of the sealants was evaluated under the SEM using the following criteria: 1 = Sealant penetrated 1/3 the total length of the fissure: 2 = Sealant penetrated 1/2 the total length of the fissure; 3 = Sealant penetrated the total length of the fissure. The results were statistically analyzed using a t-test. Results: Embrace showed consistently more intimate marginal adaptation than ClinPro in fissures of the same approximate width and depth (P < 0.05). (Am J Dent 2009-,22:89-91).
C1 [Kane, Barbara; Karren, Jordan; Garcia-Godoy, Cristina; Garcia-Godoy, Franklin] Nova SE Univ, Coll Dent Med, Biosci Res Ctr, Ft Lauderdale, FL 33328 USA.
[Garcia-Godoy, Franklin] Forsyth Inst, Boston, MA USA.
RP Garcia-Godoy, F (reprint author), Nova SE Univ, Coll Dent Med, Biosci Res Ctr, 3200 S Univ Dr, Ft Lauderdale, FL 33328 USA.
EM fgarciagodoy@gmail.com
NR 29
TC 3
Z9 4
U1 1
U2 5
PU MOSHER & LINDER, INC
PI WESTON
PA 318 INDIAN TRACE SUITE 500, WESTON, FL 33326 USA
SN 0894-8275
J9 AM J DENT
JI Am. J. Dent.
PD APR
PY 2009
VL 22
IS 2
BP 89
EP 91
PG 3
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 475FL
UT WOS:000268343900005
PM 19626971
ER
PT J
AU Satia, JA
Littman, A
Slatore, CG
Galanko, JA
White, E
AF Satia, Jessie A.
Littman, Alyson
Slatore, Christopher G.
Galanko, Joseph A.
White, Emily
TI Long-term Use of beta-Carotene, Retinol, Lycopene, and Lutein
Supplements and Lung Cancer Risk: Results From the VITamins And
Lifestyle (VITAL) Study
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE beta carotene; carotenoids; cohort studies; dietary supplements; lung
neoplasms; randomized controlled trials as topic; vitamins
ID DIETARY CAROTENOIDS; WOMENS HEALTH; CARDIOVASCULAR-DISEASE;
ALPHA-TOCOPHEROL; POOLED ANALYSIS; UNITED-STATES; COHORT; CONSUMPTION;
NUTRITION; FRUIT
AB High-dose beta-carotene supplementation in high-risk persons has been linked to increased lung cancer risk in clinical trials; whether effects are similar in the general population is unclear. The authors examined associations of supplemental beta-carotene, retinol, vitamin A, lutein, and lycopene with lung cancer risk among participants, aged 50-76 years, in the VITamins And Lifestyle (VITAL) cohort Study in Washington State. In 2000-2002, eligible persons (n = 77,126) completed a 24-page baseline questionnaire, including detailed questions about supplement use (duration, frequency, dose) during the previous 10 years from multivitamins and individual supplements/mixtures. Incident lung cancers (n = 521) through December 2005 were identified by linkage to the Surveillance, Epidemiology, and End Results cancer registry. Longer duration of use of individual beta-carotene, retinol, and lutein supplements (but not total 10-year average dose) was associated with statistically significantly elevated risk of total lung cancer and histologic cell types; for example, hazard ratio = 2.02, 95% confidence interval: 1.28, 3.17 for individual supplemental lutein with total lung cancer and hazard ratio = 3.22, 95% confidence interval: 1.29, 8.07 for individual beta-carotene with small-cell lung cancer for > 4 years versus no use. There was little evidence for effect modification by gender or smoking status. Long-term use of individual beta-carotene, retinol, and lutein supplements should not be recommended for lung cancer prevention, particularly among smokers.
C1 [Satia, Jessie A.] Univ N Carolina, Dept Nutr, Chapel Hill, NC 27599 USA.
[Satia, Jessie A.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA.
[Satia, Jessie A.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
[Satia, Jessie A.; Galanko, Joseph A.] Univ N Carolina, Div Digest Dis & Nutr, Ctr Gastrointestinal Biol & Dis, Chapel Hill, NC 27599 USA.
[Littman, Alyson; White, Emily] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Littman, Alyson] VA Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Seattle, WA USA.
[Slatore, Christopher G.] Univ Washington, Div Pulm & Crit Care Med, Seattle, WA 98195 USA.
[White, Emily] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98104 USA.
RP Satia, JA (reprint author), Univ N Carolina, Dept Nutr, 2209 McGavran Greenberg Hall,CB 7461, Chapel Hill, NC 27599 USA.
EM jsatia@unc.edu
FU NCI NIH HHS [R03 CA119683-02, R03 CA119683]
NR 41
TC 50
Z9 56
U1 0
U2 16
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD APR 1
PY 2009
VL 169
IS 7
BP 815
EP 828
DI 10.1093/aje/kwn409
PG 14
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 421VX
UT WOS:000264387500004
PM 19208726
ER
PT J
AU Fang, SC
Cavallari, JM
Eisen, EA
Chen, JC
Mittleman, MA
Christiani, DC
AF Fang, Shona C.
Cavallari, Jennifer M.
Eisen, Ellen A.
Chen, Jiu-Chiuan
Mittleman, Murray A.
Christiani, David C.
TI Vascular Function, Inflammation, and Variations in Cardiac Autonomic
Responses to Particulate Matter Among Welders
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE augmentation; C-reactive protein; disease susceptibility; heart rate;
inflammation; particulate matter; vascular diseases; welding
ID HEART-RATE-VARIABILITY; CORONARY-ARTERY-DISEASE; C-REACTIVE PROTEIN;
HEALTHY-YOUNG MEN; AIR-POLLUTION; CARDIOVASCULAR-DISEASE; OXIDATIVE
STRESS; PULSE PRESSURE; FINE PARTICLES; RISK
AB Patients with health conditions associated with impaired vascular function and inflammation may be more susceptible to the adverse health effects of fine particulate (particulate matter with a mass median aerodynamic diameter of <= 2.5 mu m (PM(2.5))) exposure. In 2006, the authors conducted a panel study to investigate directly whether vascular function and inflammation (assessed by C-reactive protein) modify PM(2.5)-associated reductions in heart rate variability among 23 young male workers (mean age, 40 years) from Massachusetts. Concurrent 24-hour ambulatory electrocardiogram and personal PM(2.5) exposure information was collected over a total of 36 person-days, including either or both welding and nonwelding days. Linear mixed models were used to examine the 5-minute standard deviation of normal-to-normal intervals (SDNN) in relation to the moving PM(2.5) averages in the preceding 1-4 hours. C-reactive protein levels and 3 measures of vascular function (augmentation index, mean arterial pressure, and pulse pressure) were determined at baseline. The authors observed an inverse association between the 1-hour PM(2.5) and 5-minute SDNN. Greater SDNN declines were observed among those with C-reactive protein (P(interaction) < 0.001) and augmentation index (P = 0.06) values at or above the 75th percentile and pulse pressure values below the 75th percentile (P < 0.001). Systemic inflammation and poorer vascular function appear to aggravate particle-related declines in heart rate variability among workers.
C1 [Fang, Shona C.; Cavallari, Jennifer M.; Eisen, Ellen A.; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA.
[Chen, Jiu-Chiuan; Mittleman, Murray A.; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Mittleman, Murray A.] Beth Israel Deaconess Med Ctr, Cardiovasc Epidemiol Res Unit, Boston, MA 02215 USA.
[Christiani, David C.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
RP Fang, SC (reprint author), 665 Huntington Ave,Bldg 1,Room 1402, Boston, MA 02115 USA.
EM sfang@hsph.harvard.edu
RI Chen, JC/I-2261-2016
FU National Institute of Environmental Health Sciences [ES009860, ES00002];
Education and Research Center of the Harvard-National Institute for
Occupational Safety and Health [T42 OH008416]; [T32 ES 07069]
FX Conflict of interest: none declared.
NR 56
TC 29
Z9 30
U1 0
U2 8
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD APR 1
PY 2009
VL 169
IS 7
BP 848
EP 856
DI 10.1093/aje/kwn405
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 421VX
UT WOS:000264387500007
PM 19153215
ER
PT J
AU Liu, W
Hahn, H
Odze, RD
Goyal, RK
AF Liu, Weitian
Hahn, Hejin
Odze, Robert D.
Goyal, Raj K.
TI Metaplastic Esophageal Columnar Epithelium Without Goblet Cells Shows
DNA Content Abnormalities Similar to Goblet Cell-Containing Epithelium
SO AMERICAN JOURNAL OF GASTROENTEROLOGY
LA English
DT Article; Proceedings Paper
CT Annual Meeting of the Society-for-Ultrastructural-Pathology
CY 2008
CL San Diego, CA
SP Soc Ultrastructural Pathol
ID BARRETTS-ESOPHAGUS; INTESTINAL METAPLASIA; GASTROESOPHAGEAL JUNCTION;
NEOPLASTIC PROGRESSION; DISTAL ESOPHAGUS; ADENOCARCINOMA; CANCER;
INSTABILITY; DYSPLASIA; DIAGNOSIS
AB OBJECTIVES: The mucosa of patients with columnar-lined esophagus recognized on endoscopy usually shows epithelium with and without goblet cells. Columnar epithelium with goblet cells ("Barrett's esophagus") is generally believed to represent a premalignant lesion and has been shown to contain DNA abnormalities. However, the biological properties of non-goblet columnar epithelium remain unknown. The purpose of this study was to determine the DNA content properties of non-goblet epithelium in patients with metaplastic columnar epithelium of the esophagus.
METHODS: Mucosal biopsies of the esophagus from 68 patients with columnar metaplasia of the esophagus (22 without goblet cells and 46 with goblet cells) and 19 patients with normal gastric mucosa (controls) were histologically evaluated for the density of goblet cells. The latter group was divided into low-density, high-density, and very high-density goblet cell subgroups. Tissue sections of non-goblet epithelium and goblet cell epithelium (where present) were evaluated by image cytometry, and high-fidelity DNA histograms were created to indicate the G0/G1 peak DNA index (DI), DNA content heterogeneity index (HI), and the percentage of cells with DNA exceeding 5N (5N-EC). G0/G1 peaks with DI >1.1 were considered aneuploid.
RESULTS: Normal gastric controls showed a mean peak DI of 1.02 +/- 0.03 and an HI of 11.6 +/- 0.7. None of the controls revealed aneuploidy or 5 N-EC. Patients with metaplastic columnar epithelium with goblet cells showed a DI of 1.15 +/- 0.12, HI of 18.2 +/- 2.1, mild aneuploidy in 54 % of the cases, and 5 N-EC in 15% of the cases, all of which were significantly higher than in controls. Patients with metaplastic columnar epithelium without goblet cells showed DNA content results statistically similar to those of patients with metaplastic columnar epithelium with goblet cells, and also revealed significantly higher values compared with those of controls. Furthermore, there were no significant differences in any of the key DNA content abnormalities between non-goblet and goblet cell-containing epithelium in patients with metaplastic columnar epithelium with goblet cells, or between these two types of epithelium according to the density of goblet cells.
CONCLUSIONS: DNA content abnormalities occur with equal frequency and extent in metaplastic columnar epithelium of the esophagus without goblet cells compared with metaplastic columnar epithelium with goblet cells. These findings suggest that metaplastic non-goblet columnar epithelium of the esophagus may have neoplastic potential.
C1 [Odze, Robert D.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Liu, Weitian; Goyal, Raj K.] Harvard Univ, Sch Med, Div Gastroenterol, Dept Med,VA Boston Healthcare Syst, W Roxbury, MA USA.
RP Odze, RD (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA.
EM rodze@partners.org
FU NCI NIH HHS [R01 CA125711]; NIDDK NIH HHS [R01 DK062867, R01
DK062867-05]; PHS HHS [62867]
NR 35
TC 99
Z9 102
U1 0
U2 5
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0002-9270
J9 AM J GASTROENTEROL
JI Am. J. Gastroenterol.
PD APR
PY 2009
VL 104
IS 4
BP 816
EP 824
DI 10.1038/ajg.2009.85
PG 9
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 431AR
UT WOS:000265034200004
PM 19293780
ER
PT J
AU Passos, MCF
Lembo, AJ
Conboy, LA
Kaptchuk, TJ
Kelly, JM
Quilty, MT
Kerr, CE
Jacobson, EE
Hu, R
Friedlander, E
Drossman, DA
AF Passos, Maria C. F.
Lembo, Anthony J.
Conboy, Lisa A.
Kaptchuk, Ted J.
Kelly, John M.
Quilty, Mary T.
Kerr, Catherine E.
Jacobson, Eric E.
Hu, Rong
Friedlander, Elizabeth
Drossman, Douglas A.
TI Adequate Relief in a Treatment Trial With IBS Patients: A Prospective
Assessment
SO AMERICAN JOURNAL OF GASTROENTEROLOGY
LA English
DT Article
ID IRRITABLE-BOWEL-SYNDROME; QUALITY-OF-LIFE; SYMPTOM IMPROVEMENT; RECEPTOR
ANTAGONIST; DOUBLE-BLIND; END-POINT; EFFICACY; SAFETY; WOMEN; ALOSETRON
AB OBJECTIVES: Adequate relief (AR) of irritable bowel syndrome (IBS) symptoms (IBS-AR) has been used as a primary end point in many randomized controlled trials of IBS and is considered by the Rome III committee to be an acceptable primary end point. However, controversy exists on whether baseline severity confounds the effect of the treatment outcome. The aim is (1) to compare a subjective report of IBS-AR with global assessment of improvement (IBS-GAI), change in IBS symptom severity scale (IBS-SSS), and IBS quality of life (IBS-QOL); (2) to explore whether initial IBS symptom severity influences the ability of these outcome measures to detect differences post treatment; and (3) to determine whether psychological symptoms influence the sensitivity of these measures, in a randomized controlled treatment trial.
METHODS: A total of 289 adult IBS patients were recruited to a treatment trial. Baseline IBS-SSS scores were used to classify IBS severity as mild (<175), moderate (175-300), or severe (>300). Questionnaires were completed at baseline and after 3 weeks of treatment with sham acupuncture or wait-list control.
RESULTS: IBS baseline severity (IBS-SSS) significantly affected the proportion of patients who reported IBS-AR at 3 weeks (mild, 70%; moderate, 49.7%; severe, 38.8%) (P<0.05). However, once the patients who reported IBS-AR at baseline (28.0%) were excluded from the analysis, baseline severity no longer affected the proportion of patients reporting IBS-AR. Baseline severity did not have a significant effect on patients reporting moderate or significant improvement on the IBS-GAI (mild, 30%; moderate, 25.3%; severe, 18.8%) (P = NS). Psychological symptoms had no significant correlations with responders after adjusting for baseline severity.
CONCLUSIONS: These data suggest that IBS-AR as an end point is inversely related to baseline symptom severity. However, if patients who report AR at screening were excluded from study participation, baseline symptom severity was no longer confounded with a report of AR at the study end point.
C1 [Passos, Maria C. F.; Lembo, Anthony J.; Friedlander, Elizabeth] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Conboy, Lisa A.; Kaptchuk, Ted J.; Quilty, Mary T.; Kerr, Catherine E.; Hu, Rong] Harvard Univ, Sch Med, Osher Inst, Boston, MA USA.
[Kelly, John M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Kelly, John M.] Endicott Coll, Beverly, MA USA.
[Jacobson, Eric E.] Harvard Univ, Sch Med, Dept Social Med, Boston, MA 02115 USA.
[Drossman, Douglas A.] Univ N Carolina, Chapel Hill, NC USA.
RP Lembo, AJ (reprint author), 330 Brookline Ave Rabb Rose 1, Boston, MA 02215 USA.
EM alembo@bidmc.harvard.edu
RI Kerr, Catherine/D-3299-2009
FU NIH [1R01 AT01414-01]; National Center for Complementary and Alternative
Medicine (NCCAM); National Institutes of Digestive, Diabetes and Kidney
Disease (NIDDK); NCCAM [1R21 AT002860-01, 1 R21 AT002564, 1K24
AT004095]; Office of Behavioral and Social Science Research (OBSSR)
FX This research was made possible by NIH Grant Numbers 1R01 AT01414-01
from the National Center for Complementary and Alternative Medicine
(NCCAM) and the National Institutes of Digestive, Diabetes and Kidney
Disease (NIDDK), Grant Number 1R21 AT002860-01 from NCCAM and the Office
of Behavioral and Social Science Research (OBSSR), and Grant Numbers 1
R21 AT002564 and 1K24 AT004095 from NCCAM. e contents of this report are
solely the responsibility of the authors and do not necessarily
represent the official views of the NIH. Maria Passos was supported by a
grant from National Council for Scientific and Technological Development
(CNPq) from Brazil.
NR 31
TC 17
Z9 18
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0002-9270
J9 AM J GASTROENTEROL
JI Am. J. Gastroenterol.
PD APR
PY 2009
VL 104
IS 4
BP 912
EP 919
DI 10.1038/ajg.2009.13
PG 8
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 431AR
UT WOS:000265034200018
PM 19293784
ER
PT J
AU Singh, H
Kadiyala, H
Bhagwath, G
Shethia, A
El-Serag, H
Walder, A
Velez, ME
Petersen, LA
AF Singh, Hardeep
Kadiyala, Himabindu
Bhagwath, Gayathri
Shethia, Anila
El-Serag, Hashem
Walder, Annette
Velez, Maria E.
Petersen, Laura A.
TI Using a Multifaceted Approach to Improve the Follow-Up of Positive Fecal
Occult Blood Test Results
SO AMERICAN JOURNAL OF GASTROENTEROLOGY
LA English
DT Article
ID COMPLETE DIAGNOSTIC EVALUATION; PRIMARY-CARE PHYSICIANS; ABNORMAL
PAP-SMEARS; COLORECTAL-CANCER; PATIENT NAVIGATION; COLON EVALUATION;
CONTROLLED-TRIAL; NATIONAL-SURVEY; TASK-FORCE; HEALTH
AB OBJECTIVES : Inadequate follow-up of abnormal fecal occult blood test (FOBT) results occurs in several types of practice settings. Our institution implemented multifaceted quality improvement (QI) activities in 2004-2005 to improve follow-up of FOBT-positive results. Activities addressed precolonoscopy referral processes and system-level factors such as electronic communication, provider education, and feedback. We evaluated their effects on timeliness and appropriateness of positive-FOBT follow-up and identified factors that affect colonoscopy performance.
METHODS: Retrospective electronic medical record review was used to determine outcomes before and after QI activities in a multispecialty ambulatory clinic of a tertiary care Veterans Affairs facility and its affiliated satellite clinics. From 1869 FOBT-positive cases, 800 were randomly selected from time periods before and after QI activities. Two reviewers used a pretested standardized data collection form to determine whether colonoscopy was appropriate or indicated based on predetermined criteria and if so, the timeliness of colonoscopy referral and performance before and after QI activities.
RESULTS: In cases where a colonoscopy was indicated, the proportion of patients who received a timely colonoscopy referral and performance were significantly higher post-implementation (60.5% vs. 31.7%, P < 0.0001 and 11.4% vs. 3.4%, P = 0.0005). A significant decrease also resulted in median times to referral and performance (6 vs. 19 days, P < 0.0001 and 96.5 vs. 190 days, P < 0.0001) and in the proportion of positive-FOBT test results that had received no follow-up by the time of chart review (24.3% vs. 35.9%, P = 0.0045). Significant predictors of absence of the performance of an indicated colonoscopy included performance of a non-colonoscopy procedure such as barium enema or flexible sigmoidoscopy (OR = 16.9; 95% CI, 1.9-145.1), patient non-adherence (OR = 33.9; 95% CI, 17.3-66.6), not providing an appropriate provisional diagnosis on the consultation (OR = 17.9; 95% CI, 11.3-28.1), and gastroenterology service not rescheduling colonoscopies after an initial cancellation (OR = 11.0; 95% CI, 5.1-23.7).
CONCLUSIONS: Multifaceted QI activities improved rates of timely colonoscopy referral and performance in an electronic medical record system. However, colonoscopy was not indicated in over one third of patients with positive FOBTs, raising concerns about current screening practices and the appropriate denominator used for performance measurement standards related to colon cancer screening.
C1 [Singh, Hardeep; Petersen, Laura A.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Hlth Policy & Qual Program, Houston VA HSR&D Ctr Excellence, Houston, TX 77030 USA.
[Singh, Hardeep; Shethia, Anila; El-Serag, Hashem; Walder, Annette; Petersen, Laura A.] Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA.
[Singh, Hardeep; Petersen, Laura A.] Baylor Coll Med, Ctr Inquiry Improve Outpatient Safety Effect Elec, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA.
[Kadiyala, Himabindu; Bhagwath, Gayathri] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Sect Gen Med, Dept Med, Houston, TX 77030 USA.
[El-Serag, Hashem; Velez, Maria E.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Gastroenterol Sect, Houston, TX 77030 USA.
RP Singh, H (reprint author), VA Med Ctr 152, 2002 Holcombe Blvd, Houston, TX 77030 USA.
EM hardeeps@bcm.tmc.edu
FU NIH K23 career development award [K23CA125585]; Houston VA HSR&D Center
of Excellence [HFP90-020]; Michael E. DeBakey Veterans Affairs Medical
Center
FX The study was supported by an NIH K23 career development award
(K23CA125585) to Dr Singh, and in part by the Houston VA HSR&D Center of
Excellence (HFP90-020) and the Michael E. DeBakey Veterans Affairs
Medical Center. These sources 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 manusc ript.
NR 62
TC 31
Z9 31
U1 0
U2 4
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0002-9270
J9 AM J GASTROENTEROL
JI Am. J. Gastroenterol.
PD APR
PY 2009
VL 104
IS 4
BP 942
EP 952
DI 10.1038/ajg.2009.55
PG 11
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 431AR
UT WOS:000265034200023
PM 19293786
ER
PT J
AU Donohue, JM
Huskamp, HA
Wilson, IB
Weissman, J
AF Donohue, Julie M.
Huskamp, Haiden A.
Wilson, Ira B.
Weissman, Joel
TI Whom Do Older Adults Trust Most to Provide Information About
Prescription Drugs?
SO AMERICAN JOURNAL OF GERIATRIC PHARMACOTHERAPY
LA English
DT Article
DE prescription drug costs; patient-provider communication; trust in
physicians; cost-related nonadherence
ID MEDICATION NONADHERENCE; PHYSICIAN COMMUNICATION; COMMON MEDICATIONS;
PATIENT TRUST; COST; CARE; KNOWLEDGE; QUALITY; BENEFIT; RELIABILITY
AB Background: Cost-related nonadherence to medications is common among older adults, yet physician-patient communication about medication cost concerns is infrequent. One factor affecting communication and adherence may be older adults' confidence in the information about prescription drugs provided by physicians and other sources.
Objectives: This study was conducted to identify which source older adults most trust to provide information on drugs and to examine the relationship between older patients' trust in physicians to provide price information and the Occurrence of cost-related nonadherence.
Methods: We conducted a cross-sectional national telephone survey of individuals aged >= 50 years who were taking at least I prescription medication. Respondents were asked how Much they would trust various Sources (physician, pharmacist, nurse, insurance plan, the Internet, Consumer groups, friends and family) to provide helpful information on "the price of the prescription medicine compared to others like it" and on "how well the prescription medicine will work for you compared to other medicines like it." The response options were a lot, somewhat, and not at all. Other measures of interest were respondents' beliefs concerning physicians' ability to lower drug costs and patient activation. We also evaluated the potential association between trust in physicians to deliver drug price information and cost-related medication nonadherence.
Results: Compared with the other Sources of information Studied, doctors and pharmacists were the sources that respondents were most likely to trust "a lot" to provide information on drug prices (55.6% and 61.7%, respectively) and to provide information on drug effectiveness (79.9% and 66.4%). Less than half (42.3%) of respondents who said that they trusted their doctor to provide drug price information "somewhat" or "not at all" agreed that there are ways doctors could lower drug Costs (P = 0.01 vs those who trusted their doctor "a lot"). Adults aged >= 65 years were more likely than those aged 50 to 64 years to trust their doctors "a lot" to provide information on drug prices (odds ratio [OR] = 1.44; 95% CI, 1.08-1.92); the same was true of members of minority groups compared with white respondents (OR = 1.72; 95% CI, 1.13-2.61). Among individuals with high drug spending, those who placed "a lot" of trust in their doctors to provide price information were less likely than those who trusted their doctor "somewhat" or "not at all" to have cost-related nonadherence (OR = 0.40; 95% Cl, 0.20-0.78).
Conclusions: In this survey, older adults trusted physicians and pharmacists more than the other Sources Studied to provide information on prescription drugs. Trust in physicians to provide price information was an important moderator of the effect of high drug spending on cost-related nonadherence. Efforts to provide patients and their providers with comparative data on drug prices and effectiveness may reduce cost-related nonadherence. (Am J Geriatr Pharmacother. 2009;7:105-116) (C) 2009 Excerpta Medica Inc.
C1 [Donohue, Julie M.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Hlth Policy & Management, Pittsburgh, PA 15261 USA.
[Huskamp, Haiden A.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
[Wilson, Ira B.] Tufts Univ New England Med Ctr, Boston, MA USA.
[Weissman, Joel] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Hlth Policy, Boston, MA USA.
RP Donohue, JM (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Hlth Policy & Management, 130 DeSoto St,Crabtree Hall A613, Pittsburgh, PA 15261 USA.
EM jdonohue@pitt.edu
RI Wilson, Ira/F-9190-2016;
OI Wilson, Ira/0000-0002-0246-738X; Donohue, Julie/0000-0003-2418-6017
FU Consumers Union's Consumer Reports Best Buy Drugs program; Engelberg
Foundation; National Library of Medicine; National Center for Research
Resources (NCRR) [KL2-RR024154-01, K24 RR020300]; National Institutes of
Health Roadmap for Medical Research
FX The survey described in this article was funded by a grant from the
Consumers Union's Consumer Reports Best Buy Drugs program, which is
Supported by grants from the Engelberg Foundation and the National
Library of Medicine. Dr. Donohue has received support from grant
KL2-RR024154-01 from the National Center for Rescarch Resources (NCRR),
a component of the National Institutes of Health Roadmap for Medical
Research. Dr. Wilson was funded by a grant from the NCRR, (K24
RR020300).; The authors thank Aiju Men, MS (Department of Health Policy
& Management, University of Pittsburgh Graduate School Of Public
Health), for assistance with programming. Ill addition, they acknowledge
the contributions of the Consumer Reports National Research Center and
Richard Grant, MD, MPH (Harvard Medical School), as well as the helpful
comments of Judith Lave, PhD (Department of Health Policy & Management,
University of Pittsburgh Graduate School of Public Health).
NR 47
TC 37
Z9 37
U1 3
U2 7
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 1543-5946
J9 AM J GERIATR PHARMAC
JI Am. J. Geriatr. Pharmacother.
PD APR
PY 2009
VL 7
IS 2
BP 105
EP 116
DI 10.1016/j.amjopharm.2009.04.005
PG 12
WC Geriatrics & Gerontology; Pharmacology & Pharmacy
SC Geriatrics & Gerontology; Pharmacology & Pharmacy
GA 440XY
UT WOS:000265734200005
PM 19447363
ER
PT J
AU Federman, AD
Safran, DG
Keyhani, S
Cole, H
Halm, EA
Siu, AL
AF Federman, Alex D.
Safran, Dana Gelb
Keyhani, Salomeh
Cole, Helen
Halm, Ethan A.
Siu, Albert L.
TI Awareness of Pharmaceutical Cost-Assistance Programs Among Inner-City
Seniors
SO AMERICAN JOURNAL OF GERIATRIC PHARMACOTHERAPY
LA English
DT Article
DE seniors; low income; pharmaceutical cost-assistance programs
ID HEALTH LITERACY; MEDICARE; CARE; ASSOCIATION; OUTCOMES; BENEFIT;
DISEASE; ACCESS; IMPACT
AB Background: Lack of awareness may be a significant barrier to participation by low- and middle-income seniors in pharmaceutical cost-assistance programs.
Objective: The goal Of this study was to determine whether older adults' awareness of 2 major state and federal pharmaceutical cost-assistance programs was associated with the seniors' ability to access and process information about assistance programs.
Methods: Data were gathered from a cross-sectional study of independently living, English- or Spanish-speaking adults aged >= 60 years. Participants were interviewed in 30 community-based settings (19 apartment complexes and 11 senior centers) in New York, New York. The analysis focused on adults aged >= 65 years who lacked Medicaid coverage. multivariable logistic regression was used to model program awareness as a function of information access (family/social support, attendance at senior or community centers and places of worship, viewing of live health insurance presentations, instrumental activities of daily living, site of medical care, computer use, and having a proxy decision maker for health insurance matters) and information-processing ability (education level, English proficiency, health literacy, and cognitive function). The main outcome measure was awareness of New York's state pharmaceutical assistance program (Elderly Pharmaceutical Insurance Coverage [EPIC]) and the federal Medicare Part D low-income subsidy program (Extra Help).
Results: A total of 269 patients were enrolled (mean [SD] age, 76.9 [7.5] years; 32.0% male; 39.9% white). Awareness of the programs differed widely: 77.3% knew of EPIC and 22.3% knew of Extra Help. In multivariable analysis, study participants were more likely to have heard of the EPIC program if they had attended a live presentation about health Insurance issues (adjusted odds ratio [AOR], 3.40; 95% CI, 1.20-9.61) and less likely if they received care in a clinic (AOR, 0.45; 95% CI, 0.23-0.92). Awareness of Extra Help in the multivariable models was more likely among Study participants who had viewed a live health insurance presentation (AOR, 3.35; 95% CI, 1.55-7.24) and less likely for those with inadequate health literacy (AOR, 0.15; 95% CI, 0.03-0.74).
Conclusions: Viewing of live health insurance presentations and adequate health literacy were associated with greater awareness of important pharmaceutical cost-assistance programs in this study, in low-income, elderly individuals. The findings Suggest that use of live presentations, in addition to health literacy materials and messages, may be important strategies in promoting knowledge of and enrollment in state and federal pharmaceutical cost-assistance programs for low-income seniors. (Am J Geriatr Pharmacother. 2009;7:117-129) (C) 2009 Excerpta Medica Inc.
C1 [Federman, Alex D.; Cole, Helen] Mt Sinai Sch Med, Div Gen Internal Med, New York, NY 10029 USA.
[Safran, Dana Gelb] Tufts Univ New England Med Ctr, Hlth Inst, Inst Clin Res & Hlth Policy Studies, Boston, MA USA.
Tufts Univ, Sch Med, Dept Med, Boston, MA 02111 USA.
[Safran, Dana Gelb] Blue Cross & Blue Shield Massachusetts, Boston, MA USA.
[Keyhani, Salomeh] Mt Sinai Sch Med, Dept Hlth Policy, New York, NY 10029 USA.
[Keyhani, Salomeh; Halm, Ethan A.] Univ Texas SW Med Ctr Dallas, Div Gen Internal Med, Dallas, TX 75390 USA.
[Siu, Albert L.] Bronx Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, Bronx, NY USA.
[Siu, Albert L.] Mt Sinai Sch Med, Brookdale Dept Geriatr & Adult Dev, New York, NY 10029 USA.
RP Federman, AD (reprint author), Mt Sinai Sch Med, Div Gen Internal Med, 1 Gustave L Levy Pl,Box 1087, New York, NY 10029 USA.
EM alex.federman@mssm.edu
FU National Institute on Aging [1K23AG028955-01]; VA Health Services
Research and Development Service; Mount Sinai School of Medicine
Alzheimer's Disease Research Center [NIH AG0051318]
FX The authors thank Paul Hebert, PhD, for technical assistance with
statistical procedures.
NR 45
TC 2
Z9 2
U1 2
U2 8
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 1543-5946
J9 AM J GERIATR PHARMAC
JI Am. J. Geriatr. Pharmacother.
PD APR
PY 2009
VL 7
IS 2
BP 117
EP 129
DI 10.1016/j.amjopharm.2009.04.003
PG 13
WC Geriatrics & Gerontology; Pharmacology & Pharmacy
SC Geriatrics & Gerontology; Pharmacology & Pharmacy
GA 440XY
UT WOS:000265734200006
PM 19447364
ER
PT J
AU Ettenhofer, ML
Hinkin, CH
Castellon, SA
Durvasula, R
Ullman, J
Lam, M
Myers, H
Wright, MJ
Foley, J
AF Ettenhofer, Mark L.
Hinkin, Charles H.
Castellon, Steven A.
Durvasula, Ramani
Ullman, Jodi
Lam, Mona
Myers, Hector
Wright, Matthew J.
Foley, Jessica
TI Aging, Neurocognition, and Medication Adherence in HIV Infection
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Article; Proceedings Paper
CT 36th Annual Meeting of the International-Neuropsychological-Society
CY FEB 06-09, 2008
CL Waikoloa, HI
SP Int Neuropsychol Soc
DE HIV; AIDS; aging; cognition; medication adherence; executive functions
ID ACTIVE ANTIRETROVIRAL THERAPY; MULTICENTER AIDS COHORT;
NEUROPSYCHOLOGICAL PERFORMANCE; AGE; DEMENTIA; DISEASE; ADULTS;
METAANALYSIS; ZIDOVUDINE; DISORDERS
AB Objective: To evaluate the hypothesis that poor adherence to highly active antiretroviral treatment (HAART) would be more strongly related to cognitive impairment among older than among younger HIV-seropositive adults. Setting and Participants: A volunteer sample of 431 HIV-infected adult patients prescribed self-administered HAART was recruited from community agencies and university-affiliated infectious disease clinics in the Los Angeles area. Measurements: Neurocognitive measures included tests of attention, information processing speed, learning/memory, verbal fluency, motor functioning, and executive functioning. Medication adherence was measured using microchip-embedded pill bottle caps (Medication Event Monitoring System) and se report. Latent/structural analysis techniques were used to evaluate factor models of cognition and adherence. Results: Mean adherence rates were higher among older (>= 50 years) than younger (<50 years) HIV-positive adults. However, latent/structural modeling demonstrated that neurocognitive impairment was associated with poorer medication adherence among older participants only. When cognitive subdomains were examined individually, executive functioning, motor functioning, and processing speed were most strongly related to adherence in this age group. CD4 count and drug problems were also more strongly associated with adherence among older than younger adults. Conclusions: Older HIV-positive individuals with neurocognitive impairment or drug problems are at increased risk of suboptimal adherence to medication. Likewise, older adults may be especially vulnerable to immunological and neurocognitive dysfunction under conditions of suboptimal LOART adherence. These findings highlight the importance of optimizing medication adherence rates and evaluating neurocognition in the growing population of older HIV-infected patients. (Am J Geriatr Psychiatry 2009; 17:281-290)
C1 [Ettenhofer, Mark L.] Univ Calif Los Angeles, Semel Inst, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA.
[Hinkin, Charles H.; Castellon, Steven A.; Lam, Mona] VA Greater Los Angeles Hlth Care Syst, Psychol Serv, Los Angeles, CA USA.
[Durvasula, Ramani] Calif State Univ Los Angeles, Dept Psychol, Los Angeles, CA 90032 USA.
[Ullman, Jodi] Calif State Univ San Bernardino, Dept Psychol & Human Dev, Los Angeles, CA USA.
[Myers, Hector] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA.
RP Ettenhofer, ML (reprint author), Univ Calif Los Angeles, Semel Inst, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, 760 Westwood Plaza, Los Angeles, CA 90095 USA.
EM MEttenhofer@mednct.ucla.edu
FU NIDA NIH HHS [R01 DA013799, R01 DA013799-01A1, R01 DA013799-02, R01
DA013799-02S1, R01 DA013799-03, R01 DA013799-04, R01 DA13799]; NIMH NIH
HHS [T32 MH019535-14, R01 MH058552, R01 MH058552-02, R01 MH058552-03,
R01 MH058552-04, R01 MH058552-05, R01 MH58552, T32 MH019535, T32
MH019535-12, T32 MH019535-13, T32 MH019535-15, T32 MH019535-16, T32
MH019535-17, T32 MH19535]
NR 40
TC 50
Z9 51
U1 3
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1064-7481
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD APR
PY 2009
VL 17
IS 4
BP 281
EP 290
PG 10
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA 432QG
UT WOS:000265148600004
PM 19307857
ER
PT J
AU Driscoll, DF
Thoma, A
Franke, R
Klotsch, K
Nehne, J
Bistrian, BR
AF Driscoll, David F.
Thoma, Andrea
Franke, Rolf
Klotsch, Karsten
Nehne, Jorg
Bistrian, Bruce R.
TI Lipid globule size in total nutrient admixtures prepared in
three-chamber plastic bags
SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY
LA English
DT Article
DE Additives; Control, quality; Electrolytes; Emulsions; Injections;
Osmolarity; Particle size; Soybean oil; Stability; Storage;
Triglycerides; Vehicles; Vitamins
ID INJECTABLE EMULSIONS; STABILITY; STANDARDS; INFUSION; GLASS; RATS
AB Purpose. The stability of injectable lipid emulsions in three-chamber plastic (3CP) bags, applying the globule-size limits established by United States Phormacopeia (USP) chapter 729, was studied.
Methods. A total of five premixed total nutrient admixture (TNA) products packaged in 3CP bags from two different lipid manufacturers containing either 20% soybean oil or a mixture of soybean oil and medium-chain-triglyceride oil as injectable lipid emulsions were tested. Two low-osmolarity 3CP bags and three high-osmolarity 3CP bags were studied. All products were tested with the addition of trace elements and multivitamins. All additive conditions (with and without electrolytes) were tested in triplicate at time 0 (immediately after mixing) and at 6, 24, 30, and 48 hours after mixing; the bags were stored at 24-26 degrees C. All additives were equally distributed in each bag for comparative testing, applying both globule sizing methods outlined in USP chapter 729,
Results. Of the bags tested, all bags from one manufacturer were coarse emulsions, showing signs of significant growth in the large-diameter tail when mixed as a TNA formulation and failing the limits set by method II of USP chapter 729 from the outset and throughout the study, while the bags from the other manufacturer were fine emulsions and met these limits. Of the bags that failed, significant instability was noted in one series containing additional electrolytes.
Conclusion. Injectable lipid emulsions provided in 3CP bags that did not meet the globule-size limits of USP chapter 729 produced coarser TNA formulations than emulsions that met the USP limits.
C1 [Driscoll, David F.] Stable Solut LLC, Goleta, CA 93117 USA.
[Driscoll, David F.] BIDMC, Nutr Infect Lab, Boston, MA USA.
[Driscoll, David F.] Harvard Univ, Sch Med, Boston, MA USA.
[Nehne, Jorg] Hosp Care Pilot Plant Pharma, Melsungen, Germany.
RP Driscoll, DF (reprint author), Stable Solut LLC, 551 Mills Way, Goleta, CA 93117 USA.
EM d.driscoll.ssi@gmail.com
FU B. Braun, Melsungen, Germany
FX Supported by a grant from B. Braun, Melsungen, Germany
NR 20
TC 14
Z9 16
U1 0
U2 1
PU AMER SOC HEALTH-SYSTEM PHARMACISTS
PI BETHESDA
PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA
SN 1079-2082
J9 AM J HEALTH-SYST PH
JI Am. J. Health-Syst. Pharm.
PD APR 1
PY 2009
VL 66
IS 7
BP 649
EP 656
DI 10.2146/ajhp080164
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 423KA
UT WOS:000264494000013
PM 19299372
ER
PT J
AU Boulev, R
Nunes, P
Brown, D
AF Boulev, Richard
Nunes, Paula
Brown, Dennis
TI TRANSFERRIN INDUCES VASOPRESSIN RECEPTOR TYPE 2 (V2R) INTERNALIZATION
AND EFFECTS WATER OSMEOSTASIS IN VIVO
SO AMERICAN JOURNAL OF KIDNEY DISEASES
LA English
DT Meeting Abstract
CT Spring Clinical Meeting of the National-Kidney-Foundation
CY MAR 25-29, 2009
CL Nashville, TN
SP Natl Kidney Fdn
C1 Massachusetts Gen Hosp, Ctr Syst Biol, Program Membrane Biol, Boston, MA 02114 USA.
Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0272-6386
J9 AM J KIDNEY DIS
JI Am. J. Kidney Dis.
PD APR
PY 2009
VL 53
IS 4
MA 31
BP A30
EP A30
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 425JI
UT WOS:000264632400056
ER
PT J
AU Ramirez, P
Al-Shahrouri, H
Fanti, P
Abboud, H
Lorenzo, C
Haffner, S
AF Ramirez, Peter
Al-Shahrouri, Hania
Fanti, Paolo
Abboud, Hanna
Lorenzo, Carlos
Haffner, Steven
TI NMR IDENTIFIES ATHEROGENIC LIPOPROTEIN ABNORMALITIES IN EARLY DIABETIC
NEPHROPATHY THAT ARE UNRECOGNIZED BY CONVENTIONAL ANALYSIS
SO AMERICAN JOURNAL OF KIDNEY DISEASES
LA English
DT Meeting Abstract
CT Spring Clinical Meeting of the National-Kidney-Foundation
CY MAR 25-29, 2009
CL Nashville, TN
SP Natl Kidney Fdn
C1 Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX USA.
S Texas Vet Hlth Care Syst, San Antonio, TX USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0272-6386
J9 AM J KIDNEY DIS
JI Am. J. Kidney Dis.
PD APR
PY 2009
VL 53
IS 4
MA 168
BP A64
EP A64
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 425JI
UT WOS:000264632400193
ER
PT J
AU Gold, J
Buonopane, RJ
Caggiano, RA
Picciotto, M
Vogeli, C
Kanner, NT
Babcock, RL
Li, ZH
Jellinek, M
Drubner, SJ
Sklar, KJ
Murphy, JM
AF Gold, Joseph
Buonopane, Ralph J.
Caggiano, Robert A.
Picciotto, Mark
Vogeli, Christine
Kanner, Natalie T.
Babcock, Rebecca L.
Li, Zhonghe
Jellinek, Michael
Drubner, Stacey J.
Sklar, Kenneth J.
Murphy, J. Michael
TI Assessing Outcomes in Child Psychiatry
SO AMERICAN JOURNAL OF MANAGED CARE
LA English
DT Article
ID GLOBAL ASSESSMENT SCALE; RATING-SCALE; ANCHORED VERSION; OPEN-LABEL;
BPRS-C; RELIABILITY; CGAS; SCHIZOPHRENIA; ADOLESCENTS; TRIAL
AB Objective: To report on the first year of a program using standardized rating scales within a large, multisite mental health system of care for children and to assess the validity, reliability, and feasibility of these scales.
Study Design: Naturalistic follow-up of clinicians' ratings.
Methods: Clinicians filled out the Brief Psychiatric Rating Scale for Children (BPRS-C) and the Children's Global Assessment Scale (CGAS) at intake and discharge/90-day follow-up for all new patients.
Results: Data were collected on 2396 patients from all 20 sites serving children in the Partners HealthCare network. Mean scores for both BPRS-C and CGAS showed worst functioning at inpatient sites, followed by Acute Residential Treatment, then partial hospital, then outpatient sites. All patients re-rated at discharge or 90-day follow-up showed a significant improvement in scores. Inter-item reliability on the BPRS-C was acceptable, with Cronbach alphas of .78 and .81. Feasibility at intake was demonstrated in that 66% of all patients had a completed form at intake. Reassessment at discharge also appeared to be feasible in more restrictive levels of care, but less feasible in outpatient sites, where fewer than 25% of all patients had a follow-up form.
Conclusions: This evaluation suggested that the 2 standardized measures appeared to be valid and reliable as part of routine intake and discharge/follow-up in a large child psychiatry system of care. Whether these measures are truly clinically useful remains to be demonstrated because there is at present no gold standard for assessing the quality of treatment or change caused by it.
C1 [Gold, Joseph; Buonopane, Ralph J.; Picciotto, Mark; Babcock, Rebecca L.] McLean Hosp, Belmont, MA 02178 USA.
[Gold, Joseph; Buonopane, Ralph J.; Picciotto, Mark; Vogeli, Christine; Jellinek, Michael; Murphy, J. Michael] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
[Caggiano, Robert A.] N Shore Med Ctr, Dept Psychiat, Salem, MA USA.
[Vogeli, Christine; Li, Zhonghe] MGH Inst Hlth Policy, Boston, MA USA.
[Drubner, Stacey J.; Sklar, Kenneth J.] Partners Psychiat & Mental Hlth, Boston, MA USA.
[Jellinek, Michael] Newton Wellesley Hosp, Dept Psychiat, Newton, MA USA.
[Kanner, Natalie T.; Babcock, Rebecca L.; Jellinek, Michael; Murphy, J. Michael] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
RP Murphy, JM (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 55 Fruit St,YAW 6A, Boston, MA 02114 USA.
EM mmurphy6@partners.org
NR 20
TC 11
Z9 11
U1 1
U2 5
PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC
PI PLAINSBORO
PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA
SN 1088-0224
J9 AM J MANAG CARE
JI Am. J. Manag. Care
PD APR
PY 2009
VL 15
IS 4
BP 210
EP 216
PG 7
WC Health Care Sciences & Services; Health Policy & Services; Medicine,
General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA 433WS
UT WOS:000265237100001
PM 19355793
ER
PT J
AU Rose, AJ
Hermos, JA
Frayne, SM
Pogach, LM
Berlowitz, DR
Miller, DR
AF Rose, Adam J.
Hermos, John A.
Frayne, Susan M.
Pogach, Leonard M.
Berlowitz, Dan R.
Miller, Donald R.
TI Does Opioid Therapy Affect Quality of Care for Diabetes Mellitus?
SO AMERICAN JOURNAL OF MANAGED CARE
LA English
DT Article
ID OPTIMAL GLYCEMIC CONTROL; WOOD-JOHNSON-FOUNDATION; CHRONIC NONCANCER
PAIN; SELF-MANAGEMENT; IMPACT; PERSPECTIVES; PERFORMANCE; PREVALENCE;
DISORDERS; BARRIERS
AB Objective: To examine whether veterans who received chronic opioid therapy had worse diabetes performance measures than patients who did not receive opioids.
Study Design: Retrospective cohort study.
Methods: We identified all patients with diabetes mellitus receiving care in US Department of Veterans Affairs facilities during 2004. Cases received at least 6 prescriptions for chronic opioids during 2004, while controls were randomly selected from among patients with diabetes who received no opioids. We compared process measures (glycosylated hemoglobin and low-density lipoprotein cholesterol levels tested and an eye examination performed) and outcome measures (glycosylated hemoglobin level <= 9.0% and low-density lipoprotein cholesterol level <= 130 mg/dL) between groups.
Results: Cases (n = 47,756) had slightly worse diabetes performance measures than controls (n = 220,912) after adjustment for covariates. For example, 86.4% of cases and 89.0% of controls had a glycosylated hemoglobin test during fiscal year 2004 (adjusted odds ratio, 0.69; P <.001). Among cases, receipt of higher-dose opioids was associated with additional decrement in diabetes performance measures, with a dose-response relationship.
Conclusions: Chronic opioid therapy among patients within the Veterans Affairs system is associated with slightly worse diabetes performance measures compared with patients who do not receive opioids. However, patients receiving higher dosages of opioids had additional decrements in diabetes performance measures; these patients may be appropriate targets for interventions to improve their care for pain and diabetes.
C1 [Rose, Adam J.; Berlowitz, Dan R.; Miller, Donald R.] Bedford VA Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA 01730 USA.
[Rose, Adam J.; Hermos, John A.; Berlowitz, Dan R.] Boston Univ, Dept Med, Boston, MA 02215 USA.
[Hermos, John A.] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA.
[Frayne, Susan M.] VA Palo Alto Healthcare Syst, Ctr Hlth Care Evaluat, Palo Alto, CA USA.
[Frayne, Susan M.] Stanford Univ, Div Gen Internal Med, Stanford, CA 94305 USA.
[Pogach, Leonard M.] Univ Med & Dent New Jersey, Newark, NJ 07103 USA.
[Pogach, Leonard M.] New Jersey Vet Healthcare Syst, Ctr Healthcare Knowledge Management, E Orange, NJ USA.
[Berlowitz, Dan R.; Miller, Donald R.] Boston Univ, Dept Hlth Policy & Management, Sch Publ Hlth, Boston, MA USA.
RP Rose, AJ (reprint author), Bedford VA Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, 200 Springs Rd,Bldg 70, Bedford, MA 01730 USA.
EM adamrose@bu.edu
FU US Department of Veterans Affairs Clinical Sciences Research and
Development Service; US Department of Veterans Affairs Health Services
Research and Development Service
FX This study was supported by a grant from the US Department of Veterans
Affairs Clinical Sciences Research and Development Service (principal
investigator DRM and coprincipal investigator LMP). Dr Rose is supported
by a career development grant from the US Department of Veterans Affairs
Health Services Research and Development Service. The views expressed in
this article are those of the authors and do not necessarily represent
the views of the US Department of Veterans Affairs.
NR 44
TC 9
Z9 9
U1 1
U2 3
PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC
PI PLAINSBORO
PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA
SN 1088-0224
J9 AM J MANAG CARE
JI Am. J. Manag. Care
PD APR
PY 2009
VL 15
IS 4
BP 217
EP 224
PG 8
WC Health Care Sciences & Services; Health Policy & Services; Medicine,
General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA 433WS
UT WOS:000265237100002
PM 19355794
ER
PT J
AU Naik, AD
Woofter, AL
Skinner, JM
Abraham, NS
AF Naik, Aanand D.
Woofter, Aaron L.
Skinner, Jessica M.
Abraham, Neena S.
TI Pharmaceutical Company Influence on Nonsteroidal Anti-Inflammatory Drug
Prescribing Behaviors
SO AMERICAN JOURNAL OF MANAGED CARE
LA English
DT Article
ID CONSENSUS PANEL; PHYSICIANS; QUALITY; OSTEOARTHRITIS; PRESCRIPTION;
IMPROVEMENT; STRATEGIES; GUIDELINES; INHIBITORS; ADHERENCE
AB Objectives: To describe the taxonomy of methods used by pharmaceutical companies to influence physicians' nonsteroidal anti-inflammatory drug (NSAID) prescribing behaviors and to elicit physicians' perceptions of and counterbalances to these influences.
Study Design: In-depth interviews analyzed using the constant comparative method of qualitative data analysis.
Methods: Qualitative interviews were conducted with physicians representing various clinical specialties. Interviews were transcribed and coded inductively using grounded theory. Recruitment was stopped at 25 participants after the attainment of thematic saturation, when no new concepts emerged from ongoing analysis of consecutive interviews.
Results: Physicians described a variety of influences that shaped their NSAID prescribing behaviors, including detailing and direct contact with pharmaceutical representatives, requests from patients inspired by direct-to-consumer advertisements, and marketing during medical school and residency training. Physicians described practice guidelines, peer-reviewed evidence, and opinions of local physician experts as important counterweights to pharmaceutical company influence. Local physician experts interpreted and provided context for new clinical evidence, practice guidelines, and NSAID-related marketing.
Conclusions: The social and communicative strategies used by pharmaceutical companies can be adapted to improve physicians' adoption of guidelines for safer NSAID prescribing. Communicative interactions between local experts and other physicians who prescribe NSAIDs may be the critical target for future interventions to promote safer NSAID prescribing.
C1 [Naik, Aanand D.; Woofter, Aaron L.; Abraham, Neena S.] Michael E DeBakey Vet Affairs Med Ctr, Res & Dev Ctr Excellence, Gastroenterol Outcomes Geriatr Unit Hlth Serv, Houston, TX USA.
[Woofter, Aaron L.] Duke Univ, Div Gastroenterol, Raleigh, NC USA.
[Naik, Aanand D.; Skinner, Jessica M.; Abraham, Neena S.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA.
RP Naik, AD (reprint author), Houston Ctr Qual Care & Utilizat Studies, Michael E DeBakey VA Med Ctr, 152,2002 Holcombe Blvd, Houston, TX 77030 USA.
EM anaik@bcm.tmc.edu
FU Houston Center for Quality of Care & Utilization Studies; Houston
Veterans Affairs Health Sciences Research and Development Center of
Excellence [HFP90-020]; National Institute on Aging Career Development
Award [5K23AG027144]; American Gastroenterological Association
Foundation-Sucampo-Association of Specialty Professors Designated
Research Award in Geriatric Gastroenterology; Department of Veterans
Affairs [VA IIR 115-05]
FX This study was supported by resources and use of facilities at the
Houston Center for Quality of Care & Utilization Studies, Houston
Veterans Affairs Health Sciences Research and Development Center of
Excellence (HFP90-020). Dr Naik is supported by a National Institute on
Aging Career Development Award (5K23AG027144). Dr Abraham is supported
by an American Gastroenterological Association
Foundation-Sucampo-Association of Specialty Professors Designated
Research Award in Geriatric Gastroenterology and by a Merit Review Award
from the Department of Veterans Affairs (VA IIR 115-05). No funding
agencies had a role in the design and conduct of the study, analysis and
interpretation of data, or preparation and approval of the manuscript.
The views expressed herein are those of the authors and do not
necessarily reflect those of the Department of Veterans Affairs or
Baylor College of Medicine.
NR 31
TC 4
Z9 4
U1 1
U2 4
PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC
PI PLAINSBORO
PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA
SN 1088-0224
J9 AM J MANAG CARE
JI Am. J. Manag. Care
PD APR
PY 2009
VL 15
IS 4
BP E9
EP E15
PG 7
WC Health Care Sciences & Services; Health Policy & Services; Medicine,
General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA 433WS
UT WOS:000265237100007
PM 19341315
ER
PT J
AU Munshi, MN
Hayes, M
Sternthal, A
Ayres, D
AF Munshi, Medha N.
Hayes, Mellody
Sternthal, Adrianne
Ayres, Darlene
TI Use of Serum c-Peptide Level to Simplify Diabetes Treatment Regimens in
Older Adults
SO AMERICAN JOURNAL OF MEDICINE
LA English
DT Article
DE Peptide; Diabetes; Older adults; Simplification; Treatment
ID ORAL ANTIDIABETIC AGENTS; ELDERLY-PATIENTS; MELLITUS
AB BACKGROUND: Diabetes management in older adults is challenging. Poor glycemic control and high risk of hypoglycemia are common in older patients on a complicated insulin regimen. Newer oral hypoglycemic agents have provided an opportunity to simplify regimens in patients with type-2 diabetes on insulin. Serum c-peptide is a test to assess endogenous production of insulin. We analyze the use of serum c-peptide level in simplifying diabetes regimen by decreasing or stopping insulin injection and adding oral hypoglycemic agents in older adults.
METHODS: One hundred patients aged over 65 years with either poor glycemic control or difficulty coping with insulin regimen seen at a geriatric diabetes clinic were analyzed for this study. The data on serum c-peptide levels and A1c, along with demographic information, were obtained from medical charts.
RESULTS: Sixty-five of 100 patients (aged 79 +/- 14 years, duration of diabetes 21 +/- 13 years) had detectable serum c-peptide levels. Forty-six of 65 patients were available for simplification of regimen. Eleven of 46 patients had other co-morbidities preventing use of oral hypoglycemic agents. In 35/65 patients, simplification was completed successfully. Nineteen of 35 patients were converted to all-oral regimens (off insulin), while 16/35 had simplification of regimen by addition of oral hypoglycemic agents and lowering the number of insulin injections from an average of 2.7 to 1.5 injections/day (P = .001). Glycemic control improved significantly in patients with a simplified regimen (8.0% +/- 1.5% vs 7.4% +/- 1.5%; P < .002), and patients reported fewer hypoglycemia episodes.
CONCLUSIONS: Serum c-peptide level can be used to simplify insulin regimen in older adults with diabetes. (C) 2009 Elsevier Inc. All rights reserved. . The American Journal of Medicine (2009) 122, 395-397
C1 [Munshi, Medha N.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Munshi, Medha N.; Hayes, Mellody; Sternthal, Adrianne; Ayres, Darlene] Joslin Diabet Ctr, Boston, MA 02215 USA.
[Munshi, Medha N.] Harvard Univ, Sch Med, Boston, MA USA.
RP Munshi, MN (reprint author), Beth Israel Deaconess Med Ctr, 110 Frances St,LMOB 1B, Boston, MA 02215 USA.
EM medha.munshi@joslin.harvard.edu
FU DERC; NIH [5P30 DK36836-19 (MM)]; ADA [1-07-CR-40 (MM)]; Office of the
Congressionally Directed Medical Research Programs
[W81XWH-07-1-0282(MM)]
FX The study was partly supported by a grant from the DERC; NIH 5P30
DK36836-19 (MM), a clinical research award from ADA 1-07-CR-40 (MM), and
Department of Defense PRMRP of the Office of the Congressionally
Directed Medical Research Programs, W81XWH-07-1-0282(MM).
NR 9
TC 4
Z9 5
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9343
J9 AM J MED
JI Am. J. Med.
PD APR
PY 2009
VL 122
IS 4
BP 395
EP 397
DI 10.1016/j.amjmed.2008.12.008
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 432OA
UT WOS:000265142400018
PM 19332236
ER
PT J
AU Nogueira, RG
Schwamm, LH
Hirsch, JA
AF Nogueira, R. G.
Schwamm, L. H.
Hirsch, J. A.
TI Endovascular Approaches to Acute Stroke, Part 1: Drugs, Devices, and
Data
SO AMERICAN JOURNAL OF NEURORADIOLOGY
LA English
DT Review
ID ACUTE ISCHEMIC-STROKE; TISSUE-PLASMINOGEN-ACTIVATOR; MIDDLE
CEREBRAL-ARTERY; SELF-EXPANDING STENT; PERCUTANEOUS TRANSLUMINAL
ANGIOPLASTY; RANDOMIZED CONTROLLED-TRIAL; MECHANICAL CLOT DISRUPTION;
AMERICAN-HEART-ASSOCIATION; INTERNAL CAROTID-ARTERY; INTRAARTERIAL
THROMBOLYSIS
AB Despite years of research and pioneering clinical work, stroke remains a massive public health concern. Since 1996, we have lived in the era of US Food and Drug Administration-approved intravenous (IV) recombinant tissue plasminogen activator (rtPA). This treatment, despite its promise, continues to exhibit its limitations. Encovascular therapy has several theoretic advantages over IV rtPA, including site specificity, longer treatment windows, and higher recanalization rates. In this article, we will review the various pharmacologic strategies for acute stroke treatment, providing both a historic context and the state of the art. The drugs will be classified on the basis of their theoretic rationale for therapy. Next, we will review the various devices and strategies for mechanical revascularization with an aim toward comprehensiveness. These range from wire disruption of thrombus to preclinical trials for novel mechanical solutions. This first installment of this 2-part series will end with an analysis of retrograde reperfusion techniques.
C1 [Nogueira, R. G.] Harvard Univ, Sch Med, Massachusetts Gen Hosp,Endovasc Neurosurg Interve, Dept Intervent Neuroradiol & Endovasc Neurosurg, Boston, MA 02114 USA.
[Nogueira, R. G.; Schwamm, L. H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Nogueira, R. G.; Schwamm, L. H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA.
[Nogueira, R. G.; Schwamm, L. H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurocrit Care & Vasc Neurol Sect, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
RP Nogueira, RG (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp,Endovasc Neurosurg Interve, Dept Intervent Neuroradiol & Endovasc Neurosurg, 55 Fruit St,GRB-2-241, Boston, MA 02114 USA.
EM rnogueira@partners.org
OI Schwamm, Lee/0000-0003-0592-9145
NR 99
TC 75
Z9 79
U1 0
U2 4
PU AMER SOC NEURORADIOLOGY
PI OAK BROOK
PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA
SN 0195-6108
J9 AM J NEURORADIOL
JI Am. J. Neuroradiol.
PD APR
PY 2009
VL 30
IS 4
BP 649
EP 661
DI 10.3174/ajnr.A1486
PG 13
WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 438VL
UT WOS:000265583700003
PM 19279271
ER
PT J
AU Konstas, AA
Goldmakher, GV
Lee, TY
Lev, MH
AF Konstas, A. A.
Goldmakher, G. V.
Lee, T. -Y.
Lev, M. H.
TI Theoretic Basis and Technical Implementations of CT Perfusion in Acute
Ischemic Stroke, Part 1: Theoretic Basis
SO AMERICAN JOURNAL OF NEURORADIOLOGY
LA English
DT Review
ID CEREBRAL-BLOOD-FLOW; POSITRON-EMISSION-TOMOGRAPHY;
TISSUE-PLASMINOGEN-ACTIVATOR; HIGH-RESOLUTION MEASUREMENT;
SUSCEPTIBILITY CONTRAST MRI; 3-DIMENSIONAL FUNCTIONAL CT; INITIAL
CLINICAL-EXPERIENCE; TRACER BOLUS PASSAGES; COMPUTED-TOMOGRAPHY;
SUBARACHNOID HEMORRHAGE
AB CT perfusion (CTP) is a functional imaging technique that provides important information about capillary-level hemodynamics of the brain parenchyma and is a natural complement to the strengths of unenhanced CT and CT angiography in the evaluation of acute stroke, vasospasm, and other neurovascular disorders. CTP is critical in determining the extent of irreversibly infarcted brain tissue (infarct "core") and the severely ischemic but potentially salvageable tissue ("penumbra"). This is achieved by generating parametric maps of cerebral blood flow, cerebral blood volume, and mean transit time.
C1 [Konstas, A. A.; Goldmakher, G. V.; Lev, M. H.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Lee, T. -Y.] Robarts Res Inst, Imaging Res Labs, London, ON N6A 5C1, Canada.
RP Konstas, AA (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA.
EM akonstas@partners.org
RI Lee, Ting-Yim/M-1721-2013
NR 73
TC 101
Z9 108
U1 0
U2 8
PU AMER SOC NEURORADIOLOGY
PI OAK BROOK
PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA
SN 0195-6108
J9 AM J NEURORADIOL
JI Am. J. Neuroradiol.
PD APR
PY 2009
VL 30
IS 4
BP 662
EP 668
DI 10.3174/ajnr.A1487
PG 7
WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 438VL
UT WOS:000265583700004
PM 19270105
ER
PT J
AU Cipriano, LE
Steinberg, ML
Gazelle, GS
Gonzalez, RG
AF Cipriano, L. E.
Steinberg, M. L.
Gazelle, G. S.
Gonzalez, R. G.
TI Comparing and Predicting the Costs and Outcomes of Patients with Major
and Minor Stroke Using the Boston Acute Stroke Imaging Scale
Neuroimaging Classification System
SO AMERICAN JOURNAL OF NEURORADIOLOGY
LA English
DT Article; Proceedings Paper
CT 46th Annual Meeting of the American-Society-of-Neuroradiology
CY MAY 31-JUN 05, 2008
CL New Orleans, LA
SP Amer Soc Neuroradiol
ID ACUTE ISCHEMIC-STROKE; ACUTE MYOCARDIAL-INFARCTION; CEREBROVASCULAR
EVENTS; INPATIENT COSTS; RESOURCE USE; CENTERS; TRIAL; RECOMMENDATIONS;
ANGIOGRAPHY; VALIDATION
AB BACKGROUND AND PURPOSE: A neuroimaging-based ischemic stroke classification system that predicts costs and outcomes would be useful for clinical prognostication and hospital resource planning. The Boston Acute Stroke Imaging Scale (BASIS), a neuroimaging-based ischemic stroke classification system, was tested to determine whether it was able to predict the costs and clinical outcomes of patients with stroke at an urban academic medical center.
MATERIALS AND METHODS: Patients with ischemic stroke who presented in the emergency department in 2000 (230 patients) and 2005 (250 patients) were classified by using BASIS as having either a major or minor stroke. Compared outcomes included death, length of hospitalization, discharge disposition, use of imaging and intensive care unit (ICU) resources, and total in-hospital cost. Continuous variables were compared by univariate analysis by using the Student t test or the Satterthwaite test adjusted for unequal variances. Categoric variables were tested with the chi(2) test. Multiple regression analyses related total hospital cost (dependent variable) to stroke severity (major versus minor), sex, age, presence of comorbidities, and death during hospitalization. Logistic regression analysis was applied to identify the significant predictive variables indicating a greater likelihood of discharge home.
RESULTS: In both years, individuals with strokes classified as major had a significantly longer length of stay, spent more days in the ICU, and had a higher cost of hospitalization than patients with minor strokes (all outcomes, P < .0001). All deaths (8 in 2000, 26 in 2005) occurred in patients with major stroke. Whereas 73% of patients with minor stroke were discharged home, only 12.2% of patients with major stroke were discharged home (P < .0001); 61% of patients with major stroke were discharged to a rehabilitation or skilled nursing facility. Patients with major stroke cost 4.4 times and 3.0 times that of patients with minor stroke in 2000 and 2005, respectively. Making up less than one third of all patients, patients with major stroke accounted for 60% of the total in-hospital cost of acute stroke care.
CONCLUSIONS: BASIS, a neuroimaging-based stroke classification system, is highly effective at predicting in-hospital resource use, acute-hospitalization cost, and outcome, Predictive ability was maintained across the years Studied.
C1 [Gonzalez, R. G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroradiol Div, Boston, MA 02114 USA.
[Cipriano, L. E.; Gazelle, G. S.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA.
[Steinberg, M. L.] Harvard Univ, Harvard Design Sch, Cambridge, MA 02138 USA.
[Gazelle, G. S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA.
[Gazelle, G. S.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02114 USA.
RP Gonzalez, RG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroradiol Div, GRB 285,55 Fruit St, Boston, MA 02114 USA.
EM rggonzalez@partners.org
RI Cipriano, Lauren/C-3521-2017
OI Cipriano, Lauren/0000-0001-5568-4516
FU NINDS NIH HHS [NS50041]
NR 34
TC 21
Z9 21
U1 0
U2 2
PU AMER SOC NEURORADIOLOGY
PI OAK BROOK
PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA
SN 0195-6108
J9 AM J NEURORADIOL
JI Am. J. Neuroradiol.
PD APR
PY 2009
VL 30
IS 4
BP 703
EP 709
DI 10.3174/ajnr.A1441
PG 7
WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 438VL
UT WOS:000265583700011
PM 19164436
ER
PT J
AU Babiarz, LS
Romero, JM
Murphy, EK
Brobeck, B
Schaefer, PW
Gonzalez, RG
Lev, MH
AF Babiarz, L. S.
Romero, J. M.
Murphy, E. K.
Brobeck, B.
Schaefer, P. W.
Gonzalez, R. G.
Lev, M. H.
TI Contrast-Enhanced MR Angiography Is Not More Accurate Than Unenhanced 2D
Time-of-Flight MR Angiography for Determining >= 70% Internal Carotid
Artery Stenosis
SO AMERICAN JOURNAL OF NEURORADIOLOGY
LA English
DT Article
ID DIGITAL-SUBTRACTION-ANGIOGRAPHY; MAGNETIC-RESONANCE ANGIOGRAPHY;
COMPUTED TOMOGRAPHIC ANGIOGRAPHY; ROW CT ANGIOGRAPHY; SYMPTOMATIC
PATIENTS; IMAGING MODALITY; DECISION-MAKING; IN-VITRO; ENDARTERECTOMY;
OCCLUSION
AB BACKGROUND AND PURPOSE: Internal carotid artery (ICA) atheromatous disease is an important cause of ischemic stroke, and endarterectomy or stent placement is typically indicated for symptomatic patients with >= 70% stenosis. Our purpose was to compare contrast-enhanced MR angiography (CE-MRA) with unenhanced 2D time-of-flight MR angiography (2D TOF MRA) in detecting hemodynamically significant ICA stenosis, by using CT angiography (CTA) as the reference standard.
MATERIALS AND METHODS: This was an institutional review board-approved retrospective study. We identified 177 consecutive patients (354 ICAs) who received correlative CE-MRA, 2D TOF MRA, and CTA. Two neuroradiologists blinded to the CTA data graded the degree of ICA stenosis according to a 5-point scale. Additionally, luminal signal-intersity characteristics including 1) signal intensity dropout, 2) distal-vessel narrowing, and 3) distal-vessel signal-intensity reduction were recorded, MRA results were correlated with those of CTA, and receiver-operating-characteristic (ROC) curves were constructed.
RESULTS: On CTA, there were 55 ICAs with and 299 without >= 70% stenosis. CE-MRA was 84% sensitive and 96% specific for detecting >= 70% stenosis, 2D TOF MRA was 80% sensitive and 95% specific. The area under the ROC curve was 0.97 for CE-MRA and 0.95 for 2D TOF MRA (P = .51, riot significant). For both MRA studies, each of the luminal signal-intensity characteristics had high specificity (>98%) but poor-to-mild sensitivity (35%-66%) in detecting >= 70% stenosis.
CONCLUSIONS: Although it is established that CF-MRA more accurately delineates neurovascular anatomy than does unenhanced 2D TOF MRA, the administration of gadolinium did not offer a significant advantage in distinguishing surgically treatable ICA stenosis. This conclusion may be important in patients with contraindications to gadolinium.
C1 [Babiarz, L. S.; Romero, J. M.; Murphy, E. K.; Brobeck, B.; Schaefer, P. W.; Gonzalez, R. G.; Lev, M. H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA.
RP Romero, JM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA.
EM jmromero@partners.org
NR 59
TC 17
Z9 19
U1 0
U2 3
PU AMER SOC NEURORADIOLOGY
PI OAK BROOK
PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA
SN 0195-6108
J9 AM J NEURORADIOL
JI Am. J. Neuroradiol.
PD APR
PY 2009
VL 30
IS 4
BP 761
EP 768
DI 10.3174/ajnr.A1464
PG 8
WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 438VL
UT WOS:000265583700021
PM 19164440
ER
PT J
AU Stefancyk, AL
AF Stefancyk, Amanda L.
TI Postponing Medication Administration
SO AMERICAN JOURNAL OF NURSING
LA English
DT Editorial Material
C1 Massachusetts Gen Hosp, Gen Med Unit, Boston, MA 02114 USA.
RP Stefancyk, AL (reprint author), Massachusetts Gen Hosp, Gen Med Unit, Boston, MA 02114 USA.
EM astefancyk@partners.org
NR 0
TC 2
Z9 2
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0002-936X
J9 AM J NURS
JI Am. J. Nurs.
PD APR
PY 2009
VL 109
IS 4
BP 21
EP 23
PG 3
WC Nursing
SC Nursing
GA 427ZV
UT WOS:000264818500014
PM 19325302
ER
PT J
AU Savar, A
Andreoli, MT
Kloek, CE
Andreoli, CM
AF Savar, Aaron
Andreoli, Michael T.
Kloek, Carolyn E.
Andreoli, Christopher M.
TI Enucleation for Open Globe Injury
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID SYMPATHETIC OPHTHALMIA; OCULAR TRAUMA; EYE INJURIES; EPIDEMIOLOGY;
CLASSIFICATION
AB PURPOSE: To report the experience of enucleation after open globe at an ophthalmic trauma referral center. DESIGN: Retrospective, observational study.
METHODS: In an ophthalmic trauma referral center the charts of all patients having Suffered an open globe injury between January 1, 2000 and June 30, 2007 were reviewed. Variables assessed were age, gender, type of injury (rupture or laceration [penetrating, intraocular foreign body, or perforating]), ocular trauma score, visual acuity, subsequent enucleation, indication for and timing of enucleation, presence of sympathetic ophthalmia, and length of follow,up.
RESULTS: Among 660 open globe injuries, 55 have undergone enucleation (including 4 eviscerations), 11 primarily and 44 secondarily. Eyes with ruptures were significantly more likely to be enucleated than those with injuries attributable to lacerations (P < .001). The most common reason for secondary enucleation was a blind, painful eye. Two patients (0.3%) developed sympathetic ophthalmia and have maintained good vision in the sympathizing eye.
CONCLUSIONS: The vast majority of open globes can be repaired without requiring primary enucleation. Secondary enucleation is most commonly carried out for pain. Eyes with no light perception can be closely observed if the patient chooses. (Am J Ophthalmol 2009; 147:595-600. (C) 2009 by Elsevier Inc. All rights reserved.)
C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA.
RP Andreoli, CM (reprint author), 133 Brookline Ave, Boston, MA 02215 USA.
EM christopher.andreoli@meei.harvard.edu
NR 33
TC 34
Z9 38
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9394
J9 AM J OPHTHALMOL
JI Am. J. Ophthalmol.
PD APR
PY 2009
VL 147
IS 4
BP 595
EP 600
DI 10.1016/j.ajo.2008.10.017
PG 6
WC Ophthalmology
SC Ophthalmology
GA 424KW
UT WOS:000264566600007
PM 19181305
ER
PT J
AU Andreoli, CM
Andreoli, MT
Kloek, CE
Ahuero, AE
Vavvas, D
Durand, ML
AF Andreoli, Christopher M.
Andreoli, Michael T.
Kloek, Carolyn E.
Ahuero, Audrey E.
Vavvas, Demetrios
Durand, Marlene L.
TI Low Rate of Endophthalmitis in a Large Series of Open Globe Injuries
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID INTRAOCULAR FOREIGN-BODIES; PENETRATING EYE INJURIES; POSTTRAUMATIC
ENDOPHTHALMITIS; ANTIBIOTIC-PROPHYLAXIS; OCULAR INJURIES; RISK-FACTORS;
TRAUMA; TRIAL; OUTCOMES; REMOVAL
AB PURPOSE: To determine the percentage of patients in whom endophthalmitis developed after open globe injury.
DESIGN: Retrospective, noncomparative, consecutive case series.
METHODS: Charts of all patients (675 in total) treated surgically for open globe injury at the Massachusetts Eye and Ear Infirmary (MEEI) between January 1, 2000 and July 31, 2007 were reviewed. Cases with at least 30 days of follow,up were included in statistical analyses (558 in total). A standardized treatment protocol was used in all cases. Intravenous vancomycin and ceftazidime were started on admission and were stopped after 48 hours. Patients were discharged on topical antibiotics, corticosteroids, and cycloplegia. Surgical repairs were performed by the chief of trauma, a full-time position rotating yearly, who is on call for all open globe trauma. Data collection variables included timing of injury and repair, mechanism of injury, details of surgical repair, and details of follow-up such as duration, presence of complications, and vision. A primary outcome measure of endophthalmitis and secondary outcome measure of risk factors for endophthalmitis were studied.
RESULTS: During 7.5 years, 675 open globe injuries were treated at MEEI. Of these, 558 had at least 30 days of follow,up (mean, 11 months) and were used in statistical analyses. The overall percentage of endophthalmitis was 0.9% (3 culture-positive cases and 2 culture-negative cases). Four of the 5 cases achieved final acuity of 20/80 or better. Risk factors for endophthalmitis included intraocular foreign body (P = .03; odds ratio, 7.52) and primary intraocular lens placement (P = .05).
CONCLUSIONS: A standardized protocol including surgical repair by a dedicated eye trauma service and 48 hours of intravenous antibiotics was associated with a posttraumatic endophthalmitis percentage of less than 1%. (Am J Ophthalmol 2009; 147:601-608. (C) 2009 by Elsevier Inc. All rights reserved.)
C1 [Andreoli, Christopher M.; Andreoli, Michael T.; Kloek, Carolyn E.; Ahuero, Audrey E.; Vavvas, Demetrios] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA.
[Andreoli, Christopher M.; Andreoli, Michael T.; Kloek, Carolyn E.; Ahuero, Audrey E.; Vavvas, Demetrios; Durand, Marlene L.] Harvard Univ, Sch Med, Boston, MA USA.
[Durand, Marlene L.] Massachusetts Eye & Ear Infirm, Infect Dis Serv, Boston, MA 02114 USA.
[Durand, Marlene L.] Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA.
[Andreoli, Christopher M.] Harvard Vanguard Med Associates, Dept Ophthalmol, Boston, MA USA.
RP Andreoli, CM (reprint author), 113 Brookline Ave, Boston, MA 02215 USA.
EM christopher_andreoli@meei.harvard.edu
OI Vavvas, Demetrios/0000-0002-8622-6478
NR 29
TC 44
Z9 51
U1 1
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9394
J9 AM J OPHTHALMOL
JI Am. J. Ophthalmol.
PD APR
PY 2009
VL 147
IS 4
BP 601
EP 608
DI 10.1016/j.ajo.2008.10.023
PG 8
WC Ophthalmology
SC Ophthalmology
GA 424KW
UT WOS:000264566600008
PM 19181306
ER
PT J
AU Ngo, L
Latham, NK
Jette, AM
Soukup, J
Iezzoni, LI
AF Ngo, Long
Latham, Nancy K.
Jette, Alan M.
Soukup, Jane
Iezzoni, Lisa I.
TI Use of Physical and Occupational Therapy by Medicare Beneficiaries
Within Five Conditions 1994-2001
SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION
LA English
DT Article
DE Physical Therapy; Occupational Therapy; Medicare; Prospective Payment
ID OBSTRUCTIVE PULMONARY-DISEASE; CARDIAC REHABILITATION;
PROSPECTIVE-PAYMENT; POSTSTROKE REHABILITATION; RANDOMIZED-TRIAL;
OLDER-ADULTS; STROKE REHABILITATION; MYOCARDIAL-INFARCTION; HEALTH
OUTCOMES; CLINICAL-TRIAL
AB Objective: To examine the use of physical therapy and occupational therapy among Medicare beneficiaries nationwide before and after the 1997 Balanced Budget Act, which introduced prospective payment for rehabilitation services.
Design: We analyzed responses from the longitudinal Medicare Current Beneficiary Survey, merged with Medicare claims, to track physical therapy and occupational therapy rates and intensity (units of service) from 1994 through 2001. This observational study focused on elderly and disabled Medicare beneficiaries within five conditions: stroke, acute myocardial infarction, chronic obstructive pulmonary disease, arthritis, and lower-limb mobility problems. We used cubic smoothing spline functions to describe trends in service intensity over time and generalized estimating equations to assess changes in service intensity.
Results: Controlling for demographic characteristics, adjusted mean level of physical therapy and occupational therapy intensity rose significantly between 1994 and 2001 for all five conditions. Service intensity leveled off in 1999 for occupational therapy and 2000 for physical therapy. With few exceptions, physical therapy and occupational therapy intensity was not significantly associated with patients' demographic characteristics.
Conclusions: Medicare beneficiaries with conditions that can potentially benefit from physical therapy or occupational therapy or both continued to get these services at similar-and sometimes increasing-intensity during years after passage of the Balanced Budget Act.
C1 [Iezzoni, Lisa I.] Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA.
[Soukup, Jane] Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA.
[Latham, Nancy K.; Jette, Alan M.] Boston Univ, Sch Publ Hlth, Hlth & Disabil Res Inst, Boston, MA 02118 USA.
RP Iezzoni, LI (reprint author), Massachusetts Gen Hosp, Inst Hlth Policy, 50 Staniford St,Room 901B, Boston, MA 02114 USA.
RI Latham, Nancy/K-3405-2012;
OI Jette, Alan/0000-0002-2117-9973
FU NICHD NIH HHS [HD043913-02, R01 HD043913, R01 HD043913-02]
NR 79
TC 3
Z9 3
U1 2
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0894-9115
J9 AM J PHYS MED REHAB
JI Am. J. Phys. Med. Rehabil.
PD APR
PY 2009
VL 88
IS 4
BP 308
EP 321
DI 10.1097/PHM.0b013e318198a791
PG 14
WC Rehabilitation; Sport Sciences
SC Rehabilitation; Sport Sciences
GA 422TY
UT WOS:000264451800010
PM 19190486
ER
EF