FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Fischer, AH
Zhao, C
Li, QK
Gustafson, KS
Eltoum, IE
Tambouret, R
Benstein, B
Savaloja, LC
Kulesza, P
AF Fischer, Andrew H.
Zhao, Chengquan
Li, Qing Kay
Gustafson, Karen S.
Eltoum, Isam-Eldin
Tambouret, Rosemary
Benstein, Barbara
Savaloja, Lynnette C.
Kulesza, Peter
TI The Cytologic Criteria of Malignancy
SO JOURNAL OF CELLULAR BIOCHEMISTRY
LA English
DT Article
DE CANCER CELL STRUCTURE; DIAGNOSIS; CRITERIA OF MALIGNANCY
ID PAPILLARY THYROID-CARCINOMA; BREAST-CANCER PROGRESSION; NUCLEAR-MEMBRANE
PROTEIN; IN-SITU HYBRIDIZATION; GRANULOSA-CELL TUMORS; RHABDOID TUMORS;
IMAGE-ANALYSIS; PROLIFERATIVE ACTIVITY; MAMMARY TUMORIGENESIS;
SIDEROBLASTIC ANEMIA
AB Cytology and cell biology are two separate fields that share a focus on cancer. Cancer is still diagnosed based on morphology, and surprisingly little is known about the molecular basis of the defining structural features. Cytology uses the smallest possible biopsy for diagnosis by reducing morphologic "criteria of malignancy" to the smallest scale. To begin to develop common ground, members of the American Society of Cytopathology Cell Biology Liaison Working Group classify some of the "criteria of malignancy" and review their relation to current cell biology concepts. The criteria of malignancy are extremely varied, apparently reflecting many different pathophysiologies in specific microenvironments. Criteria in Group 1 comprise tissue-level alterations that appear to relate to resistance to anoikis, alterations in cell adhesion molecules, and loss of apical-basal polarity. Criteria in Group 2 reflect genetic instability, including chromosomal and possibly epigenetic instability. Criteria in Groups 3 are subcellular structural changes involving cytoplasmic components, nuclear lamina, chromatin and nucleoli that cannot be accounted for by genetic instability. Some distinct criteria in Group 3 are known to be induced by cancer genes. but their precise structural basis remains obscure. The criteria of malignancy are not closely related to the histogenetic classification of cancers, and they appear to provide an alternative, biologically relevant framework for establishing common ground between cytologists and cell biologists. To understand the criteria of malignancy at a molecular level would improve diagnosis, and likely point to novel cell physiologies that are not encompassed by current cell biology concepts. J. Cell. Biochem. 110: 795-811, 2010. (C) 2010 Wiley-Liss. Inc.
C1 [Fischer, Andrew H.] Univ Massachusetts, Dept Pathol, Worcester, MA 01605 USA.
[Zhao, Chengquan] Univ Pittsburgh, Magee Womens Hosp, Sch Med, Dept Pathol, Pittsburgh, PA 15213 USA.
[Li, Qing Kay] Dept Pathol, Baltimore, MD USA.
[Gustafson, Karen S.] Fox Chase Canc Ctr, Dept Pathol, Philadelphia, PA 19111 USA.
[Eltoum, Isam-Eldin] Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA.
[Tambouret, Rosemary] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Benstein, Barbara] Univ Tennessee, Ctr Hlth Sci, Dept Clin Lab Serv, Memphis, TN 38163 USA.
[Savaloja, Lynnette C.] Reg Hosp, St Paul, MN USA.
Northwestern Univ, Feinberg Sch Med, Dept Pathol, Chicago, IL 60611 USA.
RP Fischer, AH (reprint author), Univ Massachusetts, Dept Pathol, Rm 213 Biotech 3,1 Innovat Dr, Worcester, MA 01605 USA.
EM andrew.fischer@umassmemorial.org
OI Fischer, Andrew/0000-0002-5944-4621
NR 128
TC 9
Z9 9
U1 0
U2 7
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0730-2312
J9 J CELL BIOCHEM
JI J. Cell. Biochem.
PD JUL 1
PY 2010
VL 110
IS 4
BP 795
EP 811
DI 10.1002/jcb.22585
PG 17
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 619OS
UT WOS:000279440100001
PM 20564180
ER
PT J
AU Dossa, T
Arabian, A
Windle, JJ
Dedhar, S
Teitelbaum, SL
Ross, FP
Roodman, GD
St-Arnaud, R
AF Dossa, Tanya
Arabian, Alice
Windle, Jolene J.
Dedhar, Shoukat
Teitelbaum, Steven L.
Ross, F. Patrick
Roodman, G. David
St-Arnaud, Rene
TI Osteoclast-Specific Inactivation of the Integrin-Linked Kinase (ILK)
Inhibits Bone Resorption
SO JOURNAL OF CELLULAR BIOCHEMISTRY
LA English
DT Article
DE INTEGRIN-LINKED KINASE; INTEGRINS; OSTEOCLAST
ID TUMOR-SUPPRESSOR PTEN; PROTEIN-KINASE; MICE LACKING; ACTIVATION;
PROMOTER; BIOLOGY; B/AKT; ROLES
AB Bone resorption requires the adhesion of osteoclasts to extracellular matrix (ECM) components, a process mediated by the alpha(v)beta(3) integrin. Following engagement with the ECM, integrin receptors signal via multiple downstream effectors, including the integrin-linked kinase (ILK). In order to characterize the physiological role of ILK in bone resorption, we generated mice with an osteoclast-specific Ilk gene ablation by mating mice with a floxed Ilk allele with TRAP-Cre transgenic mice. The TRAP-Cre mice specifically excised floxed alleles in osteoclasts, as revealed by crossing them with the ROSA26R reporter strain. Osteoclast-specific Ilk mutant mice appeared phenotypically normal, but histomorphometric analysis of the proximal tibia revealed an increase in bone volume and trabecular thickness. Osteoclast-specific Ilk ablation was associated with an increase in osteoclastogenesis both in vitro and in vivo. However, the mutant osteoclasts displayed a decrease in resorption activity as assessed by reduced pit formation on dentin slices in vitro and decreased serum concentrations of the C-terminal telopeptide of collagen in vivo. Interestingly, compound heterozygous mice in which one allele of Ilk and one allele of the beta(3) integrin gene were inactivated (ILK+/-; beta(+/-)(3)) also had increased trabecular thickness, confirming that beta(3) integrin and Ilk form part of the same genetic cascade. Our results show that ILK is important for the function, but not the differentiation, of osteoclasts. J. Cell. Biochem. 110: 960-967, 2010. (C) 2010 Wiley-Liss. Inc.
C1 [Dossa, Tanya; Arabian, Alice; St-Arnaud, Rene] Shriners Hosp Children, Genet Unit, Montreal, PQ H3G 1A6, Canada.
[Dossa, Tanya; St-Arnaud, Rene] McGill Univ, Dept Human Genet, Montreal, PQ H3A 2T5, Canada.
[Windle, Jolene J.] Virginia Commonwealth Univ, Richmond, VA 23298 USA.
[Dedhar, Shoukat] British Columbia Canc Agcy, Vancouver, BC V6H 3Z6, Canada.
[Dedhar, Shoukat] Vancouver Hosp, Jack Bell Res Ctr, Vancouver, BC V6H 3Z6, Canada.
[Dedhar, Shoukat] Univ British Columbia, Dept Biochem & Mol Biol, Vancouver, BC V6T 1Z3, Canada.
[Teitelbaum, Steven L.; Ross, F. Patrick] Washington Univ, Sch Med, Dept Pathol, St Louis, MO 63110 USA.
[Roodman, G. David] Univ Pittsburgh, Dept Med Hematol Oncol, Pittsburgh, PA 15232 USA.
[Roodman, G. David] VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA.
[St-Arnaud, Rene] McGill Univ, Dept Surg, Montreal, PQ H3A 2T5, Canada.
[St-Arnaud, Rene] McGill Univ, Dept Med, Montreal, PQ H3A 2T5, Canada.
RP St-Arnaud, R (reprint author), Shriners Hosp Children, Genet Unit, 1529 Cedar Ave, Montreal, PQ H3G 1A6, Canada.
EM rst-arnaud@shriners.mcgill.ca
OI Windle, Jolene/0000-0001-6690-385X; Teitelbaum,
Steven/0000-0002-4054-6679
FU Shriners of North America
FX Grant sponsor: Shriners of North America.
NR 33
TC 9
Z9 9
U1 0
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0730-2312
EI 1097-4644
J9 J CELL BIOCHEM
JI J. Cell. Biochem.
PD JUL 1
PY 2010
VL 110
IS 4
BP 960
EP 967
DI 10.1002/jcb.22609
PG 8
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 619OS
UT WOS:000279440100018
PM 20564195
ER
PT J
AU Giustina, A
Chanson, P
Bronstein, MD
Klibanski, A
Lamberts, S
Casanueva, FF
Trainer, P
Ghigo, E
Ho, K
Melmed, S
AF Giustina, A.
Chanson, P.
Bronstein, M. D.
Klibanski, A.
Lamberts, S.
Casanueva, F. F.
Trainer, P.
Ghigo, E.
Ho, K.
Melmed, S.
TI A Consensus on Criteria for Cure of Acromegaly
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID GROWTH-FACTOR-I; ACID-LABILE SUBUNIT; PREOPERATIVE OCTREOTIDE TREATMENT;
DISEASE-RELATED MORBIDITY; GLUCOSE-TOLERANCE TEST; LONG-TERM; TUMOR
SHRINKAGE; FOLLOW-UP; IGF-I; SOMATOSTATIN ANALOGS
AB Objective: The Acromegaly Consensus Group met in April 2009 to revisit the guidelines on criteria for cure as defined in 2000.
Participants: Participants included 74 neurosurgeons and endocrinologists with extensive experience of treating acromegaly.
Evidence/Consensus Process: Relevant assays, biochemical measures, clinical outcomes, and definition of disease control were discussed, based on the available published evidence, and the strength of consensus statements was rated.
Conclusions: Criteria to define active acromegaly and disease control were agreed, and several significant changes were made to the 2000 guidelines. Appropriate methods of measuring and achieving disease control were summarized. (J Clin Endocrinol Metab 95: 3141-3148, 2010)
C1 [Giustina, A.] Univ Brescia, Dept Med & Surg Sci, I-25018 Montichiari, Italy.
[Chanson, P.] Assistance Publ Hop Paris, Dept Endocrinol & Reprod Dis, F-94275 Le Kremlin Bicetre, France.
[Chanson, P.] Univ Paris Sud 11, Dept Endocrinol & Reprod Dis, F-94275 Le Kremlin Bicetre, France.
[Bronstein, M. D.] Univ Sao Paulo, Sch Med, Neuroendocrine Unit, Div Endocrinol & Metab, BR-05311970 Sao Paulo, Brazil.
[Klibanski, A.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Lamberts, S.] Erasmus MC, Dept Internal Med, Div Endocrinol, NL-3000 CA Rotterdam, Netherlands.
[Casanueva, F. F.] Univ Santiago de Compostela, Div Endocrinol CHUS, Dept Med, Santiago De Compostela 15782, Spain.
[Trainer, P.] Christie Hosp, Dept Endocrinol, Manchester M20 4BX, Lancs, England.
[Ghigo, E.] Univ Turin, Div Endocrinol, I-10129 Turin, Italy.
[Ho, K.] Garvan Inst Med Res, Pituitary Res Unit, Sydney, NSW 2010, Australia.
[Melmed, S.] Cedars Sinai Med Ctr, Dept Med, Los Angeles, CA 90048 USA.
RP Giustina, A (reprint author), Univ Brescia, Dept Med & Surg Sci, Endocrine Serv, Montichiari Hosp, Via Ciotti 154, I-25018 Montichiari, Italy.
EM a.giustina@libero.it
RI Ho, Ken/E-5832-2011; Chanson, Philippe/F-8511-2013;
OI Trainer, Peter/0000-0003-0146-3835
FU Novartis; Italfarmaco; Ipsen; Pfizer; Eli Lilly; Novo Nordsik; Sponsored
by the Pituitary Society; European Neuroendocrine Association
FX A. K. and S. L. have nothing to declare. A. G. has consulted for Ipsen,
Pfizer, and Italfarmaco and has received lecture fees from Novartis and
Italfarmaco. P. C. is a consultant for and received lecture fees from
Novartis, Ipsen, and Pfizer. The Service d'Endocrinologie et des
Maladies de la Reproduction, Hopital de Bicetre, Le Kremlin-Bicetre,
received educational and research grants from Novartis, Ipsen, and
Pfizer. M. D. B. is a consultant for Novartis and Pfizer and a speaker
for Ipsen, Novartis, and Pfizer. F. F. C. has served as a consultant for
and has received lecture fees from Novartis and Pfizer. P. T. has
received lecture fees from Pfizer and Novartis and has served on
advisory boards and received research grants from Pfizer, Novartis, and
Ipsen. E. G. has received lecture fees from Novartis and Pfizer and
received research grants from Novartis, Ipsen, Pfizer, Eli Lilly, and
Novo Nordsik. K. H. has consulted and served on advisory boards. S. M.
has consulted for Ipsen and received research grants from Ipsen and
Novartis. This work was supported by Sponsored by the Pituitary Society
and the European Neuroendocrine Association, Supported by an
unrestricted grant from Ipsen.
NR 98
TC 331
Z9 343
U1 4
U2 17
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0021-972X
EI 1945-7197
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD JUL
PY 2010
VL 95
IS 7
BP 3141
EP 3148
DI 10.1210/jc.2009-2670
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 621OS
UT WOS:000279589600009
PM 20410227
ER
PT J
AU Brent, GA
AF Brent, Gregory A.
TI The Impact of Perchlorate Exposure in Early Pregnancy: Is It Safe to
Drink the Water?
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Editorial Material
ID UNITED-STATES; URINARY PERCHLORATE; THYROID-FUNCTION; IODINE; HEALTH;
WOMEN
C1 [Brent, Gregory A.] Vet Affairs Greater Los Angeles Healthcare Syst, Endocrinol & Diabet Div, Los Angeles, CA 90073 USA.
[Brent, Gregory A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90073 USA.
[Brent, Gregory A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90073 USA.
RP Brent, GA (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Endocrinol & Diabet Div, 111D,11301 Wilshire Blvd, Los Angeles, CA 90073 USA.
EM gbrent@ucla.edu
FU NCI NIH HHS [R01 CA089364, R01 CA89364]
NR 20
TC 6
Z9 6
U1 0
U2 4
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0021-972X
EI 1945-7197
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD JUL
PY 2010
VL 95
IS 7
BP 3154
EP 3157
DI 10.1210/jc.2010-0979
PG 4
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 621OS
UT WOS:000279589600011
PM 20610607
ER
PT J
AU Trarbach, EB
Abreu, AP
Silveira, LFG
Garmes, HM
Baptista, MTM
Teles, MG
Costa, EMF
Mohammadi, M
Pitteloud, N
Mendonca, BB
Latronico, AC
AF Trarbach, Ericka B.
Abreu, Ana Paula
Gontijo Silveira, Leticia Ferreira
Garmes, Heraldo Mendes
Baptista, Maria Tereza M.
Teles, Milena Gurgel
Costa, Elaine M. F.
Mohammadi, Moosa
Pitteloud, Nelly
Mendonca, Berenice B.
Latronico, Ana Claudia
TI Nonsense Mutations in FGF8 Gene Causing Different Degrees of Human
Gonadotropin-Releasing Deficiency
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID IDIOPATHIC HYPOGONADOTROPIC HYPOGONADISM; HORMONE;
FIBROBLAST-GROWTH-FACTOR-RECEPTOR-1; INSIGHTS
AB Context: FGFR1 mutations cause isolated hypogonadotropic hypogonadism (IHH) with or without olfactory abnormalities, Kallmann syndrome, and normosmic IHH respectively. Recently, missense mutations in FGF8, a key ligand for fibroblast growth factor receptor (FGFR) 1 in the ontogenesis of GnRH, were identified in IHH patients, thus establishing FGF8 as a novel locus for human GnRH deficiency.
Objective: Our objective was to analyze the clinical, hormonal, and molecular findings of two familial IHH patients due to FGF8 gene mutations.
Methods and Patients: The entire coding region of the FGF8 gene was amplified and sequenced in two well-phenotyped IHH probands and their relatives.
Results: Two unique heterozygous nonsense mutations in FGF8(p.R127X and p.R129X) were identified in two unrelated IHH probands, which were absent in 150 control individuals. These two mutations, mapped to the core domain of FGF8, impact all four human FGF8 isoforms, and lead to the deletion of a large portion of the protein, generating nonfunctional FGF8 ligands. The p.R127X mutation was identified in an 18-yr-old Kallmann syndrome female. Her four affected siblings with normosmic IHH or delayed puberty also carried the p.R127X mutation. Additional developmental anomalies, including cleft lip and palate and neurosensorial deafness, were also present in this family. The p.R129X mutation was identified in a 30-yr-old man with familial normosmic IHH and severe GnRH deficiency.
Conclusions: We identified the first nonsense mutations in the FGF8 gene in familial IHH with variable degrees of GnRH deficiency and olfactory phenotypes, confirming that loss-of-function mutations in FGF8 cause human GnRH deficiency. (J Clin Endocrinol Metab 95: 3491-3496, 2010)
C1 [Trarbach, Ericka B.; Abreu, Ana Paula; Gontijo Silveira, Leticia Ferreira; Teles, Milena Gurgel; Costa, Elaine M. F.; Mendonca, Berenice B.; Latronico, Ana Claudia] Univ Sao Paulo, Disciplina Endocrinol, Hosp Clin,Lab Hormonios & Genet Mol LIM42, Unidade Endocrinol Desenvolvimento,Fac Med, BR-05403900 Sao Paulo, Brazil.
[Garmes, Heraldo Mendes; Baptista, Maria Tereza M.] Univ Estadual Campinas, Fac Med, Dept Clin Med, Disciplina Endocrinol, BR-13083000 Campinas, SP, Brazil.
[Mohammadi, Moosa] NYU, Sch Med, Dept Pharmacol, New York, NY 10016 USA.
[Pitteloud, Nelly] Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Boston, MA 02114 USA.
[Pitteloud, Nelly] Massachusetts Gen Hosp, Harvard Reprod Endocrine Sci Ctr, Boston, MA 02114 USA.
RP Trarbach, EB (reprint author), Univ Sao Paulo, Fac Med, Hosp Clin, Disciplina Endocrinol & Metabol, Ave Dr Eneas de Carvalho Aguiar,155,2 Degree Anda, BR-05403900 Sao Paulo, Brazil.
EM ericka@lim25.fm.usp.br
RI Mendonca, Berenice/C-2827-2012; Latronico, Ana Claudia/E-1198-2012;
Teles, Milena/H-7026-2012; Trarbach, Ericka/I-5395-2012; Silveira,
Leticia/D-3975-2014; PITTELOUD, Nelly/K-2709-2014;
OI Latronico Xavier, Ana Claudia/0000-0001-6782-693X; Mohammadi,
Moosa/0000-0003-2434-9437
FU Fundacao de Amparo a Pesquisa do Estado de Sao Paulo [FAPESP]
[07/50938-4, 06/52583-6, 05/04726-0]; Conselho Nacional de
Desenvolvimento Cientifico e Tecnologico [CNPq] [300209/2008-9,
300828/2005-5]
FX This work was supported by Fundacao de Amparo a Pesquisa do Estado de
Sao Paulo [FAPESP Grants 07/50938-4 (to E.B.T.), 06/52583-6 (to A.P.A.),
and 05/04726-0 (to A.C.L.)] and Conselho Nacional de Desenvolvimento
Cientifico e Tecnologico [CNPq Grants 300209/2008-9 (to A.C.L.) and
300828/2005-5 (to B.B.M.)].
NR 20
TC 34
Z9 35
U1 0
U2 2
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0021-972X
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD JUL
PY 2010
VL 95
IS 7
BP 3491
EP 3496
DI 10.1210/jc.2010-0176
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 621OS
UT WOS:000279589600055
PM 20463092
ER
PT J
AU Santen, RJ
Allred, DC
Ardoin, SP
Archer, DF
Boyd, N
Braunstein, GD
Burger, HG
Colditz, GA
Davis, SR
Gambacciani, M
Gower, BA
Henderson, VW
Jarjour, WN
Karas, RH
Kleerekoper, M
Lobo, RA
Manson, JE
Marsden, J
Martin, KA
Martin, L
Pinkerton, JV
Rubinow, DR
Teede, H
Thiboutot, DM
Utian, WH
AF Santen, Richard J.
Allred, D. Craig
Ardoin, Stacy P.
Archer, David F.
Boyd, Norman
Braunstein, Glenn D.
Burger, Henry G.
Colditz, Graham A.
Davis, Susan R.
Gambacciani, Marco
Gower, Barbara A.
Henderson, Victor W.
Jarjour, Wael N.
Karas, Richard H.
Kleerekoper, Michael
Lobo, Roger A.
Manson, JoAnn E.
Marsden, Jo
Martin, Kathryn A.
Martin, Lisa
Pinkerton, JoAnn V.
Rubinow, David R.
Teede, Helena
Thiboutot, Diane M.
Utian, Wulf H.
TI Postmenopausal Hormone Therapy: An Endocrine Society Scientific
Statement
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID ESTROGEN-PLUS-PROGESTIN; BREAST-CANCER RISK; RANDOMIZED
CONTROLLED-TRIAL; QUALITY-OF-LIFE; PLACEBO-CONTROLLED TRIAL; CONJUGATED
EQUINE ESTROGENS; BONE-MINERAL DENSITY; SURGICALLY MENOPAUSAL WOMEN;
LOW-DOSE ESTRADIOL; HYPOACTIVE SEXUAL DESIRE
AB Objective: Our objective was to provide a scholarly review of the published literature on menopausal hormonal therapy (MHT), make scientifically valid assessments of the available data, and grade the level of evidence available for each clinically important endpoint.
Participants in Development of Scientific Statement: The 12-member Scientific Statement Task Force of The Endocrine Society selected the leader of the statement development group (R.J.S.) and suggested experts with expertise in specific areas. In conjunction with the Task Force, lead authors (n = 25) and peer reviewers (n = 14) for each specific topic were selected. All discussions regarding content and grading of evidence occurred via teleconference or electronic and written correspondence. No funding was provided to any expert or peer reviewer, and all participants volunteered their time to prepare this Scientific Statement.
Evidence: Each expert conducted extensive literature searches of case control, cohort, and randomized controlled trials as well as meta-analyses, Cochrane reviews, and Position Statements from other professional societies in order to compile and evaluate available evidence. No unpublished data were used to draw conclusions from the evidence.
Consensus Process: A consensus was reached after several iterations. Each topic was considered separately, and a consensus was achieved as to content to be included and conclusions reached between the primary author and the peer reviewer specific to that topic. In a separate iteration, the quality of evidence was judged using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) system in common use by The Endocrine Society for preparing clinical guidelines. The final iteration involved responses to four levels of additional review: 1) general comments offered by each of the 25 authors; 2) comments of the individual Task Force members; 3) critiques by the reviewers of the Journal of Clinical Endocrinology & Metabolism; and 4) suggestions offered by the Council and members of The Endocrine Society. The lead author compiled each individual topic into a coherent document and finalized the content for the final Statement. The writing process was analogous to preparation of a multiauthored textbook with input from individual authors and the textbook editors.
Conclusions: The major conclusions related to the overall benefits and risks of MHT expressed as the number of women per 1000 taking MHT for 5yr who would experience benefit or harm. Primary areas of benefit included relief of hot flashes and symptoms of urogenital atrophy and prevention of fractures and diabetes. Risks included venothrombotic episodes, stroke, and cholecystitis. In the subgroup of women starting MHT between ages 50 and 59 or less than 10 yr after onset of menopause, congruent trends suggested additional benefit including reduction of overall mortality and coronary artery disease. In this subgroup, estrogen plus some progestogens increased the risk of breast cancer, whereas estrogen alone did not. Beneficial effects on colorectal and endometrial cancer and harmful effects on ovarian cancer occurred but affected only a small number of women. Data from the various Women's Health Initiative studies, which involved women of average age 63, cannot be appropriately applied to calculate risks and benefits of MHT in women starting shortly after menopause. At the present time, assessments of benefit and risk in these younger women are based on lower levels of evidence. (J Clin Endocrinol Metab 95: S7-S66, 2010)
C1 [Santen, Richard J.] Univ Virginia, Div Endocrinol & Metab, Charlottesville, VA 22908 USA.
[Pinkerton, JoAnn V.] Univ Virginia, Dept Obstet & Gynecol, Charlottesville, VA 22908 USA.
[Karas, Richard H.] Tufts Univ, Sch Med, Mol Cardiol Res Inst, Tufts Med Ctr, Boston, MA 02111 USA.
[Teede, Helena] Jean Hailes Res Ctr, Sch Publ Hlth, Melbourne, Vic 3168, Australia.
[Burger, Henry G.] Monash Med Ctr, Prince Henrys Inst Med Res, Melbourne, Vic 3168, Australia.
[Davis, Susan R.] Monash Univ, Dept Med, Womens Hlth Program, Melbourne, Vic 3181, Australia.
[Henderson, Victor W.] Stanford Univ, Dept Hlth Res & Policy Epidemiol, Stanford, CA 94305 USA.
[Henderson, Victor W.] Stanford Univ, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA.
[Allred, D. Craig] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
[Colditz, Graham A.] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA.
[Gower, Barbara A.] Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA.
[Kleerekoper, Michael] St Joseph Hosp, Reichert Hlth Ctr, Ypsilanti, MI 48197 USA.
[Ardoin, Stacy P.; Jarjour, Wael N.] Ohio State Univ, Sch Med, Div Rheumatol & Immunol, Columbus, OH 43219 USA.
[Gambacciani, Marco] Univ Pisa, Dept Obstet & Gynecol, I-56100 Pisa, Italy.
[Boyd, Norman; Martin, Lisa] Univ Toronto, Dept Nutr Sci, Dept Med, Toronto, ON M5G 2C1, Canada.
[Braunstein, Glenn D.] Cedars Sinai Med Ctr, Dept Med, Los Angeles, CA 90048 USA.
[Lobo, Roger A.] Columbia Univ, Med Ctr, Dept Obstet & Gynecol, New York, NY 10037 USA.
[Archer, David F.] Eastern Virginia Med Sch, Clin Res Ctr, Norfolk, VA 23507 USA.
[Utian, Wulf H.] N Amer Menopause Soc, Mayfield Hts, OH 44124 USA.
[Martin, Kathryn A.] Massachusetts Gen Hosp, Waltham, MA 02453 USA.
[Rubinow, David R.] Univ N Carolina, Chapel Hill, NC 27516 USA.
[Thiboutot, Diane M.] Penn State Univ, Sch Med, Milton S Hershey Med Ctr, Dermatol Sect, Hershey, PA 17033 USA.
[Marsden, Jo] Kings Coll Hosp London, London SE5 9RS, England.
[Manson, JoAnn E.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02215 USA.
RP Santen, RJ (reprint author), Univ Virginia Hlth Syst, Div Endocrinol, POB 801416, Charlottesville, VA 22908 USA.
EM RJS5Y@VIRGINIA.EDU
RI Colditz, Graham/A-3963-2009
OI Colditz, Graham/0000-0002-7307-0291
NR 517
TC 228
Z9 243
U1 7
U2 40
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0021-972X
EI 1945-7197
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD JUL
PY 2010
VL 95
IS 7
SU 1
BP S7
EP +
DI 10.1210/jc.2009-2509
PG 61
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 626OX
UT WOS:000279976400001
PM 20566620
ER
PT J
AU Bloch, MJ
Basile, JN
AF Bloch, Michael J.
Basile, Jan N.
TI Is There Accord in ACCORD? Lower Blood Pressure Targets in Type 2
Diabetes Does Not Lead to Fewer Cardiovascular Events Except for
Reductions in Stroke
SO JOURNAL OF CLINICAL HYPERTENSION
LA English
DT Editorial Material
ID MICROVASCULAR COMPLICATIONS; RISK; MELLITUS; HOT
C1 [Bloch, Michael J.] St Marys Reg Med Ctr, Risk Reduct Ctr, Reno, NV 89503 USA.
[Bloch, Michael J.] St Marys Reg Med Ctr, Vasc Inst, Reno, NV 89503 USA.
[Bloch, Michael J.] Univ Nevada, Sch Med, Dept Med, Reno, NV 89557 USA.
[Basile, Jan N.] Med Univ S Carolina, Div Gen Internal Med Geriat, Seinsheimer Cardiovasc Hlth Program, Charleston, SC USA.
[Basile, Jan N.] Ralph H Johnson VA Med Ctr, Charleston, SC USA.
RP Bloch, MJ (reprint author), St Marys Reg Med Ctr, Risk Reduct Ctr, 645 N Arlington St,Suite 460, Reno, NV 89503 USA.
EM mbloch@aol.com
NR 8
TC 5
Z9 5
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1524-6175
J9 J CLIN HYPERTENS
JI J. Clin. Hypertens.
PD JUL
PY 2010
VL 12
IS 7
BP 472
EP 477
DI 10.1111/j.1751-7176.2010.00333.x
PG 6
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 622NC
UT WOS:000279669500002
PM 20629807
ER
PT J
AU Greenblatt, MB
Shim, JH
Zou, WG
Sitara, D
Schweitzer, M
Hu, D
Lotinun, S
Sano, Y
Baron, R
Park, JM
Arthur, S
Xie, M
Schneider, MD
Zhai, B
Gygi, S
Davis, R
Glimcher, LH
AF Greenblatt, Matthew B.
Shim, Jae-Hyuck
Zou, Weiguo
Sitara, Despina
Schweitzer, Michelle
Hu, Dorothy
Lotinun, Sutada
Sano, Yasuyo
Baron, Roland
Park, Jin Mo
Arthur, Simon
Xie, Min
Schneider, Michael D.
Zhai, Bo
Gygi, Steven
Davis, Roger
Glimcher, Laurie H.
TI The p38 MAPK pathway is essential for skeletogenesis and bone
homeostasis in mice
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID ACTIVATED PROTEIN-KINASE; CLEIDOCRANIAL DYSPLASIA; OSTEOBLAST
DIFFERENTIATION; TRANSCRIPTION FACTOR; ESSENTIAL REGULATOR; SELECTIVE
ACTIVATION; SIGNAL-TRANSDUCTION; GENE-EXPRESSION; P38-ALPHA; CELLS
AB Nearly every extracellular ligand that has been found to play a role in regulating bone biology acts, at least in part, through MAPK pathways. Nevertheless, much remains to be learned about the contribution of MAPKs to osteoblast biology in vivo. Here we report that the p38 MAPK pathway is required for normal skeletogenesis in mice, as mice with deletion of any of the MAPK pathway member-encoding genes MAPK kinase 3 (Mkk3), Mkk6, p38a, or p38b displayed profoundly reduced bone mass secondary to defective osteoblast differentiation. Among the MAPK kinase kinase (MAP3K) family, we identified TGF-beta-activated kinase 1 (TAK1; also known as MAP3K7) as the critical activator upstream of p38 in osteoblasts. Osteoblast-specific deletion of Tak1 resulted in clavicular hypoplasia and delayed fontanelle fusion, a phenotype similar to the cleidocranial dysplasia observed in humans haploinsufficient for the transcription factor runt-related transcription factor 2 (Runx2). Mechanistic analysis revealed that the TAK1-MKK3/6-p38 MAPK axis phosphorylated Runx2, promoting its association with the coactivator CREB-binding protein (CBP), which was required to regulate osteoblast genetic programs. These findings reveal an in vivo function for p38 beta and establish that MAPK signaling is essential for bone formation in vivo. These results also suggest that selective p38 beta agonists may represent attractive therapeutic agents to prevent bone loss associated with osteoporosis and aging.
C1 [Greenblatt, Matthew B.; Shim, Jae-Hyuck; Zou, Weiguo; Sitara, Despina; Schweitzer, Michelle; Hu, Dorothy; Glimcher, Laurie H.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA.
[Greenblatt, Matthew B.; Shim, Jae-Hyuck; Zou, Weiguo; Sitara, Despina; Schweitzer, Michelle; Hu, Dorothy; Glimcher, Laurie H.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Lotinun, Sutada; Baron, Roland] Harvard Univ, Sch Dent, Dept Oral Med Infect & Immun, Boston, MA 02115 USA.
[Sano, Yasuyo; Park, Jin Mo] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA.
[Sano, Yasuyo; Park, Jin Mo] Harvard Univ, Sch Med, Charlestown, MA USA.
[Arthur, Simon] Univ Dundee, Sch Life Sci, MRC Prot Phosphorylat Unit, Dundee, Scotland.
[Xie, Min] Univ Texas SW Med Ctr Dallas, Dept Med, Dallas, TX 75390 USA.
[Schneider, Michael D.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England.
[Zhai, Bo; Gygi, Steven] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA.
[Davis, Roger] Univ Massachusetts, Sch Med, Howard Hughes Med Inst, Worcester, MA 01605 USA.
[Davis, Roger] Univ Massachusetts, Sch Med, Dept Biochem & Mol Biol, Program Mol Med, Worcester, MA USA.
RP Glimcher, LH (reprint author), FXB Rm 205,651 Huntington Ave, Boston, MA 02115 USA.
EM lglimche@hsph.harvard.edu
RI Arthur, J. Simon/B-8058-2010;
OI Arthur, J. Simon/0000-0002-8135-1958; SITARA,
DESPINA/0000-0002-4836-5039; Schneider, Michael/0000-0001-9645-1938
FU NIH [HD055601, HL52555]; Merck Pharmaceutical Company; Arthritis
Foundation
FX We would like to thank Judy Reilly, Rebecca Drapp, Nicholas Brady,
Heather De Rivera, and Yeon-suk Yang for technical assistance and Marc
Wein, Henry Kronenberg, Bjorn Olsen, Dennis Zaller, Dallas Jones, and
Antonios Aliprantis for helpful discussions. We also thank the many
individuals who provided valuable reagents. This work was supported by
NIH grant HD055601 (to L.H. Glimcher), a grant from the Merck
Pharmaceutical Company (to L.H. Glimcher), and NIH HL52555 (to M.D.
Schneider); J. Shim was supported by an Arthritis Foundation
postdoctoral fellowship.
NR 57
TC 133
Z9 143
U1 2
U2 13
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
J9 J CLIN INVEST
JI J. Clin. Invest.
PD JUL
PY 2010
VL 120
IS 7
BP 2457
EP 2473
DI 10.1172/JCI42285
PG 17
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 620ZZ
UT WOS:000279544000024
PM 20551513
ER
PT J
AU Johnson, SM
Torrice, CD
Bell, JF
Monahan, KB
Jiang, Q
Wang, Y
Ramsey, MR
Jin, JA
Wong, KK
Su, LS
Zhou, DH
Sharpless, NE
AF Johnson, Soren M.
Torrice, Chad D.
Bell, Jessica F.
Monahan, Kimberly B.
Jiang, Qi
Wang, Yong
Ramsey, Matthew R.
Jin, Jian
Wong, Kwok-Kin
Su, Lishan
Zhou, Daohong
Sharpless, Norman E.
TI Mitigation of hematologic radiation toxicity in mice through
pharmacological quiescence induced by CDK4/6 inhibition
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID COLONY-STIMULATING FACTOR; CYCLIN-DEPENDENT KINASES; CHINESE HAMSTER
CELLS; STRAND BREAK REPAIR; X-RAY SENSITIVITY; DNA-DAMAGE; HEMATOPOIETIC
STEM; IONIZING-RADIATION; IN-VIVO; MYELODYSPLASTIC SYNDROME
AB Total body irradiation (TBI) can induce lethal myelosuppression, due to the sensitivity of proliferating hematopoietic stem/progenitor cells (HSPCs) to ionizing radiation (IR). No effective therapy exists to mitigate the hematologic toxicities of TBI. Here, using selective and structurally distinct small molecule inhibitors of cyclin-dependent kinase 4 (CDK4) and CDK6, we have demonstrated that selective cellular quiescence increases radioresistance of human cell lines in vitro and mice in vivo. Cell lines dependent on CDK4/6 were resistant to IR and other DNA-damaging agents when treated with CDK4/6 inhibitors. In contrast, CDK4/6 inhibitors did not protect cell lines that proliferated independently of CDK4/6 activity. Treatment of wild-type mice with CDK4/6 inhibitors induced reversible pharmacological quiescence (PQ) of early HSPCs but not most other cycling cells in the bone marrow or other tissues. Selective PQ of HSPCs decreased the hematopoietic toxicity of TBI, even when the CDK4/6 inhibitor was administered several hours after TBI. Moreover, PQ at the time of administration of therapeutic IR to mice harboring autochthonous cancers reduced treatment toxicity without compromising the therapeutic tumor response. These results demonstrate an effective method to mitigate the hematopoietic toxicity of IR in mammals, which may be potentially useful after radiological disaster or as an adjuvant to anticancer therapy.
C1 [Johnson, Soren M.; Torrice, Chad D.; Bell, Jessica F.; Monahan, Kimberly B.; Ramsey, Matthew R.; Sharpless, Norman E.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Sch Med, Dept Genet, Chapel Hill, NC 27599 USA.
[Johnson, Soren M.; Torrice, Chad D.; Monahan, Kimberly B.; Ramsey, Matthew R.; Sharpless, Norman E.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Sch Med, Dept Med, Chapel Hill, NC 27599 USA.
[Bell, Jessica F.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Sch Med, Dept Pediat, Chapel Hill, NC 27599 USA.
[Jiang, Qi; Su, Lishan] Univ N Carolina, Lineberger Comprehens Canc Ctr, Sch Med, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA.
[Wang, Yong; Zhou, Daohong] Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA.
[Jin, Jian] Univ N Carolina, Eshelman Sch Pharm, Ctr Integrat Chem Biol & Drug Discovery, Chapel Hill, NC 27599 USA.
[Wong, Kwok-Kin] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA.
[Sharpless, Norman E.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Sch Med, Dept Toxicol, Chapel Hill, NC 27599 USA.
RP Sharpless, NE (reprint author), Univ N Carolina, Lineberger Comprehens Canc Ctr, Sch Med, Dept Genet, CB 7295, Chapel Hill, NC 27599 USA.
EM nes@med.unc.edu
OI Ramsey, Matthew/0000-0003-2402-8502; wong, kwok kin/0000-0001-6323-235X
FU Golfers Against Cancer Foundation; Ellison Medical Foundation; Burroughs
Wellcome Fund; National Institutes of Health [RO1-AG024379,
RO1-AI077454, RO1-AI080432, T32-GM008719, F30-AG034806, GM008581]; Jimmy
V foundation; National Cancer Foundation; University of North Carolina
Lineberger Comprehensive Cancer Center
FX We wish to thank Jim Bear, Arlene Bridges, Tao Cheng, Hanno Hock, Yan
Liu, Chuck Perou, Gordon Peters, and Dave Roadcap for advice and
reagents; Derrick Rossi, Sean Morrison, and Yue Xiong for critical
reading of the manuscript; and Peter Toogood and Gerrit Los of Pfizer
Inc., who supplied PD0332991 and compound-related expertise. This work
was supported by the University of North Carolina Lineberger
Comprehensive Cancer Center Mouse Phase I Unit and grants from the
Golfers Against Cancer Foundation, the Ellison Medical Foundation, the
Burroughs Wellcome Fund, and the National Institutes of Health
(RO1-AG024379, RO1-AI077454, RO1-AI080432, T32-GM008719, F30-AG034806,
GM008581). J.F. Bell was supported by a career development award from
the Jimmy V foundation. K.B. Monahan was supported by an award from the
National Cancer Foundation.
NR 60
TC 74
Z9 76
U1 2
U2 6
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
J9 J CLIN INVEST
JI J. Clin. Invest.
PD JUL
PY 2010
VL 120
IS 7
BP 2528
EP 2536
DI 10.1172/JCI41402
PG 9
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 620ZZ
UT WOS:000279544000030
PM 20577054
ER
PT J
AU Swirski, FK
Wildgruber, M
Ueno, T
Figueiredo, JL
Panizzi, P
Iwamoto, Y
Zhang, E
Stone, JR
Rodriguez, E
Chen, JW
Pittet, MJ
Weissleder, R
Nahrendorf, M
AF Swirski, Filip K.
Wildgruber, Moritz
Ueno, Takuya
Figueiredo, Jose-Luiz
Panizzi, Peter
Iwamoto, Yoshiko
Zhang, Elizabeth
Stone, James R.
Rodriguez, Elisenda
Chen, John W.
Pittet, Mikael J.
Weissleder, Ralph
Nahrendorf, Matthias
TI Myeloperoxidase-rich Ly-6C(+) myeloid cells infiltrate allografts and
contribute to an imaging signature of organ rejection in mice
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID HEART-TRANSPLANTATION; NONINVASIVE DETECTION; MONOCYTE SUBSETS;
MACROPHAGES; INFLAMMATION; DYSFUNCTION; INFECTION; BIOPSIES
AB Rates of graft rejection are high among recipients of heart transplants. The onset and progression of clinically significant heart transplant rejection are currently monitored by serial biopsy, but this approach is highly invasive and lacks sensitivity. Here, we have developed what we believe to be a new technique to measure organ rejection noninvasively that involves the exploration of tissue-infiltrating leukocytes as biomarker sources for diagnostic imaging. Specifically, we profiled the myeloid response in a murine model of heart transplantation with the aim of defining and validating an imaging signature of graft rejection. Ly-6C(hi) monocytes, which promote inflammation, accumulated progressively in allografts but only transiently in isografts. Ly-6C(lo) monocytes, which help resolve inflammation, did not accumulate, although they composed the majority of the few remaining monocytes in isografts. The persistence of Ly-6C(hi) monocytes in allografts prompted us to screen for a Ly-6C(hi) monocyte-associated imaging marker. Low-density array data revealed that Ly-6C(hi) monocytes express 10-fold higher levels of myeloperoxidase (MPO) than Ly-6C(lo) monocytes. Noninvasive magnetic resonance imaging of MPO with an MPO-activatable Gd-chelate revealed a spatially defined T1-weighted signal in rejected allografts but not in isografts or MPO-deficient allograft recipients. Flow cytometry, enzymography, and histology validated the approach by mapping MPO activity to Ly-6C(hi) monocytes and neutrophils. Thus, MPO imaging represents a potential alternative to the current invasive clinical standard by which transplants are monitored.
C1 [Weissleder, Ralph; Nahrendorf, Matthias] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02124 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, CPZN 5206,185 Cambridge St, Boston, MA 02124 USA.
EM rweissleder@mgh.harvard.edu; mnahrendorf@mgh.harvard.edu
OI Panizzi, Peter/0000-0003-0141-8807
FU NIH [R01HL095629, U24-CA092782, U01-HL080731, K08HL081170]; EC
FX The authors thank Cory Siegel, Aleksey Chudnovskiy, and Rostic Gorbatov
for technical assistance. This work was supported in parts by NIH grants
R01HL095629, U24-CA092782, U01-HL080731, K08HL081170, and the EC-Marie
Curie grant OIF (Molecular Imaging 39639).
NR 30
TC 46
Z9 46
U1 0
U2 3
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
J9 J CLIN INVEST
JI J. Clin. Invest.
PD JUL
PY 2010
VL 120
IS 7
BP 2627
EP 2634
DI 10.1172/JCI42304
PG 8
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 620ZZ
UT WOS:000279544000039
PM 20577051
ER
PT J
AU Swenson, JM
Wong, B
Simor, AE
Thomson, RB
Ferraro, MJ
Hardy, DJ
Hindler, J
Jorgensen, J
Reller, LB
Traczewski, M
McDougal, LK
Patel, JB
AF Swenson, Jana M.
Wong, Betty
Simor, Andrew E.
Thomson, Richard B.
Ferraro, Mary Jane
Hardy, Dwight J.
Hindler, Janet
Jorgensen, James
Reller, L. Barth
Traczewski, Maria
McDougal, Linda K.
Patel, Jean B.
TI Multicenter Study To Determine Disk Diffusion and Broth Microdilution
Criteria for Prediction of High- and Low-Level Mupirocin Resistance in
Staphylococcus aureus
SO JOURNAL OF CLINICAL MICROBIOLOGY
LA English
DT Article
ID INTERPRETIVE CRITERIA; SUSCEPTIBILITY; HOSPITALS; TRIAL
AB Mupirocin susceptibility testing of Staphylococcus aureus has become more important as mupirocin is used more widely to suppress or eliminate S. aureus colonization and prevent subsequent health care-and community- associated infections. The present multicenter study evaluated two susceptibility testing screening methods to detect mupirocin high-level resistance (HLR), broth microdilution (BMD) MICs of >= 512 mu g/ml, and a 6-mm zone diameter for a disk diffusion (DD) test with a 200-mu g disk. Initial testing indicated that with Clinical and Laboratory Standards Institute methods for BMD and DD testing, the optimal conditions for the detection of mupirocin HLR were 24 h of incubation and reading of the DD zone diameters with transmitted light. Using the presence or absence of mupA as the "gold standard" for HLR, the sensitivity and specificity of a single-well 256 mu g/ml BMD test were 97 and 99%, respectively, and those for the 200-mu g disk test were 98 and 99%, respectively. Testing with two disks, 200 mu g and 5 mu g, was evaluated for its ability to distinguish HLR isolates (MICs >= 512 mu g/ml), low-level-resistant (LLR) isolates (MICs = 8 to 256 mu g/ml), and susceptible isolates (MICs <= 4 mu g/ml). Using no zone with both disks as an indication of HLR and no zone with the 5-mu g disk plus any zone with the 200-mu g disk as LLR, only 3 of the 340 isolates were misclassified, with 3 susceptible isolates being classified as LLR. Use of standardized MIC or disk tests could enable the detection of emerging high-and low-level mupirocin resistance in S. aureus.
C1 [Swenson, Jana M.; Wong, Betty; McDougal, Linda K.; Patel, Jean B.] Ctr Dis Control & Prevent, Div Healthcare Qual Promot, Antimicrobial Resistance Team, Atlanta, GA 30333 USA.
[Simor, Andrew E.] Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada.
[Thomson, Richard B.] N Shore Univ Hlth Syst, Evanston Hosp, Evanston, IL 60201 USA.
[Ferraro, Mary Jane] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Hardy, Dwight J.] Univ Rochester, Med Ctr, Rochester, NY 14642 USA.
[Hindler, Janet] Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90095 USA.
[Jorgensen, James] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Reller, L. Barth] Duke Univ, Med Ctr, Durham, NC 27710 USA.
[Traczewski, Maria] Inst Clin Microbiol, Wilsonville, OR 97070 USA.
RP Swenson, JM (reprint author), Ctr Dis Control & Prevent, Div Healthcare Qual Promot, Antimicrobial Resistance Team, Mailstop G08,1600 Clifton Rd NE, Atlanta, GA 30333 USA.
EM jms1@cdc.gov
NR 23
TC 8
Z9 8
U1 0
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0095-1137
J9 J CLIN MICROBIOL
JI J. Clin. Microbiol.
PD JUL
PY 2010
VL 48
IS 7
BP 2469
EP 2475
DI 10.1128/JCM.00340-10
PG 7
WC Microbiology
SC Microbiology
GA 617YV
UT WOS:000279318700022
PM 20444971
ER
PT J
AU Monk, BJ
Herzog, TJ
Kaye, SB
Krasner, CN
Vermorken, JB
Muggia, FM
Pujade-Lauraine, E
Lisyanskaya, AS
Makhson, AN
Rolski, J
Gorbounova, VA
Ghatage, P
Bidzinski, M
Shen, K
Ngan, HYS
Vergote, IB
Nam, JH
Park, YC
Lebedinsky, CA
Poveda, AM
AF Monk, Bradley J.
Herzog, Thomas J.
Kaye, Stanley B.
Krasner, Carolyn N.
Vermorken, Jan B.
Muggia, Franco M.
Pujade-Lauraine, Eric
Lisyanskaya, Alla S.
Makhson, Anatoly N.
Rolski, Janusz
Gorbounova, Vera A.
Ghatage, Prafull
Bidzinski, Mariusz
Shen, Keng
Ngan, Hextan Yuen-Sheung
Vergote, Ignace B.
Nam, Joo-Hyun
Park, Youn Choi
Lebedinsky, Claudia A.
Poveda, Andres M.
TI Trabectedin Plus Pegylated Liposomal Doxorubicin in Recurrent Ovarian
Cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID SOFT-TISSUE SARCOMA; QUALITY-OF-LIFE; PACLITAXEL; PLATINUM; ET-743;
TOPOTECAN; WOMEN; TRIAL; HEPATOTOXICITY; COMBINATION
AB Purpose The objective of this study was to compare the efficacy and safety of trabectedin plus pegylated liposomal doxorubicin (PLD) with that of PLD alone in women with recurrent ovarian cancer after failure of first-line, platinum-based chemotherapy.
Patients and Methods Women >= 18 years, stratified by performance status (0 to 1 v 2) and platinum sensitivity, were randomly assigned to receive an intravenous infusion of PLD 30 mg/m(2) followed by a 3-hour infusion of trabectedin 1.1 mg/m(2) every 3 weeks or PLD 50 mg/m(2) every 4 weeks. The primary end point was progression-free survival (PFS) by independent radiology assessment.
Results Patients (N = 672) were randomly assigned to trabectedin/PLD (n = 337) or PLD (n = 335). Median PFS was 7.3 months with trabectedin/PLD v 5.8 months with PLD (hazard ratio, 0.79; 95% CI, 0.65 to 0.96; P = .0190). For platinum-sensitive patients, median PFS was 9.2 months v 7.5 months, respectively (hazard ratio, 0.73; 95% CI, 0.56 to 0.95; P = .0170). Overall response rate (ORR) was 27.6% for trabectedin/PLD v 18.8% for PLD (P = .0080); for platinum-sensitive patients, it was 35.3% v 22.6% (P = .0042), respectively. ORR, PFS, and overall survival among platinum-resistant patients were not statistically different. Neutropenia was more common with trabectedin/PLD. Grade 3 to 4 transaminase elevations were also more common with the combination but were transient and noncumulative. Hand-foot syndrome and mucositis were less frequent with trabectedin/PLD than with PLD alone.
Conclusion When combined with PLD, trabectedin improves PFS and ORR over PLD alone with acceptable tolerance in the second-line treatment of recurrent ovarian cancer.
C1 [Monk, Bradley J.] UCI Med Ctr, Orange, CA USA.
Univ Calif Irvine, Irvine, CA USA.
Columbia Univ, Coll Phys & Surg, New York, NY 10027 USA.
New York Univ Hosp, New York, NY USA.
Royal Marsden Hosp, Surrey, England.
Massachusetts Gen Hosp, Gillette Ctr Womens Studies, Boston, MA 02114 USA.
Univ Antwerp Hosp, Edegem, Belgium.
Univ Hosp, Leuven, Belgium.
Univ Paris 05, Hop Hotel Dieu, AP HP, Paris, France.
SPBSIH City Clin Oncol Dispensary, St Petersburg, Russia.
Moscow City Oncol Hosp, Moscow, Russia.
SI Russian Oncol Sci Ctr, Moscow, Russia.
Inst Marii Sklodowskiej Curie Oddzial Krakow, Ctr Onkol, Krakow, Poland.
Inst Maria Sklodowska, Mem Canc Ctr, Curie Warsaw, Poland.
Tom Baker Canc Clin, Calgary, AB, Canada.
Beijing Union Med Coll Hosp, Beijing, Peoples R China.
Univ Hong Kong, Queen Mary Hosp, Pokfulam, Hong Kong, Peoples R China.
Univ Ulsan, Coll Med, Asan Med Ctr, Seoul, South Korea.
Johnson & Johnson Pharmaceut Res & Dev, Raritan, NJ USA.
PharmaMar, Madrid, Spain.
Inst Valenciano Oncol, Valencia, Spain.
RP Monk, BJ (reprint author), UCI Med Ctr, 101 City Dr,Bldg 56,Suite 260, Orange, CA USA.
EM bjmonk@uci.edu
OI Muggia, Franco/0000-0003-0703-9146
FU Johnson Johnson; Johnson & Johnson Pharmaceutical Research & Development
Expert Testimony; Johnson & Johnson-Oncologic Drugs Advisory Committee
FX Research Funding: Bradley J. Monk, Johnson & Johnson; Hextan Yuen-Sheung
Ngan, Johnson & Johnson Pharmaceutical Research & Development Expert
Testimony: Bradley J. Monk, Johnson & Johnson-Oncologic Drugs Advisory
Committee (C) Other Remuneration: None
NR 28
TC 170
Z9 175
U1 0
U2 11
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 JUL 1
PY 2010
VL 28
IS 19
BP 3107
EP 3114
DI 10.1200/JCO.2009.25.4037
PG 8
WC Oncology
SC Oncology
GA 617AX
UT WOS:000279254300004
PM 20516432
ER
PT J
AU Mandelblatt, JS
Sheppard, VB
Hurria, A
Kimmick, G
Isaacs, C
Taylor, KL
Kornblith, AB
Noone, AM
Luta, G
Tallarico, M
Barry, WT
Hunegs, L
Zon, R
Naughton, M
Winer, E
Hudis, C
Edge, SB
Cohen, HJ
Muss, H
AF Mandelblatt, Jeanne S.
Sheppard, Vanessa B.
Hurria, Arti
Kimmick, Gretchen
Isaacs, Claudine
Taylor, Kathryn L.
Kornblith, Alice B.
Noone, Anne-Michelle
Luta, Gheorghe
Tallarico, Michelle
Barry, William T.
Hunegs, Lisa
Zon, Robin
Naughton, Michael
Winer, Eric
Hudis, Clifford
Edge, Stephen B.
Cohen, Harvey Jay
Muss, Hyman
TI Breast Cancer Adjuvant Chemotherapy Decisions in Older Women: The Role
of Patient Preference and Interactions With Physicians
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID QUALITY-OF-LIFE; ELDERLY-WOMEN; HORMONAL-THERAPY; CLINICAL-TRIALS;
PRIMARY-CARE; AGE; COMMUNICATION; CARCINOMA; ONCOLOGY; SURVIVAL
AB Purpose
Breast cancer chemotherapy decisions in patients >= 65 years old (older) are complex because of comorbidity, toxicity, and limited data on patient preference. We examined relationships between preferences and chemotherapy use.
Methods
Older women (n = 934) diagnosed with invasive (>= 1 cm), nonmetastatic breast cancer from 2004 to 2008 were recruited from 53 cooperative group sites. Data were collected from patient interviews (87% complete), physician survey (93% complete), and charts. Logistic regression and multiple imputation methods were used to assess associations between chemotherapy and independent variables. Chemotherapy use was also evaluated according to the following two groups: indicated (estrogen receptor [ER] negative and/or node positive) and possibly indicated (ER positive and node negative).
Results
Mean patient age was 73 years (range, 65 to 100 years). Unadjusted chemotherapy rates were 69% in the indicated group and 16% in the possibly indicated group. Women who would choose chemotherapy for an increase in survival of <= 12 months had 3.9 times (95% CI, 2.4 to 6.3 times; P < .001) higher odds of receiving chemotherapy than women with lower preferences, controlling for covariates. Stronger preferences were seen when chemotherapy could be indicated (odds ratio [OR] = 7.7; 95% CI, 3.8 to 16; P < .001) than when treatment might be possibly indicated (OR = 1.9; 95% CI, 1.0 to 3.8; P = .06). Higher patient rating of provider communication was also related to chemotherapy use in the possibly indicated group (OR = 1.9 per 5-point increase in communication score; 95% CI, 1.4 to 2.8; P < .001) but not in the indicated group (P = .15).
Conclusion
Older women's preferences and communication with providers are important correlates of chemotherapy use, especially when benefits are more equivocal.
C1 [Mandelblatt, Jeanne S.] Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA.
Georgetown Univ, Sch Med, Washington, DC USA.
City Hope Natl Med Ctr, Los Angeles, CA USA.
Duke Univ, Med Ctr, Durham, NC 27706 USA.
Canc & Leukemia Grp B Stat Ctr, Durham, NC USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
No Indiana Canc Res Consortium, South Bend, IN USA.
Washington Univ, Sch Med, St Louis, MO USA.
Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
Univ Buffalo, Roswell Pk Canc Inst, Buffalo, NY USA.
Univ Vermont, Fletcher Allen Hlth Care, Burlington, VT USA.
RP Mandelblatt, JS (reprint author), Lombardi Comprehens Canc Ctr, 3300 Whitehaven Blvd,Ste 4100, Washington, DC 20007 USA.
EM mandelbj@georgetown.edu
OI Luta, George/0000-0001-9013-2207; Luta, George/0000-0002-4035-7632
FU Abraxis BioScience, Pfizer; Gretchen Kimmick; AstraZeneca; Claudine
Isaacs, Bayer Pharmaceuticals Expert Testimony
FX Employment or Leadership Position: None Consultant or Advisory Role:
Arti Hurria, Amgen (C); Gretchen Kimmick, AstraZeneca (C), Pfizer (C),
Novartis (C) Stock Ownership: None Honoraria: Gretchen Kimmick,
AstraZeneca, Pfizer, Novartis; Claudine Isaacs, Pfizer, AstraZeneca,
Novartis, Genentech Research Funding: Arti Hurria, Abraxis BioScience,
Pfizer; Gretchen Kimmick, AstraZeneca; Claudine Isaacs, Bayer
Pharmaceuticals Expert Testimony: None Other Remuneration: None
NR 66
TC 38
Z9 38
U1 0
U2 4
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 JUL 1
PY 2010
VL 28
IS 19
BP 3146
EP 3153
DI 10.1200/JCO.2009.24.3295
PG 8
WC Oncology
SC Oncology
GA 617AX
UT WOS:000279254300009
PM 20516438
ER
PT J
AU Bhattacharya, S
Fyfe, G
Gray, R
Sargent, DL
AF Bhattacharya, Suman
Fyfe, Gwen
Gray, Robert
Sargent, Daniel L.
TI Applying Sensitivity Analyses to Overall Survival in Cancer Clinical
Trials Reply
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Letter
C1 [Bhattacharya, Suman; Fyfe, Gwen] Genentech Inc, San Francisco, CA 94080 USA.
[Gray, Robert] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Sargent, Daniel L.] Mayo Clin, Rochester, MN USA.
RP Bhattacharya, S (reprint author), Genentech Inc, San Francisco, CA 94080 USA.
NR 1
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JUL 1
PY 2010
VL 28
IS 19
BP E324
EP E324
DI 10.1200/JCO.2010.28.7300
PG 1
WC Oncology
SC Oncology
GA 617AX
UT WOS:000279254300027
ER
PT J
AU Canellos, GP
AF Canellos, George P.
TI Lymphocyte-Predominant Hodgkin's Lymphoma Reply
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Letter
C1 Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Canellos, GP (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 2
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JUL 1
PY 2010
VL 28
IS 19
BP E326
EP E326
DI 10.1200/JCO.2010.28.7243
PG 1
WC Oncology
SC Oncology
GA 617AX
UT WOS:000279254300029
ER
PT J
AU Punnoose, LR
Roh, JD
Hu, S
Udell, JA
Wagle, N
Kirshenbaum, JM
LaCasce, AS
AF Punnoose, Lynn R.
Roh, Jason D.
Hu, Stephanie
Udell, Jacob A.
Wagle, Nikhil
Kirshenbaum, James M.
LaCasce, Ann S.
TI Cardiac Presentation of Anaplastic Large-Cell Lymphoma
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID ENDOMYOCARDIAL BIOPSY; CARDIOTOXICITY; DOXORUBICIN; CHEMOTHERAPY;
DIAGNOSIS; CARDIOMYOPATHY; MANAGEMENT; CANCER; RISK
C1 [Punnoose, Lynn R.; Roh, Jason D.; Hu, Stephanie; Udell, Jacob A.; Wagle, Nikhil; Kirshenbaum, James M.; LaCasce, Ann S.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Punnoose, LR (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA.
NR 18
TC 1
Z9 1
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JUL 1
PY 2010
VL 28
IS 19
BP E314
EP E316
DI 10.1200/JCO.2009.26.7583
PG 3
WC Oncology
SC Oncology
GA 617AX
UT WOS:000279254300022
PM 20516445
ER
PT J
AU Olfson, M
Marcus, SC
Doshi, JA
AF Olfson, Mark
Marcus, Steven C.
Doshi, Jalpa A.
TI Continuity of Care After Inpatient Discharge of Patients With
Schizophrenia in the Medicaid Program: A Retrospective Longitudinal
Cohort Analysis
SO JOURNAL OF CLINICAL PSYCHIATRY
LA English
DT Article
ID MENTAL-HEALTH-CARE; PSYCHIATRIC-HOSPITALIZATION; FOLLOW-UP; PREDICTORS;
REHOSPITALIZATION; APPOINTMENTS; RECIDIVISM; STRATEGIES; PATTERNS;
ILLNESS
AB Objective: This study seeks to identify patient, facility, county, and state policy factors associated with timely schizophrenia-related outpatient treatment following hospital discharge.
Method: A retrospective longitudinal cohort analysis was performed of 2003 national Medicaid claims data supplemented with the American Hospital Association facility survey, the Area Resource File, and a Substance Abuse and Mental Health Services Administration Medicaid policy report The analysis focuses on treatment episodes of adults, aged 20 to 63 years, who received inpatient care for ICD-9-CM-diagnosed schizophrenia (59,567 total treatment episodes). Rate and adjusted odds ratio (AOR) of schizophrenia-related outpatient visits within 7 days and 30 days following hospital discharge are assessed.
Results: Of the 59,567 hospital discharges, 41 7% received schizophrenia-related outpatient visits in 7 days and 59 3% in 30 days following hospital discharge The adjusted odds of 30-day follow-up outpatient visits were significantly related to pread-mission outpatient mental health visits (AOR = 3.72, 99% CI, 3.44-4 03), depot (AOR = 2 83, 99% CI, 2 53-3.18) or oral (AOR = 1.73; 99% CI, 1 62-1.84) antipsychotics as compared with no antipsychotics, and absence of a substance use disorder diagnosis (AOR = 1.35, 99% CI, 1 25-1 45). General hospital as compared with a psychiatric hospital treatment (AOR = 1.32; 99% CI, 1 14-1 54) and patient residence in a county with a larger number of psychiatrists per capita (AOR = 1 27, 99% CI, 1.08-1.50) were related to receiving follow-up outpatient visits. By contrast, residence in a county with a high poverty rate (AOR = 0.60; 99% CI, 0.54-0 67) and treatment in a state with prior authorization requirements for < 12 annual outpatient visits (AOR = 0.69, 99% CI, 063-0.75) reduced the odds of follow-up care.
Conclusions: Patient characteristics, clinical management, geographical resource availability, and the mental health policy environment all appear to shape access to care following hospital discharge in the community treatment of adult schizophrenia. J Clin, Psychiatry 2010, 71(7):831-838 ea (C) Copyright 2010 Physicians Postgraduate Press, Inc
C1 [Olfson, Mark] Columbia Univ, Dept Psychiat, New York State Psychiat Inst, Coll Phys & Surg, New York, NY 10032 USA.
[Marcus, Steven C.] Univ Penn, Ctr Hlth Equ Res & Promot, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA.
[Marcus, Steven C.] Univ Penn, Sch Social Policy & Practice, Philadelphia, PA 19104 USA.
[Doshi, Jalpa A.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA.
[Doshi, Jalpa A.] Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA.
RP Olfson, M (reprint author), Columbia Univ, Dept Psychiat, New York State Psychiat Inst, Coll Phys & Surg, 1051 Riverside Dr,Unit 24, New York, NY 10032 USA.
RI McCarthy, Jodie/B-5760-2012
FU Bristol-Myers Squibb; Eli Lilly, Indianapolis, Indiana
FX Dr Olfson has received grant/research support from Bristol-Myers Squibb
and Eli Lilly Dr Marcus is a consultant for Eli Lilly Dr Doshi is a
consultant for Eli Lilly and Bristol-Myers Squibb; This research was
funded by a grant to Columbia University from Eli Lilly, Indianapolis,
Indiana, Dr Olfson, principal investigator
NR 35
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Z9 27
U1 0
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 JUL
PY 2010
VL 71
IS 7
BP 831
EP 838
DI 10.4088/JCP.10m05969yel
PG 8
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA 633AC
UT WOS:000280470700003
PM 20441730
ER
PT J
AU Morland, LA
Greene, CJ
Rosen, CS
Foy, D
Reilly, P
Shore, J
He, QM
Frueh, BC
AF Morland, Leslie A.
Greene, Carolyn J.
Rosen, Craig S.
Foy, David
Reilly, Patrick
Shore, Jay
He, Qimei
Frueh, B. Christopher
TI Telemedicine for Anger Management Therapy in a Rural Population of
Combat Veterans With Posttraumatic Stress Disorder: A Randomized
Noninferiority Trial
SO JOURNAL OF CLINICAL PSYCHIATRY
LA English
DT Article
ID US VETERANS; TELEPSYCHIATRY; PSYCHOTHERAPY; AFGHANISTAN; DEPRESSION;
ALLIANCE; VIETNAM; ISSUES; PTSD; IRAQ
AB Objective: To demonstrate the noninferiority of a telemedicine modality, videoteleconferencing, compared to traditional in-person service delivery of a group psychotherapy intervention for rural combat veterans with posttraumatic stress disorder (PTSD).
Method: A randomized controlled noninferiority trial of 125 male veterans with PTSD (according to DSM criteria on the Clinician-Administered PTSD Scale) and anger difficulties was conducted at 3 Veterans Affairs outpatient clinics. Participants were randomly assigned to receive anger management therapy delivered in a group setting with the therapist either in-person (n=64) or via videoteleconferencing (n=61). Participants were assessed at baseline, midtreatment (3 weeks), posttreatment (6 weeks), and 3 and 6 months posttreatment The primary clinical outcome was reduction of anger difficulties, as measured by the anger expression and trait anger subscales of the State-Trait Anger Expression Inventory-2 (STAXI-2) and by the Novaco Anger Scale total score (NAS-T). Data were collected from August 2005 to October 2008.
Results: Participants in both groups showed significant and clinically meaningful reductions in anger symptoms, with posttreatment and 3 and 6 months posttreatment effect sizes ranging from 12 to .63 Using a noninferiority margin of 2 points for STAXI-2 subscales anger expression and trait anger and 4 points for NAS-T outcomes, participants in the videoteleconferencing condition demonstrated a reduction in anger symptoms similar ("non-inferior") to symptom reductions in the in-person groups. Additionally, no significant between-group differences were found on process variables, including attrition, adherence, satisfaction, and treatment expectancy Participants in the in-person condition reported significantly higher group therapy alliance.
Conclusions: Clinical and process outcomes indicate delivering cognitive-behavioral group treatment for PTSD-related anger problems via videoteleconferencing is an effective and feasible way to increase access to evidence-based care for veterans residing in rural or remote locations
Trial Registration: clinicaltrials gov Identifier NCT00122109 J Clin Psychiatry 2010,71(7).855-863 (C) Copyright 2010 Physicians Postgraduate Press, Inc
C1 [Morland, Leslie A.; Greene, Carolyn J.] Pacific Isl Healthcare Syst, Natl Ctr PTSD, Pacific Isl Div, Dept Vet Affairs, Honolulu, HI 96819 USA.
[He, Qimei] Pacific Hlth Res Inst, Honolulu, HI USA.
[Greene, Carolyn J.; Rosen, Craig S.] Palo Alto Healthcare Syst, Natl Ctr PTSD, Disseminat & Training Div, Dept Vet Affairs, Palo Alto, CA USA.
[Rosen, Craig S.] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Palo Alto, CA 94304 USA.
[Foy, David] Pepperdine Univ, Grad Sch Educ & Psychol, Malibu, CA 90265 USA.
[Reilly, Patrick] San Francisco VA Med Ctr, San Francisco, CA USA.
[Shore, Jay] Univ Colorado, Ctr Amer Indian Native Mental Hlth, Denver, CO 80202 USA.
[Shore, Jay] Univ Colorado, Ctr Alaska Native Mental Hlth, Denver, CO 80202 USA.
[Shore, Jay] Off Rural Hlth, Dept Vet Affairs, Vet Rural Hlth Resource Ctr Western Reg, Denver, CO USA.
[Frueh, B. Christopher] Menninger Clin, Houston, TX USA.
[Frueh, B. Christopher] Baylor Coll Med, Houston, TX 77030 USA.
RP Morland, LA (reprint author), Pacific Isl Healthcare Syst, Natl Ctr PTSD, Pacific Isl Div, Dept Vet Affairs, 3375 Koapaka St,Suite I-560, Honolulu, HI 96819 USA.
FU Veterans Affairs Health Services Research and Development [TEL
03-080-3]; Office of Research and Development, Medical Research Service,
Department of Veterans Affairs
FX This work was partially supported by grant TEL 03-080-3 from the
Veterans Affairs Health Services Research and Development This work was
also supported by the Office of Research and Development, Medical
Research Service, Department of Veterans Affairs
NR 42
TC 107
Z9 108
U1 5
U2 22
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 JUL
PY 2010
VL 71
IS 7
BP 855
EP 863
DI 10.4088/JCP.09m05604blu
PG 9
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA 633AC
UT WOS:000280470700005
PM 20122374
ER
PT J
AU Zisook, S
Kasckow, JW
Lanouette, NM
Golshan, S
Fellows, I
Vahia, I
Mohamed, S
Rao, S
AF Zisook, Sidney
Kasckow, John W.
Lanouette, Nicole M.
Golshan, Shahrokh
Fellows, Ian
Vahia, Ipsit
Mohamed, Somaia
Rao, Sanjai
TI Augmentation With Citalopram for Suicidal Ideation in Middle-Aged and
Older Outpatients With Schizophrenia and Schizoaffective Disorder Who
Have Subthreshold Depressive Symptoms: A Randomized Controlled Trial
SO JOURNAL OF CLINICAL PSYCHIATRY
LA English
DT Article
ID INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; SEROTONIN REUPTAKE INHIBITORS;
CLINICAL-TRIALS; DSM-IV; RISK; SCALE; ANTIDEPRESSANTS; ASSOCIATION;
PLACEBO; ADULTS
AB Objective: To examine the effects of citalopram augmentation of antipsychotic on suicidal ideation in middle-aged and older people with schizophrenia and subthreshold depressive symptoms.
Method: In this placebo-controlled trial conducted from September 1, 2001, to August 31, 2007, 198 outpatients 40 years old with DSM-IV-diagnosed schizophrenia or schizoaffective disorder and subthreshold depressive symptoms were randomly assigned to flexible-dose citalopram (n = 104) or placebo (n = 94) augmentation of their antipsychotic for 12 weeks. Depression was measured with the Hamilton Depression Rating Scale (HDRS) and Calgary Depression Rating Scale (CDRS) Primary suicidal ideation measures were the Clinical Global Impressions-Seventy of Suicide scale (CGI-SS) and the InterSePT Scale for Suicidal Thinking (ISST), secondary outcomes were the Scale for Suicidal Ideation (SSI), Beck Hopelessness Scale (RIIS), HDRS Item 3, and CDRS item 8
Results: Compared to placebo, at the final visit, citalopram was associated with lower BHS scores (4.21 vs 4 98, P < .05) and lower likelihood of having suicidal ideation on the ISST (17 7% vs 38 7%, P < 005) and HDRS Item 3 (14 4% vs 22 6%, P < 05) Among the 114 participants with no baseline suicidal ideation, there were no significant differences between citalopram and placebo regarding "emergent" ideation on either primary outcome Among the 55 participants with baseline suicidal ideation, fewer treated with citalopram had endpoint ideation on the ISST (286% vs 66 7%, P<.05). Significantly more depression responders than nonresponders went from having baseline suicidal ideation to no suicidal ideation on both the ISST (75 0% vs 31 4%, P < 05) and CGI-SS (84 6% vs 31 3%, P < 05)
Conclusions: Treatment-emergent suicidal ideation was no more common with citalopram than placebo In participants with baseline suicidal ideation, citalopram reduced suicidal ideation, especially in those whose depressive symptoms responded to treatment
C1 [Zisook, Sidney; Golshan, Shahrokh; Fellows, Ian] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92161 USA.
[Zisook, Sidney; Lanouette, Nicole M.; Vahia, Ipsit; Rao, Sanjai] Vet Affairs San Diego Hlth Care Syst, San Diego, CA USA.
[Kasckow, John W.] Univ Pittsburgh, Dept Psychiat, Vet Affairs Pittsburgh Hlth Care Syst, Western Psychiat Inst & Clin,MIRECC,Med Ctr, Pittsburgh, PA 15260 USA.
[Mohamed, Somaia] VISN 1 MIRECC, Vet Affairs NE Program Evaluat Ctr, New Haven, CT USA.
[Mohamed, Somaia] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA.
RP Zisook, S (reprint author), Univ Calif San Diego, Dept Psychiat, 3350 La Jolla Village Dr, San Diego, CA 92161 USA.
FU PenLab; AstraZeneca; Citalopram Augmentation of Older Patients with
Schizophrenia [RO-1 MH 063931]; National Institute of Mental Health
[MH66248, MH19934, P30 MH080002]; Department of Veterans Affairs [R01
MH6398]; VISN 4 MIRECC; VISN 4 CPPF
FX Dr Zisook has received grant/research support from PenLab and has
received honoraria from GlaxoSmithKline Dr Kasckow has received
grant/research support from AstraZeneca Dr Rao is on the
speakers/advisory boards for Bristol-Myers Squibb, Eli Lilly, and
AstraZeneca Drs Lanouette, Golshan, Vahia, and Mohamed and Mr Fellows
have no personal affiliations or financial relationships with any
commercial interest to disclose relative to the article; This work was
supported by RO-1 MH 063931 Citalopram Augmentation of Older Patients
with Schizophrenia (Dr Zisook, PI), National Institute of Mental Health
grants MH66248, MH19934, P30 MH080002, and the Department of Veterans
Affairs Dr Kasckow was supported by R01 MH6398, the VISN 4 MIRECC, and a
VISN 4 CPPF award
NR 49
TC 15
Z9 15
U1 3
U2 10
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 JUL
PY 2010
VL 71
IS 7
BP 915
EP 922
DI 10.4088/JCP.09m05699gre
PG 8
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA 633AC
UT WOS:000280470700012
PM 20361918
ER
PT J
AU Prakash, P
Kalra, MK
Stone, JR
Shepard, JAO
Digumarthy, SR
AF Prakash, Priyanka
Kalra, Mannudeep K.
Stone, James R.
Shepard, Jo-Anne O.
Digumarthy, Subba R.
TI Imaging Findings of Pericardial Metastasis on Chest Computed Tomography
SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY
LA English
DT Article
DE pericardial metastasis; computed tomography; pericardial effusion
ID TUMORS; HEART; CT; INVOLVEMENT; FEATURES
AB Background: To assess imaging features of pericardial metastases on chest computed tomography (CT) scanning.
Methods: This institutional review board-approved retrospective study included 60 patients (24 men, 36 women; mean age, 62 [SD, 13] years). All chest CT scans for these patients were reviewed independently for presence of pericardial effusion, irregularity, enhancement, nodules, and masses and presence of coexistent cardiac lesions (metastasis). Location of pericardial nodules and irregularity and type and location of primary malignancy were recorded.
Results: Of these 60 patients with pericardial metastasis, 54 (90%) had pericardial effusion (small in 23/54 and moderate to large in 31/54 patients); 14 (23%) of 60 patients had nodules or masses in the pericardium; 21 (35%) of 60 had pericardial enhancement; and 27 (45%) of 60 had pericardial thickening. Prepericardial lymph nodes were present in 39 (65%) of 60 patients. The most common location of pericardial nodules and irregularity was along the free wall of the right ventricle (6/14) and right atrioventricular groove (5/14). Other 3 of 14 patients had pericardial nodule over the left ventricle, in oblique sinus of the pericardium, and interventricular groove each.
Conclusions: Most frequent CT features of pericardial metastases include pericardial effusion, prepericardial lymph nodes, and pericardial thickening, enhancement, and nodules in order of decreasing frequency.
C1 [Prakash, Priyanka; Kalra, Mannudeep K.; Shepard, Jo-Anne O.; Digumarthy, Subba R.] Massachusetts Gen Hosp, Dept Radiol, Div Thorac Radiol, Boston, MA 02114 USA.
[Stone, James R.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Stone, James R.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Digumarthy, SR (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Thorac Radiol, 202 Founders,55 Fruit St, Boston, MA 02114 USA.
EM sdigumarthy@partners.org
NR 17
TC 9
Z9 11
U1 0
U2 1
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 JUL
PY 2010
VL 34
IS 4
BP 554
EP 558
DI 10.1097/RCT.0b013e3181d77d7e
PG 5
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 630BM
UT WOS:000280246300012
PM 20657224
ER
PT J
AU Chambers, JA
Davis, MR
Rasmussen, TE
AF Chambers, James Alan
Davis, Michael R.
Rasmussen, Todd E.
TI A Band of Surgeons, a Long Healing Line: Development of Craniofacial
Surgery in Response to Armed Conflict
SO JOURNAL OF CRANIOFACIAL SURGERY
LA English
DT Article
DE Plastic surgery; craniofacial; maxillofacial; reconstruction; war;
history; military; surgery
ID PLASTIC-SURGERY; INJURIES; WAR; OTOLARYNGOLOGY; MANAGEMENT; EVOLUTION;
MEDICINE; HISTORY
AB Far removed from modern perceptions of cosmetic surgery, plastic and craniofacial surgery largely began centuries ago with efforts to redeem the destruction and loss from battlefield violence. Successive generations of surgeons responding with compassion to the functional and aesthetic loss of those wounded in war have achieved the progress that benefits 21st century patients. Although the historic role of war has to a degree been supplanted by jet travel, electronic communications, and academic medical centers, leadership continues to be the primary force responsible for advances. This article outlines the evolution of modern craniofacial surgery in 4 phases described by the Latin terms pluresartes, plurestelae, pluraloca, and pluresfontes.
C1 [Davis, Michael R.] Wright Patterson Med Ctr, Dayton, OH 45433 USA.
[Chambers, James Alan] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Rasmussen, Todd E.] Wilford Hall USAF Med Ctr, San Antonio, TX 78236 USA.
RP Davis, MR (reprint author), Wright Patterson Med Ctr, Dayton, OH 45433 USA.
EM Michael.Davis@wpafb.af.mil
NR 57
TC 1
Z9 1
U1 2
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 JUL
PY 2010
VL 21
IS 4
BP 991
EP 997
DI 10.1097/SCS.0b013e3181e1e81e
PG 7
WC Surgery
SC Surgery
GA 628UV
UT WOS:000280149100013
PM 20613570
ER
PT J
AU Biederman, J
Petty, CR
Fried, R
Wozniak, J
Micco, JA
Henin, A
Doyle, R
Joshi, G
Galdo, M
Kotarski, M
Caruso, J
Yorks, D
Faraone, SV
AF Biederman, Joseph
Petty, Carter R.
Fried, Ronna
Wozniak, Janet
Micco, Jamie A.
Henin, Aude
Doyle, Robert
Joshi, Gagan
Galdo, Maribel
Kotarski, Meghan
Caruso, Janet
Yorks, Dayna
Faraone, Stephen V.
TI Child Behavior Checklist Clinical Scales Discriminate Referred Youth
With Autism Spectrum Disorder: A Preliminary Study
SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS
LA English
DT Article
DE autism spectrum; CBCL; screening
ID PERVASIVE DEVELOPMENTAL DISORDERS; OPERATING CHARACTERISTIC ANALYSIS;
INTERVIEW-DERIVED DIAGNOSIS; BIPOLAR DISORDER; ADHD YOUTH; CBCL;
ADOLESCENTS; SAMPLE; PDD; COMORBIDITY
AB Objective: To evaluate the properties of clinical scales of the Child Behavior Checklist in discriminating referred children with autism spectrum disorders (ASDs) (autistic disorder, Asperger's disorder, and pervasive developmental disorder not otherwise specified) from psychiatrically referred children without ASDs. Method: Comparisons were made between children with ASDs (n = 65) with intelligence quotient >70 and children without ASDs (n = 83) on the clinical scales of the Child Behavior Checklist. Stepwise logistic regression was used to identify those scales that best predicted ASDs when compared with the non-ASD comparison group. Receiver operating characteristic curves examined the ability of the significant predictor T-scores to identify ASDs versus the non-ASD subjects. Results: Withdrawn, Social Problems, and Thought Problems T-scores were the best independent predictors of ASD status. The Withdrawn + Social + Thought Problems T-scores yielded an area under the curve of 0.86, indicating an 86% chance that a randomly selected sample of ASD subject will have abnormal scores on these scales than a randomly selected sample of non-ASD subjects. Conclusion: These findings suggest that a new Child Behavior Checklist-ASD profile consisting of the Child Behavior Checklist-Withdrawn, Social, and Thought Problems scales could serve as a rapid and cost-effective screening instrument to help identify cases likely to meet clinical criteria for ASDs in the clinical setting.
C1 [Biederman, Joseph; Petty, Carter R.; Fried, Ronna; Wozniak, Janet; Micco, Jamie A.; Henin, Aude; Doyle, Robert; Joshi, Gagan; Galdo, Maribel; Kotarski, Meghan; Caruso, Janet; Yorks, Dayna] Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA.
[Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA.
RP Biederman, J (reprint author), Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Warren 705,55 Fruit St, Boston, MA 02114 USA.
EM jbiederman@partners.org
OI Faraone, Stephen/0000-0002-9217-3982
FU Alan and Lorraine Bressler Clinical and Research Program for Autism
Spectrum Disorders
FX This work was supported in part by a grant to the Alan and Lorraine
Bressler Clinical and Research Program for Autism Spectrum Disorders.
NR 34
TC 15
Z9 15
U1 2
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0196-206X
J9 J DEV BEHAV PEDIATR
JI J. Dev. Behav. Pediatr.
PD JUL-AUG
PY 2010
VL 31
IS 6
BP 485
EP 490
DI 10.1097/DBP.0b013e3181e56ddd
PG 6
WC Behavioral Sciences; Psychology, Developmental; Pediatrics
SC Behavioral Sciences; Psychology; Pediatrics
GA 622GC
UT WOS:000279648300006
PM 20585266
ER
PT J
AU Nagurney, JT
Bamberg, F
Nichols, JH
Marill, K
Brown, DFM
Peak, DA
Harris, NS
Worrell, S
Parry, B
Hoffmann, U
AF Nagurney, John T.
Bamberg, Fabian
Nichols, John H.
Marill, Keith
Brown, David F. M.
Peak, David A.
Harris, N. Stuart
Worrell, Stewart
Parry, Blair
Hoffmann, Udo
TI THE DISPOSITION DECISION ON EMERGENCY DEPARTMENT PATIENTS WITH CHEST
PAIN IS AFFECTED BY THE RESULTS OF MULTI-DETECTOR COMPUTED AXIAL
TOMOGRAPHY SCAN OF THE CORONARY ARTERIES
SO JOURNAL OF EMERGENCY MEDICINE
LA English
DT Article
DE multidetector computed axial tomography; acute coronary syndrome; acute
myocardial infarction; physician predictions
ID ACUTE MYOCARDIAL-INFARCTION; DIAGNOSTIC-ACCURACY; CARDIAC ISCHEMIA;
MISSED DIAGNOSES; UNSTABLE ANGINA; ANGIOGRAPHY; DISEASE; ROOM;
CLASSIFICATION; PROTOCOL
AB Background: Few data exist on the frequency with which multidetector computed axial tomography (MDCT) scan of the coronary arteries changes the admission decisions of emergency physicians (EP) caring for patients with possible acute coronary syndrome (ACS). We measured if and how often these changes in decision-making would occur. Methods: The theoretical dispositions of 27 emergency department patients who presented with possible ACS were determined by four board-certified EPs after case presentations. Paired disposition decisions were made before and after knowledge of the MDCT scan results. Patients were selected from a sample of 103 from a prior study. Results: The study included 27 patients with a mean age of 55 +/- 9 years; 58% were male. The low-, intermediate-, and high-risk MDCT scan results were evenly distributed, as were the original providers' standard clinical risk assessments of ACS. Three patients had ACS and all were admitted both before and after review of MDCT scan results. Among 24 patients without ACS, a decision to admit was changed to discharge in 16 of 90 admission decisions (18%, 95% confidence interval [CI] 10-26%). Among 6 patients with projected discharges, 2 were inappropriately admitted after review of MDCT scan results. The odds ratio of discharge for patients without ACS increased by 3.95 (95% CI 1.96-7.95) after introduction of the MDCT scan results. Conclusion: An MDCT scan of the coronary arteries will likely change emergency physicians' decisions on the disposition of patients presenting with possible ACS, many to appropriate discharges but also a minority to inappropriate admissions. (C) 2010 Published by Elsevier Inc.
C1 [Nagurney, John T.; Marill, Keith; Brown, David F. M.; Peak, David A.; Harris, N. Stuart; Parry, Blair] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.
[Bamberg, Fabian; Nichols, John H.; Worrell, Stewart; Hoffmann, Udo] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA.
[Bamberg, Fabian; Nichols, John H.; Worrell, Stewart; Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Nagurney, JT (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Zero Emerson Pl 353, Boston, MA 02114 USA.
NR 37
TC 2
Z9 2
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0736-4679
J9 J EMERG MED
JI J. Emerg. Med.
PD JUL
PY 2010
VL 39
IS 1
BP 57
EP 64
DI 10.1016/j.jemermed.2009.04.058
PG 8
WC Emergency Medicine
SC Emergency Medicine
GA 620ZK
UT WOS:000279542200012
PM 19500937
ER
PT J
AU Walls, RM
Samuels-Kalow, M
Perkins, A
AF Walls, Ron M.
Samuels-Kalow, M.
Perkins, A.
TI A NEW MANEUVER FOR ENDOTRACHEAL TUBE INSERTION DURING DIFFICULT
GLIDESCOPE INTUBATION
SO JOURNAL OF EMERGENCY MEDICINE
LA English
DT Article
DE GlideScope (R); video laryngoscope; difficult airway; intubation;
emergency intubation; RSI
ID FACILITATE TRACHEAL INTUBATION; VIDEOLARYNGOSCOPE; LARYNGOSCOPY; TIME
AB Background: The GlideScope (R) Video Laryngoscope (Verathon, Bothell, WA) is a video laryngoscopy system that can be used for routine intubation, but is also commonly used as an alternative for difficult or failed airways. Previous reports have identified a very high incidence of grade 1 and grade 2 Cormack-Lehane glottic views, but despite these high-grade views, intubation is sometimes difficult due to the angle of insertion and shape of the endotracheal tube. Several maneuvers have been reported to increase the likelihood of successful endotracheal tube placement in these uncommon cases of failure. Case Report: We report the case of a patient who could not be intubated with the GlideScope (R) despite an easily obtained grade 1 laryngoscopic view. The impediment to intubation was identified as a sharp angulation of the trachea with respect to the larynx, such that the trachea formed a steep posterior angle with the laryngeal/glottic axis. Intubation was achieved using a previously unreported maneuver, in which the endotracheal tube with a sharply curved malleable stylet was inserted through the glottis, and then rotated 1800 to permit passage down the trachea. Discussion and Conclusion: We believe that this maneuver may be useful in other cases of failed GlideScope (R) intubation, when a high-grade laryngeal view is obtained but tube passage is not possible due to a sharp posterior angulation of the trachea. (C) 2010 Elsevier Inc.
C1 [Walls, Ron M.] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA.
[Samuels-Kalow, M.; Perkins, A.] Massachusetts Gen Hosp, Brigham & Womens Hosp, Harvard Affiliated Emergency Med Residency Traini, Boston, MA 02114 USA.
RP Walls, RM (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St,NH 2, Boston, MA 02115 USA.
NR 12
TC 10
Z9 10
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0736-4679
J9 J EMERG MED
JI J. Emerg. Med.
PD JUL
PY 2010
VL 39
IS 1
BP 86
EP 88
DI 10.1016/j.jemermed.2009.11.005
PG 3
WC Emergency Medicine
SC Emergency Medicine
GA 620ZK
UT WOS:000279542200017
PM 20097502
ER
PT J
AU Rhodes, KV
Cerulli, C
Dichter, ME
Kothari, CL
Barg, FK
AF Rhodes, Karin V.
Cerulli, Catherine
Dichter, Melissa E.
Kothari, Catherine L.
Barg, Frances K.
TI "I Didn't Want To Put Them Through That": The Influence Of Children on
Victim Decision-making in Intimate Partner Violence Cases
SO JOURNAL OF FAMILY VIOLENCE
LA English
DT Article
DE Intimate partner violence; Domestic violence; Child exposure;
Decision-making; Barriers to help-seeking
ID DOMESTIC VIOLENCE; EXPOSURE; FAMILY
AB For mothers, intimate partner violence (IPV) presents a concern not only for their own well-being but also for that of their children who are exposed to the violence and its aftermath. In focus groups with adult women (N = 39) across three jurisdictions who had experienced legal system intervention for IPV victimization, mothers raised unsolicited concerns about the negative effects of IPV exposure on their children. These comments were not prompted by the facilitator but were raised by women in all seven of the focus groups during discussions about motivations and barriers to participation in prosecution of their abusive partners. The overall message was that victims with children felt very conflicted. Children both facilitate and inhibit leaving the abusive relationship. Mothers wanted to spare their children from harmful effects of violence but also wanted to keep their families together and protect their children from potential agitation and instability caused by legal system involvement. Participants described how fears and threats of involvement from child protective services inhibited help-seeking while simultaneously voicing a desire for services that would help their children. More research is needed to help service providers understand the quagmire mothers who are victims of IPV encounter regarding their children's wellbeing.
C1 [Rhodes, Karin V.] Univ Penn, Div Emergency Care Policy & Res, Dept Emergency Med, Philadelphia, PA 19014 USA.
[Rhodes, Karin V.] Univ Penn, Sch Social Policy & Practice, Philadelphia, PA 19014 USA.
[Cerulli, Catherine] Univ Rochester, Med Ctr, Dept Psychiat, Rochester, NY 14642 USA.
[Dichter, Melissa E.] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA.
[Kothari, Catherine L.] Michigan State Univ, Kalamazoo Ctr Med Studies, Kalamazoo, MI USA.
[Barg, Frances K.] Univ Penn, Philadelphia, PA 19104 USA.
RP Rhodes, KV (reprint author), Univ Penn, Div Emergency Care Policy & Res, Dept Emergency Med, 3815 Walnut St, Philadelphia, PA 19014 USA.
EM kvr@sp2.upenn.edu
OI Kothari, Catherine/0000-0001-8072-8920
NR 30
TC 18
Z9 18
U1 2
U2 9
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0885-7482
J9 J FAM VIOLENCE
JI J. Fam. Violence
PD JUL
PY 2010
VL 25
IS 5
BP 485
EP 493
DI 10.1007/s10896-010-9310-z
PG 9
WC Psychology, Clinical; Family Studies
SC Psychology; Family Studies
GA 596XW
UT WOS:000277720200004
ER
PT J
AU Griffin, JM
Partin, MR
Noorbaloochi, S
Grill, JP
Saha, S
Snyder, A
Nugent, S
Simon, AB
Gralnek, I
Provenzale, D
van Ryn, M
AF Griffin, Joan M.
Partin, Melissa R.
Noorbaloochi, Siamak
Grill, Joseph P.
Saha, Somnath
Snyder, Annamay
Nugent, Sean
Simon, Alisha Baines
Gralnek, Ian
Provenzale, Dawn
van Ryn, Michelle
TI Variation in Estimates of Limited Health Literacy by Assessment
Instruments and Non-Response Bias
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Article
DE health literacy; veterans; prevalence; measurement; non-response bias;
REALM; S-TOFHLA
ID ELDERLY PERSONS; CARE; PREVALENCE; QUESTIONS; ENROLLEES
AB This paper compares estimates of poor health literacy using two widely used assessment tools and assesses the effect of non-response on these estimates.
A total of 4,868 veterans receiving care at four VA medical facilities between 2004 and 2005 were stratified by age and facility and randomly selected for recruitment. Interviewers collected demographic information and conducted assessments of health literacy (both REALM and S-TOFHLA) from 1,796 participants. Prevalence estimates for each assessment were computed. Non-respondents received a brief proxy questionnaire with demographic and self-report literacy questions to assess non-response bias. Available administrative data for non-participants were also used to assess non-response bias.
Among the 1,796 patients assessed using the S-TOFHLA, 8% had inadequate and 7% had marginal skills. For the REALM, 4% were categorized with 6th grade skills and 17% with 7-8th grade skills. Adjusting for non-response bias increased the S-TOFHLA prevalence estimates for inadequate and marginal skills to 9.3% and 11.8%, respectively, and the REALM estimates for a parts per thousand currency sign6th and 7-8th grade skills to 5.4% and 33.8%, respectively.
Estimates of poor health literacy varied by the assessment used, especially after adjusting for non-response bias. Researchers and clinicians should consider the possible limitations of each assessment when considering the most suitable tool for their purposes.
C1 [Griffin, Joan M.; Partin, Melissa R.; Noorbaloochi, Siamak; Grill, Joseph P.; Snyder, Annamay; Nugent, Sean; Simon, Alisha Baines] Minneapolis VA Med Ctr, Ctr Chron Dis Outcomes Res, Minneapolis, MN USA.
[Griffin, Joan M.; Partin, Melissa R.; Noorbaloochi, Siamak] Univ Minnesota, Sch Med, Dept Gen Internal Med, Minneapolis, MN 55455 USA.
[Saha, Somnath] Portland VA Med Ctr, Columbia Ctr Study Chron Comorbid Mental & Phys D, Portland, OR USA.
[Gralnek, Ian] Technion Israel Inst Technol, Bruce Rappaport Fac Med, Dept Gastroenterol, GI Outcomes Unit, IL-31096 Haifa, Israel.
[Provenzale, Dawn] Durham VA Med Ctr, Ctr Hlth Serv Res Primary Care, Durham, NC USA.
[van Ryn, Michelle] Univ Minnesota, Sch Med, Dept Family Med & Community Hlth, Minneapolis, MN 55455 USA.
RP Griffin, JM (reprint author), Minneapolis VA Med Ctr 152 3E 109, Ctr Chron Dis Outcomes Res, 1 Vet Dr, Minneapolis, MN 55417 USA.
EM joan.griffin2@va.gov
RI Griffin, Jillian/F-9415-2010; VAN RYN, MICHELLE/B-1664-2010
FU Department of Veterans Affairs; VA Health Services Research and
Development Service [CRI-03-151-1]; VA Merit Review Entry Program
(MREP); VA HSR&D Advanced Research Career Development Award; [IIS
01-191-1]
FX This research was supported by the Department of Veterans Affairs,
including a grant from VA Health Services Research and Development
Service (CRI-03-151-1). Dr. Griffin also received support as a VA Merit
Review Entry Program (MREP) awardee. Dr. Gralnek was supported by a VA
HSR&D Advanced Research Career Development Award and IIS 01-191-1. The
views expressed in this article are those of the author(s) and do not
necessarily represent the views of the Department of Veterans Affairs or
the United States Government. Part of this work was presented at the
24th Annual VA Health Services Research Meeting, Crystal City, VA,
February 17, 2006. The authors wish to thank all the veteran
participants for their time and the study interviewers for their
commitment to this project.
NR 38
TC 23
Z9 23
U1 1
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD JUL
PY 2010
VL 25
IS 7
BP 675
EP 681
DI 10.1007/s11606-010-1304-2
PG 7
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA 607RR
UT WOS:000278524700012
PM 20224964
ER
PT J
AU Bhan, I
Dubey, A
Wolf, M
AF Bhan, Ishir
Dubey, Anil
Wolf, Myles
TI Diagnosis and Management of Mineral Metabolism in CKD
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Article
DE chronic kidney disease; bisphosphonate; osteoporosis
ID CHRONIC KIDNEY-DISEASE; SUPPRESSED BONE TURNOVER; CARDIAC RISK-FACTORS;
VITAMIN-D; SECONDARY HYPERPARATHYROIDISM; RENAL OSTEODYSTROPHY;
NATIONAL-HEALTH; HEMODIALYSIS; MORTALITY; ALENDRONATE
AB Chronic kidney disease (CKD) affects over 26 million Americans and is frequently complicated early in its course by disordered mineral metabolism and metabolic bone disease. Since CKD-related bone loss is often indistinguishable from osteoporosis by standard bone densitometry, many CKD patients may be inappropriately treated with bisphosphonates rather than CKD-specific therapies.
To determine the prevalence of appropriate evaluation, diagnosis and management of metabolic bone disease among individuals with pre-dialysis CKD.
Retrospective cohort study using electronic medical records of 69,215 ambulatory patients seen in the primary care clinics of an academic medical center.
Prevalence of CKD stages 3-4, frequency of diagnostic testing and treatment of metabolic bone disease.
Based on current diagnostic criteria and consistent with national data, CKD was present in 12% of the population. Bisphosphonates were used in 7.2% of patients, 20% of whom met criteria for CKD. Fewer than half of CKD patients underwent testing for parathyroid hormone (PTH) or 25-hydroxyvitamin D (25D) levels. Among those tested, vitamin D deficiency (25D < 30 ng/ml) and secondary hyperparathyroidism (PTH > 60 pg/ml) were present in 65% and 55%, respectively. Among patients with CKD, bisphosphonate use was nearly seven times as frequent as therapy with active vitamin D (12% vs. 1.7%, p < 0.0001), a primary treatment for CKD-associated metabolic bone disease.
Disordered mineral metabolism in CKD is common, under-diagnosed and under-treated. As a result, bisphosphonates may be prescribed inappropriately in patients with CKD.
C1 [Bhan, Ishir] Harvard Univ, Dept Med, Div Nephrol, Massachusetts Gen Hosp,Med Sch, Boston, MA 02114 USA.
[Bhan, Ishir; Dubey, Anil] Harvard Univ, Dept Med, Comp Sci Lab, Massachusetts Gen Hosp,Med Sch, Boston, MA 02114 USA.
[Wolf, Myles] Univ Miami, Miller Sch Med, Dept Med, Div Nephrol & Hypertens, Miami, FL 33136 USA.
RP Bhan, I (reprint author), Harvard Univ, Dept Med, Div Nephrol, Massachusetts Gen Hosp,Med Sch, Boston, MA 02114 USA.
EM ibhan@partners.org
FU National Institutes of Health [RO1DK076116, R01DK081374, 1K23DK081677];
National Kidney Foundation
FX Support for the design and conduct of the study was provided by grants
RO1DK076116 (MW), R01DK081374(MW) and 1K23DK081677 (IB) from the
National Institutes of Health and a Young Investigator Grant from the
National Kidney Foundation (IB).
NR 43
TC 6
Z9 6
U1 0
U2 9
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD JUL
PY 2010
VL 25
IS 7
BP 710
EP 716
DI 10.1007/s11606-010-1316-y
PG 7
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA 607RR
UT WOS:000278524700017
PM 20352364
ER
PT J
AU Lefkimmiatis, K
Leronni, D
Curci, S
Hofer, AM
AF Lefkimmiatis, Konstantinos
Leronni, Daniela
Curci, Silvana
Hofer, Aldebaran M.
TI Targeting Cyclic AMP Microdomains in Living Cells
SO JOURNAL OF GENERAL PHYSIOLOGY
LA English
DT Meeting Abstract
CT 64th Annual Meeting of the Society-of-General-Physiologists
CY SEP 08-12, 2010
CL Marine Biol Lab, Woods Hole, MA
SP Soc Gen Physiologists
HO Marine Biol Lab
C1 Harvard Univ, Sch Med, Dept Surg, VA Boston Healthcare Syst, W Roxbury, MA 02132 USA.
Brigham & Womens Hosp, W Roxbury, MA 02132 USA.
RI Lefkimmiatis, Konstantinos/I-1239-2016
OI Lefkimmiatis, Konstantinos/0000-0001-7137-7866
NR 0
TC 0
Z9 0
U1 1
U2 1
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1295
J9 J GEN PHYSIOL
JI J. Gen. Physiol.
PD JUL
PY 2010
VL 136
IS 1
MA 11
BP 7A
EP 7A
PG 1
WC Physiology
SC Physiology
GA 620BH
UT WOS:000279473500023
ER
PT J
AU Maiellaro, I
Lefkimmiatis, K
Curci, S
Hofer, AM
AF Maiellaro, Isabella
Lefkimmiatis, Konstantinos
Curci, Silvana
Hofer, Aldebaran M.
TI Does a Specific Isoform of Adenylyl Cyclase Mediate Store-operated
Cyclic AMP Signaling?
SO JOURNAL OF GENERAL PHYSIOLOGY
LA English
DT Meeting Abstract
CT 64th Annual Meeting of the Society-of-General-Physiologists
CY SEP 08-12, 2010
CL Marine Biol Lab, Woods Hole, MA
SP Soc Gen Physiologists
HO Marine Biol Lab
C1 Harvard Univ, Sch Med, Dept Surg, VA Boston Healthcare Syst, W Roxbury, MA 02132 USA.
Brigham & Womens Hosp, W Roxbury, MA 02132 USA.
RI Lefkimmiatis, Konstantinos/I-1239-2016
OI Lefkimmiatis, Konstantinos/0000-0001-7137-7866
NR 0
TC 0
Z9 0
U1 1
U2 1
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1295
J9 J GEN PHYSIOL
JI J. Gen. Physiol.
PD JUL
PY 2010
VL 136
IS 1
MA 15
BP 8A
EP 9A
PG 2
WC Physiology
SC Physiology
GA 620BH
UT WOS:000279473500027
ER
PT J
AU Brouwer, KM
Lindenhovius, ALC
de Witte, PB
Jupiter, JB
Ring, D
AF Brouwer, Kim M.
Lindenhovius, Anneluuk L. C.
de Witte, Pieter Bas
Jupiter, Jesse B.
Ring, David
TI Resection of Heterotopic Ossification of the Elbow: A Comparison of
Ankylosis and Partial Restriction
SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME
LA English
DT Article
DE Ankylosis; elbow motion; heterotopic ossification; release
ID OPERATIVE RELEASE; POSTTRAUMATIC CONTRACTURE; LATERAL APPROACH;
EXCISION; MOTION; HEAD; BONE
AB Purpose This study tests the hypothesis that the results of release of elbow stiffness related to heterotopic ossification (HO) are comparable whether there is partial or complete restriction (ankylosis) of flexion and extension.
Methods Eighteen patients who had surgical release of complete bony ankylosis between the humerus and ulna were retrospectively compared to 27 matched patients who had surgical release of partial restriction of elbow flexion and extension related to HO. Patients were evaluated a minimum of 10 months after surgery, using the Disabilities of the Arm, Shoulder, and Hand questionnaire and the Broberg and Morrey rating system.
Results An average of 22 months after surgery (range, 10 to 62 mo), the arc of flexion and extension averaged 95 degrees in the ankylosis cohort and 93 degrees in the partial HO cohort. Forearm rotation averaged 131 degrees versus 134 degrees; the mean Disabilities of the Arm, Shoulder, and Hand score was 28 versus 30 points; and the mean Broberg and Morrey score was 81 versus 84 points, respectively.
Conclusions After controlling for other factors, patients with elbow stiffness related to HO can recover comparable motion after surgical release at short-term follow-up whether they have complete ankylosis or only partial restriction of motion. (J Hand Surg 2010;35A:1115-1119. (C) 2010 Published by Elsevier Inc. on behalf of the American Society for Surgery of the Hand.)
C1 [Ring, David] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Yawkey Ctr, Boston, MA 02114 USA.
Leiden Univ, Med Ctr, Leiden, Netherlands.
RP Ring, D (reprint author), Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA.
EM dring@partners.org
FU AnnaFund; VSB Fund; Marti-Keuning-Eckhardt-Fun; Joint Active Systems;
Medical Modeling
FX Support was provided by AnnaFund, VSB Fund, and
Marti-Keuning-Eckhardt-Fun (K.M.B.); Joint Active Systems, Medical
Modeling, Annafund, Marti Fund, and Prof. van Vloten Fund (A.L.C.L.);
Annafund and LUF-Fund (P.B.d.W.); Aircast (DJ), Biomet, Hand
Innovations, Linvatec, Mitek, SBI, Sythes, Wright Medical Technology,
and Zimmer (J.B.J.); Acumed LLC, Biomet, Small Bone Innovations, Smith &
Nephew, Tomier, and Wright Medical Technology (DR.).
NR 12
TC 15
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 JUL
PY 2010
VL 35A
IS 7
BP 1115
EP 1119
DI 10.1016/j.jhsa.2010.03.040
PG 5
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA 621PZ
UT WOS:000279595100012
PM 20541330
ER
PT J
AU Lu, HLT
Guitton, TG
Capo, JT
Ring, D
AF Lu, Huangling T.
Guitton, Thierry G.
Capo, John T.
Ring, David
TI Elbow Instability Associated With Bicolumnar Fracture of the Distal
Humerus: Report of Three Cases
SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME
LA English
DT Article
DE Fracture; distal humerus; instability; internal fixation; open reduction
ID ROTATORY INSTABILITY; FIXATION
AB Ulnohumeral subluxation or dislocation is rare after open reduction and internal fixation of a bicolumnar fracture of the distal humerus. We report 3 patients in whom detachment of the origins of the lateral collateral ligament and common extensor muscle origins from the lateral epicondyle contributed to postoperative instability after open reduction and internal fixation of a fracture of the distal humerus. This may be due to either unrecognized ligament injury or iatrogenic injury during surgical dissection. (J Hand Surg 2010;35A:1126-1129. (C) 2010 Published by Elsevier Inc. on behalf of the American Society for Surgery of the Hand.)
C1 [Ring, David] Harvard Univ, Massachusetts Gen Hosp, Yawkey Ctr, Orthopaed Hand & Upper Extrem Serv,Med Sch, Boston, MA 02114 USA.
UMDNJ New Jersey Med Sch, Dept Orthopaed, Div Hand & Microvasc Surg, Newark, NJ USA.
RP Ring, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Yawkey Ctr, Orthopaed Hand & Upper Extrem Serv,Med Sch, Suite 2100,55 Fruit St, Boston, MA 02114 USA.
EM dring@partners.org
OI Guitton, Thierry/0000-0002-2599-1985
FU Synthes; Joint Active Systems; Biomet; Stryker; Orthopaedic Trauma
Association
FX John T. Capo, MD, receives research funding from Synthes and is a
consultant for and receives royalties from Wright Medical. D.R. receives
study specific grants from Joint Active Systems, Biomet, Stryker, and
the Orthopaedic Trauma Association. He is a consultant for Wright
Medical, Tomier, Acumed, Skeletal Dynamics, Joint Active Systems, a nd
Biomet. He receives honoraria from AO North America and AO International
and royalties from Wright Medical. He has stock options in Illuminos and
Mimedoc He received funding fora hand surgery fellowship from AO North
America.
NR 8
TC 1
Z9 1
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 JUL
PY 2010
VL 35A
IS 7
BP 1126
EP 1129
DI 10.1016/j.jhsa.2010.04.007
PG 4
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA 621PZ
UT WOS:000279595100014
PM 20610058
ER
PT J
AU Ebrahimzadeh, MH
Amadzadeh-Chabock, H
Ring, D
AF Ebrahimzadeh, Mohamed H.
Amadzadeh-Chabock, Husain
Ring, David
TI Traumatic Elbow Instability
SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME
LA English
DT Article
DE Traumatic elbow instability; elbow fracture dislocation; radial head
fracture; coronoid fracture; collateral ligament injury
ID MEDIAL COLLATERAL LIGAMENT; RADIAL HEAD; FRACTURE-DISLOCATIONS; CORONOID
FRACTURES; COMPLEX; REPAIR
AB Trauma can render the elbow unstable via a combination of bone and ligament injuries. Some of these injuries feature subluxation rather than dislocation of the elbow. Effective treatment centers on restoring enough of the bony and ligamentous structures to keep the elbow in joint so that recovery can proceed as for a simple elbow dislocation. Recognition of distinct patterns of injury can help determine the structures injured and the best methods for repairing them. (J Hand Surg 2010;35A:1220-4225. (C) 2010 Published by Elsevier Inc. on behalf of the American Society for Surgery of the Hand.)
C1 [Ring, David] Massachusetts Gen Hosp, Dept Orthoped Surg, Yawkee Ctr, Hand & Upper Extrem Serv, Boston, MA 02114 USA.
Mashad Univ Med Sci, Dept Orthoped Surg, Orthoped Res Ctr, Mashhad, Iran.
RP Ring, D (reprint author), Massachusetts Gen Hosp, Dept Orthoped Surg, Yawkee Ctr, Hand & Upper Extrem Serv, Suite 2100,55 Fruit St, Boston, MA 02114 USA.
EM dring@partners.org
FU Joint Active Systems; Biomet; Stryker; Orthopaedic Trauma Association;
American Foundation for Surgery of the Hand; MGH Department of
Orthopaedic Surgery; AO North America
FX D.R. received study-specific grants from Joint Active Systems, Biomet,
Stryker, the Orthopaedic Trauma Association, the American Foundation for
Surgery of the Hand, and MGH Department of Orthopaedic Surgery. He is a
consultant for Wright Medical, Tornier, Acumed, Skeletal Dynamics, Joint
Active Systems, and Biomet. He receives honoraria from Depuy, AO North
America, and AO International. He receives royalties from Hand
Innovations, Wright Medical, and Skeletal Dynamics. He has stock options
with Illuminos and Mimedex. He receives funding for a hand surgery
fellowship from AO North America.
NR 23
TC 14
Z9 14
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 0363-5023
J9 J HAND SURG-AM
JI J. Hand Surg.-Am. Vol.
PD JUL
PY 2010
VL 35A
IS 7
BP 1220
EP 1225
DI 10.1016/j.jhsa.2010.05.002
PG 6
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA 621PZ
UT WOS:000279595100031
PM 20610067
ER
PT J
AU Nigam, V
Sievers, HH
Jensen, BC
Sier, HA
Simpson, PC
Srivastava, D
Mohamed, SA
AF Nigam, Vishal
Sievers, Hans H.
Jensen, Brian C.
Sier, Holger A.
Simpson, Paul C.
Srivastava, Deepak
Mohamed, Salah A.
TI Altered MicroRNAs in Bicuspid Aortic Valve: A Comparison Between
Stenotic and Insufficient Valves
SO JOURNAL OF HEART VALVE DISEASE
LA English
DT Article
ID MUSCLE-SPECIFIC MICRORNA; INTERSTITIAL-CELLS; XENOPUS SMAD7; EXPRESSION;
DISEASE; MUTATIONS; NOTCH1; HEART; CALCIFICATION; CARDIOGENESIS
AB Background and aim of the study: Bicuspid aortic valve (BAV), the most common form of congenital heart disease, is a leading cause of aortic stenosis (AS) and aortic insufficiency (AI). AS is typically caused by calcific valve disease. Recently, microRNAs (miRNAs) have been shown to modulate gene expression. The study aim was to examine the miRNAs that were altered in the aortic valve leaflets of patients with AS compared to those in patients with AI. In-vitro experiments were also carried out to determine if these miRNAs could modulate calcification-related genes.
Methods: Aortic valve samples (fused and unfused leaflets) were collected from nine male patients (mean age 44.9 +/- 13.8 years) undergoing aortic valve replacement (AVR). PIQOR (TM) miRXplore Microarrays containing 1,421 miRNAs were used and hybridized to fused leaflet samples labeled with Cy5; unfused samples were used as controls and labeled with Cy3. A quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed to validate the miRNA array results. Cultured human aortic valve interstitial cells (AVICs) were treated with miRNA mimics, and qRT-PCR was carried out to determine any changes in mRNAs.
Results: By microarray analysis, seven miRNAs were shown to be statistically different between the AS and AI patients. In the stenotic samples, the MiR-26a and miR-195 levels were shown (by qRT-PCR) to be reduced by 65% and 59%, respectively (p <0.05), and MiR-30b to be reduced by 62% (p <0.06). Human AVICs treated with miR-26a or miR-30b mimics showed decreased mRNA levels of calcification-related genes. MiR-26a repressed BMP2 by 36%, alkaline phosphatase (ALPL) by 38%, and SMAD1 by 26%, while MiR-30b reduced the expression of SMAD1 by 18% and of SMAD3 by 12%. In contrast, miR-195-treated AVICs had increased mRNA levels of calcification-related genes, such as BMP2 by 68% and RUNX2 by 11%.
Conclusion: MiR-26a, miR-30b, and miR-195 were each decreased in the aortic valves of patients requiring AVR due to AS, compared to those requiring replacement due to AI. These miRNAs appear to modulate calcification-related genes in vitro.
C1 [Sievers, Hans H.; Sier, Holger A.; Mohamed, Salah A.] Univ Clin Schleswig Holstein, Dept Cardiac Surg, D-23538 Lubeck, Germany.
[Nigam, Vishal; Srivastava, Deepak] Univ Calif San Francisco, Dept Pediat Cardiol, San Francisco, CA 94143 USA.
[Nigam, Vishal; Srivastava, Deepak] Univ Calif San Francisco, Gladstone Inst Cardiovasc Dis, San Francisco, CA 94143 USA.
[Jensen, Brian C.; Simpson, Paul C.] San Francisco VA Med Ctr, Cardiol Sect, San Francisco, CA USA.
[Jensen, Brian C.; Simpson, Paul C.] San Francisco VA Med Ctr, Res Serv, San Francisco, CA USA.
[Jensen, Brian C.; Simpson, Paul C.] Univ Calif San Francisco, Dept Med Cardiol, San Francisco, CA 94143 USA.
[Jensen, Brian C.; Simpson, Paul C.] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA.
RP Mohamed, SA (reprint author), Univ Clin Schleswig Holstein, Dept Cardiac Surg, Campus Lubeck,Ratzeburger Allee 160, D-23538 Lubeck, Germany.
EM salah.mohamed@uni-luebeck.de
FU NIH [K08 HL086775-01]
FX The authors thank the members of their respective laboratories for
helpful discussions. Dr. Nigam designed and performed the qPCR and
in-vitro experiments, Drs. Sievers and Sier assisted with the patient
valve collection, and Drs. Jensen and Simpson provided access to the
Cardiac Tissue Bank at UCSF, from which the aortic valve leaflets used
for AVIC culture were obtained. Dr. Nigam received funding from NIH
grant K08 HL086775-01.
NR 28
TC 41
Z9 42
U1 0
U2 1
PU I C R PUBLISHERS
PI NORTHWOOD
PA CRISPIN HOUSE, 12/A SOUTH APPROACH, MOOR PARK, NORTHWOOD HA6 2ET,
ENGLAND
SN 0966-8519
J9 J HEART VALVE DIS
JI J. Heart Valve Dis.
PD JUL
PY 2010
VL 19
IS 4
BP 459
EP 465
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 694FR
UT WOS:000285280900009
PM 20845893
ER
PT J
AU Patel, P
Dhaliwal, G
Rajamanickam, A
Gebresalassie, S
Harte, B
AF Patel, Preethi
Dhaliwal, Gurpreet
Rajamanickam, Anitha
Gebresalassie, Surafel
Harte, Brian
TI Continuing Medical Education Program in the Journal of Hospital Medicine
SO JOURNAL OF HOSPITAL MEDICINE
LA English
DT Editorial Material
C1 [Patel, Preethi; Rajamanickam, Anitha; Harte, Brian] Cleveland Clin Fdn, Dept Hosp Med, Cleveland, OH 44195 USA.
[Dhaliwal, Gurpreet] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Dhaliwal, Gurpreet] San Francisco VA Med Ctr, Dept Med, San Francisco, CA USA.
[Gebresalassie, Surafel] Cleveland Clin Fdn, Dept Hypertens & Nephrol, Cleveland, OH 44195 USA.
RP Patel, P (reprint author), Cleveland Clin Fdn, Dept Hosp Med, 9500 Euclid Ave, Cleveland, OH 44195 USA.
NR 0
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 JUL-AUG
PY 2010
VL 5
IS 6
BP 365
EP 365
DI 10.1002/jhm.837
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 643JD
UT WOS:000281290600011
ER
PT J
AU Patel, P
Dhaliwal, G
Rajamanickam, A
Gehresalassie, S
Harte, B
AF Patel, Preethi
Dhaliwal, Gurpreet
Rajamanickam, Anitha
Gehresalassie, Surafel
Harte, Brian
TI Unscripted
SO JOURNAL OF HOSPITAL MEDICINE
LA English
DT Editorial Material
ID THROMBOTIC THROMBOCYTOPENIC PURPURA; HEMOLYTIC-UREMIC SYNDROME;
MICROANGIOPATHY
C1 [Patel, Preethi; Rajamanickam, Anitha; Harte, Brian] Cleveland Clin Fdn, Dept Hosp Med, Cleveland, OH 44195 USA.
[Dhaliwal, Gurpreet] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Dhaliwal, Gurpreet] San Francisco VA Med Ctr, Dept Med, San Francisco, CA USA.
[Gehresalassie, Surafel] Cleveland Clin Fdn, Dept Hypertens & Nephrol, Cleveland, OH 44195 USA.
RP Patel, P (reprint author), Desk M2,9500 Euclid Ave, Cleveland, OH 44195 USA.
EM patelp3@ccf.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 JUL-AUG
PY 2010
VL 5
IS 6
BP 366
EP 370
DI 10.1002/jhm.806
PG 5
WC Medicine, General & Internal
SC General & Internal Medicine
GA 643JD
UT WOS:000281290600012
PM 20803678
ER
PT J
AU Beriou, G
Bradshaw, EM
Lozano, E
Costantino, CM
Hastings, WD
Orban, T
Elyaman, W
Khoury, SJ
Kuchroo, VK
Baecher-Allan, C
Hafler, DA
AF Beriou, Gaelle
Bradshaw, Elizabeth M.
Lozano, Ester
Costantino, Cristina M.
Hastings, William D.
Orban, Tihamer
Elyaman, Wassim
Khoury, Samia J.
Kuchroo, Vijay K.
Baecher-Allan, Clare
Hafler, David A.
TI TGF-beta Induces IL-9 Production from Human Th17 Cells
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID GROWTH-FACTOR-BETA; REGULATORY T-CELLS; TRANSCRIPTION FACTOR; T-H-17
CELLS; T(H)17 CELLS; DIFFERENTIATION; INFLAMMATION; EXPRESSION;
INDUCTION; IMMUNITY
AB The secretion of IL-9, initially recognized as a Th2 cytokine, was recently attributed to a novel CD4 T cell subset termed Th9 in the murine system. However, IL-9 can also be secreted by mouse Th17 cells and may mediate aspects of the proinflammatory activities of Th17 cells. Here we report that IL-9 is secreted by human naive CD4 T cells in response to differentiation by Th9 (TGF-beta and IL-4) or Th17 polarizing conditions. Yet, these differentiated naive cells did not coexpress IL-17 and IL-9, unless they were repeatedly stimulated under Th17 differentiation-inducing conditions. In contrast to the naive cells, memory CD4 T cells were induced to secrete IL-9 by simply providing TGF-beta during stimulation, as neither IL-4 nor proinflammatory cytokines were required. Furthermore, the addition of TGF-beta to the Th17-inducing cytokines (IL-1 beta, IL-6, IL-21, IL-23) that induce memory cells to secrete IL-17, resulted in the marked coexpression of IL-9 in IL-17 producing memory cells. The proinflammatory cytokine mediating TGF-beta-dependent coexpression of IL-9 and IL-17 was identified to be IL-1 beta. Moreover, circulating monocytes were potent costimulators of IL-9 production by Th17 cells via their capacity to secrete IL-1 beta. Finally, to determine whether IL-9/IL-17 coproducing CD4 cells were altered in an inflammatory condition, we examined patients with autoimmune diabetes and demonstrated that these subjects exhibit a higher frequency of memory CD4 cells with the capacity to transition into IL-9(+)IL-17(+) cells. These data demonstrate the presence of IL-17(+)IL-9(+)CD4 cells induced by IL-1 beta that may play a role in human autoimmune disease. The Journal of Immunology, 2010, 185: 46-54.
C1 [Beriou, Gaelle; Bradshaw, Elizabeth M.; Lozano, Ester; Costantino, Cristina M.; Hastings, William D.; Elyaman, Wassim; Khoury, Samia J.; Kuchroo, Vijay K.; Baecher-Allan, Clare; Hafler, David A.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Neurol Dis,Div Mol Immunol, Boston, MA 02215 USA.
[Orban, Tihamer] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Immunol & Immunogenet, Boston, MA 02215 USA.
[Hafler, David A.] Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06520 USA.
[Hafler, David A.] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA.
RP Baecher-Allan, C (reprint author), NRB 641,77 Ave Louis Pasteur, Boston, MA 02115 USA.
EM callan@rics.bwh.harvard.edu
RI Lozano, Ester/H-2215-2014
OI Lozano, Ester/0000-0002-6307-9807
FU National Multiple Sclerosis Society [FG1744A1, RG3825A1]; Dana Scholars
grant; National Institutes of Health [P01 AI045757, U19 AI046130, U19
AI070352, P01 AI039671, F32 AI651003]; National Institute of
Neurological Disorders and Stroke [NS2427]
FX This work was supported by National Multiple Sclerosis Society Grant
FG1744A1 (to G. B.) and Grant RG3825A1, a Dana Scholars grant (to C. B.
A.), and National Institutes of Health Grants P01 AI045757, U19
AI046130, U19 AI070352, P01 AI039671, (to D. A. H.) and F32 AI651003 (to
E. M. B). D. A. H. is also supported by Jacob Javits Merit Award NS2427
from the National Institute of Neurological Disorders and Stroke.
NR 26
TC 81
Z9 90
U1 1
U2 12
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD JUL 1
PY 2010
VL 185
IS 1
BP 46
EP 54
DI 10.4049/jimmunol.1000356
PG 9
WC Immunology
SC Immunology
GA 612VS
UT WOS:000278933800007
PM 20498357
ER
PT J
AU Singhal, A
Nagarajan, R
Hinkin, CH
Kumar, R
Sayre, J
Elderkin-Thompson, V
Huda, A
Gupta, RK
Han, SH
Thomas, MA
AF Singhal, Aparna
Nagarajan, Rajakumar
Hinkin, Charles H.
Kumar, Rajesh
Sayre, James
Elderkin-Thompson, Virginia
Huda, Amir
Gupta, Rakesh K.
Han, Steven-Huy
Thomas, M. Albert
TI Two-Dimensional MR Spectroscopy of Minimal Hepatic Encephalopathy and
Neuropsychological Correlates In Vivo
SO JOURNAL OF MAGNETIC RESONANCE IMAGING
LA English
DT Article; Proceedings Paper
CT 17th Annual Meeting of the
International-Society-of-Magnetic-Resonance-in-Medicine
CY APR 18-24, 2009
CL Honolulu, HI
SP Int Soc Magnet Resonance Med
DE MRI; MRS; COSY; neuropsychological scores; liver disease
ID MAGNETIC-RESONANCE-SPECTROSCOPY; LOCALIZED H-1-NMR SPECTROSCOPY; INDUCED
BRAIN EDEMA; LIVER-TRANSPLANTATION; BASAL GANGLIA; PORTACAVAL
ANASTOMOSIS; TAURINE TRANSPORTER; SIGNAL INTENSITY; GLOBUS-PALLIDUS;
CEREBRAL EDEMA
AB Purpose: To evaluate regional cerebral metabolic and structural changes in patients with minimal hepatic encephalopathy (MHE) using two-dimensional (2D) MR spectroscopy (MRS) and T(1)-weighted MRI, to correlate the observed MR changes with neuropsychological (NP) test scores, and to compare the diagnostic accuracy of MRI, 2D MRS, and NP tests in discriminating between patients and healthy subjects.
Materials and Methods: Thirty-three MHE patients and 30 healthy controls were investigated. The 2D localized correlated spectroscopy (L-COSY) was performed in the frontal and occipital brain on a 1.5 Testa (T) MR scanner. The NP test battery included 15 tests, grouped into 6 cognitive domains. Globus pallidus signal intensities were calculated from T(1)-weighted images.
Results: The 2D MRS showed significant differences in ratios of the following metabolite(s) peaks with respect to creatine (Cr): decreased myo-inositol (mI), choline (Ch), mICh, and increased (glutamate plus glutamine) (Glx) in patients compared with healthy subjects in both occipital and frontal lobes. Frontal lobe taurine also showed a decline in patients. The NP test results revealed declines in cognitive speed, motor function, executive function, and global cognitive status. Significant correlations were found between the altered metabolites and NP tests. Alteration in the mICh/Cr ratio was noted as a powerful discriminant between healthy subjects and the patients.
Conclusion: The study demonstrates that relative metabolite levels determined by 2D MRS, in particular mICh/Cr, provide the best diagnostic prediction for MHE. The results suggest that depletions of myo-inositol, choline and taurine with respect to creatine correlate with measures of neuropsychological impairment.
C1 [Singhal, Aparna; Nagarajan, Rajakumar; Sayre, James; Huda, Amir; Thomas, M. Albert] Univ Calif Los Angeles, David Geffen Sch Med, Dept Radiol Sci, Los Angeles, CA 90095 USA.
[Hinkin, Charles H.; Elderkin-Thompson, Virginia; Thomas, M. Albert] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat, Los Angeles, CA 90095 USA.
[Hinkin, Charles H.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
[Kumar, Rajesh] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA.
[Sayre, James] Univ Calif Los Angeles, David Geffen Sch Med, Dept Publ Hlth Biostat, Los Angeles, CA 90095 USA.
[Huda, Amir] Calif State Univ Fresno, Dept Phys, Fresno, CA 93740 USA.
[Gupta, Rakesh K.] Sanjay Gandhi Postgrad Inst Med Sci, Dept Radiol, Lucknow, Uttar Pradesh, India.
[Han, Steven-Huy] Univ Calif Los Angeles, David Geffen Sch Med, Dept Hepatol, Los Angeles, CA 90095 USA.
RP Thomas, MA (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Radiol Sci, CHS BL 428,10833 Le Conte Ave, Los Angeles, CA 90095 USA.
EM athomas@mednet.ucla.edu
RI Thomas, m. albert/A-6176-2012; Nagarajan, Rajakumar/A-7179-2013; Huda,
Amir/I-5987-2015
OI Huda, Amir/0000-0002-0171-3796
FU NIMH NIH HHS [1R01MH06569501A1]
NR 54
TC 19
Z9 22
U1 0
U2 5
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1053-1807
J9 J MAGN RESON IMAGING
JI J. Magn. Reson. Imaging
PD JUL
PY 2010
VL 32
IS 1
BP 35
EP 43
DI 10.1002/jmri.22216
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 619ON
UT WOS:000279439600004
PM 20578008
ER
PT J
AU Goren, JL
Beck, SE
Mills, BJ
Shtasel, DL
Dufresne, RL
AF Goren, Jessica L.
Beck, Stuart E.
Mills, Barry J.
Shtasel, Derri L.
Dufresne, Robert L.
TI Development and Delivery of a Quality Improvement Program to Reduce
Antipsychotic Polytherapy
SO JOURNAL OF MANAGED CARE PHARMACY
LA English
DT Article
ID PLACEBO-CONTROLLED TRIAL; RANDOMIZED CONTROLLED-TRIAL; DOUBLE-BLIND;
REFRACTORY SCHIZOPHRENIA; SULPIRIDE AUGMENTATION; DRUG-USE;
POLYPHARMACY; CLOZAPINE; RISPERIDONE; 2ND-GENERATION
AB BACKGROUND. Although antipsychotic polytherapy is considered appropriate in limited circumstances (e.g., during a brief "cross-titration" period when switching medications), its increasing prevalence indicates use beyond this limited scope Despite absence of support in the medical literature and higher costs, antipsychotic polytherapy is common in the treatment of schizophrenia and related disorders. The highest utilization of antipsychotic polytherapy occurs on psychiatric inpatient units, and in 2008, the Joint Commission released the first set of 7 hospital-based inpatient psychiatric services (HBIPS) core measures, 2 of which assess antipsychotic polytherapy at time of discharge.
OBJECTIVE: To describe the effect on antipsychotic polytherapy at time of discharge of a 2-part quality improvement program composed of educational seminars and prescriber-specific feedback provided to 11 psychiatrists in 4 acute inpatient psychiatric units in 2 hospitals.
METHODS: In a regional academic health care system, we determined the prevalence of antipsychotic monotherapy and polytherapy at time of discharge for all patients discharged on standing antipsychotic medications during 3 periods. (a) a 3-month baseline period (August 2006 through October 2006); (b) in July 2007, after delivery of 4 educational luncheon seminars to 11 psychiatrists from November 2006 through June 2007; and (c) in June 2008, following the provision of monthly prescriber-specific audit feedback from August 2007 through June 2008. To prepare nurses for the change and address possible safety concerns, an educational module was delivered to the psychiatric nursing staff at "best practice" day lectures held in the first quarter of 2007. General themes in the educational presentations included literature-based reviews of (a) safety and efficacy of antipsychotic polytherapy, (b) medical risks of antipsychotic medications, (c) specific versus nonspecific effects of these medications, and (d) effectiveness of first- versus second-generation antipsychotic medications. The prescriber-specific audit feedback was provided in paper form and masked the identity of the other prescribers. The chief of service reviewed audit feedback individually with each psychiatrist on a quarterly basis. The primary outcome measure was the percentage of patients prescribed 2 or more antipsychotics at discharge. A secondary outcome measure was the percentage of patients prescribed 3 or more antipsychotics at discharge. Differences in the primary outcome measure, comparing (a) July 2007 with the baseline period and (b) June 2008 with July 2007, were analyzed using Fisher's Exact tests. The Cochran-Armitage test for trend was used to assess the relationship between the primary outcome measure and the extent of the intervention, measured as the 3 time periods. For the secondary outcome measure, the Goodman-Kruskal gamma test for ordered categorical data was calculated to examine the association between the the proportion of patients receiving 1, 2, or 3 or more antipsychotics at discharge and the 3 time periods
RESULTS: The percentage of patients prescribed 2 or more antipsychotics at discharge declined from 33 9% at baseline (132 of 389 patients), to 21 8% after delivery of the educational modules (44 of 202 patients, P=0.002), and to 12.2% after audit feedback (18 of 147 patients, P=0.023; Cochran-Armitage test for trend P<0.001). When antipsychotic use was classified as 1, 2, or 3 or more antipsychotic medications, more extensive intervention was associated with decreased combination use (Goodman-Kruskal gamma =0.39, P<0.001) In the baseline period, 5.9% of patients were prescribed 3 or more antipsychotics at discharge. Following completion of the educational and audit components, respectively, the proportion of patients prescribed 3 or more antipsychotics declined to 2.5% and then to 0.0%.
CONCLUSION: Educational modules presented to psychiatrists and nurses in group settings were associated with a decrease in the rate of prescribing 2 or more antipsychotics at discharge from acute psychiatric inpatient units. Addition of monthly audit feedback provided to psychiatrists was associated with further decreases. J Manag Care Pharm. 2010;16(6):393-401 Copyright (C) 2010, Academy of Managed Care Pharmacy. All rights reserved.
C1 [Goren, Jessica L.] Cambridge Hlth Alliance, Pharm Adm, Somerville, MA 02143 USA.
[Goren, Jessica L.] Cambridge Hlth Alliance, Cambridge, MA USA.
[Goren, Jessica L.] Univ Rhode Isl, Kingston, RI 02881 USA.
[Beck, Stuart E.] Cambridge Hlth Alliance, Inpatient Psychiat Serv, Cambridge, MA USA.
[Mills, Barry J.] Univ Calif Santa Barbara, Santa Barbara, CA 93106 USA.
[Shtasel, Derri L.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Dufresne, Robert L.] Univ Rhode Isl, Kingston, RI 02881 USA.
RP Goren, JL (reprint author), Cambridge Hlth Alliance, Pharm Adm, 120 Beacon St,Ste 202, Somerville, MA 02143 USA.
NR 37
TC 4
Z9 4
U1 0
U2 5
PU ACAD MANAGED CARE PHARMACY
PI ALEXANDRIA
PA 100 N PITT ST, 400, ALEXANDRIA, VA 22314-3134 USA
SN 1083-4087
J9 J MANAGE CARE PHARM
JI J. Manag. Care Pharm.
PD JUL-AUG
PY 2010
VL 16
IS 6
BP 393
EP 401
PG 9
WC Health Care Sciences & Services; Pharmacology & Pharmacy
SC Health Care Sciences & Services; Pharmacology & Pharmacy
GA 632VD
UT WOS:000280456200002
PM 20635830
ER
PT J
AU Fitzgerald, RC
Hardwick, R
Huntsman, D
Carneiro, F
Guilford, P
Blair, V
Chung, DC
Norton, J
Ragunath, K
Van Krieken, JH
Dwerryhouse, S
Caldas, C
AF Fitzgerald, Rebecca C.
Hardwick, Richard
Huntsman, David
Carneiro, Fatima
Guilford, Parry
Blair, Vanessa
Chung, Daniel C.
Norton, Jeff
Ragunath, Krishnadath
Van Krieken, J. Han
Dwerryhouse, Sarah
Caldas, Carlos
CA Int Gastric Canc Linkage
TI Hereditary diffuse gastric cancer: updated consensus guidelines for
clinical management and directions for future research
SO JOURNAL OF MEDICAL GENETICS
LA English
DT Article
ID E-CADHERIN MUTATION; PROPHYLACTIC TOTAL GASTRECTOMY;
RING-CELL-CARCINOMA; GERMLINE MUTATIONS; COLORECTAL-CANCER;
FAMILY-HISTORY; BREAST-CANCER; CDH1; STOMACH; RISK
AB 25-30% of families fulfilling the criteria for hereditary diffuse gastric cancer have germline mutations of the CDH1 (E-cadherin) gene. In light of new data and advancement of technologies, a multidisciplinary workshop was convened to discuss genetic testing, surgery, endoscopy and pathology reporting. The updated recommendations include broadening of CDH1 testing criteria such that: histological confirmation of diffuse gastric criteria is only required for one family member; inclusion of individuals with diffuse gastric cancer before the age of 40 years without a family history; and inclusion of individuals and families with diagnoses of both diffuse gastric cancer (including one before the age of 50 years) and lobular breast cancer. Testing is considered appropriate from the age of consent following counselling and discussion with a multidisciplinary team. In addition to direct sequencing, large genomic rearrangements should be sought. Annual mammography and breast MRI from the age of 35 years is recommended for women due to the increased risk for lobular breast cancer. In mutation positive individuals prophylactic total gastrectomy at a centre of excellence should be strongly considered. Protocolised endoscopic surveillance in centres with endoscopists and pathologists experienced with these patients is recommended for: those opting not to have gastrectomy, those with mutations of undetermined significance, and in those families for whom no germline mutation is yet identified. The systematic histological study of prophylactic gastrectomies almost universally shows pre-invasive lesions including in situ signet ring carcinoma with pagetoid spread of signet ring cells. Expert histopathological confirmation of these early lesions is recommended.
C1 [Fitzgerald, Rebecca C.] Hutchison MRC Res Ctr, MRC Canc Cell Unit, Cambridge CB2 0XZ, England.
[Fitzgerald, Rebecca C.] Addenbrookes Hosp, Dept Gastroenterol, Cambridge CB2 2QQ, England.
[Fitzgerald, Rebecca C.; Caldas, Carlos] Univ Cambridge NHS Fdn Trust, Cambridge NIHR Biomed Res Ctr, Cambridge, England.
[Hardwick, Richard] Addenbrookes Hosp, Dept Oesophago Gastr Surg, Cambridge, England.
[Huntsman, David] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada.
[Carneiro, Fatima] Univ Porto IPATIMUP, Inst Mol Pathol & Immunol, Oporto, Portugal.
[Carneiro, Fatima] Hosp Sao Joao, Fac Med Porto, Oporto, Portugal.
[Guilford, Parry; Blair, Vanessa] Univ Otago, Dept Biochem, Christchurch, New Zealand.
[Chung, Daniel C.] Massachusetts Gen Hosp, Gastrointestinal Unit, GI Canc Genet Clin, Boston, MA 02114 USA.
[Norton, Jeff] Stanford Univ, Div Gen Surg, Stanford, CA 94305 USA.
[Ragunath, Krishnadath] Nottingham Univ Hosp NHS Trust, Queens Med Ctr, Wolfson Digest Dis Ctr, Nottingham, England.
[Van Krieken, J. Han] Radboud Univ Nijmegen, Med Ctr, Dept Pathol, NL-6525 ED Nijmegen, Netherlands.
[Dwerryhouse, Sarah] Addenbrookes Hosp, Univ Dept Oncol, Canc Res UK Familial Gastr Canc Study, Cambridge, England.
[Caldas, Carlos] Univ Cambridge, Dept Oncol, Li Ka Shing Ctr, Cambridge CB2 1TN, England.
[Caldas, Carlos] Canc Res UK Cambridge Res Inst, Cambridge, England.
RP Fitzgerald, RC (reprint author), Hutchison MRC Res Ctr, MRC Canc Cell Unit, Hills Rd, Cambridge CB2 0XZ, England.
EM rcf@hutchison-mrc.ac.uk
RI Caldas, Carlos/A-7543-2008; van Krieken, Joannes/D-4138-2009; seruca,
raquel/F-8187-2011; Hoogerbrugge, Nicoline/O-1016-2013; Carneiro,
Fatima/J-6432-2013; Lovat, Laurence/C-1986-2009; Oliveira,
Carla/F-8188-2011
OI van Krieken, Joannes/0000-0001-6544-1040; Carneiro,
Fatima/0000-0002-1964-1006; Lovat, Laurence/0000-0003-4542-3915;
Oliveira, Carla/0000-0001-8340-2264
FU British Society of Gastroenterology; Cancer Research UK
FX Other Funders: British Society of Gastroenterology; Cancer Research UK.
NR 63
TC 203
Z9 214
U1 1
U2 18
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0022-2593
J9 J MED GENET
JI J. Med. Genet.
PD JUL
PY 2010
VL 47
IS 7
BP 436
EP 444
DI 10.1136/jmg.2009.074237
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA 618BO
UT WOS:000279326400002
PM 20591882
ER
PT J
AU McGee, TL
Seyedahmadi, BJ
Sweeney, MO
Dryja, TP
Berson, EL
AF McGee, Terri L.
Seyedahmadi, Babak Jian
Sweeney, Meredith O.
Dryja, Thaddeus P.
Berson, Eliot L.
TI Novel mutations in the long isoform of the USH2A gene in patients with
Usher syndrome type II or non-syndromic retinitis pigmentosa
SO JOURNAL OF MEDICAL GENETICS
LA English
DT Article
ID SYNDROME TYPE 1F; MISSENSE SUBSTITUTIONS; PROTEIN FUNCTION; ASHKENAZI
JEWS; PREVALENCE; CLASSIFICATION; IDENTIFICATION; VARIANTS; UNDERLIE;
HARMONIN
AB Background Usher syndrome type II (USH2) is an autosomal recessive disorder characterised by retinitis pigmentosa (RP) and mild to moderate sensorineural hearing loss. Mutations in the USH2A gene are the most common cause of USH2 and are also a cause of some forms of RP without hearing loss (ie, non-syndromic RP). The USH2A gene was initially identified as a transcript comprised of 21 exons but subsequently a longer isoform containing 72 exons was identified.
Methods The 51 exons unique to the long isoform of USH2A were screened for mutations among a core set of 108 patients diagnosed with USH2 and 80 patients with non-syndromic RP who were all included in a previously reported screen of the short isoform of USH2A. For several exons, additional patients were screened.
Results In total, 35 deleterious mutations were identified including 17 nonsense mutations, 9 frameshift mutations, 5 splice-site mutations, and 4 small in-frame deletions or insertions. Twenty-seven mutations were novel. In addition, 65 rare missense changes were identified. A method of classifying the deleterious effect of the missense changes was developed using the summed results of four different mutation assessment algorithms, SIFT, pMUT, PolyPhen, and AGVGD. This system classified 8 of the 65 changes as 'likely deleterious' and 9 as 'possibly deleterious'.
Conclusion At least one mutation was identified in 57-63% of USH2 cases and 19-23% of cases of non-syndromic recessive RP (calculated without and including probable/possible deleterious changes) thus supporting that USH2A is the most common known cause of RP in the USA.
C1 [McGee, Terri L.; Berson, Eliot L.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA 02114 USA.
[McGee, Terri L.; Seyedahmadi, Babak Jian; Sweeney, Meredith O.; Dryja, Thaddeus P.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Mol Genet Inst, Boston, MA 02114 USA.
RP Berson, EL (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab, 243 Charles St, Boston, MA 02114 USA.
EM Linda_Berard@meei.harvard.edu
FU US National Institutes of Health [NIH-EY00169, NIH-EY08683,
P30-EY014104]; Foundation Fighting Blindness, Owings Mills, MD
FX This work was supported by the US National Institutes of Health grants
NIH-EY00169, NIH-EY08683, and P30-EY014104, and The Foundation Fighting
Blindness, Owings Mills, MD.
NR 41
TC 43
Z9 45
U1 0
U2 6
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0022-2593
J9 J MED GENET
JI J. Med. Genet.
PD JUL
PY 2010
VL 47
IS 7
BP 499
EP 506
DI 10.1136/jmg.2009.075143
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA 618BO
UT WOS:000279326400011
PM 20507924
ER
PT J
AU Kernisan, LP
Sudore, RL
Knight, SJ
AF Kernisan, Leslie P.
Sudore, Rebecca L.
Knight, Sara J.
TI Information-Seeking at a Caregiving Website: A Qualitative Analysis
SO JOURNAL OF MEDICAL INTERNET RESEARCH
LA English
DT Article
DE Caregivers; Internet; consumer health information
ID FAMILY CAREGIVERS; HEALTH-CARE; FOCUS GROUPS; WEB; ONLINE; INTERNET;
NEEDS; CREDIBILITY; SURVIVORS; SUPPORT
AB Background: The Internet is widely used for health information, yet little is known about the online activity of family caregivers of elders, a rapidly growing group. In order to better understand the online information-seeking activity of "e-caregivers" and other visitors at a caregiving website, we undertook a qualitative analysis of survey data from a website marketed as a comprehensive resource for adults caring for aging parents.
Objective: The objectives were to better understand what types of information are sought by those visiting a website focused on elder-care issues and to identify overarching themes that might inform future development of Internet resources related to caregiving and aging.
Methods: From March 2008 to March 2009, a 5-question pop-up survey was offered 9662 times and completed 2161 times. For 1838 respondents, included was a free text answer to the question "What were you looking for?" and 1467 offered relevant and detailed responses. The survey also asked about satisfaction with the site, gender of the respondent, and relationship to the individual being cared for. Content analysis was used to develop a coding dictionary, to code responses into information-seeking categories, and to identify overarching themes.
Results: Of the respondents (76% of whom were female), 50% indicated they were caring for parents, 17% for themselves only, and 31% for others. Over half (57%) reported finding what they were looking for, and 46% stated they were extremely likely to recommend the website. Frequently mentioned information-seeking categories included "health information," "practical caregiving," and "support." Respondents also requested information related to housing, legal, insurance, and financial issues. Many responses referred to multiple comorbid conditions and complex caregiving situations. Overarching themes included (1) a desire for assistance with a wide range of practical skills and information and (2) help interpreting symptoms and behavior, such as knowing what life impacts to expect over the course of a health condition or treatment.
Conclusion: Visitors to a website targeting adults caring for aging parents reported seeking both general information on caregiving and specific assistance with the complex custodial, medical, emotional, and financial aspects of caregiving. Visitors requested both information to build caregiving skills as well as assistance in interpreting and knowing what to expect from symptoms, health conditions, and changes in behavior and relationships. Many desired communication with and support from other caregivers. Health care providers and eHealth developers should expect that many caregivers of elders are using the Internet as a resource. Further research and development is needed to fully realize the Internet's potential for education and support of caregivers.
C1 [Kernisan, Leslie P.] Univ Calif San Francisco, Div Geriatr, San Francisco VA Med Ctr, San Francisco, CA 94121 USA.
[Sudore, Rebecca L.; Knight, Sara J.] San Francisco VA Med Ctr, Interdisciplinary Program Improve Care Vet Comple, San Francisco, CA USA.
RP Kernisan, LP (reprint author), Univ Calif San Francisco, Div Geriatr, San Francisco VA Med Ctr, 4150 Clement St,181G, San Francisco, CA 94121 USA.
EM lkernisan@gmail.com
FU VA Quality Scholars; National Institute on Aging, National Institutes of
Health; VA Career Development Award; Pfizer; Department of Veterans
Affairs, Veterans Health Administration, Office of Research and
Development, Health Services Research and Development Service
FX We are grateful to Caring.com, who shared their deidentified data with
us at no cost. Caring.com did not otherwise provide any funding or
support for this project, and the company was not involved in the study
design, analysis, or drafting of the manuscript. Dr Kernisan was
supported by a VA Quality Scholars fellowship, followed by a T32
research fellowship grant from the National Institute on Aging, National
Institutes of Health. Dr Sudore was supported by a VA Career Development
Award and a Pfizer Clear Health Communication Fellowship. Dr Knight was
supported by the Department of Veterans Affairs, Veterans Health
Administration, Office of Research and Development, Health Services
Research and Development Service. The views expressed in this article
are those of the authors and do not necessarily reflect the position or
policy of the Department of Veterans Affairs or the United States
government.
NR 41
TC 22
Z9 22
U1 3
U2 19
PU JOURNAL MEDICAL INTERNET RESEARCH
PI TORONTO
PA TORONTO GENERAL HOSPITAL, R FRASER ELLIOTT BLDG, 4TH FL, R 4S435, 190
ELIZABETH ST, TORONTO, ON M5G 2C4, CANADA
SN 1438-8871
J9 J MED INTERNET RES
JI J. Med. Internet Res.
PD JUL-SEP
PY 2010
VL 12
IS 3
AR e31
DI 10.2196/jmir.1548
PG 13
WC Health Care Sciences & Services; Medical Informatics
SC Health Care Sciences & Services; Medical Informatics
GA 661VW
UT WOS:000282761500004
PM 20675292
ER
PT J
AU Heinlen, LD
Ritterhouse, LL
McClain, MT
Keith, MP
Neas, BR
Harley, JB
James, JA
AF Heinlen, Latisha D.
Ritterhouse, Lauren L.
McClain, Micah T.
Keith, Michael P.
Neas, Barbara R.
Harley, John B.
James, Judith A.
TI Ribosomal P autoantibodies are present before SLE onset and are directed
against non-C-terminal peptides
SO JOURNAL OF MOLECULAR MEDICINE-JMM
LA English
DT Article
DE Lupus; Antibodies; Autoimmunity; Ribosomal P; Epitope
ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; PROTEIN ANTIBODIES; REVISED CRITERIA;
ASSOCIATION; DIAGNOSIS; DISEASE; EPITOPE; CLASSIFICATION; AUTOIMMUNITY;
EVENTS
AB Autoantibodies to ribosomal P (ribo P) are found in 15-30% of systemic lupus erythematosus (SLE) patients and are highly specific for SLE. The goal of this study is to assess the temporal association of anti-ribosomal P (anti-P) responses with SLE disease onset, as well as to characterize select humoral ribo P epitopes targeted in early, pre-diagnostic SLE samples. Patients with stored serial serum samples available prior to SLE diagnosis were identified from a military cohort. Each sample was tested for antibodies against ribo P utilizing standard C terminus ribo P enzyme-linked immunosorbent assays (ELISA) and a solid phase, bead-based assay with affinity-purified ribo P proteins. In this study, antibodies to ribo P were more common in African American SLE patients (p = 0.026), and anti-P-positive patients comprised a group with more measured autoantibody specificities than did other SLE patients (3.5 vs 2.2, p < 0.05). Antibodies against ribo P were present on average 1.7 years before SLE diagnosis and were detected an average of 1.08 years earlier in pre-diagnostic SLE samples using affinity-purified whole protein rather than C-terminal peptide alone (p = 0.0019). Furthermore, 61% of anti-P-positive patients initially had antibodies to aa 99-113, a known ribosomal P0 antigenic target, at a time point when no antibodies to the clinically used C terminus were detected. Our findings provide evidence that antibodies against ribosomal P frequently develop before clinical SLE diagnosis and are more broadly reactive than previously thought by targeting regions outside of the C terminus.
C1 [Heinlen, Latisha D.; Ritterhouse, Lauren L.; McClain, Micah T.; Harley, John B.; James, Judith A.] Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA.
[Heinlen, Latisha D.; Ritterhouse, Lauren L.; Neas, Barbara R.; Harley, John B.; James, Judith A.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK 73104 USA.
[Keith, Michael P.] Natl Naval Med Ctr, Bethesda, MD 20889 USA.
[Keith, Michael P.] Walter Reed Army Med Ctr, Washington, DC 20307 USA.
[Harley, John B.] US Dept Vet Affairs, Med Ctr, Oklahoma City, OK 73104 USA.
RP James, JA (reprint author), Oklahoma Med Res Fdn, 825 NE 13th St, Oklahoma City, OK 73104 USA.
EM Judith-James@omrf.org
FU National Institutes of Health [AI82714, AI31584, AR58554, AR45451,
AI47575, AR53483, AR48045, AR45084, AR45231, AR42460, AR48940, AI24717,
RR20143, RR15577, RR14467]; Presbyterian Health Foundation; Lou Kerr
Chair in Biomedical Research; Kirkland Foundation; US Department of
Veteran Affairs
FX The authors would like to thank Yasmin Akbarali MS, Roy Rindler MD, Tara
Bruner PA-C, and Gabriel Vidal for their technical assistance and Scott
Stewart MS for his statistical analysis assistance. This work has been
supported by the National Institutes of Health (AI82714, AI31584,
AR58554, AR45451, AI47575, AR53483, AR48045, AR45084, AR45231, AR42460,
AR48940, AI24717, RR20143, RR15577, and RR14467), the Presbyterian
Health Foundation, the Lou Kerr Chair in Biomedical Research, the
Kirkland Foundation, and the US Department of Veteran Affairs. The
opinions and assertions contained herein are private views of the
authors and are not to be construed as official or as reflecting the
views of the Army, Navy, or the Department of Defense.
NR 32
TC 20
Z9 20
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0946-2716
J9 J MOL MED
JI J. Mol. Med.
PD JUL
PY 2010
VL 88
IS 7
BP 719
EP 727
DI 10.1007/s00109-010-0618-1
PG 9
WC Genetics & Heredity; Medicine, Research & Experimental
SC Genetics & Heredity; Research & Experimental Medicine
GA 602DY
UT WOS:000278119900009
PM 20396862
ER
PT J
AU Cobert, J
Hochberg, E
Woldenberg, N
Hochberg, F
AF Cobert, Julien
Hochberg, Ephraim
Woldenberg, Nina
Hochberg, Fred
TI Monotherapy with methotrexate for primary central nervous lymphoma has
single agent activity in the absence of radiotherapy: a single
institution cohort
SO JOURNAL OF NEURO-ONCOLOGY
LA English
DT Article
DE Methotrexate (MTX); PCNSL; Chemotherapy; Lymphoma
ID PRIMARY CNS LYMPHOMA; HIGH-DOSE METHOTREXATE; FOLATE CARRIER GENE;
TO-TREAT ANALYSIS; SYSTEM LYMPHOMA; PHASE-II; LONG-TERM; DEFERRED
RADIOTHERAPY; INITIAL TREATMENT; CONSOLIDATING RADIOTHERAPY
AB We have retrospectively reviewed toxicities and response of a cohort of primary central nervous system lymphoma (PCNSL) patients treated with high dose parenteral methotrexate (MTX) monotherapy without whole brain radiation. From The Massachusetts General Hospital (MGH) Cancer Registry, active since 1946, we selected all immunocompetent patients with histologic and/or radiographic PCNSL diagnosed between 1980 and 2007. We identified the recipients of MTX with leucovorin rescue as sole therapy. No patient received radiation therapy (XRT). We analyzed this cohort for toxicity, response and patterns of recurrence. The cohort of 121 patients received on average 11 cycles of intravenous MTX at a median dose of 8 g/m(2). Median interval between cycles was 10 days. After 3 months of therapy, the overall response rate was 85% (58% CR, 27% PR). The overall survival (OS) for the cohort was 7 years and progression-free survival (PFS) was 3.14 years. A trend toward a higher PFS was seen in patients who continued to receive MTX (3.48 years) every three months as compared to patients who ceased MTX after one year (2.86 years). Of 68 patients who achieved initial CR, there were 40 recurrences. Twenty-six of the 40 were re-induced with MTX as above; Sixty-nine percent again achieved CR. Eighty-one treatment-related toxicities occurred in 1316 MTX cycles. These toxicities included MRI white matter changes (N = 8) and lead to MTX cessation in 16 patients. High-dose MTX monotherapy of PCNSL is well-tolerated and provides PFS of > 3 years and OS > 7 years.
C1 [Hochberg, Fred] Stephen E & Catherine Pappas Ctr Neurooncol, Boston, MA 02114 USA.
[Woldenberg, Nina] Case Western Reserve Univ, Sch Med, Cleveland, OH 44106 USA.
[Hochberg, Ephraim] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
[Cobert, Julien] Duke Univ, Sch Med, Durham, NC 27710 USA.
RP Hochberg, F (reprint author), Stephen E & Catherine Pappas Ctr Neurooncol, 55 Fruit St,YAW 9E, Boston, MA 02114 USA.
EM jmcobert@gmail.com; FHochberg@partners.org
NR 43
TC 6
Z9 6
U1 0
U2 1
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 JUL
PY 2010
VL 98
IS 3
BP 385
EP 393
DI 10.1007/s11060-009-0090-3
PG 9
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA 609WE
UT WOS:000278687900012
PM 20020180
ER
PT J
AU Suh, J
Im, DS
Moon, GJ
Ryu, KS
de Silva, R
Choi, IS
Lees, AJ
Guenette, SY
Tanzi, RE
Gwag, BJ
AF Suh, Jaehong
Im, Doo Soon
Moon, Gyeong Joon
Ryu, Keun Sil
de Silva, Rohan
Choi, In Sun
Lees, Andrew J.
Guenette, Suzanne Y.
Tanzi, Rudolph E.
Gwag, Byoung Joo
TI Hypoxic ischemia and proteasome dysfunction alter tau isoform ratio by
inhibiting exon 10 splicing
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Article
DE ischemia; proteasome; splicing; tau; tra2 beta
ID PROGRESSIVE SUPRANUCLEAR PALSY; TRANSIENT CEREBRAL-ISCHEMIA; CORTICAL
CELL-CULTURES; ALZHEIMERS-DISEASE; MUTANT UBIQUITIN;
MONOCLONAL-ANTIBODIES; OXIDATIVE STRESS; NEURONAL DEATH; MESSENGER-RNA;
CYCLE REENTRY
AB P>Alternative splicing of tau exon 10 influences microtubule assembly and stability during development and in pathological processes of the central nervous system. However, the cellular events that underlie this pre-mRNA splicing remain to be delineated. In this study, we examined the possibility that ischemic injury, known to change the cellular distribution and expression of several RNA splicing factors, alters the splicing of tau exon 10. Transient occlusion of the middle cerebral artery reduced tau exon 10 inclusion in the ischemic cortical area within 12 h, resulting in the induction of three-repeat (3R) tau in cortical neurons. Ubiquitinated protein aggregates and reduced proteasome activity were also observed. Administration of proteasome inhibitors such as MG132, proteasome inhibitor I and lactacystin reduced tau exon 10 splicing in cortical cell cultures. Decreased levels of Tra2 beta, an RNA splicing factor responsible for tau exon 10 inclusion, were detected both in cortical cell cultures exposed to MG132 and in cerebral cortex after ischemic injury. Taken together, these findings suggest that transient focal cerebral ischemia reduces tau exon 10 splicing through a mechanism involving proteasome-ubiquitin dysfunction and down-regulation of Tra2 beta.
C1 [Suh, Jaehong; Ryu, Keun Sil; Choi, In Sun; Gwag, Byoung Joo] Ajou Univ, Dept Pharmacol, Sch Med, Suwon 442749, South Korea.
[Suh, Jaehong; Im, Doo Soon; Moon, Gyeong Joon; Ryu, Keun Sil; Choi, In Sun; Gwag, Byoung Joo] Ajou Univ, Res Inst Neural Sci & Technol, Sch Med, Suwon 442749, South Korea.
[Suh, Jaehong; Guenette, Suzanne Y.; Tanzi, Rudolph E.] Massachusetts Gen Hosp, Genet & Aging Res Unit MIND, Charlestown, MA USA.
[Suh, Jaehong; Guenette, Suzanne Y.; Tanzi, Rudolph E.] Harvard Univ, Sch Med, Charlestown, MA USA.
[Im, Doo Soon; Moon, Gyeong Joon; Choi, In Sun; Gwag, Byoung Joo] Ajou Univ, Interdisciplinary Course Neurosci & Technol, Sch Med, Suwon 442749, South Korea.
[Moon, Gyeong Joon; Gwag, Byoung Joo] Neurotech Pharmaceut Co, Suwon, South Korea.
[de Silva, Rohan; Lees, Andrew J.] UCL, Reta Lila Weston Inst Neurol Studies, London, England.
RP Gwag, BJ (reprint author), Ajou Univ, Dept Pharmacol, Sch Med, San 5, Suwon 442749, South Korea.
EM bjgwag@ajou.ac.kr
FU Ajou University
FX We are grateful to Dr. Stefan Stamm (University of Erlangen, Germany)
for providing Tra2 beta antibody. We thank Dr. Hyung-Hwan Kim (Harvard
Medical School) for his scientific expertise and Mi Young Ryu for
technical assistance. This work was supported by the Brain Korea 21
Project for Medical Science, Ajou University (B.J.G.).
NR 50
TC 4
Z9 4
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0022-3042
J9 J NEUROCHEM
JI J. Neurochem.
PD JUL
PY 2010
VL 114
IS 1
BP 160
EP 170
DI 10.1111/j.1471-4159.2010.06732.x
PG 11
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 608FA
UT WOS:000278567100015
PM 20374429
ER
PT J
AU Jouvent, E
Viswanathan, A
Chabriat, H
AF Jouvent, Eric
Viswanathan, Anand
Chabriat, Hugues
TI Cerebral Atrophy in Cerebrovascular Disorders
SO JOURNAL OF NEUROIMAGING
LA English
DT Review
DE MRI; brain atrophy; cerebral atrophy; cerebrovascular disorders; white
matter lesions; lacunes
ID WHITE-MATTER LESIONS; ISCHEMIC VASCULAR-DISEASE; BRAIN VOLUME CHANGES;
MIDDLE-AGED ADULTS; BODY-MASS INDEX; GRAY-MATTER; OLDER-ADULTS;
HYPERINTENSITY VOLUME; CARDIOVASCULAR HEALTH; MULTIPLE-SCLEROSIS
AB BACKGROUND AND PURPOSE
Various neurological disorders have been shown to accelerate the natural course of brain volume loss during normal aging. Recent data suggest that brain atrophy is prominent in various cerebrovascular disorders. Studies of the effects of different cerebrovascular magnetic resonance imaging (MRI) markers and of the effects of various vascular risk factors on the cerebral volume have been analyzed.
SUMMARY OF REVIEW
A significant association between white matter hyperintensities and cerebral atrophy has been reported in population-based studies. However, these results remain controversial since they have not yet been confirmed in longitudinal studies. The association between lacunar infarctions and cerebral atrophy was only rarely investigated. This was also true for cerebral microbleeds. In contrast, different data suggest that brain atrophy is associated with elevated blood pressure values or hyperglycemia, independent of the occurrence of extension of visible MRI markers of vascular lesions.
CONCLUSION
Additional studies are needed to determine the exact impact of vascular risk factors or other cerebrovascular lesions seen on MRI on the course of cerebral atrophy. In the future, new MRI markers may help to better delineate the role of focal tissue lesions from that of diffuse effects of vascular risk factors on the cerebral atrophy process.
C1 [Jouvent, Eric; Chabriat, Hugues] Univ Paris 07, Dept Neurol, AP HP, Hop Lariboisiere, Paris 7, France.
[Viswanathan, Anand] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA.
[Viswanathan, Anand] Massachusetts Gen Hosp, Clin Trials Unit, Boston, MA 02114 USA.
RP Chabriat, H (reprint author), Univ Paris 07, Dept Neurol, AP HP, Hop Lariboisiere, Paris 7, France.
EM hugues.chabriat@lrb.aphp.fr
RI Jouvent, Eric/B-4320-2014; Chabriat, Hugues/G-5699-2010
OI Jouvent, Eric/0000-0001-7797-2236; Chabriat, Hugues/0000-0001-8436-6074
FU PHRC [AOR 02-001]; ARNEVA (Association de Recherche en Neurologie
VAsculaire), Hopital Lariboisiere, France
FX This work was supported by PHRC grant AOR 02-001 (DRC/APHP) and
performed with the help of ARNEVA (Association de Recherche en
Neurologie VAsculaire), Hopital Lariboisiere, France.
NR 81
TC 11
Z9 11
U1 0
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1051-2284
J9 J NEUROIMAGING
JI J. Neuroimaging
PD JUL
PY 2010
VL 20
IS 3
BP 213
EP 218
DI 10.1111/j.1552-6569.2009.00370.x
PG 6
WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 624RU
UT WOS:000279838700001
PM 19344366
ER
PT J
AU Thomas, AA
Rogers, JM
Amick, MM
Friedman, JH
AF Thomas, Alissa A.
Rogers, Jennifer M.
Amick, Melissa M.
Friedman, Joseph H.
TI Falls and the falls efficacy scale in Parkinson's disease
SO JOURNAL OF NEUROLOGY
LA English
DT Article
DE Parkinson's disease; Falls; Gait disorder; Patient safety
ID FEAR; BALANCE; RISK
AB The purpose of this study was to investigate the relationship between fear of falling and fall frequency among patients with idiopathic Parkinson's disease (PD). One hundred-two participants with idiopathic PD were interviewed and examined. Participants reported the number of falls they had experienced in the preceding 3 months. They completed a mini-mental state exam (MMSE) and the falls efficacy scale (FES) questionnaire. Disease severity was determined by clinical examination using the Hoehn-Yahr staging system. Excluding two outliers who fell more than once each day, the subjects fell an average of 1.2 times in a 3 month period. There was a positive correlation between the number of falls, freezing of gait and Hoehn-Yahr score, and a negative correlation with the MMSE. In a post-hoc analysis the participants were divided into four groups based on fall frequency. The outliers had the lowest FES scores on average, similar to the scores seen in the rare fallers group. This study suggests that many factors are associated with fear of falling, including fall frequency, disease severity, and mental status. In the present study, the patients who fell the most often did not report the most fear. The lack of fear of falling but frequent falls in this small subgroup may suggest that special techniques to instill suitable caution to prevent falls are necessary, or may make training of these patients impossible.
C1 [Friedman, Joseph H.] NeuroHlth, Warwick, RI 02886 USA.
[Thomas, Alissa A.] Brown Univ, Dept Neurol, Dartmouth Hitchcock Med Ctr, Warren Alpert Med Sch, Hanover, NH USA.
[Rogers, Jennifer M.] Cornell Univ, Butler Hosp, Dept Psychiat & Human Behav, Providence, RI USA.
[Amick, Melissa M.] VA Boston Healthcare Syst, Boston, MA 02130 USA.
[Friedman, Joseph H.] Brown Univ, Div Movement Disorders, Dept Neurol,Butler Hosp, Warren Alpert Med Sch,Parkinsons Dis & Movement D, Providence, RI 02912 USA.
RP Friedman, JH (reprint author), NeuroHlth, 227 Centerville Rd, Warwick, RI 02886 USA.
EM Alissa.a.thomas@hitchcock.org; Jenniferrogers224@gmail.com;
melissaamick@gmail.com
FU Acadia Pharmaceuticals; Teva; Ingelheim-Boehringer; Glaxo Smith Kline;
Cephalon; Valeant; EMD Serono; Novartis; Pfizer; NIH; MJ Fox Foundation
FX Lectures, consultations or research funds were provided by Acadia
Pharmaceuticals, Teva, Ingelheim-Boehringer, Glaxo Smith Kline,
Cephalon, Valeant, EMD Serono, Novartis, Pfizer, NIH, MJ Fox Foundation.
NR 11
TC 18
Z9 19
U1 1
U2 6
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 0340-5354
J9 J NEUROL
JI J. Neurol.
PD JUL
PY 2010
VL 257
IS 7
BP 1124
EP 1128
DI 10.1007/s00415-010-5475-x
PG 5
WC Clinical Neurology
SC Neurosciences & Neurology
GA 616RG
UT WOS:000279225900010
PM 20157723
ER
PT J
AU Dehghani, N
Cash, SS
Rossetti, AO
Chen, CC
Halgren, E
AF Dehghani, Nima
Cash, Sydney S.
Rossetti, Andrea O.
Chen, Chih Chuan
Halgren, Eric
TI Magnetoencephalography Demonstrates Multiple Asynchronous Generators
During Human Sleep Spindles
SO JOURNAL OF NEUROPHYSIOLOGY
LA English
DT Article
ID EEG; MEG; CORTEX; OSCILLATIONS; COHERENCE; ELECTROENCEPHALOGRAM; BRAIN;
LOCALIZATION; MECHANISMS; DYNAMICS
AB Dehghani N, Cash SS, Rossetti AO, Chen CC, Halgren E. Magnetoencephalography demonstrates multiple asynchronous generators during human sleep spindles. J Neurophysiol 104: 179-188, 2010. First published April 28, 2010; doi:10.1152/jn.00198.2010. Sleep spindles are similar to 1 s bursts of 10-16 Hz activity that occur during stage 2 sleep. Spindles are highly synchronous across the cortex and thalamus in animals, and across the scalp in humans, implying correspondingly widespread and synchronized cortical generators. However, prior studies have noted occasional dissociations of the magnetoencephalogram (MEG) from the EEG during spindles, although detailed studies of this phenomenon have been lacking. We systematically compared high-density MEG and EEG recordings during naturally occurring spindles in healthy humans. As expected, EEG was highly coherent across the scalp, with consistent topography across spindles. In contrast, the simultaneously recorded MEG was not synchronous, but varied strongly in amplitude and phase across locations and spindles. Overall, average coherence between pairs of EEG sensors was similar to 0.7, whereas MEG coherence was similar to 0.3 during spindles. Whereas 2 principle components explained similar to 50% of EEG spindle variance, similar to 15 were required for MEG. Each PCA component for MEG typically involved several widely distributed locations, which were relatively coherent with each other. These results show that, in contrast to current models based on animal experiments, multiple asynchronous neural generators are active during normal human sleep spindles and are visible to MEG. It is possible that these multiple sources may overlap sufficiently in different EEG sensors to appear synchronous. Alternatively, EEG recordings may reflect diffusely distributed synchronous generators that are less visible to MEG. An intriguing possibility is that MEG preferentially records from the focal core thalamocortical system during spindles, and EEG from the distributed matrix system.
C1 [Dehghani, Nima; Halgren, Eric] Univ Calif San Diego, Dept Radiol, Multimodal Imaging Lab, San Diego, CA 92103 USA.
[Dehghani, Nima; Halgren, Eric] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA.
[Dehghani, Nima; Cash, Sydney S.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Dehghani, Nima; Cash, Sydney S.] Harvard Univ, Sch Med, Martinos Ctr Biomed Imaging, Boston, MA 02115 USA.
[Dehghani, Nima] Ctr Natl Rech Sci Integrat & Computat Neurosci Un, UPR2191, Gif Sur Yvette, France.
[Rossetti, Andrea O.] Univ Lausanne, Lausanne, Switzerland.
[Rossetti, Andrea O.] Ctr Univ Hosp Vaudois, Serv Neurol, Lausanne, Switzerland.
[Chen, Chih Chuan] Natl Taiwan Univ Hosp, Dept Neurol, Taipei, Taiwan.
RP Halgren, E (reprint author), 9500 Gilman Dr,Mail Code 0841, La Jolla, CA 92093 USA.
EM ehalgren@ucsd.edu
RI Rossetti, Andrea/A-6712-2008;
OI Rossetti, Andrea/0000-0002-7878-172X; Dehghani, Nima/0000-0003-2032-8903
FU National Institutes of Health [EB-009282, NS-18741, NS-44623]
FX This research was supported by National Institutes of Health Grants
EB-009282, NS-18741, and NS-44623.
NR 41
TC 28
Z9 28
U1 1
U2 2
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3077
J9 J NEUROPHYSIOL
JI J. Neurophysiol.
PD JUL
PY 2010
VL 104
IS 1
BP 179
EP 188
DI 10.1152/jn.00198.2010
PG 10
WC Neurosciences; Physiology
SC Neurosciences & Neurology; Physiology
GA 621NU
UT WOS:000279586400016
PM 20427615
ER
PT J
AU Andrews-Hanna, JR
Reidler, JS
Huang, C
Buckner, RL
AF Andrews-Hanna, Jessica R.
Reidler, Jay S.
Huang, Christine
Buckner, Randy L.
TI Evidence for the Default Network's Role in Spontaneous Cognition
SO JOURNAL OF NEUROPHYSIOLOGY
LA English
DT Article
ID STIMULUS-INDEPENDENT THOUGHT; INTRINSIC FUNCTIONAL CONNECTIVITY; MEDIAL
TEMPORAL-LOBE; ROSTRAL PREFRONTAL CORTEX; CONSCIOUS RESTING STATE;
MENTAL TIME-TRAVEL; HUMAN OBJECT AREAS; EPISODIC MEMORY; HUMAN BRAIN;
PARAMETRIC MANIPULATION
AB Andrews-Hanna JR, Reidler JS, Huang C, Buckner RL. Evidence for the default network's role in spontaneous cognition. J Neurophysiol 104: 322-335, 2010. First published May 12, 2010; doi:10.1152/jn.00830.2009. A set of brain regions known as the default network increases its activity when focus on the external world is relaxed. During such moments, participants change their focus of external attention and engage in spontaneous cognitive processes including remembering the past and imagining the future. However, the functional contributions of the default network to shifts in external attention versus internal mentation have been difficult to disentangle because the two processes are correlated under typical circumstances. To address this issue, the present study manipulated factors that promote spontaneous cognition separately from those that change the scope of external attention. Results revealed that the default network increased its activity when spontaneous cognition was maximized but not when participants increased their attention to unpredictable foveal or peripheral stimuli. To examine the nature of participants' spontaneous thoughts, a second experiment used self-report questionnaires to quantify spontaneous thoughts during extended fixation epochs. Thoughts about one's personal past and future comprised a major focus of spontaneous cognition with considerable variability. Activity correlations between the medial temporal lobe and distributed cortical regions within the default network predicted a small, but significant, portion of the observed variability. Collectively, these results suggest that during passive states, activity within the default network reflects spontaneous, internally directed cognitive processes.
C1 [Andrews-Hanna, Jessica R.; Reidler, Jay S.; Huang, Christine; Buckner, Randy L.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA.
[Andrews-Hanna, Jessica R.; Reidler, Jay S.; Huang, Christine; 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.
[Andrews-Hanna, Jessica R.; Buckner, Randy L.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA.
[Buckner, Randy L.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA.
[Buckner, Randy L.] Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA USA.
RP Andrews-Hanna, JR (reprint author), Univ Colorado, Inst Cognit Sci, UCB 594, Boulder, CO 80309 USA.
EM Jessica.Andrews-Hanna@Colorado.edu
OI Reidler, Jay/0000-0002-9615-5351
FU National Institute on Aging [AG-021910]; Howard Hughes Medical Institute
FX This work was supported by National Institute on Aging Grant AG-021910
and the Howard Hughes Medical Institute.
NR 87
TC 212
Z9 218
U1 2
U2 26
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3077
J9 J NEUROPHYSIOL
JI J. Neurophysiol.
PD JUL
PY 2010
VL 104
IS 1
BP 322
EP 335
DI 10.1152/jn.00830.2009
PG 14
WC Neurosciences; Physiology
SC Neurosciences & Neurology; Physiology
GA 621NU
UT WOS:000279586400030
PM 20463201
ER
PT J
AU Corona, JC
Gimenez-Cassina, A
Lim, F
Diaz-Nido, J
AF Carlos Corona, Juan
Gimenez-Cassina, Alfredo
Lim, Filip
Diaz-Nido, Javier
TI Hexokinase II Gene Transfer Protects against Neurodegeneration in the
Rotenone and MPTP Mouse Models of Parkinson's Disease
SO JOURNAL OF NEUROSCIENCE RESEARCH
LA English
DT Article
DE neurodegeneration; substantia nigra; gene transfer; hexokinase II
ID ENERGY-METABOLISM; CELL-DEATH; MITOCHONDRIAL DYSFUNCTION;
ALZHEIMERS-DISEASE; OXIDATIVE STRESS; APOPTOSIS; NEURONS; COMPLEX;
BINDING; PHOSPHORYLATION
AB A typical feature of Parkinson's disease is the progressive loss of dopaminergic neurons in the substantia nigra, in which inhibition of mitochondrial complex I activity may play an important role. Rotenone or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) inhibit the mitochondrial complex I and they cause the death of substantia nigra dopaminergic neurons, thereby providing acute murine models of Parkinson's disease. We have found that increasing mitochondrial hexokinase II activity can prevent cell death in neuronal cultures treated with rotenone. As a result, we have studied the effects of hexokinase II gene transfer in vivo using a herpes simplex virus type 1 (HSV-1) amplicon vector. The placHK2 amplicon vector was injected into substantia nigra of mice that were subsequently administered rotenone or MPTP Overexpression of hexokinase II prevented both rotenone and MPTP-induced dopaminergic neuronal cell death, as well as reducing the associated motor defects. Our results provide the first proof-of-principle that hexokinase II protects against dopaminergic neurodegeneration in vivo, emphasizing the role of this enzyme in promoting neuronal survival. Thus, the increase of hexokinase II expression by gene transfer or other means represents a promising approach to treat Parkinson's and other neurodegenerative diseases. (C) 2010 Wiley-Liss, Inc.
C1 [Carlos Corona, Juan; Gimenez-Cassina, Alfredo; Lim, Filip; Diaz-Nido, Javier] Univ Autonoma Madrid, Ctr Biol Mol Severo Ochoa, E-28049 Madrid, Spain.
[Carlos Corona, Juan; Gimenez-Cassina, Alfredo; Lim, Filip; Diaz-Nido, Javier] Univ Autonoma Madrid, Dept Biol Mol, E-28049 Madrid, Spain.
[Carlos Corona, Juan; Gimenez-Cassina, Alfredo; Lim, Filip; Diaz-Nido, Javier] ISCIII, CIBERER, Area Neurogenet, Madrid, Spain.
[Gimenez-Cassina, Alfredo] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Diaz-Nido, J (reprint author), Univ Autonoma Madrid, Ctr Biol Mol Severo Ochoa, C Nicolas Cabrera 1, E-28049 Madrid, Spain.
EM javier.diaznido@cbm.uam.es
RI Diaz-Nido, Javier/L-2371-2013; Lim, Filip/C-7412-2011
OI Diaz-Nido, Javier/0000-0002-0927-7925; Gimenez-Cassina,
Alfredo/0000-0002-2768-2350; Lim, Filip/0000-0001-6570-1017
FU MAEC-AECID; CONACYT, Mexico; Plan Nacional de Investigacion en
Biomedicina [SAF 2006-12782-C03-02]; Comunidad Autonoma de Madrid [Ref
S-SAL-0202-2006]; Fundacion Alicia Koplowitz; Institut de Salud Carlos
III (ISC III)
FX The Biomedical Network Research Centre for Rare Diseases "Centro de
Investigacion Biomedica en Red sobre Enferrnedades Raras" (CIBERER) is
supported by the "Institut de Salud Carlos III" (ISC III).Contract grant
sponsor: MAEC-AECID (to J.C.C.); Contract grant sponsor: CONACYT, Mexico
(to J.C.C.); Contract grant sponsor: Plan Nacional de Investigacion en
Biomedicina; Contract grant number: SAF 2006-12782-C03-02; Contract
grant sponsor: Comunidad Autonoma de Madrid; Contract grant number:
Neurodegmodels, Ref S-SAL-0202-2006; Contract grant sponsor: Fundacion
Alicia Koplowitz.
NR 41
TC 14
Z9 14
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0360-4012
J9 J NEUROSCI RES
JI J. Neurosci. Res.
PD JUL
PY 2010
VL 88
IS 9
BP 1943
EP 1950
DI 10.1002/jnr.22357
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA 601JY
UT WOS:000278056600012
PM 20143419
ER
PT J
AU Engelhard, HH
Villano, JL
Porter, KR
Stewart, AK
Barua, M
Barker, FG
Newton, HB
AF Engelhard, Herbert H.
Villano, J. Lee
Porter, Kimberly R.
Stewart, Andrew K.
Barua, Manali
Barker, Fred G., II
Newton, Herbert B.
TI Clinical presentation, histology, and treatment in 430 patients with
primary tumors of the spinal cord, spinal meninges, or cauda equina
Clinical article
SO JOURNAL OF NEUROSURGERY-SPINE
LA English
DT Article
DE cancer registry; cauda equina; epidemiology; Karnofsky Performance
Scale; spinal cord tumor; spinal neoplasm
ID CANCER DATA-BASE; NERVOUS-SYSTEM TUMORS; OF-THE-LITERATURE;
TERM-FOLLOW-UP; SURGICAL-TREATMENT; POSTOPERATIVE RADIOTHERAPY;
RETROSPECTIVE ANALYSIS; DESCRIPTIVE EPIDEMIOLOGY; PROGNOSTIC-FACTORS;
RADIATION-THERAPY
AB Object. Patients having a primary tumor of the spinal cord, spinal meninges or cauda equina, are relatively rare. Neurosurgeons encounter and treat such patients, and need to be aware of their clinical presentation, tumor types, treatment options, and potential complications. The purpose of this paper is to report results from a series of 430 patients with primary intraspinal tumors, taken from a larger cohort of 9661 patients with primary tumors of the CNS.
Methods. Extensive information on individuals diagnosed (in the year 2000) as having a primary CNS neoplasm was prospectively collected in a Patient Care Evaluation Study conducted by the Commission on Cancer of the American College of Surgeons. Data from US hospital cancer registries were submitted directly to the National Cancer Database. Intraspinal tumor cases were identified based on ICD-O-2 topography codes C70.1, C72.0, and C72.1. Analyses were performed using SPSS.
Results. Patients with primary intraspinal tumors represented 4.5% of the CNS tumor group, and had a mean age of 49.3 years. Pain was the most common presenting symptom, while the most common tumor types were meningioma (24.4%), ependymoma (23.7%), and schwannoma (21.2%). Resection, surgical biopsy, or both were performed in 89.3% of cases. Complications were low, but included neurological worsening (2.2%) and infection (1.6%). Radiation therapy and chemotherapy were administered to 20.3% and 5.6% of patients, respectively.
Conclusions. Data from this study are suitable for benchmarking, describing prevailing patterns of care, and generating additional hypotheses for future studies. (DOI: 10.3171/2010.3.SPINE09430)
C1 [Engelhard, Herbert H.; Barua, Manali] Univ Illinois, Dept Neurosurg, Med Ctr, Chicago, IL 60612 USA.
[Villano, J. Lee] Univ Illinois, Dept Med, Med Ctr, Chicago, IL 60612 USA.
[Porter, Kimberly R.; Stewart, Andrew K.] Amer Coll Surg, Commiss Canc, Chicago, IL USA.
[Barker, Fred G., II] Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA.
[Newton, Herbert B.] Ohio State Univ, Med Ctr, Dardinger Neurooncol Ctr, Columbus, OH 43210 USA.
[Newton, Herbert B.] Ohio State Univ, Med Ctr, Dept Neurol, Columbus, OH 43210 USA.
[Newton, Herbert B.] James Canc Hosp, Columbus, OH USA.
RP Engelhard, HH (reprint author), Univ Illinois, Dept Neurosurg, Med Ctr, Mailcode 799,912 S Wood St, Chicago, IL 60612 USA.
EM hengel@uic.edu
FU American Cancer Society; American College of Surgeons
FX This work was supported by funding from the American Cancer Society and
the American College of Surgeons. The authors wish to sincerely thank
the members of the CNS PCE Study Committee (listed above); the members
and staff of the Commission on Cancer of the American College of
Surgeons; and tumor registrars in hospitals across the US for their
contributions to this study. The authors also greatly appreciate the
efforts of Dr. Roger E. McLendon (Department of Pathology, Duke
University) for his work on the histological groupings, and Drs. Peter
Inskip, Susan Chang, David Cella, and Ruth G. Ramsey for their careful
review of the manuscript and thoughtful advice.
NR 81
TC 42
Z9 45
U1 1
U2 5
PU AMER ASSOC NEUROLOGICAL SURGEONS
PI ROLLING MEADOWS
PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA
SN 1547-5654
J9 J NEUROSURG-SPINE
JI J. Neurosurg.-Spine
PD JUL
PY 2010
VL 13
IS 1
BP 67
EP 77
DI 10.3171/2010.3.SPINE09430
PG 11
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA 615BU
UT WOS:000279107000015
PM 20594020
ER
PT J
AU Sapp, AL
Kawachi, I
Sorensen, G
LaMontagne, AD
Subramanian, SV
AF Sapp, Amy L.
Kawachi, Ichiro
Sorensen, Glorian
LaMontagne, Anthony D.
Subramanian, S. V.
TI Does Workplace Social Capital Buffer the Effects of Job Stress? A
Cross-Sectional, Multilevel Analysis of Cigarette Smoking Among US
Manufacturing Workers
SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE
LA English
DT Article
ID CORONARY-HEART-DISEASE; SELF-RATED HEALTH; CARDIOVASCULAR RISK-FACTORS;
WORKSITE CANCER PREVENTION; FINNISH PUBLIC-SECTOR; INTERMITTENT SMOKERS;
DEPRESSIVE SYMPTOMS; SEDENTARY BEHAVIOR; DECISION LATITUDE; EMPLOYEE
HEALTH
AB Objective: To investigate whether workplace social capital buffers the association between job stress and smoking status. Methods: As part of the Harvard Cancer Prevention Project's Healthy Directions-Small Business Study, interviewer-administered questionnaires were completed by 1740 workers and 288 managers in 26 manufacturing firms (84% and 85% response). Social capital was assessed by multiple items measured at the individual level among workers and contextual level among managers. Job stress was operationalized by the demand-control model. Multilevel logistic regression was used to estimate associations between job stressors and smoking and test for effect modification by social capital measures. Results: Workplace social capital (both summary measures) buffered associations between high job demands and smoking. One compositional item-worker trust in managers-buffered associations between job strain and smoking. Conclusion: Workplace social capital may modify the effects of psychosocial working conditions on health behaviors.
C1 [Sapp, Amy L.; Kawachi, Ichiro; Sorensen, Glorian; Subramanian, S. V.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA.
[Sapp, Amy L.; Sorensen, Glorian] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA.
[LaMontagne, Anthony D.] Univ Melbourne, Melbourne Sch Populat Hlth, McCaughey Ctr, Melbourne, Vic, Australia.
RP Sapp, AL (reprint author), Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, 677 Huntington Ave,Bldg SPH3,7th Floor, Boston, MA 02115 USA.
EM asapp@post.harvard.edu
FU National Cancer Institute [5 T32 CA09001-28, POl CA 75308]; National
Institutes of Health [NHLBI K25 HL081275]
FX A. L. Sapp was supported by a training grant from the National Cancer
Institute (grant 5 T32 CA09001-28). G. Sorensen was supported by a grant
from the National Cancer Institute (grant POl CA 75308). S. V.
Subramanian was supported by the National Institutes of Health Career
Development Award (NHLBI K25 HL081275).
NR 94
TC 26
Z9 29
U1 2
U2 22
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1076-2752
J9 J OCCUP ENVIRON MED
JI J. Occup. Environ. Med.
PD JUL
PY 2010
VL 52
IS 7
BP 740
EP 750
DI 10.1097/JOM.0b013e3181e80842
PG 11
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 622QH
UT WOS:000279677800012
PM 20595910
ER
PT J
AU Schwerha, JJ
Hwang, DY
Pless, ML
AF Schwerha, Joseph J.
Hwang, David Y.
Pless, Misha L.
TI How can stretching maneuvers involving the neck cause vertebral artery
dissection and transient ischemic attack?
SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE
LA English
DT Editorial Material
ID STROKE
C1 [Hwang, David Y.; Pless, Misha L.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Hwang, David Y.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Hwang, David Y.; Pless, Misha L.] Harvard Univ, Sch Med, Boston, MA USA.
EM schwer@pitt.edu; dhwang@partners.org; mpless@partners.org
NR 6
TC 1
Z9 1
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1076-2752
J9 J OCCUP ENVIRON MED
JI J. Occup. Environ. Med.
PD JUL
PY 2010
VL 52
IS 7
BP 764
EP 765
DI 10.1097/JOM.0b013e3181d8d9cf
PG 2
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 622QH
UT WOS:000279677800016
ER
PT J
AU Perciaccante, VJ
Susarla, SM
Dodson, TB
AF Perciaccante, Vincent J.
Susarla, Srinivas M.
Dodson, Thomas B.
TI Validation of a Diagnostic Protocol Used to Identify Intimate Partner
Violence in the Emergency Department Setting
SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY
LA English
DT Article
ID DOMESTIC VIOLENCE; FACIAL INJURIES; WOMEN; MARKERS; HEAD; NECK
AB Purpose: To assess the internal validity of a diagnostic protocol developed to facilitate the identification of women with intimate partner violence (IPV)-related injuries.
Materials and Methods: Using a cross-sectional study design, we enrolled a sample of female subjects presenting to the emergency department for treatment of injuries with non-verifiable etiologies. The study sample was divided randomly into index and validation sets. The index set was used to develop the diagnostic protocol, and the validation set was used to assess the protocol's internal validity. The predictor study variable was risk for IPV-related injury (ie, high or low). The outcome variable was self-report of injury etiology (IPV or other etiology). Appropriate univariate, bivariate, and multivariate statistics were computed, including estimates of sensitivity, specificity, and relative risk. Goodness of fit of the diagnostic protocol was estimated with the Hosmer-Lemeshow statistic. For all analyses, P <= .05 was considered statistically significant.
Results: The index and validation samples were composed of 200 and 100 women, respectively. In the index sample, subjects categorized at high risk of IPV-related injuries were statistically associated with an increased risk for self-report of IPV-related injury (relative risk, 25.2; 95% confidence interval, 10.6-59.5 [P < .05]; sensitivity, 90.2%; specificity, 96.4%; positive predictive value, 90.1%; negative predictive value, 96.4%). The agreement between the predicted and actual observations showed excellent agreement in the index and validation samples (P =.999, Hosmer-Lemeshow chi(2)).
Conclusion: The proposed diagnostic protocol effectively stratifies risk for IPV-related injuries with good internal validity. (C) 2010 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 68:1537-1542, 2010
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.
[Perciaccante, Vincent J.] Emory Univ, Sch Med, Dept Surg, Div Oral & Maxillofacial Surg, Atlanta, GA 30322 USA.
RP Dodson, TB (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Ctr Appl Clin Invest, 55 Fruit St,WRN1201, Boston, MA 02114 USA.
EM tbdodson@partners.org
OI Susarla, Srinivas/0000-0003-0155-8260
FU Center for Applied Clinical Investigation and Education and Research
Fund, Department of Oral and Maxillofacial Surgery, Massachusetts
General Hospital; OMS Foundation; Massachusetts General Physicians
Organization
FX Funding provided by the Center for Applied Clinical Investigation and
Education and Research Fund, Department of Oral and Maxillofacial
Surgery, Massachusetts General Hospital; OMS Foundation Clinical
Investigation Fellowship; and Massachusetts General Physicians
Organization.
NR 20
TC 2
Z9 2
U1 0
U2 0
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0278-2391
J9 J ORAL MAXIL SURG
JI J. Oral Maxillofac. Surg.
PD JUL
PY 2010
VL 68
IS 7
BP 1537
EP 1542
DI 10.1016/j.joms.2010.02.012
PG 6
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 621JC
UT WOS:000279571500011
PM 20561466
ER
PT J
AU Lawler, ME
Tayebaty, FT
Williams, WB
Troulis, MJ
Kaban, LB
AF Lawler, Matthew E.
Tayebaty, Fardad T.
Williams, W. Bradford
Troulis, Maria J.
Kaban, Leonard B.
TI Histomorphometric Analysis of the Porcine Mandibular Distraction Wound
SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY
LA English
DT Article; Proceedings Paper
CT Annual Meeting of the
American-Association-for-Dental-Research/Canadian-Association-Dental-Res
earch
CY MAR 03-06, 2010
CL Washington, DC
SP Amer Assoc Dent Res, Canadian Assoc Dent Res
ID GROWTH-FACTOR-I; BONE-FORMATION; PERIOSTEAL DISTRACTION; INDUCED
OSTEOGENESIS; MECHANICAL TENSION; EXPERIMENTAL-MODEL; RAT; RABBITS;
EXPRESSION; TISSUES
AB Purpose: To analyze the sequence of histomorphometric changes in the regenerate during distraction osteogenesis (DO) of the minipig mandible.
Materials and Methods: A total of 16 minipigs underwent unilateral mandibular DO using a protocol of 0-day latency and a 1-mm/day rate for 12 days, and 24 days of fixation. The mandibles were harvested at mid-DO, end-DO, mid-fixation, and end-fixation. An additional 2 minipigs underwent acute lengthening, and 1 sham control was included. Serial gross examinations and plain radiographs were performed before paraffin embedding. The sections were stained with hematoxylin-eosin or hematoxylin/alcian blue/sirius red stain. Histomorphometric analysis was performed to determine the percentage of surface area (PSA) occupied by hematoma, fibrous tissue, cartilage, and bone.
Results: All 19 minipigs survived the operation, and 17 survived the observation period; 2 were killed because of infection (mid-DO, n = 1 and end-fixation, n = 1). No device failures occurred. Of the 17 specimens, 4 were at mid-DO, 4 at end-DO, 4 at mid-fixation, and 2 at end-fixation; 2 were in the acute lengthening group, and 1 was the sham control. Hematoma was present only at mid-DO (16.61 +/- 8.07 PSA) and end-DO (1.17 +/- 2.33 PSA). Fibrous tissue decreased from mid-DO (53.12 +/- 8.59 PSA) to end-fixation (25.00 +/- 0.83 PSA). Cartilage was present in end-DO (1.72 +/- 2.71 PSA), mid-fixation (5.82 +/- 6.64 PSA), and acute lengthening (1.43 +/- 0.95 PSA). Bone increased from mid-DO (25.18 +/- 0.99 PSA) to end-fixation (64.89 +/- 0.79 PSA) and occurred earlier in the superior and middle thirds of the wounds. Periosteal bone formation predominated over endosteal bone formation early in distraction.
Conclusion: The results of the present study indicate that bone formation in this model consists of both intramembranous and endochondral components, with intramembranous osteogenesis predominating. Bone formation occurred earlier in the superior/middle portions of the wound, possibly owing to osteoinductive properties of developing tooth buds and the inferior alveolar nerve, respectively. (C) 2010 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 68:1543-1554, 2010
C1 [Kaban, Leonard B.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Oral & Maxillofacial Surg Serv, Boston, MA 02114 USA.
[Kaban, Leonard B.] Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA.
[Lawler, Matthew E.; Tayebaty, Fardad T.; Williams, W. Bradford; Troulis, Maria J.] Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Troulis, Maria J.] Harvard Univ, Sch Dent Med, Residency Training Program, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Troulis, Maria J.] Harvard Univ, Sch Dent Med, Minimally Invas Surg Program, Massachusetts Gen Hosp, Boston, MA 02115 USA.
RP Kaban, LB (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Oral & Maxillofacial Surg Serv, Warren Bldg 1201,Fruit St, Boston, MA 02114 USA.
EM LKaban@Partners.org
NR 68
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Z9 11
U1 0
U2 1
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0278-2391
J9 J ORAL MAXIL SURG
JI J. Oral Maxillofac. Surg.
PD JUL
PY 2010
VL 68
IS 7
BP 1543
EP 1554
DI 10.1016/j.joms.2010.02.048
PG 12
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 621JC
UT WOS:000279571500012
PM 20561467
ER
PT J
AU Ryu, K
Choy, E
Yang, C
Susa, M
Hornicek, FJ
Mankin, H
Duan, ZF
AF Ryu, Keinosuke
Choy, Edwin
Yang, Cao
Susa, Michiro
Hornicek, Francis J.
Mankin, Henry
Duan, Zhenfeng
TI Activation of Signal Transducer and Activator of Transcription 3 (Stat3)
Pathway in Osteosarcoma Cells and Overexpression of Phosphorylated-Stat3
Correlates with Poor Prognosis
SO JOURNAL OF ORTHOPAEDIC RESEARCH
LA English
DT Article
DE Stat3; osteosarcoma; immunohistochemistry; prognosis; CDDO-Me
ID BREAST-CANCER CELLS; RESISTANT OVARIAN-CANCER; MOLECULAR TARGETS;
CONSTITUTIVE ACTIVATION; INDUCE APOPTOSIS; GROWTH ARREST; HUMAN TUMORS;
EXPRESSION; ACID; CARCINOMA
AB Stat3 expression in cancer may have important prognostic and therapeutic value, but there has been no reports correlating Stat3 expression with prognosis in patients with osteosarcoma. The goal of this study is to correlate patient prognosis with the expression of Stat3 in osteosarcoma tissue and determine the effectiveness of blocking this pathway in osteosarcoma cell lines by Stat3 inhibitor, CDDO-Me. We examine the expression levels of Stat3 and pStat3 in osteosarcoma cell lines and primary tissues by Western blot analysis. We also evaluate the levels of pStat3 expression in osteosarcoma tissue microarray (TMA) by immunohistochemistry. We use clinical data to determine the impact of levels of Stat3 expression on patient prognosis. Finally, we evaluated the effect of CDDO-Me on the inhibition of activated Stat3 pathway in osteosarcoma cell lines using MTT assay and Western blot analysis. Stat3 is observed to be activated in osteosarcoma tissues as well as in cultured cell lines. Overexpression of pStat3 is associated with poor prognosis. CDDO-Me inhibits the growth of osteosarcoma cell lines and induces apoptosis as well. Our results suggest that Stat3 may be a prognostic indicator and potential therapeutic target for osteosarcoma. Blocking the pathway of Stat3 may lead to develop new therapeutic strategies against osteosarcoma. (C) 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:971-978, 2010
C1 [Ryu, Keinosuke; Yang, Cao; Susa, Michiro; Hornicek, Francis J.; Mankin, Henry; Duan, Zhenfeng] Massachusetts Gen Hosp, Dept Orthoped Surg, Ctr Sarcoma & Connect Tissue Oncol, Boston, MA 02114 USA.
[Ryu, Keinosuke; Choy, Edwin; Yang, Cao; Susa, Michiro; Hornicek, Francis J.; Mankin, Henry; Duan, Zhenfeng] Massachusetts Gen Hosp, Ctr Sarcoma & Connect Tissue Oncol, Sarcoma Biol Lab, Boston, MA 02114 USA.
RP Duan, ZF (reprint author), Massachusetts Gen Hosp, Dept Orthoped Surg, Ctr Sarcoma & Connect Tissue Oncol, 55 Fruit St Jackson 1115, Boston, MA 02114 USA.
EM zduan@partners.org
RI Susa, Michiro/L-2291-2013;
OI Choy, Edwin/0000-0001-9896-8084
FU Gaetagno and Wechsler funds; Department of Orthopaedic Surgery, Nihon
University School of Medicine; Sarcoma Foundation of America; National
Cancer Institute, NIH [R01-CA119617]
FX This project was supported by a grant from the Gaetagno and Wechsler
funds. Dr. Ryu is supported by Department of Orthopaedic Surgery, Nihon
University School of Medicine. Dr. Duan is supported, in part, by a
grant from Sarcoma Foundation of America, and a grant from the National
Cancer Institute, NIH (Nanotechnology Platform Partnership),
#R01-CA119617.
NR 46
TC 34
Z9 42
U1 2
U2 3
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0736-0266
J9 J ORTHOP RES
JI J. Orthop. Res.
PD JUL
PY 2010
VL 28
IS 7
BP 971
EP 978
DI 10.1002/jor.21088
PG 8
WC Orthopedics
SC Orthopedics
GA 609KG
UT WOS:000278654500020
PM 20063378
ER
PT J
AU Vazquez, O
Rutgers, M
Ring, DC
Walsh, M
Egol, KA
AF Vazquez, Oscar
Rutgers, Marijn
Ring, David C.
Walsh, Michael
Egol, Kenneth A.
TI Fate of the Ulnar Nerve After Operative Fixation of Distal Humerus
Fractures
SO JOURNAL OF ORTHOPAEDIC TRAUMA
LA English
DT Article
DE ulnar nerve; distal humerus fracture; transposition; complication; palsy
ID INTERNAL-FIXATION; INTERCONDYLAR FRACTURES; OPEN REDUCTION; NONUNIONS;
ELBOW
AB Objectives: It is well recognized that operative treatment of a fracture of the distal humerus requires handling of the ulnar nerve, which can cause nerve dysfunction; however, the incidence of postoperative ulnar nerve dysfunction is not well studied. Our purpose was to determine the incidence of ulnar nerve dysfunction after open reduction and internal fixation of distal humerus fractures and identify factors associated with its development.
Design: Retrospective cohort study from two university-based institutions.
Patients: The medical records of 69 patients with a minimum of 12 months follow-up (median, 15 months; range, 12-72 months) after open reduction and plate and screw fixation of a bicolumnar fracture of the distal humerus (Orthopaedic Trauma Association Types 13A and C) that did not have preoperative ulnar nerve dysfunction were reviewed retrospectively.
Intervention: Surgical repair of a distal humerus fracture with or without ulnar nerve transposition.
Main Outcomes: Ulnar nerve function was graded immediately postoperatively and at final follow-up according to a modified system of McGowan. Those with and without ulnar neuropathy were analyzed for differences in final position of the nerve (anterior versus in the cubital tunnel), open injury, multiple procedures, ipsilateral injury, and demographic factors.
Results: The incidence of immediately postoperative ulnar nerve dysfunction documented in the medical record was seven of 69 patients (10.1%) (McGowan grades: 1 [57%], 2 [43%], 3 [0%]). The incidence of ulnar nerve dysfunction at final follow-up was 16% (11 of 69 patients) (McGowan grades: 1 [72%], 2 [28%], 3 [0%]). No demographic, injury, or treatment factors were associated with a risk of postoperative ulnar nerve dysfunction.
Conclusion: There is a substantial incidence of postoperative ulnar nerve dysfunction after open reduction and plate and screw fixation of the distal humerus, which is likely underestimated by this retrospective analysis. Prospective studies using careful preoperative nerve evaluation and systematic postoperative nerve assessment are likely to identify an even higher incident of postoperative ulnar nerve dysfunction. Transposition was not protective in this analysis.
C1 [Vazquez, Oscar; Walsh, Michael; Egol, Kenneth A.] NYU, Hosp Joint Dis, New York, NY USA.
[Rutgers, Marijn; Ring, David C.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Egol, KA (reprint author), 301 E 17th St, New York, NY 10003 USA.
EM kenneth.egol@nyumc.org
FU Orthopaedic Trauma Association
FX This research was made possible by a $10,000 grant from the Orthopaedic
Trauma Association.
NR 14
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U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0890-5339
J9 J ORTHOP TRAUMA
JI J. Orthop. Trauma
PD JUL
PY 2010
VL 24
IS 7
BP 395
EP 399
DI 10.1097/BOT.0b013e3181e3e273
PG 5
WC Orthopedics; Sport Sciences
SC Orthopedics; Sport Sciences
GA 620KY
UT WOS:000279500000002
PM 20577068
ER
PT J
AU Casarett, DJ
AF Casarett, David J.
TI Introduction: Finding the Future of International Palliative Care
SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT
LA English
DT Editorial Material
C1 [Casarett, David J.] Dept Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA 19104 USA.
[Casarett, David J.] Univ Penn, Philadelphia, PA 19104 USA.
RP Casarett, DJ (reprint author), Dept Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, 3615 Chestnut St, Philadelphia, PA 19104 USA.
EM casarett@med.upenn.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0885-3924
J9 J PAIN SYMPTOM MANAG
JI J. Pain Symptom Manage.
PD JUL
PY 2010
VL 40
IS 1
BP 1
EP 2
DI 10.1016/j.jpainsymman.2010.05.001
PG 2
WC Health Care Sciences & Services; Medicine, General & Internal; Clinical
Neurology
SC Health Care Sciences & Services; General & Internal Medicine;
Neurosciences & Neurology
GA 629PA
UT WOS:000280210900001
PM 20619202
ER
PT J
AU Krakauer, EL
Cham, NTP
Khue, LN
AF Krakauer, Eric L.
Cham, Nguyen Thi Phuong
Khue, Luong Ngoc
TI Vietnam's Palliative Care Initiative: Successes and Challenges in the
First Five Years
SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT
LA English
DT Article
DE Palliative care; AIDS; cancer; Vietnam; developing country; opioid
AB In 2005, Vietnam's Ministry of Health (MoH) launched a palliative care initiative that uses the World Health Organization (WHO) public health strategy for national palliative care program development. With international financial and technical support, the initiative has made significant early progress. A rapid situation analysis in 2005 led to national Guidelines on Palliative Care in 2006, radically improved opioid prescribing regulations in 2008, the training of more than 400 physicians in palliative care by early 2010 using three curricula written especially for Vietnam, and the initiation of palliative care services in some hospitals and in the community. Yet, access to palliative care services remains very limited. Many challenges must be overcome to reach the goal of access for all to essential palliative care services that are integrated into the systems of cancer care, HIV/AIDS care, and primary, care. Going forward, crucial aspects of the initiative will be continued commitment to palliative care by the MoH, careful planning and targeted funding that address each part of the 14710 public health strategy, ongoing expert technical support, and collaboration among international technical and financial supporters. J Pain Symptom Manage 2010;40:27-30. (C) 2010 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.
C1 [Krakauer, Eric L.] Harvard Univ, Sch Med, Ctr Palliat Care, Boston, MA 02115 USA.
[Krakauer, Eric L.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
[Krakauer, Eric L.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA 02115 USA.
[Krakauer, Eric L.] Massachusetts Gen Hosp, Palliat Care Serv, Boston, MA 02114 USA.
[Cham, Nguyen Thi Phuong; Khue, Luong Ngoc] Minist Hlth, Vietnam Adm Med Serv, Hanoi, Vietnam.
RP Krakauer, EL (reprint author), Harvard Univ, Sch Med, Ctr Palliat Care, 641 Huntington Ave, Boston, MA 02115 USA.
EM eric_krakauer@hms.harvard.edu
FU United States Centers for Disease Control and Prevention (CDC)
[U62/CCU122408-04]
FX This work was supported in part by Cooperative Agreement Number
U62/CCU122408-04 from the United States Centers for Disease Control and
Prevention (CDC). Its contents are solely the responsibility of the
authors and do not necessarily represent the official views of the CDC.
NR 15
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U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0885-3924
J9 J PAIN SYMPTOM MANAG
JI J. Pain Symptom Manage.
PD JUL
PY 2010
VL 40
IS 1
BP 27
EP 30
DI 10.1016/j.jpainsymman.2010.04.009
PG 4
WC Health Care Sciences & Services; Medicine, General & Internal; Clinical
Neurology
SC Health Care Sciences & Services; General & Internal Medicine;
Neurosciences & Neurology
GA 629PA
UT WOS:000280210900009
PM 20619210
ER
PT J
AU Kelley, AS
Morrison, RS
Wenger, NS
Ettner, SL
Sarkisian, CA
AF Kelley, Amy S.
Morrison, R. Sean
Wenger, Neil S.
Ettner, Susan L.
Sarkisian, Catherine A.
TI Determinants of Treatment Intensity for Patients with Serious Illness: A
New Conceptual Framework
SO JOURNAL OF PALLIATIVE MEDICINE
LA English
DT Article
ID OF-LIFE CARE; ILL HOSPITALIZED ADULTS; DECISION-MAKING; HEALTH-CARE;
HOSPICE USE; MEDICARE EXPENDITURES; REGIONAL-VARIATIONS; TREATMENT
PREFERENCES; ETHNIC-DIFFERENCES; PALLIATIVE CARE
AB Background: Research during the past few decades has greatly advanced our understanding of the cost, quality, and variability of medical care at the end of life. The current health-care policy debate has focused considerable attention on the unsustainable rate of spending and wide regional variation associated with medical treatments in the last year of life. New initiatives aim to standardize quality and reduce over-utilization at the end of life. We argue, however, that focusing exclusively on medical treatment at the end of life is not likely to lead to effective health-care policy reform or reduce costs. Specifically, end-of-life policy initiatives face the challenges of political feasibility, inaccurate prognostication, and gaps in the existing literature.
Objectives: With the ultimate aim of improving the quality and efficiency of care, we propose a research and policy agenda guided by a new conceptual framework of factors associated with treatment intensity for patients with serious and complicated medical illness. This model not only expands the population of interest to include all adults with serious illness, but also provides a blueprint for the thorough investigation of the diverse and interconnected determinants of treatment intensity.
Conclusions: The new conceptual framework presented in this paper can be used to develop future research and policy initiatives designed to improve the quality and efficiency of care for adults with serious illness.
C1 [Kelley, Amy S.; Morrison, R. Sean] Mt Sinai Sch Med, Brookdale Dept Geriatr & Palliat Med, New York, NY 10029 USA.
[Kelley, Amy S.; Morrison, R. Sean] Mt Sinai Sch Med, Hertzberg Palliat Care Inst, New York, NY 10029 USA.
[Morrison, R. Sean] James J Peters VA Med Ctr, Bronx, NY USA.
[Wenger, Neil S.; Ettner, Susan L.] Univ Calif Los Angeles, David Geffen Sch Med, Div GIM HSR, Los Angeles, CA 90095 USA.
[Sarkisian, Catherine A.] Univ Calif Los Angeles, David Geffen Sch Med, Div Genatr, Dept Med, Los Angeles, CA 90095 USA.
[Sarkisian, Catherine A.] VA Greater Angeles Healthcare Syst, Genatr Res Educ Clin Ctr, Los Angeles, CA USA.
RP Kelley, AS (reprint author), Mt Sinai Sch Med, Brookdale Dept Geriatr & Palliat Med, 1 Gustave Levy Pl, New York, NY 10029 USA.
EM amy.kelley@mssm.edu
FU NIA NIH HHS [K24 AG022345]
NR 82
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U1 4
U2 11
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1096-6218
J9 J PALLIAT MED
JI J. Palliat. Med.
PD JUL
PY 2010
VL 13
IS 7
BP 807
EP 813
DI 10.1089/jpm.2010.0007
PG 7
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA 626PG
UT WOS:000279977300012
PM 20636149
ER
PT J
AU Yung, VY
Walling, AM
Min, LL
Wenger, NS
Ganz, DA
AF Yung, Victoria Y.
Walling, Anne M.
Min, Lillian
Wenger, Neil S.
Ganz, David A.
TI Documentation of Advance Care Planning for Community-Dwelling Elders
SO JOURNAL OF PALLIATIVE MEDICINE
LA English
DT Article
ID VULNERABLE OLDER-PEOPLE; OF-LIFE CARE; DIRECTIVES; QUALITY;
INTERVENTION; ORDERS
AB Background: Advance planning for end-of-life care has gained acceptance, but actual end-of-life care is often incongruent with patients' previously stated goals. We assessed the flow of advance care planning information from patients to medical records in a community sample of older adults to better understand why advance care planning is not more successful.
Methods: Our study used structured interview and medical record data from community-dwelling older patients in two previous studies: Assessing Care of Vulnerable Elders (ACOVE)-1 (245 patients age >= 65 years and screened for high risk of death/functional decline in 1998-1999) and ACOVE-2 (566 patients age >= 75 who screened positive for falls/mobility disorders, incontinence, and/or dementia in 2002-2003). We compared interview data on patients' preferences, advance directives, and surrogate decision-makers with findings from the medical record.
Results: In ACOVE-1, 38% of surveyed patients had thought about limiting the aggressiveness of medical care; 24% of surveyed patients stated that they had spoken to their doctor about this. The vast majority of patients (88%-93%) preferred to die rather than remain permanently in a coma, on a ventilator, or tube fed. Regardless of patients' specific preferences, 15%-22% of patients had preference information in their medical record. Among patients who reported that they had completed an advance directive and had given it to their health-care provider, 15% (ACOVE-1) and 47% (ACOVE-2) had advance directive information in the medical record. Among patients who had not completed an advance directive but had given surrogate decision-maker information to their provider, 0% (ACOVE-1) and 16% (ACOVE-2) had documentation of a surrogate decision-maker in the medical record.
Conclusions: Community-dwelling elders' preferences for end-of-life care are not consistent with documentation in their medical records. Electronic health records and standardized data collection for end-of-life care could begin to ameliorate this problem.
C1 [Yung, Victoria Y.; Walling, Anne M.; Min, Lillian; Wenger, Neil S.; Ganz, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Ganz, David A.] Vet Affairs Greater Angeles Healthcare Syst, Hlth Serv Res & Dev Ctr Excellence, Los Angeles, CA USA.
[Ganz, David A.] Vet Affairs Greater Angeles Healthcare Syst, Ctr Geriatr Res Educ & Clin, Los Angeles, CA USA.
[Walling, Anne M.; Wenger, Neil S.] Univ Calif Los Angeles, Healthcare Eth Ctr, Los Angeles, CA USA.
RP Ganz, DA (reprint author), VA Greater Angeles Healthcare Syst 11G, 11301 Wilshire Blvd,Bldg 220,Room 313, Los Angeles, CA 90073 USA.
EM dganz@mednet.ucla.edu
FU NIA/AFAR & Lillian R. Gleitsman Medical Student Training in Aging
Research; National Research Service [T32 PE19001]; UCLA Specialty
Training & Advanced Research; Agency for Healthcare Research and Quality
[R21 HS017621-01]; National Institute on Aging-UCLA [K12 AG001004]; U.S.
Department of Veterans Affairs, Veterans Health Administration; VA
Health Services Research & Development (HSR&D) Service through the VA
Greater Los Angeles HSR&D Center of Excellence [VA CD2 08-012-1]; Pfizer
Inc.
FX The authors thank Carol Roth for guidance regarding the ACOVE medical
record reviews, Caren Kamberg and Patty Smith for administrative
assistance, and anonymous peer reviewers for their thoughtful feedback
on the manuscript. Ms. Yung was supported by the NIA/AFAR & Lillian R.
Gleitsman Medical Student Training in Aging Research Program. Dr.
Walling was supported by National Research Service Award Training Grant
T32 PE19001 and the UCLA Specialty Training & Advanced Research Program.
Dr. Min was supported by grants from the Agency for Healthcare Research
and Quality (R21 HS017621-01) and National Institute on Aging-UCLA (K12
AG001004). Dr. Ganz was supported by the U.S. Department of Veterans
Affairs, Veterans Health Administration, VA Health Services Research &
Development (HSR&D) Service through the VA Greater Los Angeles HSR&D
Center of Excellence (Project no. VA CD2 08-012-1). Data analyzed in
this manuscript were collected as part of the Assessing Care of
Vulnerable Elders and Assessing Care of Vulnerable Elders-2 projects,
which were supported by Pfizer Inc. The funders mentioned played no role
in the design and conduct of the study; collection, management,
analysis, and interpretation of the data; or preparation, review, or
approval of the manuscript. The views expressed in this article are
those of the authors and do not necessarily reflect the position or
policy of the National Institutes of Health, the Agency for Healthcare
Research and Quality, or the U.S. Department of Veterans Affairs.
NR 23
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U1 1
U2 10
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1096-6218
J9 J PALLIAT MED
JI J. Palliat. Med.
PD JUL
PY 2010
VL 13
IS 7
BP 861
EP 867
DI 10.1089/jpm.2009.0341
PG 7
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA 626PG
UT WOS:000279977300021
PM 20618087
ER
PT J
AU Jonker, MA
Osterby, KR
Vermeulen, LC
Kleppin, SM
Kudsk, KA
AF Jonker, Mark A.
Osterby, Kurt R.
Vermeulen, Lee C.
Kleppin, Susan M.
Kudsk, Kenneth A.
TI Does Low-Dose Heparin Maintain Central Venous Access Device Patency? A
Comparison of Heparin Versus Saline During a Period of Heparin Shortage
SO JOURNAL OF PARENTERAL AND ENTERAL NUTRITION
LA English
DT Article
DE central venous access; thrombosis; adults; heparin flush; alteplase
ID CATHETER CLOTS; DRUG SHORTAGES; THROMBOCYTOPENIA; ALTEPLASE; FLUSH;
COMPLICATIONS; METAANALYSIS; EFFICACY; SODIUM; TRIAL
AB Background: A common problem that complicates use of central venous access devices (CVADs) is occlusion by thrombosis. Alteplase, a recombinant tissue plasminogen activator, is used to restore line patency when thrombosis occurs. Heparin flush is commonly used to prevent this complication, but the effectiveness of this practice is unclear. A recent heparin shortage allowed examination of heparin effectiveness in reducing CVAD thrombosis. Methods: A retrospective cohort study was performed by querying a pharmacy database for alteplase use for CVAD thrombosis in adult patients during periods when heparin flushes (10 units/mL) were used and when saline flushes were used instead because of a nationwide heparin shortage. The number of patients receiving alteplase, the number of doses administered, and the total amount of alteplase used were compared over 1-month intervals of heparin flush use and 1-month intervals of saline flush use. Patient days and critical care patient days were compared between these time intervals. Peripherally inserted central catheter (PICC) line placements and replacements between time periods of heparin and saline flush were also compared. Results: Significant increases in the number of patients receiving alteplase (P = .04), the number of alteplase doses administered (P = .04), and total dose of alteplase used (P = .05) occurred during the heparin shortage. No significant differences in patient population were observed. The percentage of PICC line replacements also increased significantly (P < .05) when heparin was not available. Conclusions: Heparin flush (10 units/mL) decreases thrombotic occlusions of CVADs, resulting in decreased alteplase use and fewer PICC line replacements. (JPEN J Parenter Enteral Nutr. 2010; 34: 444-449)
C1 [Kudsk, Kenneth A.] William S Middleton Mem Vet Adm Med Ctr, Vet Adm Surg Serv, Madison, WI USA.
[Jonker, Mark A.; Kudsk, Kenneth A.] Univ Wisconsin, Dept Surg, Sch Med & Publ Hlth, Madison, WI USA.
[Osterby, Kurt R.; Vermeulen, Lee C.] Univ Wisconsin, Hosp & Clin, Dept Pharm, Madison, WI 53792 USA.
[Vermeulen, Lee C.] Univ Wisconsin, Sch Pharm, Madison, WI 53706 USA.
[Kleppin, Susan M.] Waukesha Mem Hosp, Dept Pharm, Waukesha, WI USA.
RP Kudsk, KA (reprint author), 600 Highland Ave,H4-736 CSC, Madison, WI 53792 USA.
EM kudsk@surgery.wisc.edu
NR 27
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U1 3
U2 16
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 JUL
PY 2010
VL 34
IS 4
BP 444
EP 449
DI 10.1177/0148607110362082
PG 6
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 638HN
UT WOS:000280884300011
PM 20631392
ER
PT J
AU Green, R
Horn, H
Erickson, JM
AF Green, Rebecca
Horn, Heather
Erickson, Jeanne M.
TI Eating Experiences of Children and Adolescents With Chemotherapy-Related
Nausea and Mucositis
SO JOURNAL OF PEDIATRIC ONCOLOGY NURSING
LA English
DT Article
DE children; cancer; eating; nutrition
ID NUTRITIONAL ISSUES; PEDIATRIC ONCOLOGY; CANCER-TREATMENT; CARE;
PERCEPTIONS; DISTRESS
AB Despite many advances in symptom management, children and adolescents with cancer still have trouble maintaining adequate oral intake during routine chemotherapy treatment. The purpose of this qualitative study was to explore the eating experiences of children and adolescents receiving chemotherapy when they had problems with nausea and mucositis. Eight children and adolescents and their caregivers were interviewed to describe how and what the children and adolescents ate when they were nauseated and/or had a sore mouth. Findings reveal that these children and adolescents all experienced nausea and frequently preferred not to eat during these periods. Eating problems related to mucositis also limited oral intake in this sample. These children and adolescents and their caregivers tried a variety of foods and strategies to maintain intake, including those recommended by health care providers. Prevention and management of nausea remains a challenge for children and adolescents receiving chemotherapy. Health care providers need to offer detailed eating suggestions throughout therapy so that these patients can maintain adequate nutrition and weight for optimal treatment tolerance as well as normal growth and development. Continued research is needed to test the effectiveness of interventions focused on maintaining oral intake during cancer treatment.
C1 [Green, Rebecca] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Horn, Heather; Erickson, Jeanne M.] Univ Virginia, Charlottesville, VA USA.
RP Erickson, JM (reprint author), 96 Claymont Dr, Earlysville, VA 22936 USA.
EM jme3a@virginia.edu
NR 22
TC 9
Z9 13
U1 1
U2 9
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1043-4542
J9 J PEDIATR ONCOL NURS
JI J. Pediatr. Oncol. Nurs.
PD JUL-AUG
PY 2010
VL 27
IS 4
BP 209
EP 216
DI 10.1177/1043454209360779
PG 8
WC Oncology; Nursing
SC Oncology; Nursing
GA 613AF
UT WOS:000278947300004
PM 20562389
ER
PT J
AU Harrod, CC
Boykin, RE
Kim, YJ
AF Harrod, Christopher C.
Boykin, Robert E.
Kim, Young J.
TI Epidural Pneumatosis of the Cervicothoracic Spine Associated With
Transient Upper Motor Neuron Findings Complicating Haemophilus
influenzae Pharyngitis, Bronchitis, and Mediastinitis
SO JOURNAL OF PEDIATRIC ORTHOPAEDICS
LA English
DT Article
DE epidural pneumatosis; pneumorrhacis; aerorachia; upper motor neuron
signs; Haemophilus Influenzae respiratory infection
ID SUBCUTANEOUS EMPHYSEMA; SPONTANEOUS PNEUMOMEDIASTINUM; AIR;
PNEUMOPERICARDIUM; PNEUMORRHACHIS; DIAGNOSIS; MANEUVERS; TRAUMA; ASTHMA
AB Background: Epidural pneumatosis and pneumomediastinum are rare findings. Reports in children are exceedingly rare. Abnormal neurologic findings have yet to be reported.
Methods: We report on the case of a 7-year-old girl who was diagnosed with epidural pneumatosis with signs of neurologic compression in the setting of Haemophilus influenzae upper and lower respiratory infection. After urgent direct laryngoscopy, bronchoscopy, esophagoscopy, and pharyngeal biopsy was carried out, CT scan of the chest revealed extensive pneumomediastinum tracking along vessels throughout the neck and chest in addition to epidural pneumatosis from C6 to T5. Upper motor neuron findings were present. Broad spectrum antibiotics were administered, and interval neurologic examination and repeat CT scans showed resolution of abnormal neurologic exam in addition to epidural pneumatosis dissipation.
Results: Rapid clinical improvement was noted on broad spectrum intravenous antibiotics with extubation on postoperative day one. She was discharged home on oral augmentin on postoperative day 4 with intact neurologic examination. At 11 month follow-up, she remained symptom-free with normal neurologic examination and unremarkable cervical and thoracic spine radiographs.
Conclusion: Resolution of clinical and radiographic findings is possible with conservative treatment.
C1 [Kim, Young J.] Childrens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA.
[Harrod, Christopher C.; Boykin, Robert E.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Kim, YJ (reprint author), Childrens Hosp, Dept Orthoped Surg, 300 Longwood Ave,Fegan Bldg,2nd Floor, Boston, MA 02115 USA.
EM young-jo-kim@children-s.harvard.edu
NR 28
TC 1
Z9 2
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0271-6798
J9 J PEDIATR ORTHOPED
JI J. Pediatr. Orthop.
PD JUL-AUG
PY 2010
VL 30
IS 5
BP 455
EP 459
DI 10.1097/BPO.0b013e3181df44b6
PG 5
WC Orthopedics; Pediatrics
SC Orthopedics; Pediatrics
GA 636NJ
UT WOS:000280743700009
PM 20574262
ER
PT J
AU Bamboat, ZM
Masiakos, PT
AF Bamboat, Zubin M.
Masiakos, Peter T.
TI Sclerosing angiomatoid nodular transformation of the spleen in an
adolescent with chronic abdominal pain
SO JOURNAL OF PEDIATRIC SURGERY
LA English
DT Article
DE Angiomatoid nodule; IgG4-related sclerosing disease; Sclerosing
angiomatoid nodular transformation; Spleen; Splenectomy
ID SANT; CELLS
AB Sclerosing angiomatoid nodular transformation (SANT) is a relatively new, benign neoplasm arising within the red pulp of the spleen. The lesion is often identified incidentally on imaging, and the diagnosis is confirmed on pathologic assessment of the resected spleen. Although there have been several reports of SANT in the adult population, data on this lesion in the pediatric population are exceedingly rare. We present a case of SANT in an adolescent male with chronic abdominal pain and discuss the management issues that arise in treating this condition in the pediatric population. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Bamboat, Zubin M.; Masiakos, Peter T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat Surg, Boston, MA 02114 USA.
RP Masiakos, PT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat Surg, Boston, MA 02114 USA.
EM pmasiakos@partners.org
NR 11
TC 9
Z9 12
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 0022-3468
J9 J PEDIATR SURG
JI J. Pediatr. Surg.
PD JUL
PY 2010
VL 45
IS 7
BP E13
EP E16
DI 10.1016/j.jpedsurg.2010.04.020
PG 4
WC Pediatrics; Surgery
SC Pediatrics; Surgery
GA 627SW
UT WOS:000280064100039
PM 20638509
ER
PT J
AU Wanner, J
Long, ME
Teng, EJ
AF Wanner, Jill
Long, Mary E.
Teng, Ellen J.
TI Multi-component Treatment for Posttraumatic Nightmares in Vietnam
Veterans: Two Case Studies
SO JOURNAL OF PSYCHIATRIC PRACTICE
LA English
DT Article
DE posttraumatic stress disorder (PTSD); imagery rescripting; nightmares;
Veterans; treatment
ID IMAGERY REHEARSAL THERAPY; STRESS-DISORDER; PSYCHOMETRIC PROPERTIES;
PTSD; TRAUMA; PSYCHOTHERAPY; IRAQ
AB Posttraumatic nightmares (PTNMs) are trauma-related distressing dreams that cause a person to wake up. PTNMs can be a devastating addition to the clinical picture of posttraumatic stress disorder (PTSD), because they can result in increased levels of PTSD symptoms and overall distress and decreased sleep; they are also often resistant to typical PTSD treatments. While specialized treatments have been developed and empirically examined in the civilian population, these treatments have not been thoroughly explored with the Veteran population, despite the fact that 50%-88% of Vietnam Veterans experience chronic PTNMs. This article presents two case reports involving Vietnam Veterans. These reports describe the initial investigation of a variant of a treatment that has been successful in treating chronic PTNMs in the civilian population and has been modified to meet the needs of the Veteran population. Analyses revealed that both Veterans reported moderate reductions in sleep disturbances over the course of treatment, as well as clinically significant reductions in PTSD and depressive symptoms across assessments. These preliminary findings provide encouraging data that warrant further study. Limitations and future research are discussed. (Journal of Psychiatric Practice 2010;16:243-249)
C1 [Long, Mary E.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Menninger Dept Psychiat & Behav Sci,Houston Ctr Q, Vet Affairs S Cent Mental Illness Res Educ & Clin, Houston, TX 77030 USA.
RP Long, ME (reprint author), Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Menninger Dept Psychiat & Behav Sci,Houston Ctr Q, Vet Affairs S Cent Mental Illness Res Educ & Clin, 2002 Holcombe Blvd 152, Houston, TX 77030 USA.
EM melong6@gmail.com
FU South Central Mental Illness, Research, Education and Clinical Center
(MIRECC); Houston VA HSR&D Center of Excellence [HFP90-020]; Office of
Academic Affiliations, Department of Veterans Affairs
FX This research was supported by start-up funds to Mary E. Long, Ph.D.
from the South Central Mental Illness, Research, Education and Clinical
Center (MIRECC) as part of the VA Special MIRECC Fellowship Program in
Advanced Psychiatry and Psychology. This work was also supported in part
by the Houston VA HSR&D Center of Excellence (HFP90-020) and the Office
of Academic Affiliations, Department of Veterans Affairs. The views
expressed in this article are those of the author(s) and do not
necessarily represent the views of the Department of Veterans Affairs.
NR 32
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U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1527-4160
J9 J PSYCHIATR PRACT
JI J. Psychiatr. Pract.
PD JUL
PY 2010
VL 16
IS 4
BP 243
EP 249
DI 10.1097/01.pra.0000386910.31817.b5
PG 7
WC Psychiatry
SC Psychiatry
GA 628EM
UT WOS:000280097200005
PM 20644359
ER
PT J
AU Binder, EB
Newport, UJ
Zach, EB
Smith, AK
Deveau, TC
Altshuler, LL
Cohen, LS
Stowe, ZN
Cubells, JF
AF Binder, Elisabeth B.
Newport, U. Jeffrey
Zach, Elizabeth B.
Smith, Alicia K.
Deveau, Todd C.
Altshuler, Lori L.
Cohen, Lee S.
Stowe, Zachary N.
Cubells, Joseph F.
TI A serotonin transporter gene polymorphism predicts peripartum depressive
symptoms in an at-risk psychiatric cohort
SO JOURNAL OF PSYCHIATRIC RESEARCH
LA English
DT Article
DE Peripartum depression; Pregnancy; Serotonin transporter; 5-HTTLPR;
Polymorphism; At-risk population
ID POSTPARTUM DEPRESSION; MATERNAL DEPRESSION; PROMOTER POLYMORPHISM;
TRYPTOPHAN DEPLETION; MAJOR DEPRESSION; PERINATAL DEPRESSION; POSTNATAL
DEPRESSION; LIFE EVENTS; ASSOCIATION; WOMEN
AB Backgroud: Peripartum major depressive disorder (MDD) is a prevalent psychiatric disorder with potential detrimental consequences for both mother and child. Despite its enormous health care relevance, data regarding genetic predictors of peripartum depression are sparse. The aim of this study was to investigate associations of the serotonin-transporter linked polymorphic region (5-HTTLPR) genotype with peripartum MDD in an at-risk population.
Methods: Two hundred and seventy four women with a prior history of MDD were genotyped for 5-HTTLPR and serially evaluated in late pregnancy (gestational weeks 31-40), early post-partum (week 1-8) and late post-partum (week 9-24) for diagnosis of a current major depressive episode (MDE) and depressive symptom severity.
Results: 5-HTTLPR S-allele carrier status predicted the occurrence of a MDE in the early post-partum period only (OR = 5.13, p = 0.017). This association persisted despite continued antidepressant treatment.
Conclusions: The 5-HTTLPR genotype may be a clinically relevant predictor of early post-partum depression in an at-risk population.
Objective: Peripartum major depressive disorder is a prevalent psychiatric disorder with potential detrimental consequences for both mother and child. Despite its enormous health care relevance, data regarding genetic predictors of peripartum depression are sparse. The aim of this study was to investigate associations of the serotonin-transporter linked polymorphic region (5-HTTLPR) genotype with peripartum MOD in an at-risk population. (C) 2009 Elsevier Ltd. All rights reserved.
C1 [Binder, Elisabeth B.] Max Planck Inst Psychiat, Munich, Germany.
[Binder, Elisabeth B.; Newport, U. Jeffrey; Zach, Elizabeth B.; Smith, Alicia K.; Deveau, Todd C.; Cubells, Joseph F.] Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA USA.
[Binder, Elisabeth B.; Smith, Alicia K.; Stowe, Zachary N.; Cubells, Joseph F.] Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA USA.
[Altshuler, Lori L.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Mood Disorders Res Program, Los Angeles, CA 90024 USA.
[Cohen, Lee S.] Massachusetts Gen Hosp, Perinatal & Reprod Psychiat Clin Res Program, Boston, MA 02114 USA.
[Stowe, Zachary N.] Emory Univ, Sch Med, Dept Gynecol & Obstet, Atlanta, GA USA.
RP Binder, EB (reprint author), Max Planck Inst Psychiat, Munich, Germany.
EM binder@mpipsykl.mpg.de
RI Binder, Elisabeth/K-8905-2014;
OI Newport, D. Jeffrey/0000-0003-1695-9710
FU NIMH [P50 MH 68036]; Doris Duke Charitable foundation
FX Funding for this study was provided a Specialized Center for Research
from NIMH to Stowe (P50 MH 68036) and the Doris Duke Charitable
foundation (Career development award to Binder); the NIMH and the Doris
Duke Charitable foundation 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 40
TC 24
Z9 25
U1 5
U2 9
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0022-3956
J9 J PSYCHIATR RES
JI J. Psychiatr. Res.
PD JUL
PY 2010
VL 44
IS 10
BP 640
EP 646
DI 10.1016/j.jpsychires.2009.12.001
PG 7
WC Psychiatry
SC Psychiatry
GA 629RO
UT WOS:000280217600003
PM 20045118
ER
PT J
AU Kane, JM
Barnes, TRE
Correll, CU
Sachs, G
Buckley, P
Eudicone, J
McQuade, R
Tran, QV
Pikalov, A
Assuncao-Talbott, S
AF Kane, John M.
Barnes, Thomas R. E.
Correll, Christoph U.
Sachs, Gary
Buckley, Peter
Eudicone, James
McQuade, Robert
Tran, Quynh-Van
Pikalov, Andrei, III
Assuncao-Talbott, Sheila
TI Evaluation of akathisia in patients with schizophrenia, schizoaffective
disorder, or bipolar I disorder: a post hoc analysis of pooled data from
short- and long-term aripiprazole trials
SO JOURNAL OF PSYCHOPHARMACOLOGY
LA English
DT Article
DE akathisia; aripiprazole; bipolar I disorder; haloperidol; olanzapine;
schizoaffective disorder; schizophrenia
ID NEUROLEPTIC-INDUCED AKATHISIA; DRUG-INDUCED AKATHISIA; DOUBLE-BLIND;
MOVEMENT-DISORDERS; RATING-SCALE; ATYPICAL ANTIPSYCHOTICS; ACUTE
EXACERBATION; OPEN-LABEL; PLACEBO; MANAGEMENT
AB The objective of this article is to assess the clinical characteristics of akathisia in patients with schizophrenia, schizoaffective disorder, or bipolar I disorder receiving aripiprazole, haloperidol, olanzapine, or placebo. We conducted post hoc analyses of pooled safety data from trials in patients with schizophrenia, schizoaffective disorder, and bipolar I disorder. Outcome measures included the incidence of akathisia, time to onset, duration, severity, and discontinuation due to akathisia, concomitant use of benzodiazepines and/or anticholinergics, Barnes Akathisia Rating Scale (BARS) scores, and the correlation between antipsychotic efficacy and akathisia. The results for schizophrenia and schizoaffective disorder were as follows: akathisia in 9% of aripiprazole- and 6% of placebo-treated patients; 12.5% of aripiprazole- versus 24% of haloperidol-treated patients; 11% of aripiprazole- versus 6% of olanzapine-treated patients. Bipolar I disorder: akathisia in 18% of aripiprazole- and 5% of placebo-treated patients. The clinical characteristics of akathisia were similar between each data set, regardless of disease. Akathisia was generally mild-to-moderate in severity. Discontinuation due to akathisia was low in both the schizophrenia trials (aripiprazole 0.3%; placebo 0%; aripiprazole 0.9%; haloperidol 2.3%; aripiprazole 1.2%; olanzapine 0.2%) and the bipolar trials (aripiprazole 2.3%; placebo 0%). Treatment-emergent akathisia was not associated with a poorer clinical response. In conclusion, akathisia with aripiprazole occurred early in treatment, was mild-to-moderate in severity, led to few study discontinuations, and did not compromise therapeutic efficacy.
C1 [Kane, John M.] Zucker Hillside Hosp, Dept Psychiat, Glen Oaks, NY 11004 USA.
[Barnes, Thomas R. E.] Univ London Imperial Coll Sci Technol & Med, London, England.
[Sachs, Gary] Harvard Massachusetts Gen Hosp, Boston, MA USA.
[Buckley, Peter] Med Coll Georgia, Augusta, GA 30912 USA.
[Eudicone, James; Assuncao-Talbott, Sheila] Bristol Myers Squibb Co, Plainsboro, NJ USA.
[McQuade, Robert] Otsuka Pharmaceut Dev & Commercializat Inc, Princeton, NJ USA.
[Tran, Quynh-Van; Pikalov, Andrei, III] Otsuka Amer Pharmaceut Inc, Rockville, MD 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
RI Correll, Christoph/D-3530-2011
FU Kakuri Omari, PhD, Phase Five Communications, Inc.; Bristol-Myers Squibb
FX Editorial support was provided by Kakuri Omari, PhD, Phase Five
Communications, Inc., with funding provided by Bristol-Myers Squibb.
NR 64
TC 24
Z9 24
U1 0
U2 4
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0269-8811
J9 J PSYCHOPHARMACOL
JI J. Psychopharmacol.
PD JUL
PY 2010
VL 24
IS 7
BP 1019
EP 1029
DI 10.1177/0269881109348157
PG 11
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 612AE
UT WOS:000278866900009
PM 20008446
ER
PT J
AU Naidu, MD
Mason, JM
Pica, RV
Fung, H
Pena, LA
AF Naidu, Mamta D.
Mason, James M.
Pica, Raymond V.
Fung, Hua
Pena, Louis A.
TI Radiation Resistance in Glioma Cells Determined by DNA Damage Repair
Activity of Ape1/Ref-1
SO JOURNAL OF RADIATION RESEARCH
LA English
DT Article
DE Glioma; Lucanthone; Radiation tolerance; DNA Repair; DNA- (Apurinic or
Apyrimidinic Site) lyase; Ape1/Ref-1/APEX; HAP1
ID BASE EXCISION-REPAIR; APURINIC/APYRIMIDINIC ENDONUCLEASE ACTIVITY; HUMAN
APURINIC ENDONUCLEASE; AP-ENDONUCLEASE; IONIZING-RADIATION;
ALKYLATING-AGENTS; BIOLOGICAL BASIS; GENE-EXPRESSION; ENZYME HAP1;
IN-VITRO
AB Since radiation therapy remains a primary treatment modality for gliomas, the radioresistance of elioma cells and targets to modify their radiation tolerance are of significant interest. Human apurinic endonuclease I (Apel, Ref-1, APEX, HAP1, AP endo) is a multifunctional protein involved in base excision repair of DNA and a redox-dependent transcriptional co-activator. This study investigated whether there is a direct relationship between Ape I and radioresistance in glioma cells, employing the human U87 and U251 cell lines. U87 is intrinsically more radioresistant than U251, which is partly attributable to more cycling U25I cells found in G2/M, the most radiosensitive cell stage, while more U87 cells are found in S and GI, the more radioresistant cell stages. But observed radioresistance is also related to Apel activity. U87 has higher levels of Apel than does U251, as assessed by Western blot and enzyme activity assays (-1.5-2 fold higher in cycling cells, and -10 fold higher at G2/M). A direct relationship was seen in cells transfected with CMV-Apel constructs; there was a dose-dependent relationship between increasing Ape I overexpression and increasing radioresistance. Conversely, knock down by siRNA or by pharmacological down regulation of Apel resulted in decreased radioresistance. The inhibitors lucanthone and CRT004876 were employed, the former a thioxanthene previously under clinical evaluation as a radiosensitizer for brain tumors and the latter a more specific Apel inhibitor. These data suggest that Ape I may be a useful target for modifying radiation tolerance.
C1 [Pena, Louis A.] Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA.
[Naidu, Mamta D.] Brookhaven Natl Lab, Dept Biol, Upton, NY 11973 USA.
[Mason, James M.; Pica, Raymond V.] NS LIJ Feinstein Inst Med Res, Manhasset, NY USA.
[Fung, Hua] Dana Farber Canc Res Inst, Dept Genet & Complex Dis, Boston, MA USA.
RP Pena, LA (reprint author), Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA.
EM lpena@bnl.gov
OI Naidu, Mamta/0000-0002-2754-2470
FU DOE [KP-1401020/M0-079]; NIH [R01-CA86897]
FX This work was supported in part by DOE grant KP-1401020/M0-079 to L.A.
Pena and NIH grants R01-CA86897 to B.M. Sutherland. We thank Drs. Betsy
Sutherland and Fritz Henn for their support to MN. We thank Dr. Carl
Anderson and John Dunn (BNL), Bruce Demple (Harvard University), Michael
Waring (Cambridge University), and Mark Kelley (Indiana University) for
valuable suggestions. We thank statistician Keith Thompson for the two
components fit calculations. BNL is managed by Brookhaven Science
Associates. L.L.C. for the U.S. Department of Energy under Contract
DE-ACO2-98CH10886.
NR 60
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U1 0
U2 3
PU JAPAN RADIATION RESEARCH SOC
PI CHIBA
PA C/O NAT INST RADIOLOGICAL SCI 9-1 ANAGAWA-4-CHOME INAGE-KU, CHIBA, 263,
JAPAN
SN 0449-3060
J9 J RADIAT RES
JI J. Radiat. Res.
PD JUL
PY 2010
VL 51
IS 4
BP 393
EP 404
DI 10.1269/jrr.09077
PG 12
WC Biology; Radiology, Nuclear Medicine & Medical Imaging
SC Life Sciences & Biomedicine - Other Topics; Radiology, Nuclear Medicine
& Medical Imaging
GA 637MX
UT WOS:000280823300004
PM 20679741
ER
PT J
AU Folkins, A
Cruz, L
Goldstein, DP
Berkowitz, RS
Crum, C
Kindelberger, D
AF Folkins, Ann
Cruz, Lilliam
Goldstein, Donald P.
Berkowitz, Ross S.
Crum, Christopher
Kindelberger, David
TI Utility of Chromosomal Chromogenic in Situ Hybridization as an
Alternative to Flow Cytometry and Cytogenetics in the Diagnosis of Early
Partial Hydatidiform Moles A Validation Study
SO JOURNAL OF REPRODUCTIVE MEDICINE
LA English
DT Article; Proceedings Paper
CT 15th World Congress on Gestational Trophoblastic Diseases
CY NOV 12-15, 2009
CL Kochi, INDIA
SP Int Soc Study Trophoblast Dis
DE chromosome; flow cytometry; hybridization; hydatidiform mole; ploidy
ID GESTATIONAL TROPHOBLASTIC DISEASE; DIFFERENTIAL-DIAGNOSIS;
EARLY-PREGNANCY; PLOIDY; IMMUNOHISTOCHEMISTRY
AB OBJECTIVE: The introduction of p57 immunohistochemistry has aided the distinction between early complete moles (CMs) and hydropic abortus (HA), but no single technique has emerged for the distinction between early partial moles (PMs) cytogenetics have been used, but these require specialized equipment/expertise. The. goal of this study is validation of chromosome in situ hybridization (CrISH), focusing on comparing the results to those obtained by cytogenetic methods.
STUDY DESIGN: Archival paraffin blocks from molar and nonmolar gestations were retrieved. Sections were labeled with a chromosome 10 probe. Hybridization and visualization were performed using standard protocols. One hundred nuclei per sample were scored for the number of signals.
RESULTS: Of 50 hydatidiform moles, 22 were PMs and 28 were CMs. The CMs showed 2 signals in 25 cases and 4 signals in 3 cases. The PMs showed 3 signals in 21 cases and 2 signals in 1 case. For the HAs there were 2 signals in 24 cases, and 1 case had 3 signals. Concordance between CrISH and flow cytometry studies for molar gestations was 95%.
CONCLUSION: CrISH is a highly effective adjunct in differentiating between PM and CM and between PM and HA. CrISH is a simple, cost effective adjunct in evaluating molar gestations. (J Reprod Med 2010;55:275-278)
C1 [Kindelberger, David] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
Harvard Univ, Brigham & Womens Hosp, Sch Med,Dept Obstet & Gynecol,Div Gynecol Oncol, Dana Farber Canc Inst,New England Trophoblast Dis, Boston, MA 02115 USA.
RP Kindelberger, D (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA.
EM dkindelberger@partners.org
NR 14
TC 2
Z9 3
U1 0
U2 1
PU SCI PRINTERS & PUBL INC
PI ST LOUIS
PA PO DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA
SN 0024-7758
J9 J REPROD MED
JI J. Reprod. Med.
PD JUL-AUG
PY 2010
VL 55
IS 7-8
BP 275
EP 278
PG 4
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 639IP
UT WOS:000280968800002
PM 20795338
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 Low-Risk Gestational Trophoblastic Neoplasia and Methotrexate Resistance
Predictors of Response to Treatment with Actinomycin D and Need for
Combination Chemotherapy
SO JOURNAL OF REPRODUCTIVE MEDICINE
LA English
DT Article; Proceedings Paper
CT 15th World Congress on Gestational Trophoblastic Diseases
CY NOV 12-15, 2009
CL Kochi, INDIA
SP Int Soc Study Trophoblast Dis
DE gestational trophoblastic disease; molar pregnancy
ID POSTEVACUATION HCG LEVELS; COMPLETE MOLAR PREGNANCY; LOW-DOSE
METHOTREXATE; DISEASE; WOMEN; CHEMOTHERAPY; MANAGEMENT; TUMORS; REGIMEN
AB OBJECTIVE: To determine whether any clinical parameters predict the need for multiagent chemotherapy for treatment of low-risk gestational trophoblastic neoplasia (GTN) after the development of methotrexate (MTX) resistance.
STUDY DESIGN: We retrospectively analyzed clinical data from the New England Trophoblastic Disease Center from women with post molar GTN between 1973 and 2003.
RESULTS: We analyzed data from 150 women (40 with partial mole, 110 with complete mole) who received single-agent MTX for low-risk GTN using FIGO and WHO scoring systems. Of the 45 women who developed MTX resistance, the majority (37/45) of these patients received actinomycin D, with 10 patients ultimately requiring multiagent chemotherapy. The requirement for multiagent chemotherapy following MTX resistance was associated with a beta-hCG > 600 mIU/mL 1 week following initial MTX therapy (p < 0.03). Conversely, a beta-hCG < 600 mIU/mL 1 week following initial MTX therapy was associated with a 93% probability of remission with actinomycin D alone. All patients went into durable remission.
CONCLUSION: The prognosis for patients with low-risk GTN following molar gestation is excellent, with 100% remission rate, though a small but significant proportion (7%) required multiagent chemotherapy. The need for multiagent chemotherapy was associated with beta-hCG levels 1 week following initial MTX therapy. (J Reprod Med 2010;55:279-284)
C1 [Berkowitz, Ross S.] Brigham & Womens Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, Boston, MA 02115 USA.
Dana Farber Harvard Canc Ctr, Boston, MA USA.
Harvard Univ, Sch Med, Div Clin & Epidemiol Res, Boston, MA USA.
Tufts Univ New England Med Ctr, Dept Obstet & Gynecol, Div Maternal Fetal Med, Boston, MA 02111 USA.
[Goldstein, Donald P.] New England Trophoblast Dis Ctr, Trophoblast Tumor Registry, Boston, MA USA.
RP Berkowitz, RS (reprint author), Brigham & Womens Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, 75 Francis St, Boston, MA 02115 USA.
EM rberkowitz@partners.org
NR 25
TC 10
Z9 10
U1 1
U2 4
PU SCI PRINTERS & PUBL INC
PI ST LOUIS
PA PO DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA
SN 0024-7758
J9 J REPROD MED
JI J. Reprod. Med.
PD JUL-AUG
PY 2010
VL 55
IS 7-8
BP 279
EP 284
PG 6
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 639IP
UT WOS:000280968800003
PM 20795339
ER
PT J
AU Luderer, HF
Demay, MB
AF Luderer, Hilary F.
Demay, Marie B.
TI The vitamin D receptor, the skin and stem cells
SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
LA English
DT Article; Proceedings Paper
CT 14th Workshop on Vitamin D
CY OCT 04-08, 2009
CL Burgge, BELGIUM
DE Nuclear receptor; Hair follicle; Stem cell; Keratinocyte; Anagen
ID HAIR FOLLICLE; MOUSE EPIDERMIS; KNOCKOUT MICE; BETA-CATENIN; NULL MICE;
DIFFERENTIATION; KERATINOCYTES; ALOPECIA; GROWTH; TUMORS
AB The active metabolite of vitamin D, 1,25-dihydroxyvitamin D, has been shown to have pro-differentiation and antiproliferative effects on keratinocytes that are mediated by interactions with its nuclear receptor. Other cutaneous actions of the vitamin D receptor have been brought to light by the cutaneous phenotype of humans and mice with non-functional vitamin D receptors. Although mice lacking functional vitamin D receptors develop a normal first coat of hair, they exhibit impaired cyclic regeneration of hair follicles that leads to the development of alopecia. Normal hair cycling involves reciprocal interactions between the dermal papilla and the epidermal keratinocyte. Studies in mice with targeted ablation of the vitamin D receptor demonstrate that the abnormality in the hair cycle is due to a defect in the keratinocyte component of the hair follicle. Furthermore, expression of mutant vitamin D receptor transgenes in the keratinocytes of vitamin D receptor knockout mice demonstrates that the effects of the receptor that maintain hair follicle homeostasis are ligand-independent. Absence of a functional vitamin D receptor leads to impaired function of keratinocyte stem cells, both in vivo and in vitro. This is manifested by impaired cyclic regeneration of the hair follicle, a decrease in bulge keratinocyte stem cells with ageing and an abnormality in lineage progression of these cells, leading to their preferential differentiation into sebocytes. (C) 2010 Published by Elsevier Ltd.
C1 [Luderer, Hilary F.; Demay, Marie B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02114 USA.
RP Demay, MB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, 50 Blossom St,Thier 11, Boston, MA 02114 USA.
EM demay@helix.mgh.harvard.edu
FU NIDDK NIH HHS [DK46974]
NR 26
TC 12
Z9 14
U1 0
U2 2
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-0760
J9 J STEROID BIOCHEM
JI J. Steroid Biochem. Mol. Biol.
PD JUL
PY 2010
VL 121
IS 1-2
SI SI
BP 314
EP 316
DI 10.1016/j.jsbmb.2010.01.015
PG 3
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 634RC
UT WOS:000280600200069
PM 20138991
ER
PT J
AU Schuman-Olivier, Z
Albanese, M
Nelson, SE
Roland, L
Puopolo, F
Klinker, L
Shaffer, HJ
AF Schuman-Olivier, Zev
Albanese, Mark
Nelson, Sarah E.
Roland, Lolita
Puopolo, Francyne
Klinker, Lauren
Shaffer, Howard J.
TI Self-treatment: Illicit buprenorphine use by opioid-dependent treatment
seekers
SO JOURNAL OF SUBSTANCE ABUSE TREATMENT
LA English
DT Article
DE Buprenorphine; Illicit; Self-treatment; Pain; Depression
ID OFFICE-BASED TREATMENT; METHADONE-MAINTENANCE; DEPRESSIVE SYMPTOMS;
SUBSTANCE USE; PRIMARY-CARE; DRUG-USERS; DIVERSION; HEROIN; MISUSE;
PREVALENCE
AB Outpatient-based opioid treatment (OBOT) with buprenorphine is an important treatment for people with opioid dependence. No quantitative empirical research has examined rationales for use of illicit buprenorphine by U.S. opioid-dependent treatment seekers. The current study sequentially screened OBOT admissions (n = 129) during a 6-month period in 2009. This study had two stages: (a) a cross-sectional epidemiological analysis of new intakes and existing patients already receiving a legal OBOT prescription (n = 78) and (b) a prospective longitudinal cohort design that followed 76% of the initial participants for 3 months of treatment (n = 42). The primary aims were to establish 2009 prevalence rates for illicit buprenorphine use among people seeking OBOT treatment, to use quantitative methods to investigate reasons for this illicit use, and to examine the effect of OBOT treatment on illicit buprenorphine use behavior. These data demonstrate a decrease in illicit use when opioid-dependent treatment seekers gain access to legal prescriptions. These data also suggest that the use of illicit buprenorphine rarely represents an attempt to attain euphoria. Rather, illicit use is associated with attempted self-treatment of symptoms of opioid dependence, pain, and depression. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Schuman-Olivier, Zev] Harvard Univ, Sch Med, Dept Psychiat, MGH Ctr Addict Med,Cambridge Hlth Alliance, Cambridge, MA 02138 USA.
[Schuman-Olivier, Zev] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Addict Med, Cambridge, MA 02138 USA.
[Schuman-Olivier, Zev; Albanese, Mark; Nelson, Sarah E.; Shaffer, Howard J.] Cambridge Hlth Alliance, Div Addict, Cambridge, MA USA.
RP Schuman-Olivier, Z (reprint author), Harvard Univ, Sch Med, Dept Psychiat, MGH Ctr Addict Med,Cambridge Hlth Alliance, Cambridge, MA 02138 USA.
EM zschuman@partners.org
NR 35
TC 30
Z9 30
U1 2
U2 5
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0740-5472
J9 J SUBST ABUSE TREAT
JI J. Subst. Abus. Treat.
PD JUL
PY 2010
VL 39
IS 1
BP 41
EP 50
DI 10.1016/j.jsat.2010.03.014
PG 10
WC Psychology, Clinical; Substance Abuse
SC Psychology; Substance Abuse
GA 615MC
UT WOS:000279138400005
PM 20434868
ER
PT J
AU Rajput, A
Romanus, D
Weiser, MR
Ter Veer, A
Niland, J
Wilson, J
Skibber, JM
Wong, YN
Benson, A
Earle, CC
Schrag, D
AF Rajput, A.
Romanus, D.
Weiser, M. R.
Ter Veer, A.
Niland, J.
Wilson, J.
Skibber, J. M.
Wong, Y. -N.
Benson, A.
Earle, C. C.
Schrag, D.
TI Meeting the 12 Lymph Node (LN) Benchmark in Colon Cancer
SO JOURNAL OF SURGICAL ONCOLOGY
LA English
DT Article; Proceedings Paper
CT 43rd Annual Meeting of the American-Society-of-Clinical-Oncology
CY JUN 01-05, 2007
CL Chicago, IL
SP Amer Soc Clin Oncol
DE colon cancer; lymph nodes; outcomes
ID COLORECTAL-CARCINOMA; RESECTION SPECIMENS; RECTAL-CANCER; SURVIVAL;
NUMBER; RATIO; RECOMMENDATIONS; ADENOCARCINOMA; DISSECTION; PROGNOSIS
AB Background: Examining >= 12 LN in colon cancer has been suggested as a quality metric The purpose of this study was to determine whether the 12 LN benchmark is achieved at NCCN centers compared to a US population-based sample
Methods: Patients with stage I-III disease resected at NCCN centers were identified front a prospective database (n = 718) and were compared to 12,845 stage I-III par tents diagnosed in a SEER region Age. gender, location, stage, number of positive nodes were compared or NCCN and SEER data in regards to number of nodes evaluated Multivariate logistic regression models were developed to Identify factors associated with evaluating 12 LNs
Results: 92% of NCCN and 58% of SEER patients had >= 12 LN evaluated For patients treated at NCCN centers, factors associated with not meeting the 12 LN target were left-sided urinals. stage I disease and BMI >30
Conclusions: >= 12 LN are almost always evaluated in NCCN patients In contrast, this target is achieved in 58% of SEER pat rents With longer follow-up of the NCCN cohort we will be able to link this quality metric to patterns of recurrence and survival and thereby better understand whether increasing the number of nodes evaluated is a priority for cancer control Sing Oncol 2010, 102 3-9 (C) 2010 Wiley-Liss, Inc
C1 [Rajput, A.] Roswell Pk Canc Inst, Dept Surg Oncol, Buffalo, NY 14263 USA.
[Romanus, D.; Earle, C. C.; Schrag, D.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Weiser, M. R.] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10021 USA.
[Ter Veer, A.; Niland, J.] City Hope Canc Ctr, Dept Biostat, Duarte, CA USA.
[Wilson, J.] Ohio State Univ, Dept Urol, Columbus, OH 43210 USA.
[Skibber, J. M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Wong, Y. -N.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
[Benson, A.] Northwestern Univ, Div Hematol Oncol, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA.
RP Rajput, A (reprint author), Univ New Mexico, Hlth Sci Ctr, Dept Surg, Div Surg Oncol, MSC10 5610,1 Univ New Mexico, Albuquerque, NM 87131 USA.
RI Wilson, John/I-9406-2012
NR 33
TC 20
Z9 20
U1 0
U2 0
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0022-4790
J9 J SURG ONCOL
JI J. Surg. Oncol.
PD JUL 1
PY 2010
VL 102
IS 1
BP 3
EP 9
DI 10.1002/jso.21532
PG 7
WC Oncology; Surgery
SC Oncology; Surgery
GA 620OZ
UT WOS:000279510500002
PM 20578172
ER
PT J
AU Seidler, EM
Kimball, AB
AF Seidler, Elizabeth M.
Kimball, Alexa B.
TI Meta-analysis comparing efficacy of benzoyl peroxide, clindamycin,
benzoyl peroxide with salicylic acid, and combination benzoyl
peroxide/clindamycin in acne
SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
LA English
DT Article
DE acne vulgaris; benzoyl peroxide; clindamycin; combination benzoyl
peroxide/clindamycin; meta-analysis; salicylic acid
ID TOPICAL CLINDAMYCIN; SINGLE-BLIND; VULGARIS; GEL; MODERATE; MULTICENTER;
ADAPALENE; PHOSPHATE; THERAPY; VEHICLE
AB Background. Comparative efficacy of the multiple treatments containing benzoyl peroxide (BPO) and clindamycin (CL) is not established.
Objective: We compared the efficacy of topical 5% BPO, 1% to 1.2% CL, 5% BPO with salicylic acid (SA) preparation, and combination BPO/CL in acne lesion reduction.
Methods: A meta-analysis was conducted using the Cochrane collaboration guidelines in accordance with the PRISMA statement.
Results: A total of 23 studies including 7309 patients were used in the meta-analysis. At 2 to 4 weeks, 5% BPO + SA had statistically greater percent lesion reductions over other groups (weighted mean inflammatory lesion reduction: BPO = 33.4%, CL = 21.5%, BPO + SA = 55.2%, BPO/CL = 40.7%, placebo = 7.3%; weighted mean noninflammatory lesion reduction: BPO = 19.1%, CL = 10.0%, BPO + SA = 42.7%, BPO/CL = 26.2%, placebo = 6.7%). At 10- to 12-week end points, 5% BPO + SA and BPO/CL were similar, with overlapping confidence intervals (weighted mean inflammatory lesion reduction: BPO = 43.7%, CL = 45.9%, BPO + SA = 51.8%, BPO/CL = 55.6%, placebo = 26.8%; weighted mean noninflammatory lesion reduction: BPO = 30.9%, CL = 32.6%, BPO + SA = 47.8%, BPO/CL = 40.3%, placebo = 17.0%).
Limitations: Trial heterogeneity, publication bias, and deficits in the reporting of individual primary studies may affect results.
Conclusion: At early time points, 5% BPO + SA had the best profile. BPO/CL was only incrementally better than BPO alone but was superior to CL alone. At later time points, 5% BPO + SA was similar to BPO/CL. (J Am Acad Dermatol 2010;63:52-62.)
C1 [Seidler, Elizabeth M.] Massachusetts Gen Hosp, Clin Unit Res Trials Skin, Boston, MA 02114 USA.
[Kimball, Alexa B.] Harvard Univ, Sch Med, Boston, MA USA.
RP Kimball, AB (reprint author), 50 Staniford St,Suite 240, Cambridge, MA 02139 USA.
EM harvardskinstudies@partners.org
FU Obagi Medical Products Inc
FX Supported by Obagi Medical Products Inc.
NR 27
TC 24
Z9 24
U1 1
U2 6
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 JUL
PY 2010
VL 63
IS 1
BP 52
EP 62
DI 10.1016/j.jaad.2009.07.052
PG 11
WC Dermatology
SC Dermatology
GA 617HZ
UT WOS:000279272900006
PM 20488582
ER
PT J
AU Patti, JA
AF Patti, John A.
TI Expanding Our Educational Horizons
SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY
LA English
DT Editorial Material
C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
RP Patti, JA (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,FND 202, Boston, MA 02114 USA.
EM jpatti@partners.org
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1546-1440
J9 J AM COLL RADIOL
JI J. Am. Coll. Radiol.
PD JUL
PY 2010
VL 7
IS 7
BP 469
EP 469
DI 10.1016/j.jacr.2010.05.028
PG 1
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA V23SQ
UT WOS:000208362900001
PM 20630375
ER
PT J
AU Kopans, DB
AF Kopans, Daniel B.
TI Re: "Saving Lives: Mammograms, Breast Cancer, and Health Insurance
Reform"
SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY
LA English
DT Letter
C1 Massachusetts Gen Hosp, Dept Radiol, Breast Imaging Div, Boston, MA 02114 USA.
RP Kopans, DB (reprint author), Massachusetts Gen Hosp, Dept Radiol, Breast Imaging Div, 55 Fruit St, Boston, MA 02114 USA.
EM dkopans@partners.org
NR 7
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 1546-1440
J9 J AM COLL RADIOL
JI J. Am. Coll. Radiol.
PD JUL
PY 2010
VL 7
IS 7
BP 545
EP 545
DI 10.1016/j.jacr.2010.05.001
PG 1
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA V23SQ
UT WOS:000208362900021
PM 20630396
ER
PT J
AU Kopans, DB
AF Kopans, Daniel B.
TI Re: "Quality of Life and Diagnostic Imaging Outcomes"
SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY
LA English
DT Letter
C1 Massachusetts Gen Hosp, Dept Radiol, Breast Imaging Div, Boston, MA 02114 USA.
RP Kopans, DB (reprint author), Massachusetts Gen Hosp, Dept Radiol, Breast Imaging Div, 55 Fruit St, Boston, MA 02114 USA.
EM dkopans@partners.org
NR 2
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 1546-1440
J9 J AM COLL RADIOL
JI J. Am. Coll. Radiol.
PD JUL
PY 2010
VL 7
IS 7
BP 546
EP 546
DI 10.1016/j.jacr.2010.05.003
PG 1
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA V23SQ
UT WOS:000208362900023
PM 20630398
ER
PT J
AU Li, G
Shofer, JB
Rhew, IC
Kukull, WA
Peskind, ER
McCormick, W
Bowen, JD
Schellenberg, GD
Crane, PK
Breitner, JCS
Larson, EB
AF Li, Ge
Shofer, Jane B.
Rhew, Isaac C.
Kukull, Walter A.
Peskind, Elaine R.
McCormick, Wayne
Bowen, James D.
Schellenberg, Gerard D.
Crane, Paul K.
Breitner, John C. S.
Larson, Eric B.
TI Age-Varying Association Between Statin Use and Incident Alzheimer's
Disease
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article
DE statin; old age; APOE genotype; Alzheimer's disease
ID PROSPECTIVE COHORT; APOLIPOPROTEIN-E; DEMENTIA; RISK; ALLELE;
SIMVASTATIN; THERAPY; HEALTH; TRIAL; LIFE
AB OBJECTIVES: To determine whether risk reduction of statins for Alzheimer's disease (AD) varies by age or presence of apolipoprotein E (APOE) epsilon 4 allele.
DESIGN: A cohort of cognitively intact elderly participants was assessed biennially for dementia and AD.
SETTING: Community based.
PARTICIPANTS: Three thousand three hundred ninety-two members of a health maintenance organization (HMO) aged 65 and older and without dementia.
MEASUREMENTS: Statin use was identified from the HMO pharmacy database, and proportional hazards models were applied with statin use as a time-dependent covariate to assess the association between statins and AD and the modifying effects of age and the APOE epsilon 4 allele.
RESULTS: Over an average of 6.1 years of follow-up of 3,099 participants, 263 participants developed probable AD. The adjusted hazard ratio (aHR) for statin use was 0.62 (95% confidence interval (CI) = 0.40-0.97) for AD in models including demographic characteristics and vascular risk factors as covariates. The strength of the association between statins and AD diminished with age (statin-by-age at entry interaction P = .04); the aHR in those younger than 80 was 0.44 (95% CI = 0.25-0.78), versus 1.22 (95% CI = 0.61-2.42) for aged 80 and older. The interaction term for statin use-by-APOE epsilon 4 was not significant (P = .65).
CONCLUSION: This enlarged study confirms earlier findings that statin therapy in early old age, but not in late age, may be associated with a lower risk of AD. The relationship between statin use and AD was consistent across APOE genotypes. J Am Geriatr Soc 58: 1311-1317, 2010.
C1 [Li, Ge; Peskind, Elaine R.] VA Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA 98108 USA.
[Li, Ge; Shofer, Jane B.; Peskind, Elaine R.; Breitner, John C. S.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
[Rhew, Isaac C.; Kukull, Walter A.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[McCormick, Wayne; Crane, Paul K.; Larson, Eric B.] Univ Washington, Dept Med, Seattle, WA 98195 USA.
[Bowen, James D.] Swedish Med Ctr, Swedish Neurosci Inst, Seattle, WA USA.
[Breitner, John C. S.] VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA 98108 USA.
[Schellenberg, Gerard D.] Univ Penn, Philadelphia, PA 19104 USA.
[Larson, Eric B.] Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA USA.
RP Li, G (reprint author), VA Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Mail Code S-116 6EMIRECC,1660 S Columbian Way, Seattle, WA 98108 USA.
EM gli@u.washington.edu
RI Crane, Paul/C-8623-2014;
OI Kukull, Walter/0000-0001-8761-9014; Crane, Paul/0000-0003-4278-7465
FU National Institute of Aging [AG20020, AG06781, AG16976, AG05136];
Department of Veterans Affairs; Friends of Alzheimer's Research
FX This study was supported by Grants AG20020, AG06781, AG16976, and
AG05136 from the National Institute of Aging, by the Department of
Veterans Affairs, and by the Friends of Alzheimer's Research.
NR 25
TC 52
Z9 53
U1 0
U2 5
PU WILEY-BLACKWELL
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 JUL
PY 2010
VL 58
IS 7
BP 1311
EP 1317
DI 10.1111/j.1532-5415.2010.02906.x
PG 7
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 619RS
UT WOS:000279448500011
PM 20533968
ER
PT J
AU D'Avolio, LW
Nguyen, TM
Farwell, WR
Chen, YM
Fitzmeyer, F
Harris, OM
Fiore, LD
AF D'Avolio, Leonard W.
Nguyen, Thien M.
Farwell, Wildon R.
Chen, Yongming
Fitzmeyer, Felicia
Harris, Owen M.
Fiore, Louis D.
TI Evaluation of a generalizable approach to clinical information retrieval
using the automated retrieval console (ARC)
SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION
LA English
DT Article
ID DE-IDENTIFICATION; MEDICAL-RECORDS; RADIOLOGY; QUALITY; ERA
AB Reducing custom software development effort is an important goal in information retrieval (IR). This study evaluated a generalizable approach involving with no custom software or rules development. The study used documents "consistent with cancer" to evaluate system performance in the domains of colorectal (CRC), prostate (PC), and lung (LC) cancer. Using an end-user-supplied reference set, the automated retrieval console (ARC) iteratively calculated performance of combinations of natural language processing-derived features and supervised classification algorithms. Training and testing involved 10-fold cross-validation for three sets of 500 documents each. Performance metrics included recall, precision, and F-measure. Annotation time for five physicians was also measured. Top performing algorithms had recall, precision, and F-measure values as follows: for CRC, 0.90, 0.92, and 0.89, respectively; for PC, 0.97, 0.95, and 0.94; and for LC, 0.76, 0.80, and 0.75. In all but one case, conditional random fields outperformed maximum entropy-based classifiers. Algorithms had good performance without custom code or rules development, but performance varied by specific application.
C1 [D'Avolio, Leonard W.; Nguyen, Thien M.; Farwell, Wildon R.; Chen, Yongming; Fitzmeyer, Felicia; Harris, Owen M.; Fiore, Louis D.] VA Boston Healthcare Syst, Coordinating Ctr, Cooperat Studies, Massachusetts Vet Epidemiol Res & Informat Ctr MA, Jamaica Plain, MA 02130 USA.
[D'Avolio, Leonard W.] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA 02115 USA.
[D'Avolio, Leonard W.; Farwell, Wildon R.] Brigham & Womens Hosp, Dept Med, Div Ageing, Boston, MA 02115 USA.
[D'Avolio, Leonard W.; Farwell, Wildon R.] Harvard Univ, Sch Med, Boston, MA USA.
[Farwell, Wildon R.] VA Boston Healthcare Syst, Dept Med, Boston, MA USA.
[Fiore, Louis D.] Boston Univ, Sch Publ Hlth, Boston, MA USA.
[Fiore, Louis D.] Boston Univ, Sch Med, Boston, MA 02118 USA.
RP D'Avolio, LW (reprint author), VA Boston Healthcare Syst, MAVERIC 151 MAV, 150 S Huntington Ave, Jamaica Plain, MA 02130 USA.
EM leonard.davolio@va.gov
FU VA Cooperative Studies Program; Veterans Affairs Health Services
Research and Development; Consortium for Health Informatics Research
(CHIR) [HIR 09-007]
FX This work was supported by VA Cooperative Studies Program as well as the
Veterans Affairs Health Services Research and Development grant,
Consortium for Health Informatics Research (CHIR), grant HIR 09-007.
Other funders: VA Cooperative Studies Program; Veterans Affairs Health
Services Research and Development; Consortium for Health Informatics
Research. The views expressed here are those of the authors, and not
necessarily those of the Department of Veterans Affairs.
NR 42
TC 32
Z9 32
U1 4
U2 11
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1067-5027
J9 J AM MED INFORM ASSN
JI J. Am. Med. Inf. Assoc.
PD JUL
PY 2010
VL 17
IS 4
BP 375
EP 382
DI 10.1136/jamia.2009.001412
PG 8
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 626YZ
UT WOS:000280005800005
PM 20595303
ER
PT J
AU Agarwal, R
Angst, CM
DesRoches, CM
Fischer, MA
AF Agarwal, Ritu
Angst, Corey M.
DesRoches, Catherine M.
Fischer, Michael A.
TI Technological viewpoints (frames) about electronic prescribing in
physician practices
SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION
LA English
DT Article
ID INFORMATION-TECHNOLOGY; UNINTENDED CONSEQUENCES; INCUMBENT ENTRY; MARKET
NICHES; HEALTH-CARE; IMPLEMENTATION; ORGANIZATIONS; RESISTANCE; SUPPORT;
SYSTEMS
AB Objective Physician practices may adopt and use electronic prescribing (eRx) in response to mandates, incentives, and perceived value of the technology. Yet, for the most part, diffusion has been limited and geographically confined, and even when adopted, use of eRx in many practices has been low. One explanation for this phenomenon is that decision-makers in the practices possess different technological viewpoints (frames) related to eRx and these frames have formed the basis for the adoption decision, expectations about the technology, and patterns of use. In this study eRx technological frames were examined.
Design Focus groups, direct observation, and semi-structured interviews were conducted with physicians, practice managers, nurses, and other medical staff.
Measurements Focus groups were observed, taped, transcribed, and analyzed to reveal themes. These themes guided the observational visits and subsequent interviews. A triangulation process was used to confirm the findings.
Results Seven frames emerged from the qualitative analysis ranging from positive to neutral to negative: (1) eRx as an efficiency and effectiveness enhancing tool; (2) eRx as the harbinger of new practices; (3) eRx as core to the clinical workflow; (4) eRx as an administrative tool; (5) eRx: the artifact; (6) eRx as a necessary evil; and (7) eRx as an unwelcome disruption.
Conclusion Frames provide a unique perspective within which to explore the adoption and use of eRx and may explain why perceptions of value vary greatly. Some frames facilitate effective use of eRx while others impose barriers. Electronic prescribing can be viewed as a transitional technology on the path to greater digitization at the physician practice level. Understanding the impact of technological frames on the effectiveness of eRx use may provide lessons for the implementation of future health information technology innovations.
C1 [Angst, Corey M.] Univ Notre Dame, Mendoza Coll Business, Dept Management, Notre Dame, IN 46556 USA.
[DesRoches, Catherine M.] Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA.
[Agarwal, Ritu] Univ Maryland, Robert H Smith Sch Business, Ctr Hlth Informat & Decis Syst, College Pk, MD 20742 USA.
[Fischer, Michael A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Pharmacoepidemiol & Pharmacoecon,Dept Med, Boston, MA 02115 USA.
RP Angst, CM (reprint author), Univ Notre Dame, Mendoza Coll Business, Dept Management, Notre Dame, IN 46556 USA.
EM cangst@nd.edu
FU Agency for Healthcare Research and Quality [R18 HS017151-01]
FX This study was funded by a grant from the Agency for Healthcare Research
and Quality, # R18 HS017151-01.
NR 48
TC 12
Z9 12
U1 3
U2 8
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1067-5027
EI 1527-974X
J9 J AM MED INFORM ASSN
JI J. Am. Med. Inf. Assoc.
PD JUL
PY 2010
VL 17
IS 4
BP 425
EP 431
DI 10.1136/jamia.2009.001826
PG 7
WC Computer Science, Information Systems; Computer Science,
Interdisciplinary Applications; Health Care Sciences & Services;
Information Science & Library Science; Medical Informatics
SC Computer Science; Health Care Sciences & Services; Information Science &
Library Science; Medical Informatics
GA 626YZ
UT WOS:000280005800012
PM 20595310
ER
PT J
AU Rudski, LG
Lai, WW
Afilalo, J
Hua, LQ
Handschumacher, MD
Chandrasekaran, K
Solomon, SD
Louie, EK
Schiller, NB
AF Rudski, Lawrence G.
Lai, Wyman W.
Afilalo, Jonathan
Hua, Lanqi
Handschumacher, Mark D.
Chandrasekaran, Krishnaswamy
Solomon, Scott D.
Louie, Eric K.
Schiller, Nelson B.
TI Guidelines for the Echocardiographic Assessment of the Right Heart in
Adults: A Report from the American Society of Echocardiography Endorsed
by the European Association of Echocardiography, a registered branch of
the European Society of Cardiology, and the Canadian Society of
Echocardiography
SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY
LA English
DT Article
DE Right ventricle; Echocardiography; Right atrium; Guidelines
ID RIGHT-VENTRICULAR-FUNCTION; TIME 3-DIMENSIONAL ECHOCARDIOGRAPHY;
MYOCARDIAL PERFORMANCE INDEX; PULMONARY-ARTERY PRESSURE; RIGHT ATRIAL
PRESSURE; TWO-DIMENSIONAL ECHOCARDIOGRAPHY; TISSUE
DOPPLER-ECHOCARDIOGRAPHY; OBSTRUCTIVE SLEEP-APNEA; INFERIOR VENA-CAVA;
EJECTION FRACTION
C1 [Rudski, Lawrence G.; Afilalo, Jonathan] McGill Univ, Jewish Gen Hosp, Montreal, PQ H3T 1E2, Canada.
[Lai, Wyman W.] Morgan Stanley Childrens Hosp New York Presbyteri, New York, NY USA.
[Hua, Lanqi; Handschumacher, Mark D.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Chandrasekaran, Krishnaswamy] Mayo Clin, Phoenix, AZ USA.
[Solomon, Scott D.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
[Louie, Eric K.] Sg2 LLC, London, England.
[Schiller, Nelson B.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
RP Rudski, LG (reprint author), Amer Soc Echocardiog, 2100 Gateway Ctr Blvd,Suite 310, Morrisville, NC 27560 USA.
EM ase@asecho.org
RI Solomon, Scott/I-5789-2013
FU GE Healthcare; Abbott Vascular Structural Heart; EBR Systems, Inc.;
Boston Scientific Corporation; Toshiba America Medical Systems and
Philips; Medtronic; Actor Medical
FX The following members of the ASE Guidelines and Standards Committee,
JASE Editorial staff and ASE Board of Directors reported a relationship
with one or more commercial interests. According to ACCME policy, the
ASE implemented mechanisms to resolve all conflicts of interest prior to
the planning and implementation of this activity. Theodore Abraham, MD,
FASE receives honoraria and research grant support from GE Healthcare.
Patrick D. Coon, RDCS, FASE is on the speaker's bureau for Philips.
Victor G. Davila-Roman, MD, FASE is a consultant for St. Jude Medical,
AGA Medical, Medtronic, Boston Scientific Corporation, and Sadra
Medical. Elyse Foster, MD receives grant support from Abbott Vascular
Structural Heart, EBR Systems, Inc., and Boston Scientific Corporation.
Julius M. Gardin, MD, FASE is a consultant/advisor to Arena
Pharmaceuticals. Jeffrey C. Hill, BS, RDCS, FASE receives grant/research
support from Toshiba America Medical Systems and Philips; is a
consultant to Medtronic; and is on the speaker's bureau for Philips.
Martin G. Keane, MD, FASE is a consultant/advisor to Pfizer, Inc. and
Otsuka Pharmaceuticals. Gilead I. Lancaster, MD, FASE owns stock in, and
is a consultant/advisor to, Cardiogal. Jonathan R. Linder, MD, FASE is a
consultant/advisor to VisualSonics. Carol C. Mitchell, PhD, RDMS, RDCS,
RVT, RT(R), FASE is a speaker and consultant for GE Healthcare. Marti
McCulloch, MBA, BS, RDCS, FASE is a speaker for Lantheus and
advisor/consultant for Siemens. Tasneem Z. Naqvi, MD, FASE is a
consultant/advisor to Edwards Lifesciences and St. Jude Medical, and
receives grant support from Medtronic and Actor Medical. Kofo O.
Ogunyankin, MD, FASE is on the speaker's bureau for Lantheus. Vera
Rigolin, MD, FASE is on the speaker's bureau for Edwards Lifesciences
and St. Jude Medical and owns stock in Abbott Labs; Hospira; Johnson and
Johnson; and Medtronic. Lawrence G. Rudski, MD receives grant support
from Genzyme. Stephen G. Sawada, MD owns stock in GE Healthcare. Alan D.
Waggoner, MHS, RDCS is a consultant/advisor for Boston Scientific
Corporation and St. Jude Medical, Inc.
NR 182
TC 1651
Z9 1761
U1 8
U2 64
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0894-7317
J9 J AM SOC ECHOCARDIOG
JI J. Am. Soc. Echocardiogr.
PD JUL
PY 2010
VL 23
IS 7
BP 685
EP 713
DI 10.1016/j.echo.2010.05.010
PG 29
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 614NY
UT WOS:000279067900002
PM 20620859
ER
PT J
AU Basnayake, K
Ying, WZ
Wang, PX
Sanders, PW
AF Basnayake, Kolitha
Ying, Wei-Zhong
Wang, Pei-Xuan
Sanders, Paul W.
TI Immunoglobulin Light Chains Activate Tubular Epithelial Cells through
Redox Signaling
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID MOLECULAR-WEIGHT PROTEINS; BENCE-JONES PROTEINS; NF-KAPPA-B; TYROSINE
KINASE; HYDROGEN-PEROXIDE; MULTIPLE-MYELOMA; CAST NEPHROPATHY; REACTIVE
OXYGEN; KIDNEY; SRC
AB The renal proximal tubule metabolizes circulating low-molecular-weight proteins such as Ig free light chains. In the setting of plasma cell dyscrasias, the burden of filtered protein can be very high. Endocytosis of certain nephrotoxic light chains induces H(2)O(2) production and monocyte chemoattractant protein-1 (MCP-1) release, leading to recruitment of inflammatory cells and interstitial fibrosis, but how these processes are linked mechanistically is not well understood. This study investigated the relationship between H(2)O(2) generated after light chain endocytosis by human proximal tubular (HK-2) cells and activation of c-Src, a redox-sensitive tyrosine kinase. HK-2 cells exposed to two different light chains upregulated c-Src activity, which increased the production of MCP-1. In parallel, we observed a time-dependent oxidation of c-Src. Inhibition of c-Src activity and silencing c-Src expression abrogated the light chain induced MCP-1 response, but had no effect on H(2)O(2), indicating that production of H(2)O(2) is upstream of c-Src in the signaling cascade. Silencing megalin and cubilin expression inhibited the MCP-1 response, whereas extracellular catalase did not, indicating that endocytosis is required and that intracellular generation of reactive oxygen species activates c-Src. These data show that intracellular H(2)O(2) induced by endocytosis of monoclonal free light chains oxidizes and activates c-Src, which promotes release of MCP-1.
C1 [Sanders, Paul W.] Univ Alabama, Div Nephrol, Dept Med, Nephrol Res & Training Ctr, Birmingham, AL 35294 USA.
[Basnayake, Kolitha] Univ Birmingham, Birmingham, W Midlands, England.
[Sanders, Paul W.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA.
RP Sanders, PW (reprint author), Univ Alabama, Div Nephrol, Dept Med, Nephrol Res & Training Ctr, 642 Lyons Harrison Res Bldg,1530,3rd Ave S, Birmingham, AL 35294 USA.
OI Sanders, Paul/0000-0002-2915-5714
FU National Institutes of Health [R01 DK46199, P30 DK079337]; Office of
Research and Development, Medical Research Service, Department of
Veterans Affairs; Dr Basnayake's clinical fellowship
FX Portions of the data contained within this manuscript have been
submitted in abstract form to the 42nd Annual Meeting and Scientific
Exposition of the American Society of Nephrology; October 27 through
November 1, 2009, San Diego, CA National Institutes of Health grant (R01
DK46199) and P30 DK079337 (George M. O'Brien Kidney and Urological
Research Centers Program) and the Office of Research and Development,
Medical Research Service, Department of Veterans Affairs, supported this
research. We thank the Binding Site Ltd. for then unrestricted support
of Dr Basnayake's clinical fellowship and their expertise in protein
chemistry
NR 49
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U1 2
U2 4
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD JUL
PY 2010
VL 21
IS 7
BP 1165
EP 1173
DI 10.1681/ASN.2009101089
PG 9
WC Urology & Nephrology
SC Urology & Nephrology
GA 632SD
UT WOS:000280447100017
PM 20558542
ER
PT J
AU Prakash, S
Rodriguez, RA
Austin, PC
Saskin, R
Fernandez, A
Moist, LM
O'Hare, AM
AF Prakash, Suma
Rodriguez, Rudolph A.
Austin, Peter C.
Saskin, Refik
Fernandez, Alicia
Moist, Louise M.
O'Hare, Ann M.
TI Racial Composition of Residential Areas Associates with Access to
Pre-ESRD Nephrology Care
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID CHRONIC KIDNEY-DISEASE; STAGE RENAL-DISEASE; DISPARITIES GEOCODING
PROJECT; NEIGHBORHOOD POVERTY; PERITONEAL-DIALYSIS; UNITED-STATES;
ARTERIOVENOUS-FISTULAS; REPLACEMENT THERAPY; MORTALITY; TRANSPLANTATION
AB Referral to a nephrologist before initiation of chronic dialysis occurs less frequently for blacks than whites, but the reasons for this disparity are incompletely understood. Here, we examined the contribution of racial composition by zip code on access and quality of nephrology care before initiation of renal replacement therapy (RRT). We retrospectively studied a cohort study of 92,000 white and black adults who initiated RRT in the United States between June 1, 2005, and October 5, 2006. The percentage of patients without pre-ESRD nephrology care ranged from 30% among those who lived in zip codes with <5% black residents to 41% among those who lived in areas with >50% black residents In adjusted analyses, as the percentage of blacks in residential areas increased, the likelihood of not receiving pre-ESRD nephrology care increased. Among patients who received nephrology care, the quality of care (timing of care and proportion of patients who received a pre-emptive renal transplant, who initiated therapy with peritoneal dialysis, or who had a permanent hemodialysis access) did not differ by the racial composition of their residential area. In conclusion, racial composition of residential areas associates with access to nephrology care but not with quality of the nephrology care received.
C1 [Prakash, Suma] Univ Toronto, Dept Med, Toronto, ON, Canada.
VA Puget Sound Healthcare Syst, Div Nephrol, Dept Med, Seattle, WA USA.
[Rodriguez, Rudolph A.; O'Hare, Ann M.] Univ Washington, Seattle, WA 98195 USA.
[Austin, Peter C.] Univ Toronto, Dept Hlth Policy Management & Evaluat, Toronto, ON, Canada.
[Austin, Peter C.; Saskin, Refik] Inst Clin Evaluat Sci, Toronto, ON, Canada.
[Fernandez, Alicia] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Moist, Louise M.] Univ Western Ontario, Dept Med, Div Nephrol, London, ON, Canada.
RP Prakash, S (reprint author), Univ Toronto, Dept Med, Toronto, ON, Canada.
OI Austin, Peter/0000-0003-3337-233X
FU Heart and Stroke Foundation of Ontario; National Institutes of
Health/National Centre for Research Resources [K23121218342]; National
Institute of Aging [K23AG28980]
FX S P received a travel grant to present an abstract from this work at the
World Congress of Nephrology ni Milan, Italy, in May 2009 P C.A is
supported by a Career Investigator Award from the Heart and Stroke
Foundation of Ontario A F is supported by a K23121218342 award from the
National Institutes of Health/National Centre for Research Resources A M
0 is supported by a Beeson Career Development Award front the National
Institute of Aging (K23AG28980) and receives royalties from UpToDate and
an honorarium from the Japanese Society for Foot Care
NR 47
TC 28
Z9 28
U1 0
U2 3
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1046-6673
EI 1533-3450
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD JUL
PY 2010
VL 21
IS 7
BP 1192
EP 1199
DI 10.1681/ASN.2009101008
PG 8
WC Urology & Nephrology
SC Urology & Nephrology
GA 632SD
UT WOS:000280447100020
PM 20558541
ER
PT J
AU Kimball, A
Goffe, B
Bissonnette, R
Yeilding, N
Li, S
Fakharzadeh, S
Papp, K
AF Kimball, A.
Goffe, B.
Bissonnette, R.
Yeilding, N.
Li, S.
Fakharzadeh, S.
Papp, K.
CA Phoenix I Investigators
TI Efficacy of ustekinumab is sustained through 3 years of treatment for
patients with moderate-to-severe psoriasis maintained on q12 week dosing
based on body weight
SO JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY
LA English
DT Meeting Abstract
C1 [Kimball, A.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Mass Gen Hosp, Boston, MA USA.
[Goffe, B.] PLLC, Dermatol Associates, Seattle, WA USA.
[Bissonnette, R.] Innovaderm Res, Montreal, PQ, Canada.
[Yeilding, N.; Li, S.] Centocor Res & Dev Inc, Malvern, PA USA.
[Fakharzadeh, S.] LLC, Centocor Ortho Biotech Serv, Horsham, PA USA.
[Papp, K.] Prob Med Res, Waterloo, ON, Canada.
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 0926-9959
J9 J EUR ACAD DERMATOL
JI J. Eur. Acad. Dermatol. Venereol.
PD JUL
PY 2010
VL 24
SU 4
MA 044
BP 20
EP 20
PG 1
WC Dermatology
SC Dermatology
GA 621TR
UT WOS:000279607700045
ER
PT J
AU Greenberg, DL
Verfaellie, M
AF Greenberg, Daniel L.
Verfaellie, Mieke
TI Effects of fixed- and varied-context repetition on associative
recognition in amnesia
SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY
LA English
DT Article
DE Amnesia; Anterograde; Memory disorders; Hippocampus; Neuropsychology;
Anoxia; Encephalitis
ID ENCODING VARIABILITY; RELATIONAL MEMORY; FREE-RECALL; ITEM; PERFORMANCE;
IMPAIRMENTS; HIPPOCAMPUS; PARADIGM; PATIENT; MODELS
AB This study compared the effects of fixed- and varied-context repetition on associative recognition in amnesia. Controls and amnesic participants were presented with a set of three-word phrases. Each was presented three times. In the varied-context condition, the verb changed with each presentation; in the fixed-context condition, it remained constant. At test, participants performed an associative-recognition task in which they were shown pairs of words from the study phase and asked to distinguish between intact and recombined pairs. For corrected recognition (hits false alarms), controls performed better in the varied-context than in the fixed-context repetition condition, whereas amnesic participants' performance did not differ between conditions. Similarly, controls had lower false-alarm rates in the varied-context condition, but there was no significant effect of condition for the amnesic participants. Thus, varied-context repetition does not improve amnesic participants' performance on a recollection-dependent associative-recognition task, possibly because the amnesic participants were unable to take advantage of the additional cues that the varied-context encoding condition provided. (JINS, 2010, 16, 596-602.)
C1 [Greenberg, Daniel L.] VA Boston Healthcare Syst, Memory Disorders Res Ctr, Boston, MA 02130 USA.
Boston Univ, Sch Med, Boston, MA 02215 USA.
RP Greenberg, DL (reprint author), VA Boston Healthcare Syst, Memory Disorders Res Ctr, 150 S Huntington Ave 151-A, Boston, MA 02130 USA.
EM dlg@bu.edu
OI Verfaellie, Mieke/0000-0001-5535-4584
FU NIH [MH71783]; Office of Research and Development, Medical Research
Service, Department of Veterans Affairs
FX This research was supported by NIH grant MH71783 and the Office of
Research and Development, Medical Research Service, Department of
Veterans Affairs. The authors have no financial or other relationships
that could be interpreted as a conflict of interest affecting this
manuscript.
NR 41
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Z9 1
U1 0
U2 2
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 1355-6177
J9 J INT NEUROPSYCH SOC
JI J. Int. Neuropsychol. Soc.
PD JUL
PY 2010
VL 16
IS 4
BP 596
EP 602
DI 10.1017/S1355617710000287
PG 7
WC Clinical Neurology; Neurosciences; Psychiatry; Psychology
SC Neurosciences & Neurology; Psychiatry; Psychology
GA 619HE
UT WOS:000279419100003
PM 20374672
ER
PT J
AU Pa, J
Possin, KL
Wilson, SM
Quitania, LC
Kramer, JH
Boxer, AL
Weiner, MW
Johnson, JK
AF Pa, Judy
Possin, Katherine L.
Wilson, Stephen M.
Quitania, Lovingly C.
Kramer, Joel H.
Boxer, Adam L.
Weiner, Michael W.
Johnson, Julene K.
TI Gray matter correlates of set-shifting among neurodegenerative disease,
mild cognitive impairment, and healthy older adults
SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY
LA English
DT Article
DE D-KEFS; Design fluency; Trail making test; Color word interference;
Executive function; Voxel-based morphometry
ID CARD SORTING TEST; FRONTOTEMPORAL LOBAR DEGENERATION; LATERAL PREFRONTAL
CORTEX; FRONTAL-LOBE; PARKINSONS-DISEASE; SWITCHING DEFICITS; BASAL
GANGLIA; HUNTINGTONS-DISEASE; ALZHEIMERS-DISEASE; TEST-PERFORMANCE
AB There is increasing recognition that set-shifting, a form of cognitive control, is mediated by different neural structures. However, these regions have not yet been carefully identified as many studies do not account for the influence of component processes (e.g., motor speed). We investieated gray matter correlates of set-shifting while controlling for component processes. Using the Design Fluency (DE), Trail Making Test (TMT), and Color Word Interference (CWI) subtests from the Delis-Kaplan Executive Function System (D-KEFS), we investigated the correlation between set-shifting performance and gray matter volume in 160 subjects with neurodegenerative disease, mild cognitive impairment, and healthy older adults using voxel-based morphometry. All three set-shifting tasks correlated with multiple, widespread gray matter regions. After controlling for the component processes, set-shifting performance correlated with focal regions in prefrontal and posterior parietal cortices. We also identified bilateral prefrontal cortex and the right posterior parietal lobe as common sites for set-shifting across the three tasks. There was a high degree of multicollinearity between the set-shifting conditions and the component processes of TMT and CWI, suggesting DF may better isolate set-shifting regions. Overall, these findings highlight the neuroanatomical correlates of set-shifting and the importance of controlling for component processes when investigating complex cognitive tasks. (JINS, 2010, 16, 640-650.)
C1 [Pa, Judy; Possin, Katherine L.; Wilson, Stephen M.; Kramer, Joel H.; Boxer, Adam L.; Johnson, Julene K.] Univ Calif San Francisco, Dept Neurol, Alzheimer Dis Res Ctr, San Francisco, CA 94143 USA.
[Quitania, Lovingly C.] Univ Calif Davis, Dept Neurol, Alzheimer Dis Ctr, Davis, CA 95616 USA.
[Weiner, Michael W.] San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis, San Francisco, CA USA.
[Johnson, Julene K.] Univ Calif San Francisco, Inst Hlth & Aging, San Francisco, CA 94143 USA.
RP Pa, J (reprint author), UCSF Mission Bay, Genentech Hall,Room N474,600 16th St, San Francisco, CA 94158 USA.
EM judy.pa@ucsf.edu
FU National Institute on Aging (NIA) [R01-AG022538, R01-AG010897,
K01-AG034175-01, K23-AG0300601, P01-AG1972403, P50-AG0300601]; John D.
French Foundation
FX This work was supported by National Institute on Aging (NIA)
R01-AG022538, R01-AG010897, K01-AG034175-01, K23-AG0300601,
P01-AG1972403, and P50-AG0300601, and John D. French Foundation.
NR 71
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Z9 24
U1 5
U2 9
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 1355-6177
J9 J INT NEUROPSYCH SOC
JI J. Int. Neuropsychol. Soc.
PD JUL
PY 2010
VL 16
IS 4
BP 640
EP 650
DI 10.1017/S1355617710000408
PG 11
WC Clinical Neurology; Neurosciences; Psychiatry; Psychology
SC Neurosciences & Neurology; Psychiatry; Psychology
GA 619HE
UT WOS:000279419100008
PM 20374676
ER
PT J
AU Sun, K
Zhang, ZH
Suzuki, T
Wenk, JF
Stander, N
Einstein, DR
Saloner, DA
Wallace, AW
Guccione, JM
Ratcliffe, MB
AF Sun, Kay
Zhang, Zhihong
Suzuki, Takamaro
Wenk, Jonathan F.
Stander, Nielen
Einstein, Daniel R.
Saloner, David A.
Wallace, Arthur W.
Guccione, Julius M.
Ratcliffe, Mark B.
TI Dor procedure for dyskinetic anteroapical myocardial infarction fails to
improve contractility in the border zone
SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
LA English
DT Article
ID LEFT-VENTRICULAR ANEURYSM; FINITE-ELEMENT MODEL; ENDOVENTRICULAR PATCH
PLASTY; CANINE LEFT-VENTRICLE; MATRIX METALLOPROTEINASE-2; MECHANICAL
DYSFUNCTION; ACTIVE CONTRACTION; CARDIAC-MUSCLE; RECONSTRUCTION; STRESS
AB Background: Endoventricular patch plasty (Dor) is used to reduce left ventricular volume after myocardial infarction and subsequent left ventricular remodeling.
Methods and Results: End-diastolic and end-systolic pressure-volume and Starling relationships were measured, and magnetic resonance images with noninvasive tags were used to calculate 3-dimensional myocardial strain in 6 sheep 2 weeks before and 2 and 6 weeks after the Dor procedure. These experimental results were previously reported.
The imaging data from 1 sheep were incomplete. Animal specific finite element models were created from the remaining 5 animals using magnetic resonance images and left ventricular pressure obtained at early diastolic filling. Finite element models were optimized with 3-dimensional strain and used to determine systolic material properties, T(max,skinned-fiber), and diastolic and systolic stress in remote myocardium and border zone.
Six weeks after the Dor procedure, end-diastolic and end-systolic stress in the border zone were substantially reduced. However, although there was a slight increase in Tmax, skinned-fiber in the border zone near the myocardial infarction at 6 weeks, the change was not significant.
Conclusions: The Dor procedure decreases end-diastolic and end-systolic stress but fails to improve contractility in the infarct border zone. Future work should focus on measures that will enhance border zone function alone or in combination with surgical remodeling. (J Thorac Cardiovasc Surg 2010; 140: 233-9)
C1 [Sun, Kay; Zhang, Zhihong; Suzuki, Takamaro; Wenk, Jonathan F.; Guccione, Julius M.; Ratcliffe, Mark B.] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA.
[Guccione, Julius M.; Ratcliffe, Mark B.] Univ Calif San Francisco, Dept Bioengn, San Francisco, CA 94143 USA.
[Wallace, Arthur W.] Univ Calif San Francisco, Dept Anesthesia, San Francisco, CA 94143 USA.
[Saloner, David A.] Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA.
[Sun, Kay; Zhang, Zhihong; Suzuki, Takamaro; Wenk, Jonathan F.; Saloner, David A.; Wallace, Arthur W.; Guccione, Julius M.; Ratcliffe, Mark B.] Vet Affairs Med Ctr, San Francisco, CA 94121 USA.
[Stander, Nielen] Livermore Software Technol Corp, Livermore, CA USA.
[Einstein, Daniel R.] Pacific NW Natl Lab, Olympia, WA USA.
RP Ratcliffe, MB (reprint author), San Francisco VA Med Ctr, Surg Serv 112, 4150 Clement St, San Francisco, CA 94121 USA.
EM mark.ratcliffe@med.va.gov
FU National Institutes of Health [R01-HL-77921, R01-HL-63348]
FX This study was supported by National Institutes of Health grant
R01-HL-77921 (to Dr Guccione), VA Merit Review (to Dr Wallace), and
R01-HL-63348 (to Dr Ratcliffe).
NR 38
TC 15
Z9 15
U1 0
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5223
J9 J THORAC CARDIOV SUR
JI J. Thorac. Cardiovasc. Surg.
PD JUL
PY 2010
VL 140
IS 1
BP 233
EP U269
DI 10.1016/j.jtcvs.2009.11.055
PG 11
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA 612QG
UT WOS:000278915600038
PM 20299030
ER
PT J
AU Liberman, M
Wain, JC
AF Liberman, Moishe
Wain, John C.
TI Balloon-guided, tapered, Polyflex stent guidance: An atraumatic
technique for successful stent placement through tight, rigid airway
stenoses
SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
LA English
DT Editorial Material
C1 [Liberman, Moishe] Univ Montreal, Dept Thorac Surg, Ctr Hosp, Div Thorac Surg, Montreal, PQ H2L 4M1, Canada.
[Wain, John C.] Harvard Univ, Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02115 USA.
RP Liberman, M (reprint author), Univ Montreal, Dept Thorac Surg, Ctr Hosp, Div Thorac Surg, 1560 Rue Sherbrooke Est 8E CD,Room D-8051, Montreal, PQ H2L 4M1, Canada.
EM moishe.liberman@umontreal.ca
NR 4
TC 0
Z9 0
U1 0
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5223
J9 J THORAC CARDIOV SUR
JI J. Thorac. Cardiovasc. Surg.
PD JUL
PY 2010
VL 140
IS 1
BP 248
EP U281
DI 10.1016/j.jtcvs.2009.09.061
PG 4
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA 612QG
UT WOS:000278915600043
PM 20080268
ER
PT J
AU Otsuji, Y
Sakata, R
Kubota, K
Levine, RA
Tei, C
AF Otsuji, Yutaka
Sakata, Ryuzo
Kubota, Kayoko
Levine, Robert A.
Tei, Chuwa
TI HOW CAN WE PREVENT FUNCTIONAL MITRAL STENOSIS AFTER SURGERY? Reply
SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
LA English
DT Letter
ID REGURGITATION
C1 [Otsuji, Yutaka] Univ Occupat & Environm Hlth, Kitakyushu, Fukuoka 807, Japan.
[Sakata, Ryuzo] Kyoto Univ, Kyoto, Japan.
[Kubota, Kayoko; Tei, Chuwa] Kagoshima Univ, Kagoshima 890, Japan.
[Levine, Robert A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Otsuji, Y (reprint author), Univ Occupat & Environm Hlth, Kitakyushu, Fukuoka 807, Japan.
NR 5
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5223
J9 J THORAC CARDIOV SUR
JI J. Thorac. Cardiovasc. Surg.
PD JUL
PY 2010
VL 140
IS 1
BP 252
EP 253
DI 10.1016/j.jtcvs.2010.03.033
PG 3
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA 612QG
UT WOS:000278915600047
ER
PT J
AU Yeo, WL
Riely, GJ
Yeap, BY
Lau, MW
Warner, JL
Bodio, K
Huberman, MS
Kris, MG
Tenen, DG
Pao, W
Kobayashi, S
Costa, DB
AF Yeo, Wee-Lee
Riely, Gregory J.
Yeap, Beow Y.
Lau, Michelle W.
Warner, Jeremy L.
Bodio, Kelly
Huberman, Mark S.
Kris, Mark G.
Tenen, Daniel G.
Pao, William
Kobayashi, Susumu
Costa, Daniel B.
TI Erlotinib at a Dose of 25 mg Daily for Non-small Cell Lung Cancers with
EGFR Mutations
SO JOURNAL OF THORACIC ONCOLOGY
LA English
DT Article
DE Epidermal growth factor receptor; EGFR; Mutation; Tyrosine kinase
inhibitors; Gefitinib; Erlotinib; L858R; Exon 19 deletions; Lung cancer;
Non-small cell lung cancer
ID GROWTH-FACTOR-RECEPTOR; TYROSINE KINASE INHIBITOR; ACQUIRED-RESISTANCE;
GEFITINIB RESISTANCE; ACTIVATING MUTATIONS; T790M MUTATIONS;
GENE-MUTATIONS; PHASE-I; ADENOCARCINOMA; SENSITIVITY
AB Purpose: The tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib are effective in non-small cell lung cancers (NSCLCs) with epidermal growth factor receptor (EGFR) gene mutations. The usual clinical dose of gefitinib (250 mg/d) is only one third of its maximum tolerated dose, whereas the dose of erlotinib (150 mg/d) is at its maximum tolerated dose. In NSCLC cell lines, both TKIs have similar micromolar inhibitory concentrations. We explored whether erlotinib at 25 mg/d (trough serum concentration similar to gefitinib 250 mg/d) would be efficacious in EGFR-mutated NSCLC.
Methods: To study the inhibitory concentrations of gefitinib and erlotinib, we exposed EGFR-mutated cell lines (HCC827, H3255, PC-9, and H1975) to increasing concentrations of these TKIs. Further on, we performed a retrospective evaluation of seven patients with advanced EGFR-mutated (exon 19 deletions and L858R) NSCLC that were given erlotinib at 25 mg/d as their first EGFR TKI.
Results: Gefitinib and erlotinib generated similar inhibitory curves across our panel of EGFR-mutated NSCLC cell lines with overlapping mean 50% inhibitory concentration 95% confidence intervals for HCC827, PC-9, and H1975. Both drugs also displayed a high degree of correlation in mean 50% inhibitory concentration (Pearson's r = 0.99, p = 0.0417). Of the seven patients, five patients (71.5%) had partial responses to erlotinib 25 mg/d. Median progression-free survival was 17 months (95% confidence interval, 6-35 months). Toxicities were minimal, with only two (28.5%) patients having a rash and none experiencing (0%) diarrhea.
Conclusions: In NSCLC cell lines, gefitinib and erlotinib have similar inhibitory profiles. In patients with NSCLC and EGFR-activating mutations, a dose of erlotinib 25 mg/d (equivalent to gefitinib 250 mg/d) leads to impressive response rates and progression- free survival similar to the growing experience with the approved doses of gefitinib (250 mg/d) and erlotinib (150 mg/d). Identifying prospectively the lowest and clinically active dose ranges of erlotinib and gefitinib will help further to personalize care for patients with tumors harboring EGFR mutations.
C1 [Costa, Daniel B.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Hematol Oncol, Boston, MA 02215 USA.
[Yeo, Wee-Lee; Tenen, Daniel G.] Natl Univ Singapore, Canc Sci Inst, Singapore 117548, Singapore.
[Riely, Gregory J.; Kris, Mark G.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Yeap, Beow Y.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Pao, William] Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Nashville, TN USA.
RP Costa, DB (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Hematol Oncol, 330 Brookline Ave, Boston, MA 02215 USA.
EM skobayas@bidmc.harvard.edu; dbcosta@bidmc.harvard.edu
OI Warner, Jeremy/0000-0002-2851-7242; Kris, Mark/0000-0002-7317-5341;
Costa, Daniel/0000-0002-0689-395X; Tenen, Daniel/0000-0002-6423-3888
FU Astra Zeneca; Boehringer Ingelheim; Pfizer; Novartis; National
Institutes of Health (NIH) [R00CA126026-03, 2PA50-CA090578-07]; American
Association for Cancer Research [07-40-12-COST]; American Society of
Clinical Oncology Cancer Foundation [CDA-15431]; National Medical
Research Council, Ministry of Health, Singapore
FX W.P., G.J.R., and M.G.K. received consulting fees from Astra Zeneca.
G.J.R. and M.G.K. received fees from Boehringer Ingelheim; M. G. K. also
received fees from Pfizer and Novartis. The EGFR T790M patent is
licensed to MolecularMD (W.P.).; Supported in part by National
Institutes of Health (NIH) grants R00CA126026-03 (to S. K.) and
2PA50-CA090578-07 (to D. B. C., D. G. T., and B.Y.Y.); the American
Association for Cancer Research 07-40-12-COST (to D. B. C.); a Career
Development Award by the American Society of Clinical Oncology Cancer
Foundation CDA-15431 (to D. B. C.); and a Research Fellowship Award by
the National Medical Research Council, Ministry of Health, Singapore (to
W.Y.).
NR 37
TC 40
Z9 40
U1 0
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1556-0864
EI 1556-1380
J9 J THORAC ONCOL
JI J. Thorac. Oncol.
PD JUL
PY 2010
VL 5
IS 7
BP 1048
EP 1053
DI 10.1097/JTO.0b013e3181dd1386
PG 6
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA 615VE
UT WOS:000279165200020
PM 20512075
ER
PT J
AU Ray, KK
Nazer, B
Cairns, R
Gibson, CM
Cannon, CP
AF Ray, Kausik K.
Nazer, Babak
Cairns, Richard
Gibson, C. Michael
Cannon, Christopher P.
TI Association between percutaneous coronary intervention and long-term
C-reactive protein levels in patients with acute coronary syndromes
SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS
LA English
DT Article
DE Percutaneous coronary intervention; Inflammation; Acute coronary
syndromes; C-reactive protein
ID STENT IMPLANTATION; TRIAL; ATORVASTATIN; ELEVATION; STATINS
AB C-reactive protein (CRP) is an independent predictor of risk in ACS patients, and it has been previously shown that percutaneous coronary intervention (PCI) is associated with an early rise in CRP. To assess the long-term relationship between PCI and CRP, we compared CRP levels at baseline, 30 days, 4 months and 24 months among patients in the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 trial who were treated with PCI and those who did not receive PCI. At study entry, CRP was significantly higher among patients who had undergone PCI (13.2 vs. 9.5 mg/l, P < 0.001). However, by day 30 CRP was significantly lower among patients who had undergone PCI for management of the index event (1.5 vs. 2.1 mg/l, P < 0.001) and remained lower at 4 months and by end of study (average 2 years after ACS). Using a multivariable model, we observed that PCI was associated with 8.6% lower CRP level at month 4 (P = 0.05) and 14.2% at approximately 2 years (P = 0.0028). These analyses suggest that although PCI may acutely increase inflammation, it may also serve a role in decreasing inflammation associated with atherosclerotic plaques via long-term mechanical stabilization.
C1 [Cannon, Christopher P.] Brigham & Womens Hosp, Thrombolysis Myocardial Infarct TIMI Study Grp, Div Cardiovasc, Boston, MA 02115 USA.
[Gibson, C. Michael] Harvard Univ, Sch Med, Beth Israel Deaconess Hosp, Div Cardiovasc, Boston, MA 02115 USA.
[Cairns, Richard] Worldwide Clin Trials, Nottingham, England.
[Nazer, Babak] Brigham & Womens Hosp, Dept Internal Med, Boston, MA 02115 USA.
[Ray, Kausik K.] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.
RP Cannon, CP (reprint author), Brigham & Womens Hosp, Thrombolysis Myocardial Infarct TIMI Study Grp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA.
EM cpcannon@partners.org
FU Bristol-Myers Squibb; Sankyo; BHF; Accumetrics; AstraZeneca;
GlaxoSmithKline; Intekrin Therapeutics; Merck; Novartis; Takeda; Eli
Lilly
FX PROVE IT-TIMI 22 was funded by Bristol-Myers Squibb and Sankyo.
http://www.clinicaltrials.gov/ registration number NCT00382460. Dr. Ray
is funded by a BHF Intermediate Fellowship. Dr. Nazer has nothing to
disclose. Dr. Cannon reports having received research grant support from
Accumetrics, AstraZeneca, Bristol-Myers Squibb/Sanofi Partnership,
GlaxoSmithKline, Intekrin Therapeutics, Merck, Merck/Schering Plough
Partnership, Novartis, and Takeda. He has served as a clinical advisor
to and has equity in Automedics Medical Systems. Dr. Gibson reports
research support from Eli Lilly, Daichi Sankyo, Bayer and
Schering-Plough (now Merck).
NR 14
TC 2
Z9 4
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 JUL
PY 2010
VL 30
IS 1
BP 10
EP 13
DI 10.1007/s11239-010-0463-7
PG 4
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 612WG
UT WOS:000278935800003
PM 20354760
ER
PT J
AU De Luca, G
Gibson, CM
Bellandi, F
Noc, M
Maioli, M
Zorman, S
Zeymer, U
Gabriel, HM
Emre, A
Cutlip, D
Arntz, HR
Dudek, D
Rakowski, T
Gyongyosi, M
Huber, K
van't Hof, AWJ
AF De Luca, Giuseppe
Gibson, C. Michael
Bellandi, Francesco
Noc, Marko
Maioli, Mauro
Zorman, Simona
Zeymer, Uwe
Gabriel, H. Mesquita
Emre, Ayse
Cutlip, Donald
Arntz, Hans-Richard
Dudek, Dariusz
Rakowski, Tomasz
Gyongyosi, Maryann
Huber, Kurt
van't Hof, Arnoud W. J.
TI Impact of distal embolization on myocardial perfusion and survival among
patients undergoing primary angioplasty with glycoprotein IIb-IIIa
inhibitors: insights from the EGYPT cooperation
SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS
LA English
DT Article
DE Primary angioplasty; Distal embolization; Gp IIb-IIIa inhibitors
ID PERCUTANEOUS CORONARY INTERVENTION; INFARCT-RELATED ARTERY; NO-REFLOW
PHENOMENON; THROMBUS-ASPIRATION; RANDOMIZED-TRIALS; REPERFUSION;
THERAPY; GRADE; FLOW; THROMBECTOMY
AB Even though primary angioplasty is able to obtain TIMI 3 flow in the vast majority of STEMI patients, epicardial recanalization does not guarantee optimal myocardial perfusion, that remain suboptimal in a relatively large proportion of patients. Large interest has been focused in recent years on the role of distal embolization as major determinant of impaired reperfusion. The aim of the current study was to investigate in a large cohort of STEMI undergoing primary angioplasty with Gp IIb-IIIa inhibitors the impact of distal embolization on myocardial perfusion and survival. Our population is represented by patients undergoing primary angioplasty for STEMI included in the EGYPT database. Distal embolization was defined as an abrupt ''cutoff'' in the main vessel or one of the coronary branches of the infarct-related artery, distal to the angioplasty site. Myocardial perfusion was evaluated by angiography or ST-segment resolution, whereas infarct size was estimated by using peak CK and CK-MB. Follow-up data were collected between 30 days and 1 year after primary angioplasty. Data on distal embolization were available in a total of 1182 patients (71% of total population). Distal embolization was observed in 132 patients (11.1%). Patients with distal embolization were older (P < 0.001), with larger prevalence of diabetes (P = 0.01), previous MI (P = 0.048) and advanced Killip class at presentation (P = 0.018), abciximab administration (P < 0.001), with a lower prevalence of smoking (P = 0.04). Patients with distal embolization had more often poor preprocedural recanalization (P = 0.061), less often postprocedural TIMI 3 flow (P < 0.001), postprocedural MBG 2-3 (P < 0.001), complete ST-segment resolution (P = 0.021) and larger infarct size (CK-MB: 328 +/- A 356 U/l vs. 259 +/- A 226 U/l, P = 0.012). The impact of distal embolization on myocardial perfusion was confirmed after correction for baseline confounding factors as evaluated by MBG 2-3 (adjusted OR [95% CI] = 3.14 [2.06-4.77], P < 0.0001) but not complete ST-segment resolution (adjusted OR [95% CI] = 1.23 [0.84-1.92], P = 0.26). At 208 +/- A 160 days follow-up, distal embolization was associated with a significantly higher mortality (9.2% vs. 2.7%, HR [95% CI] = 3.41 [1.73-6.71], P < 0.0001), that was confirmed after correction for baseline confounding factors (adjusted HR [95% CI] = 2.23 [1.1-4.7], P = 0.026). This study showed among STEMI patients treated with Gp IIb-IIIa inhibitors, that distal embolization is independently associated with impaired myocardial perfusion and survival.
C1 [De Luca, Giuseppe] Eastern Piedmont Univ, Maggiore della Carita Hosp, Div Cardiol, Novara, Italy.
[Gibson, C. Michael] Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, Boston, MA 02115 USA.
[Bellandi, Francesco; Maioli, Mauro] Prato Hosp, Div Cardiol, Prato, Italy.
[Noc, Marko; Zorman, Simona] Univ Med Ctr, Ctr Intens Internal Med, Ljubljana, Slovenia.
[Zeymer, Uwe] Herzzentrum Ludwigshafen, Div Cardiol, Ludwigshafen, Germany.
[Gabriel, H. Mesquita] Hosp Santa Maria, Div Cardiol, Lisbon, Portugal.
[Emre, Ayse] Siyami Ersek Thorac & Cardiovasc Surg Ctr, Istanbul, Turkey.
[Cutlip, Donald] Beth Israel Deaconess Med Ctr, Intervent Cardiol Sect, Boston, MA 02215 USA.
[Arntz, Hans-Richard] Charite, Med Klin 2, Berlin, Germany.
[Dudek, Dariusz; Rakowski, Tomasz] Jagiellonian Univ, Inst Cardiol, Dept Cardiol 2, Krakow, Poland.
[Gyongyosi, Maryann] Med Univ Vienna, Dept Cardiol, Vienna, Austria.
[Huber, Kurt] Wilhelminenspital Stadt Wien, Dept Med Cardiol & Emergency Med 3, Vienna, Austria.
[van't Hof, Arnoud W. J.] Hosp Weezenlanden, Div Cardiol, Zwolle, Netherlands.
RP De Luca, G (reprint author), Eastern Piedmont Univ, Maggiore della Carita Hosp, Div Cardiol, Novara, Italy.
EM giuseppe.deluca@maggioreosp.novara.it
NR 29
TC 11
Z9 11
U1 0
U2 2
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0929-5305
J9 J THROMB THROMBOLYS
JI J. Thromb. Thrombolysis
PD JUL
PY 2010
VL 30
IS 1
BP 23
EP 28
DI 10.1007/s11239-009-0419-y
PG 6
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 612WG
UT WOS:000278935800005
PM 19921103
ER
PT J
AU Cohen, MJ
Serkova, NJ
Wiener-Kronish, J
Pittet, JF
Niemann, CU
AF Cohen, Mitchell J.
Serkova, Natalie J.
Wiener-Kronish, Jeanine
Pittet, Jean-Francois
Niemann, Claus U.
TI H-1-NMR-Based Metabolic Signatures of Clinical Outcomes in Trauma
Patients-Beyond Lactate and Base Deficit
SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE
LA English
DT Article; Proceedings Paper
CT 68th Annual Meeting of the
American-Association-for-the-Surgery-of-Trauma (AAST)
CY OCT 01-03, 2009
CL Pittsburgh, PA
SP Amer Assoc Surg Trauma (AAST)
DE Trauma; Metabolism; Body fluids; Quantitative metabolomics; Nuclear
magnetic resonance spectroscopy; Biomarkers
ID MULTIPLE ORGAN FAILURE; PERSISTENT OCCULT HYPOPERFUSION;
INFLAMMATORY-BOWEL-DISEASE; FATTY-ACID PATTERN; MAJOR TRAUMA;
END-POINTS; SIGNIFICANT INCREASE; INFECTION-RATE; INJURY; RESUSCITATION
AB The determination of reliable biomarkers capable to predict clinical outcome of a trauma patient remains essential toward better therapeutic management of the patient in the intensive care unit. Assessment of global metabolic profiling using quantitative nuclear magnetic resonance (NMR)-based metabolomics offers an attractive modern methodology for fast and comprehensive determination of multiple circulating metabolites and for establishing metabolic phenotype of survivors versus nonsurvivors. Multivariate data analysis on 43 quantitative metabolic parameters identified three lipid metabolites, triacylglycerol, glycerol heads of phospholipids, and monounsaturated fatty acids, as being the most discriminative markers to separate survivors versus nonsurvivors at the time of admission. Glucose and glutamate were intermediate predictors, followed by lactate and hydroxybutyrate as two low-weight predictors. Ultimately, cellular and subcellular failure in nonsurviving trauma patients results in multiple systemic biochemical effects and in changes in circulating metabolites in the blood that are characteristic for decreased lipid synthesis and urea cycle activity in the liver, and for increased hyperglycemia, lactic, and ketoacidosis.
C1 [Cohen, Mitchell J.; Niemann, Claus U.] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA.
[Serkova, Natalie J.] Univ Colorado, Hlth Sci Ctr, Canc Ctr Small Anim Imaging Core, Dept Anesthesiol, Aurora, CO USA.
[Wiener-Kronish, Jeanine] Harvard Univ, Sch Med, Dept Anesthesia, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Pittet, Jean-Francois; Niemann, Claus U.] Univ Calif San Francisco, Dept Anesthesia & Perioperat Care, San Francisco, CA 94143 USA.
RP Cohen, MJ (reprint author), San Francisco Gen Hosp, Dept Surg, Ward 3A, San Francisco, CA 94110 USA.
EM mcohen@sfghsurg.ucsf.edu
FU NIGMS NIH HHS [K08 GM-085689]; PHS HHS [R 380T10586]
NR 32
TC 25
Z9 25
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0022-5282
EI 1529-8809
J9 J TRAUMA
JI J. Trauma-Injury Infect. Crit. Care
PD JUL
PY 2010
VL 69
IS 1
BP 31
EP 40
DI 10.1097/TA.0b013e3181e043fe
PG 10
WC Critical Care Medicine; Surgery
SC General & Internal Medicine; Surgery
GA 627AQ
UT WOS:000280010600005
PM 20622576
ER
PT J
AU Findley, JK
Park, LT
Siefert, CJ
Chiou, GJ
Lancaster, RT
DeMoya, M
Gervasini, A
Velmahos, GC
AF Findley, John K.
Park, Lawrence T.
Siefert, Caleb J.
Chiou, Grace J.
Lancaster, Robert T.
DeMoya, Marc
Gervasini, Alice
Velmahos, George C.
TI Two Routine Blood Tests-Mean Corpuscular Volume and Aspartate
Aminotransferase-as Predictors of Delirium Tremens in Trauma Patients
SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE
LA English
DT Article
DE Delirium tremens; Alcohol withdrawal; Laboratory testing
ID MECHANICALLY VENTILATED PATIENTS; ALCOHOL-WITHDRAWAL SYNDROME;
INTENSIVE-CARE-UNIT; LABORATORY TESTS; RISK-FACTORS; SEDATION; SCALE;
CAGE
AB Background: Delirium tremens (DT) in trauma patients is associated with significant morbidity and mortality. Short interview tools have been used to determine the risk of DT but require an alert, compliant patient and a motivated physician. The mean corpuscular volume (MCV) and aspartate aminotransferase (AST) levels are parts of routine laboratory testing, influenced by excessive alcohol consumption, and may serve as predictors of DT. This study examines the predictive ability of these two readily available biological markers.
Methods: The records of 423 consecutive trauma patients who presented to a Level I trauma center with a positive toxicology screen for alcohol were reviewed. The outcome variable was DT, as defined by the presence of tremor, diaphoresis, autonomic instability, and hallucinations. The positive predictive value (PPV), negative predictive value (NPV), and likelihood ratio (LR) of the admission MCV and AST values were calculated for the prediction of DT.
Results: Of the 336 patients who met the criteria for study participation, 110 were diagnosed with DT due to alcohol withdrawal. When the admission MCV and AST were normal, only 3 patients (3.8%) developed DT. The NPV, PPV, and LR with two normal values together were 58.2%, 3.8%, and 0.080, respectively. When both were abnormal, 72 patients (64.3%) developed DT. The NPV, PPV, and LR with two abnormal values together were 83%, 64.3%, and 3.698, respectively.
Conclusion: Normal admission MCV and AST values in intoxicated trauma patients nearly exclude the development of DT.
C1 [Findley, John K.; Chiou, Grace J.; Lancaster, Robert T.; DeMoya, Marc; Gervasini, Alice; Velmahos, George C.] Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA.
[Findley, John K.; Park, Lawrence T.; Siefert, Caleb J.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Findley, JK (reprint author), Gray Bigelow 1303,55 Fruit St, Boston, MA 02114 USA.
EM jfindley@partners.org
NR 26
TC 3
Z9 3
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0022-5282
J9 J TRAUMA
JI J. Trauma-Injury Infect. Crit. Care
PD JUL
PY 2010
VL 69
IS 1
BP 199
EP 201
DI 10.1097/TA.0b013e3181bee583
PG 3
WC Critical Care Medicine; Surgery
SC General & Internal Medicine; Surgery
GA 627AQ
UT WOS:000280010600031
PM 20093979
ER
PT J
AU Ramsey, SD
Zeliadt, SB
Arora, NK
Blough, DK
Penson, DF
Oakley-Girvan, I
Hamilton, AS
Van Den Eeden, SK
Fedorenko, CR
Potosky, AL
AF Ramsey, Scott D.
Zeliadt, Steven B.
Arora, Neeraj K.
Blough, David K.
Penson, David F.
Oakley-Girvan, Ingrid
Hamilton, Ann S.
Van Den Eeden, Stephen K.
Fedorenko, Catherine R.
Potosky, Arnold L.
TI Unanticipated and Underappreciated Outcomes During Management of Local
Stage Prostate Cancer: A Prospective Survey
SO JOURNAL OF UROLOGY
LA English
DT Article
DE prostatic neoplasms; surgical procedures, operative; information
services
ID QUALITY-OF-LIFE; ANDROGEN DEPRIVATION; TREATMENT DECISIONS; MEN; REGRET;
BRACHYTHERAPY; RADIOTHERAPY; SATISFACTION; SURGERY
AB Purpose: Due to the complexity of factors that must be considered when choosing a therapy for prostate cancer, we hypothesized that many men will find that certain factors such as side effects gain or lose importance after therapy relative to their expectations before therapy.
Materials and Methods: We conducted a prospective survey of men deciding on a therapy for local stage prostate cancer in 3 geographic regions. Men were asked to rate the importance of 11 personal factors before starting therapy and again 6 months after therapy.
Results: Among 448 eligible men completing the most common treatment options, overall satisfaction with treatment choice was high across all therapies. While most men changed rankings of importance in at least 1 of the 11 factors, the majority of pre-post evaluations were highly consistent. In adjusted analyses the 2 factors that emerged as significantly underappreciated for all major prostate cancer treatments were 1) the impact of treatment on usual daily activities, and 2) the recommendations of friends and relatives who were affected with prostate cancer.
Conclusions: Initial patient expectations of the importance of the majority of factors related to prostate cancer treatment are generally accurate. Better counseling may improve the accuracy of patient expectations of the personal burden of treatment, and their evaluation of the advice of affected friends and relatives.
C1 [Ramsey, Scott D.; Zeliadt, Steven B.; Fedorenko, Catherine R.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA.
[Blough, David K.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Ctr Excellence, Seattle, WA USA.
[Blough, David K.] Univ Washington, Sch Pharm, Seattle, WA 98195 USA.
[Arora, Neeraj K.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Penson, David F.] Vanderbilt Univ, Med Ctr, Nashville, TN USA.
[Hamilton, Ann S.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Potosky, Arnold L.] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA.
[Van Den Eeden, Stephen K.] Kaiser Permanente, Div Res, Oakland, CA USA.
RP Ramsey, SD (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,M3-B232, Seattle, WA 98109 USA.
EM sramsey@fhcrc.org
NR 21
TC 6
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 0022-5347
J9 J UROLOGY
JI J. Urol.
PD JUL
PY 2010
VL 184
IS 1
BP 120
EP 125
DI 10.1016/j.juro.2010.03.023
PG 6
WC Urology & Nephrology
SC Urology & Nephrology
GA 609FW
UT WOS:000278642300040
PM 20478590
ER
PT J
AU Thulin, H
Kreicbergs, U
Wijkstrom, H
Steineck, G
Henningsohn, L
AF Thulin, Helena
Kreicbergs, Ulrika
Wijkstrom, Hans
Steineck, Gunnar
Henningsohn, Lars
TI Sleep Disturbances Decrease Self-Assessed Quality of Life in Individuals
Who Have Undergone Cystectomy
SO JOURNAL OF UROLOGY
LA English
DT Article
DE urinary diversion; sleep disorders; nocturnal enuresis; quality of life
ID ORTHOTOPIC BLADDER SUBSTITUTION; URETHRAL KOCK POUCH; RADICAL
CYSTECTOMY; URINARY-DIVERSION; DISTRESSFUL SYMPTOMS; ILEAL CONDUIT;
CANCER; NEOBLADDER; EXPERIENCE; COMPLICATIONS
AB Purpose: The best possible urinary diversion after cystectomy, if any, is yet to be defined to our knowledge. Therefore, we investigated nocturnal urinary disturbances and quality of life in individuals who have undergone cystectomy with urinary diversion for bladder cancer.
Materials and Methods: All patients 30 to 80 years old who had undergone cystectomy with urinary diversion at 7 urological centers in Sweden were included in the study. Sleep disturbances, nocturnal urinary leakage and urine evacuation frequency, as well as their effect on self-assessed quality of life variables were measured with a study specific questionnaire. We received the questionnaire from 452 (92%) of 491 identified individuals. Outcome variables were dichotomized and the results are presented as relative risks.
Results: Those individuals with an orthotopic neobladder had an increased risk of nocturnal urinary leakage and/or urine evacuation frequency compared to those with a noncontinent urostomy or cutaneous continent reservoir. Of the patients with an orthotopic neobladder 37% reported negative effects on nocturnal sleep compared to 22% and 14% of those with a noncontinent or continent urostomy, respectively. Of those patients reporting that the urinary diversion had a negative effect on nocturnal sleep 88% had a decreased quality of life vs 65% of those who stated that the urinary diversion had no or little influence on nocturnal sleep.
Conclusions: Nocturnal urinary problems are of great concern for individuals with urinary diversion, especially those with an orthotopic neobladder. Regular disruption of sleep decreases quality of life.
C1 [Thulin, Helena; Kreicbergs, Ulrika; Steineck, Gunnar; Henningsohn, Lars] Karolinska Inst, Div Clin Canc Epidemiol, Dept Pathol & Oncol, Stockholm, Sweden.
[Kreicbergs, Ulrika] Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.
[Wijkstrom, Hans; Henningsohn, Lars] Karolinska Inst, Karolinska Univ Hosp Huddinge, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.
[Steineck, Gunnar] Sahlgrens Acad, Div Clin Canc Epidemiol, Dept Oncol, Gothenburg, Sweden.
[Kreicbergs, Ulrika] Dana Farber Canc Inst, Phyllis F Cantor Ctr, Boston, MA 02115 USA.
RP Thulin, H (reprint author), Karolinska Univ Hosp Z5 U1, S-17176 Stockholm, Sweden.
EM Helena.Thulin@ki.se
OI Steineck, Gunnar/0000-0002-0787-3969
FU Swedish Cancer Society; Stockholm Cancer Society; Stockholm County
Council
FX Supported by grants from Swedish Cancer Society, Stockholm Cancer
Society and Stockholm County Council.
NR 29
TC 12
Z9 12
U1 1
U2 2
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 JUL
PY 2010
VL 184
IS 1
BP 198
EP 202
DI 10.1016/j.juro.2010.03.009
PG 5
WC Urology & Nephrology
SC Urology & Nephrology
GA 609FW
UT WOS:000278642300067
PM 20478603
ER
PT J
AU Abularrage, CJ
Crawford, RS
Conrad, MF
Lee, H
Kwolek, CJ
Brewster, DC
Cambria, RP
LaMuraglia, GM
AF Abularrage, Christopher J.
Crawford, Robert S.
Conrad, Mark F.
Lee, Hang
Kwolek, Christopher J.
Brewster, David C.
Cambria, Richard P.
LaMuraglia, Glenn M.
TI Preoperative variables predict persistent type 2 endoleak after
endovascular aneurysm repair
SO JOURNAL OF VASCULAR SURGERY
LA English
DT Article; Proceedings Paper
CT 36th Annual Meeting of the New-England-Society-for-Vascular-Surgery
CY OCT 02-04, 2009
CL Boston, MA
SP New England Soc Vasc Surg
ID ABDOMINAL AORTIC-ANEURYSM; INFERIOR MESENTERIC-ARTERY; II ENDOLEAKS;
SELECTIVE INTERVENTION; THROMBIN INJECTION; NATURAL-HISTORY; FOLLOW-UP;
EMBOLIZATION; OUTCOMES; SAC
AB Objective: Persistent type 2 endoleaks (PT2, present >= 6 months) after endovascular aneurysm repair (EVAR) are associated with adverse outcomes. This study evaluated the preoperative risk factors and natural history of PT2 in order to define a population at high risk.
Methods: From January 1999 to December 2007, 595 of 832 EVAR patients had long-term computed tomography follow-up and comprised the study cohort. Preoperative anatomic and clinical variables were correlated with PT2 using Cox regression. Composite hazard ratios (HRs) were constructed with clusters of high-risk preoperative variables. Primary end points, including spontaneous resolution, sac enlargement >5 mm, and freedom from reintervention, were. evaluated using Kaplan-Meier analysis.
Results:There were 136 PT2 patients (23%) with a median follow-up of 34.8 months (range, 6.4-121.2 months). Positive predictive factors included patent inferior mesenteric artery (IMA; HR, 4.00; 95% confidence interval [CI], 1.62-9.90; P = .003), increasing number of patent lumbar arteries (HR, 1.24; 95% CI, 1.10-1.41; P = .0006), increasing age (HR, 1.04; 95% Cl, 1.01-1.06; P = .005), and increasing luminal diameter on CT-contrast pacified lumen (HR, 1.03; 95% CI, 1.02-1.05; P = .0001). During follow-up, spontaneous PT2 resolution occurred in 34 patients (25%), sac diameter remained stable in 63 (46%), and rupture occurred in 2 (1.5%). Kaplan-Meier analysis estimated that 35.2% +/- 5.6% (95% CI, 23.8%-46.2%) of PT2 resolve spontaneously at 5 years after the index procedure. Freedom from sac enlargement >5 mm was 54.6% +/- 7.2% (95% CI, 40.6%-69.4%) at 5 years. Fifty-nine reinterventions were performed in 39 patients with PT2. Freedom from reintervention was 67.3% +/- 5.0% (95% CI, 57.0%-77.0%) at 5 years. The combination of a patent IMA and one risk factor of more than six patent lumbar arteries, maximum luminal diameter >30 mm, or age >70 years increased the odds of PT2 approximately ninefold. The combination of a patent IMA and any two risk factors increased the odds of PT2 approximately 18-fold.
Conclusions: Several readily identifiable preoperative variables are associated with PT2 whose natural history was benign in but 35% of patients. On the basis of the composite high-risk HRs, there is accordingly a cohort of patients in whom perioperative interventions to preclude PT2 should be considered. ( J Vase Surg 2010;52:19-24.)
C1 [Abularrage, Christopher J.; Crawford, Robert S.; Conrad, Mark F.; Kwolek, Christopher J.; Brewster, David C.; Cambria, Richard P.; LaMuraglia, Glenn M.] Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, Boston, MA 02114 USA.
[Lee, Hang] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP LaMuraglia, GM (reprint author), Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, WAC440,15 Parkman St, Boston, MA 02114 USA.
EM glamuraglia@partners.org
NR 26
TC 41
Z9 41
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 JUL
PY 2010
VL 52
IS 1
BP 19
EP 24
DI 10.1016/j.jvs.2010.02.023
PG 6
WC Surgery; Peripheral Vascular Disease
SC Surgery; Cardiovascular System & Cardiology
GA 625IP
UT WOS:000279889000004
PM 20478685
ER
PT J
AU Chan, WH
Ng, AKL
Robb, NC
Lam, MKH
Chan, PKS
Au, SWN
Wang, JH
Fodor, E
Shaw, PC
AF Chan, Wai-Hon
Ng, Andy Ka-Leung
Robb, Nicole C.
Lam, Mandy Ka-Han
Chan, Paul Kay-Sheung
Au, Shannon Wing-Ngor
Wang, Jia-Huai
Fodor, Ervin
Shaw, Pang-Chui
TI Functional Analysis of the Influenza Virus H5N1 Nucleoprotein Tail Loop
Reveals Amino Acids That Are Crucial for Oligomerization and
Ribonucleoprotein Activities
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID TEMPERATURE-SENSITIVE MUTANTS; A VIRUS; RNA-BINDING; MUTATIONAL
ANALYSIS; POLYMERASE; REPLICATION; COMPLEX; IDENTIFICATION;
TRANSCRIPTION; LOCALIZATION
AB Homo-oligomerization of the nucleoprotein (NP) of influenza A virus is crucial for providing a major structural framework for the assembly of viral ribonucleoprotein (RNP) particles. The nucleoprotein is also essential for transcription and replication during the virus life cycle. In the H5N1 NP structure, the tail loop region is important for NP to form oligomers. Here, by an RNP reconstitution assay, we identified eight NP mutants that had different degrees of defects in forming functional RNPs, with the RNP activities of four mutants being totally abolished (E339A, V408S P410S, R416A, and L418S P419S mutants) and the RNP activities of the other four mutants being more than 50% decreased (R267A, I406S, R422A, and E449A mutants). Further characterization by static light scattering showed that the totally defective protein variants existed as monomers in vitro, deviating from the trimeric/oligomeric form of wild-type NP. The I406S, R422A, and E449A variants existed as a mixture of unstable oligomers, thus resulting in a reduction of RNP activity. Although the R267A variant existed as a monomer in vitro, it resumed an oligomeric form upon the addition of RNA and retained a certain degree of RNP activity. Our data suggest that there are three factors that govern the NP oligomerization event: (i) interaction between the tail loop and the insertion groove, (ii) maintenance of the tail loop conformation, and (iii) stabilization of the NP homo-oligomer. The work presented here provides information for the design of NP inhibitors for combating influenza virus infection.
C1 [Chan, Wai-Hon; Ng, Andy Ka-Leung; Lam, Mandy Ka-Han; Au, Shannon Wing-Ngor; Shaw, Pang-Chui] Chinese Univ Hong Kong, Dept Biochem, Shatin, Hong Kong, Peoples R China.
[Chan, Wai-Hon; Ng, Andy Ka-Leung; Lam, Mandy Ka-Han; Au, Shannon Wing-Ngor; Shaw, Pang-Chui] Chinese Univ Hong Kong, Ctr Prot Sci & Crystallog, Shatin, Hong Kong, Peoples R China.
[Chan, Wai-Hon; Ng, Andy Ka-Leung; Au, Shannon Wing-Ngor; Shaw, Pang-Chui] Chinese Univ Hong Kong, Mol Biotechnol Programme, Shatin, Hong Kong, Peoples R China.
[Chan, Paul Kay-Sheung] Chinese Univ Hong Kong, Dept Microbiol, Shatin, Hong Kong, Peoples R China.
[Robb, Nicole C.; Fodor, Ervin] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England.
[Wang, Jia-Huai] Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst,Dept Pediat,Dept Biol Chem, Boston, MA 02115 USA.
RP Shaw, PC (reprint author), Chinese Univ Hong Kong, Dept Biochem, Shatin, Hong Kong, Peoples R China.
EM pcshaw@cuhk.edu.hk
RI Chan, Paul/J-9360-2013
FU General Research Fund [CUHK 472808]; Research Grants Council of Hong
Kong SAR; Medical Research Council, United Kingdom [G0700848]
FX This work was supported by a General Research Fund grant (grant CUHK
472808) from the Research Grants Council of Hong Kong SAR and by the
Medical Research Council (grant G0700848), United Kingdom.
NR 33
TC 36
Z9 38
U1 0
U2 7
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 JUL
PY 2010
VL 84
IS 14
BP 7337
EP 7345
DI 10.1128/JVI.02474-09
PG 9
WC Virology
SC Virology
GA 612WF
UT WOS:000278935700042
PM 20463064
ER
PT J
AU Wieland, D
Boland, R
Baskins, J
Kinosian, B
AF Wieland, Darryl
Boland, Rebecca
Baskins, Judith
Kinosian, Bruce
TI Five-Year Survival in a Program of All-Inclusive Care For Elderly
Compared With Alternative Institutional and Home- and Community-Based
Care
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE Comparative effectiveness research; Risk stratification; Long-term care;
Dual eligibles
ID SERVICES
AB Community-based services are preferred to institutional care for people requiring long-term care (LTC). States are increasing their Medicaid waiver programs, although Program of All-Inclusive Care For Elderly (PACE)-prepaid, community-based comprehensive care-is available in 31 states. Despite emerging alternatives, little is known about their comparative effectiveness.
Methods. For a two-county region of South Carolina, we contrast long-term survival among entrants (n = 2040) to an aged and disabled waiver program, PACE, and nursing homes (NHs), stratifying for risk. Participants were followed for 5 years or until death; those lost to follow-up or surviving less than 5 years as on August 8, 2005 were censored. Analyses included admission descriptive statistics and Kaplan Meier curves. To address cohort risk imbalance, we employed an established mortality risk index, which showed external validity in waiver, PACE, and NH cohorts (log-rank tests = 105.42, 28.72, and 52.23, respectively, all p<.001; c-statistics = .67, .58, .65, p<.001).
Results. Compared with waiver (n = 1,018) and NH (n = 468) admissions, PACE participants (n = 554) were older, more cognitively impaired, and had intermediate activities of daily living dependency. PACE mortality risk (72.6% high-to-intermediate) was greater than in waiver (58.8%), and similar to NH (71.6%). Median NH survival was 2.3 years. Median PACE survival was 4.2 years versus 3.5 in waiver (unstratified, log rank = .394; p = .53), but accounting for risk, PACE's advantage is significant (log rank = 5.941 (1); p = .015). Compared with waiver, higher risk admissions to PACE were most likely to benefit (moderate: PACE median survival = 4.7 years vs waiver 3.4; high risk: 3.0 vs 2.0).
Conclusion. Long-term outcomes of LTC alternatives warrant greater research and policy attention.
C1 [Wieland, Darryl] Univ S Carolina, Div Geriatr, Dept Med, Sch Med, Columbia, SC 29208 USA.
[Wieland, Darryl; Boland, Rebecca; Baskins, Judith] Palmetto Hlth Richland, Div Geriatr Serv, Columbia, SC USA.
[Kinosian, Bruce] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA.
[Kinosian, Bruce] Univ Penn, Dept Med, Philadelphia, PA 19104 USA.
RP Wieland, D (reprint author), 3010 Farrow Rd,300A, Columbia, SC 29203 USA.
EM darryl.wieland@palmettohealth.org
NR 13
TC 10
Z9 10
U1 2
U2 6
PU GERONTOLOGICAL SOC AMER
PI WASHINGTON
PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA
SN 1079-5006
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD JUL
PY 2010
VL 65
IS 7
BP 721
EP 726
DI 10.1093/gerona/glq040
PG 6
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 615CN
UT WOS:000279109500005
PM 20354065
ER
PT J
AU Ayotte, BJ
Yang, FM
Jones, RN
AF Ayotte, Brian J.
Yang, Frances M.
Jones, Richard N.
TI Physical Health and Depression: A Dyadic Study of Chronic Health
Conditions and Depressive Symptomatology in Older Adult Couples
SO JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL
SCIENCES
LA English
DT Article
DE Chronic illness; Depression; Dyadic; Spouses
ID CHRONIC DISEASE; UNITED-STATES; FIT INDEXES; LIFE-SPAN; SYMPTOMS;
PREVALENCE; SPOUSES; EPIDEMIOLOGY; AMERICANS; SUPPORT
AB This study examined the associations among chronic health conditions, sociodemographic factors, and depressive symptomatology in older married couples. Data from the 2004 wave of the Health and Retirement Study (n = 2,184 couples) were analyzed. Results indicated a reciprocal relationship in depressive symptoms between spouses. Additionally, post hoc analyses indicated that husbands' stroke and high blood pressure were related to increased depressive symptomatology among wives. Beyond the reciprocal relationship, husbands were unaffected by wives' health. These results suggest sex differences underlying psychological distress in the context of physical health among older adults and that older women with husbands who have high levels of depressive symptomatology. high blood pressure, or a history of stroke may be at particular risk of experiencing depressive symptoms.
C1 [Ayotte, Brian J.] VA Boston Healthcare Syst, Boston, MA USA.
[Yang, Frances M.] Harvard Univ, Sch Med, Dept Psychiat, Brigham & Womens Hosp, Boston, MA 02115 USA.
[Yang, Frances M.; Jones, Richard N.] Hebrew SeniorLife, Inst Aging Res, Boston, MA USA.
[Jones, Richard N.] Harvard Univ, Beth Israel Deaconess Med Ctr, Div Gerontol, Sch Med, Boston, MA 02215 USA.
RP Ayotte, BJ (reprint author), Univ Massachusetts Dartmouth, Dept Psychol, N Dartmouth, MA 02747 USA.
RI Jones, Richard/J-3488-2013
OI Jones, Richard/0000-0002-1049-218X
FU National Institutes of Health (NIH)/National Institute on Aging (NIA)
[5-T35AG026781, 5-T32AG023480, 5 R01 AG025308-02, P60AG008812]; Harvard
Medical School; NARSAD
FX This research was made possible through the National Institutes of
Health (NIH)/National Institute on Aging (NIA) 5-T35AG026781,
5-T32AG023480 award. NIH/NIA 5 R01 AG025308-02, NIH/NIA 5 R01
AG025308-02 Diversity Supplement. NIH/NIA P60AG008812, Harvard Medical
School Livingston Fellowship, and the NARSAD Young Investigator Award
NR 47
TC 25
Z9 25
U1 3
U2 16
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5014
EI 1758-5368
J9 J GERONTOL B-PSYCHOL
JI J. Gerontol. Ser. B-Psychol. Sci. Soc. Sci.
PD JUL
PY 2010
VL 65
IS 4
BP 438
EP 448
DI 10.1093/geronb/gbq033
PG 11
WC Geriatrics & Gerontology; Gerontology; Psychology; Psychology,
Multidisciplinary
SC Geriatrics & Gerontology; Psychology
GA 642WA
UT WOS:000281250500005
PM 20498455
ER
PT J
AU Miranda, KC
Bond, DT
McKee, M
Skog, J
Paunescu, TG
Da Silva, N
Brown, D
Russo, LM
AF Miranda, Kevin C.
Bond, Daniel T.
McKee, Mary
Skog, Johan
Paunescu, Teodor G.
Da Silva, Nicolas
Brown, Dennis
Russo, Leileata M.
TI Nucleic acids within urinary exosomes/microvesicles are potential
biomarkers for renal disease
SO KIDNEY INTERNATIONAL
LA English
DT Article
DE acute kidney injury; chronic kidney disease; exosome; transcriptional
profiling
ID DIAGNOSTIC BIOMARKERS; EXOSOMES; CELLS; MEMBRANE; MARKER; ATPASE; RNAS
AB Urinary exosomes or microvesicles are being studied intensively to identify potential new biomarkers for renal disease. We sought to identify whether these microvesicles contain nucleic acids. We isolated microvesicles from human urine in the same density range as that previously described for urinary exosomes and found them to have an RNA integrity profile similar to that of kidney tissue, including 18S and 28S rRNA. This profile was better preserved in urinary microvesicles compared with whole cells isolated from urine, suggesting that microvesicles may protect RNA during urine passage. We were able to detect mRNA in the human urinary microvesicles encoding proteins from all regions of the nephron and the collecting duct. Further, to provide a proof of principle, we found that microvesicles isolated from the urine of the V-ATPase B1 subunit knockout mice lacked mRNA of this subunit while containing a normal amount of the B2 subunit and aquaporin 2. The microvesicles were found to be contaminated with extraneous DNA potentially on their surface; therefore, we developed a rapid and reliable means to isolate nucleic acids from within urine microvesicles devoid of this extraneous contamination. Our study provides an experimental strategy for the routine isolation and use of urinary microvesicles as a novel and non-invasive source of nucleic acids to further renal disease biomarker discovery. Kidney International (2010) 78, 191-199; doi:10.1038/ki.2010.106; published online 28 April 2010
C1 [Miranda, Kevin C.; Bond, Daniel T.; McKee, Mary; Paunescu, Teodor G.; Da Silva, Nicolas; Brown, Dennis; Russo, Leileata M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Membrane Biol, Boston, MA 02114 USA.
[Skog, Johan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nephrol,Ctr Syst Biol, Boston, MA 02114 USA.
[Skog, Johan] Harvard Univ, Sch Med, Charlestown, MA USA.
[Skog, Johan] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA.
[Skog, Johan] Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA USA.
[Skog, Johan] Massachusetts Gen Hosp, Neurosci Program, Charlestown, MA USA.
RP Russo, LM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Membrane Biol, 185 Cambridge St,Room 8206, Boston, MA 02114 USA.
EM Lrusso@mgh.harvard.edu
FU Juvenile Diabetes Research Foundation; Boston Area Diabetes and
Endocrinology Research Center [DK57521]; National Kidney Foundation; NIH
[DK73266, DK38452, DK42956]; Stiftelsen Olle Engkvist Byggmastare Grant;
Center for the Study of Inflammatory Bowel Disease [DK43341]
FX This research was supported by the Juvenile Diabetes Research Foundation
International Innovation Award (LMR, KCM). LMR also received a Juvenile
Diabetes Research Foundation International Transition Award and a Boston
Area Diabetes and Endocrinology Research Center P&F Grant (DK57521). KCM
received a National Kidney Foundation Postdoctoral Fellowship Award. TGP
was supported by NIH grant DK73266. JS was supported by a Stiftelsen
Olle Engkvist Byggmastare Grant. DB was supported by NIH grants DK38452
and DK42956. The microscopy core facility of the MGH Program in Membrane
Biology receives additional support from the Boston Area Diabetes and
Endocrinology Research Center (DK57521) and the Center for the Study of
Inflammatory Bowel Disease (DK43341).
NR 26
TC 137
Z9 146
U1 4
U2 28
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 JUL
PY 2010
VL 78
IS 2
BP 191
EP 199
DI 10.1038/ki.2010.106
PG 9
WC Urology & Nephrology
SC Urology & Nephrology
GA 618SE
UT WOS:000279375200011
PM 20428099
ER
PT J
AU Bassett, IV
Sax, PE
AF Bassett, Ingrid V.
Sax, Paul E.
TI Untreated HIV: harmful even at high CD4 cell counts
SO LANCET
LA English
DT Editorial Material
ID GENERAL-POPULATION; INFECTED ADULTS; MORTALITY; AIDS; MORBIDITY; RISK
C1 [Bassett, Ingrid V.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[Bassett, Ingrid V.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA.
[Sax, Paul E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Infect Dis, Boston, MA 02115 USA.
RP Bassett, IV (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
FU NIAID NIH HHS [K23 AI068458]; NIMH NIH HHS [R01 MH090326]
NR 15
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 0140-6736
J9 LANCET
JI Lancet
PD JUL-AUG
PY 2010
VL 376
IS 9738
BP 306
EP 308
DI 10.1016/S0140-6736(10)61033-1
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 636FW
UT WOS:000280717900005
PM 20638117
ER
PT J
AU Jansen, M
Yip, S
Louis, DN
AF Jansen, Michael
Yip, Stephen
Louis, David N.
TI Molecular pathology in adult gliomas: diagnostic, prognostic, and
predictive markers
SO LANCET NEUROLOGY
LA English
DT Review
ID GROWTH-FACTOR-RECEPTOR; MGMT PROMOTER METHYLATION; LOW-GRADE
OLIGODENDROGLIOMAS; REPAIR GENE MGMT; PHASE-III TRIAL;
GLIOBLASTOMA-MULTIFORME; MALIGNANT GLIOMAS; 1P/19Q LOSS;
O-6-METHYLGUANINE-DNA METHYLTRANSFERASE; RADIATION-THERAPY
AB Over the past 10 years, there has been an increasing use of molecular markers in the assessment and management of adult malignant gliomas. Some molecular signatures are used diagnostically to help pathologists classify tumours, whereas others are used to estimate prognosis for patients. Most crucial, however, are those markers that are used to predict response to certain therapies, thereby directing clinicians to a particular treatment while avoiding other potentially deleterious therapies. Recently, large-scale genome-wide surveys have been used to identify new biomarkers that have been rapidly developed as diagnostic and prognostic tools. Given these developments, the pace of discovery of new molecular assays will quicken to facilitate personalised medicine in the setting of malignant glioma.
C1 [Louis, David N.] Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Pathol Serv, Boston, MA 02114 USA.
[Louis, David N.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
[Louis, David N.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Jansen, Michael] Cork Univ Hosp, Dept Histopathol, Cork, Ireland.
[Yip, Stephen] British Columbia Canc Agcy, Dept Pathol & Lab Med, Vancouver, BC V5Z 4E6, Canada.
[Yip, Stephen] British Columbia Canc Agcy, Ctr Translat & Appl Genom, Vancouver, BC V5Z 4E6, Canada.
RP Louis, DN (reprint author), Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Pathol Serv, 55 Fruit St,Warren 225, Boston, MA 02114 USA.
EM dlouis@partners.org
FU NCI NIH HHS [R01 CA057683, R01 CA057683-18]
NR 100
TC 112
Z9 120
U1 2
U2 13
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1474-4422
J9 LANCET NEUROL
JI Lancet Neurol.
PD JUL
PY 2010
VL 9
IS 7
BP 717
EP 726
DI 10.1016/S1474-4422(10)70105-8
PG 10
WC Clinical Neurology
SC Neurosciences & Neurology
GA 617NF
UT WOS:000279286900016
PM 20610347
ER
PT J
AU Herbst, RS
Sun, Y
Eberhardt, WEE
Germonpre, P
Saijo, N
Zhou, CC
Wang, J
Li, LY
Kabbinavar, F
Ichinose, Y
Qin, SK
Zhang, L
Biesma, B
Heymach, JV
Langmuir, P
Kennedy, SJ
Tada, H
Johnson, BE
AF Herbst, Roy S.
Sun, Yon
Eberhardt, Wilfried E. E.
Germonpre, Paul
Saijo, Nagahiro
Zhou, Caicun
Wang, Jie
Li, Longyun
Kabbinavar, Fairooz
Ichinose, Yukito
Qin, Shukui
Zhang, Li
Biesma, Bonne
Heymach, John V.
Langmuir, Peter
Kennedy, Sarah J.
Tada, Hiroomi
Johnson, Bruce E.
TI Vandetanib plus docetaxel versus docetaxel as second-line treatment for
patients with advanced non-small-cell lung cancer (ZODIAC): a
double-blind, randomised, phase 3 trial
SO LANCET ONCOLOGY
LA English
DT Article
ID QUALITY-OF-LIFE; III TRIAL; FUNCTIONAL ASSESSMENT; TUMOR-GROWTH;
SUPPORTIVE CARE; GEFITINIB; CHEMOTHERAPY; CARBOPLATIN; PACLITAXEL;
THERAPY
AB Background Vandetanib is a once-daily oral inhibitor of vascular endothelial growth factor receptor (VEGFR), epidermal growth factor receptor (EGFR), and rearranged during transfection (RET) tyrosine kinases. In a randomised phase 2 study in patients with previously treated non-small-cell lung cancer (NSCLC), adding vandetanib 100 mg to docetaxel significantly improved progression-free survival (PFS) compared with docetaxel alone, including a longer PFS in women. These results supported investigation of the combination in this larger, definitive phase 3 trial (ZODIAC).
Methods Between May, 2006, and April, 2008, patients with locally advanced or metastatic (stage IIIB-IV) NSCLC after progression following first-line chemotherapy were randomly assigned 1:1 through a third-party interactive voice system to receive vandetanib (100 mg/day) plus docetaxel (75 mg/m(2) intravenously every 21 days; maximum six cycles) or placebo plus docetaxel. The primary objective was comparison of PFS between the two groups in the intention-to-treat population. Women were a coprimary analysis population. This study has been completed and is registered with ClinicalTrials.gov, number NCT00312377.
Findings 1391 patients received vandetanib plus docetaxel (n=694 [197 women]) or placebo plus docetaxel (n=697 [224 women]). Vandetanib plus docetaxel led to a significant improvement in PFS versus placebo plus docetaxel (hazard ratio [HR] 0-79, 97.58% CI 0.70-0.90; p<0.0001); median PFS was 4.0 months in the vandetanib group versus 3.2 months in placebo group. A similar improvement in PFS with vandetanib plus docetaxel versus placebo plus docetaxel was seen in women (HR 0.79, 0-62-1.00, p=0-024); median PFS was 4.6 months in the vandetanib group versus 4.2 months in the placebo group. Among grade 3 or higher adverse events, rash (63/689 [9%] vs 7/690 [1%]), neutropenia (199/689 [29%] vs 164/690 [24%]), leukopenia (99/689 [14%] vs 77/690 [11%]), and febrile neutropenia (61/689 [9%] vs 48/690 [7%]) were more common with vandetanib plus docetaxel than with placebo plus docetaxel. The most common serious adverse event was febrile neutropenia (46/689 [7%] in the vandetanib group vs 38/690 [6%] in the placebo group).
Interpretation The addition of vandetanib to docetaxel provides a significant improvement in PFS in patients with advanced NSCLC after progression following first-line therapy.
C1 [Herbst, Roy S.] Univ Texas MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Houston, TX 77030 USA.
[Sun, Yon] Canc Hosp, Beijing, Peoples R China.
[Eberhardt, Wilfried E. E.] Univ Duisburg Essen, W German Tumor Ctr, Dept Med Canc Res, Essen, Germany.
[Germonpre, Paul] Univ Antwerp Hosp, Antwerp, Belgium.
[Saijo, Nagahiro] Kinki Univ, Sch Med, Osaka 589, Japan.
[Zhou, Caicun] Tongji Univ, Sch Med, Shanghai Pulm Hosp, Shanghai 200092, Peoples R China.
[Wang, Jie] Peking Univ, Beijing Canc Hosp & Inst, Sch Oncol, Beijing 100871, Peoples R China.
[Li, Longyun] Peking Union Med Coll, Beijing 100021, Peoples R China.
[Kabbinavar, Fairooz] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA.
[Ichinose, Yukito] Kyushu Natl Canc Ctr, Fukuoka, Japan.
[Qin, Shukui] Nanjing Bayi Hosp, Nanjing, Peoples R China.
[Zhang, Li] Sun Yat Sen Univ, Ctr Canc, Guangzhou 510275, Guangdong, Peoples R China.
[Biesma, Bonne] Jeroen Bosch Ziekenhuis, Afdeling Longziekten, sHertogenbosch, Netherlands.
[Langmuir, Peter; Tada, Hiroomi] AstraZeneca, Wilmington, DE USA.
[Kennedy, Sarah J.] AstraZeneca, Macclesfield, Cheshire, England.
[Johnson, Bruce E.] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Herbst, RS (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, 1515 Holcombe Blvd,Unit 432, Houston, TX 77030 USA.
EM rherbst@mdanderson.org
FU AstraZeneca
FX RSH received grant support and consultancy fees (ZODIAC steering
committee) from AstraZeneca. WEEE received fees for an advisory board
(ZODIAC steering committee) and a speaker's bureau from AstraZeneca. PG
received fees for an advisory board (ZODIAC steering committee) and
accommodation expenses from AstraZeneca. YI received fees for honoraria
from AstraZeneca. LZ received fees from AstraZeneca for presentation of
data from this study at a regional meeting. JVH received fees for
consultancy, grants, and honoraria from AstraZeneca. PL, SJK, and HT are
employees of AstraZeneca and PL has stock in the company. BE) received
grant support, consultancy and honoraria fees (ZODIAC steering
committee), and travel support from AstraZeneca. All other authors
declared no conflicts of interest.; We acknowledge the valuable
contribution of the independent data monitoring committee (Malcolm
Ranson, Philip Bonomi, Stuart Pocock, Tomohide Tamura, Pan-Chyr Yang)
and the independent statistical data analysis centre (Duolao Wang) to
the oversight and conduct of this study. This study was supported
financially by AstraZeneca. We thank John Matthew of Mudskipper
Bioscience for editorial assistance funded by AstraZeneca. FK worked on
the study on behalf of the Translational Oncology Research International
(TORI) Network of investigators.
NR 30
TC 251
Z9 263
U1 1
U2 41
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1470-2045
J9 LANCET ONCOL
JI Lancet Oncol.
PD JUL
PY 2010
VL 11
IS 7
BP 619
EP 626
DI 10.1016/S1470-2045(10)70132-7
PG 8
WC Oncology
SC Oncology
GA 624ZG
UT WOS:000279860300015
PM 20570559
ER
PT J
AU Janeway, KA
Grier, HE
AF Janeway, Katherine A.
Grier, Holcombe E.
TI Sequelae of osteosarcoma medical therapy: a review of rare acute
toxicities and late effects
SO LANCET ONCOLOGY
LA English
DT Review
ID HIGH-DOSE METHOTREXATE; PEDIATRIC-ONCOLOGY-GROUP; ACUTE
LYMPHOBLASTIC-LEUKEMIA; DEXRAZOXANE-ASSOCIATED RISK; IFOSFAMIDE-INDUCED
NEPHROTOXICITY; 2ND MALIGNANT NEOPLASMS; TERM-FOLLOW-UP; NEOADJUVANT
CHEMOTHERAPY; CISPLATIN NEPHROTOXICITY; SECONDARY MALIGNANCIES
AB Since the introduction of multi-agent chemotherapy for osteosarcoma over 30 years ago, overall survival has exceeded 50%. A clear understanding of the acute complications and late effects of osteosarcoma therapy is required to care effectively for patients with osteosarcoma undergoing active treatment, and for the increasing number of osteosarcoma survivors. There has now been sufficient cumulative experience treating patients with osteosarcoma with active antiosteosarcoma chemotherapy agents, high-dose methotrexate, doxorubicin, cisplatin, ifosfamide, and etoposide to recognise and understand rare toxicities associated with these agents, and to identify the late effects of osteosarcoma therapy. Late effects and rare toxicities of osteosarcoma include cardiac toxicity, acute and chronic nephrotoxicity, neurotoxicity, hearing loss, infertility, and second malignant neoplasms. Reducing the complications of osteosarcoma therapy is an important goal that will require the identification of clear prognostic indicators, the development of biologically-based therapies, and improved antidotes for the active anti-osteosarcoma cytotoxic drugs.
C1 [Janeway, Katherine A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol,Childrens Hosp Boston, Boston, MA 02115 USA.
RP Janeway, KA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol,Childrens Hosp Boston, 44 Binney St, Boston, MA 02115 USA.
EM katherine_janeway@dfci.harvard.edu
NR 77
TC 60
Z9 68
U1 1
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1470-2045
EI 1474-5488
J9 LANCET ONCOL
JI Lancet Oncol.
PD JUL
PY 2010
VL 11
IS 7
BP 670
EP 678
DI 10.1016/S1470-2045(10)70062-0
PG 9
WC Oncology
SC Oncology
GA 624ZG
UT WOS:000279860300021
PM 20347613
ER
PT J
AU Kobler, JB
Chang, EW
Zeitels, SM
Yun, SH
AF Kobler, James B.
Chang, Ernest W.
Zeitels, Steven M.
Yun, Seok-Hyun
TI Dynamic Imaging of Vocal Fold Oscillation With Four-Dimensional Optical
Coherence Tomography
SO LARYNGOSCOPE
LA English
DT Article
DE Optical coherence tomography; oscillation; vocal fold; mucosal wave;
stroboscopy; laryngology; biomechanics; dynamics; biomaterials; rheology
ID MEDIAL SURFACE DYNAMICS; STROBOSCOPY; PHONATION; LARYNX; LASER
AB Objectives/Hypothesis: Optical coherence tomography (OCT) can provide high-resolution (similar to 10-15 mu m/pixel) images of vocal fold microanatomy, as demonstrated previously. We explored physiologically triggered Fourier-domain OCT for imaging vocal folds during phonation. The goal is to visualize dynamic histological cross sections and four-dimensional data sets where multiple planes are displayed in synchronized motion. If feasible, this approach could be a useful research tool and spur development of new clinical instrumentation.
Study Design: A Fourier-domain, triggered OCT system was created and tested in experiments on excised calf larynges to obtain preliminary observations and characterize important factors affecting image quality.
Methods: Larynges were imaged during phonation driven by warm, humidified air. A subglottal pressure signal was used to synchronize the OCT system with the phonatory cycle. Image sequences were recorded as functions of anatomical location or subglottal pressure. Implant materials were also imaged during vibration, both in isolation and after injection into a vocal fold.
Results: Oscillations of epithelium and lamina propria were observed, and parameters such as shape, amplitude, and velocity of the vocal fold mucosal waves were found to be measurable. Ripples of mucosal wave as small as 100 mu m in vertical height were clearly visible. Internal strain was also observed in normal and implanted vocal folds.
Conclusions: Four-dimensional OCT of the vocal fold may help to more directly relate biomechanics to anatomy and disease. It may also be useful for assaying the functional rheology of implants in the context of real tissue. With further development, this technology has potential for clinical endoscopic application.
C1 [Kobler, James B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Laryngeal Surg Res Lab,Dept Surg,Ctr Laryngeal Su, Boston, MA 02114 USA.
[Chang, Ernest W.; Yun, Seok-Hyun] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.
[Chang, Ernest W.] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA.
[Yun, Seok-Hyun] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA.
RP Kobler, JB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Laryngeal Surg Res Lab,Dept Surg,Ctr Laryngeal Su, 55 Fruit St,620 Their Bldg, Boston, MA 02114 USA.
EM james.kobler@mgh.harvard.edu; syun@hms.harvard.edu
FU Eugene B. Casey Foundations; Institute of Laryngology and Voice
Restoration; NIH [RC1DK086242]; Wellman graduate student fellowship
FX This work was supported in part by the Eugene B. Casey Foundations and
the Institute of Laryngology and Voice Restoration, NIH grant
RC1DK086242, and a Wellman graduate student fellowship (Ernest W.
Chang). The authors have no other funding, financial relationships, or
conflicts of interest to disclose.
NR 27
TC 19
Z9 19
U1 1
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0023-852X
J9 LARYNGOSCOPE
JI Laryngoscope
PD JUL
PY 2010
VL 120
IS 7
BP 1354
EP 1362
DI 10.1002/lary.20938
PG 9
WC Medicine, Research & Experimental; Otorhinolaryngology
SC Research & Experimental Medicine; Otorhinolaryngology
GA 620KM
UT WOS:000279498500015
PM 20564724
ER
PT J
AU Busaba, N
AF Busaba, Nicolas
TI In Response to Reformation of Concha Bullosa Following Treatment by
Crushing Surgical Technique: Implication for Balloon Sinuplasty
SO LARYNGOSCOPE
LA English
DT Letter
C1 [Busaba, Nicolas] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA.
[Busaba, Nicolas] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA.
RP Busaba, N (reprint author), Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA.
NR 1
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0023-852X
J9 LARYNGOSCOPE
JI Laryngoscope
PD JUL
PY 2010
VL 120
IS 7
BP 1492
EP 1492
PG 1
WC Medicine, Research & Experimental; Otorhinolaryngology
SC Research & Experimental Medicine; Otorhinolaryngology
GA 620KM
UT WOS:000279498500038
ER
PT J
AU Franco, W
Kothare, A
Ronan, SJ
Grekin, RC
McCalmont, TH
AF Franco, Walfre
Kothare, Amogh
Ronan, Stephen J.
Grekin, Roy C.
McCalmont, Timothy H.
TI Hyperthermic Injury to Adipocyte Cells by Selective Heating of
Subcutaneous Fat With a Novel Radiofrequency Device: Feasibility Studies
SO LASERS IN SURGERY AND MEDICINE
LA English
DT Article
DE radiofrequency heating; subcutaneous fat; adipocyte cell viability
ID SKIN NOCICEPTORS; BLOOD-FLOW; THRESHOLDS; LASER; POWER
AB Background and Objective: The main objective of the present study is to demonstrate the feasibility of utilizing a novel non-invasive radiofrequency (RF) device to induce lethal thermal damage to subcutaneous adipose tissue only by establishing a controlled electric field that heats up fat preferentially.
Study Design/Materials and Methods: Adipocyte cells in six-well plates were subjected to hyperthermic conditions: 45, 50, 55, 60, and 65 degrees C during 1, 2, and 3 minutes. Cell viability was assessed 72 hours after exposure. Two groups of abdominoplasty patients were treated with the RF device during and days before their surgical procedure. Temperatures of cutaneous and subcutaneous tissues were measured during treatment (3 minutes) of the first group. The immediate tissue response to heating was assessed by acute histology. The delayed tissue response was assessed by histology analysis of the second group, 4, 9, 10, 17, and 24 days after treatment (22 minutes). A mathematical model was used to estimate treatment temperatures of the second group. The model uses patient-based diagnostic measurements as input and was validated with in vivo clinical temperature measurements.
Results: Cell viability dropped from 89% to 20% when temperature increased from 45 to 50 degrees C during 1 minute exposures. Three minutes at 45 degrees C resulted in 40% viability. In vivo, the temperature of adipose tissue at 7-12 mm depth from the surface increased to 50 degrees C while the temperature of cutaneous tissues was <30 degrees C during RF exposure. Acute and longitudinal histology evaluations show normal epidermal and dermal layers. Subcutaneous tissues were also normal acutely. Subcutaneous vascular alterations, starting at day 4, and fat necrosis, starting at day 9, were consistently observed within 4.5-19 mm depth from the skin surface. Subcutaneous tissue temperatures were estimated to be 43-45 degrees C for 15 minutes.
Conclusions: A controlled internal electric field perpendicular to the skin fat interface is selective in heating up fat and, consequently, has the ability to induce lethal thermal damage to subcutaneous adipose tissues while sparing overlying and underlying tissues. In vitro adipocyte cells are heat sensitive to thermal exposures of 50 and 45 degrees C on the order of minutes, 1 and 3 minutes, respectively. In vivo, 15 minutes thermal exposures to 43-45 degrees C result in a delayed adipocyte cellular death response in this study, 9 days. The novel RF device presented herein effectively delivers therapeutic thermal exposures to subcutaneous adipose tissues while protecting epidermal and dermal layers. Lasers Surg. Med. 42:361-370, 2010. (C) 2010 Wiley-Liss, Inc.
C1 [Franco, Walfre; Kothare, Amogh] Cutera Inc, Brisbane, CA USA.
[Ronan, Stephen J.] Blackhawk Plast Surg, Danville, CA USA.
[Grekin, Roy C.] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA.
[McCalmont, Timothy H.] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA.
RP Franco, W (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.
EM wfranco@partners.org
NR 27
TC 37
Z9 37
U1 5
U2 6
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0196-8092
J9 LASER SURG MED
JI Lasers Surg. Med.
PD JUL
PY 2010
VL 42
IS 5
BP 361
EP 370
DI 10.1002/lsm.20925
PG 10
WC Dermatology; Surgery
SC Dermatology; Surgery
GA 618EO
UT WOS:000279334500002
PM 20583242
ER
PT J
AU Ragas, X
Dai, TH
Tegos, GP
Agut, M
Nonell, S
Hamblin, MR
AF Ragas, Xavier
Dai, Tianhong
Tegos, George P.
Agut, Montserrat
Nonell, Santi
Hamblin, Michael R.
TI Photodynamic Inactivation of Acinetobacter baumannii Using
Phenothiazinium Dyes: In Vitro and In Vivo Studies
SO LASERS IN SURGERY AND MEDICINE
LA English
DT Article
DE photodynamic inactivation; burn infection; new methylene blue;
bioluminescence imaging
ID GRAM-NEGATIVE BACTERIA; METHYLENE-BLUE; TOLUIDINE BLUE;
PHOTOBACTERICIDAL ACTIVITY; STAPHYLOCOCCUS-AUREUS; EFFICIENT
PHOTOSENSITIZERS; ESCHERICHIA-COLI; THERAPY; DERIVATIVES; INFECTIONS
AB Background and Objective: Phenothiazinium dyes have been reported to be effective photosensitizers inactivating a wide range of microorganisms in vitro after illumination with red light. However, their application in vivo has not extensively been explored. This study evaluates the bactericidal activity of phenothiazinium dyes against multidrug-resistant Acinetobacter baumannii both in vitro and in vivo.
Study Design/Materials and Methods: We report the investigation of toluidine blue 0, methylene blue, 1,9-dimethylmethylene blue, and new methylene blue for photodynamic inactivation of multidrug-resistant A. baumannii in vitro. The most effective dye was selected to carry out in vivo studies using third-degree mouse burns infected with a bioluminescent A. baumannii strain, upon irradiation with a 652 nm noncoherent light source. The mice were imaged daily for 2 weeks to observe differences in the bioluminescence time curve between the photodynamic therapy (PDT)-treated mice in comparison with untreated burns.
Results: All the dyes were effective in vitro against A. baumannii after 30 J/cm(2) irradiation of 635 or 652 nm red light had been delivered, with more effective killing when the dye remained in solution. New methylene blue was the most effective of the four dyes, achieving a 3.2-log reduction of the bacterial luminescence during PDT in vivo after 360 J/cm(2) and an 800 mu M dye dose. Moreover, a statistically significant reduction of the area under the bioluminescence time curve of PDT-treated mice was observed showing that the infection did not recur after PDT.
Conclusions: Phenothiazinium dyes, and especially new methylene blue, are potential photosensitizers for PDT to treat burns infected with multidrug-resistant A. baumannii in vivo. Lasers Surg. Med. 42:384-390, 2010. (C) 2010 Wiley-Liss, Inc.
C1 [Ragas, Xavier; Dai, Tianhong; Tegos, George P.; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.
[Ragas, Xavier; Agut, Montserrat; Nonell, Santi] Univ Ramon Llull, Inst Quim Sarria, Barcelona, Spain.
[Dai, Tianhong; Tegos, George P.; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA.
[Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, BAR414,40 Blossom St, Boston, MA 02114 USA.
EM hamblin@helix.mgh.harvard.edu
RI Tegos, George/C-8830-2011; Nonell, Santi/L-2561-2013; Agut,
Montserrat/L-5905-2013;
OI Nonell, Santi/0000-0002-8900-5291; Agut, Montserrat/0000-0001-9173-9684;
Hamblin, Michael/0000-0001-6431-4605
FU US NIH [R01AI050875]; Generalitat de Catalunya (DURSI); Fons Social
Europeu; Bullock-Wellman Postdoctoral Fellowship Award; Massachusetts
Technology Transfer Center Award
FX Contract grant sponsor: US NIH; Contract grant number: R01AI050875;
Contract grant sponsor: Generalitat de Catalunya (DURSI); Contract grant
sponsor: Fons Social Europeu.; This research was supported by US NIH
grant R01AI050875 to M.R.H. X.R. was supported by the Generalitat de
Catalunya (DURSI) and Fons Social Europeu with a predoctoral fellowship.
T.D. was supported by the Bullock-Wellman Postdoctoral Fellowship Award.
G.P.T. was supported by a Massachusetts Technology Transfer Center
Award.
NR 41
TC 43
Z9 45
U1 1
U2 13
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0196-8092
J9 LASER SURG MED
JI Lasers Surg. Med.
PD JUL
PY 2010
VL 42
IS 5
BP 384
EP 390
DI 10.1002/lsm.20922
PG 7
WC Dermatology; Surgery
SC Dermatology; Surgery
GA 618EO
UT WOS:000279334500005
PM 20583252
ER
PT J
AU Tefferi, A
Lasho, TL
Abdel-Wahab, O
Guglielmelli, P
Patel, J
Caramazza, D
Pieri, L
Finke, CM
Kilpivaara, O
Wadleigh, M
Mai, M
McClure, RF
Gilliland, DG
Levine, RL
Pardanani, A
Vannucchi, AM
AF Tefferi, A.
Lasho, T. L.
Abdel-Wahab, O.
Guglielmelli, P.
Patel, J.
Caramazza, D.
Pieri, L.
Finke, C. M.
Kilpivaara, O.
Wadleigh, M.
Mai, M.
McClure, R. F.
Gilliland, D. G.
Levine, R. L.
Pardanani, A.
Vannucchi, A. M.
TI IDH1 and IDH2 mutation studies in 1473 patients with chronic-, fibrotic-
or blast-phase essential thrombocythemia, polycythemia vera or
myelofibrosis
SO LEUKEMIA
LA English
DT Article
DE JAK2; MPL; TET2; myeloproliferative
ID JAK2 46/1 HAPLOTYPE; INTERNATIONAL WORKING GROUP;
ISOCITRATE-DEHYDROGENASE 1; PROGNOSTIC SCORING SYSTEM;
MYELOPROLIFERATIVE NEOPLASMS; CONFERS SUSCEPTIBILITY; ACTIVATING
MUTATION; MYELOID METAPLASIA; TET2 MUTATIONS; LEUKEMIA
AB In a multi-institutional collaborative project, 1473 patients with myeloproliferative neoplasms (MPN) were screened for isocitrate dehydrogenase 1 (IDH1)/IDH2 mutations: 594 essential thrombocythemia (ET), 421 polycythemia vera (PV), 312 primary myelofibrosis (PMF), 95 post-PV/ET MF and 51 blast-phase MPN. A total of 38 IDH mutations (18 IDH1-R132, 19 IDH2-R140 and 1 IDH2-R172) were detected: 5 (0.8%) ET, 8 (1.9%) PV, 13 (4.2%) PMF, 1 (1%) post-PV/ET MF and 11 (21.6%) blast-phase MPN (P < 0.01). Mutant IDH was documented in the presence or absence of JAK2, MPL and TET2 mutations, with similar mutational frequencies. However, IDH-mutated patients were more likely to be nullizygous for JAK2 46/1 haplotype, especially in PMF (P = 0.04), and less likely to display complex karyotype, in blast-phase disease (P < 0.01). In chronic-phase PMF, JAK2 46/1 haplotype nullizygosity (P < 0.01; hazard ratio (HR) 2.9, 95% confidence interval (CI) 1.7-5.2), but not IDH mutational status (P = 0.55; HR 1.3, 95% CI 0.5-3.4), had an adverse effect on survival. This was confirmed by multivariable analysis. In contrast, in both blast-phase PMF (P = 0.04) and blast-phase MPN (P = 0.01), the presence of an IDH mutation predicted worse survival. The current study clarifies disease- and stage-specific IDH mutation incidence and prognostic relevance in MPN and provides additional evidence for the biological effect of distinct JAK2 haplotypes. Leukemia (2010) 24, 1302-1309; doi:10.1038/leu.2010.113; published online 27 May 2010
C1 [Tefferi, A.; Lasho, T. L.; Finke, C. M.; Pardanani, A.] Mayo Clin, Div Hematol, Dept Med, Rochester, MN 55905 USA.
[Abdel-Wahab, O.; Patel, J.; Kilpivaara, O.; Levine, R. L.] Mem Sloan Kettering Canc Ctr, Dept Med, Human Oncol & Pathogenesis Program, New York, NY 10021 USA.
[Abdel-Wahab, O.; Patel, J.; Kilpivaara, O.; Levine, R. L.] Mem Sloan Kettering Canc Ctr, Dept Med, Leukemia Serv, New York, NY 10021 USA.
[Guglielmelli, P.; Pieri, L.; Vannucchi, A. M.] Univ Florence, UF Ematol, Dipartimento Area Crit Med Chirurg, Azienda Osped Univ Careggi,Ist Toscano Tumori, Florence, Italy.
[Caramazza, D.] Policlin Univ Palermo, Cattedra & UO Ematol, Palermo, Italy.
[Wadleigh, M.; Gilliland, D. G.] Harvard Univ, Brigham & Womens Hosp, Div Hematol,Dept Med, Dana Farber Canc Inst,Sch Med, Boston, MA 02115 USA.
[Mai, M.; McClure, R. F.] Mayo Clin, Div Hematopathol, Dept Lab Med, Rochester, MN USA.
RP Tefferi, A (reprint author), Mayo Clin, Div Hematol, Dept Med, Rochester, MN 55905 USA.
EM tefferi.ayalew@mayo.edu
RI Guglielmelli, Paola/K-7509-2016; Pieri, Lisa/K-1762-2016;
OI Guglielmelli, Paola/0000-0003-1809-284X; Pieri,
Lisa/0000-0003-1812-8072; Abdel-Wahab, Omar/0000-0002-3907-6171
FU Myeloproliferative Disorders Foundation, Chicago, IL, USA; Henry J.
Predolin Foundation for Research in Leukemia, Mayo Clinic, Rochester,
MN, USA; Associazione Italiana per la Ricerca sul Cancro-AIRC Milan,
Italy
FX This study is supported in part by grants from the 'Myeloproliferative
Disorders Foundation, Chicago, IL, USA', 'The Henry J. Predolin
Foundation for Research in Leukemia, Mayo Clinic, Rochester, MN, USA'
and 'Associazione Italiana per la Ricerca sul Cancro-AIRC Milan, Italy,
to AMV'.
NR 43
TC 163
Z9 170
U1 2
U2 13
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0887-6924
J9 LEUKEMIA
JI Leukemia
PD JUL
PY 2010
VL 24
IS 7
BP 1302
EP 1309
DI 10.1038/leu.2010.113
PG 8
WC Oncology; Hematology
SC Oncology; Hematology
GA 625KB
UT WOS:000279892900009
PM 20508616
ER
PT J
AU Kumar, SK
Flinn, I
Noga, SJ
Hari, P
Rifkin, R
Callander, N
Bhandari, M
Wolf, JL
Gasparetto, C
Krishnan, A
Grosman, D
Glass, J
Sahovic, EA
Shi, H
Webb, IJ
Richardson, PG
Rajkumar, SV
AF Kumar, S. K.
Flinn, I.
Noga, S. J.
Hari, P.
Rifkin, R.
Callander, N.
Bhandari, M.
Wolf, J. L.
Gasparetto, C.
Krishnan, A.
Grosman, D.
Glass, J.
Sahovic, E. A.
Shi, H.
Webb, I. J.
Richardson, P. G.
Rajkumar, S. V.
TI Bortezomib, dexamethasone, cyclophosphamide and lenalidomide combination
for newly diagnosed multiple myeloma: phase 1 results from the
multicenter EVOLUTION study
SO LEUKEMIA
LA English
DT Article
DE multiple myeloma; clinical trial; bortezomib; lenalidomide; multidrug
combination; phase 1
ID STEM-CELL TRANSPLANTATION; LONG-TERM SURVIVAL; PERIPHERAL NEUROPATHY;
PLUS DEXAMETHASONE; COMPLETE RESPONSE; FOLLOW-UP; TRIAL; THERAPY;
PROGRESSION; IMPROVEMENT
AB This phase 1 study (Clinicaltrials.gov: NCT00507442) was conducted to determine the maximum tolerated dose (MTD) of cyclophosphamide in combination with bortezomib, dexamethasone and lenalidomide (VDCR) and to assess the safety and efficacy of this combination in untreated multiple myeloma patients. Cohorts of three to six patients received a cyclophosphamide dosage of 100, 200, 300, 400 or 500 mg/m(2) (on days 1 and 8) plus bortezomib 1.3 mg/m(2) (on days 1, 4, 8 and 11), dexamethasone 40 mg (on days 1, 8 and 15) and lenalidomide 15 mg (on days 1-14), for eight 21-day induction cycles, followed by four 42-day maintenance cycles (bortezomib 1.3 mg/m(2), on days 1, 8, 15 and 22). The MTD was the cyclophosphamide dose below which more than one of six patients experienced a dose-limiting toxicity (DLT). Twenty-five patients were treated. Two DLTs were seen, of grade 4 febrile neutropenia (cyclophosphamide 400 mg/m(2)) and grade 4 herpes zoster despite antiviral prophylaxis (cyclophosphamide 500 mg/m(2)). No cumulative hematological toxicity or thromboembolic episodes were reported. The overall response rate was 96%, including 20% stringent complete response (CR), 40% CR/near-complete response and 68% >= very good partial response. VDCR is well tolerated and highly active in this population. No MTD was reached; the recommended phase 2 cyclophosphamide dose in VDCR is 500 mg/m(2), which was the highest dose tested. Leukemia (2010) 24, 1350-1356; doi:10.1038/leu.2010.116; published online 27 May 2010
C1 [Kumar, S. K.; Rajkumar, S. V.] Mayo Clin, Div Hematol, Rochester, MN 55905 USA.
[Flinn, I.] Sarah Cannon Res Inst, Nashville, TN USA.
[Noga, S. J.] Sinai Hosp, Dept Med Hematol Oncol, Baltimore, MD 21215 USA.
[Hari, P.] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA.
[Rifkin, R.] Rocky Mt Canc Ctr, Dept Haematol Oncol, Denver, CO USA.
[Callander, N.] Univ Wisconsin, Ctr Comprehens Canc, Dept Hematol, Madison, WI USA.
[Bhandari, M.] Christ Hosp, Dept Haematol Oncol, Cincinnati, OH 45219 USA.
[Wolf, J. L.] Univ Calif Med Ctr, Div Hematol & Oncol, San Francisco, CA USA.
[Gasparetto, C.] Clin Duke Univ, Durham, NC USA.
[Krishnan, A.] City Hope Natl Med Ctr, Duarte, CA 91010 USA.
[Grosman, D.] Mem Canc Inst, Pembroke Pines, FL USA.
[Glass, J.] Louisiana State Univ, Hlth Sci Ctr, Shreveport, LA 71105 USA.
[Sahovic, E. A.] Western Penn Hosp, Cell Transplantat Program, Pittsburgh, PA 15224 USA.
[Shi, H.; Webb, I. J.] Millennium Pharmaceut Inc, Cambridge, MA USA.
[Richardson, P. G.] Dana Farber Canc Ctr, Dept Med Oncol, Boston, MA USA.
RP Kumar, SK (reprint author), Mayo Clin, Div Hematol, 200 1st St SW, Rochester, MN 55905 USA.
EM kumar.shaji@mayo.edu
RI Kumar, Shaji/A-9853-2008;
OI Kumar, Shaji/0000-0001-5392-9284; Rajkumar, S.
Vincent/0000-0002-5862-1833; Hari, Parameswaran/0000-0002-8800-297X
FU Millennium Pharmaceuticals, Celgene; Millennium Pharmaceuticals; Celgene
FX SKK has a consultancy/advisory relationship, and has received research
funding from Millennium Pharmaceuticals, Celgene; IF has received
honoraria and research funding from Millennium Pharmaceuticals; SJN has
received honoraria from Millennium Pharmaceuticals; PH has a
consultancy/advisory relationship with Millennium Pharmaceuticals and
Celgene; has received honoraria from Celgene and research funding from
Millennium Pharmaceuticals; RR has a consultancy/advisory relationship
with Millennium Pharmaceuticals and has received honoraria from
Millennium Pharmaceuticals, Celgene and Amgen; NC has received research
funding from Millennium Pharmaceuticals; MB has received honoraria from
Pfizer, Spectrum Pharmaceuticals, Millennium Pharmaceuticals and
Cephalon; JLW has received honoraria from Millennium Pharmaceuticals,
Celgene and Ortho Biotech; CG has a consultancy/advisory relationship,
and has received honoraria and research funding from Millennium
Pharmaceuticals and Celgene; AK has stock/ownership interest in Celgene,
and has received honoraria from Millennium Pharmaceuticals and Celgene;
DG has a consultancy/advisory relationship with and has received
honoraria from Millennium Pharmaceuticals; EAS has a
consultancy/advisory relationship with Millennium Pharmaceuticals and
has received honoraria from Millennium Pharmaceuticals and Celgene; HS
and IJW are employees of Millennium Pharmaceuticals; PGR has a
consultancy/advisory role in Millennium Pharmaceuticals and Celgene and
has received research funding from Millennium Pharmaceuticals; JG and
SVR declare no conflict of interest.
NR 29
TC 46
Z9 50
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0887-6924
J9 LEUKEMIA
JI Leukemia
PD JUL
PY 2010
VL 24
IS 7
BP 1350
EP 1356
DI 10.1038/leu.2010.116
PG 7
WC Oncology; Hematology
SC Oncology; Hematology
GA 625KB
UT WOS:000279892900015
PM 20508619
ER
PT J
AU Weisberg, E
Deng, X
Choi, HG
Barrett, R
Adamia, S
Ray, A
Moreno, D
Kung, AL
Gray, N
Griffin, JD
AF Weisberg, E.
Deng, X.
Choi, H. G.
Barrett, R.
Adamia, S.
Ray, A.
Moreno, D.
Kung, A. L.
Gray, N.
Griffin, J. D.
TI Beneficial effects of combining a type II ATP competitive inhibitor with
an allosteric competitive inhibitor of BCR-ABL for the treatment of
imatinib-sensitive and imatinib-resistant CML
SO LEUKEMIA
LA English
DT Letter
ID KINASE; MUTANT
C1 [Weisberg, E.; Barrett, R.; Adamia, S.; Ray, A.; Griffin, J. D.] Dana Farber Canc Inst, Dept Med Oncol Hematol Neoplasia, Boston, MA 02115 USA.
[Deng, X.; Choi, H. G.; Gray, N.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Moreno, D.] Dana Farber Canc Inst, Anim Resources Facil, Boston, MA 02115 USA.
[Kung, A. L.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Kung, A. L.] Childrens Hosp, Boston, MA 02115 USA.
RP Weisberg, E (reprint author), Dana Farber Canc Inst, Dept Med Oncol Hematol Neoplasia, Boston, MA 02115 USA.
EM Ellen_Weisberg@dfci.harvard.edu; Nathanael_Gray@dfci.harvard.edu
OI Kung, Andrew/0000-0002-9091-488X
FU NCI NIH HHS [R01 CA130876, CA36167, CA66996, P01 CA066996, R01 CA036167,
R37 CA036167]; NIDDK NIH HHS [DK50654, P01 DK050654]
NR 8
TC 15
Z9 15
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 JUL
PY 2010
VL 24
IS 7
BP 1375
EP 1378
DI 10.1038/leu.2010.107
PG 5
WC Oncology; Hematology
SC Oncology; Hematology
GA 625KB
UT WOS:000279892900023
PM 20508612
ER
PT J
AU Abel, GA
Van Bennekom, CM
Stone, RM
Anderson, TE
Kaufman, DW
AF Abel, Gregory A.
Van Bennekom, Carla M.
Stone, Richard M.
Anderson, Theresa E.
Kaufman, David W.
TI Classification of the myelodysplastic syndrome in a national registry of
recently diagnosed patients
SO LEUKEMIA RESEARCH
LA English
DT Article
DE Myelodysplasia; Hematologic malignancy; Epidemiology; Health services
research
AB Background: It is not known to what extent the WHO classification scheme for MDS has been adopted in clinical practice.
Methods: We reviewed the medical records of 200 newly diagnosed MDS patients enrolled in our national registry during the years 2006-2008 to determine the scheme used.
Results: Clear WHO subtypes were recorded for 45.0% of patients, compared to 5.5% for FAB subtypes; 28.0% had MDS documented but without WHO or FAB subtype, and for 22.5%, the schema was unclear.
Conclusion: Although many MDS patients do not have a subtype or schema documented, when they do, the WHO system is widely used. (C) 2009 Elsevier Ltd. All rights reserved.
C1 [Abel, Gregory A.] Harvard Univ, Sch Med, Ctr Outcomes & Policy Res,Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Van Bennekom, Carla M.; Anderson, Theresa E.; Kaufman, David W.] Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA.
[Abel, Gregory A.; Stone, Richard M.] Harvard Univ, Sch Med, Div Hematol Oncol, Dept Med Oncol,Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Abel, GA (reprint author), Harvard Univ, Sch Med, Ctr Outcomes & Policy Res,Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,Smith 271, Boston, MA 02115 USA.
EM gregory_abel@dfci.harvard.edu
FU Celgene Corporation
FX The Patient Registries at Slone: MDS" is funded in part by a grant from
Celgene Corporation.
NR 8
TC 3
Z9 3
U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0145-2126
J9 LEUKEMIA RES
JI Leuk. Res.
PD JUL
PY 2010
VL 34
IS 7
BP 939
EP 941
DI 10.1016/j.leukres.2009.12.012
PG 3
WC Oncology; Hematology
SC Oncology; Hematology
GA 598KS
UT WOS:000277836300021
PM 20138359
ER
PT J
AU Shafaroodi, H
Ebrahimi, F
Moezi, L
Hashemi, M
Doostar, Y
Ghasemi, M
Dehpour, AR
AF Shafaroodi, Hamed
Ebrahimi, Farzad
Moezi, Leila
Hashemi, Mehrdad
Doostar, Yousef
Ghasemi, Mehdi
Dehpour, Ahmad Reza
TI Cholestasis induces apoptosis in mice cardiac cells: the possible role
of nitric oxide and oxidative stress
SO LIVER INTERNATIONAL
LA English
DT Article
DE apoptosis; cholestasis; heart; mice; nitric oxide; reactive oxygen
species
ID DUCT-LIGATED RATS; OBSTRUCTIVE-JAUNDICE; LIVER-DISEASE; HEPATOCYTE
APOPTOSIS; SUPEROXIDE-DISMUTASE; PORTOSYSTEMIC SHUNT; ENDOGENOUS
OPIOIDS; HEART-FAILURE; CIRRHOSIS; ACID
AB Background/Aims
Acute cholestasis is associated with cardiovascular complications. The purpose of the present study was to investigate the effect of cholestasis on heart apoptosis and the involvement of nitric oxide (NO) and oxidative stress in the possible altered apoptosis of cholestatic hearts.
Methods
Cholestasis was induced by bile duct-ligation, and sham-operated mice served as controls. Three days after the surgery, heart tissues were evaluated for apoptosis and the level of malondialdehyde (MDA), and the activities of catalase (CAT), glutathione peroxidase (GSHPx) and superoxide dismutase (SOD) have been studied in cardiac tissues. The role of treatment with l-NAME, a non-selective inhibitor of NO synthase, or with d-NAME, an inactive isomer of l-NAME, on cholestatic and sham cardiac apoptosis, level of MDA and CAT, SOD and GSHPx activities was also investigated. The content of NO in cardiac tissue was also determined.
Results
Cholestatic hearts showed structural abnormalities and increased apoptosis compared with sham hearts. Treatment with l-NAME, but not d-NAME, improved both structural abnormalities and enhanced apoptosis of cholestatic hearts. Cholestatic hearts also had an increased level of MDA and decreased activities of CAT and GSHPx, which were not modified by d-NAME treatment. By l-NAME treatment, the level of MDA decreased and activities of CAT, GSHPx and SOD increased in BDL mice. The content of NO was higher in cholestatic cardiac tissue, which was decreased by l-NAME treatment.
Conclusion
In conclusion, apoptosis in cholestatic heart might have occurred because of NO overproduction, which could induce oxidative stress in the heart of cholestatic mice.
C1 [Ghasemi, Mehdi; Dehpour, Ahmad Reza] Univ Tehran Med Sci, Sch Med, Dept Pharmacol, Tehran, Iran.
[Ghasemi, Mehdi] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA.
[Ghasemi, Mehdi] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA.
[Doostar, Yousef] Islamic Azad Univ, Tabriz Branch, Dept Pathol, Tabriz, Iran.
[Hashemi, Mehrdad] Islamic Azad Univ, Tehran Med Branch, Dept Mol Genet, Tabriz, Iran.
[Moezi, Leila] Shiraz Univ Med Sci, Sch Med, Dept Pharmacol, Shiraz, Iran.
[Ebrahimi, Farzad] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA USA.
[Shafaroodi, Hamed] Islamic Azad Univ, Pharmaceut Sci Branch, Dept Pharmacol & Toxicol, Tehran, Iran.
RP Dehpour, AR (reprint author), Univ Tehran Med Sci, Sch Med, Dept Pharmacol, POB 13145-784, Tehran, Iran.
EM dehpour@yahoo.com
RI moezi, leila/D-5127-2012;
OI Moezi, Leila/0000-0002-6990-9138; dehpour, ahmad
reza/0000-0002-8001-5565
NR 49
TC 13
Z9 13
U1 0
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1478-3223
J9 LIVER INT
JI Liver Int.
PD JUL
PY 2010
VL 30
IS 6
BP 898
EP 905
DI 10.1111/j.1478-3231.2010.02249.x
PG 8
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 604XM
UT WOS:000278311800017
PM 20492516
ER
PT J
AU Rathi, Y
Malcolm, JG
Michailovich, O
Westin, CF
Shenton, ME
Bouix, S
AF Rathi, Yogesh
Malcolm, James G.
Michailovich, Oleg
Westin, Carl-Fredrik
Shenton, Martha E.
Bouix, Sylvain
TI Tensor Kernels for Simultaneous Fiber Model Estimation and Tractography
SO MAGNETIC RESONANCE IN MEDICINE
LA English
DT Article
DE diffusion-weighted MRI; tractography; diffusion tensor estimation; high
order tensors; spherical harmonics
ID DIFFUSION-WEIGHTED MRI; SPHERICAL DECONVOLUTION; ORIENTATIONS;
RECONSTRUCTION; DECOMPOSITION; PROFILES; TRACKING
AB This paper proposes a novel framework for joint orientation distribution function estimation and tractography based on a new class of tensor kernels. Existing techniques estimate the local fiber orientation at each voxel independently so there is no running knowledge of confidence in the measured signal or estimated fiber orientation. In this work, fiber tracking is formulated as recursive estimation: at each step of tracing the fiber, the current estimate of the orientation distribution function is guided by the previous. To do this, second-and higher-order tensor-based kernels are employed. A weighted mixture of these tensor kernels is used for representing crossing and branching fiber structures. While tracing a fiber, the parameters of the mixture model are estimated based on the orientation distribution function at that location and a smoothness term that penalizes deviation from the previous estimate along the fiber direction. This ensures smooth estimation along the direction of propagation of the fiber.
In synthetic experiments, using a mixture of two and three components it is shown that this approach improves the angular resolution at crossings. In vivo experiments using two and three components examine the corpus callosum and corticospinal tract and confirm the ability to trace through regions known to contain such crossing and branching. Magn Reson Med 64:138-148, 2010. (C) 2009 Wiley-Liss, Inc.
C1 [Rathi, Yogesh; Malcolm, James G.; Shenton, Martha E.; Bouix, Sylvain] Harvard Univ, Brigham & Womens Hosp, Sch Med, Psychiat Neuroimaging Lab, Boston, MA 02215 USA.
[Michailovich, Oleg] Univ Waterloo, Dept Elect Engn, Waterloo, ON N2L 3G1, Canada.
[Westin, Carl-Fredrik] Harvard Univ, Brigham & Womens Hosp, Sch Med, Lab Math Imaging, Boston, MA 02215 USA.
[Shenton, Martha E.] VA Boston Healthcare Syst, Brockton Div, Brockton, MA USA.
RP Rathi, Y (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Psychiat Neuroimaging Lab, 1249 Boylston St, Boston, MA 02215 USA.
EM yogesh@bwh.harvard.edu
OI Bouix, Sylvain/0000-0003-1326-6054
FU NCRR NIH HHS [P41 RR013218, P41 RR013218-14]; NIBIB NIH HHS [U54
EB005149, U54 EB005149-07]; NIMH NIH HHS [R01 MH074794-05, R01 MH082918,
R01 MH074794, R01 MH050740-15, R01 MH050740]
NR 40
TC 3
Z9 3
U1 0
U2 1
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0740-3194
J9 MAGN RESON MED
JI Magn. Reson. Med.
PD JUL
PY 2010
VL 64
IS 1
BP 138
EP 148
DI 10.1002/mrm.22292
PG 11
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 617SL
UT WOS:000279301500017
PM 20572129
ER
PT J
AU Ross, JS
Maynard, C
Krumholz, HM
Sun, HL
Rumsfeld, JS
Normand, SLT
Wang, Y
Fihn, SD
AF Ross, Joseph S.
Maynard, Charles
Krumholz, Harlan M.
Sun, Haili
Rumsfeld, John S.
Normand, Sharon-Lise T.
Wang, Yun
Fihn, Stephan D.
TI Use of Administrative Claims Models to Assess 30-Day Mortality Among
Veterans Health Administration Hospitals
SO MEDICAL CARE
LA English
DT Article
DE acute myocardial infarction; heart failure; pneumonia; mortality; risk
adjustment; veterans
ID ACUTE MYOCARDIAL-INFARCTION; RISK ADJUSTMENT; CARE QUALITY; SYSTEM;
RATES
AB Background: The Centers for Medicare and Medicaid Services (CMS) publicly reports hospital-specific risk-standardized, 30-day, all-cause, mortality rates (RSMRs) for all hospitalizations among fee-for-service Medicare beneficiaries for acute myocardial infarction (AMI), heart failure (HF), and pneumonia at non-Federal hospitals.
Objective: To examine the performance of the statistical models used by CMS among veterans at least 65 years of age hospitalized for AMI, HF, and pneumonia in Veterans Health Administration (VHA) hospitals.
Research Design: Cross-sectional analysis of VHA administrative claims data between October 1, 2006 and September 30, 2009. Subjects: Thirteen thousand forty-six veterans hospitalized for AMI among 123 VHA hospitals; 26,379 veterans hospitalized for HF among 124 VHA hospitals; and 31,126 veterans hospitalized for pneumonia among 124 VHA hospitals.
Measures: Hospital-specific RSMR for AMI, HF, and pneumonia hospitalizations calculated using hierarchical generalized linear models.
Results: Median number of AMI hospitalizations per VHA hospital was 87. Average AMI RSMR was 14.3% [95% confidence interval (CI), 13.9%-14.6%] with modest heterogeneity among VHA hospitals (RSMR range: 8.4%-20.3%). The c-statistic for the AMI RSMR statistical model was 0.79. Median number of HF hospitalizations was 188. Average HF RSMR was 10.1% (95% CI, 9.9%-10.4%) with modest heterogeneity (RSMR range: 6.1%-14.9%). The c-statistic for the HF RSMR statistical model was 0.73. Median number of pneumonia hospitalizations was 221.5. Average pneumonia RSMR was 13.0% (95% CI, 12.7%-13.3%) with modest heterogeneity (RSMR range: 9.0%-18.4%). The c-statistic for the pneumonia RSMR statistical model was 0.72.
Conclusions: The statistical models used by CMS to estimate RSMRs for AMI, HF, and pneumonia hospitalizations at non-Federal hospitals demonstrate similar discrimination when applied to VHA hospitals.
C1 [Ross, Joseph S.] James J Peters Vet Adm Med Ctr, HSR&D Res Enhancement Award Program, Bronx, NY 10468 USA.
[Ross, Joseph S.] James J Peters Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Bronx, NY 10468 USA.
[Ross, Joseph S.] Mt Sinai Sch Med, Dept Geriatr & Palliat Med, New York, NY USA.
[Maynard, Charles; Sun, Haili; Fihn, Stephan D.] Puget Sound Hlth Care Syst, VA NW Hlth Serv Res & Dev Ctr Excellence, Seattle, WA USA.
[Krumholz, Harlan M.; Wang, Yun] Yale New Haven Med Ctr, Ctr Outcomes Res & Evaluat, New Haven, CT 06504 USA.
[Krumholz, Harlan M.] Yale Univ, Sch Med, Sect Cardiovasc Med, New Haven, CT USA.
[Krumholz, Harlan M.] Yale Univ, Sch Med, Dept Internal Med, Robert Wood Johnson Clin Scholars Program, New Haven, CT 06510 USA.
[Krumholz, Harlan M.] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, Div Hlth Policy & Adm, New Haven, CT 06510 USA.
[Rumsfeld, John S.] Denver VA Med Ctr, Denver, CO USA.
[Rumsfeld, John S.] Univ Colorado Hlth Sci Ctr, Dept Med, Div Cardiol, Denver, CO USA.
[Normand, Sharon-Lise T.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
[Normand, Sharon-Lise T.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Fihn, Stephan D.] Univ Washington, Dept Med, Seattle, WA USA.
RP Ross, JS (reprint author), James J Peters Vet Adm Med Ctr, HSR&D Res Enhancement Award Program, 130 W Kingsbridge Rd,Room 4A-17, Bronx, NY 10468 USA.
EM joseph.ross@mssm.edu
RI Maynard, Charles/N-3906-2015
OI Maynard, Charles/0000-0002-1644-7814
FU NIA NIH HHS [K08 AG032886-02, K08 AG032886]
NR 22
TC 11
Z9 11
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0025-7079
J9 MED CARE
JI Med. Care
PD JUL
PY 2010
VL 48
IS 7
BP 652
EP 658
DI 10.1097/MLR.0b013e3181dbe35d
PG 7
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 619KD
UT WOS:000279428200013
PM 20548253
ER
PT J
AU Solberg, LI
Asche, SE
Sepucha, K
Thygeson, NM
Madden, JE
Morrissey, L
Kraemer, KK
Anderson, LH
AF Solberg, Leif I.
Asche, Stephen E.
Sepucha, Karen
Thygeson, N. Marcus
Madden, Joan E.
Morrissey, Larry
Kraemer, Karen K.
Anderson, Louise H.
TI Informed Choice Assistance for Women Making Uterine Fibroid Treatment
Decisions: A Practical Clinical Trial
SO MEDICAL DECISION MAKING
LA English
DT Article
DE group decision making; obstetrics; gynecology; women's health; decision
aids
ID CARE; RISK
AB Background. There is limited evidence about how to ensure that patients are helped to make informed medical care decisions. Objective. To test a decision support intervention for uterine fibroid treatments. Design and Setting. Practical clinical trial to test informed choice assistance in 4 randomly assigned gynecology clinics compared to 5 others providing a pamphlet. Patients. Three hundred women facing a treatment decision for fibroids over a 13-month period. Intervention. Mailed DVD and brochure about fibroid treatments plus the Ottawa decision guide and an offer of counseling soon after an index visit. Measurements. Mailed survey 6 to 8 weeks later asking about knowledge, preferences, and satisfaction with decision support. Results. In total, 244 surveys were completed for an adjusted response rate of 85.4%. On a 5-point scale, intervention subjects reported more treatment options being mentioned (3.0 v. 2.4), had a higher knowledge score (3.3 v. 2.8), and were more likely to report being adequately informed (4.4 v. 4.0), and their decision was both more satisfactory (4.3 v. 4.0) and more consistent with their personal values (4.5 v. 4.2). Neither knowledge nor use of the intervention was associated with greater concordance between preferences and decisions. Limitations. Implementation of intervention may not have been well timed to the decision for some patients, limiting their use of the materials and counseling. Conclusion. It is difficult to integrate structured decision support consistently into practice. Decision support for benign uterine conditions showed effects on knowledge and satisfaction but not on concordance.
C1 [Solberg, Leif I.; Asche, Stephen E.; Thygeson, N. Marcus; Madden, Joan E.; Kraemer, Karen K.; Anderson, Louise H.] HealthPartners Res Fdn, Minneapolis, MN 55440 USA.
[Solberg, Leif I.; Asche, Stephen E.; Thygeson, N. Marcus; Madden, Joan E.; Kraemer, Karen K.; Anderson, Louise H.] HealthPartners, HealthPartners Med Grp, Minneapolis, MN USA.
[Sepucha, Karen] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Morrissey, Larry] Stillwater Med Grp, Stillwater, OK USA.
RP Solberg, LI (reprint author), HealthPartners Res Fdn, POB 1524,MS 21111R, Minneapolis, MN 55440 USA.
EM Leif.I.Solberg@healthpartners.com
FU Foundation for Informed Medical Decision Making (FIMDM)
FX Received 25 February 2009 from HealthPartners, HealthPartners Medical
Group, and HealthPartners Research Foundation, Minneapolis, Minnesota
(LIS, SEA, NMT, JEM, KKK, LHA); Massachusetts General Hospital, Boston
(KS); and Stillwater Medical Group, Stillwater, Minnesota (LM). Support
for this study was provided by the Foundation for Informed Medical
Decision Making (FIMDM). Revision accepted for publication 29 September
2009.
NR 13
TC 11
Z9 11
U1 0
U2 1
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0272-989X
J9 MED DECIS MAKING
JI Med. Decis. Mak.
PD JUL-AUG
PY 2010
VL 30
IS 4
BP 444
EP 452
DI 10.1177/0272989X09353947
PG 9
WC Health Care Sciences & Services; Medical Informatics
SC Health Care Sciences & Services; Medical Informatics
GA 625ZG
UT WOS:000279934800005
PM 19949063
ER
PT J
AU Sarfehnia, A
Clasie, B
Chung, E
Lu, HM
Flanz, J
Cascio, E
Engelsman, M
Paganetti, H
Seuntjens, J
AF Sarfehnia, A.
Clasie, B.
Chung, E.
Lu, H. M.
Flanz, J.
Cascio, E.
Engelsman, M.
Paganetti, H.
Seuntjens, J.
TI Direct absorbed dose to water determination based on water calorimetry
in scanning proton beam delivery
SO MEDICAL PHYSICS
LA English
DT Article
DE water calorimetry; primary standard; absolute dosimetry; double
scattering; spot scanning; proton radiation; absorbed dose
ID DOSIMETRY; THERAPY; RADIATION; PHOTON
AB Purpose: The aim of this manuscript is to describe the direct measurement of absolute absorbed dose to water in a scanned proton radiotherapy beam using a water calorimeter primary standard.
Methods: The McGill water calorimeter, which has been validated in photon and electron beams as well as in HDR (192)Ir brachytherapy, was used to measure the absorbed dose to water in double scattering and scanning proton irradiations. The measurements were made at the Massachusetts General Hospital proton radiotherapy facility. The correction factors in water calorimetry were numerically calculated and various parameters affecting their magnitude and uncertainty were studied. The absorbed dose to water was compared to that obtained using an Exradin T1 Chamber based on the IAEA TRS-398 protocol.
Results: The overall 1-sigma uncertainty on absorbed dose to water amounts to 0.4% and 0.6% in scattered and scanned proton water calorimetry, respectively. This compares to an overall uncertainty of 1.9% for currently accepted IAEA TRS-398 reference absorbed dose measurement protocol. The absorbed dose from water calorimetry agrees with the results from TRS-398 well to within 1-sigma uncertainty.
Conclusions: This work demonstrates that a primary absorbed dose standard based on water calorimetry is feasible in scattered and scanned proton beams. (c) 2010 American Association of Physicists in Medicine. [DOI: 10.1118/1.3427317]
C1 [Sarfehnia, A.; Chung, E.; Seuntjens, J.] McGill Univ, Med Phys Unit, Montreal, PQ H3G 1A4, Canada.
[Clasie, B.; Lu, H. M.; Flanz, J.; Cascio, E.; Engelsman, M.; Paganetti, H.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Clasie, B.; Lu, H. M.; Flanz, J.; Cascio, E.; Engelsman, M.; Paganetti, H.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Seuntjens, J (reprint author), McGill Univ, Med Phys Unit, Montreal, PQ H3G 1A4, Canada.
EM jseuntjens@medphys.mcgill.ca
FU Natural Sciences and Engineering Research Council of Canada [RG-PIN
298181]; CIHR
FX This work has been supported in part by Grant No. RG-PIN 298181 of the
Natural Sciences and Engineering Research Council of Canada. The
assistance of all BPTC technical staff is acknowledged. A.S. is a
recipient of a CIHR doctoral fellowship. The water calorimeter in this
work was constructed with the help of Robin Van Gils at McGill, while
the thermistors were built and provided by David Marchington of Ionizing
Radiation Standards division of National Research Council of Canada.
NR 22
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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 JUL
PY 2010
VL 37
IS 7
BP 3541
EP 3550
DI 10.1118/1.3427317
PG 10
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 624TV
UT WOS:000279845300007
PM 20831061
ER
PT J
AU Chan, HP
Wu, YT
Sahiner, B
Wei, J
Helvie, MA
Zhang, YH
Moore, RH
Kopans, DB
Hadjiiski, L
Way, T
AF Chan, Heang-Ping
Wu, Yi-Ta
Sahiner, Berkman
Wei, Jun
Helvie, Mark A.
Zhang, Yiheng
Moore, Richard H.
Kopans, Daniel B.
Hadjiiski, Lubomir
Way, Ted
TI Characterization of masses in digital breast tomosynthesis: Comparison
of machine learning in projection views and reconstructed slices
SO MEDICAL PHYSICS
LA English
DT Article
DE digital breast tomosynthesis; computer-aided diagnosis; mass; SART
ID COMPUTER-AIDED DIAGNOSIS; RADIOLOGISTS CHARACTERIZATION; MAMMOGRAPHIC
MASSES; SERIAL MAMMOGRAMS; CLASSIFICATION; IMPROVEMENT; PERFORMANCE;
FEATURES; IMAGES; ROC
AB Purpose: In digital breast tomosynthesis (DBT), quasi-three-dimensional (3D) structural information is reconstructed from a small number of 2D projection view (PV) mammograms acquired over a limited angular range. The authors developed preliminary computer-aided diagnosis (CADx) methods for classification of malignant and benign masses and compared the effectiveness of analyzing lesion characteristics in the reconstructed DBT slices and in the PVs.
Methods: A data set of MLO view DBT of 99 patients containing 107 masses (56 malignant and 51 benign) was collected at the Massachusetts General Hospital with IRB approval. The DBTs were obtained with a GE prototype system which acquired 11 PVs over a 50 arc. The authors reconstructed the DBTs at 1 mm slice interval using a simultaneous algebraic reconstruction technique. The region of interest (ROI) containing the mass was marked by a radiologist in the DBT volume and the corresponding ROIs on the PVs were derived based on the imaging geometry. The subsequent processes were fully automated. For classification of masses using the DBT-slice approach, the mass on each slice was segmented by an active contour model initialized with adaptive k-means clustering. A spiculation likelihood map was generated by analysis of the gradient directions around the mass margin and spiculation features were extracted from the map. The rubber band straightening transform (RBST) was applied to a band of pixels around the segmented mass boundary. The RBST image was enhanced by Sobel filtering in the horizontal and vertical directions, from which run-length statistics texture features were extracted. Morphological features including those from the normalized radial length were designed to describe the mass shape. A feature space composed of the spiculation features, texture features, and morphological features extracted from the central slice alone and seven feature spaces obtained by averaging the corresponding features from three to 19 slices centered at the central slice were compared. For classification of masses using the PV approach, a feature extraction process similar to that described above for the DBT approach was performed on the ROIs from the individual PVs. Six feature spaces obtained from the central PV alone and by averaging the corresponding features from three to 11 PVs were formed. In each feature space for either the DBT-slice or the PV approach, a linear discriminant analysis classifier with stepwise feature selection was trained and tested using a two-loop leave-one-case-out resampling procedure. Simplex optimization was used to guide feature selection automatically within the training set in each leave-one-case-out cycle. The performance of the classifiers was evaluated by the area (A(z)) under the receiver operating characteristic curve.
Results: The test Az values from the DBT-slice approach ranged from 0.87 +/- 0.03 to 0.93 +/- 0.02, while those from the PV approach ranged from 0.78 +/- 0.04 to 0.84 +/- 0.04. The highest test Az of 0.93 +/- 0.02 from the nine-DBT-slice feature space was significantly (p=0.006) better than the highest test Az of 0.84 +/- 0.04 from the nine-PV feature space.
Conclusion: The features of breast lesions extracted from the DBT slices consistently provided higher classification accuracy than those extracted from the PV images. (c) 2010 American Association of Physicists in Medicine. [DOI: 10.1118/1.3432570]
C1 [Chan, Heang-Ping; Wu, Yi-Ta; Sahiner, Berkman; Wei, Jun; Helvie, Mark A.; Zhang, Yiheng; Hadjiiski, Lubomir; Way, Ted] Univ Michigan, Dept Radiol, Ann Arbor, MI 48109 USA.
[Moore, Richard H.; Kopans, Daniel B.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
RP Chan, HP (reprint author), Univ Michigan, Dept Radiol, Ann Arbor, MI 48109 USA.
EM chanhp@umich.edu
FU USPHS [R33 CA120234, RO1 CA91713]; USAMRMC [DAMD17-98-1-8309]
FX This work is supported in part by USPHS Grant Nos. R33 CA120234 and RO1
CA91713 (PI: Paul Carson). The development of the prototype digital
breast tomosynthesis system and the collection of the DBT cases were
supported by a USAMRMC Grant No. DAMD17-98-1-8309 awarded to the MGH.
The content of this paper does not necessarily reflect the position of
the funding agencies and no official endorsement of any equipment and
product of any companies mentioned should be inferred. The authors are
grateful to Charles E. Metz, Ph.D., for the ROCKIT program provided on
the University of Chicago website
http://xray.bsd.uchicago.edu/krl/index.htm.
NR 32
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U2 6
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 JUL
PY 2010
VL 37
IS 7
BP 3576
EP 3586
DI 10.1118/1.3432570
PG 11
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 624TV
UT WOS:000279845300011
PM 20831065
ER
PT J
AU Li, XH
Zhang, D
Liu, B
AF Li, Xinhua
Zhang, Da
Liu, Bob
TI A generic geometric calibration method for tomographic imaging systems
with flat-panel detectors-A detailed implementation guide
SO MEDICAL PHYSICS
LA English
DT Article
DE geometric calibration; tomographic imaging; flat-panel detector
ID CONE-BEAM TOMOGRAPHY; COMPUTED-TOMOGRAPHY; CT; PARAMETERS; MISALIGNMENT;
ALIGNMENT
AB Purpose: To present a generic geometric calibration method for tomographic imaging systems with flat-panel detectors in a very detailed manner, in the aim to provide a useful tool to the public domain.
Methods: The method is based on a projection matrix which represents a mapping from 3D object coordinate system to 2D projection image plane. The projection matrix can be determined experimentally through the imaging of a phantom of known marker geometry. Accurate implementation was accomplished through direct computation algorithms, including a novel ellipse fitting using singular value decomposition and data normalization. Benefits of the method include: (1) It is capable of being applied to systems of different scan trajectories, source-detector alignments, and detector orientations; (2) projection matrices can be utilized in image reconstructions or in the extraction of explicit geometrical parameters; and (3) the method imposes minimal limits on the design of calibration phantom. C++ programs that calculate projection matrices and extract geometric parameters from them are also provided. For validation, the calibration method was applied to the computer simulation of a cone-beam CT system, as well as to three tomosynthesis prototypes of different source-detector movement patterns: Source and detector rotating synchronizedly; source rotating and detector wobbling; and source rotating and detector staying stationary.
Results: Projection matrices were computed on a view by view basis. Geometric parameters extracted from projection matrices were consistent with actual settings. Images were reconstructed by directly using projection matrices, and were compared to virtual Shepp-Logan image for CT simulation and to central projection images of CIRS breast phantoms for tomosynthesis prototypes. They showed no obvious distortion or blurring, indicating the high quality of geometric calibration results. When the computed central ray offsets were perturbed with Gaussian noises of 1 pixel standard deviation, the reconstructed image showed apparent distortion, which further demonstrated the accuracy of the geometric calibration method.
Conclusions: The method is suitable for tomographic imaging systems with flat-panel detectors. (C) 2010 American Association of Physicists in Medicine. [DOI: 10.1118/1.3431996]
C1 [Li, Xinhua; Zhang, Da; Liu, Bob] Massachusetts Gen Hosp, Dept Radiol, Div Diagnost Imaging Phys, Boston, MA 02114 USA.
RP Li, XH (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Diagnost Imaging Phys, Boston, MA 02114 USA.
EM bliu7@bics.bwh.harvard.edu
FU Enterprise Research IS group at Partners Healthcare
FX The authors would like to acknowledge Hologic Inc. and GE Medical
Systems for allowing the use of their prototype tomosynthesis systems
for experimental tests. The authors would also like to thank Dr. Mitchel
M. Goodsitt of the University of Michigan for insights on improving the
manuscript. This work used the High Performance Clusters of the Partners
Cooperation for computer simulation, and the authors would like to
acknowledge Dennis J. Gurgul and Jerry Xu of the Enterprise Research IS
group at Partners Healthcare for their in-depth support and for
provision of the HPC facilities.
NR 32
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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 JUL
PY 2010
VL 37
IS 7
BP 3844
EP 3854
DI 10.1118/1.3431996
PG 11
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 624TV
UT WOS:000279845300038
PM 20831092
ER
PT J
AU Soares, CN
Thase, ME
Clayton, A
Guico-Pabia, CJ
Focht, K
Jiang, Q
Kornstein, SG
Ninan, P
Kane, CP
Cohen, LS
AF Soares, Claudio N.
Thase, Michael E.
Clayton, Anita
Guico-Pabia, Christine J.
Focht, Kristen
Jiang, Qin
Kornstein, Susan G.
Ninan, Phil
Kane, Cecelia P.
Cohen, Lee S.
TI Desvenlafaxine and escitalopram for the treatment of postmenopausal
women with major depressive disorder
SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY
LA English
DT Article
DE Menopause; Depression; Escitalopram; Desvenlafaxine; Clinical trial
ID PLACEBO-CONTROLLED TRIAL; MENOPAUSAL TRANSITION; DOUBLE-BLIND;
INTEGRATED ANALYSIS; REUPTAKE INHIBITOR; CLINICAL-TRIAL; 100 MG/DAY;
EFFICACY; SEROTONIN; SAFETY
AB Objective: This study assessed the efficacy, safety, and tolerability of the serotonin-norepinephrine reuptake inhibitor desvenlafaxine and the selective serotonin reuptake inhibitor escitalopram for major depressive disorder (MDD) in postmenopausal women.
Methods: In this randomized, double-blind study, postmenopausal outpatients (aged 40-70 y) with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition MDD received flexible-dose desvenlafaxine (100-200 mg/d) or escitalopram (10-20 mg/d) for 8 weeks. Acute-phase responders, that is, women with a 50% or greater reduction from baseline in the 17-item Hamilton Rating Scale for Depression (HAM-D(17)) total score, were eligible to continue the same double-blind treatment in the 6-month continuation phase. The primary efficacy outcomes were mean change from baseline in HAM-D(17) total score (acute phase), analyzed using a mixed-effects model for repeated measures, and the proportion of women who maintained response (continuation phase), analyzed using logistic regression.
Results: Reductions in HAM-D(17) total score at acute-phase endpoint were similar for desvenlafaxine- and escitalopram-treated women (-13.6 vs -14.3, respectively; P = 0.24). No significant difference was observed between groups at continuation-phase endpoint in the proportion of women who maintained response (desvenlafaxine, 82%; escitalopram, 80%; P = 0.70). In both phases, desvenlafaxine and escitalopram were generally safe and well tolerated.
Conclusions: Among postmenopausal outpatients with MDD, there were no significant differences in the efficacy of desvenlafaxine and escitalopram based on primary efficacy analyses. The results do not support the overall hypothesis that the serotonin-norepinephrine reuptake inhibitor desvenlafaxine has an efficacy advantage for the treatment of MDD in postmenopausal women because, in this particular subgroup, desvenlafaxine failed to prove superiority over escitalopram. Safety and tolerability were comparable.
C1 [Soares, Claudio N.] McMaster Univ, Dept Psychiat & Behav Neurosci, Mood Disorders Div, Hamilton, ON L8P 3B6, Canada.
[Thase, Michael E.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
[Clayton, Anita] Univ Virginia, Charlottesville, VA USA.
[Guico-Pabia, Christine J.; Focht, Kristen; Jiang, Qin; Ninan, Phil; Kane, Cecelia P.] Pfizer Inc, Collegeville, PA USA.
[Kornstein, Susan G.] Virginia Commonwealth Univ, Richmond, VA USA.
[Cohen, Lee S.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Soares, CN (reprint author), McMaster Univ, Dept Psychiat & Behav Neurosci, Mood Disorders Div, 301 James St S,FB 638, Hamilton, ON L8P 3B6, Canada.
EM csoares@mcmaster.ca
OI Ninan, Philip/0000-0001-6633-1142
FU FRPC; Eli Lilly; AstraZeneca; Physicians Services Inc. (PSI) Foundation;
Allergen National Centre of Excellence; Hamilton Community Foundation;
Lundbeck; Wyeth; Canadian Institute of Health Research; National
Alliance for Research on Schizophrenia and Depression Foundation;
Guilford Press; GlaxoSmithKline; National Institute of Mental Health;
Sepracor Inc. Speakers bureau: AstraZeneca; BristolMyers Squibb Company;
Pfizer (formerly Wyeth Ayerst Pharmaceuticals); MedAvante, Inc; American
Psychiatric Publishing, Inc.; Guilford Publications; Herald House; W. W.
Norton & Company, Inc. Spouse's employment: Advogent (Formerly Cardinal
Health); BioSante Pharmaceuticals; Boehringer-Ingelheim; Brain Resource
Limited; Bristol-Myers Squibb; Novartis; Repligen Corporation;
Labopharm, Inc.; New England Research Institute; PGxHealth;
Sanofi-Aventis; Takeda; TransTech Pharma, Inc.; Ballantine Books/Random
House; Healthcare Technology Systems, Inc; Astra-Zeneca Pharmaceuticals;
Wyeth-Ayerst Pharmaceuticals; Sepracor, Inc.; Bayer HealthCare
Pharmaceuticals; Forest Laboratories, Inc.; National Institute on Aging;
National Institutes of Health
FX Claudio N. Soares, MD, PhD, FRPC-Grant/research support: Eli Lilly,
AstraZeneca, Physicians Services Inc. (PSI) Foundation, Allergen
National Centre of Excellence, Hamilton Community Foundation, Lundbeck,
Wyeth, Canadian Institute of Health Research, National Alliance for
Research on Schizophrenia and Depression Foundation. Research
consultant: Wyeth, Pfizer, Lundbeck, Bayer Healthcare Pharmaceuticals.
Speaker's bureau or advisory boards: AstraZeneca, Wyeth, Pfizer,
Lundbeck. Susan G. Kornstein, MD-Grants/research: Department of Health
and Human Services, National Institute of Mental Health, Bristol-Myers
Squibb Co., Pfizer Inc., Lilly Inc., Forest Laboratories Inc., Wyeth
Inc., Novartis Pharmaceuticals Inc., Sepracor Inc. Boehringer-Ingelheim,
Sanofi-Aventis, AstraZeneca, Takeda. Advisory boards: Wyeth, Pfizer
Inc., Lilly Inc., Forest Laboratories, Takeda, Biovail, Endo
Pharmaceuticals. Book royalties: Guilford Press. Michael E. Thase,
MD-Advisory/consultant: AstraZeneca, Bristol-Myers Squibb Company, Eli
Lilly & Co., Forest Laboratories, GlaxoSmithKline, MedAvante, Inc.,
Neuronetics, Inc., Novartis, Pfizer (formerly Wyeth Ayerst
Pharmaceuticals), Schering-Plough, Shire US Inc., Supernus
Pharmaceuticals, Takeda, Transcept Pharmaceuticals. Grants: Eli Lilly &
Co., GlaxoSmithKline, National Institute of Mental Health, Sepracor Inc.
Speakers bureau: AstraZeneca, BristolMyers Squibb Company, Eli Lilly &
Co., Pfizer (formerly Wyeth Ayerst Pharmaceuticals). Equity holding:
MedAvante, Inc. Royalties: American Psychiatric Publishing, Inc.,
Guilford Publications, Herald House, W. W. Norton & Company, Inc.
Spouse's employment: Advogent (Formerly Cardinal Health). Anita H.
Clayton, MD-Grants: BioSante Pharmaceuticals, Boehringer-Ingelheim,
Brain Resource Limited, Bristol-Myers Squibb, Novartis, Pfizer Inc.,
Repligen Corporation. Advisory board fee/consultant fee:
Boehringer-Ingelheim, Bristol-Myers Squibb, Eli Lilly and Company,
Labopharm, Inc., New England Research Institute, Pfizer, Inc.,
PGxHealth, Sanofi-Aventis, Takeda, TransTech Pharma, Inc., Wyeth.
Speaker's bureau/honorarium: Eli Lilly and Company. Royalties/copyright:
Ballantine Books/Random House, Guilford Publications, Healthcare
Technology Systems, Inc. US Provisional patent application, Compositions
and Methods for Diagnosing and Monitoring the Development of Tardive
Dyskinesia, Inventors: Atmaram Yarlagadda and Anita Clayton, Patent
Foundation University of Virginia. Lee S. Cohen, MD-Research support:
Astra-Zeneca Pharmaceuticals, GlaxoSmithKline, Wyeth-Ayerst
Pharmaceuticals, Sepracor, Inc., Bayer HealthCare Pharmaceuticals,
Bristol-Myers Squibb, Forest Laboratories, Inc., National Institute on
Aging, National Institutes of Health, National Institute of Mental
Health. Advisory/consulting: Eli Lilly and Company.
NR 47
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U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1072-3714
J9 MENOPAUSE
JI Menopause-J. N. Am. Menopause Soc.
PD JUL-AUG
PY 2010
VL 17
IS 4
BP 700
EP 711
DI 10.1097/gme.0b013e3181d88962
PG 12
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 624EO
UT WOS:000279799300010
PM 20539246
ER
PT J
AU Kornstein, SG
Young, EA
Harvey, AT
Wisniewski, SR
Barkin, JL
Thase, ME
Trivedi, MH
Nierenberg, AA
Rush, AJ
AF Kornstein, Susan G.
Young, Elizabeth A.
Harvey, Annie T.
Wisniewski, Stephen R.
Barkin, Jennifer L.
Thase, Michael E.
Trivedi, Madhukar H.
Nierenberg, Andrew A.
Rush, A. John
TI The influence of menopause status and postmenopausal use of hormone
therapy on presentation of major depression in women
SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY
LA English
DT Article
DE Menopause; Hormone therapy; Depression; Major depressive disorder
ID STAR-ASTERISK-D; DIAGNOSTIC SCREENING QUESTIONNAIRE; SEQUENCED TREATMENT
ALTERNATIVES; ESTROGEN REPLACEMENT THERAPY; NATIONAL COMORBIDITY SURVEY;
ILLNESS RATING-SCALE; REPORT QIDS-SR; GENDER-DIFFERENCES;
SEX-DIFFERENCES; CONTROLLED-TRIAL
AB Objective: The purpose of this study was to determine whether there are differences in depression characteristics among premenopausal, perimenopausal, and postmenopausal women with major depressive disorder. This study also evaluated these differences between postmenopausal women with major depressive disorder who are taking and not taking hormone therapy.
Methods: Analyses conducted with data from the Sequenced Treatment Alternatives to Relieve Depression study focused on female outpatients with nonpsychotic major depressive disorder seeking treatment in 41 primary or psychiatric care settings across the United States. Baseline demographic and clinical characteristics were compared among women not taking hormone therapy who were premenopausal (n = 950), perimenopausal (n = 380), or postmenopausal (n = 562). These comparisons were also made between postmenopausal women (n = 768) taking (n = 171) or not taking (n = 562) hormone therapy.
Results: After adjusting for sociodemographic and clinical baseline differences, premenopausal women were more likely to present with irritability than were either perimenopausal or postmenopausal women and were more likely to have decreased appetite and less likely to have early-morning insomnia than were perimenopausal women. Postmenopausal women were more likely to have suicidal ideation and poorer physical functioning than were either of the other groups and were more likely to have sympathetic arousal and gastrointestinal symptoms than were premenopausal women. After adjusting for baseline differences, postmenopausal women taking hormone therapy had better physical functioning, fewer melancholic features, less sympathetic arousal, and more lack of involvement in activities than did women not taking hormone therapy.
Conclusions: Menopause status and postmenopausal use of hormone therapy may influence the clinical presentation of major depressive episodes in women.
C1 [Kornstein, Susan G.] Virginia Commonwealth Univ, Sch Med, Dept Psychiat, Richmond, VA 23298 USA.
[Kornstein, Susan G.] Virginia Commonwealth Univ, Inst Womens Hlth, Richmond, VA 23298 USA.
[Young, Elizabeth A.] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA.
[Young, Elizabeth A.] Univ Michigan, Mol & Behav Neurosci Inst, Ann Arbor, MI 48109 USA.
[Harvey, Annie T.] Via Christi Reg Med Ctr, Wichita, KS USA.
[Wisniewski, Stephen R.] Univ Pittsburgh, GSPH, Epidemiol Data Ctr, Pittsburgh, PA USA.
[Barkin, Jennifer L.] Univ Pittsburgh, Western Psychiat Inst & Clin, Med Ctr, Pittsburgh, PA 15213 USA.
[Thase, Michael E.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA.
[Trivedi, Madhukar H.] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA.
[Nierenberg, Andrew A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Rush, A. John] Univ Texas SW Med Ctr Dallas, Dept Clin Sci & Psychiat, Dallas, TX 75390 USA.
[Rush, A. John] Duke Natl Univ Singapore, Singapore, Singapore.
RP Kornstein, SG (reprint author), Virginia Commonwealth Univ, Sch Med, Dept Psychiat, POB 980710, Richmond, VA 23298 USA.
EM skornste@vcu.edu
OI Wisniewski, Stephen/0000-0002-3877-9860; Rush,
Augustus/0000-0003-2004-2382
FU National Institute of Mental Health, National Institutes of Health
[N01MH90003]
FX Funding/support: This project has been funded with federal funds from
the National Institute of Mental Health, National Institutes of Health,
under contract N01MH90003 to University of Texas Southwestern Medical
Center at Dallas (principal investigator, A.J. Rush). The content of
this publication does not necessarily reflect the views or policies of
the Department of Health and Human Services, nor does mention of trade
names, commercial products, or organizations imply endorsement by the US
Government.
NR 55
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U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1072-3714
EI 1530-0374
J9 MENOPAUSE
JI Menopause-J. N. Am. Menopause Soc.
PD JUL-AUG
PY 2010
VL 17
IS 4
BP 828
EP 839
DI 10.1097/gme.0b013e3181d770a8
PG 12
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 624EO
UT WOS:000279799300028
PM 20616669
ER
PT J
AU Kramer, BJ
Finke, B
Saliba, D
Jouldjian, S
Yano, EM
AF Kramer, B. Josea
Finke, Bruce
Saliba, Debra
Jouldjian, Stella
Yano, Elizabeth M.
TI Fostering Closer Alignment of the Veterans Health Administration and the
Indian Health Service
SO MILITARY MEDICINE
LA English
DT Editorial Material
ID CARE
C1 [Kramer, B. Josea; Saliba, Debra; Jouldjian, Stella] VA Greater Los Angeles Healthcare Syst, Ctr Geriatr Res Educ & Clin, Sepulveda, CA 91343 USA.
[Kramer, B. Josea; Saliba, Debra] Univ Calif Los Angeles, David Geffen Sch Med, Div Geriatr, Los Angeles, CA 90095 USA.
[Finke, Bruce] Indian Hlth Serv, Nashville Area, Nashville, TN 37214 USA.
[Saliba, Debra; Yano, Elizabeth M.] VA Greater Los Angeles Healthcare Syst, Ctr Study Healthcare Provider Behav, Sepulveda, CA 91343 USA.
[Saliba, Debra] RAND Corp, Santa Monica, CA 90401 USA.
RP Kramer, BJ (reprint author), VA Greater Los Angeles Healthcare Syst, Ctr Geriatr Res Educ & Clin, 16111 Plummer St,11E, Sepulveda, CA 91343 USA.
NR 10
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U1 2
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PU ASSOC MILITARY SURG US
PI BETHESDA
PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA
SN 0026-4075
J9 MIL MED
JI Milit. Med.
PD JUL
PY 2010
VL 175
IS 7
BP 463
EP 465
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 624EN
UT WOS:000279799200002
PM 20684447
ER
PT J
AU Dickstein, BD
McLean, CP
Mintz, J
Conoscenti, LM
Steenkamp, MM
Benson, TA
Isler, WC
Peterson, AL
Litz, BT
AF Dickstein, Benjamin D.
McLean, Carmen P.
Mintz, Jim
Conoscenti, Lauren M.
Steenkamp, Maria M.
Benson, Trisha A.
Isler, William C.
Peterson, Alan L.
Litz, Brett T.
TI Unit Cohesion and PTSD Symptom Severity in Air Force Medical Personnel
SO MILITARY MEDICINE
LA English
DT Article
ID POSTTRAUMATIC-STRESS-DISORDER; HEALTH-CARE PROVIDERS; WAR-ZONE;
DEPLOYMENT; STRATEGIES; PREDICTORS; EXPOSURE; SUPPORT; TRAUMA; RISK
AB Research suggests that military unit cohesion may protect against the development of post-traumatic stress disorder (PTSD). However, equivocal findings have led researchers to hypothesize a potential curvilinear interaction between unit cohesion and warzone stress. This hypothesis states that the protective effects of cohesion increase as warzone stress exposure intensifies from low to moderate levels, but at high levels of warzone stress exposure, cohesion loses its protective effects and is potentially detrimental. To test this theory, we conducted a test for curvilinear moderation using a sample of 705 Air Force medical personnel deployed as part of Operation Iraqi Freedom. Results did not support the curvilinear interaction hypothesis, although evidence of cohesion's protective effects was found, suggesting that unit cohesion protects against PTSD regardless of level of stress exposure.
C1 [Dickstein, Benjamin D.; McLean, Carmen P.; Conoscenti, Lauren M.; Steenkamp, Maria M.; Litz, Brett T.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA.
[Dickstein, Benjamin D.; Steenkamp, Maria M.; Litz, Brett T.] Boston Univ, Dept Psychol, Boston, MA 02215 USA.
[Mintz, Jim; Benson, Trisha A.; Peterson, Alan L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA.
[Isler, William C.; Peterson, Alan L.] Wilford Hall USAF Med Ctr, Lackland AFB, TX 78236 USA.
RP Dickstein, BD (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, 150 S Huntington Ave, Boston, MA 02130 USA.
FU United States Air Force Surgeon General's Operational Medicine Research
Program [FA7014-07-C-0036]
FX This work was supported by theUnited States Air Force Surgeon General's
Operational Medicine Research Program (FA7014-07-C-0036).
NR 25
TC 21
Z9 21
U1 1
U2 4
PU ASSOC MILITARY SURG US
PI BETHESDA
PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA
SN 0026-4075
J9 MIL MED
JI Milit. Med.
PD JUL
PY 2010
VL 175
IS 7
BP 482
EP 486
PG 5
WC Medicine, General & Internal
SC General & Internal Medicine
GA 624EN
UT WOS:000279799200006
PM 20684451
ER
PT J
AU Adluri, RS
Zhan, LJ
Bagchi, M
Maulik, N
Maulik, G
AF Adluri, Ram Sudheer
Zhan, Lijun
Bagchi, Manashi
Maulik, Nilanjana
Maulik, Gautam
TI Comparative effects of a novel plant-based calcium supplement with two
common calcium salts on proliferation and mineralization in human
osteoblast cells
SO MOLECULAR AND CELLULAR BIOCHEMISTRY
LA English
DT Article
DE Calcium supplement; Osteoporosis; Mineralization; Proliferation;
Oxidative stress; DNA synthesis
ID BONE HEALTH; VEGETABLE CONSUMPTION; POSTMENOPAUSAL WOMEN; OXIDATIVE
STRESS; DIETARY BORON; VITAMIN-D; FRUIT; DENSITY; METABOLISM; SILICON
AB Calcium is an essential mineral to support bone health and serves as a major therapeutic intervention to prevent and delay the incidence of osteoporosis. Many individuals do not obtain the optimum amount of calcium from diets and depend on bioavailable calcium supplements. The present study was conducted to examine the effect of a novel plant-based calcium supplement, derived from marine algae, and contains high levels of calcium, magnesium, and other bone supporting minerals [commercially known as AlgaeCal (AC)], on proliferation, mineralization, and oxidative stress in cultured human osteoblast cells, and compared with inorganic calcium carbonate and calcium citrate salts. Cultured human fetal osteoblast cells (hFOB 1.19) were treated with AC (0.5 mg/ml, fixed by MTT assay), calcium carbonate, or calcium citrate. These cells were harvested after 4 days of treatment for ALP activity, PCNA expression, and DNA synthesis, and 2 days for Ca(2+) deposition in the presence and absence of vitamin D3 (5 nM). The ability of AC to reduce H(2)O(2) (0.3 mM)-induced oxidative stress was assessed after 24 h of treatment. ALP activity was significantly increased with AC treatment when compared to control, calcium carbonate, or calcium citrate (4.0-, 2.0-, and 2.5-fold, respectively). PCNA expression (immunocytochemical analysis), DNA synthesis (4.0-, 3.0-, and 4.0-fold, respectively), and Ca(2+) deposition (2.0-, 1.0-, and 4.0-fold, respectively) were significantly increased in AC-treated cells when compared with control, calcium carbonate, or calcium citrate treatment. These markers were further enhanced following additional supplementation of vitamin D3 in the AC-treated group cells. AC treatment significantly reduced the H(2)O(2)-induced oxidative stress when compared to calcium carbonate or calcium citrate (1.5- and 1.4-fold, respectively). These findings suggest that AC may serve as a superior calcium supplement as compared to other calcium salts tested in the present study. Hence, AC may be developed as a novel anti-osteoporotic supplement in the near future.
C1 [Maulik, Gautam] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Bagchi, Manashi] NutriToday, Boston, MA USA.
[Adluri, Ram Sudheer; Zhan, Lijun; Maulik, Nilanjana] Univ Connecticut, Ctr Hlth, Dept Surg, Mol Cardiol & Angiogenesis Lab, Farmington, CT USA.
RP Maulik, G (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St, Boston, MA 02115 USA.
EM Gautam_Maulik@dfci.harvard.edu
RI Shah, Mohd /E-4826-2010
FU M/s. AlgaeCal, Vancouver, Canada
FX This study was supported by M/s. AlgaeCal, Vancouver, Canada. We thank
T. Mahesh for his help in finalizing all the figures.
NR 36
TC 17
Z9 17
U1 1
U2 11
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0300-8177
J9 MOL CELL BIOCHEM
JI Mol. Cell. Biochem.
PD JUL
PY 2010
VL 340
IS 1-2
BP 73
EP 80
DI 10.1007/s11010-010-0402-0
PG 8
WC Cell Biology
SC Cell Biology
GA 610OJ
UT WOS:000278742300010
PM 20213262
ER
PT J
AU Namekawa, SH
Payer, B
Huynh, KD
Jaenisch, R
Lee, JT
AF Namekawa, Satoshi H.
Payer, Bernhard
Huynh, Khanh D.
Jaenisch, Rudolf
Lee, Jeannie T.
TI Two-Step Imprinted X Inactivation: Repeat versus Genic Silencing in the
Mouse
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID SEX-CHROMOSOME INACTIVATION; MARSUPIAL MONODELPHIS-DOMESTICA; HUMAN XIST
GENE; DOSAGE COMPENSATION; Y-CHROMOSOMES; MICE; EMBRYOS; RNA; MAMMALS;
CHROMATIN
AB Mammals compensate for unequal X-linked gene dosages between the sexes by inactivating one X chromosome in the female. In marsupials and in the early mouse embryo, X chromosome inactivation (XCI) is imprinted to occur selectively on the paternal X chromosome (X(P)). The mechanisms and events underlying X(P) imprinting remain unclear. Here, we find that the imprinted XP can be functionally divided into two domains, one comprising traditional coding genes (genic) and the other comprising intergenic repetitive elements. X(P) repetitive element silencing occurs by the two-cell stage, does not require Xist, and occurs several divisions prior to genic silencing. In contrast, genic silencing initiates at the morula-toblastocyst stage and absolutely requires Xist. Genes translocate into the presilenced repeat region as they are inactivated, whereas active genes remain outside. Thus, during the gamete-embryo transition, imprinted XCI occurs in two steps, with repeat silencing preceding genic inactivation. Nucleolar association may underlie the epigenetic asymmetry of X(P) and X(M). We hypothesize that transgenerational information (the imprint) is carried by repeats from the paternal germ line or that, alternatively, repetitive elements are silenced at the two-cell stage in a parent-of-origin-specific manner. Our model incorporates aspects of the so-called classical, de novo, and preinactivation hypotheses and suggests that Xist RNA functions relatively late during preimplantation mouse development.
C1 [Namekawa, Satoshi H.; Payer, Bernhard; Huynh, Khanh D.; Lee, Jeannie T.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Mol Biol,Massachusetts Gen Hosp,Dept Genet, Boston, MA 02115 USA.
[Jaenisch, Rudolf] MIT, Whitehead Inst Biomed Res, Boston, MA USA.
[Jaenisch, Rudolf] MIT, Dept Biol, Boston, MA USA.
RP Lee, JT (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Mol Biol,Massachusetts Gen Hosp,Dept Genet, Boston, MA 02115 USA.
EM lee@molbio.mgh.harvard.edu
RI Payer, Bernhard/F-7353-2010
OI Payer, Bernhard/0000-0002-4694-2082
FU Japan Society for the Promotion of Science (JSPS); Charles King Trust;
Human Frontier Science Program (HFSP); NIH [RO1-HDO45022, R37-CA084198,
RO1-GM58839]
FX S.H.N. is supported by research fellowships of the Japan Society for the
Promotion of Science (JSPS) and the Charles King Trust; B. P. by a
fellowship from the Human Frontier Science Program (HFSP); K. D. H. by
an NIH KO1 award; R.J. by NIH grants RO1-HDO45022 and R37-CA084198; and
J.T.L. by NIH RO1-GM58839. J.T.L. is an Investigator of the Howard
Hughes Medical Institute.
NR 67
TC 66
Z9 67
U1 0
U2 9
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 JUL 1
PY 2010
VL 30
IS 13
BP 3187
EP 3205
DI 10.1128/MCB.00227-10
PG 19
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 609AC
UT WOS:000278626100005
PM 20404085
ER
PT J
AU Wells, J
Rivera, MN
Kim, WJ
Starbuck, K
Haber, DA
AF Wells, Julie
Rivera, Miguel N.
Kim, Woo Jae
Starbuck, Kristen
Haber, Daniel A.
TI The Predominant WT1 Isoform ( plus KTS) Encodes a DNA-Binding Protein
Targeting the Planar Cell Polarity Gene Scribble in Renal Podocytes
SO MOLECULAR CANCER RESEARCH
LA English
DT Article
ID EWS-WT1 TRANSLOCATION PRODUCT; WILMS-TUMOR; FRASIER-SYNDROME; SUBNUCLEAR
LOCALIZATION; SPLICE ISOFORMS; FUSION PROTEIN; MIGRATION; RECEPTOR;
MOUSE; IDENTIFICATION
AB WT1 encodes a tumor suppressor first identified by its inactivation in Wilms' Tumor. Although one WT1 splicing variant encodes a well-characterized zinc finger transcription factor, little is known about the function of the most prevalent WT1 isoform, whose DNA binding domain is disrupted by a three-amino acid (KTS) insertion. Using cells that conditionally express WT1(+KTS), we undertook a genome-wide chromatin immunoprecipitation and cloning analysis to identify candidate WT1(+KTS)-regulated promoters. We identified the planar cell polarity gene Scribble (SCRB) as the first WT1(+KTS) target gene in podocytes of the kidney. WT1 and SCRB expression patterns overlap precisely in developing renal glomeruli of mice, and WT1(+KTS) binds to a 33-nucleotide region within the Scribble promoter in mouse and human cell lines and kidneys. Together, our results support a role for the predominant WT1(+KTS) isoform in transcriptional regulation and suggest a link between the WT1-dependent tumor suppressor pathway and a key component of the planar cell polarity pathway. Mol Cancer Res; 8(7); 975-85. (C) 2010 AACR.
C1 [Wells, Julie; Rivera, Miguel N.; Kim, Woo Jae; Starbuck, Kristen; Haber, Daniel A.] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA.
[Wells, Julie; Rivera, Miguel N.; Kim, Woo Jae; Starbuck, Kristen; Haber, Daniel A.] Harvard Univ, Sch Med, Charlestown, MA USA.
[Rivera, Miguel N.; Haber, Daniel A.] Howard Hughes Med Inst, Chevy Chase, MD USA.
RP Haber, DA (reprint author), Massachusetts Gen Hosp, Ctr Canc, Canc Ctr Bldg,149 13th St, Charlestown, MA 02129 USA.
EM DHaber@partners.org
FU NIH [R37CA58596, K08DK080175, T32CA009216]; Burroughs Wellcome Fund;
Howard Hughes Medical Institute; Massachusetts General Hospital;
Massachusetts Biomedical Research Corp.
FX NIH grants R37CA58596 (D.A. Haber), K08DK080175 (M.N. Rivera),
T32CA009216 (W.J. Kim); the Burroughs Wellcome Fund (M.N. Rivera), the
Howard Hughes Medical Institute, Massachusetts General Hospital (M.N.
Rivera), and a Tosteson postdoctoral fellowship from the Massachusetts
Biomedical Research Corp. (J. Wells).
NR 53
TC 13
Z9 13
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1541-7786
J9 MOL CANCER RES
JI Mol. Cancer Res.
PD JUL
PY 2010
VL 8
IS 7
BP 975
EP 985
DI 10.1158/1541-7786.MCR-10-0033
PG 11
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 625HH
UT WOS:000279885600004
PM 20571064
ER
PT J
AU Ahmad, R
Liu, SY
Weisberg, E
Nelson, E
Galinsky, I
Meyer, C
Kufe, D
Kharbanda, S
Stone, R
AF Ahmad, Rehan
Liu, Suiyang
Weisberg, Ellen
Nelson, Erik
Galinsky, Ilene
Meyer, Colin
Kufe, Donald
Kharbanda, Surender
Stone, Richard
TI Combining the FLT3 Inhibitor PKC412 and the Triterpenoid CDDO-Me
Synergistically Induces Apoptosis in Acute Myeloid Leukemia with the
Internal Tandem Duplication Mutation
SO MOLECULAR CANCER RESEARCH
LA English
DT Article
ID ACUTE MYELOGENOUS LEUKEMIA; NF-KAPPA-B; TYROSINE KINASE; ACTIVATING
MUTATION; SIGNAL TRANSDUCER; POOR-PROGNOSIS; HUMAN TUMORS; JAK-STAT;
CANCER; CELLS
AB Mutations of the FLT3 receptor tyrosine kinase consisting of internal tandem duplications (ITD) have been detected in blasts from 20% to 30% of patients with acute myeloid leukemia (AML) and are associated with a poor prognosis. FLT3/ITD results in constitutive autophosphorylation of the receptor and factor-independent survival in leukemia cell lines. The C-28 methyl ester of the oleane triterpenoid ( CDDO-Me) is a multifunctional molecule that induces apoptosis of human myeloid leukemia cells. Here, we report that CDDO-Me blocks targeting of NF kappa B to the nucleus by inhibiting I kappa B kinase beta-mediated phosphorylation of I kappa B alpha. Moreover, CDDO-Me blocked constitutive activation of the signal transducer and activator of transcription 3. We report the potent and selective antiproliferative effects of CDDO-Me on FLT3/ITD-positive myeloid leukemia cell lines and primary AML cells. The present studies show that CDDO-Me treatment results in caspase-3-mediated induction of apoptosis of FLT3/ITD-expressing cells and its antiproliferative effects are synergistic with PKC412, a FLT3-tyrosine kinase inhibitor currently in clinical trials. Taken together, our studies indicate that CDDO-Me greatly enhanced the efficacy of the FLT3 inhibitor PKC412, suggesting that combining two separate pathway inhibitors might be a viable therapeutic strategy for AML associated with a FLT3/ITD mutation. Mol Cancer Res; 8(7); 986-93. (C) 2010 AACR.
C1 [Ahmad, Rehan; Liu, Suiyang; Weisberg, Ellen; Nelson, Erik; Galinsky, Ilene; Kufe, Donald; Kharbanda, Surender; Stone, Richard] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Meyer, Colin] Reata Pharmaceut Inc, Dallas, TX USA.
RP Stone, R (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA.
EM rstone@partners.org
FU National Cancer Institute [PO1CA5PO1CA669]; Kristen Sesselman Amico Fund
FX National Cancer Institute (PO1CA5PO1CA669) and the Kristen Sesselman
Amico Fund.
NR 49
TC 14
Z9 14
U1 1
U2 4
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1541-7786
J9 MOL CANCER RES
JI Mol. Cancer Res.
PD JUL
PY 2010
VL 8
IS 7
BP 986
EP 993
DI 10.1158/1541-7786.MCR-10-0154
PG 8
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 625HH
UT WOS:000279885600005
PM 20571062
ER
PT J
AU Pilot-Storck, F
Chopin, E
Rual, JF
Baudot, A
Dobrokhotov, P
Robinson-Rechavi, M
Brun, C
Cusick, ME
Hill, DE
Schaeffer, L
Vidal, M
Goillot, E
AF Pilot-Storck, Fanny
Chopin, Emilie
Rual, Jean-Francois
Baudot, Anais
Dobrokhotov, Pavel
Robinson-Rechavi, Marc
Brun, Christine
Cusick, Michael E.
Hill, David E.
Schaeffer, Laurent
Vidal, Marc
Goillot, Evelyne
TI Interactome Mapping of the Phosphatidylinositol 3-Kinase-Mammalian
Target of Rapamycin Pathway Identifies Deformed Epidermal Autoregulatory
Factor-1 as a New Glycogen Synthase Kinase-3 Interactor
SO MOLECULAR & CELLULAR PROTEOMICS
LA English
DT Article
ID PROTEIN INTERACTION NETWORK; POSITRON-EMISSION-TOMOGRAPHY; RECEPTOR GENE
POLYMORPHISM; INSULIN ACTION; C-ELEGANS; PHOSPHOINOSITIDE 3-KINASE;
ALZHEIMERS-DISEASE; CELL-PROLIFERATION; CARBOXYPEPTIDASE-E; PREFRONTAL
CORTEX
AB The phosphatidylinositol 3-kinase-mammalian target of rapamycin (PI3K-mTOR) pathway plays pivotal roles in cell survival, growth, and proliferation downstream of growth factors. Its perturbations are associated with cancer progression, type 2 diabetes, and neurological disorders. To better understand the mechanisms of action and regulation of this pathway, we initiated a large scale yeast two-hybrid screen for 33 components of the PI3K-mTOR pathway. Identification of 67 new interactions was followed by validation by co-affinity purification and exhaustive literature curation of existing information. We provide a nearly complete, functionally annotated interactome of 802 interactions for the PI3K-mTOR pathway. Our screen revealed a predominant place for glycogen synthase kinase-3 (GSK3) A and B and the AMP-activated protein kinase. In particular, we identified the deformed epidermal autoregulatory factor-1 (DEAF1) transcription factor as an interactor and in vitro substrate of GSK3A and GSK3B. Moreover, GSK3 inhibitors increased DEAF1 transcriptional activity on the 5-HT1A serotonin receptor promoter. We propose that DEAF1 may represent a therapeutic target of lithium and other GSK3 inhibitors used in bipolar disease and depression. Molecular & Cellular Proteomics 9:1578-1593, 2010.
C1 [Pilot-Storck, Fanny; Chopin, Emilie; Schaeffer, Laurent; Goillot, Evelyne] Ecole Normale Super Lyon, Lab Biol Mol Cellule, UMR5239, F-69007 Lyon, France.
[Baudot, Anais] Spanish Natl Canc Res Ctr, E-28029 Madrid, Spain.
[Rual, Jean-Francois; Cusick, Michael E.; Hill, David E.; Vidal, Marc] Harvard Univ, Sch Med, Ctr Canc Syst Biol, Boston, MA 02115 USA.
[Rual, Jean-Francois; Cusick, Michael E.; Hill, David E.; Vidal, Marc] Harvard Univ, Sch Med, Dept Canc Biol, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Rual, Jean-Francois; Cusick, Michael E.; Hill, David E.; Vidal, Marc] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Dobrokhotov, Pavel; Robinson-Rechavi, Marc] Univ Lausanne, Dept Ecol & Evolut, CH-1015 Lausanne, Switzerland.
[Brun, Christine] Univ Aix Marseille 2, Technol Avancees Genome & Clin INSERM U928, F-13009 Marseille, France.
RP Goillot, E (reprint author), Ecole Normale Super Lyon, Lab Biol Mol Cellule, UMR5239, 46 Allee Italie, F-69007 Lyon, France.
EM evelyne.goillot@ens-lyon.fr
RI Robinson-Rechavi, Marc/E-9727-2011; Baudot, Anais/G-9963-2011; Hill,
David/B-6617-2011; Brun, Christine/B-4922-2008;
OI Robinson-Rechavi, Marc/0000-0002-3437-3329; Rual,
Jean-Francois/0000-0003-4465-8819; Baudot, Anais/0000-0003-0885-7933;
Brun, Christine/0000-0002-5563-6765; zaraat, javad/0000-0001-5341-7481
FU Association de Recherche sur le Cancer [3853]; Association Francaise
contre les Myopathies
FX This work was supported in part by Association de Recherche sur le
Cancer Grant 3853.; Supported by an Association Francaise contre les
Myopathies grant. Present address: UMR955 Inst. National de la Recherche
Agronomique, Ecole Nationale Veterinaire d'Alfort, 7 ave. du General de
Gaulle, F-94700 Maisons-Alfort, France.
NR 102
TC 23
Z9 24
U1 1
U2 5
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 1535-9476
J9 MOL CELL PROTEOMICS
JI Mol. Cell. Proteomics
PD JUL
PY 2010
VL 9
IS 7
BP 1578
EP 1593
DI 10.1074/mcp.M900568-MCP200
PG 16
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 619AC
UT WOS:000279397200017
PM 20368287
ER
PT J
AU Encinales, L
Zuniga, J
Granados-Montiel, J
Yunis, M
Granados, J
Almeciga, I
Clavijo, O
Awad, C
Collazos, V
Vargas-Rojas, MI
Banales-Mendez, JL
Vazquez-Castaneda, L
Stern, JN
Romero, V
Fridkis-Hareli, M
Terreros, D
Fernandez-Vina, M
Yunis, EJ
AF Encinales, Liliana
Zuniga, Joaquin
Granados-Montiel, Julio
Yunis, Maria
Granados, Julio
Almeciga, Ingrid
Clavijo, Olga
Awad, Carlos
Collazos, Vilma
Ines Vargas-Rojas, Maria
Luis Banales-Mendez, Jose
Vazquez-Castaneda, Lilia
Stern, Joel N.
Romero, Viviana
Fridkis-Hareli, Masha
Terreros, Daniel
Fernandez-Vina, Marcelo
Yunis, Edmond J.
TI Humoral immunity in tuberculin skin test anergy and its role in
high-risk persons exposed to active tuberculosis (vol 47, pg 1066, 2010)
SO MOLECULAR IMMUNOLOGY
LA English
DT Correction
C1 [Fernandez-Vina, Marcelo] Univ Texas MD Anderson Canc Ctr, Dept Lab Med, Houston, TX 77030 USA.
[Encinales, Liliana; Granados-Montiel, Julio; Almeciga, Ingrid; Clavijo, Olga; Stern, Joel N.; Romero, Viviana; Fridkis-Hareli, Masha; Yunis, Edmond J.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
[Zuniga, Joaquin; Ines Vargas-Rojas, Maria; Luis Banales-Mendez, Jose; Vazquez-Castaneda, Lilia] Inst Nacl Enfermedades Resp, Lab Immunobiol & Genet, Mexico City, DF, Mexico.
[Luis Banales-Mendez, Jose] Inst Nacl Cardiol Ignacio Chavez, Mol Biol Lab, Mexico City, DF, Mexico.
[Granados, Julio] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Immunol & Rheumatol, Mexico City, DF, Mexico.
[Terreros, Daniel] Paul L Foster SOM, Texas Tech Hlth Sci Ctr, Dept Biomed Sci, El Paso, TX 79905 USA.
[Fernandez-Vina, Marcelo] Univ Texas Houston, Sch Med, Div Immunol & Organ Transplantat, Houston, TX USA.
[Awad, Carlos] Hosp Santa Clara, Bogota, Colombia.
[Collazos, Vilma] Hosp Tebaida Armenia, Armenia, Colombia.
[Yunis, Maria] MyDesign, Arlington, MA USA.
RP Fernandez-Vina, M (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Lab Med, Houston, TX 77030 USA.
EM mfernand@mdanderson.org; edmond_yunis@dfci.harvard.edu
NR 1
TC 0
Z9 0
U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0161-5890
J9 MOL IMMUNOL
JI Mol. Immunol.
PD JUL
PY 2010
VL 47
IS 11-12
BP 2152
EP 2152
DI 10.1016/j.molimm.2010.04.001
PG 1
WC Biochemistry & Molecular Biology; Immunology
SC Biochemistry & Molecular Biology; Immunology
GA 621KY
UT WOS:000279578800025
ER
PT J
AU Wang, T
Yang, SH
Petrenko, VA
Torchilin, VP
AF Wang, Tao
Yang, Shenghong
Petrenko, Valery A.
Torchilin, Vladimir P.
TI Cytoplasmic Delivery of Liposomes into MCF-7 Breast Cancer Cells
Mediated by Cell-Specific Phage Fusion Coat Protein
SO MOLECULAR PHARMACEUTICS
LA English
DT Article
DE Drug delivery; liposome; cytoplasmic delivery; endosomal escape;
membrane fusion; phage display; landscape phage; Doxil; breast cancer
ID PH-SENSITIVE LIPOSOMES; GENE DELIVERY; AMPHIPATHIC PEPTIDE; CYTOSOLIC
DELIVERY; LONGEVITY; MECHANISM; PATHWAYS; DRUG
AB Earlier, we have shown that doxorubicin-loaded liposomes (Doxil) modified with a chimeric phage fusion coat protein specific toward MCF-7 breast cancer cells identified from a phage landscape library demonstrated a significantly enhanced association with target cells and an increased cytotoxicity. Based on some structural similarities between the N-terminus of the phage potein and known fusogenic peptides, we hypothesized that, in addition to the specific targeting, the phage protein may possess endosome-escaping potential and an increased cytotoxicity of drug-loaded phage protein-targeted liposomes may be explained by an advantageous combination of both, cell targeting and endosomal escape of drug-loaded nanocarrier. The use of the fluorescence resonance energy transfer (FRET) technique allowed us to clearly demonstrate the pH-dependent membrane fusion activity of the phage protein. Endosomal escape and cytosolic delivery of phage-liposomes was visualized with fluorescence microscopy. Endosome acidification inhibition by bafilomycin A 1 resulted in decreased cytotoxicity of the phage-Doxil, while the endosome disruption by chloroquine had a negligible effect on efficacy of phage-Doxil, confirming its endosomal escape. Our results demonstrated an endosome-escaping property of the phage protein and provided an insight on mechanism of the enhanced cytotoxicity of phage-Doxil.
C1 [Wang, Tao; Torchilin, Vladimir P.] Northeastern Univ, Ctr Pharmaceut Biotechnol & Nanomed, Boston, MA 02115 USA.
[Yang, Shenghong] Harvard Univ, Dept Radiat Oncol, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA.
[Petrenko, Valery A.] Auburn Univ, Dept Pathobiol, Coll Vet Med, Auburn, AL 36849 USA.
RP Torchilin, VP (reprint author), Northeastern Univ, Ctr Pharmaceut Biotechnol & Nanomed, 312 Mugar Life Sci Bldg,360 Huntington Ave, Boston, MA 02115 USA.
EM v.torchilin@neu.edu
FU NIH [1 R01 CA125063-01]; College of Veterinary Medicine Auburn
University [2006-9]
FX This work was supported by NIH Grant No. 1 R01 CA125063-01 and Animal
Health and Disease Research Grant 2006-9, College of Veterinary Medicine
Auburn University, to V.A.P.
NR 26
TC 33
Z9 34
U1 2
U2 14
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1543-8384
J9 MOL PHARMACEUT
JI Mol. Pharm.
PD JUL-AUG
PY 2010
VL 7
IS 4
BP 1149
EP 1158
DI 10.1021/mp1000229
PG 10
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA 632SM
UT WOS:000280448100024
PM 20438086
ER
PT J
AU Kramarenko, II
Bunni, MA
Raymond, JR
Garnovskaya, MN
AF Kramarenko, Inga I.
Bunni, Marlene A.
Raymond, John R.
Garnovskaya, Maria N.
TI Bradykinin B-2 Receptor Interacts with Integrin alpha 5 beta 1 to
Transactivate Epidermal Growth Factor Receptor in Kidney Cells
SO MOLECULAR PHARMACOLOGY
LA English
DT Article
ID MEDULLARY COLLECTING DUCT; PROTEIN-COUPLED RECEPTORS; FOCAL ADHESION
KINASE; SIGNAL-TRANSDUCTION; EGF RECEPTOR; TYROSINE KINASES; MATRIX;
ACTIVATION; MIGRATION; BINDING
AB We have shown previously that the vasoactive peptide bradykinin (BK) stimulates proliferation of a cultured murine cell model of the inner medullary collecting duct (mIMCD-3 cells) via transactivation of epidermal growth factor receptor (EGFR) by a mechanism that involves matrix metalloproteinases (collagenase- 2 and -3). Because collagenases lack an integral membrane domain, we hypothesized that receptors for extracellular matrix proteins, integrins, may play a role in BK-induced signaling by targeting collagenases to the membrane, thus forming a functional signaling complex. BK-induced phosphorylation of extracellular signal-regulated protein kinase (ERK) in mIMCD-3 cells was reduced by similar to 65% by synthetic peptides containing an Arg-Gly-Asp sequence, supporting roles for integrins in BK-induced signaling. Neutralizing antibody against alpha 5 beta 1 integrin partially (similar to 60%) blocked BK-induced ERK activation but did not affect EGF-induced ERK activation. Silencing of alpha 5 and beta 1 expression by transfecting cells with small interfering RNAs (siRNA) significantly decreased BK-induced ERK activation (similar to 80%) and EGFR phosphorylation (similar to 50%). This effect was even more pronounced in cells that were cotransfected with siRNAs directed against both collagenases and alpha 5 beta 1 integrin. On the basis of our results, we suggested that integrin alpha 5 beta 1 is involved in BK-induced signaling in mIMCD-3 cells. Using immunoprecipitation/Western blotting, we demonstrated association of BK B-2 receptor with alpha 5 beta 1 integrin upon BK treatment. Furthermore, BK induced association of alpha 5 beta 1 integrin with EGFR. These data provide the first evidence that specific integrins are involved in BK B-2 receptor-induced signaling in kidney cells, and ultimately might lead to development of new strategies for treatment of renal tubulointerstitial fibrosis.
C1 [Garnovskaya, Maria N.] Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA.
Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, Med Serv, Charleston, SC 29425 USA.
Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, Res Serv, Charleston, SC 29425 USA.
RP Garnovskaya, MN (reprint author), Med Univ S Carolina, Dept Med, Div Nephrol, 96 Jonathan Lucas St,MSC 629, Charleston, SC 29425 USA.
EM garnovsk@musc.edu
FU National Institutes of Health National Institute of Diabetes and
Digestive and Kidney Diseases [DK52448]; National Institutes of Health
National Institute of General Medical Sciences [GM3909]; Department of
Veterans Affairs Merit and Research Enhancement Award Program; American
Heart Association [0655445U]; Medical University of South Carolina
Division of Nephrology and Dialysis Clinics, Incorporated
FX This work was supported by the National Institutes of Health National
Institute of Diabetes and Digestive and Kidney Diseases [Grant DK52448],
the National Institutes of Health National Institute of General Medical
Sciences [Grant GM3909], the Department of Veterans Affairs Merit and
Research Enhancement Award Program ( to J.R.R. and M.N.G.), the American
Heart Association [Grant-in-Aid 0655445U], and a laboratory endowment
jointly supported by the Medical University of South Carolina Division
of Nephrology and Dialysis Clinics, Incorporated.
NR 35
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U1 0
U2 0
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 JUL
PY 2010
VL 78
IS 1
BP 126
EP 134
DI 10.1124/mol.110.064840
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 612XO
UT WOS:000278939300013
PM 20385709
ER
PT J
AU Ma'ayan, A
He, JC
AF Ma'ayan, Avi
He, John C.
TI Protein Kinase Target Discovery From Genome-Wide Messenger RNA
Expression Profiling
SO MOUNT SINAI JOURNAL OF MEDICINE
LA English
DT Article
DE cell signaling; ChIP-X enrichment analysis; computational systems
biology; mRNA profiling; promoter analysis; regulatory mechanisms;
transcription factors
ID NETWORKS; PROTEOMICS; CELLS
AB Genome-wide messenger RNA profiling provides a snapshot of the global state of the cell under different experimental conditions such as diseased versus normal cellular states. However, because measurements are in the form of quantitative changes in messenger RNA levels, such experimental data does not provide direct understanding of the regulatory molecular mechanisms responsible for the observed changes. Identifying potential cell signaling regulatory mechanisms responsible for changes in gene expression under different experimental conditions or in different tissues has been the focus of many computational systems biology studies. Most popular approaches include promoter analysis, gene ontology, or pathway enrichment analysis, as well as reverse engineering of networks from messenger RNA expression data. Here we present a rational approach for identifying and ranking protein kinases that are likely responsible for observed changes in gene expression. By combining promoter analysis; data from various chromatin immunoprecipitation studies such as chromatin immunoprecipitation sequencing, chromatin immunoprecipitation coupled with paired-end (Nag, and chromatin immunoprecipitation-on-chip; protein-protein interactions; and kinase-protein phosphorylation reactions collected from the literature, we can identify and rank candidate protein kinases for knock-down, or other types of functional validations, based on genome-wide changes in gene expression. We describe how protein kinase candidate identification and ranking can be made robust by cross-validation with phosphoproteomics data as well as through a literature-based text-mining approach. In conclusion, data integration can produce robust candidate rankings for understanding cell regulation through identification of protein kinases responsible for gene expression changes, and thus rapidly advancing drug target discovery and unraveling drug mechanisms of action. Mt Sinai J Med 77:345-349, 2010. (C) 2010 Mount Sinai School of Medicine
C1 [Ma'ayan, Avi; He, John C.] Mt Sinai Sch Med, Dept Pharmacol & Syst Therapeut, New York, NY 10029 USA.
[Ma'ayan, Avi] Mt Sinai Sch Med, Syst Biol Ctr New York, New York, NY USA.
[Ma'ayan, Avi] Mt Sinai Sch Med, Expt Therapeut Inst, New York, NY USA.
[He, John C.] Mt Sinai Sch Med, Dept Med, New York, NY USA.
[He, John C.] James J Peters VA Med Ctr, Bronx, NY USA.
RP Ma'ayan, A (reprint author), Mt Sinai Sch Med, Dept Pharmacol & Syst Therapeut, New York, NY 10029 USA.
EM avi.maayan@mssm.edu
FU NIH [R01-DK088541, R01-DK078897, P50-GM071558-01A27398]
FX The research presented is supported by NIH grants R01-DK088541 to JCH
and AM, R01-DK078897 to JCH, and P50-GM071558-01A27398 to AM.
NR 21
TC 3
Z9 3
U1 0
U2 1
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0027-2507
J9 MT SINAI J MED
JI Mt. Sinai J. Med.
PD JUL-AUG
PY 2010
VL 77
IS 4
BP 345
EP 349
DI 10.1002/msj.20192
PG 5
WC Medicine, General & Internal
SC General & Internal Medicine
GA 632MF
UT WOS:000280428100004
PM 20687179
ER
PT J
AU Healy, BC
Ikle, D
Macklin, EA
Cutter, G
AF Healy, Brian C.
Ikle, David
Macklin, Eric A.
Cutter, Gary
TI Optimal design and analysis of phase I/II clinical trials in multiple
sclerosis with gadolinium-enhanced lesions as the endpoint
SO MULTIPLE SCLEROSIS JOURNAL
LA English
DT Article
DE clinical trial design; disease modifying therapies; gadolinium-enhanced
lesions; MRI; multiple sclerosis; sample size calculation
ID MRI; MULTICENTER; COUNTS
AB Many phase I/II clinical trials in multiple sclerosis use gadolinium-enhanced lesions as the outcome measure. The best scanning interval and analysis for this outcome has not been determined. The objective of this study was to compare timing schemes and analysis techniques in terms of power for phase I/II clinical trials. Data were simulated under four scenarios assuming a negative binomial distribution for the number of new lesions and an exponential distribution for the duration of enhancement. The first scenario assumed an immediate treatment effect on the number of new lesions, while the second scenario assumed a delayed treatment effect. The third scenario assumed a higher proportion of patients had no new lesions, and the final scenario assumed an immediate treatment effect on the duration of enhancement. For each scenario, power for a six-month trial with 100 patients per arm was calculated using 10 analysis strategies. The scanning intervals tested were monthly scans, bimonthly scans and a single end-of-study scan. In addition, cost-effectiveness of each trial design and analysis was compared. Negative binomial regression models for the total number of new lesions were the most powerful analyses under an immediate treatment effect, and repeated measures models with a categorical time effect were the most powerful analyses under a delayed treatment effect. Although monthly scans generally provided most power, this design was also most costly. Designs with fewer scans per patient provide similar power and are more cost-effective. Negative binomial regression models are more powerful than non-parametric approaches.
C1 [Healy, Brian C.] Brigham & Womens Hosp, Partners MS Ctr, Brookline, MA USA.
[Healy, Brian C.; Macklin, Eric A.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA.
[Ikle, David] Rho Inc, Chapel Hill, NC USA.
[Cutter, Gary] Univ Alabama Birmingham, Dept Biostat, Birmingham, AL 35294 USA.
RP Healy, BC (reprint author), Harvard Univ, Sch Med, Partners MS Ctr, 1 Brookline Pl,Suite 602, Brookline, MA 02445 USA.
EM bchealy@partners.org
RI Macklin, Eric/E-2955-2013
OI Macklin, Eric/0000-0003-1618-3502
NR 11
TC 7
Z9 7
U1 0
U2 1
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1352-4585
J9 MULT SCLER J
JI Mult. Scler. J.
PD JUL
PY 2010
VL 16
IS 7
BP 840
EP 847
DI 10.1177/1352458510371409
PG 8
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 623GC
UT WOS:000279725800010
PM 20530124
ER
PT J
AU Ryberg, H
An, JY
Darko, S
Lustgarten, JL
Jaffa, M
Gopalakrishnan, V
Lacomis, D
Cudkowicz, M
Bowser, R
AF Ryberg, Henrik
An, Jiyan
Darko, Samuel
Lustgarten, Jonathan Llyle
Jaffa, Matt
Gopalakrishnan, Vanathi
Lacomis, David
Cudkowicz, Merit
Bowser, Robert
TI DISCOVERY AND VERIFICATION OF AMYOTROPHIC LATERAL SCLEROSIS BIOMARKERS
BY PROTEOMICS
SO MUSCLE & NERVE
LA English
DT Article
DE amyotrophic lateral sclerosis; biomarkers; cerebrospinal fluid; cystatin
C; mass spectrometry
ID C-REACTIVE PROTEIN; CEREBROSPINAL-FLUID; CYSTATIN-C; ALZHEIMERS-DISEASE;
MASS-SPECTROMETRY; PROSTATE-CANCER; TOF MS; IDENTIFICATION; SERUM; ALS
AB Recent studies using mass spectrometry have discovered candidate biomarkers for amyotrophic lateral sclerosis (ALS). However, those studies utilized small numbers of ALS and control subjects. Additional studies using larger subject cohorts are required to verify these candidate biomarkers. Cerebrospinal fluid (CSF) samples from 100 patients with ALS, 100 disease control, and 41 healthy control subjects were examined by mass spectrometry. Sixty-one mass spectral peaks exhibited altered levels between ALS and controls. Mass peaks for cystatin C and transthyretin were reduced in ALS, whereas mass peaks for posttranslational modified transthyretin and C-reactive protein (CRP) were increased. CRP levels were 5.84 +/- 1.01 ng/ml for controls and 11.24 +/- 1.52 ng/ml for ALS subjects, as determined by enzyme-linked immunoassay. This study verified prior mass spectrometry results for cystatin C and transthyretin in ALS. CRP levels were increased in the CSF of ALS patients, and cystatin C level correlated with survival in patients with limb-onset disease. Our biomarker panel predicted ALS with an overall accuracy of 82%. Muscle Nerve 42: 104-111, 2010
C1 [Ryberg, Henrik; An, Jiyan; Darko, Samuel; Bowser, Robert] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA 15261 USA.
[Lacomis, David] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA.
[Gopalakrishnan, Vanathi; Lacomis, David; Bowser, Robert] Univ Pittsburgh, Sch Med, Ctr ALS Res, Pittsburgh, PA 15261 USA.
[Lustgarten, Jonathan Llyle; Gopalakrishnan, Vanathi] Univ Pittsburgh, Dept Biomed Informat, Pittsburgh, PA 15261 USA.
[Jaffa, Matt; Cudkowicz, Merit] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurol Clin Trial Unit,Dept Neurol, Boston, MA USA.
RP Bowser, R (reprint author), Univ Pittsburgh, Sch Med, Dept Pathol, BST S-420,200 Lothrop St, Pittsburgh, PA 15261 USA.
EM Bowserrp@upmc.edu
OI Ryberg, Henrik/0000-0002-2652-6612
FU ALS Association; NIH [GM071951, ES013469, NS061867]
FX This study was supported by funding from the ALS Association (to R.B.
and MC.), NIH Grants GM071951 (to VG.) and ES013469 and NS061867 (to
R.B.). The authors thank Fran Lutka, Darlene Pulley, Pat Butsch, and
Allitia Dibernardo for assistance with CSF sample collection and
storage, and Philip Ganchev for assistance in mass spectrometry data
analysis. We also thank Michael Irizarry for providing CSF samples from
Alzheimer's disease patients.
NR 40
TC 46
Z9 47
U1 0
U2 6
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0148-639X
J9 MUSCLE NERVE
JI Muscle Nerve
PD JUL
PY 2010
VL 42
IS 1
BP 104
EP 111
DI 10.1002/mus.21683
PG 8
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 619US
UT WOS:000279456400013
PM 20583124
ER
PT J
AU Aghajan, M
Jonai, N
Flick, K
Fu, F
Luo, ML
Cai, XL
Ouni, I
Pierce, N
Tang, XB
Lomenick, B
Damoiseaux, R
Hao, R
del Moral, PM
Verma, R
Li, Y
Li, C
Houk, KN
Jung, ME
Zheng, N
Huang, L
Deshaies, RJ
Kaiser, P
Huang, J
AF Aghajan, Mariam
Jonai, Nao
Flick, Karin
Fu, Fei
Luo, Manlin
Cai, Xiaolu
Ouni, Ikram
Pierce, Nathan
Tang, Xiaobo
Lomenick, Brett
Damoiseaux, Robert
Hao, Rui
del Moral, Pierre M.
Verma, Rati
Li, Ying
Li, Cheng
Houk, Kendall N.
Jung, Michael E.
Zheng, Ning
Huang, Lan
Deshaies, Raymond J.
Kaiser, Peter
Huang, Jing
TI Chemical genetics screen for enhancers of rapamycin identifies a
specific inhibitor of an SCF family E3 ubiquitin ligase
SO NATURE BIOTECHNOLOGY
LA English
DT Article
ID IN-VIVO; SACCHAROMYCES-CEREVISIAE; QUANTITATIVE-ANALYSIS; SIGNALING
NETWORK; MASS-SPECTROMETRY; CANCER-THERAPY; MTOR; COMPLEX; TARGET;
GROWTH
AB The target of rapamycin (TOR) plays a central role in eukaryotic cell growth control(1). With prevalent hyperactivation of the mammalian TOR (mTOR) pathway in human cancers(2), strategies to enhance TOR pathway inhibition are needed. We used a yeast-based screen to identify small-molecule enhancers of rapamycin (SMERs) and discovered an inhibitor (SMER3) of the Skp1-Cullin-F-box (SCF)(Met30) ubiquitin ligase, a member of the SCF E3-ligase family, which regulates diverse cellular processes including transcription, cell-cycle control and immune response(3). We show here that SMER3 inhibits SCF(Met30) in vivo and in vitro, but not the closely related SCF(Cdc4). Furthermore, we demonstrate that SMER3 diminishes binding of the F-box subunit Met30 to the SCF core complex in vivo and show evidence for SMER3 directly binding to Met30. Our results show that there is no fundamental barrier to obtaining specific inhibitors to modulate function of individual SCF complexes.
C1 [Aghajan, Mariam; Jonai, Nao; Fu, Fei; Lomenick, Brett; Hao, Rui; Huang, Jing] Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA.
[Aghajan, Mariam; Jonai, Nao; Fu, Fei; Lomenick, Brett; Hao, Rui; Huang, Jing] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90024 USA.
[Flick, Karin; Ouni, Ikram; Kaiser, Peter] Univ Calif Irvine, Dept Biol Chem, Sch Med, Irvine, CA 92717 USA.
[Luo, Manlin] MIT, Dept Biol Engn, Cambridge, MA 02139 USA.
[Cai, Xiaolu; Li, Ying; Houk, Kendall N.; Jung, Michael E.] Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90024 USA.
[Pierce, Nathan; Verma, Rati; Deshaies, Raymond J.] CALTECH, Howard Hughes Med Inst, Dept Biol, Pasadena, CA 91125 USA.
[Tang, Xiaobo; Zheng, Ning] Univ Washington, Howard Hughes Med Inst, Dept Pharmacol, Seattle, WA 98195 USA.
[del Moral, Pierre M.] Roche Diagnost Corp, Roche Appl Sci, Indianapolis, IN USA.
[Li, Cheng] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Huang, Lan] Univ Calif Irvine, Dept Physiol & Biophys, Irvine, CA 92717 USA.
[Huang, Lan] Univ Calif Irvine, Dept Dev & Cell Biol, Irvine, CA 92717 USA.
RP Huang, J (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA.
EM pkaiser@uci.edu; jinghuang@mednet.ucla.edu
RI Lomenick, Brett/E-7291-2010; hao, rui/E-4965-2011; Huang,
Lan/C-3618-2011; Damoiseaux, Robert/F-1086-2011; Liu, Peng/D-1233-2013;
Hao, Rui/I-5162-2013; Deshaies, Raymond/B-8354-2014
OI Damoiseaux, Robert/0000-0002-7611-7534; Deshaies,
Raymond/0000-0002-3671-9354
FU American Cancer Society; U.S. National Institutes of Health; NIH UCLA
Chemistry-Biology Interface Predoctoral Training Program; Roche
Diagnostics Corporation
FX We are grateful for grant support from the American Cancer Society and
the U.S. National Institutes of Health and for traineeship support of M.
A. and B. L. by the NIH UCLA Chemistry-Biology Interface Predoctoral
Training Program. N.Z. and R.J.D. are investigators of the Howard Hughes
Medical Institute. We thank D. Skowyra (Saint Louis University) and M.
Tyers (University of Edinburgh, UK) for their generous gifts of bacculo
virus constructs and anti-Met4 antibody, respectively. We also thank J.
Salcedo (Roche Diagnostics Corporation) for support toward differential
scanning fluorimetry experiments.
NR 40
TC 76
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U1 2
U2 23
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1087-0156
J9 NAT BIOTECHNOL
JI Nat. Biotechnol.
PD JUL
PY 2010
VL 28
IS 7
BP 738
EP U1750
DI 10.1038/nbt.1645
PG 7
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA 623FL
UT WOS:000279723900032
PM 20581845
ER
PT J
AU Raychaudhuri, S
Ripke, S
Li, MY
Neale, BM
Fagerness, J
Reynolds, R
Sobrin, L
Swaroop, A
Abecasis, G
Seddon, JM
Daly, MJ
AF Raychaudhuri, Soumya
Ripke, Stephan
Li, Mingyao
Neale, Benjamin M.
Fagerness, Jesen
Reynolds, Robyn
Sobrin, Lucia
Swaroop, Anand
Abecasis, Goncalo
Seddon, Johanna M.
Daly, Mark J.
TI Associations of CFHR1-CFHR3 deletion and a CFH snp to age-related
macular degeneration are not independent
SO NATURE GENETICS
LA English
DT Letter
ID GENES; POLYMORPHISM; HAPLOTYPES; VARIANT; FAMILY; RISK
C1 [Raychaudhuri, Soumya] Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA.
[Raychaudhuri, Soumya; Ripke, Stephan; Neale, Benjamin M.; Fagerness, Jesen; Daly, Mark J.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Raychaudhuri, Soumya; Ripke, Stephan; Neale, Benjamin M.; Fagerness, Jesen; Daly, Mark J.] Harvard Univ, Broad Inst, Cambridge, MA 02138 USA.
[Raychaudhuri, Soumya; Ripke, Stephan; Neale, Benjamin M.; Fagerness, Jesen; Daly, Mark J.] MIT, Cambridge, MA 02139 USA.
[Li, Mingyao] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
[Neale, Benjamin M.] Kings Coll London, Inst Psychiat, Social Genet & Dev Psychiat Ctr, London WC2R 2LS, England.
[Reynolds, Robyn; Seddon, Johanna M.] Tufts Med Ctr, New England Eye Ctr, Ophthalm Epidemiol & Genet Serv, Boston, MA USA.
[Sobrin, Lucia] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA.
[Sobrin, Lucia] Harvard Univ, Sch Med, Boston, MA USA.
[Swaroop, Anand] NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA.
[Abecasis, Goncalo] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.
[Seddon, Johanna M.] Tufts Med Ctr, Dept Ophthalmol, Boston, MA USA.
RP Raychaudhuri, S (reprint author), Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, 75 Francis St, Boston, MA 02115 USA.
EM soumya@broad.mit.edu; jseddon@tuftsmedicalcenter.org;
mjdaly@chgr.mgh.harvard.edu
RI Abecasis, Goncalo/B-7840-2010;
OI Abecasis, Goncalo/0000-0003-1509-1825; Swaroop,
Anand/0000-0002-1975-1141
FU Intramural NIH HHS; NEI NIH HHS [R01 EY011309, K12 EY016335,
K12-EY16335, R01-EY11309]; NHGRI NIH HHS [R01 HG004517, R01-HG004517];
NHLBI NIH HHS [R01 HL087676, R01HL087676]; NIAMS NIH HHS [K08 AR055688,
K08 AR055688-03, K08 AR055688-04, K08AR055688-01A1]; NIMH NIH HHS [U01
MH085520, U01 MH085520-01]
NR 10
TC 29
Z9 29
U1 0
U2 5
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 JUL
PY 2010
VL 42
IS 7
BP 553
EP 555
DI 10.1038/ng0710-553
PG 3
WC Genetics & Heredity
SC Genetics & Heredity
GA 616WO
UT WOS:000279242400002
PM 20581873
ER
PT J
AU Voight, BF
Scott, LJ
Steinthorsdottir, V
Morris, AP
Dina, C
Welch, RP
Zeggini, E
Huth, C
Aulchenko, YS
Thorleifsson, G
McCulloch, LJ
Ferreira, T
Grallert, H
Amin, N
Wu, GM
Willer, CJ
Raychaudhuri, S
McCarroll, SA
Langenberg, C
Hofmann, OM
Dupuis, J
Qi, L
Segre, AV
van Hoek, M
Navarro, P
Ardlie, K
Balkau, B
Benediktsson, R
Bennett, AJ
Blagieva, R
Boerwinkle, E
Bonnycastle, LL
Bostrom, KB
Bravenboer, B
Bumpstead, S
Burtt, NP
Charpentier, G
Chines, PS
Cornelis, M
Couper, DJ
Crawford, G
Doney, ASF
Elliott, KS
Elliott, AL
Erdos, MR
Fox, CS
Franklin, CS
Ganser, M
Gieger, C
Grarup, N
Green, T
Griffin, S
Groves, CJ
Guiducci, C
Hadjadj, S
Hassanali, N
Herder, C
Isomaa, B
Jackson, AU
Johnson, PRV
Jorgensen, T
Kao, WHL
Klopp, N
Kong, A
Kraft, P
Kuusisto, J
Lauritzen, T
Li, M
Lieverse, A
Lindgren, CM
Lyssenko, V
Marre, M
Meitinger, T
Midthjell, K
Morken, MA
Narisu, N
Nilsson, P
Owen, KR
Payne, F
Perry, JRB
Petersen, AK
Platou, C
Proenca, C
Prokopenko, I
Rathmann, W
Rayner, NW
Robertson, NR
Rocheleau, G
Roden, M
Sampson, MJ
Saxena, R
Shields, BM
Shrader, P
Sigurdsson, G
Sparso, T
Strassburger, K
Stringham, HM
Sun, Q
Swift, AJ
Thorand, B
Tichet, J
Tuomi, T
van Dam, RM
van Haeften, TW
van Herpt, T
van Vliet-Ostaptchouk, JV
Walters, GB
Weedon, MN
Wijmenga, C
Witteman, J
Bergman, RN
Cauchi, S
Collins, FS
Gloyn, AL
Gyllensten, U
Hansen, T
Hide, WA
Hitman, GA
Hofman, A
Hunter, DJ
Hveem, K
Laakso, M
Mohlke, KL
Morris, AD
Palmer, CNA
Pramstaller, PP
Rudan, I
Sijbrands, E
Stein, LD
Jaakko, T
Uitterlinden, A
Walker, M
Wareham, NJ
Watanabe, RM
Abecasis, GR
Boehm, BO
Campbell, H
Daly, MJ
Hattersley, AT
Hu, FB
Meigs, JB
Pankow, JS
Pedersen, O
Wichmann, HE
Barroso, I
Florez, JC
Frayling, TM
Groop, L
Sladek, R
Thorsteinsdottir, U
Wilson, JF
Illig, T
Froguel, P
van Duijn, CM
Stefansson, K
Altshuler, D
Boehnke, M
McCarthy, MI
AF Voight, Benjamin F.
Scott, Laura J.
Steinthorsdottir, Valgerdur
Morris, Andrew P.
Dina, Christian
Welch, Ryan P.
Zeggini, Eleftheria
Huth, Cornelia
Aulchenko, Yurii S.
Thorleifsson, Gudmar
McCulloch, Laura J.
Ferreira, Teresa
Grallert, Harald
Amin, Najaf
Wu, Guanming
Willer, Cristen J.
Raychaudhuri, Soumya
McCarroll, Steve A.
Langenberg, Claudia
Hofmann, Oliver M.
Dupuis, Josee
Qi, Lu
Segre, Ayellet V.
van Hoek, Mandy
Navarro, Pau
Ardlie, Kristin
Balkau, Beverley
Benediktsson, Rafn
Bennett, Amanda J.
Blagieva, Roza
Boerwinkle, Eric
Bonnycastle, Lori L.
Bostrom, Kristina Bengtsson
Bravenboer, Bert
Bumpstead, Suzannah
Burtt, Noisel P.
Charpentier, Guillaume
Chines, Peter S.
Cornelis, Marilyn
Couper, David J.
Crawford, Gabe
Doney, Alex S. F.
Elliott, Katherine S.
Elliott, Amanda L.
Erdos, Michael R.
Fox, Caroline S.
Franklin, Christopher S.
Ganser, Martha
Gieger, Christian
Grarup, Niels
Green, Todd
Griffin, Simon
Groves, Christopher J.
Guiducci, Candace
Hadjadj, Samy
Hassanali, Neelam
Herder, Christian
Isomaa, Bo
Jackson, Anne U.
Johnson, Paul R. V.
Jorgensen, Torben
Kao, Wen H. L.
Klopp, Norman
Kong, Augustine
Kraft, Peter
Kuusisto, Johanna
Lauritzen, Torsten
Li, Man
Lieverse, Aloysius
Lindgren, Cecilia M.
Lyssenko, Valeriya
Marre, Michel
Meitinger, Thomas
Midthjell, Kristian
Morken, Mario A.
Narisu, Narisu
Nilsson, Peter
Owen, Katharine R.
Payne, Felicity
Perry, John R. B.
Petersen, Ann-Kristin
Platou, Carl
Proenca, Christine
Prokopenko, Inga
Rathmann, Wolfgang
Rayner, N. William
Robertson, Neil R.
Rocheleau, Ghislain
Roden, Michael
Sampson, Michael J.
Saxena, Richa
Shields, Beverley M.
Shrader, Peter
Sigurdsson, Gunnar
Sparso, Thomas
Strassburger, Klaus
Stringham, Heather M.
Sun, Qi
Swift, Amy J.
Thorand, Barbara
Tichet, Jean
Tuomi, Tiinamaija
van Dam, Rob M.
van Haeften, Timon W.
van Herpt, Thijs
van Vliet-Ostaptchouk, Jana V.
Walters, G. Bragi
Weedon, Michael N.
Wijmenga, Cisca
Witteman, Jacqueline
Bergman, Richard N.
Cauchi, Stephane
Collins, Francis S.
Gloyn, Anna L.
Gyllensten, Ulf
Hansen, Torben
Hide, Winston A.
Hitman, Graham A.
Hofman, Albert
Hunter, David J.
Hveem, Kristian
Laakso, Markku
Mohlke, Karen L.
Morris, Andrew D.
Palmer, Colin N. A.
Pramstaller, Peter P.
Rudan, Igor
Sijbrands, Eric
Stein, Lincoln D.
Tuomilehto, Jaakko
Uitterlinden, Andre
Walker, Mark
Wareham, Nicholas J.
Watanabe, Richard M.
Abecasis, Goncalo R.
Boehm, Bernhard O.
Campbell, Harry
Daly, Mark J.
Hattersley, Andrew T.
Hu, Frank B.
Meigs, James B.
Pankow, James S.
Pedersen, Oluf
Wichmann, H-Erich
Barroso, Ines
Florez, Jose C.
Frayling, Timothy M.
Groop, Leif
Sladek, Rob
Thorsteinsdottir, Unnur
Wilson, James F.
Illig, Thomas
Froguel, Philippe
van Duijn, Cornelia M.
Stefansson, Kari
Altshuler, David
Boehnke, Michael
McCarthy, Mark I.
CA MAGIC Investigators
GIANT Consortium
TI Twelve type 2 diabetes susceptibility loci identified through
large-scale association analysis
SO NATURE GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; C-REACTIVE PROTEIN; FASTING PLASMA-GLUCOSE; QT
INTERVAL DURATION; INSULIN-RESISTANCE; COMMON VARIANTS; COMPLEX
DISEASES; GENE-EXPRESSION; HNF1-ALPHA GENE; CROHNS-DISEASE
AB By combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals with combined P < 5 x 10(-8). These include a second independent signal at the KCNQ1 locus; the first report, to our knowledge, of an X-chromosomal association (near DUSP9); and a further instance of overlap between loci implicated in monogenic and multifactorial forms of diabetes (at HNF1A). The identified loci affect both beta-cell function and insulin action, and, overall, T2D association signals show evidence of enrichment for genes involved in cell cycle regulation. We also show that a high proportion of T2D susceptibility loci harbor independent association signals influencing apparently unrelated complex traits.
C1 [Voight, Benjamin F.; Raychaudhuri, Soumya; McCarroll, Steve A.; Segre, Ayellet V.; Ardlie, Kristin; Burtt, Noisel P.; Crawford, Gabe; Elliott, Amanda L.; Green, Todd; Guiducci, Candace; Saxena, Richa; Daly, Mark J.; Florez, Jose C.; Altshuler, David] Harvard Univ, Broad Inst, Cambridge, MA 02138 USA.
[Voight, Benjamin F.; Raychaudhuri, Soumya; McCarroll, Steve A.; Segre, Ayellet V.; Ardlie, Kristin; Burtt, Noisel P.; Crawford, Gabe; Elliott, Amanda L.; Green, Todd; Guiducci, Candace; Saxena, Richa; Daly, Mark J.; Florez, Jose C.] MIT, Cambridge, MA 02139 USA.
[Raychaudhuri, Soumya; Segre, Ayellet V.; Green, Todd; Saxena, Richa; Daly, Mark J.; Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Voight, Benjamin F.; Shrader, Peter; Meigs, James B.; Florez, Jose C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Scott, Laura J.; Willer, Cristen J.; Ganser, Martha; Jackson, Anne U.; Stringham, Heather M.; Abecasis, Goncalo R.; Boehnke, Michael] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.
[Steinthorsdottir, Valgerdur; Thorleifsson, Gudmar; Kong, Augustine; Walters, G. Bragi; Thorsteinsdottir, Unnur; Stefansson, Kari] deCODE Genet, Reykjavik, Iceland.
[Morris, Andrew P.; Zeggini, Eleftheria; Ferreira, Teresa; Elliott, Katherine S.; Lindgren, Cecilia M.; Prokopenko, Inga; Rayner, N. William; Robertson, Neil R.; McCarthy, Mark I.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
[Dina, Christian; Proenca, Christine; Cauchi, Stephane] CNRS, UMR 8090, Inst Biol, Lille, France.
[Dina, Christian; Proenca, Christine; Cauchi, Stephane] Univ Lille 2, Inst Pasteur, Lille, France.
[Dina, Christian] CNRS, UMR915, INSERM, ERL3147, Nantes, France.
[Welch, Ryan P.] Univ Michigan, Bioinformat Program, Ann Arbor, MI 48109 USA.
[Zeggini, Eleftheria; Bumpstead, Suzannah; Payne, Felicity; Barroso, Ines] Wellcome Trust Sanger Inst, Hinxton, England.
[Huth, Cornelia; Grallert, Harald; Gieger, Christian; Klopp, Norman; Petersen, Ann-Kristin; Thorand, Barbara; Wichmann, H-Erich; Illig, Thomas] Helmholtz Zentrum Muenchen, Inst Epidemiol, Neuherberg, Germany.
[Huth, Cornelia; Grallert, Harald; Wichmann, H-Erich] Univ Munich, Inst Med Informat Biometry & Epidemiol, Munich, Germany.
[Aulchenko, Yurii S.; Amin, Najaf; Witteman, Jacqueline; Hofman, Albert; van Duijn, Cornelia M.] Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.
[McCulloch, Laura J.; Bennett, Amanda J.; Groves, Christopher J.; Hassanali, Neelam; Owen, Katharine R.; Prokopenko, Inga; Rayner, N. William; Robertson, Neil R.; Gloyn, Anna L.; McCarthy, Mark I.] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.
[Wu, Guanming; Stein, Lincoln D.] Ontario Inst Canc Res, Toronto, ON, Canada.
Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA.
[Raychaudhuri, Soumya; McCarroll, Steve A.; Segre, Ayellet V.; Elliott, Amanda L.; Froguel, Philippe] Harvard Univ, Sch Med, Dept Mol Biol, Boston, MA 02115 USA.
[Langenberg, Claudia; Griffin, Simon; Wareham, Nicholas J.] Addenbrookes Hosp, Inst Metab Sci, MRC, Epidemiol Unit, Cambridge, England.
[Hofmann, Oliver M.; Hide, Winston A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Dupuis, Josee; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Qi, Lu; Kraft, Peter; Sun, Qi; Hunter, David J.; Hu, Frank B.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Qi, Lu; Kraft, Peter; Sun, Qi; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Qi, Lu; Cornelis, Marilyn; van Dam, Rob M.; Hu, Frank B.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA.
[van Hoek, Mandy; van Herpt, Thijs; Sijbrands, Eric; Uitterlinden, Andre] Erasmus Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands.
[Navarro, Pau] Western Gen Hosp, Inst Genet & Mol Med, MRC, Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland.
[Balkau, Beverley] CESP Ctr Res Epidemiol & Populat Hlth, INSERM, U1018, Villejuif, France.
[Balkau, Beverley] Univ Paris 11, UMRS 1018, Villejuif, France.
[Benediktsson, Rafn; Sigurdsson, Gunnar] Landspitali Univ Hosp, Reykjavik, Iceland.
[Benediktsson, Rafn; Sigurdsson, Gunnar] Iceland Heart Assoc, Kopavogur, Iceland.
[Blagieva, Roza; Boehm, Bernhard O.] Univ Ulm, Div Endocrinol Diabet & Metab, Ulm, Germany.
[Boerwinkle, Eric] Univ Texas Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA.
[Boerwinkle, Eric] Univ Texas Hlth Sci Ctr, Inst Mol Med, Houston, TX USA.
[Bonnycastle, Lori L.; Chines, Peter S.; Erdos, Michael R.; Morken, Mario A.; Narisu, Narisu; Swift, Amy J.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Bostrom, Kristina Bengtsson] Skaraborg Primary Care, Ctr Res & Dev, Skovde, Sweden.
[Bravenboer, Bert] Catharina Hosp, Dept Internal Med, Eindhoven, Netherlands.
[Charpentier, Guillaume] Corbeil Essonnes Hosp, Endocrinol Diabetol Unit, Corbeil Essonnes, France.
[Couper, David J.] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA.
[Couper, David J.] Univ N Carolina, Collaborat Studies Coordinating Ctr, Chapel Hill, NC USA.
[Doney, Alex S. F.; Morris, Andrew D.; Palmer, Colin N. A.] Univ Dundee, Ninewells Hosp, Biomed Res Inst, Diabet Res Ctr, Dundee, Scotland.
[Doney, Alex S. F.; Morris, Andrew D.; Palmer, Colin N. A.] Univ Dundee, Ninewells Hosp, Biomed Res Inst, Pharmacogenom Ctr, Dundee, Scotland.
[Elliott, Amanda L.; Saxena, Richa] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA.
[Fox, Caroline S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA.
[Franklin, Christopher S.; Rudan, Igor; Campbell, Harry; Wilson, James F.] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland.
[Grarup, Niels; Sparso, Thomas; Hansen, Torben; Pedersen, Oluf] Hagedorn Res Inst, Gentofte, Denmark.
[Hadjadj, Samy] Univ Poitiers, INSERM, U927, Ctr Hosp Univ Poitiers,UFR,CIC INSERM 0801, Poitiers, France.
[Herder, Christian; Roden, Michael] Univ Dusseldorf, Leibniz Ctr Diabet Res, German Diabet Ctr, Inst Clin Diabetol, Dusseldorf, Germany.
[Isomaa, Bo; Tuomi, Tiinamaija] Folkhalsan Res Ctr, Helsinki, Finland.
[Isomaa, Bo] Malmska Municipal Hlth Ctr & Hosp, Pietarsaari, Finland.
[Johnson, Paul R. V.] Univ Oxford, Diabet Res & Wellness Fdn Human Islet Isolat Faci, Oxford, England.
[Johnson, Paul R. V.] Univ Oxford, Oxford Islet Transplant Programme, Oxford, England.
[Jorgensen, Torben] Glostrup Univ Hosp, Res Ctr Prevent & Hlth, Glostrup, Denmark.
[Jorgensen, Torben] Univ Copenhagen, Fac Hlth Sci, Copenhagen, Denmark.
[Kao, Wen H. L.; Li, Man] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA.
[Kao, Wen H. L.] Johns Hopkins Univ, Dept Med, Baltimore, MD USA.
[Kao, Wen H. L.] Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA.
[Kuusisto, Johanna; Laakso, Markku] Univ Kuopio, Dept Med, SF-70210 Kuopio, Finland.
[Kuusisto, Johanna; Laakso, Markku] Kuopio Univ Hosp, SF-70210 Kuopio, Finland.
[Lauritzen, Torsten] Univ Aarhus, Dept Gen Med Practice, Aarhus, Denmark.
[Lieverse, Aloysius; van Herpt, Thijs] Maxima Med Ctr, Dept Internal Med, Eindhoven, Netherlands.
[Lyssenko, Valeriya; Nilsson, Peter; Groop, Leif] Lund Univ, Malmo Univ Hosp, Diabet & Endocrinol Res Unit, Dept Clin Sci, Malmo, Sweden.
[Marre, Michel] Bichat Claude Bernard Univ Hosp, AP HP, Dept Endocrinol Diabetol & Nutr, Paris, France.
[Marre, Michel] Univ Paris 07, INSERM, U695, Paris, France.
[Meitinger, Thomas] Helmholtz Zentrum Muenchen, Inst Human Genet, Neuherberg, Germany.
[Meitinger, Thomas] Tech Univ Munich, Klinikum Rechts Isar, Inst Human Genet, D-8000 Munich, Germany.
[Midthjell, Kristian; Platou, Carl; Hveem, Kristian] Norwegian Univ Sci & Technol, Dept Community Med & Gen Practice, Nord Trondelag Hlth Study HUNT Res Ctr, N-7034 Trondheim, Norway.
[Perry, John R. B.; Shields, Beverley M.; Weedon, Michael N.; Hattersley, Andrew T.; Frayling, Timothy M.] Univ Exeter, Peninsula Med Sch, Inst Biomed & Clin Sci, Exeter, Devon, England.
[Rathmann, Wolfgang; Strassburger, Klaus] Univ Dusseldorf, Leibniz Ctr Diabet Res, German Diabet Ctr, Inst Biometr & Epidemiol, Dusseldorf, Germany.
[Rocheleau, Ghislain; Sladek, Rob] McGill Univ, Dept Human Genet, Montreal, PQ, Canada.
[Rocheleau, Ghislain; Sladek, Rob] McGill Univ, Fac Med, Dept Med, Montreal, PQ, Canada.
[Rocheleau, Ghislain; Sladek, Rob] Genome Quebec Innovat Ctr, Montreal, PQ, Canada.
[Roden, Michael] Univ Dusseldorf, Dept Metab Dis, Dusseldorf, Germany.
[Sampson, Michael J.] Norfolk & Norwich Univ Hosp Natl Hlth Serv Trust, Dept Endocrinol & Diabet, Norwich, Norfolk, England.
[Shrader, Peter; Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA.
[Tichet, Jean] Inst Interreg Sante IRSA, La Riche, France.
[Tuomi, Tiinamaija; Groop, Leif] Univ Helsinki, Helsinki Univ Hosp, Dept Med, Helsinki, Finland.
[van Haeften, Timon W.] Univ Med Ctr Utrecht, Dept Internal Med, Utrecht, Netherlands.
[van Vliet-Ostaptchouk, Jana V.] Univ Med Ctr Groningen, Dept Pathol & Med Biol, Med Biol Sect, NL-9713 AV Groningen, Netherlands.
[van Vliet-Ostaptchouk, Jana V.; Wijmenga, Cisca] Univ Groningen, Groningen, Netherlands.
[Wijmenga, Cisca] Univ Med Ctr Groningen, Dept Genet, NL-9713 AV Groningen, Netherlands.
[Bergman, Richard N.; Watanabe, Richard M.] Univ So Calif, Sch Med, Dept Physiol & Biophys, Los Angeles, CA 90033 USA.
[Collins, Francis S.] NIH, Bethesda, MD 20892 USA.
[Gyllensten, Ulf] Uppsala Univ, Rudbeck Lab, Dept Genet & Pathol, Uppsala, Sweden.
[Hansen, Torben] Univ So Denmark, Odense, Denmark.
[Hitman, Graham A.] Queen Mary Univ London, Barts & London Sch Med & Dent, Ctr Diabet, London, England.
[Hveem, Kristian] Hosp Levanger, Dept Med, Levanger, Norway.
[Mohlke, Karen L.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
[Pramstaller, Peter P.] European Acad Bozen Bolzano EURAC, Inst Med Genet, Bolzano, Italy.
[Rudan, Igor] Univ Split, Fac Med, Croatian Ctr Global Hlth, Split, Croatia.
[Rudan, Igor] Univ Hosp Sestre Milosrdnice, Inst Clin Med Res, Zagreb, Croatia.
[Tuomilehto, Jaakko] Univ Helsinki, Dept Publ Hlth, Helsinki, Finland.
[Tuomilehto, Jaakko] S Ostrobothnia Cent Hosp, Seinajoki, Finland.
[Tuomilehto, Jaakko] Hosp Univ La Paz, Red RECAVA Grp RD06 0014 0015, Madrid, Spain.
[Walker, Mark] Newcastle Univ, Inst Cellular Med, Diabet Res Grp, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Watanabe, Richard M.] Univ So Calif, Keck Sch Med, Dept Preventat Med, Los Angeles, CA 90033 USA.
[Pankow, James S.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Pedersen, Oluf] Univ Copenhagen, Fac Hlth Sci, Dept Biomed Sci, Copenhagen, Denmark.
[Pedersen, Oluf] Univ Aarhus, Fac Hlth Sci, Aarhus, Denmark.
[Wichmann, H-Erich] Univ Munich, Klinikum Grosshadern, D-8000 Munich, Germany.
[Florez, Jose C.] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA.
[Thorsteinsdottir, Unnur; Stefansson, Kari] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Froguel, Philippe] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, London, England.
[McCarthy, Mark I.] Churchill Hosp, Hlth Res Biomed Res Ctr, Oxford Natl Inst, Oxford OX3 7LJ, England.
RP Altshuler, D (reprint author), Harvard Univ, Broad Inst, Cambridge, MA 02138 USA.
EM jim.wilson@hgu.mrc.ac.uk; illig@helmholtz-muenchen.de;
froguel@good.ibl.fr; c.vanduijn@erasmusmc.nl; kstefans@decode.is;
altshuler@molbio.mgh.harvard.edu; boehnke@umich.edu;
mark.mccarthy@drl.ox.ac.uk
RI Hofmann, Oliver/F-1800-2013; Abecasis, Goncalo/B-7840-2010; Altshuler,
David/A-4476-2009; Aulchenko, Yurii/M-8270-2013; Huth,
Cornelia/B-5350-2014; Palmer, Colin/C-7053-2008; Voight,
Benjamin/F-1775-2011; van Dam, Rob/F-9674-2010; Segre,
Ayellet/E-9800-2010; Elliott, Amanda/G-5120-2012; Rudan,
Igor/I-1467-2012; Grallert, Harald/B-3424-2013; van Hoek,
Mandy/B-9325-2014; Wijmenga, Cisca/D-2173-2009; Pramstaller,
Peter/C-2357-2008; Dina, Christian/D-3535-2015; Boehm,
Bernhard/F-8750-2015; Wilson, James F/A-5704-2009; Meitinger,
Thomas/O-1318-2015; Prokopenko, Inga/H-3241-2014; Thorand,
Barbara/B-5349-2014; Grarup, Niels/K-2807-2015; Study,
GoDARTS/K-9448-2016;
OI Willer, Cristen/0000-0001-5645-4966; Sijbrands,
Eric/0000-0001-8857-7389; Griffin, Simon/0000-0002-2157-4797; Marre,
Michel/0000-0002-3071-1837; Hide, Winston/0000-0002-8621-3271; Abecasis,
Goncalo/0000-0003-1509-1825; Zeggini, Eleftheria/0000-0003-4238-659X;
Hofmann, Oliver/0000-0002-7738-1513; Altshuler,
David/0000-0002-7250-4107; Aulchenko, Yurii/0000-0002-7899-1575; Huth,
Cornelia/0000-0003-2421-433X; Palmer, Colin/0000-0002-6415-6560; van
Dam, Rob/0000-0002-7354-8734; Rudan, Igor/0000-0001-6993-6884; Dupuis,
Josee/0000-0003-2871-3603; Gieger, Christian/0000-0001-6986-9554;
Wijmenga, Cisca/0000-0002-5635-1614; Tuomi,
Tiinamaija/0000-0002-8306-6202; Jorgensen, Torben/0000-0001-9453-2830;
Sladek, Robert/0000-0002-2730-1204; Payne, Felicity/0000-0003-4228-581X;
Dina, Christian/0000-0002-7722-7348; Wilson, James
F/0000-0001-5751-9178; Prokopenko, Inga/0000-0003-1624-7457; Thorand,
Barbara/0000-0002-8416-6440; Grarup, Niels/0000-0001-5526-1070; van
Vliet-Ostaptchouk, Jana/0000-0002-7943-3153; Pankow,
James/0000-0001-7076-483X
FU Chief Scientist Office [CZB/4/710]; Department of Health
[DHCS/07/07/008]; Medical Research Council [G0600331, G0601261,
G0700222, G0700222(81696), G0701863, MC_U106179471, MC_U106179474,
MC_U127592696]; NCRR NIH HHS [UL1 RR025005, UL1RR025005]; NHGRI NIH HHS
[U01 HG004171, U01 HG004399, U01 HG004402, U01HG004171, U01HG004399,
U01HG004402, Z01 HG000024]; NHLBI NIH HHS [1K99HL094535-01A1, K99
HL094535, N01-HC-25195, N01-HC-55015, N01-HC-55016, N01-HC-55018,
N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, N01HC25195,
N01HC55015, N01HC55016, N01HC55018, N01HC55019, N01HC55020, N01HC55021,
N01HC55022, N02-HL-6-4278, R01 HL059367, R01 HL086694, R01 HL087641,
R01HL086694, R01HL087641, R01HL59367]; NIAMS NIH HHS [K08 AR055688,
1K08AR055688, K08 AR055688-03]; NIDA NIH HHS [U54 DA021519]; NIDDK NIH
HHS [DK062370, DK069922, DK072193, DK073490, DK078616, DK58845, K23
DK065978, K23-DK65978, K24 DK080140, K24-DK080140, R01 DK029867, R01
DK058845, R01 DK062370, R01 DK069922, R01 DK072193, R01 DK073490, R01
DK078616, R56 DK062370, U01 DK062370, U01 DK078616]; PHS HHS
[HHSN268200625226C]; Wellcome Trust [064890, 072960, 075491, 076113,
077016, 079557, 081682, 083270, 086596, 088885, 090532]
NR 69
TC 911
Z9 938
U1 12
U2 122
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 JUL
PY 2010
VL 42
IS 7
BP 579
EP U155
DI 10.1038/ng.609
PG 13
WC Genetics & Heredity
SC Genetics & Heredity
GA 616WO
UT WOS:000279242400010
PM 20581827
ER
PT J
AU Johnson, AD
Yanek, LR
Chen, MH
Faraday, N
Larson, MG
Tofler, G
Lin, SJ
Kraja, AT
Province, MA
Yang, QO
Becker, DM
O'Donnell, CJ
Becker, LC
AF Johnson, Andrew D.
Yanek, Lisa R.
Chen, Ming-Huei
Faraday, Nauder
Larson, Martin G.
Tofler, Geoffrey
Lin, Shiow J.
Kraja, Aldi T.
Province, Michael A.
Yang, Qiong
Becker, Diane M.
O'Donnell, Christopher J.
Becker, Lewis C.
TI Genome-wide meta-analyses identifies seven loci associated with platelet
aggregation in response to agonists
SO NATURE GENETICS
LA English
DT Article
ID GLYCOPROTEIN-VI; RECEPTOR EXPRESSION; PRION PROTEIN; GENE; ACTIVATION;
MOLECULE; ASPIRIN; VARIANT; DISEASE; RESPONSIVENESS
C1 [Johnson, Andrew D.; Chen, Ming-Huei; Larson, Martin G.; Yang, Qiong; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Johnson, Andrew D.; O'Donnell, Christopher J.] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA.
[Yanek, Lisa R.; Becker, Diane M.; Becker, Lewis C.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
[Chen, Ming-Huei] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[Faraday, Nauder] Johns Hopkins Univ, Sch Med, Dept Anesthesia & Crit Care Med, Baltimore, MD USA.
[Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
[Tofler, Geoffrey] Univ Sydney, Royal N Shore Hosp, Sydney, NSW 2006, Australia.
[Lin, Shiow J.; Kraja, Aldi T.; Province, Michael A.] Washington Univ Med, Div Stat Genom, St Louis, MO USA.
[Yang, Qiong] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[O'Donnell, Christopher J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiol Div, Boston, MA USA.
RP Johnson, AD (reprint author), NHLBI, Framingham Heart Study, Framingham, MA USA.
EM johnsonad2@nhlbi.nih.gov
RI Johnson, Andrew/G-6520-2013; Yang, Qiong/G-5438-2014;
OI Larson, Martin/0000-0002-9631-1254
FU US National Heart, Lung, and Blood Institute [N01-HC-25195,
N02-HL-6-4278, U01 HL72518, R01 HL087698-01, R01-HL-48157]; National
Center for Research Resources [M01-RR000052]; Washington University DSG
FX This work was supported by the US National Heart, Lung, and Blood
Institute's Framingham Heart Study (Contract No. N01-HC-25195) and its
contract with Affymetrix, Inc. for genotyping services (Contract No.
N02-HL-6-4278). This research was conducted in part using data and
resources from the Framingham Heart Study of the National Heart, Lung,
and Blood Institute of the National Institutes of Health and Boston
University School of Medicine. The analyses reflect intellectual input
and resource development from the Framingham Heart Study investigators
participating in the SNP Health Association Resource (SHARe) project. A
portion of this research used the Linux Cluster for Genetic Analysis
(LinGA-II) funded by the Robert Dawson Evans Endowment of the Department
of Medicine at Boston University School of Medicine and Boston Medical
Center. This work was supported by the National Heart, Lung, and Blood
Institute through the PROGENI (U01 HL72518) and STAMPEED (R01
HL087698-01) consortia, and through R01-HL-48157. This research was
conducted in part using the resources of the Johns Hopkins General
Clinical Research Center, funded through the National Center for
Research Resources, M01-RR000052 and the Washington University DSG
cluster. We thank G. Ehret and S. Ganesh for providing R code that was
modified to generate plots displayed in Figures 1 and 2 and
Supplementary Figure 2.
NR 49
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U2 14
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 JUL
PY 2010
VL 42
IS 7
BP 608
EP U186
DI 10.1038/ng.604
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA 616WO
UT WOS:000279242400014
PM 20526338
ER
PT J
AU Zhu, H
Shah, S
Shyh-Chang, N
Shinoda, G
Einhorn, WS
Viswanathan, SR
Takeuchi, A
Grasemann, C
Rinn, JL
Lopez, MF
Hirschhorn, JN
Palmert, MR
Daley, GQ
AF Zhu, Hao
Shah, Samar
Shyh-Chang, Ng
Shinoda, Gen
Einhorn, William S.
Viswanathan, Srinivas R.
Takeuchi, Ayumu
Grasemann, Corinna
Rinn, John L.
Lopez, Mary F.
Hirschhorn, Joel N.
Palmert, Mark R.
Daley, George Q.
TI Lin28a transgenic mice manifest size and puberty phenotypes identified
in human genetic association studies
SO NATURE GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; CHROMOSOME SUBSTITUTION STRAINS;
BECKWITH-WIEDEMANN SYNDROME; MESSENGER-RNA; PYRUVATE-KINASE;
SELF-RENEWAL; EXPRESSION; GROWTH; CELLS; LIN-28
AB Recently, genome-wide association studies have implicated the human LIN28B locus in regulating height and the timing of menarche(1-5). LIN28B and its homolog LIN28A are functionally redundant RNA-binding proteins that block biogenesis of let-7 microRNAs(6-9). lin-28 and let-7 were discovered in Caenorhabditis elegans as heterochronic regulators of larval and vulval development but have recently been implicated in cancer, stem cell aging and pluripotency(10-13). The let-7 targets Myc, Kras, Igf2bp1 and Hmga2 are known regulators of mammalian body size and metabolism(14-18). To explore the function of the Lin28-Let-7 pathway in vivo, we engineered transgenic mice to express Lin28a and observed in them increased body size, crown-rump length and delayed onset of puberty. Investigation of metabolic and endocrine mechanisms of overgrowth in these transgenic mice revealed increased glucose metabolism and insulin sensitivity. Here we report a mouse that models the human phenotypes associated with genetic variation in the Lin28-Let-7 pathway.
C1 [Zhu, Hao; Shah, Samar; Shyh-Chang, Ng; Shinoda, Gen; Einhorn, William S.; Viswanathan, Srinivas R.; Takeuchi, Ayumu; Daley, George Q.] Childrens Hosp, Div Pediat Hematol Oncol, Stem Cell Transplantat Program, Boston, MA 02115 USA.
[Zhu, Hao] Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02115 USA.
[Zhu, Hao; Shah, Samar; Shyh-Chang, Ng; Shinoda, Gen; Einhorn, William S.; Viswanathan, Srinivas R.; Takeuchi, Ayumu; Daley, George Q.] Harvard Stem Cell Inst, Boston, MA USA.
[Einhorn, William S.; Daley, George Q.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA.
[Grasemann, Corinna; Palmert, Mark R.] Hosp Sick Children, Div Endocrinol, Toronto, ON M5G 1X8, Canada.
[Grasemann, Corinna; Palmert, Mark R.] Univ Toronto, Dept Paediat, Toronto, ON M5S 1A1, Canada.
[Rinn, John L.; Hirschhorn, Joel N.] Harvard Univ, Broad Inst, Cambridge, MA 02138 USA.
[Rinn, John L.; Hirschhorn, Joel N.] MIT, Cambridge, MA 02139 USA.
[Rinn, John L.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Pathol, Boston, MA 02215 USA.
[Lopez, Mary F.; Hirschhorn, Joel N.] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.
[Hirschhorn, Joel N.] Childrens Hosp, Program Genom, Div Genet, Boston, MA 02115 USA.
[Hirschhorn, Joel N.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA.
[Daley, George Q.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Daley, George Q.] Howard Hughes Med Inst, Boston, MA 02115 USA.
[Daley, George Q.] Manton Ctr Orphan Dis Res, Boston, MA USA.
RP Daley, GQ (reprint author), Childrens Hosp, Div Pediat Hematol Oncol, Stem Cell Transplantat Program, 300 Longwood Ave, Boston, MA 02115 USA.
EM george.daley@childrens.harvard.edu
OI Zhu, Hao/0000-0002-8417-9698; Shyh-Chang, Ng/0000-0003-3138-9525
FU Graduate Training in Cancer Research [5 T32 CA09172-35]; NIH
[R01HD048960]
FX Lin28a knockout mice were generously provided by Eric Moss at The
University of Medicine and Dentistry of New Jersey and will be described
separately (S.R.V., G.S., H.Z., W.S.E., G.C. Heffner et al., unpublished
data). We acknowledge J. Powers, H. Rajagopalan and M. Kharas for
invaluable discussions and advice regarding this work. We also thank
Y.-H. Loh, M. White, L. Wang and J. Majzoub for in-depth discussion and
endocrine expertise. This work was supported by a Graduate Training in
Cancer Research Grant (5 T32 CA09172-35) to H.Z., a NIH grant
(R01HD048960) to M.R.P., a NIH Directors Pioneer Award and a HHMI grant
to G.Q.D.
NR 40
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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 JUL
PY 2010
VL 42
IS 7
BP 626
EP U106
DI 10.1038/ng.593
PG 6
WC Genetics & Heredity
SC Genetics & Heredity
GA 616WO
UT WOS:000279242400017
PM 20512147
ER
PT J
AU Ouyang, W
Beckett, O
Ma, QA
Paik, JH
DePinho, RA
Li, MO
AF Ouyang, Weiming
Beckett, Omar
Ma, Qian
Paik, Ji-hye
DePinho, Ronald A.
Li, Ming O.
TI Foxo proteins cooperatively control the differentiation of Foxp3(+)
regulatory T cells
SO NATURE IMMUNOLOGY
LA English
DT Article
ID TRANSCRIPTION FACTOR FOXP3; NF-KAPPA-B; LINEAGE COMMITMENT; DENDRITIC
CELLS; TGF-BETA; AKT-MTOR; RECEPTOR; EXPRESSION; HOMEOSTASIS;
SPECIFICATION
AB CD4(+) regulatory T cells (T-reg cells) characterized by expression of the transcription factor Foxp3 have a pivotal role in maintaining immunological tolerance. Here we show that mice with T cell-specific deletion of both the Foxo1 and Foxo3 transcription factors (collectively called 'Foxo proteins' here) developed a fatal multifocal inflammatory disorder due in part to T-reg cell defects. Foxo proteins functioned in a T-reg cell-intrinsic manner to regulate thymic and transforming growth factor-beta (TGF-beta)-induced Foxp3 expression, in line with the ability of Foxo proteins to bind to Foxp3 locus and control Foxp3 promoter activity. Transcriptome analyses showed that Foxo proteins regulated the expression of additional T-reg cell-associated genes and were essential for inhibiting the acquisition of effector T cell characteristics by T-reg cells. Thus, Foxo proteins have crucial roles in specifying the T-reg cell lineage.
C1 [Ouyang, Weiming; Beckett, Omar; Ma, Qian; Li, Ming O.] Mem Sloan Kettering Canc Ctr, Program Immunol, New York, NY 10021 USA.
[Paik, Ji-hye; DePinho, Ronald A.] Harvard Univ, Sch Med,Belfer Inst Appl Canc Sci, Dana Farber Canc Inst, Dept Oncol,Dept Med, Boston, MA 02115 USA.
[Paik, Ji-hye; DePinho, Ronald A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Genet, Boston, MA 02115 USA.
RP Li, MO (reprint author), Mem Sloan Kettering Canc Ctr, Program Immunol, 1275 York Ave, New York, NY 10021 USA.
EM lim@mskcc.org
FU Starr Cancer Consortium [13-A123]; National Institute of Arthritis,
Musculoskeletal and Skin Diseases [K01 AR053595]; Arthritis Foundation;
Robert A. and Renee E. Belfer Family Foundation; Damon-Runyon Cancer
Research Foundation; Rita Allen Foundation
FX We thank R. Flavell (Yale University) for the Foxp3-RFP mouse strain; S.
Ghosh (Columbia University) for luciferase reporter constructs; A.
Brunet (Stanford University) for the Foxo3-specific antibody; and A.
Rudensky, M. Huse and Y. Zheng for discussions. Supported by the Starr
Cancer Consortium (13-A123 to M.O.L.), the National Institute of
Arthritis, Musculoskeletal and Skin Diseases (K01 AR053595 to M.O.L.),
the Arthritis Foundation (M.O.L.), the Robert A. and Renee E. Belfer
Family Foundation (R.A.D.), the Damon-Runyon Cancer Research Foundation
(J.-h.P.) and the Rita Allen Foundation (M.O.L.).
NR 50
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U1 3
U2 9
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1529-2908
J9 NAT IMMUNOL
JI Nat. Immunol.
PD JUL
PY 2010
VL 11
IS 7
BP 618
EP U91
DI 10.1038/ni.1884
PG 11
WC Immunology
SC Immunology
GA 612TO
UT WOS:000278926400018
PM 20467422
ER
PT J
AU Ellisen, LW
AF Ellisen, Leif W.
TI Smoking and emphysema: the stress connection
SO NATURE MEDICINE
LA English
DT Editorial Material
ID HYPOXIA; DISEASE; REDD1
AB The stress response protein Rtp801 mediates damage to the lung in response to smoke. This finding might lead to new ways to treat chronic obstructive pulmonary disease and emphysema ( pages 767-773).
C1 [Ellisen, Leif W.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Ellisen, Leif W.] Harvard Univ, Sch Med, Boston, MA USA.
RP Ellisen, LW (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.
EM ellisen@helix.mgh.harvard.edu
FU NCI NIH HHS [R01 CA122589]
NR 11
TC 7
Z9 7
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
J9 NAT MED
JI Nat. Med.
PD JUL
PY 2010
VL 16
IS 7
BP 754
EP 755
DI 10.1038/nm0710-754
PG 3
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA 622BA
UT WOS:000279631900021
PM 20613751
ER
PT J
AU Weinberg, R
Fisher, DE
Rich, J
AF Weinberg, Robert
Fisher, David E.
Rich, Jeremy
TI Dynamic and transient cancer stem cells nurture melanoma
SO NATURE MEDICINE
LA English
DT Editorial Material
C1 [Weinberg, Robert] Whitehead Inst Biomed Res, Cambridge, MA USA.
[Weinberg, Robert] Massachusetts Inst Tech, Cambridge, MA USA.
[Fisher, David E.] Harvard Med Sch, Massachusetts Gen Hosp, Melanoma Program, Boston, MA USA.
[Rich, Jeremy] Lerner Res Inst, Dept Stem Cell Biol & Regenerative Med, Cleveland, OH USA.
RP Weinberg, R (reprint author), Whitehead Inst Biomed Res, Cambridge, MA USA.
FU NIAMS NIH HHS [R01 AR043369]
NR 3
TC 7
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U1 1
U2 5
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
J9 NAT MED
JI Nat. Med.
PD JUL
PY 2010
VL 16
IS 7
BP 758
EP 758
DI 10.1038/nm0710-758
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA 622BA
UT WOS:000279631900037
PM 20613753
ER
PT J
AU Uygun, BE
Soto-Gutierrez, A
Yagi, H
Izamis, ML
Guzzardi, MA
Shulman, C
Milwid, J
Kobayashi, N
Tilles, A
Berthiaume, F
Hertl, M
Nahmias, Y
Yarmush, ML
Uygun, K
AF Uygun, Basak E.
Soto-Gutierrez, Alejandro
Yagi, Hiroshi
Izamis, Maria-Louisa
Guzzardi, Maria A.
Shulman, Carley
Milwid, Jack
Kobayashi, Naoya
Tilles, Arno
Berthiaume, Francois
Hertl, Martin
Nahmias, Yaakov
Yarmush, Martin L.
Uygun, Korkut
TI Organ reengineering through development of a transplantable
recellularized liver graft using decellularized liver matrix
SO NATURE MEDICINE
LA English
DT Article
ID HEPATOCYTE TRANSPLANTATION; EXTRACELLULAR-MATRIX; STEM-CELLS; IN-VITRO;
FAILURE; OXYGEN; DIFFERENTIATION; ATTACHMENT; PERFUSION; SURVIVAL
AB Orthotopic liver transplantation is the only available treatment for severe liver failure, but it is currently limited by organ shortage. One technical challenge that has thus far limited the development of a tissue-engineered liver graft is oxygen and nutrient transport. Here we demonstrate a novel approach to generate transplantable liver grafts using decellularized liver matrix. The decellularization process preserves the structural and functional characteristics of the native microvascular network, allowing efficient recellularization of the liver matrix with adult hepatocytes and subsequent perfusion for in vitro culture. The recellularized graft supports liver-specific function including albumin secretion, urea synthesis and cytochrome P450 expression at comparable levels to normal liver in vitro. The recellularized liver grafts can be transplanted into rats, supporting hepatocyte survival and function with minimal ischemic damage. These results provide a proof of principle for the generation of a transplantable liver graft as a potential treatment for liver disease.
C1 [Uygun, Basak E.; Soto-Gutierrez, Alejandro; Yagi, Hiroshi; Izamis, Maria-Louisa; Guzzardi, Maria A.; Shulman, Carley; Milwid, Jack; Tilles, Arno; Berthiaume, Francois; Nahmias, Yaakov; Yarmush, Martin L.; Uygun, Korkut] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med,Shriners Hosp Children, Boston, MA 02129 USA.
[Guzzardi, Maria A.] Scuola Super Sant Anna, Sector Med, Pisa, Italy.
[Kobayashi, Naoya] Okayama Univ, Grad Sch Med & Dent, Dept Surg, Shikata, Okayama, Japan.
[Berthiaume, Francois; Yarmush, Martin L.] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ USA.
[Hertl, Martin] Massachusetts Gen Hosp, Transplantat Unit, Boston, MA 02114 USA.
RP Uygun, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med,Shriners Hosp Children, Boston, MA 02129 USA.
EM kuygun@partners.org
RI Nahmias, Yaakov/H-4725-2013; Sano, Michael/E-1715-2011; Uygun,
Basak/I-1792-2012; Guzzardi, Maria-Angela/K-1389-2016;
OI Uygun, Basak/0000-0002-2600-7900; Guzzardi,
Maria-Angela/0000-0001-9574-5088; Nahmias, Yaakov/0000-0002-6051-616X
FU US National Institutes of Health [R01DK59766, R01DK084053, K99/R00
DK080942, K99DK083556]; US National Science Foundation [CBET-0853569];
Shriners Hospitals for Children [8503]; American Liver Foundation;
Massachusetts General Hospital; Shriners Hospitals for Children
FX This work was supported by grants from the US National Institutes of
Health, R01DK59766 and R01DK084053 to M.L.Y., K99/R00 DK080942 to K. U.
and K99DK083556 to A. S.-G., and US National Science Foundation
CBET-0853569 to K. U. We thank the support of the Shriners Hospitals for
Children to B. E. U. (grant no. 8503), the American Liver Foundation to
A. S.-G. and Massachusetts General Hospital Junior Faculty Grant to K.
U. and the Shriners Hospitals for Children. We would like to thank A.
Vitalo, C. Calhoun and B. Crowther for technical support.
NR 38
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U2 200
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
J9 NAT MED
JI Nat. Med.
PD JUL
PY 2010
VL 16
IS 7
BP 814
EP U120
DI 10.1038/nm.2170
PG 8
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA 622BA
UT WOS:000279631900033
PM 20543851
ER
PT J
AU Liedl, T
Hogberg, B
Tytell, J
Ingber, DE
Shih, WM
AF Liedl, Tim
Hogberg, Bjorn
Tytell, Jessica
Ingber, Donald E.
Shih, William M.
TI Self-assembly of three-dimensional prestressed tensegrity structures
from DNA
SO NATURE NANOTECHNOLOGY
LA English
DT Article
ID SINGLE-STRANDED-DNA; MOLECULES; ORIGAMI; SHAPES; LIFE
AB Tensegrity, or tensional integrity, is a property of a structure indicating a reliance on a balance between components that are either in pure compression or pure tension for stability(1,2). Tensegrity structures exhibit extremely high strength-to-weight ratios and great resilience, and are therefore widely used in engineering, robotics and architecture(3,4). Here, we report nanoscale, prestressed, three-dimensional tensegrity structures in which rigid bundles of DNA double helices resist compressive forces exerted by segments of single-stranded DNA that act as tension-bearing cables. Our DNA tensegrity structures can self-assemble against forces up to 14 pN, which is twice the stall force of powerful molecular motors such as kinesin or myosin(5,6). The forces generated by this molecular prestressing mechanism can be used to bend the DNA bundles or to actuate the entire structure through enzymatic cleavage at specific sites. In addition to being building blocks for nanostructures, tensile structural elements made of single-stranded DNA could be used to study molecular forces, cellular mechano-transduction and other fundamental biological processes.
C1 [Liedl, Tim; Hogberg, Bjorn; Shih, William M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Liedl, Tim; Hogberg, Bjorn; Shih, William M.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Liedl, Tim; Hogberg, Bjorn; Tytell, Jessica; Ingber, Donald E.; Shih, William M.] Harvard Univ, Wyss Inst Biol Inspired Engn, Cambridge, MA 02138 USA.
[Tytell, Jessica; Ingber, Donald E.] Harvard Univ, Sch Med, Childrens Hosp, Vasc Biol Program, Boston, MA 02115 USA.
[Tytell, Jessica; Ingber, Donald E.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Tytell, Jessica; Ingber, Donald E.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
RP Liedl, T (reprint author), Univ Munich, Fak Phys, CENS, Ctr Nanosci, Geschwister Scholl Pl 1, D-80539 Munich, Germany.
EM William_Shih@dfci.harvard.edu
RI Liedl, Tim/O-7539-2014;
OI Liedl, Tim/0000-0002-0040-0173; Hogberg, Bjorn/0000-0003-2715-7887
FU Wyss Institute for Biologically Inspired Engineering; Deutscher
Akademischer Austauschdienst (DAAD); Swedish Science Council; Claudia
Adams Barr Program; NIH [1DP2OD004641-01]
FX The authors thank O. Hallatschek, R. Neher, H. Dietz and S. Douglas for
helpful discussions and advice. This work was funded by the Wyss
Institute for Biologically Inspired Engineering, and Deutscher
Akademischer Austauschdienst (DAAD; T. L.), Swedish Science Council
(Vetenskapsradet) Fellowship (B.H.) and Claudia Adams Barr Program
Investigator and NIH New Innovator (1DP2OD004641-01; W.M.S.) grants.
NR 26
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U1 12
U2 118
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1748-3387
J9 NAT NANOTECHNOL
JI Nat. Nanotechnol.
PD JUL
PY 2010
VL 5
IS 7
BP 520
EP 524
DI 10.1038/NNANO.2010.107
PG 5
WC Nanoscience & Nanotechnology; Materials Science, Multidisciplinary
SC Science & Technology - Other Topics; Materials Science
GA 633TO
UT WOS:000280529800015
PM 20562873
ER
PT J
AU Heyer, J
Kwong, LN
Lowe, SW
Chin, L
AF Heyer, Joerg
Kwong, Lawrence N.
Lowe, Scott W.
Chin, Lynda
TI Non-germline genetically engineered mouse models for translational
cancer research
SO NATURE REVIEWS CANCER
LA English
DT Review
ID GROWTH-FACTOR RECEPTOR; IN-VIVO; BREAST-CANCER; HUMAN SKIN; TUMOR
MAINTENANCE; MAMMALIAN-CELLS; SONIC HEDGEHOG; MAMMARY-TUMORS;
LIVER-CANCER; K-RAS
AB Genetically engineered mouse models (GEMMs) of cancer have affected virtually all areas of cancer research. However, the accelerated discovery of new cancer genes emerging from large-scale cancer genomics and new chemical entities pouring from the drug discovery pipeline have strained the capacity of traditional germline mouse models to provide crucial insights. This Review introduces new approaches to modelling cancer, with emphasis on a growing collection of non-germline GEMMs (nGEMMs). These offer flexibility, speed and uniformity at reduced costs, thus paving the way for much needed throughput and practical preclinical therapeutic testing models.
C1 [Kwong, Lawrence N.; Chin, Lynda] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02115 USA.
[Kwong, Lawrence N.; Chin, Lynda] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Heyer, Joerg] AVEO Pharmaceut, Cambridge, MA 02139 USA.
[Lowe, Scott W.] Cold Spring Harbor Lab, Howard Hughes Med Inst, Cold Spring Harbor, NY 11724 USA.
[Chin, Lynda] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA.
RP Chin, L (reprint author), Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02115 USA.
EM Lynda_Chin@dfci.harvard.edu
RI Bell, Tiffany/F-4403-2010
FU NCI NIH HHS [P01 CA013106, P30 CA008748]
NR 86
TC 75
Z9 77
U1 0
U2 13
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1474-175X
J9 NAT REV CANCER
JI Nat. Rev. Cancer
PD JUL
PY 2010
VL 10
IS 7
BP 470
EP 480
DI 10.1038/nrc2877
PG 11
WC Oncology
SC Oncology
GA 615DF
UT WOS:000279111900009
PM 20574449
ER
PT J
AU Higano, CS
Small, EJ
Schellhammer, P
Yasothan, U
Gubernick, S
Kirkpatrick, P
Kantoff, PW
AF Higano, Celestia S.
Small, Eric J.
Schellhammer, Paul
Yasothan, Uma
Gubernick, Steven
Kirkpatrick, Peter
Kantoff, Philip W.
TI Sipuleucel-T
SO NATURE REVIEWS DRUG DISCOVERY
LA English
DT Article
ID REFRACTORY PROSTATE-CANCER; DENDRITIC CELLS; TRIAL
C1 [Higano, Celestia S.] Univ Washington, Dept Med, Seattle, WA 98195 USA.
[Higano, Celestia S.] Fred Hutchinson Canc Res Ctr, Seattle, WA USA.
[Small, Eric J.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Small, Eric J.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA.
[Yasothan, Uma; Gubernick, Steven] IMS Hlth, London NW1 6JB, England.
[Kantoff, Philip W.] Harvard Univ, Sch Med, Dept Med, Dana Farber Canc Inst, Cambridge, MA 02138 USA.
RP Higano, CS (reprint author), Univ Washington, Dept Med, Seattle, WA 98195 USA.
EM thigano@u.washington.edu; UYasothan@de.imshealth.com;
p.kirkpatrick@nature.com; Philip_Kantoff@dfci.harvard.edu
NR 14
TC 68
Z9 74
U1 0
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1474-1776
J9 NAT REV DRUG DISCOV
JI Nat. Rev. Drug Discov.
PD JUL
PY 2010
VL 9
IS 7
BP 513
EP 514
DI 10.1038/nrd3220
PG 2
WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy
SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy
GA 628TF
UT WOS:000280143900016
PM 20592741
ER
PT J
AU Lawler, EV
Gagnon, DR
Fink, J
Seliger, S
Fonda, J
Do, TP
Gaziano, JM
Bradbury, BD
AF Lawler, Elizabeth V.
Gagnon, David R.
Fink, Jeffrey
Seliger, Stephen
Fonda, Jennifer
Do, Thy P.
Gaziano, J. Michael
Bradbury, Brian D.
TI Initiation of anaemia management in patients with chronic kidney disease
not on dialysis in the Veterans Health Administration
SO NEPHROLOGY DIALYSIS TRANSPLANTATION
LA English
DT Article
DE anaemia; chronic kidney disease; dialysis; ESA agents; iron therapy
ID UNITED-STATES; HEMODIALYSIS-PATIENTS; RENAL-DISEASE; PREVALENCE;
MORTALITY; ASSOCIATIONS; POPULATION; PREDICTORS; CARE
AB Methods. A retrospective cohort study of Veterans Health Administration data from 2003 to 2005 for 89 585 patients identified as having CKD and anaemia based on two outpatient estimated glomerular filtration rates < 60 ml/min/1.73 m(2) and at least one outpatient haemoglobin (Hb) < 11 g/dL. Hb levels, patient demographics, clinical and provider characteristics and procedures predicted ESA treatment initiation over 1 year of follow-up. Multivariable logistic and pooled logistic survival models identified predictors of ESA initiation.
Results. Overall, 6381 subjects (7.1%) initiated ESAs within 1 year of the index Hb; initiation was more common (8.6%) for patients with Hb < 10 g/dL. Iron therapy use varied by initial Hb levels (27.6% to 52.4%) as did transfusions (12.5% to 42.8%); each was more common at lower Hb levels. Hbs rose to above 11 g/dL for 25-50% of patients in the absence of any treatment or by transfusion/iron therapy. Factors predicting time to ESA initiation included: nephrologist [odds ratio (OR = 2.3)] or haematologist care (OR = 2.2) and iron therapy (OR = 1.6). Transfusions increased for patients with increasing follow-up time.
Conclusion. Iron therapy is more common than ESA treatment in patients with CKD and Hbs < 11 g/dL in the VA. Correction of anaemia in the absence of any ESA treatment was common at higher Hbs levels, but much less so when Hb levels fell below 10 g/dL.
C1 [Lawler, Elizabeth V.; Gagnon, David R.; Fonda, Jennifer; Gaziano, J. Michael] VA Boston Healthcare Syst, MAVERIC, VA Cooperat Studies Program, Boston, MA USA.
[Lawler, Elizabeth V.; Gagnon, David R.; Fonda, Jennifer; Gaziano, J. Michael] Harvard Univ, Sch Med, Boston, MA USA.
[Lawler, Elizabeth V.; Gaziano, J. Michael] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA.
[Fink, Jeffrey; Seliger, Stephen] Univ Maryland, Med Ctr, Baltimore, MD 21201 USA.
[Fink, Jeffrey; Seliger, Stephen] Baltimore VA Healthcare Syst, Baltimore, MD USA.
[Do, Thy P.; Bradbury, Brian D.] Amgen Inc, Dept Biostat & Epidemiol, Thousand Oaks, CA 91320 USA.
RP Lawler, EV (reprint author), VA Boston Healthcare Syst, MAVERIC, VA Cooperat Studies Program, Boston, MA USA.
EM Elizabeth.Lawler@med.va.gov
OI Gagnon, David/0000-0002-6367-3179; Fink, Jeffrey/0000-0002-5622-5052
FU VA Cooperative Studies Program; VA Boston Healthcare System; Amgen, Inc.
FX The authors would like to thank James Kaufman MD for his thoughtful
review of this manuscript. This material was the result of work
supported with the resources of the VA Cooperative Studies Program and
the use of facilities of the VA Boston Healthcare System. E.V.L.,
J.M.G., J.F. and S.S. received research grant funding from Amgen, Inc.
with no restrictions on publication. B.D.B. and T.P.D. work for the
Department of Biostatistics and Epidemiology.
NR 20
TC 8
Z9 8
U1 0
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0931-0509
J9 NEPHROL DIAL TRANSPL
JI Nephrol. Dial. Transplant.
PD JUL
PY 2010
VL 25
IS 7
BP 2237
EP 2244
DI 10.1093/ndt/gfp758
PG 8
WC Transplantation; Urology & Nephrology
SC Transplantation; Urology & Nephrology
GA 616DR
UT WOS:000279189400030
PM 20083469
ER
PT J
AU Wang, S
Jacobs, D
Andrews, H
Tsai, WY
Luo, XD
Bergmann, C
Sano, M
AF Wang, Sophia
Jacobs, Diane
Andrews, Howard
Tsai, Wei-Yann
Luo, Xiaodong
Bergmann, Christine
Sano, Mary
TI Cardiovascular risk and memory in non-demented elderly women
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE Cognitive aging; Memory; Neuropsychological assessment; Cardiac
ID CORONARY-HEART-DISEASE; ALZHEIMERS-DISEASE; METABOLIC SYNDROME; PROFILE
AB Objective: To determine whether cardiovascular (CV) risk is associated with subtle memory deficits in non-demented, healthy older women with a family history of Alzheimer disease (AD).
Methods: Baseline data of 375 participants from a randomized, double-blind placebo-controlled primary prevention trial to test the efficacy of hormone replacement therapy in delaying AD and cognitive decline were analyzed. All subjects were women over 65 with a family history of AD who had normal cognition and no active heart disease at baseline. A baseline memory composite score was calculated, consisting of immediate and delayed recall of verbal and nonverbal material. Multiple linear regression was performed to examine the association of relative CV risk with memory functioning; age, ethnicity and education level were included as covariates.
Results: Mean baseline memory composite score was significantly higher in those with low relative CHD risk than those with high relative CHD risk.
Conclusion: These findings suggest that subtle elevation of CHD risk may negatively affect memory functioning even in otherwise healthy, non-demented older women without a history of heart disease. (C) 2008 Elsevier Inc. All rights reserved.
C1 [Wang, Sophia; Jacobs, Diane; Luo, Xiaodong; Bergmann, Christine; Sano, Mary] Mt Sinai Sch Med, Dept Psychiat, Alzheimer Dis Res Ctr, New York, NY 10029 USA.
[Wang, Sophia; Jacobs, Diane; Luo, Xiaodong; Bergmann, Christine; Sano, Mary] James J Peters VAMC, Dept Psychiat, Bronx, NY 10468 USA.
[Andrews, Howard; Tsai, Wei-Yann] Columbia Univ, Mailman Sch Publ Hlth, New York, NY 10032 USA.
RP Wang, S (reprint author), James J Peters VAMC, Dept Psychiat, 130 W Kingsbridge Rd,Room 1F01C, Bronx, NY 10468 USA.
EM sophia.wang@mssm.edu; mary.sano@mssm.edu
FU National Institute of Aging [R01 AG15922]
FX This study was supported by National Institute of Aging (R01 AG15922).
NR 10
TC 4
Z9 4
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0197-4580
J9 NEUROBIOL AGING
JI Neurobiol. Aging
PD JUL
PY 2010
VL 31
IS 7
BP 1250
EP 1253
DI 10.1016/j.neurobiolaging.2008.08.007
PG 4
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA 606PD
UT WOS:000278438300017
PM 18805604
ER
PT J
AU Xing, CH
Arai, K
Park, KP
Lo, EH
AF Xing, Changhong
Arai, Ken
Park, Kyung-Pil
Lo, Eng H.
TI Induction of Vascular Endothelial Growth Factor and Matrix
Metalloproteinase-9 via CD47 Signaling in Neurovascular Cells
SO NEUROCHEMICAL RESEARCH
LA English
DT Article
DE Endothelial cell; Pericyte; Astrocyte; Blood-brain barrier; Stroke;
Integrin
ID BLOOD-BRAIN-BARRIER; ACUTE ISCHEMIC-STROKE; CEREBRAL-ISCHEMIA;
THROMBOSPONDIN-1; INFLAMMATION; DEATH; MECHANISMS; THERAPY; NEURONS;
DISEASE
AB Neurovascular injury comprises a wide spectrum of pathophysiology that underlies the progression of brain injury after cerebral ischemia. Recently, it has been shown that activation of the integrin-associated protein CD47 mediates the development of blood-brain barrier injury and edema after cerebral ischemia. However, the mechanisms that mediate these complex neurovascular effects of CD47 remain to be elucidated. Here, we compare the effects of CD47 signaling in brain endothelial cells, astrocytes, and pericytes. Exposure to 4N1 K, a specific CD47-activating peptide derived from the major CD47 ligand thrombospondin-1, upregulated two major neurovascular mediators, vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9), in brain endothelial cells and astrocytes. No changes were detected in pericytes. These findings may provide a potential mechanism for CD47-induced changes in blood-brain barrier homeostasis, and further suggest that CD47 may be a relevant neurovascular target in stroke.
C1 [Xing, Changhong; Arai, Ken; Park, Kyung-Pil; Lo, Eng H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol & Neurol,Neuroprotect Res Lab, Charlestown, MA 02129 USA.
RP Lo, EH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol & Neurol,Neuroprotect Res Lab, MGH E,149-2401,13th St, Charlestown, MA 02129 USA.
EM Lo@helix.mgh.harvard.edu
OI Park, Kyung-Pil/0000-0003-4952-3796
FU NIH [R37-NS37074, R01-NS48422, R01-NS53560, P01-NS55104]; American Heart
Association
FX Supported in part by NIH grants R37-NS37074, R01-NS48422, R01-NS53560,
P01-NS55104, and a Bugher award from the American Heart Association.
NR 30
TC 6
Z9 7
U1 0
U2 1
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0364-3190
J9 NEUROCHEM RES
JI Neurochem. Res.
PD JUL
PY 2010
VL 35
IS 7
BP 1092
EP 1097
DI 10.1007/s11064-010-0159-6
PG 6
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 606GP
UT WOS:000278411000016
PM 20364320
ER
PT J
AU Willette, AA
Bendlin, BB
McLaren, DG
Canu, E
Kastman, EK
Kosmatka, KJ
Xu, G
Field, AS
Alexander, AL
Colman, RJ
Weindruch, RH
Coe, CL
Johnson, SC
AF Willette, A. A.
Bendlin, B. B.
McLaren, D. G.
Canu, E.
Kastman, E. K.
Kosmatka, K. J.
Xu, G.
Field, A. S.
Alexander, A. L.
Colman, R. J.
Weindruch, R. H.
Coe, C. L.
Johnson, S. C.
TI Age-related changes in neural volume and microstructure associated with
interleukin-6 are ameliorated by a calorie-restricted diet in old rhesus
monkeys
SO NEUROIMAGE
LA English
DT Article
DE Monkey; Voxel-based morphometry; Calorie restriction; Aging;
Interleukin-6; Atrophy
ID VOXEL-BASED MORPHOMETRY; ALZHEIMERS-DISEASE; IN-VIVO; SICKNESS BEHAVIOR;
ADIPOSE-TISSUE; CHRONIC NEURODEGENERATION; INFLAMMATORY BIOMARKERS;
FRACTIONAL ANISOTROPY; GENE-EXPRESSION; MATTER VOLUME
AB Systemic levels of proinflammatory cytokines such as interleukin-6 (IL-6) increase in old age and may contribute to neural atrophy in humans. We investigated IL-6 associations with age in T1-weighted segments and microstructural diffusion indices using MRI in aged rhesus monkeys (Macaca mulatto). Further, we determined if long-term 30% calorie restriction (CR) reduced IL-6 and attenuated its association with lower tissue volume and density. Voxel-based morphometry (VBM) and diffusion-weighted voxelwise analyses were conducted. IL-6 was associated with less global gray and white matter (GM and WM), as well as smaller parietal and temporal GM volumes. Lower fractional anisotropy (FA) was associated with higher IL-6 levels along the corpus callosum and various cortical and subcortical tracts. Higher IL-6 concentrations across subjects were also associated with increased mean diffusivity (MD) throughout many brain regions. particularly in corpus callosum, cingulum, and parietal, frontal, and prefrontal areas. CR monkeys had significantly lower IL-6 and less associated atrophy. An IL-6 x CR interaction across modalities also indicated that CR mitigated IL-6 related changes in several brain regions compared to controls. Peripheral IL-6 levels were correlated with atrophy in regions sensitive to aging, and this relationship was decreased by CR. Published by Elsevier Inc.
C1 [Bendlin, B. B.; McLaren, D. G.; Canu, E.; Kastman, E. K.; Xu, G.; Weindruch, R. H.; Johnson, S. C.] William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Madison, WI 53705 USA.
[Willette, A. A.] Dept Psychol, Harlow Primate Lab, Madison, WI 53715 USA.
[McLaren, D. G.] Univ Wisconsin, Neurosci Training Program, Madison, WI 53706 USA.
[Bendlin, B. B.; McLaren, D. G.; Kastman, E. K.; Kosmatka, K. J.; Weindruch, R. H.; Johnson, S. C.] Univ Wisconsin, Dept Med, Madison, WI 53705 USA.
[Alexander, A. L.] Univ Wisconsin, Waisman Imaging Ctr, Madison, WI 53705 USA.
[Field, A. S.; Weindruch, R. H.] Univ Wisconsin, Dept Radiol, Madison, WI 53792 USA.
[Colman, R. J.; Johnson, S. C.] Wisconsin Natl Primate Res Ctr, Madison, WI 53715 USA.
RP Johnson, SC (reprint author), D4225 Vet Adm Hosp, Geriatr Res Educ & Clin Ctr, 2500 Overlook Terrace, Madison, WI 53705 USA.
EM scj@medicine.wisc.edu
RI McLaren, Donald/G-9906-2011; Kastman, Erik/N-6645-2016; Canu,
Elisa/K-1423-2016
OI Kastman, Erik/0000-0001-7221-9042; Bendlin, Barbara/0000-0002-0580-9875;
Canu, Elisa/0000-0001-5804-3378
FU National Institutes of Health [RR000167, AG011915, AG000213, GM007507,
MH085051, MH062015]; Ford Foundation; Marian S. Schwartz fellowship;
National Science Foundation; William S. Middleton Memorial Veterans
Hospital, Madison, WI, USA
FX The assistance of Michele E. Fitzgerald, Ron Fisher, Scott T. Baum, Josh
Smith, Mary Lou Voytko, and the Waisman Center for Brain Imaging is
greatly appreciated. GRECC manuscript number: 2010-XX. This study was
supported in part by the National Institutes of Health grants RR000167,
AG011915, AG000213, GM007507, MH085051, and MH062015. The study was also
supported with resources and use of facilities at the William S.
Middleton Memorial Veterans Hospital, Madison, WI, USA. A.A.W. was
supported by a pre-doctoral fellowship from the Ford Foundation, and
professional funding from a Marian S. Schwartz fellowship and National
Science Foundation-Alliances for Graduate Education and the
Professoriate award.
NR 70
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Z9 31
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 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD JUL 1
PY 2010
VL 51
IS 3
BP 987
EP 994
DI 10.1016/j.neuroimage.2010.03.015
PG 8
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 594JF
UT WOS:000277532900005
PM 20298794
ER
PT J
AU Zaitchik, D
Walker, C
Miller, S
LaViolette, P
Feczko, E
Dickerson, BC
AF Zaitchik, Deborah
Walker, Caren
Miller, Saul
LaViolette, Pete
Feczko, Eric
Dickerson, Bradford C.
TI Mental state attribution and the temporoparietal junction: An fMRI study
comparing belief, emotion, and perception
SO NEUROPSYCHOLOGIA
LA English
DT Article
DE Functional magnetic resonance imaging; Theory of mind; Parietal cortex;
Temporal cortex
ID TEMPORO-PARIETAL JUNCTION; SOCIAL COGNITION; FALSE BELIEFS; MIND; BRAIN;
PERSPECTIVE; THINKING; CORTEX; REPRESENTATIONS; METAANALYSIS
AB By age 2, children attribute referential mental states such as perceptions and emotions to themselves and others, yet it is not until age 4 that they attribute representational mental states such as beliefs. This raises an interesting question: is attribution of beliefs different from attribution of perceptions and emotions in terms of its neural substrate? To address this question with a high degree of anatomic specificity, we partitioned the TPJ, a broad area often found to be recruited in theory of mind tasks, into 2 neuroanatomically specific regions of interest: Superior Temporal Sulcus (STS) and Inferior Parietal Lobule (IPL). To maximize behavioral specificity, we designed a tightly controlled verbal task comprised of sets of single sentences - sentences identical except for the type of mental state specified in the verb (belief, emotion, perception, syntax control). Results indicated that attribution of beliefs more strongly recruited both regions of interest than did emotions or perceptions. This is especially surprising with respect to STS, since it is widely reported in the literature to mediate the detection of referential states among them emotions and perceptions - rather than the inference of beliefs. An explanation is offered that focuses on the differences between verbal stimuli and visual stimuli, and between a process of sentence comprehension and a process of visual detection. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Zaitchik, Deborah] Massachusetts Gen Hosp, Gerontol Res Unit, Dept Psychiat, Charlestown, MA 02129 USA.
[Dickerson, Bradford C.] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA.
[Dickerson, Bradford C.] Massachusetts Gen Hosp, Massachusetts Alzheimers Dis Res Ctr, Charlestown, MA 02129 USA.
[Dickerson, Bradford C.] Massachusetts Gen Hosp, Frontotemporal Dementia Unit, Charlestown, MA 02129 USA.
[Dickerson, Bradford C.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
[Zaitchik, Deborah; Dickerson, Bradford C.] Harvard Univ, Sch Med, Boston, MA USA.
[Walker, Caren] Univ Calif Berkeley, Berkeley, CA 94720 USA.
[Miller, Saul] Florida State Univ, Tallahassee, FL 32306 USA.
[LaViolette, Pete] Med Coll Wisconsin, Milwaukee, WI 53226 USA.
[Feczko, Eric] Washington Univ, St Louis, MO USA.
RP Zaitchik, D (reprint author), Massachusetts Gen Hosp, Gerontol Res Unit, Dept Psychiat, 149 13th St,Suite 2691, Charlestown, MA 02129 USA.
EM dzaitchiksamet@partners.org
FU NIA [K23-AG22509, R01-AG29411]; NCRR [P41-RR14075, U24-RR021382]; Mental
Illness and Neuroscience Discovery (MIND) Institute
FX This study was supported by the NIA (K23-AG22509, R01-AG29411), the NCRR
(P41-RR14075, U24-RR021382), and the Mental Illness and Neuroscience
Discovery (MIND) Institute. The authors thank Mary Foley, Larry White,
and Jill Clark for technical assistance.
NR 51
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Z9 20
U1 2
U2 13
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0028-3932
J9 NEUROPSYCHOLOGIA
JI Neuropsychologia
PD JUL
PY 2010
VL 48
IS 9
BP 2528
EP 2536
DI 10.1016/j.neuropsychologia.2010.04.031
PG 9
WC Behavioral Sciences; Neurosciences; Psychology, Experimental
SC Behavioral Sciences; Neurosciences & Neurology; Psychology
GA 634ID
UT WOS:000280573300013
PM 20435051
ER
PT J
AU Verfaellie, M
LaRocque, KF
Rajaram, S
AF Verfaellie, Mieke
LaRocque, Karen F.
Rajaram, Suparna
TI Benefits of Immediate Repetition Versus Long Study Presentation on
Memory in Amnesia
SO NEUROPSYCHOLOGY
LA English
DT Article
DE amnesia; repetition; recognition memory
ID MEDIAL TEMPORAL-LOBE; RECOGNITION MEMORY; MIXING COSTS; MIRROR;
INFORMATION; RECALL; TIME; ALLOCATION; MODALITY; ACCOUNT
AB Objective: This study aimed to resolve discrepant findings in the literature regarding the effects of massed repetition and a single long study presentation on memory in amnesia. Method: Experiment I assessed recognition memory in 9 amnesic patients and 18 controls following presentation of a study list that contained items shown for a single short study presentation, a single long study presentation, and three massed repetitions. In Experiment 2, the same encoding conditions were presented in a blocked rather than intermixed format to all participants from Experiment I. Results: In Experiment I. control participants showed benefits associated with both types of extended exposure, and massed repetition was more beneficial than long study presentation, F(2, 34) = 14.03, p < .001, partial 12 = .45. In contrast, amnesic participants failed to show benefits of either type of extended exposure, F < I. In Experiment 2, both groups benefited from repetition, but did so in different ways, F(2, 50) = 4.80, p = .012, partial eta(2) = .16. Amnesic patients showed significant and equivalent benefit associated with both types of extended exposure, F(2, 16) = 5.58, p = .015, partial eta(2) = .41, but control participants again benefited more from massed repetition than from long study presentation, F(2, 34) = 23.74, p < .001, partial eta(2) = .58. Conclusions: The findings suggest that previous inconsistencies in the literature were due to procedural differences across studies. We discuss group differences in terms of the mechanisms by which both forms of extended exposure facilitate performance in each group.
C1 [Verfaellie, Mieke; LaRocque, Karen F.] VA Boston Healthcare Syst, Memory Disorders Res Ctr, Boston, MA 02130 USA.
[Verfaellie, Mieke; LaRocque, Karen F.] Boston Univ, Sch Med, Boston, MA 02215 USA.
[Rajaram, Suparna] SUNY Stony Brook, Dept Psychol, Stony Brook, NY USA.
RP Verfaellie, M (reprint author), VA Boston Healthcare Syst, Memory Disorders Res Ctr 151A, 150 S Huntington Avenue, Boston, MA 02130 USA.
EM verf@bu.edu
OI Verfaellie, Mieke/0000-0001-5535-4584; LaRocque,
Karen/0000-0002-6058-2706
FU NIH [MH71783]; Medical Research Service of the Department of Veterans
Affairs
FX This research was supported by NIH grant MH71783 and by the Medical
Research Service of the Department of Veterans Affairs. The authors have
no financial or other relationships that could be interpreted as a
conflict of interest affecting this article.
NR 30
TC 0
Z9 0
U1 2
U2 2
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0894-4105
J9 NEUROPSYCHOLOGY
JI Neuropsychology
PD JUL
PY 2010
VL 24
IS 4
BP 457
EP 464
DI 10.1037/a0018625
PG 8
WC Psychology, Clinical; Neurosciences; Psychology
SC Psychology; Neurosciences & Neurology
GA 619HN
UT WOS:000279420500005
PM 20604620
ER
PT J
AU Thompson, EM
Dosa, E
Kraemer, DF
Neuwelt, EA
AF Thompson, Eric M.
Dosa, Edit
Kraemer, Dale F.
Neuwelt, Edward A.
TI Treatment With Bevacizumab Plus Carboplatin for Recurrent Malignant
Glioma
SO NEUROSURGERY
LA English
DT Article
DE Bevacizumab; Carboplatin; Imaging response; Recurrent malignant glioma;
Toxicity
ID HIGH-GRADE GLIOMAS; PHASE-II; INTRAVENOUS CARBOPLATIN; BRAIN-TUMORS;
IRINOTECAN; SURVIVAL; CANCER; CHEMOTHERAPY; AGREEMENT; EFFICACY
AB OBJECTIVE: To estimate overall survival (OS), progression-free survival (PFS), imaging responses, and toxicities of bevacizumab plus carboplatin for the treatment of recurrent malignant glioma. The secondary objective was to estimate the agreement between postcontrast T1-weighted and T2-weighted magnetic resonance imaging.
METHODS: A retrospective analysis of 9 patients who received bevacizumab (10 mg/kg intravenously) and carboplatin (AUC 5 intravenously) for recurrent malignant glioma (World Health Organization grades III and IV) is presented. Eight of 9 patients received this regimen at first recurrence.
RESULTS: The median age and Karnofsky performance score were 51 years and 70, respectively. For the 5 patients with grade III gliomas, the median PFS was 126 days, whereas median OS was not attained at 517 days of follow-up. Six-month PFS was 40%, whereas 6-month OS was 60%. For the 4 patients with grade IV gliomas, the median PFS was 216 days, whereas the median OS was not attained at 482 days of follow-up. Six-month PFS was 50%, whereas 6-month OS was 75%. The agreement between contrast-enhanced T1-weighted and T2-weighted images to determine recurrence was moderate (kappa = 0.5714). Three patients had grade 3 and 4 toxicities including hyponatremia and thrombocytopenia.
CONCLUSION: Patients who received the combination of bevacizumab plus carboplatin for recurrent malignant glioma had reasonable PFS, OS, and toxicities. The median OS in our series is promising at well over 1 year. Agreement between postcontrast T1- and T2-weighted images is only moderate in the context of bevacizumab therapy.
C1 [Neuwelt, Edward A.] Oregon Hlth & Sci Univ, Dept Neurol, Blood Brain Barrier Program, Portland Vet Affairs Med Ctr, Portland, OR 97239 USA.
[Neuwelt, Edward A.] Oregon Hlth & Sci Univ, Dept Neurol Surg, Portland Vet Affairs Med Ctr, Portland, OR 97239 USA.
[Kraemer, Dale F.] Oregon Hlth & Sci Univ, Dept Med Informat Clin Epidemiol & Hlth & Prevent, Dept Pharm Practice, Oregon State Univ,Coll Med, Portland, OR 97239 USA.
RP Neuwelt, EA (reprint author), Oregon Hlth & Sci Univ, Dept Neurol, Blood Brain Barrier Program, Portland Vet Affairs Med Ctr, 3181 Sam Jackson Pkwy Rd,L603, Portland, OR 97239 USA.
EM neuwelte@ohsu.edu
FU National Institutes of Health, National Institute of Neurological
Disorders and Stroke [NS33618, NS34608, NS44687]; Department of Veterans
Affairs
FX Supported by National Institutes of Health grants NS33618, NS34608, and
NS44687 from the National Institute of Neurological Disorders and Stroke
(E.A.N.). This work was supported in part by the Department of Veterans
Affairs (E.A.N.). The authors have no personal financial or
institutional interest in any of the drugs or materials described in
this article.
NR 32
TC 12
Z9 12
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0148-396X
J9 NEUROSURGERY
JI Neurosurgery
PD JUL
PY 2010
VL 67
IS 1
BP 87
EP 93
DI 10.1227/01.NEU.0000370918.51053.BC
PG 7
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA 612CW
UT WOS:000278875400024
PM 20559095
ER
PT J
AU Bauman, ML
AF Bauman, Margaret L.
TI Medical Comorbidities in Autism: Challenges to Diagnosis and Treatment
SO NEUROTHERAPEUTICS
LA English
DT Review
DE Autism; medical conditions; atypical behaviors; diagnosis; management
ID SPECTRUM DISORDERS; SLEEP DISORDERS; INTERVENTION; PREVALENCE; BEHAVIOR;
EPILEPSY; CHILDREN; RISK; ASDS
AB Ever since its original description by Leo Kanner in l943, autism has been generally defined by its clinical characteristics and core symptoms that include impaired social skills, isolated areas of interest, and delayed and disordered language. Over time, it has become apparent that autism is a heterogeneous disorder with regard to its clinical presentation, etiology, underlying neurobiology, and degree of severity. As a result, the termed diagnosis of autism spectrum disorders (ASDs) has come into common usage. With advancements in clinical care, there has come the appreciation that many ASD children, adolescents, and adults may have medically relevant disorders that may negatively impact their developmental progress and behavior, but which frequently go undetected. Many of these medical conditions are treatable, often resulting in improved developmental gains and quality of life for the patient and family. In addition, the possibility exists that some of these medical conditions may suggest the presence of important genetic and/or biologic markers, which, if identified, can refine our ability to be more precise in categorizing clinical and genetic subtypes within the autism spectrum.
C1 [Bauman, Margaret L.] Massachusetts Gen Hosp, Dept Neurol, Dept Pediat, Boston, MA 02114 USA.
[Bauman, Margaret L.] Massachusetts Gen Hosp, Lurie Ctr, LADDERS Program, Boston, MA 02114 USA.
[Bauman, Margaret L.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA.
RP Bauman, ML (reprint author), Lurie Ctr LADDERS, 1 Maguire Rd, Lexington, MA 02421 USA.
EM drb@ladders.org
NR 42
TC 70
Z9 71
U1 2
U2 14
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1933-7213
J9 NEUROTHERAPEUTICS
JI Neurotherapeutics
PD JUL
PY 2010
VL 7
IS 3
BP 320
EP 327
PG 8
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 627SQ
UT WOS:000280063300013
PM 20643385
ER
PT J
AU Deshmukh, U
Adams, J
Dhillon, R
McCarthy, K
Macklin, E
Holmes, L
AF Deshmukh, Uma
Adams, Jane
Dhillon, Ruby
McCarthy, Katherine
Macklin, Eric
Holmes, Lewis
TI Behavioral outcome in children exposed prenatally to lamotrigine,
valproate, or carbamazepine: Increased risks for valproate
SO NEUROTOXICOLOGY AND TERATOLOGY
LA English
DT Meeting Abstract
CT 34th Annual Meeting of the Neurobehavioral-Teratology-Society/50th
Annual Meeting of the Teratology-Society/23rd Annual Meeting of the
Organization-of-Teratology-Information-Specialists
CY JUN 26-30, 2010
CL Louisville, KY
SP Neurobehav Teratol Soc, Teratol Soc, Org Teratol Informat Specialists
C1 [Deshmukh, Uma; Dhillon, Ruby; McCarthy, Katherine; Macklin, Eric; Holmes, Lewis] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Adams, Jane] Univ Massachusetts, Boston, MA 02125 USA.
[Holmes, Lewis] Harvard Univ, Sch Med, Boston, MA USA.
RI Macklin, Eric/E-2955-2013
OI Macklin, Eric/0000-0003-1618-3502
NR 0
TC 0
Z9 0
U1 0
U2 1
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0892-0362
J9 NEUROTOXICOL TERATOL
JI Neurotoxicol. Teratol.
PD JUL-AUG
PY 2010
VL 32
IS 4
MA NBTS45
BP 509
EP 509
DI 10.1016/j.ntt.2010.04.046
PG 1
WC Neurosciences; Toxicology
SC Neurosciences & Neurology; Toxicology
GA 620VF
UT WOS:000279528000053
ER
PT J
AU Parikh, JR
Klinger, B
Xia, Y
Marto, JA
Bluthgen, N
AF Parikh, Jignesh R.
Klinger, Bertram
Xia, Yu
Marto, Jarrod A.
Bluethgen, Nils
TI Discovering causal signaling pathways through gene-expression patterns
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID GROWTH-FACTOR; MYELOID-LEUKEMIA; OMNIBUS GEO; TRANSCRIPTION; CANCER;
IDENTIFICATION; LIPOPOLYSACCHARIDE; PHOSPHORYLATION; BIOINFORMATICS;
MACROPHAGES
AB High-throughput gene-expression studies result in lists of differentially expressed genes. Most current meta-analyses of these gene lists include searching for significant membership of the translated proteins in various signaling pathways. However, such membership enrichment algorithms do not provide insight into which pathways caused the genes to be differentially expressed in the first place. Here, we present an intuitive approach for discovering upstream signaling pathways responsible for regulating these differentially expressed genes. We identify consistently regulated signature genes specific for signal transduction pathways from a panel of single-pathway perturbation experiments. An algorithm that detects overrepresentation of these signature genes in a gene group of interest is used to infer the signaling pathway responsible for regulation. We expose our novel resource and algorithm through a web server called SPEED: Signaling Pathway Enrichment using Experimental Data sets. SPEED can be freely accessed at http://speed.sys-bio.net/.
C1 [Klinger, Bertram; Bluethgen, Nils] Charite Univ Med Berlin, Inst Pathol, Berlin, Germany.
[Parikh, Jignesh R.; Xia, Yu] Boston Univ, Bioinformat Program, Boston, MA 02115 USA.
[Klinger, Bertram; Bluethgen, Nils] Humboldt Univ, Inst Theoret Biol, Berlin, Germany.
[Xia, Yu] Boston Univ, Dept Chem, Boston, MA 02115 USA.
[Xia, Yu] Boston Univ, Dept Biomed Engn, Boston, MA 02115 USA.
[Marto, Jarrod A.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Marto, Jarrod A.] Dana Farber Canc Inst, Blais Prote Ctr, Boston, MA 02115 USA.
[Marto, Jarrod A.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
RP Bluthgen, N (reprint author), Charite Univ Med Berlin, Inst Pathol, Berlin, Germany.
EM nils.bluethgen@charite.de
RI Bluthgen, Nils/A-1711-2011;
OI Bluthgen, Nils/0000-0002-0171-7447; Xia, Yu/0000-0002-5596-5518
FU Germany's Federal Ministry for Education and Research (BMBF) [Forsys
Partner]; European Commission [CancerSys HEALTH-F4-2008-223188];
National Science Foundation [DGE-0654108]
FX Germany's Federal Ministry for Education and Research (BMBF) (grant
Forsys Partner to N.B.); the European Commission (grant number CancerSys
HEALTHF-4-2008-223188 to N.B.); National Science Foundation Integrative
Graduate Education and Research Traineeship (IGERT) (grant number
DGE-0654108 to J.P.). Funding for open access charge: National Science
Foundation Integrative Graduate Education and Research Traineeship
(IGERT) (grant number DGE-0654108).
NR 39
TC 15
Z9 15
U1 0
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JUL
PY 2010
VL 38
SU 2
BP W109
EP W117
DI 10.1093/nar/gkq424
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 679GD
UT WOS:000284148900019
PM 20494976
ER
PT J
AU Sander, JD
Maeder, ML
Reyon, D
Voytas, DF
Joung, JK
Dobbs, D
AF Sander, Jeffry D.
Maeder, Morgan L.
Reyon, Deepak
Voytas, Daniel F.
Joung, J. Keith
Dobbs, Drena
TI ZiFiT (Zinc Finger Targeter): an updated zinc finger engineering tool
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID ARTIFICIAL TRANSCRIPTION FACTORS; DNA-RECOGNITION; ZIF268-DNA COMPLEXES;
RESTRICTION ENZYMES; CRYSTAL-STRUCTURE; NUCLEASES; CONSTRUCTION;
PROTEINS; CLEAVAGE; DOMAINS
AB ZiFiT (Zinc Finger Targeter) is a simple and intuitive web-based tool that provides an interface to identify potential binding sites for engineered zinc finger proteins (ZFPs) in user-supplied DNA sequences. In this updated version, ZiFiT identifies potential sites for ZFPs made by both the modular assembly and OPEN engineering methods. In addition, ZiFiT now integrates additional tools and resources including scoring schemes for modular assembly, an interface with the Zinc Finger Database (ZiFDB) of engineered ZFPs, and direct querying of NCBI BLAST servers for identifying potential off-target sites within a host genome. Taken together, these features facilitate design of ZFPs using reagents made available to the academic research community by the Zinc Finger Consortium. ZiFiT is freely available on the web without registration at http://bindr.gdcb.iastate.edu/ZiFiT/.
C1 [Sander, Jeffry D.; Maeder, Morgan L.; Joung, J. Keith] Massachusetts Gen Hosp, Mol Pathol Unit, Ctr Canc Res, Charlestown, MA 02129 USA.
[Sander, Jeffry D.; Maeder, Morgan L.; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Charlestown, MA 02129 USA.
[Sander, Jeffry D.; Joung, J. Keith] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Maeder, Morgan L.; Joung, J. Keith] Harvard Univ, Sch Med, Biol & Biomed Sci Program, Boston, MA 02115 USA.
[Reyon, Deepak; Dobbs, Drena] Iowa State Univ, Dept Genet Dev & Cell Biol, Interdept Grad Program Bioinformat & Computat Bio, Ames, IA 50011 USA.
[Voytas, Daniel F.] Univ Minnesota, Dept Genet Cell Biol & Dev, Ctr Genome Engn, Minneapolis, MN 55455 USA.
RP Sander, JD (reprint author), Massachusetts Gen Hosp, Mol Pathol Unit, Ctr Canc Res, Charlestown, MA 02129 USA.
EM jsander@partners.org
FU National Institutes of Health [T32CA009216, R01 GM069906, R01 GM072621,
R01 GM088040]; National Science Foundation [2009080622, DBI 0923827, DBI
0501678]; Massachusetts General Hospital Pathology Service
FX National Institutes of Health [T32CA009216] to J.D.S.; National Science
Foundation Graduate Research Fellowship [2009080622] to M.L.M.; National
Science Foundation [DBI 0923827, DBI 0501678] to D.F.V.; National
Institutes of Health [R01 GM069906, R01 GM072621, R01 GM088040], the
National Science Foundation [DBI 0923827] and Massachusetts General
Hospital Pathology Service to J.K.J.; National Science Foundation [DBI
0923827] to D.D. and D.R. Funding for open access charge: National
Science Foundation [DBI 0923827].
NR 42
TC 114
Z9 124
U1 2
U2 18
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JUL
PY 2010
VL 38
SU 2
BP W462
EP W468
DI 10.1093/nar/gkq319
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 679GD
UT WOS:000284148900075
PM 20435679
ER
PT J
AU Donelan, K
Buerhaus, PI
DesRoches, C
Burke, SP
AF Donelan, Karen
Buerhaus, Peter I.
DesRoches, Catherine
Burke, Sheila P.
TI Health policy thoughtleaders' views of the health workforce in an era of
health reform
SO NURSING OUTLOOK
LA English
DT Article
ID PHYSICIANS
AB Although registered nurses rank similarly with physicians in the public's esteem, physicians are more visible than nurses in media coverage, public policy, and political spheres. Thus, nursing workforce issues are overshadowed by those of other health priorities, including Medicare and health reform.
The purpose of this research was to understand the visibility and salience of the health workforce in general, gain an understanding about the effectiveness of messages concerning the nursing workforce in particular, and to understand why nursing workforce issues do not appear to have gained more traction in national health care policymaking.
The National Survey of Thoughtleaders about the Health Workforce was administered via mail, telephone and online to health workforce and policy thoughtleaders from August 2009-October 2009. Of 301 thoughtleaders contacted, 123 completed questionnaires for a response rate of 41%.
Thoughtleaders agree that nurses are critical to the quality and safety of our healthcare system, that there are current nursing shortages, and that nursing shortages will be intensified by health reform. Thoughtleaders reported that while they do hear about nursing issues frequently, they do not view most sources of information as proposing effective policy solutions.
This study highlights a critical gap in effective policy advocacy and leadership to advance nurse workforce issues higher on the national health agenda.
C1 [Buerhaus, Peter I.] Vanderbilt Univ, Ctr Interdisciplinary Hlth Workforce Studies, Inst Med & Publ Hlth, Med Ctr, Nashville, TN USA.
[Donelan, Karen; DesRoches, Catherine] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA.
[Burke, Sheila P.] Harvard Univ, John F Kennedy Sch Govt, Cambridge, MA 02138 USA.
RP Donelan, K (reprint author), Massachusetts Gen Hosp, Mongan Inst Hlth Policy, 50 Staniford St,9th Floor, Boston, MA 02114 USA.
EM kdonelan@partners.org
FU Johnson & Johnson Compaign for Nursing's Future to the Vanderbilt
University School of Nursing
FX This project was funded by an unrestricted grant from the Johnson &
Johnson Compaign for Nursing's Future to the Vanderbilt University
School of Nursing. The authors gratefully acknowledge the advice of Dr.
Paul Feldstein and Mr. John Iglehart in the development of our survey
and survey sample, the support and assistance of SSRS in data collection
(Dr. David Dutwin) and the assistance of Johanna Mailhot, MSc, in
manuscript preparation.
NR 9
TC 7
Z9 7
U1 0
U2 2
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 JUL-AUG
PY 2010
VL 58
IS 4
BP 175
EP 180
DI 10.1016/j.outlook.2010.06.003
PG 6
WC Nursing
SC Nursing
GA 635LN
UT WOS:000280657200005
PM 20637930
ER
PT J
AU Penson, RT
Schapira, L
Mack, S
Stanzler, M
Lynch, TJ
AF Penson, Richard T.
Schapira, Lidia
Mack, Sally
Stanzler, Marjorie
Lynch, Thomas J., Jr.
TI Connection: Schwartz Center Rounds at Massachusetts General Hospital
Cancer Center
SO ONCOLOGIST
LA English
DT Article
ID PERSPECTIVE; CARE
AB Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital, founded the Kenneth B. Schwartz Center (R), a nonprofit organization dedicated to supporting and advancing compassionate health care. The Center sponsors Schwartz Rounds (R), a multidisciplinary forum in which doctors, nurses, chaplains, social workers, and other staff reflect on important psychosocial issues that arise in caring for patients. Attendees participate in an interactive discussion about issues anchored in a case presentation and share their experiences, thoughts, and feelings. The patient narratives may center on wonderful events and transcendent experiences or tragic stories, during which staff can only bear witness to the suffering. The Rounds focus on caregivers' experiences, and encourage staff to share insights, own their vulner-abilities, and support each other. The primary objective is to foster healing relationships and provide support to professional caregivers, enhance communication among caregivers, and improve the connection between patients and caregivers. Currently, >50,000 clinicians attend monthly Schwartz Rounds at 195 sites in 31 states, numbers that are rapidly growing. In this article we explore the reasons that contribute to the success of this model of multidisciplinary reflection. The Oncologist 2010;15:760-764
C1 [Penson, Richard T.; Schapira, Lidia] Massachusetts Gen Hosp, Ctr Canc, Dept Med, Div Hematol Oncol, Boston, MA USA.
[Stanzler, Marjorie] Kenneth B Schwartz Ctr, Boston, MA USA.
[Lynch, Thomas J., Jr.] Yale Canc Ctr, New Haven, CT USA.
RP Penson, RT (reprint author), Yawkey 9064,55 Fruit St, Boston, MA 02114 USA.
EM rpenson@partners.org
FU Genentech, Inc.; Lilly and Company; GlaxoSmithKline; CuraGen
Corporation; PDL BioPharma, Inc.; ImClone Systems, Inc.; Endocyte, Inc.;
AstraZeneca
FX Richard T. Penson: Employment/leadership position: Data Safety
Monitoring Committee for Genentech; Consultant/advisory role: National
Comprehensive Cancer Network; Research funding/contracted research:
Genentech, Inc., Lilly and Company, GlaxoSmithKline, CuraGen
Corporation, PDL BioPharma, Inc., ImClone Systems, Inc., Endocyte, Inc.,
AstraZeneca; Lidia Schapira: None; Sally Mack: None; Marjorie Stanzler:
None; Thomas J. Lynch, Jr.: Leadership position: Board of Directors,
Infinity, and Board Chair for Kenneth Schwartz Center; Intellectual
property/patent: EGFR mutation patent; Consultant/advisory role:
AstraZeneca, Boehringer Ingelheim, Roche.
NR 12
TC 5
Z9 5
U1 3
U2 7
PU ALPHAMED PRESS
PI DURHAM
PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA
SN 1083-7159
J9 ONCOLOGIST
JI Oncologist
PD JUL
PY 2010
VL 15
IS 7
BP 760
EP 764
DI 10.1634/theoncologist.2009-0329
PG 5
WC Oncology
SC Oncology
GA 633FH
UT WOS:000280484600011
PM 20584809
ER
PT J
AU Nguyen, PL
D'Amico, AV
AF Nguyen, Paul L.
D'Amico, Anthony V.
TI Deciding Which Patients to Treat With Salvage Radiotherapy After
Prostatectomy
SO ONCOLOGY-NEW YORK
LA English
DT Editorial Material
ID PELVIC LYMPH-NODES; PHASE-III TRIAL; RADICAL PROSTATECTOMY; BIOCHEMICAL
RECURRENCE; ANDROGEN SUPPRESSION; RANDOMIZED-TRIALS; RADIATION-THERAPY;
CANCER; RISK; MEN
C1 [Nguyen, Paul L.; D'Amico, Anthony V.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol,Brigham & Womens Hosp, Boston, MA 02115 USA.
RP Nguyen, PL (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol,Brigham & Womens Hosp, 44 Binney St, Boston, MA 02115 USA.
NR 13
TC 0
Z9 0
U1 0
U2 0
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 JUL
PY 2010
VL 24
IS 8
BP 705
EP 711
PG 2
WC Oncology
SC Oncology
GA 800BJ
UT WOS:000293331700003
PM 20718250
ER
PT J
AU Liu, J
Matulonis, UA
AF Liu, Joyce
Matulonis, Ursula A.
TI New Advances in Ovarian Cancer Ovarian Cancer Care: It's Time for
"Personalized" Approaches
SO ONCOLOGY-NEW YORK
LA English
DT Article
ID PHASE-III TRIAL; PLATINUM-BASED CHEMOTHERAPY;
GYNECOLOGIC-ONCOLOGY-GROUP; LIPOSOMAL DOXORUBICIN PLD; STAGE-III;
INTRAPERITONEAL CISPLATIN; EPITHELIAL OVARIAN; INTRAVENOUS PACLITAXEL;
PLUS CARBOPLATIN; CARCINOMA
AB Epithelial ovarian cancer is the leading cause of death from gynecologic malignancy in the United States, with approximately 15,000 deaths per year. Platinum/taxane doublets have long been considered the standard treatment regimen for advanced-stage disease; however, recent studies have sought to improve on the outcome from this therapy. Intraperitoneal (IP) chemotherapy has been shown to yield superior progression-free survival (PFS) and overall survival (OS); however, logistical problems and toxicities have limited more widespread adoption. Recent studies have also suggested that a "dose-dense" schedule of paclitaxel in combination with carboplatin may result in improved outcomes, and the impact of biological therapies in the first-line setting is under active investigation. In the setting of recurrent disease, preliminary results suggest that novel doublet regimens such as carboplatin and pegylated liposomal doxorubicin may have similar activity to standard platinum/taxane doublets while carrying a reduced risk of allergic reactions. Additionally, targeted therapy remains an active area of investigation, with evidence of activity from agents such as PARP inhibitors, anti-angiogenics, and PI3 kinase inhibitors. Here, we review recent advances in our understanding of ovarian cancer and its treatment in both the newly diagnosed and recurrent settings.
C1 [Liu, Joyce; Matulonis, Ursula A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
RP Liu, J (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
FU Genentech; AstraZeneca
FX Dr. Matulonis has received clinical research support from Genentech and
AstraZeneca.
NR 40
TC 16
Z9 19
U1 0
U2 2
PU UBM MEDICA
PI NORWALK
PA 535 CONNECTICUT AVE, STE 300, NORWALK, CT 06854 USA
SN 0890-9091
J9 ONCOLOGY-NY
JI Oncology-NY
PD JUL
PY 2010
VL 24
IS 8
BP 721
EP 728
PG 8
WC Oncology
SC Oncology
GA 800BJ
UT WOS:000293331700005
PM 20718251
ER
PT J
AU Jakobiec, FA
Bhat, P
Kropp, TM
AF Jakobiec, Frederick A.
Bhat, Pooja
Kropp, Thomas M.
TI Palpebro-Orbital Apocrine Cystadenoma: Immunohistochemical Verification
of a Unique Variant With a Critical Differential Diagnosis
SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY
LA English
DT Article
ID SUDORIFEROUS CYST; LIESEGANG RINGS; DERMOID CYST; MANAGEMENT; ORIGIN;
HIDROCYSTOMA; MUCOCELE; SAC
AB Purpose: To describe a unique apocrine cystadenoma of the superonasal eyelid and anterior orbit.
Methods: Clinical evaluation with axial and coronal CT; histopathologic and immunohistochemical studies including sections stained with hematoxylin-eosin, periodic acid Schiff, alcian blue, mucicarmine, and Prussian blue for iron; and monoclonal antibodies against cytokeratin-7, epithelial membrane antigen, smooth muscle actin for myoepithelial cells, gross cystic disease fluid protein-15 for apocrine differentiation, and CD-68 and lysozyme for histiocytes.
Results: The cyst possessed a multilaminar lining composed of polygonal to low cuboidal cells. A stalk of solid tumor ingrowth from the wall was composed of adenomatous units of eosinophilic cells with apical snouts ("decapitation secretion"). No goblet cells were discovered. Both the cyst's lining cells and the adenoma expressed gross cystic disease fluid protein-15 indicative of apocrine differentiation. The adenoma displayed inner adlumenal cells that were CK-7 and epithelial membrane antigen positive, and outer myoepithelial cells that were smooth muscle actin positive. Simple local excision was curative.
Conclusion: This unique lesion is the first example in the ophthalmic and dermatopathologic literatures of a solid adenoma encompassed by an apocrine cyst, which more typically features short or blunt papillae. It must be distinguished from other eyelid and/or anterior orbital cystic lesions including eccrine hydrocystomas; classical and extratarsal dermoid cysts; congenital and acquired conjunctival cysts and dermoids; dacryocystocoeles/mucoceles; canaliculops and lacrimal gland dacryops; and congenital cystic odontogenic choristomas.
C1 [Jakobiec, Frederick A.; Bhat, Pooja] Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, Dept Ophthalmol, Boston, MA 02114 USA.
[Kropp, Thomas M.] Florida Hosp, Dept Ophthalmol, Oculoplast Serv, Orlando, FL USA.
RP Jakobiec, FA (reprint author), Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA.
EM fred_jakobiec@meei.harvard.edu
NR 35
TC 11
Z9 13
U1 0
U2 2
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 JUL-AUG
PY 2010
VL 26
IS 4
BP 245
EP 249
DI 10.1097/IOP.0b013e3181b9e87b
PG 5
WC Ophthalmology; Surgery
SC Ophthalmology; Surgery
GA 628JC
UT WOS:000280114500004
PM 20502368
ER
PT J
AU Jung, YS
Kim, SY
Park, SY
Choi, YD
Park, HS
AF Jung, Young-Soo
Kim, Sang Yoon
Park, Sung-Yeon
Choi, Young-Dal
Park, Hyung-Sik
TI Changes of transverse mandibular width after intraoral vertical ramus
osteotomy
SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND
ENDODONTOLOGY
LA English
DT Article
ID HEAD FILM MEASUREMENTS; RELIABILITY; SETBACK
AB Objective. The purpose of this study was to analyze the long-term changes in the horizontal transverse mandibular width (TMW) between the angles of mandible after intraoral vertical ramus osteotomy (IVRO) with respect to hard and soft tissues.
Study design. A total of 107 from a pool of 207 patients with mandibular prognathism who had undergone bilateral IVRO were retrospectively evaluated radiographically and photographically. A comparison study of the changes of horizontal transverse width in hard and soft tissues after surgery was performed using preoperative, and 1-, 3-, 6-, and 12-month postoperative posteroanterior (PA) cephalograms and clinical photos. Three groups were divided according to the amount of mandibular setback performed (Group 1: <5 mm, Group 2: 5-10 mm, Group 3: >10 mm).
Results. The overall average amount of mandibular setback in all patients was 8.58 mm. Statistically significant increases of TMW in hard and soft tissue from preoperative to postoperative 1 month were seen. TMW in hard tissue showed a gradually decreasing pattern postoperatively from 1 month to 1 year, and the changes were statistically significant at 1 year postop. TMW in soft tissue was not changed uniformly after 1 month, and showed less than 1% change at 1-year postoperatively compared with preoperatively. The amount of increase in the TMW postoperatively was not proportional or statistically significant to the amount of mandibular setback performed.
Conclusions. The results show that mandibular setback using BIVRO did not significantly influence the TMW changes in soft tissue. Therefore, IVRO technique can be safely used without compromising esthetic results through soft tissue TMW increase. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010;110:25-31)
C1 [Jung, Young-Soo; Park, Sung-Yeon; Choi, Young-Dal; Park, Hyung-Sik] Yonsei Univ, Coll Dent, Dept Oral & Maxillofacial Surg, Oral Sci Res Ctr, Seoul 120752, South Korea.
[Kim, Sang Yoon] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA.
RP Park, HS (reprint author), Yonsei Univ, Coll Dent, Dept Oral & Maxillofacial Surg, Oral Sci Res Ctr, 250 Seongsan No, Seoul 120752, South Korea.
EM hspark709@yuhs.ac
OI kim, sang/0000-0002-5860-3491
NR 13
TC 7
Z9 7
U1 0
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1079-2104
J9 ORAL SURG ORAL MED O
JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod.
PD JUL
PY 2010
VL 110
IS 1
BP 25
EP 31
DI 10.1016/j.tripleo.2009.11.004
PG 7
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 611MK
UT WOS:000278819200009
PM 20188605
ER
PT J
AU Rhee, JS
Weaver, EM
Park, SS
Baker, SR
Hilger, PA
Kriet, JD
Murakami, C
Senior, BA
Rosenfeld, RM
DiVittorio, D
AF Rhee, John S.
Weaver, Edward M.
Park, Stephen S.
Baker, Shan R.
Hilger, Peter A.
Kriet, J. David
Murakami, Craig
Senior, Brent A.
Rosenfeld, Richard M.
DiVittorio, Danielle
TI Clinical consensus statement: Diagnosis and management of nasal valve
compromise
SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY
LA English
DT Article
ID CHEST PHYSICIANS; AMERICAN-COLLEGE
AB OBJECTIVE: To create a clinical consensus statement to address ambiguities and disparities in the diagnosis and management of nasal valve compromise (NVC).
SUBJECTS AND METHODS: An updated systematic review of the literature was conducted. In addition, a Modified Delphi Method was used to refine expert opinion and facilitate a consensus position.
RESULTS: After two rounds of surveys and conference calls, 36 items reached consensus, six items reached near consensus, and 10 items reached no consensus. The categories that had the greatest percentage of consensus or near consensus items were as follows: definition, history and physical examination, outcome measures, and management. Conversely, the categories with greater percentage of no consensus items were adjunctive tests and coding.
CONCLUSION: The consensus panel agreed that NVC is a distinct clinical entity that is best evaluated with history and physical examination findings. Endoscopy and photography are useful but not routinely indicated, whereas radiographic studies are not useful in evaluating NVC. Other objective nasal outcome measures may not be useful or accepted for NVC. Nasal steroid medication is not useful for treatment of NVC in the absence of rhinitis, and mechanical treatments may be useful in selected patients. Surgical treatment is the primary mode of treatment of NVC, but bill coding remains ambiguous and confusing. (C) 2010 American Academy of Otolaryngology-Head and Neck Surgery Foundation. All rights reserved.
C1 [Rhee, John S.] Med Coll Wisconsin, Dept Otolaryngol & Commun Sci, Milwaukee, WI 53226 USA.
[Weaver, Edward M.] VA Puget Sound Healthcare Syst, Seattle, WA USA.
[Weaver, Edward M.] Univ Washington, Dept Otolaryngol Head & Neck Surg, Sch Med, Seattle, WA 98195 USA.
[Park, Stephen S.] Univ Virginia Hlth Syst, Dept Otolaryngol, Charlottesville, VA USA.
[Baker, Shan R.] Univ Michigan, Ctr Facial Cosmet Surg, Livonia, MI USA.
[Hilger, Peter A.] Univ Minnesota, Dept Otolaryngol Head & Neck Surg, Minneapolis, MN USA.
[Kriet, J. David] Univ Kansas, Dept Otolaryngol Head & Neck Surg, Kansas City, KS USA.
[Murakami, Craig] Virginia Mason Med Ctr, Seattle, WA 98101 USA.
[Senior, Brent A.] Univ N Carolina, Div Otolaryngol Head & Neck Surg, Chapel Hill, NC USA.
[Rosenfeld, Richard M.] Suny Downstate Med Ctr, Dept Otolaryngol, Brooklyn, NY 11203 USA.
[Rosenfeld, Richard M.] Long Isl Coll Hosp, Brooklyn, NY 11201 USA.
[DiVittorio, Danielle] Amer Acad Otolaryngol Head & Neck Surg, Alexandria, VA USA.
RP Rhee, JS (reprint author), Med Coll Wisconsin, Dept Otolaryngol & Commun Sci, 9200 W Wisconsin Ave, Milwaukee, WI 53226 USA.
EM jrhee@mcw.edu
FU American Academy of Otolaryngology-Head and Neck Surgery
FX Funded by the American Academy of Otolaryngology-Head and Neck Surgery
(role: study design and conduct; collection, analysis, and
interpretation of the data; and writing or approval of the manuscript.)
NR 11
TC 39
Z9 39
U1 0
U2 0
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 JUL
PY 2010
VL 143
IS 1
BP 48
EP 59
DI 10.1016/j.otohns.2010.04.019
PG 12
WC Otorhinolaryngology; Surgery
SC Otorhinolaryngology; Surgery
GA 617DW
UT WOS:000279262100009
PM 20620619
ER
PT J
AU Kakarala, K
Bhattacharyya, N
AF Kakarala, Kiran
Bhattacharyya, Neil
TI Survival in oral cavity minor salivary gland carcinoma
SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY
LA English
DT Article; Proceedings Paper
CT 113th Annual Meeting of the
American-Academy-of-Otolaryngology-Head-and-Neck-Surgery-Foundation
CY OCT 04-07, 2009
CL San Diego, CA
SP Amer Acad Otolaryngol Head & Neck Surg Fdn
ID RADIATION-THERAPY; TUMORS; EXPERIENCE; NEOPLASMS
AB OBJECTIVE: To describe the epidemiology and comparative survival for minor salivary gland cancer of the oral cavity.
STUDY DESIGN: Historical cohort study.
SETTING: Academic medical center.
SUBJECTS AND METHODS: Cases of minor salivary gland cancer of the oral cavity were extracted from the Surveillance, Epidemiology, and End Results database (1988-2005) and staged. Kaplan-Meier survivals were compared according to histology as well as T stage and N stage. A Cox proportional hazards model incorporating histology, T stage, N stage, age, and sex was analyzed.
RESULTS: A total of 639 salivary gland cancers of the oral cavity (55% female; mean age, 56 years) were identified with complete staging information, consisting of 318 mucoepidermoid, 169 adenoid cystic, 139 adenocarcinoma, and 14 acinic cell cancers. The hard palate and gums were the most common subsites involved (87.6%), followed by lip (7.2%) and tongue (5.2%). At presentation, T1 and T4 tumors predominated (42.6% and 35.2%, respectively); 93.4 percent were NO. Overall mean survival (months) was 157.9 and was similar across histologic subtypes: mucoepidermoid (172.4), adenoid cystic (141.4), acinic cell (138.7), and adenocarcinoma (147.2). Survival for low- and intermediate-grade mucoepidermoid carcinoma (171.0 and 182.3, respectively) was better than survival for high-grade mucoepidermoid carcinoma (50.3, P < 0.001). On multivariate analysis, N stage (P < 0.001) was the most powerful predictor of survival, along with T stage (P = 0.013), age (P < 0.001), and sex (P < 0.001).
CONCLUSION: T stage and N stage are the most powerful predictors of survival in minor salivary gland carcinoma of the oral cavity. With the exception of high-grade mucoepidermoid carcinoma, survival for these lesions is generally favorable. (C) 2010 American Academy of Otolaryngology-Head and Neck Surgery Foundation. All rights reserved.
C1 [Kakarala, Kiran] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA.
[Kakarala, Kiran; Bhattacharyya, Neil] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA.
[Bhattacharyya, Neil] Brigham & Womens Hosp, Div Otolaryngol Head & Neck Surg, Boston, MA 02115 USA.
RP Bhattacharyya, N (reprint author), Brigham & Womens Hosp, Div Otolaryngol Head & Neck Surg, 45 Francis St, Boston, MA 02115 USA.
EM neiloy@massmed.org
OI Kakarala, Kiran/0000-0002-1003-8024
NR 16
TC 21
Z9 22
U1 0
U2 1
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 JUL
PY 2010
VL 143
IS 1
BP 122
EP 126
DI 10.1016/j.otohns.2010.02.033
PG 5
WC Otorhinolaryngology; Surgery
SC Otorhinolaryngology; Surgery
GA 617DW
UT WOS:000279262100020
PM 20620630
ER
PT J
AU Wieland, AM
Sundback, CA
Hart, A
Kulig, K
Masiakos, PT
Hartnick, CJ
AF Wieland, Aaron M.
Sundback, Cathryn A.
Hart, Allison
Kulig, Katherine
Masiakos, Peter T.
Hartnick, Christopher J.
TI Poly(glycerol sebacate)-engineered plugs to repair chronic tympanic
membrane perforations in a chinchilla model
SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY
LA English
DT Article
ID ANIMAL-MODEL; OTITIS-MEDIA; TYMPANOPLASTY; CLASSIFICATION; SEBACATE)
AB OBJECTIVE: To evaluate the degree of neovascularization and efficacy of repair of chronic tympanic membrane perforations in a chinchilla model using poly(glycerol sebacate) (PUS), a novel bioengineered scaffold material.
STUDY DESIGN: A feasibility study in which chinchilla ears with chronic perforations were randomly assigned to repair with PUS plugs or Gelfilm overlay myringoplasty.
SETTING: Interventions were performed in the animal care facility of a tertiary care academic institution.
SUBJECTS AND METHODS: Sixteen adult female chinchillas. Perforations were established under microscopic visualization with thermal cautery. The animals were examined six weeks later, and those ears with stable perforations were randomly assigned to repair with PUS or Gelfilm. All ears were evaluated six weeks after repair, and resected membranes underwent histological evaluation.
RESULTS: Chronic perforations were established in 22 of 32 (69%) chinchilla tympanic membranes. Nineteen tympanic membranes were included in the study group (3 ears were excluded secondary to death from anesthesia during the repair); 11 were implanted with PGS, and eight underwent Gelfilm myringoplasty. Of the 11 tympanic membranes implanted with PGS, 10 were healed at six weeks, while six of the eight tympanic membranes repaired with Gelfilm had healed at six weeks. Imaging of the medial mucosal and lateral epithelial surfaces of the tympanic membranes revealed PGS plug incorporation with neovascularization. Histology demonstrated a confluent cell layer on both sides of the graft.
CONCLUSIONS: PGS plugs are easily placed and allow for perforation closure and graft neovascularization in a chinchilla model. (C) 2010 American Academy of Otolaryngology-Head and Neck Surgery Foundation. All rights reserved.
C1 [Wieland, Aaron M.; Hartnick, Christopher J.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA.
[Wieland, Aaron M.; Hartnick, Christopher J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA.
[Sundback, Cathryn A.; Hart, Allison; Kulig, Katherine; Masiakos, Peter T.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp,Ctr Regenerat Med, Boston, MA 02115 USA.
RP Wieland, AM (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, 243 Charles St, Boston, MA 02114 USA.
EM awieland@partners.org
FU United States Army Medical Research and Material Command
FX United States Army Medical Research and Material Command.
NR 22
TC 14
Z9 14
U1 0
U2 3
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 JUL
PY 2010
VL 143
IS 1
BP 127
EP 133
DI 10.1016/j.otohns.2010.01.025
PG 7
WC Otorhinolaryngology; Surgery
SC Otorhinolaryngology; Surgery
GA 617DW
UT WOS:000279262100021
PM 20620631
ER
PT J
AU Bhattacharyya, N
Lee, LN
AF Bhattacharyya, Neil
Lee, Linda N.
TI Evaluating the diagnosis of chronic rhinosinusitis based on clinical
guidelines and endoscopy
SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY
LA English
DT Article
ID COMPUTED-TOMOGRAPHY; STAGING SYSTEMS; SINUSITIS; SYMPTOM
AB OBJECTIVE: To validate the diagnosis of chronic rhinosinusitis (CRS) according to recent clinical practice guidelines and determine the added utility of nasal endoscopy.
STUDY DESIGN: Prospective diagnostic cohort study.
SETTING: Academic medical center.
SUBJECTS AND METHODS: A consecutive series of adult patients presenting for evaluation of CRS were prospectively studied with the use of the rhinosinusitis symptom inventory (RSI), nasal endoscopy, and sinus computed tomography (CT). Symptom scores were tabulated from the RSI. Nasal endoscopy was performed to evaluate for purulence or polyps. Sinus CT scans were scored with the Lund system, with the reviewers blinded to the RSI scores and endoscopic findings. The clinical diagnosis of CRS was determined on the basis of the published adult sinusitis guideline criteria and compared with the diagnostic gold standard, CT.
RESULTS: A total of 202 patients were studied. The prevalence of CRS was 39.6 percent, as defined by CT (Lund score 4). For symptom criteria alone, the sensitivity, specificity, positive predictive value, and negative predictive value were 88.7, 12.3, 39.9, and 62.5 percent, respectively, for CRS (P = 0.82). The addition of endoscopic findings to symptom criteria significantly improved the specificity, predictive value, and negative predictive value to 84.1, 66.0, and 70.3 percent (P < 0.0001). The odds ratio of a true diagnosis of CRS improved from 1.1 to 4.6 (95% confidence interval, 2.3-9.2). Sensitivity analysis adjusting symptom severity did not significantly alter diagnostic accuracy.
CONCLUSION: In patients meeting current guideline symptom criteria for CRS, the addition of nasal endoscopy improves diagnostic accuracy and should be emphasized as an early diagnostic tool. Diagnostic endoscopy may help reduce the use of CT, reducing costs and radiation exposure. (C) 2010 American Academy of Otolaryngology-Head and Neck Surgery Foundation. All rights reserved.
C1 [Bhattacharyya, Neil] Harvard Univ, Brigham & Womens Hosp, Dept Otol & Laryngol, Div Otolaryngol,Sch Med, Boston, MA 02115 USA.
[Bhattacharyya, Neil; Lee, Linda N.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA.
[Lee, Linda N.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA.
RP Bhattacharyya, N (reprint author), Harvard Univ, Brigham & Womens Hosp, Dept Otol & Laryngol, Div Otolaryngol,Sch Med, 45 Francis St, Boston, MA 02115 USA.
EM neiloy@massmed.org
NR 15
TC 50
Z9 50
U1 0
U2 1
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 JUL
PY 2010
VL 143
IS 1
BP 147
EP 151
DI 10.1016/j.otohns.2010.04.012
PG 5
WC Otorhinolaryngology; Surgery
SC Otorhinolaryngology; Surgery
GA 617DW
UT WOS:000279262100024
PM 20620634
ER
PT J
AU Adelstein, EC
Shalaby, A
Saba, S
AF Adelstein, Evan C.
Shalaby, Alaa
Saba, Samir
TI Response to Cardiac Resynchronization Therapy in Patients with Heart
Failure and Renal Insufficiency
SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY
LA English
DT Article
DE cardiac resynchronization; renal insufficiency; heart failure;
implantable cardioverter-defibrillator
ID GLOMERULAR-FILTRATION-RATE; CARDIOVASCULAR-DISEASE; SERUM CREATININE;
MEDICAL THERAPY; COMPANION TRIAL; MORTALITY; DEFIBRILLATOR
AB Methods: We analyzed 787 CRT-defibrillator (CRT-D) recipients with a glomerular filtration rate (GFR) measured prior to implant. Patients were grouped by GFR (in mL/min/1.73 m2): >= 60 (n = 376), 30-59 (n = 347), and < 30 (n = 64). Overall survival, changes in left ventricular (LV) ejection fraction and LV end-systolic diameter, and GFR change at 3-6 months were compared among CRT-D groups and with a control cohort (n = 88), also stratified by GFR, in whom LV lead implant was unsuccessful and a standard defibrillator (SD) was placed. All patients met clinical criteria for CRT-D.
Results: Among CRT-D recipients, overall survival improved incrementally with higher baseline GFR (for each 10 mL/min/1.73 m2 increase, corrected hazard ratio [HR] 1.21, 95% confidence interval [CI] 1.13-1.30, P < 0.0001). Survival among SD and CRT-D patients within GFR < 30 and GFR >= 60 groups was similar, whereas CRT-D recipients with GFR 30-59 had significantly better survival compared to SD counterparts (HR 2.23, 95% CI 1.34-3.70; P = 0.002). This survival benefit was associated with improved renal and cardiac function. CRT recipients with GFR >= 60 derived significant echocardiographic benefit but experienced a GFR decline, whereas those with GFR < 30 had no echocardiographic benefit but did improve GFR.
Conclusions: CRT may provide the largest survival benefit in HF patients with moderate RI, perhaps by improving GFR and LV function. Severe baseline RI predicts poor survival and limited echocardiographic improvement despite a modest GFR increase, such that CRT may not benefit those with GFR < 30 mL/min/1.73 m2. CRT recipients with normal renal function derive echocardiographic benefit but no overall survival advantage. (PACE 2010; 850-859).
C1 [Adelstein, Evan C.; Saba, Samir] Univ Pittsburgh, Med Ctr, Electrophysiol Sect, Cardiovasc Inst, Pittsburgh, PA USA.
[Shalaby, Alaa] VA Pittsburgh Healthcare Syst, Div Cardiol, Pittsburgh, PA USA.
RP Adelstein, EC (reprint author), 200 Lothrop St,PUH B535, Pittsburgh, PA 15213 USA.
EM adelsteinec@upmc.edu
NR 26
TC 26
Z9 26
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0147-8389
J9 PACE
JI PACE-Pacing Clin. Electrophysiol.
PD JUL
PY 2010
VL 33
IS 7
BP 850
EP 859
DI 10.1111/j.1540-8159.2010.02705.x
PG 10
WC Cardiac & Cardiovascular Systems; Engineering, Biomedical
SC Cardiovascular System & Cardiology; Engineering
GA 619ST
UT WOS:000279451300014
PM 20202138
ER
PT J
AU Kim, HY
Kim, K
Li, HY
Chung, G
Park, CK
Kim, JS
Jung, SJ
Lee, MK
Ahn, DK
Hwang, SJ
Kang, Y
Binshtok, AM
Bean, BP
Woolf, CJ
Oh, SB
AF Kim, Hyun Yeong
Kim, Kihwan
Li, Hai Ying
Chung, Gehoon
Park, Chul-Kyu
Kim, Joong Soo
Jung, Sung Jun
Lee, Min Kyung
Ahn, Dong Kuk
Hwang, Se Jin
Kang, Youngnam
Binshtok, Alexander M.
Bean, Bruce P.
Woolf, Clifford J.
Oh, Seog Bae
TI Selectively targeting pain in the trigeminal system
SO PAIN
LA English
DT Article
DE Action potentials; Local anesthetics; QX-314; Trigeminal system; TRPV1;
Voltage-gated sodium channels
ID PRIMARY AFFERENT NEURONS; PERIPHERAL-NERVE; SENSORY NEURONS; NOCICEPTIVE
NEURONS; CAPSAICIN RECEPTOR; LOCAL-ANESTHETICS; PORE DILATION; ION
CHANNELS; RAT; MECHANISMS
AB We tested whether it is possible to selectively block pain signals in the orofacial area by delivering the permanently charged lidocaine derivative QX-314 into nociceptors via TPRV1 channels. We examined the effects of co-applied QX-314 and capsaicin on nociceptive, proprioceptive, and motor function in the rat trigeminal system. QX-314 alone failed to block voltage-gated sodium channel currents (I(Na)) and action potentials (APs) in trigeminal ganglion (TG) neurons. However, co-application of QX-314 and capsaicin blocked I(Na) and APs in TRPV1-positive TG and dental nociceptive neurons, but not in TRPV1-negative TG neurons or in small neurons from TRPV1 knock-out mice. Immunohistochemistry revealed that TRPV1 is not expressed by trigeminal motor and trigeminal mesencephalic neurons. Capsaicin had no effect on rat trigeminal motor and proprioceptive mesencephalic neurons and therefore should not allow QX-314 to enter these cells. Co-application of QX-314 and capsaicin inhibited the jaw-opening reflex evoked by noxious electrical stimulation of the tooth pulp when applied to a sensory but not a motor nerve, and produced long-lasting analgesia in the orofacial area. These data show that selective block of pain signals can be achieved by co-application of QX-314 with TRPV1 agonists. This approach has potential utility in the trigeminal system for treating dental and facial pain. (C) 2010 International Association for the Study of Pain. Published by Elsevier B. V. All rights reserved.
C1 [Kim, Hyun Yeong; Kim, Kihwan; Li, Hai Ying; Chung, Gehoon; Park, Chul-Kyu; Kim, Joong Soo; Oh, Seog Bae] Seoul Natl Univ, Sch Dent, Dept Physiol, Seoul 110749, South Korea.
[Kim, Hyun Yeong; Kim, Kihwan; Li, Hai Ying; Chung, Gehoon; Park, Chul-Kyu; Kim, Joong Soo; Oh, Seog Bae] Seoul Natl Univ, Dent Res Inst, Natl Res Lab Pain, Seoul 110749, South Korea.
[Jung, Sung Jun] Hanyang Univ, Sch Med, Dept Physiol, Seoul 133791, South Korea.
[Lee, Min Kyung; Ahn, Dong Kuk] Kyungpook Natl Univ, Sch Dent, Dept Oral Physiol & Neurobiol, Taegu 700412, South Korea.
[Hwang, Se Jin] Hanyang Univ, Coll Med, Dept Anat & Cell Biol, Seoul 133791, South Korea.
[Kang, Youngnam] Osaka Univ, Grad Sch Dent, Dept Neurosci & Oral Physiol, Suita, Osaka 5650871, Japan.
[Binshtok, Alexander M.; Woolf, Clifford J.] Massachusetts Gen Hosp, Neural Plast Res Grp, Charlestown, MA 02129 USA.
[Binshtok, Alexander M.; Woolf, Clifford J.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
[Bean, Bruce P.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA.
RP Oh, SB (reprint author), Seoul Natl Univ, Sch Dent, Dept Physiol, 28-2 Yeongeon Dong, Seoul 110749, South Korea.
EM odolbae@snu.ac.kr
RI Chung, Gehoon/C-5714-2008
OI Chung, Gehoon/0000-0002-8036-0879
FU National Research Laboratory [R0A-2008-000-20101-0]; Ministry of
Education, Science and Technology, Republic of Korea [2009K001256];
Department of Neurobiology; Harvard Medical School; LG Yonam Foundation
FX This research was supported by Grant (R0A-2008-000-20101-0) from
National Research Laboratory Program and a Grant (2009K001256) from the
Brain Research Center of the 21st Century Frontier Research Program
funded by the Ministry of Education, Science and Technology, Republic of
Korea. S.B.O was supported by Alice and Joseph Brooks Fund in the
Department of Neurobiology, Harvard Medical School and LG Yonam
Foundation during part of this work. Drs. Bean and Woolf are inventors
on a filed patent related to targeting impermeant sodium channel
blockers into nociceptors that has been licensed by Endo Pharmaceuticals
from Harvard University.
NR 37
TC 28
Z9 30
U1 2
U2 12
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0304-3959
J9 PAIN
JI Pain
PD JUL
PY 2010
VL 150
IS 1
BP 29
EP 40
DI 10.1016/j.pain.2010.02.016
PG 12
WC Anesthesiology; Clinical Neurology; Neurosciences
SC Anesthesiology; Neurosciences & Neurology
GA 608AI
UT WOS:000278549900010
PM 20236764
ER
PT J
AU Manchikanti, L
Datta, S
Gupta, S
Munglani, R
Bryce, DA
Ward, SP
Benyamin, RM
Sharma, ML
Helm, S
Fellows, B
Hirsch, JA
AF Manchikanti, Laxmaiah
Datta, Sukdeb
Gupta, Sanjeeva
Munglani, Rajesh
Bryce, David A.
Ward, Stephen P.
Benyamin, Ramsin M.
Sharma, Manohar Lal
Helm, Standiford, II
Fellows, Bert
Hirsch, Joshua A.
TI A Critical Review of the American Pain Society Clinical Practice
Guidelines For Interventional Techniques: Part 2. Therapeutic
Interventions
SO PAIN PHYSICIAN
LA English
DT Review
DE Guidelines; evidence-based medicine; systematic reviews; American Pain
Society; interventional pain management; interventional techniques
ID LOW-BACK-PAIN; SPINAL-CORD STIMULATION; EPIDURAL STEROID INJECTIONS;
EVIDENCE-BASED MEDICINE; CHRONIC NONCANCER PAIN; RANDOMIZED
CONTROLLED-TRIALS; JOINT NERVE BLOCKS; LUMBAR RADICULAR PAIN; MEDIAL
BRANCH BLOCKS; SERVICES-TASK-FORCE
AB Background: Clinical guidelines are a constructive response to the reality that practicing physicians require assistance in assimilating and applying the exponentially expanding, often contradictory body of medical knowledge. They attempt to define practices that meet the needs of most patients under most circumstances. Ideally, specific clinical recommendations contained within practice guidelines are systematically developed by expert panels who have access to all the available evidence, have an understanding of the clinical problem, and have clinical experience with the procedure being assessed, as well as knowledge of relevant research methods. The recent development of American Pain Society (APS) guidelines has created substantial controversy because of their perceived lack of objective analysis and recommendations perceived to be biased due to conflicts of interest.
Objectives: To formally and carefully assess the APS guidelines' evidence synthesis for low back pain for therapeutic interventions using the same methodology utilized by the APS authors. The interventions examined were therapeutic interventions for managing low back pain, including epidural injections, adhesiolysis, facet joint interventions, and spinal cord stimulation.
Methods: A literature search by 2 authors was carried out utilizing appropriate databases from 1966 through July 2008. Articles in which conflicts arose were reviewed and mediated by a third author to arrive at a consensus. Selections of manuscripts and methodologic quality assessment was also performed by at least 2 authors utilizing the same criteria applied in the APS guidelines. The guideline reassessment process included the evaluation of individual studies and systematic reviews and their translation into practice recommendations.
Results: The conclusions of APS and our critical assessment based on grading of good, fair, and poor, agreed that there is fair evidence for spinal cord stimulation in post lumbar surgery syndrome, and poor evidence for lumbar intraarticular facet joint injections, lumbar interlaminar epidural injections, caudal epidural steroids for conditions other than disc herniation or radiculitis, sacroiliac joint injections, intradiscal electrothermal therapy, endoscopic adhesiolysis, and intrathecal therapy. However, our assessment of APS guidelines for other interventional techniques, utilizing their own criteria, showed fair evidence for therapeutic lumbar facet joint nerve blocks, caudal epidural injections in disc herniation or radiculitis, percutaneous adhesiolysis in post lumbar surgery syndrome, radiofrequency neurotomy, and transforaminal epidural injections in radiculitis. Also it is illustrated that inclusion of latest literature will change the conclusions, with improved grading caudal epidural, adhesiolysis, and lumbar facet joint nerve blocks from fair to good or poor to fair.
The present critical assessment review illustrates that APS guidelines have utilized multiple studies inappropriately and have excluded appropriate studies. Our integrity assessment shows deep concerns that the APS guidelines illustrating significant methodologic failures which raise concerns about transparency, accountability consistency, and independence.
Conclusion: The current reassessment, using appropriate methodology, shows evidence similar to APS guidelines for several procedures, but differs extensively from published APS guidelines for multiple other procedures including caudal epidural injections, lumbar facet joint nerve blocks, lumbar radiofrequency neurotomy, and percutaneous adhesiolysis.
C1 [Manchikanti, Laxmaiah; Fellows, Bert] Pain Management Ctr Paducah, Paducah, KY USA.
[Datta, Sukdeb] Vanderbilt Univ, Med Ctr, Nashville, TN USA.
[Gupta, Sanjeeva] Bradford Teaching Hosp NHS Fdn Trust, Bradford, W Yorkshire, England.
[Munglani, Rajesh] Spire Cambridge Lea Hosp, Cambridge Nuffield Hosp, Cambridge, England.
[Bryce, David A.] Adv Pain Management, Madison, WI USA.
[Ward, Stephen P.] Brighton & Sussex Univ Hosp NHS Trust, Brighton, E Sussex, England.
[Benyamin, Ramsin M.] Millennium Pain Ctr, Bloomington, IL USA.
[Sharma, Manohar Lal] Walton Ctr Neurol & Neurosurg NHS Fdn Trust, Liverpool, Merseyside, England.
[Helm, Standiford, II] 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
FU Sucampo Pharmaceuticals
FX Dr. Hirsch is a consultant for Cardinal Healthcare. He is a minor
shareholder in Medtronic and Cardinal Healthcare. He serves on the
Steering Committee for KAVIAR trial (volunteer position) and on the Data
and Safety Monitoring Board (DSMB): CEEP trial (volunteer position). Dr.
Datta receives research support from Sucampo Pharmaceuticals and an
honorarium from Smith and Nephew.
NR 275
TC 128
Z9 132
U1 1
U2 13
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 JUL-AUG
PY 2010
VL 13
IS 4
BP E215
EP E264
PG 50
WC Anesthesiology; Clinical Neurology
SC Anesthesiology; Neurosciences & Neurology
GA 857KR
UT WOS:000297717900001
PM 20648212
ER
PT J
AU Palacios, N
Weisskopf, M
Simon, K
Gao, X
Schwarzschild, M
Ascherio, A
AF Palacios, N.
Weisskopf, M.
Simon, K.
Gao, X.
Schwarzschild, M.
Ascherio, A.
TI Polymorphisms of caffeine metabolism and estrogen receptor genes and
risk of Parkinson's disease in men and women
SO PARKINSONISM & RELATED DISORDERS
LA English
DT Article
DE Parkinson's disease (PD); Epidemiology; Caffeine; Estrogen; Polymorphism
ID COFFEE CONSUMPTION; CYP1A2 ACTIVITY; BREAST-CANCER; ASSOCIATION;
GENOTYPE; BETA; 1A2
AB Caffeine intake has been associated with a decreased risk of Parkinson's disease (PD) in men but the effect in women is less clear, and appears to be modified by use of post-menopausal estrogens. In a nested case control study within the Nurses Health Study (NHS) and the Health Professionals Follow-up Study (HPFS), we examined associations between single nucleotide polymorphisms (SNPs) of caffeine metabolizing genes (CYP1A2 and NAT2) and estrogen receptors (ESR1 and ESR2), their interaction with caffeine intake and hormone replacement therapy (PMH) use (collected prospectively) and risk of PD. We matched 159 female cases to 724 controls and 139 male cases to 561 controls on birth year, source of DNA (blood or buccal smear), age and sex. The CYP1A2 rs762551 polymorphism (lower enzyme inducibility) was marginally associated with an increased risk of PD (RR, for increasing number of minor alleles = 1.34; 95% CI 1.02, 1.78 in women, but not in men. None of the NAT2 (classified as slow vs. fast acetylator), ESR1 or ESR2 polymorphisms were significantly associated with an altered risk of PD. Marginally significant interactions were observed between caffeine intake and the ESR1 polymorphism rs3798577 (p = 0.07) and ESR2 polymorphism rs1255998 (p = 0.07). The observed increased risk of PD among female but not male carriers of the rs762551 polymorphism of CYP1A2 and the interactions of caffeine with ESR1 rs3798577 and ESR2 rs1255998 may provide clues to explain the relationship between gender, caffeine intake, estrogen status and risk of PD and need to be replicated. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Palacios, N.; Ascherio, A.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Weisskopf, M.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA.
[Weisskopf, M.; Simon, K.; Ascherio, A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Gao, X.; Ascherio, A.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA.
[Gao, X.; Ascherio, A.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Schwarzschild, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Palacios, N (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 655 Huntington Ave, Boston, MA 02115 USA.
EM palacios@hsph.harvard.edu
FU NIH [R01 NS048517, T32 ES07069, T32 ES16645-01]
FX This work was funded by NIH grant R01 NS048517. Natalia Palacios is
supported by the Training Program in Environmental Epidemiology, NIH
Kirshstein National Research Service Award, T32 ES07069. K. Simon is
supported by NIH Kirshstein National Research Service Award T32
ES16645-01.
NR 31
TC 12
Z9 13
U1 4
U2 9
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1353-8020
J9 PARKINSONISM RELAT D
JI Parkinsonism Relat. Disord.
PD JUL
PY 2010
VL 16
IS 6
BP 370
EP 375
DI 10.1016/j.parkreldis.2010.02.012
PG 6
WC Clinical Neurology
SC Neurosciences & Neurology
GA 620TF
UT WOS:000279522100002
PM 20304699
ER
PT J
AU Galvin, JE
Duda, JE
Kaufer, DI
Lippa, CF
Taylor, A
Zarit, SH
AF Galvin, James E.
Duda, John E.
Kaufer, Daniel I.
Lippa, Carol F.
Taylor, Angela
Zarit, Steven H.
TI Lewy body dementia: The caregiver experience of clinical care
SO PARKINSONISM & RELATED DISORDERS
LA English
DT Article
DE Lewy body dementia; Caregiver experiences; Diagnosis
ID GENERAL-PRACTITIONERS; PARKINSONS-DISEASE; ALZHEIMER-DISEASE; BODIES;
DIAGNOSIS; MANAGEMENT; CRITERIA; RIVASTIGMINE; DLB
AB Background: Lewy body dementia (LBD) is the second most common cause of dementia, however, little is known about how the clinical diagnosis of LBD is obtained in the community or the caregiver experience while seeking the diagnosis.
Methods: The Lewy Body Dementia Association (www.LBDA.org) conducted a web-based survey of 962 caregivers over a 6-month period.
Results: The mean age of respondents was 55.9y; 88% were female and 64% had daily contact with patients. The mean age of LBD patients was 75.4y; 62% were male and 46% lived with a caregiver. The most common presentation of symptoms as reported by LBD caregivers was cognitive (48%), motor (39%) or both (13%). The first diagnoses given to the patients were Parkinson disease or other movement disorder (39%), Alzheimer disease or other cognitive disorder (36%), or mental illness (24%). Fifty percent of patients saw >3 doctors for more than 10 visits over the course of 1 year before an LBD diagnosis was established. Neurologists diagnosed most cases (62%), while primary care providers diagnosed only 6% of cases. No differences were found between the presentation of disease and the number of physicians, number of office visits, length of time to establish diagnosis, or type of doctor who finally made an LBD diagnosis. Caregivers viewed physicians as knowledgeable about disease manifestations and treatment options, but not about disease course/prognosis and available community resources and referrals.
Conclusions: These data highlight a need for increasing physician awareness and knowledge of LBD, which will facilitate accurate diagnosis and treatment. Community resources such as the Lewy Body Dementia Association may serve this end, while also providing practical information and support for caregivers. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Galvin, James E.] NYU, Ctr Excellence Brain Aging, Langone Sch Med, Dept Neurol, New York, NY 10016 USA.
[Duda, John E.] Philadelphia VA Med Ctr, PADRECC, Philadelphia, PA USA.
[Duda, John E.] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA.
[Kaufer, Daniel I.] Univ N Carolina, Dept Neurol, Chapel Hill, NC USA.
[Lippa, Carol F.] Drexel Univ, Dept Neurol, Coll Med, Philadelphia, PA 19104 USA.
[Taylor, Angela] Lewy Body Dementia Assoc, Atlanta, GA USA.
[Zarit, Steven H.] Penn State Univ, Dept Psychol, University Pk, PA 16802 USA.
RP Galvin, JE (reprint author), NYU, Ctr Excellence Brain Aging, Langone Sch Med, Dept Neurol, 145 E 32nd St,2nd Floor, New York, NY 10016 USA.
EM James.Galvin@nyumc.org
FU Lewy Body Dementia Association
FX The authors thank the LBD patients and their caregivers for their time
in completing this survey. The study was supported by the Lewy Body
Dementia Association (www.LBDA.org).
NR 21
TC 7
Z9 7
U1 1
U2 9
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1353-8020
J9 PARKINSONISM RELAT D
JI Parkinsonism Relat. Disord.
PD JUL
PY 2010
VL 16
IS 6
BP 388
EP 392
DI 10.1016/j.parkreldis.2010.03.007
PG 5
WC Clinical Neurology
SC Neurosciences & Neurology
GA 620TF
UT WOS:000279522100006
PM 20434939
ER
PT J
AU Horton, TM
Sposto, R
Brown, P
Reynolds, CP
Hunger, SP
Winick, NJ
Raetz, EA
Carroll, WL
Arceci, RJ
Borowitz, MJ
Gaynon, PS
Gore, L
Jeha, S
Maurer, BJ
Siegel, SE
Biondi, A
Kearns, PR
Narendran, A
Silverman, LB
Smith, MA
Zwaan, CM
Whitlock, JA
AF Horton, Terzah M.
Sposto, Richard
Brown, Patrick
Reynolds, C. Patrick
Hunger, Stephen P.
Winick, Naomi J.
Raetz, Elizabeth A.
Carroll, William L.
Arceci, Robert J.
Borowitz, Michael J.
Gaynon, Paul S.
Gore, Lia
Jeha, Sima
Maurer, Barry J.
Siegel, Stuart E.
Biondi, Andrea
Kearns, Pamela R.
Narendran, Aru
Silverman, Lewis B.
Smith, Malcolm A.
Zwaan, C. Michel
Whitlock, James A.
TI Toxicity Assessment of Molecularly Targeted Drugs Incorporated into
Multiagent Chemotherapy Regimens for Pediatric Acute Lymphocytic
Leukemia (ALL): Review From an International Consensus Conference
SO PEDIATRIC BLOOD & CANCER
LA English
DT Review
DE ALL; ALL relapse; developmental therapeutics; dose-limiting toxicity;
maximum tolerated dose
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; ACUTE MYELOID-LEUKEMIA; FLT3 INHIBITOR;
THERAPY; PATHWAYS; CHILDREN; RELAPSE; TRIALS; CANCER
AB One of the challenges of incorporating molecularly targeted drugs into multi-agent chemotherapy (backbone) regimens is defining dose-limiting toxicities (DLTs) of the targeted agent against the background of toxicities of the backbone regimen. An international panel of 22 pediatric acute lymphocytic leukemia (ALL) experts addressed this issue (www.ALLNA.org). Two major questions surrounding DLT assessment were explored: (1) how toxicities can be best defined, assessed, and attributed; and (2) how effective dosing of new agents incorporated into multi-agent ALL clinical trials can be safely established in the face of disease- and therapy-related systemic toxicities. The consensus DLT definition incorporates tolerance of resolving Grade 3 and some resolving Grade 4 toxicities with stringent safety monitoring. This functional DLT definition is being tested in two Children's Oncology Group (COG) ALL clinical trials. Pediatr Blood Cancer 2010;54:872-878. (C) 2010 Wiley-Liss, Inc.
C1 [Horton, Terzah M.] Baylor Coll Med, Texas Childrens Canc Ctr, Houston, TX 77030 USA.
[Sposto, Richard; Gaynon, Paul S.; Siegel, Stuart E.] Childrens Hosp Los Angeles, USC CHLA Inst Pediat Clin Res, Los Angeles, CA 90027 USA.
[Brown, Patrick; Arceci, Robert J.; Borowitz, Michael J.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA.
[Reynolds, C. Patrick; Maurer, Barry J.] Texas Tech Univ Hlth Sci Ctr, Ctr Canc, Sch Med, Lubbock, TX USA.
[Hunger, Stephen P.; Gore, Lia] Univ Colorado Denver, Sch Med, Childrens Hosp, Aurora, CO USA.
[Winick, Naomi J.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Raetz, Elizabeth A.; Carroll, William L.] NYU, Dept Pediat Oncol, New York, NY USA.
[Jeha, Sima] St Jude Childrens Hosp, Memphis, TN 38105 USA.
[Biondi, Andrea] Clin Pediat Univ, Ctr M Tettamanti, Milano Bicocca Hosp, Monza, Italy.
[Kearns, Pamela R.] Univ Birmingham, Inst Canc Studies, Birmingham, W Midlands, England.
[Narendran, Aru] So Alberta Childrens Canc Program, Calgary, AB, Canada.
[Silverman, Lewis B.] Childrens Hosp Boston, Dana Farber Canc Inst, Boston, MA USA.
[Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
[Zwaan, C. Michel] Sophia Childrens Univ Hosp, Erasmus Med Ctr, I BFM SG New Agents Working Grp, Rotterdam, Netherlands.
[Whitlock, James A.] Vanderbilt Univ, Dept Pediat, Div Pediat Hematol Oncol, Nashville, TN USA.
RP Horton, TM (reprint author), Baylor Coll Med, Texas Childrens Canc Ctr, 6621 Fannin,MC 3-3320, Houston, TX 77030 USA.
EM tmhorton@txccc.org
OI Reynolds, C. Patrick/0000-0002-2827-8536
FU Genzyme
FX Conflict of interest: (1) Pamela Kearns: Honoraria from Genzyme;
advisory boards for Genzyme. BMS, Johnson & Johnson and Wyeth. (2) Paul
Gaynon: Research funding (>10,000/12 months) and honoraria <10,000/12
months) from Genzyme.; Grant sponsor: USC-CHLA Institute for Pediatric
Clinical Research; Grant sponsor: Monroe Carell Jr. Children's Hospital
at Vanderbilt; Grant sponsor: Vanderbilt-Ingram Cancer Center; Grant
sponsor: Ladies Leukemia League; Grant number: K23 CA113775.
NR 13
TC 11
Z9 11
U1 0
U2 4
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1545-5009
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD JUL 1
PY 2010
VL 54
IS 7
BP 872
EP 878
DI 10.1002/pbc.22414
PG 7
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 594GU
UT WOS:000277525200001
PM 20127846
ER
PT J
AU Frazier, AL
Shamberger, RC
Henderson, TO
Diller, L
AF Frazier, A. Lindsay
Shamberger, Robert C.
Henderson, Tara O.
Diller, Lisa
TI Decision Analysis to Compare Treatment Strategies for Stage I/Favorable
Histology Wilms Tumor
SO PEDIATRIC BLOOD & CANCER
LA English
DT Article
DE clinical trial design; decision analysis; Wilms tumor
ID CANCER-STUDY-GROUP; INITIAL TREATMENT; CHILDHOOD-CANCER; LATE MORTALITY;
ACTINOMYCIN-D; VINCRISTINE; SURVIVORS; AGE; 2ND
AB Background. Decision analysis was used to clarify differences in survival and complication rates comparing surgery alone versus surgery plus chemotherapy for Stage I, favorable histology Wilms tumor patients. Procedure. A state transition model was used to simulate treatment with nephrectomy-only, nephrectomy with adjuvant vincristine (VCR) or with vincristine plus dactinomcyin (NWTS Regimen EE4A). Rates of relapse and complications of therapy were obtained from the literature. In sensitivity analysis, the model was probed for the value(s) at which the treatment of choice changes. Results. The overall survival (OS) is essentially the same for patients treated with any of the three strategies (OS(Nephrectomy) = 98.8%; OS(EE4A) = 98.8%; OS(VCR) = 98.6%). Rates of serious long-term complications in the surviving population are also similar across treatment strategies (nephrectomy = 1.4%; VCR = 1.2%; EE4A = 0.3%). Both the progression and salvage rates after nephrectomy-only would have to be much worse than expected for nephrectomy-only to be an unacceptable strategy. Conclusions. The differences in overall survival and rates of long-term complications between the three different initial strategies were negligible in the model. Based on this analysis, it was decided by the Children's Oncology Group that it was acceptable to continue to include nephrectomy without adjuvant chemotherapy as an experimental arm of the low risk Wilms tumor protocol with stringent eligibility criteria and close follow-up. Decision analysis can have a role in clinical trial design by making the tradeoffs between strategies more explicit. The robustness of these conclusions can be tested by widely varying the underlying assumptions. Pediatr Blood Cancer 2010;54:879 884. (C) 2010 Wiley-Liss, Inc.
C1 [Frazier, A. Lindsay; Diller, Lisa] Harvard Univ, Sch Med, Dept Pediat Oncol, Dana Farber Childrens Hosp Canc Care, Boston, MA USA.
[Frazier, A. Lindsay] Harvard Univ, Brigham & Womens Hosp, Channing Lab, Sch Med, Boston, MA 02115 USA.
[Shamberger, Robert C.] Harvard Univ, Sch Med, Dept Surg, Boston Childrens Hosp, Boston, MA 02115 USA.
[Henderson, Tara O.] Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA.
RP Frazier, AL (reprint author), Dana Farber Canc Inst, Binney St, Boston, MA 02115 USA.
EM lindsay_frazier@dfci.harvard.edu
FU Quality of Life Clinic for Childhood Cancer Survivor
FX Support: David B. Perini, Jr. Quality of Life Clinic for Childhood
Cancer Survivor.
NR 29
TC 6
Z9 6
U1 2
U2 2
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1545-5009
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD JUL 1
PY 2010
VL 54
IS 7
BP 879
EP 884
DI 10.1002/pbc.22396
PG 6
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 594GU
UT WOS:000277525200002
PM 20052778
ER
PT J
AU Huttner, AJ
Kieran, MW
Yao, XP
Cruz, L
Ladner, J
Quayle, K
Goumnerova, LC
Irons, MB
Ullrich, NJ
AF Huttner, Anita J.
Kieran, Mark W.
Yao, Xiaopan
Cruz, Lilliam
Ladner, Jesse
Quayle, Katherine
Goumnerova, Liliana C.
Irons, Mira B.
Ullrich, Nicole J.
TI Clinicopathologic Study of Glioblastoma in Children With
Neurofibromatosis Type 1
SO PEDIATRIC BLOOD & CANCER
LA English
DT Article
DE glioblastoma; molecular markers; neurofibromatosis type 1; outcome
ID CHILDHOOD MALIGNANT GLIOMAS; CENTRAL-NERVOUS-SYSTEM; VONRECKLINGHAUSENS
NEUROFIBROMATOSIS; PEDIATRIC GLIOBLASTOMA; EGFR AMPLIFICATION; TUMORS;
GRADE; ASTROCYTOMAS; PATHWAY; PATIENT
AB Background. Neurofibromatosis type 1 (NF1) is characterized by low-grade tumors of the central and peripheral nervous system. There is also an increased risk of developing malignant tumors. Glioblastoma is an uncommon, malignant tumor of children that is even less frequently observed in children with NF1. Procedure. We performed a retrospective review of patients with NF1 and glioblastoma to determine specific clinical and pathologic indicators of overall prognosis. Results. Five patients were identified from the CHB/DFCI database for whom pathologic and imaging studies were available. All pathologic specimens demonstrated vascular proliferation and necrosis. All samples stained positively for p53. Chromogenic in situ hybridization (CISH) for epidermal growth factor receptor (EGFR) copy numbers was increased, PTEN copy numbers were normal and the promoter of the O(6)-methylguanine-DNA methyltransferase (MGMT) gene was unmethylated in the one patient evaluated. In the same time period, there were 56 patients without NF1 diagnosed with glioblastoma who were treated at our institution. Although the small sample size precludes formal statistical analysis, the 2-year survival of patients with NF1 is 60% with median overall survival of 9.25 years compared to non-NF1 patients with a 2-year survival of 25% and median overall survival 1.08 years. Conclusions. This study provides preliminary evidence that children with NF1 may be at risk for glioblastoma, but that these patients have an increased survival compared to children without NF1. Additional molecular studies will be required to determine if the pathogenesis of these tumors differs from glioblastoma in children without NF1 Pediatr Blood Cancer 2010;54:890-896. (C) 2010 Wiley-Liss, Inc.
C1 [Quayle, Katherine; Ullrich, Nicole J.] Childrens Hosp, Dept Neurol, Boston, MA 02446 USA.
[Huttner, Anita J.; Cruz, Lilliam; Ladner, Jesse] Childrens Hosp, Dept Pathol, Boston, MA 02446 USA.
[Kieran, Mark W.; Goumnerova, Liliana C.; Ullrich, Nicole J.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Yao, Xiaopan] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Goumnerova, Liliana C.] Childrens Hosp, Dept Neurosurg, Boston, MA 02446 USA.
[Irons, Mira B.] Childrens Hosp, Dept Med, Boston, MA 02446 USA.
RP Ullrich, NJ (reprint author), Childrens Hosp, Dept Neurol, 300 Longwood Ave, Boston, MA 02446 USA.
EM nicole.ullrich@childrens.harvard.edu
OI Kieran, Mark/0000-0003-2184-7692
NR 34
TC 21
Z9 21
U1 0
U2 0
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1545-5009
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD JUL 1
PY 2010
VL 54
IS 7
BP 890
EP 896
DI 10.1002/pbc.22462
PG 7
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 594GU
UT WOS:000277525200004
PM 20310005
ER
PT J
AU Huh, WW
Anderson, JR
Rodeberg, D
Teot, L
Yock, T
Raney, RB
AF Huh, Winston W.
Anderson, James R.
Rodeberg, David
Teot, Lisa
Yock, Torunn
Raney, R. Beverly
TI Orbital Sarcoma With Metastases at Diagnosis: A Report From the Soft
Tissue Sarcoma Committee of the Children's Oncology Group
SO PEDIATRIC BLOOD & CANCER
LA English
DT Article
DE metastasis; orbit; pediatric; rhabdomyosarcoma; sarcoma
ID INTERGROUP RHABDOMYOSARCOMA; PROGNOSTIC-FACTORS; CHILDHOOD; TUMORS; IV
AB We reviewed clinicopathologic features and treatment outcomes in seven patients diagnosed with Stage 4/Group IV orbital sarcoma and treated on IRSG protocols I-III. Three patients had embryonal rhabdomyosarcoma (RMS), and two patients each had alveolar RMS or unclassified sarcoma. Median age at diagnosis was 1.8 years (range 0.2-6.9 years). All patients had bone marrow involvement, including six with normal complete blood count at diagnosis. Cerebrospinal fluid was normal in six patients. Three patients survived >5 years, including one with local recurrence. In conclusion, further study is needed to determine necessity of bone marrow and CSF examination in orbital sarcoma patients. Pediatr Blood Cancer 2010;54:1045-1047. (C) 2010 Wiley-Liss, Inc.
C1 [Huh, Winston W.; Raney, R. Beverly] Univ Texas MD Anderson Canc Ctr, Div Pediat, Houston, TX 77030 USA.
[Anderson, James R.] Univ Nebraska Med Ctr, Dept Biostat, Coll Publ Hlth, Omaha, NE USA.
[Rodeberg, David] Univ Pittsburgh, Med Ctr, Dept Pediat Surg, Pittsburgh, PA USA.
[Teot, Lisa] Childrens Hosp Boston, Dept Pathol, Boston, MA USA.
[Yock, Torunn] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
RP Huh, WW (reprint author), Univ Texas MD Anderson Canc Ctr, Div Pediat, 1515 Holcombe Blvd,Unit 87, Houston, TX 77030 USA.
EM whuh@mdanderson.org
FU National Cancer Institute, National Institutes of Health, Bethesda, MD,
USA [U10 CA98543, U10 CA98413]
FX This study was supported by the Chair's Grant U10 CA98543 and the
Statistics and Data Center Grant U10 CA98413; of the Children's Oncology
Group from the National Cancer Institute, National Institutes of Health,
Bethesda, MD, USA.
NR 10
TC 1
Z9 1
U1 0
U2 0
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1545-5009
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD JUL 1
PY 2010
VL 54
IS 7
BP 1045
EP 1047
DI 10.1002/pbc.22434
PG 3
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 594GU
UT WOS:000277525200033
PM 20162686
ER
PT J
AU Dredge, DC
Parsons, EC
Carter, LP
Staley, KJ
AF Dredge, David C.
Parsons, Elizabeth C.
Carter, Lindsay P.
Staley, Kevin J.
TI Anticonvulsant Hypersensitivity Syndrome Treated With Intravenous
Immunoglobulin
SO PEDIATRIC NEUROLOGY
LA English
DT Article
ID TOXIC EPIDERMAL NECROLYSIS; CUTANEOUS REACTIONS; CORTICOSTEROIDS;
CHILDREN; DRUGS; RISK
AB Anticonvulsant hypersensitivity syndrome is a severe, potentially life-threatening, reaction to the aromatic anticonvulsant medications. Reported here is a case of anticonvulsant hypersensitivity syndrome secondary to phenobarbital in a 2-year-old boy; he responded to drug withdrawal, corticosteroids, and intravenous immunoglobulin. The literature regarding treatment of this syndrome is reviewed. (C) 2010 by Elsevier Inc. All rights reserved.
C1 [Dredge, David C.; Staley, Kevin J.] Massachusetts Gen Hosp, Dept Neurol, Child Neurol Unit, Boston, MA 02114 USA.
[Parsons, Elizabeth C.; Carter, Lindsay P.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA.
RP Dredge, DC (reprint author), Baystate Childrens Hosp, Div Pediat Neurol, 3300 Main St,Suite 4C, Springfield, MA 01199 USA.
EM david.dredge@bhs.org
NR 21
TC 4
Z9 5
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0887-8994
J9 PEDIATR NEUROL
JI Pediatr. Neurol.
PD JUL
PY 2010
VL 43
IS 1
BP 65
EP 69
DI 10.1016/j.pediatrneurol.2010.03.010
PG 5
WC Clinical Neurology; Pediatrics
SC Neurosciences & Neurology; Pediatrics
GA 614EB
UT WOS:000279037000014
PM 20682208
ER
PT J
AU Russell, G
Kaplan, J
Ferraro, M
Michelow, IC
AF Russell, George
Kaplan, Jess
Ferraro, MaryJane
Michelow, Ian C.
TI Fecal Bacteriotherapy for Relapsing Clostridium difficile Infection in a
Child: A Proposed Treatment Protocol
SO PEDIATRICS
LA English
DT Article
DE fecal bacteriotherapy; fecal transplant; child; Clostridium difficile;
therapy; relapse; probiotics; protocol
ID UNITED-STATES; COLITIS; EPIDEMIOLOGY; DISEASE; TOXIN; MICROBIOME;
AMERICA; STRAIN
AB Clostridium difficile infection (CDI) is a potentially serious emerging infectious disease. The incidences of CDI in childhood and CDI cases complicated by relapses have increased by 50% or more in North America during the past 2 decades. We report here the case of a 2-year-old child with relapsing CDI caused by the epidemic strain BI/NAP1/027 that was refractory to Saccharomyces boulardii and Lactobacillus rhamnosus GG probiotics and to intensive therapy with traditional (metronidazole, vancomycin) and experimental (rifaximin, nitazoxanide) antibiotics despite its apparent antimicrobial-susceptible phenotype. After excluding other infectious causes of diarrhea and inflammatory bowel disease, we designed a protocol to safely administer fecal bacteriotherapy via a temporary nasogastric tube. We demonstrated for the first time that fecal transplantation is practical and effective for treating relapsing CDI in a young child. We recommend that this strategy be reserved for complicated cases of CDI that fail conventional therapy until randomized studies can confirm the safety and effectiveness of fecal bacteriotherapy in children. Pediatrics 2010;126:e239-e242
C1 [Russell, George; Kaplan, Jess] Massachusetts Gen Hosp, Dept Pediat, Div Gastroenterol, Boston, MA 02114 USA.
[Ferraro, MaryJane] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Ferraro, MaryJane] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Michelow, Ian C.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[Michelow, Ian C.] Massachusetts Gen Hosp, Dept Pediat, Program Dev Immunol, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Michelow, IC (reprint author), Massachusetts Gen Hosp, Div Pediat Infect Dis, 55 Fruit St,POB 530, Boston, MA 02114 USA.
EM imichelow@partners.org
FU National Institutes of Health (NIH)
FX Funded by the National Institutes of Health (NIH).
NR 23
TC 52
Z9 55
U1 0
U2 8
PU AMER ACAD PEDIATRICS
PI ELK GROVE VILLAGE
PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA
SN 0031-4005
J9 PEDIATRICS
JI Pediatrics
PD JUL
PY 2010
VL 126
IS 1
BP E239
EP E242
DI 10.1542/peds.2009-3363
PG 4
WC Pediatrics
SC Pediatrics
GA 619LF
UT WOS:000279431000055
PM 20547640
ER
PT J
AU Winickoff, JP
Van Cleave, J
Oreskovic, NM
AF Winickoff, Jonathan P.
Van Cleave, Jeanne
Oreskovic, Nicolas M.
TI Tobacco Smoke Exposure and Chronic Conditions of Childhood
SO PEDIATRICS
LA English
DT Editorial Material
C1 [Winickoff, Jonathan P.; Van Cleave, Jeanne; Oreskovic, Nicolas M.] Massachusetts Gen Hosp Children, Ctr Child & Adolescent Hlth Policy, Boston, MA 02114 USA.
[Winickoff, Jonathan P.] Massachusetts Gen Hosp, Div Gen Med, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA.
[Winickoff, Jonathan P.; Van Cleave, Jeanne; Oreskovic, Nicolas M.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
RP Winickoff, JP (reprint author), Massachusetts Gen Hosp Children, Ctr Child & Adolescent Hlth Policy, 50 Staniford St,Suite 901, Boston, MA 02114 USA.
EM jwinickoff@partners.org
OI Oreskovic, Nicolas/0000-0001-8702-8636
NR 6
TC 9
Z9 9
U1 0
U2 1
PU AMER ACAD PEDIATRICS
PI ELK GROVE VILLAGE
PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA
SN 0031-4005
J9 PEDIATRICS
JI Pediatrics
PD JUL
PY 2010
VL 126
IS 1
BP E251
EP E252
DI 10.1542/peds.2010-1182
PG 2
WC Pediatrics
SC Pediatrics
GA 619LF
UT WOS:000279431000058
PM 20587681
ER
PT J
AU Blais, MA
Little, JA
AF Blais, Mark A.
Little, Jessica A.
TI Toward an Integrative Study of Narcissism
SO PERSONALITY DISORDERS-THEORY RESEARCH AND TREATMENT
LA English
DT Article
C1 [Blais, Mark A.; Little, Jessica A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Blais, Mark A.; Little, Jessica A.] Harvard Univ, Med Sch, Cambridge, MA 02138 USA.
RP Blais, MA (reprint author), Massachusetts Gen Hosp, Psychol Evaluat & Res Lab, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA.
EM mblais@partners.org
NR 19
TC 7
Z9 7
U1 0
U2 4
PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA
SN 1949-2715
J9 PERSONAL DISORD
JI Personal. Disord.
PD JUL
PY 2010
VL 1
IS 3
BP 197
EP 199
DI 10.1037/a0020573
PG 3
WC Psychology, Clinical
SC Psychology
GA V27OI
UT WOS:000208622100007
PM 22448638
ER
PT J
AU Kim, MM
Metlay, J
Cohen, A
Feldman, H
Hennessy, S
Kimmel, S
Strom, B
Doshi, JA
AF Kim, Michelle M.
Metlay, Joshua
Cohen, Abigail
Feldman, Harold
Hennessy, Sean
Kimmel, Stephen
Strom, Brian
Doshi, Jalpa A.
TI Hospitalization costs associated with warfarin-related bleeding events
among older community-dwelling adults
SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY
LA English
DT Article
DE costs; warfarin; warfarin management; patient safety; adverse events;
elderly
ID ADVERSE DRUG EVENTS; COMPLICATIONS; CARE; RISK
AB Purpose A prior paper from this study demonstrated that patient report of receiving medication instructions from health care professionals is associated with reduced risk of warfarin-related bleeding hospitalizations. The objective of this analysis was to describe the hospitalization costs due to warfarin-related bleeding events in older community-dwelling adults and to estimate the hospitalization costs avoided due to the receipt of medication instruction from different sources.
Methods We estimated the expected hospitalization costs associated with four instruction sources based on the respective incidence rate of observed hospitalizations and mean hospitalization cost for warfarin-related bleeding episodes from a prospective cohort study of beneficiaries of the Pennsylvania Pharmaceutical Assistance Contract for the Elderly (PACE). We estimated hospitalization costs avoided due to each instruction source compared to no instructions using the payer's perspective. We conducted probabilistic sensitivity analysis to account for uncertainty in our parameters.
Results One hundred twenty-six warfarin-related bleeding hospitalizations occurred during the observation period with a mean cost of $10 819 (SD: $11 536). The mean expected hospitalization cost from a warfarin-related bleeding hospitalization without instruction was $835 per year per person. Hospitalization costs avoided with instruction from a health care professional ranged from $443 to $481 per year per person.
Conclusions The costs per hospitalization associated with warfarin-related bleeding events are substantial. Instructions for warfarin management from a health care professional may reduce the number of warfarin-related bleeding hospitalizations and associated costs. Investments in interventions to improve communication regarding warfarin management may be justified economically based on the potential cost savings estimated in this study. Copyright (C) 2010 John Wiley & Sons, Ltd.
C1 [Metlay, Joshua; Doshi, Jalpa A.] Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA.
[Kim, Michelle M.] Univ Penn, Wharton Sch Business, Dept Hlth Care Management, Philadelphia, PA 19104 USA.
[Metlay, Joshua; Cohen, Abigail; Feldman, Harold; Hennessy, Sean; Kimmel, Stephen; Strom, Brian] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[Metlay, Joshua; Doshi, Jalpa A.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA.
[Metlay, Joshua] Ctr Hlth Equ Res & Promot, Dept Vet Affairs, Philadelphia, PA USA.
[Cohen, Abigail] Univ Sci Philadelphia, Dept Hlth Policy & Publ Hlth, Philadelphia, PA USA.
[Feldman, Harold] Univ Penn, Sch Med, Div Renal Electrolyte & Hypertens, Philadelphia, PA 19104 USA.
[Kimmel, Stephen] Univ Penn, Sch Med, Div Cardiovasc Med, Philadelphia, PA 19104 USA.
RP Doshi, JA (reprint author), Univ Penn, Sch Med, Div Gen Internal Med, 1222 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA.
EM jdoshi@mail.med.upenn.edu
RI Cohen, Abigail/K-9180-2013
OI Cohen, Abigail/0000-0002-7425-7218
FU Agency for Healthcare Research and Quality [P01-HS11530]; National
Institute of Aging [1R01-AG024451-01]
FX This study was supported by grant P01-HS11530 from the Agency for
Healthcare Research and Quality and grant 1R01-AG024451-01 from the
National Institute of Aging.
NR 15
TC 22
Z9 22
U1 0
U2 3
PU JOHN WILEY & SONS LTD
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND
SN 1053-8569
J9 PHARMACOEPIDEM DR S
JI Pharmacoepidemiol. Drug Saf.
PD JUL
PY 2010
VL 19
IS 7
BP 731
EP 736
DI 10.1002/pds.1953
PG 6
WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
GA 626YM
UT WOS:000280004500010
PM 20583203
ER
PT J
AU Verhoef, TI
Redekop, WK
Darba, J
Geitona, M
Hughes, DA
Siebert, U
de Boer, A
Zee, AHMVD
AF Verhoef, Talitha I.
Redekop, William K.
Darba, Josep
Geitona, Mary
Hughes, Dyfrig A.
Siebert, Uwe
de Boer, Anthonius
Zee, Anke-Hilse Maitland-van der
CA EU-PACT Grp
TI A systematic review of cost effectiveness analyses of
pharmacogenetic-guided dosing in treatment with coumarin derivatives
SO PHARMACOGENOMICS
LA English
DT Review
DE coumarins; CYP2C9; economics; pharmacogenetics; VKORC1
ID ORAL ANTICOAGULANT-THERAPY; INTERNATIONAL NORMALIZED RATIO; WARFARIN
THERAPY; BLEEDING COMPLICATIONS; ATRIAL-FIBRILLATION; CYTOCHROME
P4502C9; ECONOMIC OUTCOMES; DOSE REQUIREMENT; CYP2C9; VKORC1
AB Anticoagulant therapy with coumarin derivatives is often sub- or supra-therapeutic, resulting in an increased risk of thromboembolic events or hemorrhage, respectively. Pharmacogenetic-guided dosing has been proposed as an effective way of reducing bleeding rates. Clinical trials to confirm the safety, efficacy and effectiveness of this strategy are ongoing, but in addition, it is also necessary to consider the cost effectiveness of this strategy. This article describes the findings of a systematic review of published cost effectiveness analyses of pharmacogenetic-guided dosing of coumarin derivatives. Similarities and differences in the approaches used were examined and the quality of the analyses was assessed. The results of the analyses are not sufficient to determine whether or not pharmacogenetic-guided dosing of coumarins is cost effective. More reliable cost effectiveness estimates need to become available before it is possible to recommend whether or not this strategy should be applied in clinical practice.
C1 [Verhoef, Talitha I.; Zee, Anke-Hilse Maitland-van der] Utrecht Inst Pharmaceut Sci, Div Pharmaco & Pharmacotherapy, NL-3908 TB Utrecht, Netherlands.
[Redekop, William K.] Erasmus Univ, Inst Med Technol Assessment, Rotterdam, Netherlands.
[Darba, Josep] Univ Barcelona, Dept Econ, Barcelona, Spain.
[Darba, Josep] Univ Thessaly, Dept Econ, Volos, Greece.
[Geitona, Mary] Univ Hlth Sci Med Informat & Technol, Dept Publ Hlth Informat Syst & HTA, Hall In Tirol, Austria.
[Hughes, Dyfrig A.] Harvard Univ, Sch Med, Dept Hlth Policy & Management, Boston, MA USA.
[Siebert, Uwe] Harvard Univ, Sch Med, Inst Technol Assessment, Massachusetts Gen Hosp, Boston, MA USA.
Bangor Univ, Ctr Econ & Policy Hlth, Bangor, Gwynedd, Wales.
RP Zee, AHMVD (reprint author), Utrecht Inst Pharmaceut Sci, Div Pharmaco & Pharmacotherapy, POB 80082, NL-3908 TB Utrecht, Netherlands.
EM a.h.maitland@uu.nl
RI Hughes, Dyfrig/H-5252-2012; Wadelius, Mia/C-7740-2016;
OI Hughes, Dyfrig/0000-0001-8247-7459; Wadelius, Mia/0000-0002-6368-2622;
Pirmohamed, Munir/0000-0002-7534-7266
FU European Community [HEALTH-F2-2009-223062]
FX This project is funded by the European Community's Seventh Framework
Programme under grant agreement number HEALTH-F2-2009-223062. The
authors have no other relevant affiliations or financial involvement
with any organization or entity with a financial interest in or
financial conflict with the subject matter or materials discussed in the
manuscript apart from those disclosed.
NR 42
TC 18
Z9 18
U1 1
U2 8
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 1462-2416
J9 PHARMACOGENOMICS
JI Pharmacogenomics
PD JUL
PY 2010
VL 11
IS 7
BP 989
EP 1002
DI 10.2217/PGS.10.74
PG 14
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 626ZP
UT WOS:000280007600016
PM 20602617
ER
PT J
AU Shin, JT
Pomerantsev, EV
Mably, JD
MacRae, CA
AF Shin, Jordan T.
Pomerantsev, Eugene V.
Mably, John D.
MacRae, Calum A.
TI High-resolution cardiovascular function confirms functional orthology of
myocardial contractility pathways in zebrafish
SO PHYSIOLOGICAL GENOMICS
LA English
DT Article
DE heart; inotropy
ID MULTIPLE SEQUENCE ALIGNMENT; HYPERTROPHIC CARDIOMYOPATHY; NA+/K+-ATPASE;
HEART; PERFORMANCE; BINDING; VERAPAMIL; MUTATION; SUBUNIT;
ECHOCARDIOGRAPHY
AB Shin JT, Pomerantsev EV, Mably JD, MacRae CA. High-resolution cardiovascular function confirms functional orthology of myocardial contractility pathways in zebrafish. Physiol Genomics 42: 300-309, 2010. First published April 13, 2010; doi: 10.1152/physiolgenomics.00206.2009.-Phenotype- driven screens in larval zebrafish have transformed our understanding of the molecular basis of cardiovascular development. Screens to define the genetic determinants of physiological phenotypes have been slow to materialize as a result of the limited number of validated in vivo assays with relevant dynamic range. To enable rigorous assessment of cardiovascular physiology in living zebrafish embryos, we developed a suite of software tools for the analysis of high-speed video microscopic images and validated these, using established cardiomyopathy models in zebrafish as well as modulation of the nitric oxide (NO) pathway. Quantitative analysis in wild-type fish exposed to NO or in a zebrafish model of dilated cardiomyopathy demonstrated that these tools detect significant differences in ventricular chamber size, ventricular performance, and aortic flow velocity in zebrafish embryos across a large dynamic range. These methods also were able to establish the effects of the classic pharmacological agents isoproterenol, ouabain, and verapamil on cardiovascular physiology in zebrafish embryos. Sequence conservation between zebrafish and mammals of key amino acids in the pharmacological targets of these agents correlated with the functional orthology of the physiological response. These data provide evidence that the quantitative evaluation of subtle physiological differences in zebrafish can be accomplished at a resolution and with a dynamic range comparable to those achieved in mammals and provides a mechanism for genetic and small-molecule dissection of functional pathways in this model organism.
C1 [Shin, Jordan T.; MacRae, Calum A.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA.
[Shin, Jordan T.; Pomerantsev, Eugene V.; MacRae, Calum A.] Massachusetts Gen Hosp, Div Cardiol, Charlestown, MA 02129 USA.
[Shin, Jordan T.; Pomerantsev, Eugene V.; MacRae, Calum A.] Harvard Univ, Sch Med, Charlestown, MA USA.
[Mably, John D.] Childrens Hosp, Boston, MA 02115 USA.
RP Shin, JT (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 149 13th St, Charlestown, MA 02129 USA.
EM jshin1@partners.org
FU Novartis Foundation; National Institutes of Health (NIH) [GM-075946,
HL-085280]; Muscular Dystrophy Association
FX Support to J. T. Shin and C. A. MacRae was received from the Novartis
Foundation. Support to C. A. MacRae was also received from National
Institutes of Health (NIH) Grant GM-075946 and the Muscular Dystrophy
Association. J. T. Shin is also supported by NIH Grant HL-085280.
NR 37
TC 25
Z9 25
U1 0
U2 5
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1094-8341
J9 PHYSIOL GENOMICS
JI Physiol. Genomics
PD JUL
PY 2010
VL 42
IS 2
BP 300
EP 309
DI 10.1152/physiolgenomics.00206.2009
PG 10
WC Cell Biology; Genetics & Heredity; Physiology
SC Cell Biology; Genetics & Heredity; Physiology
GA 621NZ
UT WOS:000279586900014
PM 20388839
ER
PT J
AU Maggard, MA
Harness, NG
Chang, WT
Parikh, JA
Asch, SM
Nuckols, TK
AF Maggard, Melinda A.
Harness, Neil G.
Chang, Walter T.
Parikh, Janak A.
Asch, Steven M.
Nuckols, Teryl K.
CA Carpal Tunnel Quality Grp
TI Indications for Performing Carpal Tunnel Surgery: Clinical Quality
Measures
SO PLASTIC AND RECONSTRUCTIVE SURGERY
LA English
DT Article
ID APPROPRIATENESS METHOD; OUTCOMES; RELEASE; CARE; TRIAL; GUIDELINES;
SEVERITY; SYMPTOMS; CRITERIA; THERAPY
AB Background: Rates of carpal tunnel surgery vary for unclear reasons. In this study, the authors developed measures determining when surgery is necessary (benefits exceed risks), inappropriate (risks outweigh benefits), or optional.
Methods: Measures were developed using a modified-Delphi panel. Clinical scenarios were defined incorporating symptom severity, symptom duration, clinical probability of carpal tunnel syndrome, electrodiagnostic testing, and nonoperative treatment response. A multidisciplinary panel of 11 carpal tunnel syndrome experts rated appropriateness of surgery for each scenario on a scale ranging from 1 to 9 scale (7 to 9, surgery is necessary; 1 to 3, surgery is inappropriate).
Results: Of 90 scenarios (36 for mild, 36 for moderate, and 18 for severe symptoms), panelists judged carpal tunnel surgery as necessary for 16, inappropriate for 37, and optional for 37 scenarios. For mild symptoms, surgery is generally necessary when clinical probability of carpal tunnel syndrome is high, there is a positive electrodiagnostic test, and there has been unsuccessful nonoperative treatment. For moderate symptoms, surgery is generally necessary with a positive electrodiagnostic test involving two or more of the following: high clinical probability, unsuccessful nonoperative treatment, and symptoms lasting longer than 12 months. Surgery is generally inappropriate for mild to moderate symptoms involving two or more of the following: low clinical probability, no electrodiagnostic confirmation, and nonoperative treatment not attempted. For severe symptoms, surgery is generally necessary with a positive electrodiagnostic test or unsuccessful nonoperative treatment.
Conclusions: These are the first formal measures assessing appropriateness of carpal tunnel surgery. Applying these measures can identify underuse (failure to provide necessary care) and overuse (providing inappropriate care), giving insight into variations in receipt of this procedure. (Plast. Reconstr. Surg. 126: 169, 2010.)
C1 [Maggard, Melinda A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA.
Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90095 USA.
Olive View UCLA, Sylmar, CA USA.
Kaiser Permanente, Fontana Med Ctr, Dept Hand Surg, Fontana, CA USA.
Kaiser Permanente, Yorba Linda Med Off, Dept Hand Surg, Yorba Linda, CA USA.
RAND Corp, Santa Monica, CA USA.
Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
RP Maggard, MA (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, CHS 72-215,10833 Le Conte Ave, Los Angeles, CA 90095 USA.
EM mmaggard@mednet.ucla.edu
FU California Commission on Health and Safety and Workers' Compensation
FX This project was supported by equal contributions from the California
Commission on Health and Safety and Workers' Compensation, a
state-sponsored joint labor/management body charged with overseeing the
health and safety and workers' compensation systems in California and
recommending administrative or legislative modifications to improve
their operation; and from Zenith Insurance, a workers' compensation
insurance company based in Woodland Hills, California. The funders
played no role in the design, execution, or reporting of the study.
NR 41
TC 12
Z9 12
U1 1
U2 7
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 JUL
PY 2010
VL 126
IS 1
BP 169
EP 179
DI 10.1097/PRS.0b013e3181da8685
PG 11
WC Surgery
SC Surgery
GA 614ZD
UT WOS:000279097500021
PM 20595866
ER
PT J
AU Hett, EC
Chao, MC
Rubin, EJ
AF Hett, Erik C.
Chao, Michael C.
Rubin, Eric J.
TI Interaction and Modulation of Two Antagonistic Cell Wall Enzymes of
Mycobacteria
SO PLOS PATHOGENS
LA English
DT Article
ID PENICILLIN-BINDING PROTEINS; ESCHERICHIA-COLI; BACILLUS-SUBTILIS;
CHRONIC TUBERCULOSIS; MUREIN HYDROLASES; SYNTHASE PBP1B; IN-VITRO;
GROWTH; RESUSCITATION; PEPTIDOGLYCAN
AB Bacterial cell growth and division require coordinated cell wall hydrolysis and synthesis, allowing for the removal and expansion of cell wall material. Without proper coordination, unchecked hydrolysis can result in cell lysis. How these opposing activities are simultaneously regulated is poorly understood. In Mycobacterium tuberculosis, the resuscitation-promoting factor B (RpfB), a lytic transglycosylase, interacts and synergizes with Rpf-interacting protein A (RipA), an endopeptidase, to hydrolyze peptidoglycan. However, it remains unclear what governs this synergy and how it is coordinated with cell wall synthesis. Here we identify the bifunctional peptidoglycan-synthesizing enzyme, penicillin binding protein 1 (PBP1), as a RipA-interacting protein. PBP1, like RipA, localizes both at the poles and septa of dividing cells. Depletion of the ponA1 gene, encoding PBP1 in M. smegmatis, results in a severe growth defect and abnormally shaped cells, indicating that PBP1 is necessary for viability and cell wall stability. Finally, PBP1 inhibits the synergistic hydrolysis of peptidoglycan by the RipA-RpfB complex in vitro. These data reveal a post-translational mechanism for regulating cell wall hydrolysis and synthesis through protein-protein interactions between enzymes with antagonistic functions.
C1 [Hett, Erik C.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
[Hett, Erik C.; Chao, Michael C.; Rubin, Eric J.] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA.
[Chao, Michael C.; Rubin, Eric J.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA.
RP Hett, EC (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
EM erubin@hsph.harvard.edu
OI Chao, Michael/0000-0002-6046-585X; Rubin, Eric/0000-0001-5120-962X
FU Burroughs Wellcome Fund; National Institutes of Health [R01 AI51929, R01
AI48704, P01 AI56296]
FX This work was supported by the Burroughs Wellcome Fund and the National
Institutes of Health grants R01 AI51929, R01 AI48704, and P01 AI56296
(EJR). The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 49
TC 42
Z9 49
U1 0
U2 7
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 JUL
PY 2010
VL 6
IS 7
AR e1001020
DI 10.1371/journal.ppat.1001020
PG 14
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 633SW
UT WOS:000280527000047
PM 20686708
ER
PT J
AU Irazoqui, JE
Troemel, ER
Feinbaum, RL
Luhachack, LG
Cezairliyan, BO
Ausubel, FM
AF Irazoqui, Javier E.
Troemel, Emily R.
Feinbaum, Rhonda L.
Luhachack, Lyly G.
Cezairliyan, Brent O.
Ausubel, Frederick M.
TI Distinct Pathogenesis and Host Responses during Infection of C. elegans
by P. aeruginosa and S. aureus
SO PLOS PATHOGENS
LA English
DT Article
ID RESISTANT STAPHYLOCOCCUS-AUREUS; OUTER-MEMBRANE VESICLES; AIRWAY
EPITHELIAL-CELLS; INNATE IMMUNE-SYSTEM; TOLL-LIKE RECEPTOR;
CAENORHABDITIS-ELEGANS; PSEUDOMONAS-AERUGINOSA;
MICROBACTERIUM-NEMATOPHILUM; SIGNALING PATHWAY; VIRULENCE FACTORS
AB The genetically tractable model host Caenorhabditis elegans provides a valuable tool to dissect host-microbe interactions in vivo. Pseudomonas aeruginosa and Staphylococcus aureus utilize virulence factors involved in human disease to infect and kill C. elegans. Despite much progress, virtually nothing is known regarding the cytopathology of infection and the proximate causes of nematode death. Using light and electron microscopy, we found that P. aeruginosa infection entails intestinal distention, accumulation of an unidentified extracellular matrix and P. aeruginosa-synthesized outer membrane vesicles in the gut lumen and on the apical surface of intestinal cells, the appearance of abnormal autophagosomes inside intestinal cells, and P. aeruginosa intracellular invasion of C. elegans. Importantly, heat-killed P. aeruginosa fails to elicit a significant host response, suggesting that the C. elegans response to P. aeruginosa is activated either by heat-labile signals or pathogen-induced damage. In contrast, S. aureus infection causes enterocyte effacement, intestinal epithelium destruction, and complete degradation of internal organs. S. aureus activates a strong transcriptional response in C. elegans intestinal epithelial cells, which aids host survival during infection and shares elements with human innate responses. The C. elegans genes induced in response to S. aureus are mostly distinct from those induced by P. aeruginosa. In contrast to P. aeruginosa, heat-killed S. aureus activates a similar response as live S. aureus, which appears to be independent of the single C. elegans Toll-Like Receptor (TLR) protein. These data suggest that the host response to S. aureus is possibly mediated by pathogen-associated molecular patterns (PAMPs). Because our data suggest that neither the P. aeruginosa nor the S. aureus-triggered response requires canonical TLR signaling, they imply the existence of unidentified mechanisms for pathogen detection in C. elegans, with potentially conserved roles also in mammals.
C1 [Irazoqui, Javier E.; Luhachack, Lyly G.] Harvard Univ, Sch Med, Dept Pediat, Program Dev Immunol,Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Troemel, Emily R.] Univ Calif San Diego, Sect Cell & Dev Biol, La Jolla, CA 92093 USA.
[Feinbaum, Rhonda L.; Cezairliyan, Brent O.; Ausubel, Frederick M.] Harvard Univ, Sch Med, Dept Mol Biol, Massachusetts Gen Hosp,Dept Genet, Boston, MA 02115 USA.
RP Irazoqui, JE (reprint author), Harvard Univ, Sch Med, Dept Pediat, Program Dev Immunol,Massachusetts Gen Hosp, Boston, MA 02115 USA.
EM javier@molbio.mgh.harvard.edu
RI Irazoqui, Javier/A-8028-2013;
OI Irazoqui, Javier/0000-0001-6553-1329
FU NIH [R01 AI064332, P01 AI044220, P30 DK040561]; Jane Coffin Childs
Memorial Fund for Medical Research; Charles A. King Trust, Bank of
America, Co-Trustee (Boston, MA); Leukemia/Lymphoma Society
FX This work was funded by NIH grants R01 AI064332, P01 AI044220, and P30
DK040561, by postdoctoral fellowships awarded to JEI from the Jane
Coffin Childs Memorial Fund for Medical Research and the Charles A. King
Trust, Bank of America, Co-Trustee (Boston, MA), and a Leukemia/Lymphoma
Society Fellowship to ERT. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 97
TC 104
Z9 105
U1 5
U2 31
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 JUL
PY 2010
VL 6
IS 7
AR e1000982
DI 10.1371/journal.ppat.1000982
PG 24
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 633SW
UT WOS:000280527000016
PM 20617181
ER
PT J
AU Chi, YW
Jaff, MR
AF Chi, Yung-Wei
Jaff, Michael R.
TI Peripheral Artery Disease and Genetics: Is There a Cause-and-Effect
Relationship?
SO POSTGRADUATE MEDICINE
LA English
DT Article
DE peripheral artery disease; genetic associations; ankle-brachial index
ID ABDOMINAL AORTIC-ANEURYSM; ANKLE-BRACHIAL INDEX; FACTOR-II G20210A;
OCCLUSIVE DISEASE; RISK-FACTORS; INSERTION/DELETION POLYMORPHISM;
CARDIOVASCULAR-DISEASE; INFLAMMATORY MARKERS; DIABETES-MELLITUS;
CIGARETTE-SMOKING
AB Peripheral artery disease (PAD) is a major health problem worldwide, affecting millions of patients. Although cardiovascular risk factors, such as diabetes, tobacco use, hypertension, and hypercholesterolemia have been associated with the development of PAD, the possible existence of an inherited genetic predisposition to PAD has been investigated in numerous familial aggregation studies. A link between genetics and PAD may open new avenues for the prevention of this morbid and mortal disorder. This is an overview of the potential association between genetics and PAD.
C1 [Chi, Yung-Wei] Ochsner Clin Fdn, Dept Cardiol, Div Vasc Med, Metairie, LA 70002 USA.
[Jaff, Michael R.] Massachusetts Gen Hosp, Vasc Ctr, Boston, MA 02114 USA.
[Jaff, Michael R.] Harvard Univ, Sch Med, Boston, MA USA.
RP Chi, YW (reprint author), Ochsner Clin Fdn, Dept Cardiol, Div Vasc Med, 2005 Vet Blvd, Metairie, LA 70002 USA.
EM ychi@ochsner.org
NR 48
TC 2
Z9 2
U1 1
U2 1
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 JUL
PY 2010
VL 122
IS 4
BP 170
EP 176
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 711TL
UT WOS:000286614200014
PM 20675979
ER
PT J
AU Rosenthal, NF
Ellis, H
Shioda, K
Mahoney, C
Coser, KR
Shioda, T
AF Rosenthal, N. F.
Ellis, H.
Shioda, K.
Mahoney, C.
Coser, K. R.
Shioda, T.
TI High-throughput applicable genomic sex typing of chicken by TaqMan
real-time quantitative polymerase chain reaction
SO POULTRY SCIENCE
LA English
DT Article
DE chicken sexing; real-time quantitative polymerase chain reaction; TaqMan
assay; high-throughput; multiplexing quantitative polymerase chain
reaction
ID DNA EXTRACTION; DOMESTIC-FOWL; GENE; PCR; EMBRYOS; BIRDS;
DIFFERENTIATION; CHROMOSOMES; EVOLUTION; SEQUENCES
AB Genetic sex typing of vertebrate animals is an essential technique for research on reproductive phenomena such as sex determination of embryonic tissues. Polymerase chain reaction amplification of genomic DNA segments in the Z and W sex chromosomes has been widely used as a standard laboratory method to determine genetic sex of the chicken (Gallus gallus domesticus). However, conventional protocols for PCR determination of avian sex typically involve tedious steps of genomic DNA isolation, which often require relatively large amounts of tissue samples, and the purity of genomic DNA specimens significantly affects PCR efficiency. Moreover, detection of sex chromosome-specific PCR products by gel electrophoresis is prone to misjudgment caused by amplification of contaminating genomic DNA segments derived from tissue or DNA samples as well as previously generated PCR products. Thus, the credibility of genetic sex typing by conventional PCR-based methods that measure the relative amounts of the end product DNA amplicons critically depends on several experimental steps that are potentially vulnerable to errors. Here, we describe an optimized protocol of chicken genetic sex typing by TaqMan real-time quantitative PCR amplification of markers on the sex chromosomes. This TaqMan sex typing method accurately quantifies relative amounts of the Z and W sex chromosome markers directly from only 0.5 to 2 mu L of total blood lysate without nucleic acid purification. The real-time amplification curves of the quantitative PCR reaction readily distinguishe truly homozygous (ZZ) and heterozygous (ZW) sex chromosomes from contamination of the sex chromosomal DNA, ensuring highly credible sex determination. Thus, the TaqMan typing of chicken genetic sex has several advantageous features for high-throughput operation compared with conventional methods.
C1 [Shioda, T.] Massachusetts Gen Hosp, Mol Profiling Lab, Ctr Canc Res, Charlestown, MA 02129 USA.
Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
RP Shioda, T (reprint author), Massachusetts Gen Hosp, Mol Profiling Lab, Ctr Canc Res, Charlestown, MA 02129 USA.
EM tshioda@partners.org
FU Friends of Mel's Foundation
FX We thank Sabrina C. Collins and Shannon L. Smith (Molecular Profiling
Laboratory, Massachusetts General Hospital Center for Cancer Research)
for initial technical contributions to the study. This study was
supported by Friends of Mel's Foundation gift to TS.
NR 21
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U1 2
U2 7
PU POULTRY SCIENCE ASSOC INC
PI SAVOY
PA 1111 N DUNLAP AVE, SAVOY, IL 61874-9604 USA
SN 0032-5791
J9 POULTRY SCI
JI Poult. Sci.
PD JUL 1
PY 2010
VL 89
IS 7
BP 1451
EP 1456
DI 10.3382/ps.2010-00638
PG 6
WC Agriculture, Dairy & Animal Science
SC Agriculture
GA 617TQ
UT WOS:000279305200014
PM 20548072
ER
PT J
AU Thomas, S
Judge, T
Lowell, MJ
MacDonald, RD
Madden, J
Pickett, K
Werman, HA
Shear, ML
Patel, P
Starr, G
Chesney, M
Domeier, R
Frantz, P
Funk, D
Greenberg, RD
AF Thomas, Stephen
Judge, Tom
Lowell, Mark J.
MacDonald, Russell D.
Madden, John
Pickett, Kimberly
Werman, Howard A.
Shear, Melissa L.
Patel, Pina
Starr, Greg
Chesney, Michael
Domeier, Robert
Frantz, Pam
Funk, Deb
Greenberg, Robert D.
TI AIRWAY MANAGEMENT SUCCESS AND HYPOXEMIA RATES IN AIR AND GROUND CRITICAL
CARE TRANSPORT: A PROSPECTIVE MULTICENTER STUDY
SO PREHOSPITAL EMERGENCY CARE
LA English
DT Article
DE airway management; critical care transport; intubation; air medical;
helicopter
ID RAPID-SEQUENCE INTUBATION; TRAUMATIC BRAIN-INJURY; HOSPITAL ENDOTRACHEAL
INTUBATION; MEDICAL-SERVICE; IMPACT; MODERATE; HYPOXIA; US
AB Objective. To assess critical care transport (CCT) crews' endotracheal intubation (ETI) attempts, success rates, and peri-ETI oxygenation. Methods. Participants were adult and pediatric patients undergoing attempted advanced airway management during the period from July 2007 to December 2008 by crews from 11 CCT programs varying in geography, crew configuration, and casemix; all crews had access to neuromuscular-blocking agents. Data collected included airway management variables defined per national consensus criteria. Descriptive analysis focused on ETI success rates (reported with exact binomial 95% confidence intervals [CIs]) and occurrence of new hypoxemia (oxygen saturation [SpO(2)] dropping below 90% during or after ETI); to assess categorical variables, Fisher's exact test, Pearson chi(2), and logistic regression were employed to explore associations between predictor variables and ETI failure or new hypoxemia. For all tests, p < 0.05 defined significance. Results. There were 603 total attempts at airway management, with successful oral or nasal ETI in 582 cases, or 96.5% (95% CI 94.7-97.8%). In 182 cases (30.2%, 95% CI 26.5-34.0%), there were failed ETI attempts prior to CCT crew arrival; CCT crew ETI success on these patients (96.2%, 95% CI 92.2-98.4%) was just as high as in the patients in whom there was no pre-CCT ETI attempt (p = 0.81). New hypoxemia occurred in only six cases (1.6% of the 365 cases with ongoing SpO2 monitoring; 95% CI 0.6-3.5%); the only predictor of new hypoxemia was pre-ETI hypotension (p < 0.001). A requirement for multiple ETI attempts by CCT crews was not associated with new hypoxemia (Fisher's exact p = 0.13). Conclusions. CCT crews' ETI success rates were very high, and even when ETI required multiple attempts, airway management was rarely associated with SpO2 derangement. CCT crews' ETI success rates were equally high in the subset of patients in whom ground emergency medical services (EMS) ETI failed prior to arrival of transport crews.
C1 [Thomas, Stephen] Univ Oklahoma, Sch Community Med, OU Schusterman Ctr, Dept Emergency Med, Tulsa, OK 74135 USA.
[Judge, Tom] LifeFlight Maine, Bangor, ME USA.
[Lowell, Mark J.] Univ Michigan, Dept Emergency Med, Ann Arbor, MI 48109 USA.
[MacDonald, Russell D.] Orange Transport Med, Toronto, ON, Canada.
[MacDonald, Russell D.] Univ Toronto, Dept Med, Div Emergency Med, Toronto, ON, Canada.
[Madden, John] Christiana Care Hlth Syst, LifeNet, Wilmington, DE USA.
[Madden, John] Christiana Care Hlth Syst, Dept Emergency Med, Wilmington, DE USA.
[Pickett, Kimberly] Sunstar Crit Care Transport, Largo, FL USA.
[Werman, Howard A.] Ohio State Univ, Dept Emergency Med, Columbus, OH 43210 USA.
[Shear, Melissa L.; Patel, Pina] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA.
[Chesney, Michael] Univ Michigan Survival Flight, Ann Arbor, MI USA.
[Domeier, Robert] Washtenaw Livingston Cty Med Control Author, Ann Arbor, MI USA.
[Frantz, Pam] Flight Life Colorado, Denver, CO USA.
[Funk, Deb] City San Diego EMS, San Diego, CA USA.
[Greenberg, Robert D.] Texas A&M Hlth Sci Ctr, Coll Med, Dept Emergency Med, Temple, TX USA.
[Greenberg, Robert D.] Scott & White Hosp & Clin, Temple, TX USA.
RP Thomas, S (reprint author), Univ Oklahoma, Sch Community Med, OU Schusterman Ctr, Dept Emergency Med, 4502 E 41st St, Tulsa, OK 74135 USA.
EM stephen-thomas@ouhsc.edu
FU MedEvac Foundation International
FX The study's multicenter collaborative research group (the Critical Care
Transport Collaborative Outcomes Research Effort, CCT CORE) is supported
by an unrestricted grant from the MedEvac Foundation International.
There are no conflicts of interest or financial disclosures, and the
authors are responsible for all of the content in the manuscript.
NR 25
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U1 2
U2 2
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1090-3127
EI 1545-0066
J9 PREHOSP EMERG CARE
JI Prehosp. Emerg. Care
PD JUL-SEP
PY 2010
VL 14
IS 3
BP 283
EP 291
DI 10.3109/10903127.2010.481758
PG 9
WC Emergency Medicine; Public, Environmental & Occupational Health
SC Emergency Medicine; Public, Environmental & Occupational Health
GA 666MC
UT WOS:000283118400001
PM 20507218
ER
PT J
AU Benacerraf, BR
AF Benacerraf, Beryl R.
TI The history of the second-trimester sonographic markers for detecting
fetal Down syndrome, and their current role in obstetric practice
SO PRENATAL DIAGNOSIS
LA English
DT Review
DE fetal ultrasound; fetal imaging; Down syndrome; ultrasound markers;
nuchal fold; echogenic intracardiac focus; screening
ID ECHOGENIC INTRACARDIAC FOCUS; NUCHAL-TRANSLUCENCY THICKNESS; NASAL BONE
HYPOPLASIA; ADVANCED MATERNAL AGE; CHOROID-PLEXUS CYSTS; 2ND TRIMESTER;
GENETIC SONOGRAPHY; PRENATAL DETECTION; CHROMOSOMAL-ABNORMALITIES;
SCORING INDEX
AB This review summarizes the development, history and use of second-trimester sonographic markers for the detection of fetal Down syndrome over three decades. Starting with the nuchal fold thickening in 1985 and culminating in the genetic sonogram in the 1990s. The combination of second-trimester serum screening with the ultrasound markers improved the detection rate of affected fetuses but also allowed patients to decrease their risk of carrying a fetus with Down syndrome if the genetic sonogram was normal. More recently the role of the genetic sonogram and its markers have changed with the wide spread use of first-trimester screening. This prior screening ultimately decreases the prevalence of fetal Down syndrome in the second trimester to less than 85% of what it was in the first-trimester as most fetuses with Down syndrome are now identified early. Current interpretation of the second-trimester Down syndrome markers must be based on the result of the first trimester and combined screening to achieve the most accurate risk estimate of an affected fetus. Copyright (C) 2010 John Wiley & Sons, Ltd.
C1 [Benacerraf, Beryl R.] Diagnost Ultrasound Associates, Boston, MA 02115 USA.
[Benacerraf, Beryl R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
[Benacerraf, Beryl R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
RP Benacerraf, BR (reprint author), Diagnost Ultrasound Associates, 333 Longwood Ave, Boston, MA 02115 USA.
EM bbsono@aol.com
NR 90
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Z9 23
U1 1
U2 9
PU JOHN WILEY & SONS LTD
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND
SN 0197-3851
J9 PRENATAL DIAG
JI Prenat. Diagn.
PD JUL
PY 2010
VL 30
IS 7
BP 644
EP 652
DI 10.1002/pd.2531
PG 9
WC Genetics & Heredity; Obstetrics & Gynecology
SC Genetics & Heredity; Obstetrics & Gynecology
GA 624QW
UT WOS:000279835800013
PM 20572106
ER
PT J
AU Shanmugam, R
Kusumanchi, P
Cheng, LA
Crooks, P
Neelakantan, S
Matthews, W
Nakshatri, H
Sweeney, CJ
AF Shanmugam, Rajasubramaniam
Kusumanchi, Praveen
Cheng, Liang
Crooks, Peter
Neelakantan, Sundar
Matthews, William
Nakshatri, Harikrishna
Sweeney, Christopher J.
TI A Water-Soluble Parthenolide Analogue Suppresses In Vivo Prostate Cancer
Growth by Targeting NF kappa B and Generating Reactive Oxygen Species
SO PROSTATE
LA English
DT Article
DE parthenolide analogue; apoptosis; androgen independence
ID SESQUITERPENE LACTONE PARTHENOLIDE; MYELOGENOUS LEUKEMIA STEM;
DOUBLE-EDGED-SWORD; TRANSCRIPTION FACTOR; INDUCED APOPTOSIS; PROGENITOR
CELLS; BREAST-CANCER; JNK; ACTIVATION; TRIAL
AB BACKGROUND. To characterize the molecular changes associated with DMAPT-induced prostate cancer cell death and its in vivo activity.
METHODS. CWR22Rv1 and PC-3 were subjected to flow cytometry, electrophoretic mobility shift assays, and Western blot studies to measure DMAPT's ability to generate reactive oxygen species (ROS), inhibit NF kappa B DNA binding, and cause changes in anti-apoptotic proteins. N-acetyl cysteine (NAC) and short hairpin RNA (shRNA) were used to determine the contribution of ROS and JNK2 activation, respectively. The BrdU incorporation assay was used to measure proliferation and trypan blue studies assessed cell viability after DMAPT treatment. The in vivo activity of DMAPT as a single agent and in combination with bicalutamide or docetaxel was assessed in a subcutaneous xenograft model with athymic nude female mice.
RESULTS. DMAPT generated ROS with subsequent JNK activation and inhibited NF kappa B DNA binding and expression of NF kappa B-regulated anti-apoptotic proteins. DMAPT increased necrotic and apoptotic cell death in a cell-type-dependent manner and both types of cell death were blocked by NAC. Additionally, shRNA JNK2 partially blocked the anti-proliferative activity of DMAPT. DMAPT inhibited CWR22Ryl and PC-3 cellular proliferation by 100% with 10 and 20 mu M respectively and in vivo, DMAPT was more effective at inhibiting growth than biclutamide (CWR22v1) and docetaxel (PC-3).
CONCLUSIONS. DMAPT promotes cell death by both generating ROS and inhibition of NF kappa B. Its in vivo activity supports the conduct of clinical trials in patients with castrate-resistant disease. Prostate 70: 1074-1086, 2010. (C) 2010 Wiley-Liss, Inc.
C1 [Sweeney, Christopher J.] Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Dept Med, Boston, MA 02115 USA.
[Shanmugam, Rajasubramaniam; Kusumanchi, Praveen; Sweeney, Christopher J.] Indiana Univ, Dept Med, Indianapolis, IN USA.
[Cheng, Liang] Indiana Univ, Dept Pathol, Indianapolis, IN 46204 USA.
[Crooks, Peter; Neelakantan, Sundar] Univ Kentucky, Coll Pharm, Lexington, KY USA.
[Matthews, William] Leuchemix Inc, Woodside, CA USA.
[Nakshatri, Harikrishna; Sweeney, Christopher J.] Indiana Univ, Dept Surg, Indianapolis, IN 46204 USA.
[Nakshatri, Harikrishna] Walther Canc Inst, Indianapolis, IN USA.
[Nakshatri, Harikrishna] Indiana Univ, Dept Biochem & Mol Biol, Indianapolis, IN 46204 USA.
RP Sweeney, CJ (reprint author), Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Dept Med, 44 Binney St,DA 1230, Boston, MA 02115 USA.
EM christopher_sweeney@dfci.harvard.edu
FU Department of Defense [DAMD W81XWH-06-1-0225]; Walther Cancer Institute
FX Grant sponsor: Department of Defense; Grant number: DAMD
W81XWH-06-1-0225; Grant sponsor: Walther Cancer Institute.
NR 46
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U1 0
U2 5
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 JUL 1
PY 2010
VL 70
IS 10
BP 1074
EP 1086
DI 10.1002/pros.21141
PG 13
WC Endocrinology & Metabolism; Urology & Nephrology
SC Endocrinology & Metabolism; Urology & Nephrology
GA 619NR
UT WOS:000279437400005
PM 20209491
ER
PT J
AU Feusner, JD
Neziroglu, F
Wilhelm, S
Mancusi, L
Bohon, C
AF Feusner, Jamie D.
Neziroglu, Fugen
Wilhelm, Sabine
Mancusi, Lauren
Bohon, Cara
TI What Causes BDD: Research Findings and a Proposed Model
SO PSYCHIATRIC ANNALS
LA English
DT Article
ID BODY DYSMORPHIC DISORDER; OBSESSIVE-COMPULSIVE DISORDER; SPECTRUM
DISORDERS; ATTRACTIVENESS; ASSOCIATION; INFORMATION; FAMILY; CROSS
C1 [Feusner, Jamie D.; Bohon, Cara] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90095 USA.
[Neziroglu, Fugen; Mancusi, Lauren] Biobehav Inst, Great Neck, NY USA.
[Wilhelm, Sabine] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Wilhelm, Sabine] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
RP Feusner, JD (reprint author), 300 UCLA Med Plaza,Suite 2345, Los Angeles, CA 90095 USA.
EM jfeusner@mednet.ucla.edu
RI Feusner, Jamie/K-2312-2012
OI Feusner, Jamie/0000-0002-0391-345X
FU NIMH NIH HHS [K23 MH079212, L30 MH081669]
NR 49
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U1 2
U2 16
PU SLACK INC
PI THOROFARE
PA 6900 GROVE RD, THOROFARE, NJ 08086 USA
SN 0048-5713
J9 PSYCHIAT ANN
JI Psychiatr. Ann.
PD JUL
PY 2010
VL 40
IS 7
BP 349
EP 355
DI 10.3928/00485713-20100701-08
PG 7
WC Psychiatry
SC Psychiatry
GA 627TZ
UT WOS:000280067100009
PM 24347738
ER
PT J
AU Buchholz, JR
Malte, CA
Calsyn, DA
Baer, JS
Nichol, P
Kivlahan, DR
Caldeiro, RM
Saxon, AJ
AF Buchholz, Jonathan R.
Malte, Carol A.
Calsyn, Donald A.
Baer, John S.
Nichol, Paul
Kivlahan, Daniel R.
Caldeiro, Ryan M.
Saxon, Andrew J.
TI Associations of Housing Status With Substance Abuse Treatment and
Service Use Outcomes Among Veterans
SO PSYCHIATRIC SERVICES
LA English
DT Article
ID ADDICTION SEVERITY INDEX; HOMELESS PERSONS; RANDOMIZED-TRIAL; DISORDERS;
ALCOHOL; CARE
AB Objective: This secondary analysis evaluated the prevalence and stability of homelessness over one year among veterans entering substance abuse treatment and explored associations among housing status, treatment outcomes, and Veterans Affairs (VA) service utilization. Methods: Participants in a trial of on-site primary care for veterans entering substance abuse treatment (N=622) were placed in four groups based on housing status: housed at baseline and final follow-up (41%), homeless at baseline and final follow-up (27%), housed at baseline but homeless at final follow-up (8%), and homeless at baseline but housed at final follow-up (24%). Groups were compared on treatment retention, changes in Addiction Severity Index (ASI) composite scores, and VA service utilization and costs. Results: Treatment retention and changes in ASI alcohol composites did not differ between groups. Compared with scores in the consistently housed group, the ASI drug composites improved less over time in the consistently homeless group (p=.031) and the ASI psychiatric composites improved less in the group housed at baseline and homeless at final follow-up (p=.019). All homeless groups were more likely than the consistently housed group to have inpatient admissions and incurred higher total treatment costs. The consistently homeless group was more likely to use emergency care than the consistently housed group. Conclusions: Homelessness affects substance abuse treatment outcomes and costs. Interventions are needed to reduce homelessness among veterans entering substance abuse treatment. (Psychiatric Services 61: 698-706, 2010)
C1 [Malte, Carol A.; Baer, John S.; Kivlahan, Daniel R.; Saxon, Andrew J.] VA Puget Sound Hlth Care Syst, VA Ctr Excellence Subst Abuse Treatment & Educ, Seattle, WA 98108 USA.
[Buchholz, Jonathan R.] US Dept Vet Affairs, VA Puget Sound Hlth Care Syst, Seattle, WA USA.
[Baer, John S.] Univ Washington, Dept Psychol, Seattle, WA 98195 USA.
[Kivlahan, Daniel R.; Saxon, Andrew J.] Univ Washington, Dept Psychiat & Behav Sci, Sch Med, Seattle, WA 98195 USA.
[Calsyn, Donald A.; Caldeiro, Ryan M.] Grp Hlth Cooperat Puget Sound, Seattle, WA USA.
[Nichol, Paul] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA.
RP Malte, CA (reprint author), VA Puget Sound Hlth Care Syst, VA Ctr Excellence Subst Abuse Treatment & Educ, 1660 S Columbian Way,MS S-116-ATC, Seattle, WA 98108 USA.
EM carol.malte@va.gov
FU Health Services Research and Development, U.S. Department of Veterans
Affairs [SUI 99-109-1]; Center of Excellence in Substance Abuse
Treatment and Education at VA Puget Sound Health Care System, Seattle;
Ortho-McNeil Janssen; Titan Pharmaceuticals; U.S. World Meds
FX This study was based on work supported by grant SUI 99-109-1 from Health
Services Research and Development, U.S. Department of Veterans Affairs,
and by the Center of Excellence in Substance Abuse Treatment and
Education at VA Puget Sound Health Care System, Seattle.; Dr. Saxon has
worked as a consultant to Reckitt Benckiser Pharmaceuticals and received
research support from Ortho-McNeil Janssen, Titan Pharmaceuticals, and
U.S. World Meds, as well as honoraria from Forest Pharmaceuticals,
Alkermes, and Cephalon. The other authors report no competing interests.
NR 32
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U1 0
U2 3
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 1075-2730
J9 PSYCHIAT SERV
JI Psychiatr. Serv.
PD JUL
PY 2010
VL 61
IS 7
BP 698
EP 706
PG 9
WC Health Policy & Services; Public, Environmental & Occupational Health;
Psychiatry
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health; Psychiatry
GA 618YV
UT WOS:000279393200013
PM 20592005
ER
PT J
AU Kasckow, J
Brown, C
Morse, JQ
Karpov, I
Bensasi, S
Thomas, SB
Ford, A
Reynolds, C
AF Kasckow, John
Brown, Charlotte
Morse, Jennifer Q.
Karpov, Irina
Bensasi, Salem
Thomas, Stephen B.
Ford, Angela
Reynolds, Charles
TI Racial Preferences for Participation in a Depression Prevention Trial
Involving Problem-Solving Therapy
SO PSYCHIATRIC SERVICES
LA English
DT Article
ID PRIMARY-CARE PATIENTS; AFRICAN-AMERICANS; OLDER
AB Objectives: This study compared African Americans' and Caucasians' willingness to participate in an indicated intervention to prevent depression with problem-solving therapy. It also examined participants' problem-solving skills. Hypotheses stated that there would be no racial differences in consent rates and that social problem-solving coping skills would be lower among African Americans than Caucasians. Methods: Proportions of African Americans and Caucasians who consented were compared, as were Social Problem Solving Inventory scores between the groups. Results: Of 2,788 individuals approached, 82 (4%) of 1,970 Caucasians and 46 (6%) of 818 African Americans signed consent, and the difference was not significant (p=.09). Racial differences were observed in neither Social Problem Solving Inventory scores nor in the relationship between problem-solving skills and depressive symptoms. Conclusions: African Americans with depression demonstrated a willingness to participate in an indicated trial of depression prevention. Furthermore, both groups would appear to benefit from the problem-solving process. (Psychiatric Services 61: 722-724, 2010)
C1 [Kasckow, John] Pittsburgh Hlth Care Syst, US Dept Vet Affairs, Dept Behav Hlth, Pittsburgh, PA 15206 USA.
[Brown, Charlotte; Morse, Jennifer Q.; Karpov, Irina; Bensasi, Salem; Reynolds, Charles] Univ Pittsburgh, Western Psychiat Inst & Clin, Med Ctr, Pittsburgh, PA 15213 USA.
[Thomas, Stephen B.; Ford, Angela] Univ Pittsburgh, Grad Sch Publ Hlth, Med Ctr, Pittsburgh, PA 15213 USA.
RP Kasckow, J (reprint author), Pittsburgh Hlth Care Syst, US Dept Vet Affairs, Dept Behav Hlth, 7180 Highland Dr, Pittsburgh, PA 15206 USA.
EM kasckowjw@upmc.edu
FU National Center on Minority Health and Health Disparities
[P60-MD000107]; National Institute of Mental Health [P30-MH71944, NIMH
6398-01, 2P60-MD000207-07]
FX This work was supported primarily by grant P60-MD000107 from the
National Center on Minority Health and Health Disparities and by grants
P30-MH71944, NIMH 6398-01, and 2P60-MD000207-07 from the National
Institute of Mental Health.
NR 10
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U1 0
U2 2
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 1075-2730
J9 PSYCHIAT SERV
JI Psychiatr. Serv.
PD JUL
PY 2010
VL 61
IS 7
BP 722
EP 724
PG 3
WC Health Policy & Services; Public, Environmental & Occupational Health;
Psychiatry
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health; Psychiatry
GA 618YV
UT WOS:000279393200017
PM 20592009
ER
PT J
AU Ganzini, L
Socherman, R
Duckart, J
Shores, M
AF Ganzini, Linda
Socherman, Robert
Duckart, Jonathan
Shores, Molly
TI End-of-Life Care for Veterans With Schizophrenia and Cancer
SO PSYCHIATRIC SERVICES
LA English
DT Article
ID SERIOUS MENTAL-ILLNESS
AB Objective: This study compared the quality of end-of-life care between veterans with and without schizophrenia who died of cancer in the northwestern United States. Methods: In this cross-sectional study, medical records of 60 veterans with schizophrenia and 196 with no major mental illness who died of cancer were compared on hospice enrollment, palliative and life-sustaining interventions, advance directives, and site of death. Results: Among veterans with schizophrenia, 58% had an advance directive, 73% received an opiate before hospice enrollment, 63% had a physician order to forgo cardiopulmonary resuscitation, 55% were hospice enrolled, and 27% died in the hospital. Schizophrenia patients had longer hospice stays (107 +/- 144 versus 63 +/- 96 days, p=.05) and more physician orders for life-sustaining treatment (15% versus 5%, p=.006) compared with veterans without mental illness. Conclusions: On most measures, veterans with schizophrenia who died of cancer received comparable or better end-of-life care than veterans without mental illness. (Psychiatric Services 61: 725-728, 2010)
C1 [Ganzini, Linda] Vet Adm Med Ctr, Div Mental Hlth, Portland, OR 97207 USA.
[Shores, Molly] VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA.
RP Ganzini, L (reprint author), Vet Adm Med Ctr, Div Mental Hlth, R&D 66,POB 1034, Portland, OR 97207 USA.
EM linda.ganzini@va.gov
FU VA Health Services Research and Development
FX This study was supported in part by the VA Health Services Research and
Development Research Enhancement Award Program, Portland, Oregon. The
views expressed in this article are those of the authors and do not
necessarily reflect the position or policy of the VA or the U.S.
government.
NR 13
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U1 0
U2 3
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 1075-2730
J9 PSYCHIAT SERV
JI Psychiatr. Serv.
PD JUL
PY 2010
VL 61
IS 7
BP 725
EP 728
PG 4
WC Health Policy & Services; Public, Environmental & Occupational Health;
Psychiatry
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health; Psychiatry
GA 618YV
UT WOS:000279393200018
PM 20592010
ER
PT J
AU Wozniak, J
Faraone, SV
Mick, E
Monuteaux, M
Coville, A
Biederman, J
AF Wozniak, J.
Faraone, S. V.
Mick, E.
Monuteaux, M.
Coville, A.
Biederman, J.
TI A controlled family study of children with DSM-IV bipolar-I disorder and
psychiatric co-morbidity
SO PSYCHOLOGICAL MEDICINE
LA English
DT Article
DE Bipolar; children; family study
ID DEFICIT HYPERACTIVITY DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY
DISORDER; SUBSTANCE USE DISORDERS; DOPAMINE TRANSPORTER GENE; SPECTRUM
DISORDERS; MAJOR DEPRESSION; MOOD DISORDERS; RISK ANALYSIS; ONSET MANIA;
ADOLESCENT
AB Background. To estimate the spectrum of familial risk for psychopathology in first-degree relatives of children with unabridged DSM-IV bipolar-I disorder (BP-I).
Method. We conducted a blinded, controlled family study using structured diagnostic interviews of 157 children with BP-I probands (n = 487 first-degree relatives), 162 attention deficit hyperactivity disorder (ADHD) (without BP-I) probands (is = 511 first-degree relatives), and 136 healthy control (without ADHD or BP-I) probands (n = 411 first-degree relatives).
Results. The morbid risk (MR) of BP-I disorder in relatives of BP-I probands (MR = 0.18) was increased 4-fold [95% confidence interval (CI) 2.3-6.9, p<0.001] over the risk to relatives of control probands (MR = 0.05) and 3.5-fold (95% CI 2.1-5.8, p<0.001) over the risk to relatives of ADHD probands (MR = 0.06). In addition, relatives of children with BP-I disorder had high rates of psychosis, major depression, multiple anxiety disorders, substance use disorders, ADHD and antisocial disorders compared with relatives of control probands. Only the effect for antisocial disorders lost significance after accounted for by the corresponding diagnosis in the proband. Familial rates of ADHD did not differ between ADHD and BP-I probands.
Conclusions. Our results document an increased familial risk for BP-I disorder in relatives of pediatric probands with DSM-IV BP-I. Relatives of probands with BP-I were also at increased risk for other psychiatric disorders frequently associated with pediatric BP-l. These results support the validity of the diagnosis of BP-I in children as defined by DSM-IV. More work is needed to better understand the nature of the association between these disorders in probands and relatives.
C1 [Wozniak, J.; Monuteaux, M.; Coville, A.; Biederman, J.] Massachusetts Gen Hosp, Pediat Psychopharmacol & Adult ADHD, Clin & Res Program, Boston, MA 02114 USA.
[Wozniak, J.; Mick, E.; Monuteaux, M.; Biederman, J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
[Faraone, S. V.] SUNY Upstate Med Univ, Dept Psychiat, New York, NY USA.
[Faraone, S. V.] SUNY Upstate Med Univ, Dept Neurosci & Physiol, New York, NY USA.
RP Wozniak, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol & Adult ADHD, Clin & Res Program, 55 Fruit St,Warren 705, Boston, MA 02114 USA.
EM jwozniak@partners.org
OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982
FU National Institutes of Health (NIH) [K08MH001503, R01MH066237,
R01MH050657, R01HD036317, K01MH065523]; Susan G. Berk Endowed Fund for
Juvenile Bipolar Disorder; Heinz C. Prechter Bipolar Research Fund; MGH
Pediatric Psychopharmacology Council; McNeil Pediatrics; Ortho-McNeil
Janssen Scientific Affairs; Pfizer; Shire Pharmaceuticals; National
Institute of Mental Health (NIMH); Alza; AstraZeneca; Bristol Myers
Squibb; Eli Lilly and Co.; Janssen Pharmaceuticals Inc.; McNeil; Merck;
Organon; Otsuka; Shire; NICHD; Abbott; Celltech; Cephalon; Esai; Forest;
Glaxo; Gliatech; NARSAD; NIDA; New River; Novartis; Noven; Neurosearch;
Pharmacia; Prechter Foundation; Stanley Foundation; Wyeth; Shire, Inc.;
Boehringer-Ingelheim; GlaxoSmithKline; UCB (Schwarz) Pharma; Sepracor
FX This work was supported by National Institutes of Health (NIH) grants
K08MH001503 and R01MH066237 to Dr Wozniak, R01MH050657 and R01HD036317
to Dr Biederman and K01MH065523 to Dr Mick. This work was also supported
by a grant from the Susan G. Berk Endowed Fund for Juvenile Bipolar
Disorder. The Heinz C. Prechter Bipolar Research Fund and the support of
members of the MGH Pediatric Psychopharmacology Council. All sponsors of
this research supported only the collection of the data and played no
other role in the design, analysis or interpretation of these findings.;
Dr Eric Mick 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. Dr Eric Mick receives research support from the following
sources and is on an advisory board for the following sources: McNeil
Pediatrics, Ortho-McNeil Janssen Scientific Affairs, Pfizer, Shire
Pharmaceuticals and the National Institute of Mental Health (NIMH) and
has had an advisory or consulting relationship with Pfizer and Shire
Pharmaceutical. Dr Joseph Biederman is currently receiving research
support from the following sources: Alza, AstraZeneca, Bristol Myers
Squibb, Eli Lilly and Co., Janssen Pharmaceuticals Inc., McNeil, Merck,
Organon, Otsuka, Shire, NIMH and NICHD. Dr Biederman is currently a
consultant/advisory board member for the following pharmaceutical
companies: Janssen, McNeil, Novartis and Shire. He is currently a
speaker for the following speaker's bureaux: Janssen, McNeil, Novartis,
Shire and UCB Pharma, Inc. In previous years, Dr. Biederman has received
research support, consultation fees or speaker's fees for/from the
following additional sources: Abbott, AstraZeneca, Celltech, Cephalon,
Eli Lilly and Co., Esai, Forest, Glaxo, Gliatech, NARSAD, NIDA, New
River, Novartis, Noven, Neurosearch, Pfizer, Pharmacia, The Prechter
Foundation, The Stanley Foundation and Wyeth. Dr Michael Monuteaux was a
speaker in a symposia sponsored by Shire, Inc. Dr Faraone receives
research support from and consults to Shire Pharmaceutical Development.
He receives grant support from Eli Lilly and the NIH. Dr Wozniak has
been a speaker for McNeil, Primedia/MGH Psychiatry Academy, on the
Advisory Board for Pfizer and Shire and received research support from
NIMH, McNeil, Shire and Lilly. Her spouse, John Winkelman MD, PhD, has
been on the Speakers Bureau for Boehringer-Ingelheim, Cephalon,
GlaxoSmithKline, King, Sanofi-Aventis, Sepracor, Takeda, on the Advisory
Board for Axon Labs, Boehringer-Ingelheim, GlaxoSmithKline, Jazz
Pharmaceuticals, Novartis, Neurogen, Novadel Pharma, Pfizer, UCB
(Schwarz) Pharma, Sepracor, Takeda and received research support from
Boehringer-Ingelheim, GlaxoSmithKline, UCB (Schwarz) Pharma, Sepracor.
NR 52
TC 23
Z9 24
U1 2
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 JUL
PY 2010
VL 40
IS 7
BP 1079
EP 1088
DI 10.1017/S0033291709991437
PG 10
WC Psychology, Clinical; Psychiatry; Psychology
SC Psychology; Psychiatry
GA 619GT
UT WOS:000279418000003
PM 19891803
ER
PT J
AU McDermott, MJ
Tull, MT
Soenke, M
Jakupcak, M
Gratz, KL
AF McDermott, Michael J.
Tull, Matthew T.
Soenke, Melissa
Jakupcak, Matthew
Gratz, Kim L.
TI Masculine Gender Role Stress and Posttraumatic Stress Disorder Symptom
Severity Among Inpatient Male Crack/Cocaine Users
SO PSYCHOLOGY OF MEN & MASCULINITY
LA English
DT Article
DE masculine gender role stress; masculinity; posttraumatic stress
disorder; risk factor; vulnerability
ID ADMINISTERED PTSD SCALE; PSYCHOMETRIC PROPERTIES; INTERPERSONAL
VIOLENCE; THOUGHT SUPPRESSION; ANXIETY SENSITIVITY; RACIAL IDENTITY;
ROLE CONFLICT; MEN; METAANALYSIS; PREDICTORS
AB This study examined the association between masculine gender role stress (MGRS) and posttraumatic stress disorder (PTSD) symptom severity, above and beyond other factors previously found to be associated with PTSD symptoms (e.g., anxiety sensitivity and thought suppression) among 33 crack/cocaine-dependent patients in residential substance abuse treatment. Participants completed a series of questionnaires and were interviewed to determine current PTSD symptom severity. MGRS accounted for a significant amount of additional variance in PTSD symptom severity above and beyond other identified risk factors for PTSD. Results are discussed in terms of their implications for reducing PTSD risk among men following exposure to a potentially traumatic event.
C1 [McDermott, Michael J.; Tull, Matthew T.; Soenke, Melissa; Gratz, Kim L.] Univ Mississippi, Med Ctr, Dept Psychiat & Human Behav, Jackson, MS 39216 USA.
[Jakupcak, Matthew] VA Puget Sound Hlth Care Syst, MIRECC, Seattle, WA USA.
[Jakupcak, Matthew] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
RP Tull, MT (reprint author), Univ Mississippi, Med Ctr, Dept Psychiat & Human Behav, 2500 N State St, Jackson, MS 39216 USA.
EM mtull@psychiatry.umsmed.edu
NR 53
TC 8
Z9 8
U1 4
U2 9
PU EDUCATIONAL PUBLISHING FOUNDATION
PI WASHINGTON
PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA
SN 1524-9220
J9 PSYCHOL MEN MASCULIN
JI Psychol. Men Masculinity
PD JUL
PY 2010
VL 11
IS 3
BP 225
EP 232
DI 10.1037/a0016671
PG 8
WC Psychology, Social
SC Psychology
GA 626VG
UT WOS:000279994800007
ER
PT J
AU Vranceanu, AM
Safren, SA
Cowan, J
Ring, DC
AF Vranceanu, Ana-Maria
Safren, Steven A.
Cowan, James
Ring, David C.
TI Health Concerns and Somatic Symptoms Explain Perceived Disability and
Idiopathic Hand and Arm Pain in an Orthopedics Surgical Practice: A
Path-Analysis Model
SO PSYCHOSOMATICS
LA English
DT Article
ID COGNITIVE-BEHAVIORAL THERAPY; HYPOCHONDRIASIS; SOMATIZATION; ANXIETY;
EFFICACY; SHOULDER
AB Background: Upper-limb pain disorders are relatively common, and often result in disability, lost time from work, and significant use of healthcare services. Objective: The authors adapted and tested a cognitive-behavioral model of health anxiety in 100 patients with hand and arm pain in an orthopedics surgical practice, hypothesizing that increased health concerns would relate to increased perceived disability, and investigating whether patients' pain is related to other increased somatic symptoms. Method: Patients with (non-traumatic) hand and arm pain received the Health Anxiety Inventory, the Whitley Index, and the Somatic Symptoms Inventory. Primary analyses were conducted via structural-equation modeling. Results: There was a strong, positive, and direct relationship between health concerns and perceived disability. Health concerns were significantly and positively related to somatic symptoms, which, in turn, were significantly positively related to perceived disability and to having idiopathic versus discrete pain. Conclusion: The health-anxiety model is relevant to the development of nonspecific, vague, and diffuse (idiopathic) hand and arm pain. (Psychosomatics 2010; 51:330-337)
C1 [Vranceanu, Ana-Maria] Massachusetts Gen Hosp, Dept Behav Med, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Vranceanu, AM (reprint author), Massachusetts Gen Hosp, Dept Behav Med, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA.
EM avranceanu@partners.org
NR 45
TC 10
Z9 12
U1 0
U2 5
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 0033-3182
J9 PSYCHOSOMATICS
JI Psychosomatics
PD JUL-AUG
PY 2010
VL 51
IS 4
BP 330
EP 337
PG 8
WC Psychiatry; Psychology
SC Psychiatry; Psychology
GA 617YK
UT WOS:000279317600008
PM 20587761
ER
PT J
AU McCollister, DH
Beutz, M
McLaughlin, V
Rumsfeld, J
Masoudi, FA
Tripputi, M
Yaeger, T
Weintraub, P
Badesch, DB
AF McCollister, Deborah H.
Beutz, Michelle
McLaughlin, Vallerie
Rumsfeld, John
Masoudi, Frederick A.
Tripputi, Mark
Yaeger, Thomas
Weintraub, Philippe
Badesch, David B.
TI Depressive Symptoms in Pulmonary Arterial Hypertension: Prevalence and
Association With Functional Status
SO PSYCHOSOMATICS
LA English
DT Article
ID CONTINUOUS INTRAVENOUS EPOPROSTENOL; BRAIN NATRIURETIC PEPTIDE;
QUALITY-OF-LIFE; PLASMA SEROTONIN; CONTROLLED-TRIAL; HEART-FAILURE;
6-MINUTE WALK; DOUBLE-BLIND; THERAPY; DISEASE
AB Background: In patients with left-heart disease, depressive symptoms have a significant impact on functional status and quality of life. The prevalence of depressive symptoms, and their impact on patients with pulmonary arterial hypertension (PAH) is understudied. Objective: The authors investigated the prevalence of depressive symptoms in PAH and their correlation with physical functioning. Method: Consecutive outpatients with PAH ( idiopathic; or associated with scleroderma, congenital heart disease, or anorexiant use) seen in two university PAH clinics were screened. At two outpatient visits, 8 to 16 weeks apart, patients completed the PHQ-8, a well-validated instrument for grading severity of depressive symptoms; they were assessed for cardiac functional class (FC), and performed a 6-minute walk-distance test (6MWD). Results: A group of 100 patients (88% women, 50% with idiopathic PAH) were enrolled. At baseline, 15% of subjects had symptoms suggestive of major depressive disorder; 40% had mild-to-moderate depressive symptoms; and 45% had no-to-minimal depressive symptoms. Conclusion: Depression is common in patients with PAH, with 55% demonstrating depressive symptoms. These results suggest that screening patients with PAH will identify a large proportion of patients who might benefit from depression therapy. (Psychosomatics 2010; 51:339-339.e8)
C1 [McCollister, Deborah H.] Univ Colorado Denver, Pulm Hypertens Ctr, Aurora, CO 80045 USA.
Natl Jewish Hlth, Denver, CO USA.
Univ Michigan, Ann Arbor, MI 48109 USA.
Denver VA Hosp, Denver, CO USA.
Denver Hlth Med Ctr, Denver, CO USA.
RP McCollister, DH (reprint author), Univ Colorado Denver, Pulm Hypertens Ctr, 12401 E 17th Ave,Box L957, Aurora, CO 80045 USA.
EM Deb.McCollister@ucdenver.edu
FU Actelion, Inc.; University of Colorado Denver; University of Michigan;
Actelion/CoTherix; Gilead/Myogen; Encysive; Pfizer;
MondoBiotech/mondoGEN; United Therapeutics/Lung Rx; GlaxoSmithKline;
Lilly/ICOS; Bayer
FX This study was funded by an Investigator-Initiated Proposal by Actelion,
Inc., in the form of a grant to the University of Colorado Denver and
the University of Michigan. Dr. Badesch has received honoraria for
service on steering committees and advisory boards from
Actelion/CoTherix, Gilead/Myogen, Encysive, Pfizer,
MondoBiotech/mondoGEN, United Therapeutics/Lung Rx, GlaxoSmithKline,
Lilly/ICOS, and Bayer. The work was conducted independently, without
direction from the sponsor.
NR 45
TC 29
Z9 32
U1 1
U2 4
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 0033-3182
J9 PSYCHOSOMATICS
JI Psychosomatics
PD JUL-AUG
PY 2010
VL 51
IS 4
BP 339
EP U81
PG 9
WC Psychiatry; Psychology
SC Psychiatry; Psychology
GA 617YK
UT WOS:000279317600010
PM 20587763
ER
PT J
AU Casamassima, F
Lattanzi, L
Perlis, RH
Litta, A
Fui, E
Bonuccelli, U
Fricchione, G
Cassano, GB
AF Casamassima, Francesco
Lattanzi, Lorenzo
Perlis, Roy H.
Litta, Antonella
Fui, Erika
Bonuccelli, Ubaldo
Fricchione, Gregory
Cassano, Giovanni B.
TI Neuroleptic Malignant Syndrome: Further Lessons From a Case Report
SO PSYCHOSOMATICS
LA English
DT Article
ID PARKINSONISM-HYPERPYREXIA SYNDROME; DOPAMINE-D-2 RECEPTOR GENE;
ELECTROCONVULSIVE-THERAPY; PSYCHOGENIC CATATONIA; RISK-FACTORS; ECT;
DISORDERS; LITHIUM; ENCEPHALITIS; ASSOCIATION
AB Background: Neuroleptic malignant syndrome (NMS) represents an iatrogenic form of malignant catatonia, and simple catatonia has been shown to predispose to NMS. Objective: The authors present the case of a bipolar patient with catatonic features who developed NMS after receiving haloperidol. Method: Supportive therapy, including rehydration, electrolyte restoration, and blood pressure aids were given, together with antipyretics, antibiotics, and anticoagulants. The patient was also started on bromocriptine and diazepam. Results: Supportive care, diazepam, and dopamine agonists yielded only partial benefit. However, switching from diazepam to lorazepam, in combination with electroconvulsive therapy (ECT) and a long-acting dopamine agonist led to the resolution of NMS. Conclusion: This case sheds further light on the relationship between catatonia and NMS. As noted in the literature, ECT in combination with lorazepam proved to be safe and effective for NMS. (Psychosomatics 2010; 51:349-354)
C1 [Casamassima, Francesco] Mass Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
Univ Pisa, Dept Psychiat, Pisa, Italy.
RP Casamassima, F (reprint author), Mass Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
EM fcasamassima@hotmail.it; llattanzi@blu.it
RI Bonuccelli, Ubaldo/K-8681-2016
OI Bonuccelli, Ubaldo/0000-0001-6218-6312
NR 56
TC 10
Z9 10
U1 0
U2 3
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 0033-3182
J9 PSYCHOSOMATICS
JI Psychosomatics
PD JUL-AUG
PY 2010
VL 51
IS 4
BP 349
EP 354
PG 6
WC Psychiatry; Psychology
SC Psychiatry; Psychology
GA 617YK
UT WOS:000279317600013
PM 20587766
ER
PT J
AU Loftis, JM
Turner, EH
AF Loftis, Jennifer M.
Turner, Erick H.
TI Novel Treatment Strategies for Depression in Patients With Hepatitis C
SO PSYCHOSOMATICS
LA English
DT Letter
ID INTERFERON-INDUCED DEPRESSION; 5-HYDROXYTRYPTOPHAN; SEROTONIN
C1 [Loftis, Jennifer M.; Turner, Erick H.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland VA Med Ctr, Div Mental Hlth & Clin Neurosci, Portland, OR 97201 USA.
RP Loftis, JM (reprint author), Oregon Hlth & Sci Univ, Dept Psychiat, Portland VA Med Ctr, Div Mental Hlth & Clin Neurosci, Portland, OR 97201 USA.
NR 5
TC 4
Z9 4
U1 0
U2 1
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 0033-3182
J9 PSYCHOSOMATICS
JI Psychosomatics
PD JUL-AUG
PY 2010
VL 51
IS 4
BP 357
EP 358
PG 2
WC Psychiatry; Psychology
SC Psychiatry; Psychology
GA 617YK
UT WOS:000279317600016
PM 20587769
ER
PT J
AU Courtwright, A
Turner, AN
AF Courtwright, Andrew
Turner, Abigail Norris
TI Tuberculosis and Stigmatization: Pathways and Interventions
SO PUBLIC HEALTH REPORTS
LA English
DT Article
ID HEALTH-SEEKING BEHAVIOR; DIRECTLY OBSERVED THERAPY; SOUTH-AFRICA;
PULMONARY TUBERCULOSIS; GENERAL-POPULATION; COMPARATIVE STIGMA;
CULTURAL-FACTORS; RURAL DISTRICT; CARE PROVIDERS; SOCIAL STIGMA
AB The institutional and community norms that lead to the stigmatization of tuberculosis (TB) are thought to hinder TB control. We performed a systematic review of the literature on TB stigma to identify the causes and evaluate the impact of stigma on TB diagnosis and treatment. Several themes emerged: fear of infection is the most common cause of TB stigma; TB stigma has serious socioeconomic consequences, particularly for women; qualitative approaches to measuring TB stigma are more commonly utilized than quantitative surveys; TB stigma is perceived to increase TB diagnostic delay and treatment noncompliance, although attempts to quantify its impact have produced mixed results; and interventions exist that may reduce TB stigma.
Future research should continue to characterize TB stigma in different populations; use validated survey instruments to quantify the impact of TB stigma on TB diagnostic delay, treatment compliance, and morbidity and mortality; and develop additional TB stigma-reduction strategies.
C1 [Courtwright, Andrew] Harvard Univ, Massachusetts Gen Hosp, Dept Med, Sch Med, Boston, MA 02114 USA.
[Turner, Abigail Norris] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA.
RP Courtwright, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Med, Sch Med, 55 Fruit St,Yawkey 4B,Ste 4700, Boston, MA 02114 USA.
EM acourt1500@gmail.com
NR 99
TC 63
Z9 66
U1 0
U2 12
PU ASSOC SCHOOLS PUBLIC HEALTH
PI WASHINGTON
PA 1101 15TH ST NW, STE 910, WASHINGTON, DC 20005 USA
SN 0033-3549
J9 PUBLIC HEALTH REP
JI Public Health Rep.
PD JUL-AUG
PY 2010
VL 125
SU 4
BP 34
EP 42
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 609QT
UT WOS:000278672900007
PM 20626191
ER
PT J
AU Sawyer, AM
Deatrick, JA
Kuna, ST
Weaver, TE
AF Sawyer, Amy M.
Deatrick, Janet A.
Kuna, Samuel T.
Weaver, Terri E.
TI Differences in Perceptions of the Diagnosis and Treatment of Obstructive
Sleep Apnea and Continuous Positive Airway Pressure Therapy Among
Adherers and Nonadherers
SO QUALITATIVE HEALTH RESEARCH
LA English
DT Article
DE adherence; compliance; content analysis; decision making; health
behavior; mixed methods; sleep disorders; social cognitive theory
ID LONG-TERM COMPLIANCE; QUALITATIVE CONTENT-ANALYSIS; CPAP THERAPY; NASAL
CPAP; APNOEA/HYPOPNOEA SYNDROME; APNEA/HYPOPNEA SYNDROME; BREATHING
DISORDERS; PATIENT COMPLIANCE; SELF-EFFICACY; ADULTS
AB Obstructive sleep apnea (OSA) patients' consistent use of continuous positive airway pressure (CPAP) therapy is critical to realizing improved functional outcomes and reducing untoward health risks associated with OSA. We conducted a mixed methods, concurrent, nested study to explore OSA patients' beliefs and perceptions of the diagnosis and CPAP treatment that differentiate adherent from nonadherent patients prior to and after the first week of treatment, when the pattern of CPAP use is established. Guided by social cognitive theory, themes were derived from 30 interviews conducted postdiagnosis and after 1 week of CPAP use. Directed content analysis, followed by categorization of participants as adherent/nonadherent from objectively measured CPAP use, preceded across-case analysis among 15 participants with severe OSA. Beliefs and perceptions that differed between adherers and nonadherers included OSA risk perception, symptom recognition, self-efficacy, outcome expectations, treatment goals, and treatment facilitators/barriers. Our findings suggest opportunities for developing and testing tailored interventions to promote CPAP use.
C1 [Sawyer, Amy M.; Deatrick, Janet A.] Univ Penn, Sch Nursing, Ctr Hlth Equ Res, Philadelphia, PA 19104 USA.
[Weaver, Terri E.] Univ Penn, Sch Nursing, Biobehav Res Ctr, Philadelphia, PA 19104 USA.
[Kuna, Samuel T.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA.
[Weaver, Terri E.] Univ Penn, Sch Nursing, Biobehav Hlth Sci Div, Philadelphia, PA 19104 USA.
[Kuna, Samuel T.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
RP Sawyer, AM (reprint author), Univ Penn, Sch Nursing, Ctr Hlth Equ Res, Claire M Fagin Hall,307B,418 Curie Blvd, Philadelphia, PA 19104 USA.
EM asawyer@nursing.upenn.edu
FU NINR NIH HHS [F31 NR009315, F31NR9315, F31 NR009315-01]
NR 62
TC 23
Z9 24
U1 1
U2 8
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1049-7323
J9 QUAL HEALTH RES
JI Qual. Health Res.
PD JUL
PY 2010
VL 20
IS 7
BP 873
EP 892
DI 10.1177/1049732310365502
PG 20
WC Information Science & Library Science; Social Sciences,
Interdisciplinary; Social Sciences, Biomedical
SC Information Science & Library Science; Social Sciences - Other Topics;
Biomedical Social Sciences
GA 610SV
UT WOS:000278757400002
PM 20354236
ER
PT J
AU Angelone, LM
Bit-Babik, G
Chou, CK
AF Angelone, Leonardo M.
Bit-Babik, Giorgi
Chou, Chung-Kwang
TI Computational Electromagnetic Analysis in a Human Head Model with EEG
Electrodes and Leads Exposed to RF-Field Sources at 915 MHz and 1748 MHz
SO RADIATION RESEARCH
LA English
DT Article
ID METALLIC IMPLANTS; 7 TESLA; MRI; SAR; TEMPERATURE; SIMULATION; SAFETY;
STIMULATOR; ELEVATION; COILS
AB An electromagnetic analysis of a human head with EEC electrodes and leads exposed to RF-field sources was performed by means of Finite-Difference Time-Domain simulations on a 1-mm(3) MRI-based human head model. RF-field source models included a half-wave dipole, a patch antenna, and a realistic CAD-based mobile phone at 915 MHz and 1748 MHz. EEC electrodes/leads models included two configurations of EEG leads, both a standard 10-20 montage with 19 electrodes and a 32-electrode cap, and metallic and high resistive leads. Whole-head and peak 10-g average SAR showed less than 20% changes with and without leads. Peak 1-g and 10-g average SARs were below the ICNIRP and IEEE guideline limits. Conversely, a comprehensive volumetric assessment of changes in the RF field with and without metallic EEG leads showed an increase of two orders of magnitude in single-voxel power absorption in the epidermis and a 40-fold increase in the brain during exposure to the 915 MHz mobile phone. Results varied with the geometry and conductivity of EEG electrodes/leads. This enhancement confirms the validity of the question whether any observed effects in studies involving EEG recordings during RE-field exposure are directly related to the RE fields generated by the source or indirectly to the RF-field-induced currents due to the presence of conductive EEG leads. (C) 2010 by Radiation Research Society
C1 [Angelone, Leonardo M.] US FDA, Div Phys, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
[Angelone, Leonardo M.] Massachusetts Gen Hosp, Athinoula Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA USA.
[Bit-Babik, Giorgi; Chou, Chung-Kwang] Motorola Inc, Enterprise Mobil Solut, Ft Lauderdale, FL USA.
RP Angelone, LM (reprint author), 10903 New Hampshire Ave,WO62 Rm 1109, Silver Spring, MD 20993 USA.
EM leonardo.angelone@fda.hhs.gov
OI Angelone, Leonardo/0000-0002-1105-021X
FU Mobile Manufacturer Forum; NCRR [P41RR14075]; MIND Institute; Athinoula
A. Martinos Center for Biomedical Imaging
FX This study was supported by the Mobile Manufacturer Forum, the NCRR
(grant P41RR14075), the MIND Institute, and the Athinoula A. Martinos
Center for Biomedical Imaging. Giorgi Bit-Babik and CK. Chou are
employees of Motorola whose research focuses on the safe use of
electromagnetic energy. They contributed their time on this project with
the support of the company. The authors would like to thank Bruce Rosen,
Giorgio Bonmassar, Christos Vasios, Nikos Makris, David Kennedy,
Jonathan Kaiser, George Papadimitriou at the A.Martinos Center for
Biomedical Imaging and Mark Cronin-Golomb and Sergio Fantini at Tufts
University for the help and the useful insights during the completion of
the study. The mention of commercial products, their sources, or their
use in connection with material reported herein is not to be construed
as either an actual or implied endorsement of such products by the
Department of Health and Human Services.
NR 46
TC 8
Z9 8
U1 0
U2 6
PU RADIATION RESEARCH SOC
PI LAWRENCE
PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA
SN 0033-7587
EI 1938-5404
J9 RADIAT RES
JI Radiat. Res.
PD JUL
PY 2010
VL 174
IS 1
BP 91
EP 100
DI 10.1667/RR1933.1
PG 10
WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging
SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology,
Nuclear Medicine & Medical Imaging
GA 626SA
UT WOS:000279986000011
PM 20681803
ER
PT J
AU Taylor, CM
Blum, A
Abbara, S
AF Taylor, Carolyn M.
Blum, Andrew
Abbara, Suhny
TI Patient Preparation and Scanning Techniques
SO RADIOLOGIC CLINICS OF NORTH AMERICA
LA English
DT Article
DE Scanning techniques; Patient preparation; Artifacts
ID TOMOGRAPHY CORONARY-ANGIOGRAPHY; SPIRAL COMPUTED-TOMOGRAPHY;
HEART-RATE-VARIABILITY; CT ANGIOGRAPHY; IMAGE QUALITY;
DIAGNOSTIC-ACCURACY; CARDIAC CT; ARTERY-DISEASE; STENT PATENCY; RISK
AB Cardiac computed tomographic angiography (CCTA) is a unique diagnostic modality that can provide a comprehensive assessment of cardiac anatomy Rapid advances in scanner and software technology have resulted in the ability to noninvasively image the coronary arteries However, careful patient preparation and scanning technique is required to ensure optimal image quality while minimizing radiation dose delivered. Important components of patient preparation include knowledge of the indications and contraindications for CCTA, patient screening, patient premedication, patient positioning, prescan instruction, and electrocardiograph lead placement Scanning technique should be determined on a patient by patient basis and tailored according to age and radiation risk, body mass index and chest circumference, heart rate and variability, presence of stents, and coronary calcification.
C1 [Taylor, Carolyn M.] Univ British Columbia, St Pauls Hosp, Div Cardiol, Vancouver, BC V6Z 1Y6, Canada.
[Blum, Andrew; Abbara, Suhny] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Imaging Sect, Boston, MA 02114 USA.
RP Taylor, CM (reprint author), Univ British Columbia, St Pauls Hosp, Div Cardiol, 1081 Burrard St,Room B344, Vancouver, BC V6Z 1Y6, Canada.
EM cmtaylor@providencehealth.bc.ca
NR 47
TC 7
Z9 7
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 0033-8389
J9 RADIOL CLIN N AM
JI Radiol. Clin. N. Am.
PD JUL
PY 2010
VL 48
IS 4
BP 675
EP +
DI 10.1016/j.rcl.2010.04.011
PG 13
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 649AQ
UT WOS:000281738100003
PM 20705165
ER
PT J
AU Kopans, DB
AF Kopans, Daniel B.
TI The 2009 US Preventive Services Task Force Guidelines Ignore Important
Scientific Evidence and Should Be Revised or Withdrawn
SO RADIOLOGY
LA English
DT Editorial Material
ID BREAST-CANCER MORTALITY; RANDOMIZED CONTROLLED-TRIAL; POSITIVE
PREDICTIVE-VALUE; SCREENING MAMMOGRAPHY; DIFFERENT PERSPECTIVE;
CARCINOMA MORTALITY; AGE 40; WOMEN; RISK; REDUCTION
C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
RP Kopans, DB (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, 15 Parkman St,Suite 219, Boston, MA 02114 USA.
NR 45
TC 18
Z9 18
U1 1
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 JUL
PY 2010
VL 256
IS 1
BP 15
EP 20
DI 10.1148/radiol.10100057
PG 6
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 615BT
UT WOS:000279106900004
PM 20574081
ER
PT J
AU Prakash, P
Kalra, MK
Ackman, JB
Digumarthy, SR
Hsieh, J
Do, S
Shepard, JAO
Gilman, MD
AF Prakash, Priyanka
Kalra, Mannudeep K.
Ackman, Jeanne B.
Digumarthy, Subba R.
Hsieh, Jiang
Do, Synho
Shepard, Jo-Anne O.
Gilman, Matthew D.
TI Diffuse Lung Disease: CT of the Chest with Adaptive Statistical
Iterative Reconstruction Technique
SO RADIOLOGY
LA English
DT Article
ID HIGH-RESOLUTION CT; COMPUTED-TOMOGRAPHY; DIAGNOSTIC-ACCURACY; DOSE
REDUCTION; EXPERIENCE
AB Purpose: To compare visualization of subtle normal and abnormal findings at computed tomography (CT) of the chest for diffuse lung disease with images reconstructed with filtered back projection and adaptive statistical iterative reconstruction (ASIR) techniques.
Materials and Methods: In this HIPAA-compliant, institutional review board-approved study, 24 patients underwent 64-section multi-detector row CT of the chest for evaluation of diffuse lung disease. Scanning parameters included a pitch of 0.984:1 and 120 kVp in thin-section mode, with 2496 views per rotation compared with 984 views acquired for normal mode. The 0.625-mm-thick images were reconstructed with filtered back projection, ASIR, and ASIR high-definition (ASIR-HD) kernels. Two thoracic radiologists independently assessed the filtered back projection, ASIR, and ASIR-HD images for small anatomic details (interlobular septa, centrilobular region, and small bronchi and bronchioles), abnormal findings (reticulation, tiny nodules, altered attenuation, bronchiectasis), image quality (graded by using a six-point scale, where 1 = excellent image quality, and 5 = interpretation impossible), image noise, and artifacts. Data were tabulated for statistical testing.
Results: For visualization of normal and pathologic structures, CT image series reconstructed with ASIR-HD were rated substantially better than those reconstructed with filtered back projection and ASIR (P < .001). ASIR-HD images were superior to filtered back projection images in 15 of 24 (62%) patients for visualization of normal structures and in 24 of 24 (100%) patients for pathologic findings. ASIR-HD was superior to ASIR in three of 24 (12%) images for normal anatomic findings and in seven of 24 (29%) images for pathologic evaluation. None of the images in the three groups were rated as unacceptable for noise (P < .001).
Conclusion: ASIR-HD reconstruction results in superior visualization of subtle and tiny anatomic structures and lesions in diffuse lung disease compared with ASIR and filtered back projection reconstructions.
C1 [Prakash, Priyanka; Kalra, Mannudeep K.; Ackman, Jeanne B.; Digumarthy, Subba R.; Do, Synho; Shepard, Jo-Anne O.; Gilman, Matthew D.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Prakash, Priyanka; Kalra, Mannudeep K.; Ackman, Jeanne B.; Digumarthy, Subba R.; Do, Synho; Shepard, Jo-Anne O.; Gilman, Matthew D.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Hsieh, Jiang] GE Healthcare, Waukesha, WI USA.
RP Kalra, MK (reprint author), Massachusetts Gen Hosp, Dept Radiol, 25 New Chardon St,4th Floor, Boston, MA 02114 USA.
EM mkalra@partners.org
NR 17
TC 103
Z9 109
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 JUL
PY 2010
VL 256
IS 1
BP 261
EP 269
DI 10.1148/radiol.10091487
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 615BT
UT WOS:000279106900031
PM 20574099
ER
PT J
AU Thames, HD
Kuban, D
Levy, LB
Horwitz, EM
Kupelian, P
Martinez, A
Michalski, J
Pisansky, T
Sandler, H
Shipley, W
Zelefsky, M
Zietman, A
AF Thames, Howard D.
Kuban, Deborah
Levy, Larry B.
Horwitz, Eric M.
Kupelian, Patrick
Martinez, Alvaro
Michalski, Jeffrey
Pisansky, Thomas
Sandler, Howard
Shipley, William
Zelefsky, Michael
Zietman, Anthony
TI The role of overall treatment time in the outcome of radiotherapy of
prostate cancer: An analysis of biochemical failure in 4839 men treated
between 1987 and 1995
SO RADIOTHERAPY AND ONCOLOGY
LA English
DT Article
DE Prostate cancer; Radiation; Prostate-specific antigen; Time factor
ID ALPHA/BETA RATIO; RADIATION-THERAPY; TUMOR-CONTROL; LOCAL-CONTROL;
CARCINOMA; FRACTIONATION; HYPOFRACTIONATION; PROTRACTION; ONCOLOGY;
DURATION
AB Purpose: Assess the importance of overall time (OT) and dose for biochemical failure (BF) after external-beam radiotherapy of prostate cancer in a retrospective analysis of a nine-institution database with 4839 patients.
Patients and methods: Relevant baseline factors (T stage, Gleason score, initial PSA) were available for 4338 men. Cox models were used to estimate the effects of dose and OT corrected for baseline factors, treatment year, institution and interactions, and differences in post-treatment PSA-measurement intervals. After exclusion of very short and long intervals, patient numbers were 1445 events/3426 at risk (endpoint all BFs), and 1177 events/3354 at risk (endpoint exclusion of BFs that were likely distant failures). Separate analyses were carried out by risk group for men who received <70 Gy and >= 70 Gy.
Results: Neither dose nor OT was significant when the analysis was restricted to doses <70 Gy, while for patients treated to 70 Gy or higher there were significant influences of both dose and OT on outcome in low- and intermediate-risk patients. These effects were quantified as a relative increase after 5 years followup of 6% in BFs for a 1-week increase in OT, a relative decrease of 15% in BFs for a 6-Gy increase in dose, and a dose equivalent of proliferation of 0.24 Gy/day. As the dose per fraction was nearly constant, the data contain no information on the alpha/beta ratio.
Conclusion: The results show that OT and dose are significant determinants of outcome of radiotherapy in low- and intermediate-risk patients treated to 70 Gy or higher, and suggest that meaningful improvements in outcome may be targeted by modest increases in total dose and decreases in OT. (C) 2010 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 96 (2010) 6-12
C1 [Thames, Howard D.] Univ Texas MD Anderson Canc Ctr, Div Quantitat Sci, Houston, TX 77030 USA.
[Kuban, Deborah; Levy, Larry B.] Univ Texas MD Anderson Canc Ctr, Div Radiat Oncol, Houston, TX 77030 USA.
[Horwitz, Eric M.] Fox Chase Canc Ctr, Dept Radiat Oncol, Philadelphia, PA 19111 USA.
[Kupelian, Patrick] Univ Calif Los Angeles, Dept Radiat Oncol, Los Angeles, CA 90024 USA.
[Martinez, Alvaro] William Beaumont Hosp, Royal Oak, MI 48072 USA.
[Michalski, Jeffrey] Mallinckrodt Inst Radiol, Dept Radiat Oncol, St Louis, MO USA.
[Pisansky, Thomas] Mayo Clin & Mayo Grad Sch Med, Div Radiat Oncol, Rochester, MN USA.
[Sandler, Howard] Univ Michigan, Dept Radiat Oncol, Ann Arbor, MI 48109 USA.
[Shipley, William; Zietman, Anthony] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Zelefsky, Michael] Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10021 USA.
RP Thames, HD (reprint author), Univ Texas MD Anderson Canc Ctr, Div Quantitat Sci, Box 237,1515 Holcombe Blvd, Houston, TX 77030 USA.
EM hdt@wotan.mdacc.tmc.edu
NR 30
TC 45
Z9 45
U1 0
U2 2
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0167-8140
J9 RADIOTHER ONCOL
JI Radiother. Oncol.
PD JUL
PY 2010
VL 96
IS 1
BP 6
EP 12
DI 10.1016/j.radonc.2010.03.020
PG 7
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 630GP
UT WOS:000280261500002
PM 20400191
ER
PT J
AU Cohen, SP
Rathmell, JP
AF Cohen, Steven P.
Rathmell, James P.
TI Tackling the Technical Challenges That Hinder the Success of Facet Joint
Radiofrequency Treatment for Spinal Pain
SO REGIONAL ANESTHESIA AND PAIN MEDICINE
LA English
DT Editorial Material
ID LOW-BACK-PAIN; DENERVATION; EFFICACY; TRIAL; PREVALENCE; NEUROTOMY
C1 [Cohen, Steven P.] Johns Hopkins Sch Med, Dept Anesthesiol & Crit Care, Baltimore, MD USA.
[Cohen, Steven P.] Walter Reed Army Med Ctr, Washington, DC 20307 USA.
[Rathmell, James P.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
[Rathmell, James P.] Harvard Univ, Sch Med, Boston, MA USA.
RP Cohen, SP (reprint author), 550 N Broadway,Suite 301, Baltimore, MD 21029 USA.
EM scohen40@jhmi.edu
NR 21
TC 3
Z9 3
U1 0
U2 2
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 JUL-AUG
PY 2010
VL 35
IS 4
BP 327
EP 328
DI 10.1097/AAP.0b013e3181e82d66
PG 2
WC Anesthesiology
SC Anesthesiology
GA 622EH
UT WOS:000279643100001
PM 20588147
ER
PT J
AU Wilcox, SR
Bittner, E
George, E
Buckley, VF
Schmidt, UH
AF Wilcox, Susan R.
Bittner, Edward
George, Edward
Buckley, Valerie Farias
Schmidt, Ulrich H.
TI Improvement in Emergency Airway Equipment Transport
SO RESPIRATORY CARE
LA English
DT Article
DE airway equipment; transport; laryngoscope bag; nosocomial infection;
fomite; infection control
ID RESISTANT STAPHYLOCOCCUS-AUREUS; ENVIRONMENTAL CONTAMINATION; TRACHEAL
INTUBATION; INTENSIVE-CARE; INFECTION; STETHOSCOPE; ENTEROCOCCI; UNIT
AB BACKGROUND: Airway management out of the operating room in many major institutions is often performed by teams, requiring airway providers to carry their own materials at all times. The bag containing airway equipment must be light enough to be carried easily, while containing sufficient equipment to manage airways in various settings. Additionally, transport of the bag throughout the hospital raises concern about transmission of infection. We hypothesized that a new system of multiple, smaller bags would decrease weight, facilitate prompt location of equipment, and reduce the risk of bags acting as fomites. METHODS: The service purchased small, nylon laryngoscope bags with dividers to keep equipment organized. The contents of the original bag and a new replacement bag were cataloged and both bags were weighed. Fourteen clinicians working on emergency airway consults at the time of the study were timed as they searched the bags for predetermined equipment with 2 scenarios and intubated a mannequin. The surfaces of the bags were swabbed for culture. RESULTS: Clinicians were significantly faster to locate equipment with the new compared to the original bag, with a difference of 39 s (P < .001, 95% CI 19-58 s) in the first scenario, and 22 s (P < .001, 95% CI 13-32 s) in the second. The cultures from the original bag demonstrated coagulase-negative Staphylococcus, enterococcus, Bacillus species, alpha-hemolytic Streptococcus, non-hemolytic Streptococcus, and a Staphylococcus species of a second type. The culture of the new bag after clinical use but before cleaning grew rare Aspergillosis species. The culture of the new bag after undergoing proper cleaning demonstrated no growth. CONCLUSIONS: Exchanging a large canvas bag for several smaller nylon bags has improved the transport of emergency airway equipment, with benefits in carrying the bag, locating equipment, and reducing the transport of pathogens throughout the hospital.
C1 [Wilcox, Susan R.; Bittner, Edward; George, Edward; Buckley, Valerie Farias; Schmidt, Ulrich H.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA.
RP Wilcox, SR (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA.
EM swilcox1@partners.org
NR 16
TC 3
Z9 3
U1 0
U2 0
PU DAEDALUS ENTERPRISES INC
PI IRVING
PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA
SN 0020-1324
J9 RESP CARE
JI Respir. Care
PD JUL
PY 2010
VL 55
IS 7
BP 852
EP 857
PG 6
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 627KE
UT WOS:000280037300003
PM 20587096
ER
PT J
AU Young, AS
Niv, N
Cohen, AN
Kessler, C
McNagny, K
AF Young, Alexander S.
Niv, Noosha
Cohen, Amy N.
Kessler, Christopher
McNagny, Kirk
TI The Appropriateness of Routine Medication Treatment for Schizophrenia
SO SCHIZOPHRENIA BULLETIN
LA English
DT Article
DE antipsychotics; community mental health; drug side effects; quality
measurement; health service research; quality of care; weight management
ID INDUCED WEIGHT-GAIN; RESEARCH-TEAM PORT; ANTIPSYCHOTIC MEDICATIONS;
TREATMENT RECOMMENDATIONS; ATYPICAL ANTIPSYCHOTICS; TARDIVE-DYSKINESIA;
QUALITY-ASSURANCE; CONTROLLED-TRIAL; MENTAL-HEALTH; RATING-SCALE
AB Objective: Although national guidelines specify appropriate strategies for the treatment of schizophrenia, this disorder presents challenges to clinicians and health-care organizations. To improve care, it is useful to understand how often patients receive appropriate treatment. Most research evaluating treatment was performed when first-generation antipsychotic medications were the modal treatment. Given that most prescriptions are now for second-generation medications, this study describes current clinical problems and the appropriateness of treatment in routine practice. Method: Between 2002 and 2004, a random sample of patients (n = 398) were interviewed at baseline and 1 year at 3 Department of Veterans Affairs mental health clinics. Symptoms and side effects were assessed. Analyses examined whether prescribing were consistent with guidelines in patients with significant psychosis, depression, parkinsonism, akathisia, tardive dyskinesia, or elevated weight. Results: Few patients met criteria for depression, parkinsonism, or akathisia. A total of 44% of patients had significant psychosis, 11% had tardive dyskinesia, and 46% were overweight. Medication was appropriate in 27% of patients with psychosis, 25% of patients with tardive dyskinesia, and 2% of patients with elevated weight. Management of elevated weight improved modestly over time. Treatment was more likely to improve for patients whose psychiatrists had more than 12 patients with schizophrenia in their caseload. Conclusion: Compared with the 1990s, outpatients are more likely to have significant psychosis. The rate of appropriate treatment of psychosis is unchanged. Weight gain has become a prevalent side effect, yet treatment is rarely changed in response to weight. There is a need for interventions that improve management of psychosis and weight.
C1 [Young, Alexander S.; Niv, Noosha; Cohen, Amy N.] Desert Pacific Mental Illness Res Educ & Clin Ctr, Dept Vet Affairs, Los Angeles, CA USA.
[Young, Alexander S.; Niv, Noosha; Kessler, Christopher] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90073 USA.
[Kessler, Christopher] Greater Los Angeles VA Healthcare Ctr, Los Angeles, CA USA.
[McNagny, Kirk] Long Beach Vet Affairs Healthcare, Long Beach, CA USA.
RP Young, AS (reprint author), W Los Angeles Vet Affairs Healthcare Ctr, 11301 Wilshire Blvd 210A, Los Angeles, CA 90073 USA.
EM ayoung@ucla.edu
RI Young, Alexander/A-1523-2009
OI Young, Alexander/0000-0002-9367-9213
FU Department of Veterans Affairs, Veterans Health Administration through
the Office of Research and Development Health Services Research and
Development Service [RCD 00-033, CPI 99-383, MNT 03-213]; Desert Pacific
Mental Illness Research, Education and Clinical Center, Los Angeles, CA;
National Institute of Mental Health UCLA-RAND Center for Research on
Quality in Managed Care, Los Angeles, CA [MH 068639]
FX Department of Veterans Affairs, Veterans Health Administration through
the Office of Research and Development Health Services Research and
Development Service (RCD 00-033, CPI 99-383, MNT 03-213), and the Desert
Pacific Mental Illness Research, Education and Clinical Center, Los
Angeles, CA; and by the National Institute of Mental Health UCLA-RAND
Center for Research on Quality in Managed Care, Los Angeles, CA (MH
068639).
NR 52
TC 10
Z9 10
U1 1
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0586-7614
J9 SCHIZOPHRENIA BULL
JI Schizophr. Bull.
PD JUL
PY 2010
VL 36
IS 4
BP 732
EP 739
DI 10.1093/schbul/sbn138
PG 8
WC Psychiatry
SC Psychiatry
GA 620DO
UT WOS:000279479400011
PM 18997159
ER
PT J
AU Fisher, M
Holland, C
Subramaniam, K
Vinogradov, S
AF Fisher, Melissa
Holland, Christine
Subramaniam, Karuna
Vinogradov, Sophia
TI Neuroplasticity-Based Cognitive Training in Schizophrenia: An Interim
Report on the Effects 6 Months Later
SO SCHIZOPHRENIA BULLETIN
LA English
DT Article
DE schizophrenia; cognitive remediation; neuroplasticity; durability
ID RANDOMIZED CONTROLLED-TRIAL; QUALITY-OF-LIFE; VOCATIONAL-REHABILITATION;
SUPPORTED EMPLOYMENT; ENHANCEMENT THERAPY; REMEDIATION THERAPY;
PERFORMANCE; MISMATCH; DEFICITS; FMRI
AB Background: New cognitive treatments for schizophrenia are needed that drive persistent gains in cognition and functioning. Using an innovative neuroplasticity-based cognitive training approach, we report our interim findings on the effects on cognition and functional outcome at 6 months after treatment. Methods: Thirty-two clinically stable schizophrenia subjects were randomly assigned to either targeted cognitive training (TCT, N = 22) or a computer games (CGs) control condition (N = 10). Twelve TCT subjects completed 50 hours of auditory based training; 10 TCT subjects completed an additional 50 hours of training targeting visual and cognitive control processes. Subjects were assessed on neurocognition and functional outcome after training and at 6-month follow-up. Results: Both TCT subject groups showed significant durable gains at 6 months on measures of verbal learning/memory and cognitive control. Only TCT subjects who completed 100 hours of training showed durable gains on processing speed and global cognition, with nonsignificant improvement in functional outcome. Improved cognition was significantly associated with improved functional outcome at 6 months for TCT subjects. Conclusions: A total of 50 hours of neuroplasticity-based computerized cognitive training appears sufficient to drive improvements in verbal learning/memory and cognitive control that endure 6 months beyond the intervention, but a higher "dose" and more "broad-spectrum" training may be necessary to drive enduring gains in processing speed and global cognition. Training-induced cognitive improvement is related to enhanced functioning at 6 months. These data suggest that (1) higher and "broader" doses of cognitive training may confer the most benefits for schizophrenia patients; (2) the posttraining period opens a critical window for aggressive adjunctive psychosocial rehabilitation.
C1 [Fisher, Melissa; Holland, Christine; Subramaniam, Karuna; Vinogradov, Sophia] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA.
[Fisher, Melissa; Holland, Christine; Subramaniam, Karuna; Vinogradov, Sophia] San Francisco VA Med Ctr, San Francisco, CA 94121 USA.
RP Vinogradov, S (reprint author), Univ Calif San Francisco, Dept Psychiat, Mail Code 116C,4150 Clement St, San Francisco, CA 94121 USA.
EM Sophia.Vinogradov@ucsf.edu
FU National Institute of Mental Health [MH068725-01A1]; National Institutes
of Health [1 R42 MH073358-01]; San Francisco Veterans Affairs Medical
Center
FX National Institute of Mental Health (RO1 grant MH068725-01A1); National
Institutes of Health (STTR grant 1 R42 MH073358-01); San Francisco
Veterans Affairs Medical Center. The training software used in this
study and all technical support were provided to us free of charge by
PositScience, Inc. All authors of this study report no conflicts of
interest. The National Institute of Mental Health, National Institutes
of Health, San Francisco Veterans Affairs Medical Center, and
PositScience, Inc. had no further role in study design; collection,
analysis, and interpretation of data; writing of the report; and
decision to submit the article for publication.
NR 46
TC 72
Z9 73
U1 9
U2 33
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0586-7614
J9 SCHIZOPHRENIA BULL
JI Schizophr. Bull.
PD JUL
PY 2010
VL 36
IS 4
BP 869
EP 879
DI 10.1093/schbul/sbn170
PG 11
WC Psychiatry
SC Psychiatry
GA 620DO
UT WOS:000279479400024
PM 19269924
ER
PT J
AU Kempton, MJ
Stahl, D
Williams, SCR
DeLisi, LE
AF Kempton, Matthew J.
Stahl, Daniel
Williams, Steven C. R.
DeLisi, Lynn E.
TI Progressive lateral ventricular enlargement in schizophrenia: A
meta-analysis of longitudinal MRI studies
SO SCHIZOPHRENIA RESEARCH
LA English
DT Article
DE MRI; Schizophrenia; Meta-analysis; Longitudinal; Progressive; Ventricle
ID CHILDHOOD-ONSET SCHIZOPHRENIA; BRAIN VOLUME CHANGES; FIRST-EPISODE
SCHIZOPHRENIA; TWIN PAIRS DISCORDANT; GRAY-MATTER VOLUME; 1ST-EPISODE
SCHIZOPHRENIA; 1ST EPISODE; ANTIPSYCHOTIC TREATMENT; SUBVOXEL
REGISTRATION; MORPHOLOGICAL-CHANGES
AB Background: Lateral ventricular enlargement is one of the most consistent findings in patients with schizophrenia; however whether progressive ventricular dilation occurs during the course of the illness has been controversial. To clarify this we conducted a meta-analysis of longitudinal studies measuring the lateral ventricles in patients with schizophrenia and a control group.
Methods: The MEDLINE database was searched from 1980 to 2009 for longitudinal MRI studies of patients with schizophrenia. We identified 13 studies that measured the lateral ventricles in both patients and controls and these were included in a random effects meta-analysis. The effect of various clinical variables was investigated in a meta-regression analysis.
Results: Patients showed evidence of progressive ventricular enlargement after illness onset greater than that seen in controls (effect size = 0.45, 95%CI 0.19-0.71, p = 0.0006). A sub-analysis of chronic patients with schizophrenia with a mean duration of illness of 7.6 years at baseline scan also showed progressive ventricular enlargement (p = 0.002). The results were robust to inclusion criteria, and no significant effect of age of onset, duration of illness, or age at baseline scan, was found in the meta-regression analysis.
Conclusions: The meta-analysis shows progressive changes in ventricular volume a number of years after illness onset and challenges an exclusively neurodevelopmental model of schizophrenia. (C) 2010 Elsevier B.V. All rights reserved.
C1 [Kempton, Matthew J.; Williams, Steven C. R.] Kings Coll London, Inst Psychiat, Ctr Neuroimaging Sci, London SE5 8AF, England.
[DeLisi, Lynn E.] VA Boston Healthcare Syst, Brockton, MA USA.
[DeLisi, Lynn E.] Harvard Univ, Sch Med, Brockton, MA 02401 USA.
RP Kempton, MJ (reprint author), Kings Coll London, Inst Psychiat, Ctr Neuroimaging Sci, Box PO89,De Crespigny Pk, London SE5 8AF, England.
EM matthew.kempton@iop.kcl.ac.uk
RI Stahl, Daniel/B-9713-2011; Kempton, Matthew/F-8683-2011; Williams,
Steve/D-6979-2011;
OI Stahl, Daniel/0000-0001-7987-6619; Williams, Steve/0000-0003-4299-1941;
Kempton, Matthew/0000-0003-3541-9947
FU National Institute for Health Research (NIHR) Specialist Biomedical
Research Centre for Mental Health; Institute of Psychiatry, King's
College London; Wellcome Trust; EPSRC Medical Centre Initiative
FX The authors acknowledge the financial support from the National
Institute for Health Research (NIHR) Specialist Biomedical Research
Centre for Mental Health award to the South London and Maudsley NHS
Foundation Trust and the Institute of Psychiatry, King's College London.
M J Kempton was also supported by a Wellcome Trust Value in People
Award. S C R Williams and the Centre for Neuroimaging Sciences are
supported by the Wellcome Trust and EPSRC Medical Centre Initiative. The
above funders 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 69
TC 65
Z9 65
U1 8
U2 21
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0920-9964
J9 SCHIZOPHR RES
JI Schizophr. Res.
PD JUL
PY 2010
VL 120
IS 1-3
BP 54
EP 62
DI 10.1016/j.schres.2010.03.036
PG 9
WC Psychiatry
SC Psychiatry
GA 636IO
UT WOS:000280725500008
PM 20537866
ER
PT J
AU Jimenez-Castro, L
Hare, E
Medina, R
Raventos, H
Nicolini, H
Mendoza, R
Ontiveros, A
Jerez, A
Munoz, R
Dassori, A
Escamilla, M
AF Jimenez-Castro, Lorena
Hare, Elizabeth
Medina, Rolando
Raventos, Henriette
Nicolini, Humberto
Mendoza, Ricardo
Ontiveros, Alfonso
Jerez, Alvaro
Munoz, Rodrigo
Dassori, Albana
Escamilla, Michael
TI Substance use disorder comorbidity with schizophrenia in families of
Mexican and Central American Ancestry
SO SCHIZOPHRENIA RESEARCH
LA English
DT Article
DE Alcohol; Drug abuse; Substance misuse; Dual diagnosis; Schizophrenia;
Latino populations
ID NATIONAL EPIDEMIOLOGIC SURVEY; IV PSYCHIATRIC-DISORDERS; SEVERE
MENTAL-ILLNESS; GENERAL-POPULATION; LIFETIME PREVALENCE; UNITED-STATES;
DRUG-ABUSE; PSYCHOTIC DISORDERS; SURVEY REPLICATION; ALCOHOL
AB Objectives: The aims of this study were to estimate the frequency and course of substances use disorders in Latino patients with schizophrenia and to ascertain risk factors associated with substance use disorders in this population.
Method: We studied 518 subjects with schizophrenia recruited for a genetic study from the Southwest United States, Mexico, and Central America (Costa Rica and Guatemala). Subjects were assessed using structured interviews and a best estimate consensus process. Logistic regression, chi(2), t test, Fisher's exact test, and Yates' correction, as appropriate, were performed to assess the sociodemographic variables associated with dual diagnosis. We defined substance use disorder as either alcohol or substance abuse or dependence.
Results: Out of 518 patients with schizophrenia, 121 (23.4%) had substance use disorders. Comorbid substance use disorders were associated with male gender, residence in the United States, immigration of Mexican men to the United States, history of depressive syndrome or episode, and being unemployed. The most frequent substance use disorder was alcohol abuse/dependence, followed by marijuana abuse/dependence, and solvent abuse/dependence.
Conclusion: This study provides data suggesting that depressive episode or syndrome, unemployment, male gender, and immigration of Mexican men to the United States were factors associated with substance use disorder comorbidity in schizophrenia. Binary logistic regression showed that country of residence was associated with substance use disorder in schizophrenic patients. The percentage of subjects with comorbid substance use disorders was higher in the Latinos living in the United States compared with subjects living in Central America and Mexico. (C) 2010 Published by Elsevier B.V.
C1 [Hare, Elizabeth; Escamilla, Michael] Texas Tech Univ, Hlth Sci Ctr, Paul L Foster Sch Med, Neurosci Ctr Excellence, El Paso, TX 79905 USA.
[Jimenez-Castro, Lorena; Hare, Elizabeth; Medina, Rolando; Escamilla, Michael] Texas Tech Univ, Hlth Sci Ctr, Paul L Foster Sch Med, S Texas Psychiat Genet Res Ctr, San Antonio, TX USA.
[Jimenez-Castro, Lorena; Raventos, Henriette] Univ Costa Rica, Ctr Invest Biol Mol & Celular, San Jose, Costa Rica.
[Medina, Rolando; Dassori, Albana] S Texas Vet Hlth Syst, Dept Psychiat, San Antonio, TX USA.
[Nicolini, Humberto] Grp Estudios Med & Familiares Carraci SC, Mexico City, DF, Mexico.
[Mendoza, Ricardo] Univ Calif Los Angeles, Los Angeles Med Ctr, Dept Psychiat & Biobehav Sci, Los Angeles, CA USA.
[Ontiveros, Alfonso] Inst Informac & Invest Salud Mental, Monterrey, Mexico.
[Jerez, Alvaro] Ctr Invest Biomed, Guatemala City, Guatemala.
[Munoz, Rodrigo] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA.
[Escamilla, Michael] Texas Tech Univ, Hlth Sci Ctr, Paul L Foster Sch Med, Dept Psychiat, El Paso, TX 79905 USA.
RP Escamilla, M (reprint author), Texas Tech Univ, Hlth Sci Ctr, Paul L Foster Sch Med, Neurosci Ctr Excellence, 5001 El Paso Dr, El Paso, TX 79905 USA.
EM m.escamilla@ttuhsc.edu
OI Nicolini, Humberto/0000-0003-2494-0067; Raventos,
Henriette/0000-0001-9423-8308; Jerez Magana, Alvaro
Antonio/0000-0002-1208-3769
FU National Institute of Mental Health [MH60881, MH60875, D43 TW06152-01];
National Institute of Drug Abuse; Fogarty Institute
FX This research was supported by the following grants from the National
Institute of Mental Health: MH60881 and MH60875. Dr Jimenez-Castro was
supported by a fellowship of grant D43 TW06152-01 from the National
Institute of Mental Health, the National Institute of Drug Abuse and the
Fogarty Institute. These institutions had no further role in the study
design, in the collection, analysis and interpretation of data, in
writing of the report, and in the decision to submit the paper for
publication.
NR 46
TC 6
Z9 6
U1 0
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0920-9964
EI 1573-2509
J9 SCHIZOPHR RES
JI Schizophr. Res.
PD JUL
PY 2010
VL 120
IS 1-3
BP 87
EP 94
DI 10.1016/j.schres.2010.02.1053
PG 8
WC Psychiatry
SC Psychiatry
GA 636IO
UT WOS:000280725500013
PM 20303714
ER
PT J
AU Wang, Y
Wang, JD
Wu, HR
Zhang, BS
Fang, H
Ma, QM
Liu, H
Chen, DC
Xiu, MH
Hail, CN
Kosten, TR
Zhang, XY
AF Wang, Yu
Wang, Jiang Dong
Wu, Hao Ran
Zhang, Ben Shu
Fang, Hui
Ma, Qi Min
Liu, Hong
Chen, Da Chun
Xiu, Mei Hong
Hail, Colin N.
Kosten, Thomas R.
Zhang, Xiang Yang
TI The Val66Met polymorphism of the brain-derived neurotrophic factor gene
is not associated with risk for schizophrenia and tardive dyskinesia in
Han Chinese population
SO SCHIZOPHRENIA RESEARCH
LA English
DT Letter
ID BDNF VAL66MET
C1 [Wang, Yu; Zhang, Ben Shu; Liu, Hong] Tianjin Med Univ, Gen Hosp, Dept Neurol, Tianjin 300052, Peoples R China.
[Wang, Jiang Dong; Fang, Hui] Hebei Med Univ, Dept Endocrinol 2, Tangshan Gongren Hosp, Tangshan 06300, Peoples R China.
[Wang, Jiang Dong; Fang, Hui] Hebei Med Univ, Dept Endocrinol, Shijiazhuang 050017, Peoples R China.
[Wu, Hao Ran; Ma, Qi Min] Rongjun Hosp Hebei Prov, Baoding 071000, Peoples R China.
[Chen, Da Chun; Xiu, Mei Hong; Zhang, Xiang Yang] Beijing HuiLongGuan Hosp, Ctr Biol Psychiat, Beijing 100096, Peoples R China.
[Hail, Colin N.; Kosten, Thomas R.; Zhang, Xiang Yang] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA.
RP Kosten, TR (reprint author), VA Med Ctr, Res Bldg 110,Room 229,2002 Holcombe Blvd, Houston, TX 77030 USA.
EM kosten@bcm.edu; xyzhang@bcm.edu
NR 11
TC 8
Z9 10
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0920-9964
J9 SCHIZOPHR RES
JI Schizophr. Res.
PD JUL
PY 2010
VL 120
IS 1-3
BP 240
EP 242
DI 10.1016/j.schres.2010.03.020
PG 3
WC Psychiatry
SC Psychiatry
GA 636IO
UT WOS:000280725500038
PM 20395113
ER
PT J
AU Rucker, D
Thadhani, R
Tonelli, M
AF Rucker, Diana
Thadhani, Ravi
Tonelli, Marcello
TI Trace Element Status in Hemodialysis Patients
SO SEMINARS IN DIALYSIS
LA English
DT Review
ID DIALYSIS ENCEPHALOPATHY SYNDROME; SERUM SELENIUM CONCENTRATION;
PLACEBO-CONTROLLED TRIAL; CHRONIC-RENAL-FAILURE; MYOCARDIAL-INFARCTION;
ZINC-DEFICIENCY; OXIDATIVE STRESS; BLOOD-PRESSURE; DOUBLE-BLIND; ARSENIC
CARCINOGENESIS
AB Patients with chronic kidney disease undergoing hemodialysis (HD) are potentially at risk of deficiency and excess of trace elements. HD exposes patients to large volumes of water (> 120 l/week) in the form of dialysate. Although levels of certain ions (such as potassium and calcium) are carefully regulated in dialysate, many others are measured infrequently, if ever. As a result, substances in lower concentrations in the dialysis may be leached from the body. Conversely, toxic trace elements present in water but not in blood may accumulate and cause toxicity. Given that essential trace elements play key roles in multiple biological systems including immunological defense against oxidation and infection, it has been hypothesized that the increased morbidity and mortality seen in HD patients may in part be due to the imbalance of trace elements that has not been recognized. A recent systematic review has shown that compared with healthy controls, HD patients have significantly lower blood levels of zinc, manganese, and selenium, while blood levels of lead are likely to accumulate. Other trace elements, such as mercury and arsenic, are biologically plausible causes of excess mortality in dialysis patients, but available evidence is inconclusive as to whether they consistently accumulate in this population. Whether altered trace element levels are potentially reversible causes of adverse clinical outcomes in dialysis patients remains to be determined. This review highlights key issues related to this hypothesis, with special emphasis on zinc, manganese, selenium, lead, mercury, and arsenic.
C1 [Rucker, Diana; Tonelli, Marcello] Univ Alberta, Dept Med, Edmonton, AB, Canada.
[Thadhani, Ravi] Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA.
[Tonelli, Marcello] Univ Alberta, Dept Publ Hlth Sci, Edmonton, AB, Canada.
RP Tonelli, M (reprint author), 7-129 Clin Sci Bldg,8440-112 St, Edmonton, AB T6G 2G3, Canada.
EM mtonelli@ualberta.ca
RI Tonelli, Marcello/B-3028-2009
NR 132
TC 27
Z9 27
U1 0
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0894-0959
J9 SEMIN DIALYSIS
JI Semin. Dial.
PD JUL-AUG
PY 2010
VL 23
IS 4
BP 389
EP 395
DI 10.1111/j.1525-139X.2010.00746.x
PG 7
WC Urology & Nephrology
SC Urology & Nephrology
GA 635NN
UT WOS:000280662500008
PM 20557491
ER
PT J
AU Bhan, I
Hewison, M
Thadhani, R
AF Bhan, Ishir
Hewison, Martin
Thadhani, Ravi
TI Dietary Vitamin D Intake in Advanced CKD/ESRD
SO SEMINARS IN DIALYSIS
LA English
DT Article
ID CHRONIC KIDNEY-DISEASE; STAGE RENAL-DISEASE; CATHELICIDIN ANTIMICROBIAL
PEPTIDE; HEMODIALYSIS-PATIENTS; D DEFICIENCY; D INSUFFICIENCY;
ERGOCALCIFEROL; PREVALENCE; MORTALITY; 25-HYDROXYVITAMIN-D
AB In healthy individuals, vitamin D produced in the skin or derived from nutritional sources is converted to 25-hydroxyvitamin D (25[OH]D) in the liver, and then 1,25-dihydroxyvitamin D (1,25[OH](2)D) by 1 alpha-hydroxylase in the kidney. Chronic kidney disease (CKD) is accompanied by a progressive decline in the ability to produce 1,25(OH)(2)D; thus, replacement of this hormonal form of vitamin D has been the focus of therapeutic interventions to prevent and treat complications such as hypocalcemia, and secondary hyperparathyroidism. New research suggests that conversion of 25(OH)D to 1,25(OH)(2)D outside of the kidney may have important biological roles beyond those traditionally ascribed to vitamin D. 25(OH)D levels have increasingly been linked to important clinical outcomes in CKD. This article reviews vitamin D metabolism, emerging new roles for vitamin D, and data surrounding the potential importance of nutritional sources of vitamin D in the management of patients with CKD.
C1 [Bhan, Ishir; Thadhani, Ravi] Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA.
[Hewison, Martin] Univ Calif Los Angeles, David Geffen Sch Med, UCLA Orthopaed Hosp, Dept Orthopaed Surg, Los Angeles, CA 90095 USA.
RP Bhan, I (reprint author), 50 Staniford St,Suite 750, Boston, MA 02114 USA.
EM ibhan@partners.org
FU Abbott Laboratories
FX Dr. Thadhani has a research grant from Abbott Laboratories.
NR 32
TC 6
Z9 7
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0894-0959
J9 SEMIN DIALYSIS
JI Semin. Dial.
PD JUL-AUG
PY 2010
VL 23
IS 4
BP 407
EP 410
DI 10.1111/j.1525-139X.2010.00751.x
PG 4
WC Urology & Nephrology
SC Urology & Nephrology
GA 635NN
UT WOS:000280662500011
PM 20701720
ER
PT J
AU Segura-Orti, E
Johansen, KL
AF Segura-Orti, Eva
Johansen, Kirsten L.
TI Exercise in End-Stage Renal Disease
SO SEMINARS IN DIALYSIS
LA English
DT Article
ID QUALITY-OF-LIFE; MAINTENANCE HEMODIALYSIS-PATIENTS; WEIGHT-LOSS;
PHYSICAL FUNCTION; DIALYSIS PATIENTS; AEROBIC CAPACITY;
CONTROLLED-TRIAL; MUSCLE STRENGTH; KIDNEY-DISEASE; HEALTH-STATUS
AB This article will outline the clinical reasoning for exercise counseling in end-stage renal disease (ESRD) patients and give healthcare providers detailed information on the different programs that can be implemented in this population according to patients' specific needs. End-stage renal disease patients often have other health problems that can be improved by participation in regular exercise programs. Research accumulated during the last 30 years on exercise for the ESRD population supports its numerous beneficial effects including those on cardiovascular capacity, sarcopenia, and health-related quality of life. We describe the different types of exercise, aerobic and resistance programs (including their frequency, intensity and progression) that are recommended for the ESRD population, as well as the potential goals of each program. Groups with special needs among the ESRD population are considered, as well as safety, potential adverse events, and adherence to exercise programs. Finally, recommendations for future researches are highlighted.
C1 [Segura-Orti, Eva] Univ CEU Cardenal Herrera, Dept Phys Therapy, Valencia, Spain.
[Johansen, Kirsten L.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Johansen, Kirsten L.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Johansen, Kirsten L.] San Francisco VA Med Ctr, Nephrol Sect, San Francisco, CA USA.
RP Segura-Orti, E (reprint author), Univ CEU Cardenal Herrera, Dept Phys Therapy, Valencia, Spain.
EM eva.segura@gmail.com
FU CEU-Banco Santander; Universidad CEU-Cardenal Herrera
FX E. Segura-Orti is supported by the "5th Edition of research fellowships
CEU-Banco Santander" and by the Universidad CEU-Cardenal Herrera.
NR 52
TC 13
Z9 16
U1 1
U2 9
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0894-0959
J9 SEMIN DIALYSIS
JI Semin. Dial.
PD JUL-AUG
PY 2010
VL 23
IS 4
BP 422
EP 430
DI 10.1111/j.1525-139X.2010.00766.x
PG 9
WC Urology & Nephrology
SC Urology & Nephrology
GA 635NN
UT WOS:000280662500014
PM 20701722
ER
PT J
AU Bussel, JB
Kuter, DJ
AF Bussel, James B.
Kuter, David J.
TI New Thrombopoietic Agents: Introduction
SO SEMINARS IN HEMATOLOGY
LA English
DT Editorial Material
C1 [Bussel, James B.] Weill Cornell Univ, Dept Pediat Hematol, Div Pediat Hematol, New York Presbyterian Hosp, New York, NY USA.
[Kuter, David J.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Bussel, JB (reprint author), Weill Cornell Univ, Dept Pediat Hematol, Div Pediat Hematol, New York Presbyterian Hosp, New York, NY USA.
NR 0
TC 2
Z9 2
U1 0
U2 0
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0037-1963
J9 SEMIN HEMATOL
JI Semin. Hematol.
PD JUL
PY 2010
VL 47
IS 3
BP 211
EP 211
PG 1
WC Hematology
SC Hematology
GA 617BV
UT WOS:000279256700001
PM 20620430
ER
PT J
AU Kuter, DJ
AF Kuter, David J.
TI Biology and Chemistry of Thrombopoietic Agents
SO SEMINARS IN HEMATOLOGY
LA English
DT Article
ID C-MPL LIGAND; RECEPTOR AGONIST; MEGAKARYOCYTE GROWTH; PLATELET
PRODUCTION; IN-VITRO; BINDING; THROMBOCYTOPENIA; ELTROMBOPAG; CYTOKINE;
IDENTIFICATION
AB Endogenous thrombopoietin (eTPO) regulates platelet production by increasing the number, ploidy, and maturation rate of bone marrow megakaryocytes. Early attempts to treat thrombocytopenia by the administration of recombinant TPO were successful but were complicated by the development of antibodies to one of the recombinant proteins. Two new TPO mimetics have recently been approved by the US Food and Drug Administration (FDA) for the treatment of immune thrombocytopenia (ITP). Romiplostim is a peptide TPO mimetic composed of an IgG Fc fragment to which are attached four 14-amino acid TPO peptides that activate the TPO receptor by binding to the extracytoplasmic domain just like eTPO. Romiplostim is administered as a weekly subcutaneous injection. Eltrombopag, a nonpeptide TPO mimetic, is a 442-d drug that binds to a transmembrane site on the TPO receptor and thereby activates it. It is administered daily as an oral tablet. Administration of both romiplostim and eltrombopag to healthy volunteers produced a dose-dependent rise in platelet count beginning on day 5 and peaking at days 12 to 15. Both have been highly effective in increasing the platelet count in patients with ITP and are currently being studied in the treatment of other thrombocytopenic conditions (myelodysplastic syndrome, chemotherapy, liver disease). Semin Hematol 47:243-248. (C) 2010 Elsevier Inc. All rights reserved.
C1 Massachusetts Gen Hosp, Div Hematol, Boston, MA 02114 USA.
RP Kuter, DJ (reprint author), Massachusetts Gen Hosp, Div Hematol, Yawkey 7940,55 Fruit St, Boston, MA 02114 USA.
EM kuter.david@MGH.harvard.edu
FU National Institutes of Health [HL82889, HL072299]
FX Supported in part by Grants No. HL82889 and HL072299 from the National
Institutes of Health.
NR 31
TC 39
Z9 45
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 0037-1963
J9 SEMIN HEMATOL
JI Semin. Hematol.
PD JUL
PY 2010
VL 47
IS 3
BP 243
EP 248
DI 10.1053/j.seminhematol.2010.02.005
PG 6
WC Hematology
SC Hematology
GA 617BV
UT WOS:000279256700006
PM 20620435
ER
PT J
AU Kakarala, K
Richmon, JD
Durand, ML
Borges, LF
Deschler, DG
AF Kakarala, Kiran
Richmon, Jeremy D.
Durand, Marlene L.
Borges, Lawrence F.
Deschler, Daniel G.
TI Reconstruction of a Nasopharyngeal Defect from Cervical Spine
Osteoradionecrosis
SO SKULL BASE-AN INTERDISCIPLINARY APPROACH
LA English
DT Article
DE Head and neck; reconstruction; microvascular; nasopharynx;
osteoradionecrosis; cervical spine
ID MANAGEMENT
AB Osteoradionecrosis of the cervical spine is a rare complication of radiation treatment of head and neck tumors that requires a multidisciplinary approach to management and reconstruction. The case of a 57-year-old man with osteoradionecrosis of the cervical spine secondary to radiation for metastatic hepatocellular carcinoma is presented. Operative debridement of the necrotic bone was performed and the pharyngeal soft soft tissue defect was reconstructed with a radial forearm free flap. The management and reconstruction options for osteoradionecrosis of the cervical spine are discussed.
C1 [Deschler, Daniel G.] Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Div Head & Neck Surg,Med Sch, Boston, MA 02114 USA.
[Durand, Marlene L.] Harvard Univ, Sch Med, Dept Med, Div Infect Dis, Boston, MA 02114 USA.
[Borges, Lawrence F.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA.
[Kakarala, Kiran; Deschler, Daniel G.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA.
[Richmon, Jeremy D.] Dept Otolaryngol Head & Neck Surg, Div Head & Neck Surg, Baltimore, MD USA.
RP Deschler, DG (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Div Head & Neck Surg,Med Sch, 243 Charles St, Boston, MA 02114 USA.
EM daniel_deschler@meei.harvard.edu
OI Kakarala, Kiran/0000-0002-1003-8024
NR 7
TC 1
Z9 1
U1 0
U2 1
PU THIEME MEDICAL PUBL INC
PI NEW YORK
PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA
SN 1531-5010
J9 SKULL BASE-INTERD AP
JI Skull Base-Interdiscip. Appr.
PD JUL
PY 2010
VL 20
IS 4
BP 289
EP 292
DI 10.1055/s-0030-1249244
PG 4
WC Clinical Neurology; Otorhinolaryngology; Surgery
SC Neurosciences & Neurology; Otorhinolaryngology; Surgery
GA 621JW
UT WOS:000279573800011
PM 21311624
ER
PT J
AU Frisbie, JH
AF Frisbie, J. H.
TI Anemia and hypoalbuminemia of chronic spinal cord injury: prevalence and
prognostic significance
SO SPINAL CORD
LA English
DT Article
DE anemia; hypoalbuminemi; hypoalbuminemia; spinal cord injury
ID MORTALITY; ALBUMIN; DISEASE
AB Study design: The study was a retrospective analysis.
Objective: The objective of the study was to survey a chronic spinal cord injury (SCI) population for the prevalence and prognostic significance of anemia (AN) and hypoalbuminemia (HA).
Setting: The study was conducted at VA Boston Healthcare System, USA.
Methods: A review of records of 322 SCI subjects (318 males) scheduled for annual examination was carried out for the period from 1998 to 2007. The number of follow-up years with AN (hematocrit <40%) or severe anemia (SAN) (hematocrit <30%) or HA (serum albumin <3 g%) was recorded for all subjects, divided between survivor and deceased subjects.
Results: A total of 239 subjects survived to an average age of 60 and 30 years of paralysis and 83 subjects died at an average age of 70 and 27 years of paralysis (P<0.01 and P<0.06, respectively). The level and grade of paralysis were similar in these groups. The average prevalence rates of AN, SAN and HA were 34, 6 and 6% of survey years in the survivor group and 83, 18 and 22% in the deceased group; the respective ratios were 2.4, 3.0 and 3.7 (P<0.001). The fractions of survey years that were positive for SAN and/or HA among causes of death were sepsis, 42%; cancer, 33%; pulmonary failure 30%; cardiovascular disease, 25%; and undetermined causes, 9%. The mortality rate for the 95 subjects with a recurrence of SAN or HA was 40% within 3 years.
Conclusion: The prevalence of AN, SAN and HA among chronic SCI subjects is high; repeated SAN and HA often precede death, particularly due to sepsis. Spinal Cord (2010) 48, 566-569; doi:10.1038/sc.2009.163; published online 1 December 2009
C1 [Frisbie, J. H.] Harvard Univ, Sch Med, Dept Med, Res Serv,VA Boston Healthcare Syst, Boston, MA USA.
RP Frisbie, JH (reprint author), 832 Woodland Dr, Mahtomedi, MN 55115 USA.
EM jfrisbie@comcast.net
FU New England Chapter of the Paralyzed Veterans of America
FX This paper is the result of a study supported with resources and the use
of facilities at the VA Boston Healthcare System, Boston, MA, USA.
Funding was provided by the New England Chapter of the Paralyzed
Veterans of America. Data collection was carried out by Elizabeth
Tammaro.
NR 13
TC 5
Z9 6
U1 2
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 JUL
PY 2010
VL 48
IS 7
BP 566
EP 569
DI 10.1038/sc.2009.163
PG 4
WC Clinical Neurology; Rehabilitation
SC Neurosciences & Neurology; Rehabilitation
GA 618VM
UT WOS:000279384000010
PM 19949419
ER
PT J
AU Parmar, K
Kim, JM
Sykes, SM
Shimamura, A
Stuckert, P
Zhu, KY
Hamilton, A
Deloach, MK
Kutok, JL
Akashi, K
Gilliland, DG
D'andrea, A
AF Parmar, Kalindi
Kim, Jungmin
Sykes, Stephen M.
Shimamura, Akiko
Stuckert, Patricia
Zhu, Kaya
Hamilton, Abigail
Deloach, Mary Kathryn
Kutok, Jeffery L.
Akashi, Koichi
Gilliland, D. Gary
D'andrea, Alan
TI Hematopoietic Stem Cell Defects in Mice with Deficiency of Fancd2 or
Usp1
SO STEM CELLS
LA English
DT Article
DE Hematopoiesis and Stem Cells; Fancd2 mice; Usp1 mice
ID FANCONI-ANEMIA PATHWAY; CROSS-LINK REPAIR; DNA-REPAIR; TARGETED
DISRUPTION; MYELOID PROGENITOR; OXIDATIVE STRESS; SELF-RENEWAL;
BONE-MARROW; MOUSE MODEL; IFN-GAMMA
AB Fanconi anemia (FA) is a human genetic disease characterized by a DNA repair defect and progressive bone marrow failure. Central events in the FA pathway are the monoubiquitination of the Fancd2 protein and the removal of ubiquitin by the deubiquitinating enzyme, Usp1. Here, we have investigated the role of Fancd2 and Usp1 in the maintenance and function of murine hematopoietic stem cells (HSCs). Bone marrow from Fancd2-/- mice and Usp1-/- mice exhibited marked hematopoietic defects. A decreased frequency of the HSC populations including Lin-Sca-1+Kit+ cells and cells enriched for dormant HSCs expressing signaling lymphocyte activation molecule (SLAM) markers, was observed in the bone marrow of Fancd2-deficient mice. In addition, bone marrow from Fancd2-/- mice contained significantly reduced frequencies of late-developing cobblestone area-forming cell activity in vitro compared to the bone marrow from wild-type mice. Furthermore, Fancd2-deficient and Usp1-deficient bone marrow had defective long-term in vivo repopulating ability. Collectively, our data reveal novel functions of Fancd2 and Usp1 in maintaining the bone marrow HSC compartment and suggest that FA pathway disruption may account for bone marrow failure in FA patients. STEM CELLS 2010:28:1186-1195
C1 [D'andrea, Alan] Harvard Univ, Div Genom Stabil & DNA Repair, Dept Radiat Oncol, Dana Farber Canc Inst,Sch Med, Boston, MA 02115 USA.
[Akashi, Koichi] Dana Farber Canc Inst, Dept Immunol, Boston, MA 02115 USA.
[Sykes, Stephen M.; Gilliland, D. Gary] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Kutok, Jeffery L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Shimamura, Akiko] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA.
RP D'andrea, A (reprint author), Harvard Univ, Div Genom Stabil & DNA Repair, Dept Radiat Oncol, Dana Farber Canc Inst,Sch Med, 44 Binney St, Boston, MA 02115 USA.
EM alan_dandrea@dfci.harvard.edu
FU NIH [RO1DK43889, RO1HL52725, U19A1067751]
FX We are thankful to Mark Umphrey II, Dmitry Mirzon, and members of the
DFCI flow cytometry facility for technical assistance. We thank Lisa
Moreau for cytogenetic analyses. We thank Drs. Peter Mauch and Julian
Down for valuable advice. This study was supported by NIH grants
(RO1DK43889. RO1HL52725, U19A1067751) to A.D.D.
NR 54
TC 47
Z9 49
U1 0
U2 6
PU ALPHAMED PRESS
PI DURHAM
PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA
SN 1066-5099
J9 STEM CELLS
JI Stem Cells
PD JUL
PY 2010
VL 28
IS 7
BP 1186
EP 1195
DI 10.1002/stem.437
PG 10
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology;
Oncology; Cell Biology; Hematology
SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology
GA 636OF
UT WOS:000280746400008
PM 20506303
ER
PT J
AU Larauche, M
Gourcerol, G
Million, M
Adelson, DW
Tache, Y
AF Larauche, Muriel
Gourcerol, Guillaume
Million, Mulugeta
Adelson, David W.
Tache, Yvette
TI Repeated psychological stress-induced alterations of visceral
sensitivity and colonic motor functions in mice: Influence of surgery
and postoperative single housing on visceromotor responses
SO STRESS-THE INTERNATIONAL JOURNAL ON THE BIOLOGY OF STRESS
LA English
DT Article
DE Chronic water avoidance stress; colonic motor function; defecation;
irritable bowel syndrome; social isolation; visceral pain
ID CORTICOTROPIN-RELEASING-FACTOR; IRRITABLE-BOWEL-SYNDROME;
WATER-AVOIDANCE STRESS; OPIOID-RECEPTOR AGONISTS; ISOLATED MOUSE COLON;
NERVE GROWTH-FACTOR; COLORECTAL DISTENSION; PROTEASE ACTIVITY;
NEW-MODEL; PAIN
AB Visceral pain modulation by chronic stress in mice has been little studied. Electromyography (EMG) recording of abdominal muscle contractions, as a proxy to the visceromotor response (VMR), requires electrode implantation and post-surgical single housing (SH) which could affect the VMR to stress. To test this hypothesis, male mice had electrode implantation surgery ( S) plus SH, or no surgery and were group housed (NS-GH) or single housed (NS-SH) and exposed to either water avoidance stress ( WAS, 1 h/day) or left undisturbed in their home cages for 10 days. The VMR to phasic ascending colorectal distension (CRD) was assessed before ( basal) and 24 h after 10 days of WAS or no stress using a surgery-free method of intraluminal colonic pressure (ICP) recording (solid-state manometry). WAS heightened significantly the VMR to CRD at 30, 45, and 60 mmHg in S-SH vs. NS-GH, but not compared to NS-SH conscious mice. Compared to basal CRD, WAS increased VMR at 60 mmHg in the S-SH group and decreased it at 30-60 mmHg in NS-GH mice, while having no effect in NS-SH mice. The average defecation during the hour of repeated WAS over 10 days was 1.9 and 2.4 fold greater in S-SH vs. NS-GH and NS-SH mice, respectively. These data indicate that the combination of S-SH required for VMR monitoring with EMG is an important component of repeated WAS-induced post-stress visceral hypersensitivity and defecation in mice.
C1 [Larauche, Muriel; Gourcerol, Guillaume; Million, Mulugeta; Adelson, David W.; Tache, Yvette] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Digest Dis, Los Angeles, CA 90073 USA.
[Larauche, Muriel; Gourcerol, Guillaume; Million, Mulugeta; Adelson, David W.; Tache, Yvette] CURE Digest Dis Res Ctr, Los Angeles, CA 90073 USA.
[Larauche, Muriel; Gourcerol, Guillaume; Million, Mulugeta; Adelson, David W.; Tache, Yvette] Ctr Neurobiol Stress, Los Angeles, CA 90073 USA.
[Larauche, Muriel; Gourcerol, Guillaume; Million, Mulugeta; Adelson, David W.; Tache, Yvette] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA.
RP Larauche, M (reprint author), VA Hlth Care Syst, UCLA Ctr Neurobiol Stress, CURE Bldg 115,Rm 111,11301 Wilshire Blvd, Los Angeles, CA 90073 USA.
EM mlarauche@mednet.ucla.edu
OI Larauche, Muriel/0000-0003-3320-3675; Adelson, David/0000-0002-4623-6030
FU VA Career Scientist Award; NIHDDK [R01 DK-57238, DK-33061, P50 DK-64539,
DK AM 41301, DK-78676, T32 DK07180-33]; French Society of
Gastroenterology
FX The authors would like to thank Ms Chrysanthy Ha, Dr Agata Mulak, and Dr
Yong Sung Kim for their technical help. The research was supported by a
VA Career Scientist Award (YT), NIHDDK grants R01 DK-57238 (YT),
DK-33061 (YT), P50 DK-64539 (YT), DK AM 41301 (Animal Model Core, YT,
MM), DK-78676 (MM), T32 DK07180-33 (ML) and the French Society of
Gastroenterology (GG).
NR 57
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U2 2
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1025-3890
J9 STRESS
JI Stress
PD JUL
PY 2010
VL 13
IS 4
BP 344
EP 355
DI 10.3109/10253891003664166
PG 12
WC Behavioral Sciences; Endocrinology & Metabolism; Neurosciences
SC Behavioral Sciences; Endocrinology & Metabolism; Neurosciences &
Neurology
GA 628TW
UT WOS:000280146300007
ER
PT J
AU Saver, JL
Smith, EE
Fonarow, GC
Reeves, MJ
Zhao, X
Olson, DM
Schwamm, LH
AF Saver, Jeffrey L.
Smith, Eric E.
Fonarow, Gregg C.
Reeves, Mathew J.
Zhao, Xin
Olson, DaiWai M.
Schwamm, Lee H.
CA GWTG-Stroke Steering Comm Investig
TI The "Golden Hour" and Acute Brain Ischemia Presenting Features and Lytic
Therapy in > 30 000 Patients Arriving Within 60 Minutes of Stroke Onset
SO STROKE
LA English
DT Article
DE acute care; acute therapy; acute stroke; emergency medical services;
emergency medicine; stroke care; stroke delivery; therapy; thrombolysis;
thrombolytic therapy
ID TISSUE-PLASMINOGEN ACTIVATOR; CARE; THROMBOLYSIS; ALTEPLASE; TIME;
RECOMMENDATIONS; PROGRAM; SYSTEMS; ATTACK; STATES
AB Background and Purpose-The benefit of intravenous thrombolytic therapy in acute brain ischemia is strongly time dependent.
Methods-The Get With the Guidelines-Stroke database was analyzed to characterize ischemic stroke patients arriving at hospital Emergency Departments within 60 minutes of the last known well time from April 1, 2003, to December 30, 2007.
Results-During the 4.75-year study period, among 253 148 ischemic stroke patients arriving directly by ambulance or private vehicle at 905 hospital Emergency Departments, 106 924 (42.2%) had documented, exact last known well times. Onset to door time was <= 60 minutes in 30 220 (28.3%), 61 to 180 minutes in 33 858 (31.7%), and >180 minutes in 42 846 (40.1%). Features most strongly distinguishing the patients arriving at <= 60, 61 to 180, and >180 minutes were greater stroke severity (median National Institutes of Health Stroke Scale score, 8.0 vs 6.0 vs 4.0, P<0.0001) and more frequent arrival by ambulance (79.0%. vs 72.2% vs 55.0%, P<0.0001). Compared with patients arriving at 61 to 180 minute, "golden hour" patients received intravenous thrombolytic therapy more frequently (27.1% vs 12.9%; odds ratio=2.51; 95% CI, 2.41-2.61; P<0.0001), but door-to-needle time was longer (mean, 90.6 vs 76.7 minutes, P<0.0001). A door-to-needle time of <= 60 minutes was achieved in 18.3% of golden hour patients.
Conclusions-At Get With the Guidelines-Stroke hospital Emergency Departments, more than one quarter of patients with documented onset time and at least one eighth of all ischemic stroke patients arrived within 1 hour of onset, where they received thrombolytic therapy more frequently but more slowly than late arrivers. These findings support public health initiates to increase early presentation and shorten door-to-needle times in patients arriving within the golden hour. (Stroke. 2010;41:1431-1439.)
C1 [Saver, Jeffrey L.] Univ Calif Los Angeles, Stroke Ctr, Dept Neurol, Los Angeles, CA 90095 USA.
[Smith, Eric E.] Univ Calgary, Hotchkiss Brain Inst, Dept Clin Neurosci, Calgary, AB, Canada.
[Fonarow, Gregg C.] Univ Calif Los Angeles, Div Cardiol, Los Angeles, CA 90095 USA.
[Reeves, Mathew J.] Michigan State Univ, Dept Epidemiol, E Lansing, MI 48824 USA.
[Zhao, Xin; Olson, DaiWai M.] Duke Univ, Clin Res Ctr, Durham, NC USA.
[Schwamm, Lee H.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
RP Saver, JL (reprint author), Univ Calif Los Angeles, Stroke Ctr, Dept Neurol, 710 Westwood Plaza, Los Angeles, CA 90095 USA.
EM jsaver@ucla.edu
RI Smith, Eric/C-5443-2012;
OI Smith, Eric/0000-0003-3956-1668; Schwamm, Lee/0000-0003-0592-9145;
Saver, Jeffrey/0000-0001-9141-2251
FU American Heart Association; American Stroke Association; Pfizer, Inc,
New York, NY; Merck-Schering Plough; American Heart Association PRT
Outcomes Research Center; NIH-NINDS [P50 NS044378, U01 NS 44364];
Boehringer Ingelheim; NIH [NINDS R01 NS062028]; Canadian Stroke Network;
Hotchkiss Brain Institute; Canadian Institutes for Health Research; NIH;
Michigan Stroke Registry
FX GWTG-Stroke is funded by the American Heart Association and the American
Stroke Association. The program is also supported in part by
unrestricted educational grants to the American Heart Association by
Pfizer, Inc, New York, NY, and the Merck-Schering Plough Partnership
(North Wales, Pa), who did not participate in the design, analysis,
manuscript preparation, or approval. J. L. S. was supported for this
work by an American Heart Association PRT Outcomes Research Center Award
and by NIH-NINDS Awards P50 NS044378 and U01 NS 44364.; Dr Saver serves
as a member of the GWTG Science Subcommittee and as a scientific
consultant regarding trial design and conduct to CoAxia, Concentric
Medical, Talecris, and Ev3 (all modest); received lecture honoraria from
Ferrer and Boehringer Ingelheim (modest); was an unpaid investigator in
a multicenter prevention trial sponsored by Boehringer Ingelheim; has
declined consulting/ honoraria monies from Genentech since 2002; and is
an employee of the University of California, which holds a patent on
retriever devices for stroke. Dr Smith receives research support from
the NIH (NINDS R01 NS062028), the Canadian Stroke Network, the Hotchkiss
Brain Institute, and Canadian Institutes for Health Research and
receives salary support from the Canadian Institutes for Health
Research. Dr Fonarow receives research support from the NIH
(significant); serves as a consultant to Pfizer, Merck, Schering Plough,
Bristol Myers Squibb, and Sanofi-Aventis (all modest); receives speaker
honoraria from Pfizer, Merck, Schering Plough, Bristol Myers Squibb, and
Sanofi-Aventis (all significant); and is an employee of the University
of California, which holds a patent on retriever devices for stroke. Dr
Reeves receives salary support from the Michigan Stroke Registry. Dr
Zhao is a member of the Duke Clinical Research Institute, which serves
as the American Heart Association GWTG data coordinating center. Dr
Olson is a member of the Duke Clinical Research Institute, which serves
as the American Heart Association GWTG data coordinating center. Dr
Schwamm serves as a consultant to the Research Triangle Institute,
CryoCath, and the Massachusetts Department of Public Health.
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PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
EI 1524-4628
J9 STROKE
JI Stroke
PD JUL
PY 2010
VL 41
IS 7
BP 1431
EP 1439
DI 10.1161/STROKEAHA.110.583815
PG 9
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 617HS
UT WOS:000279272200023
PM 20522809
ER
PT J
AU Ovbiagele, B
Schwamm, LH
Smith, EE
Hernandez, AF
Olson, DM
Pan, WQ
Fonarow, GC
Saver, JL
AF Ovbiagele, Bruce
Schwamm, Lee H.
Smith, Eric E.
Hernandez, Adrian F.
Olson, DaiWai M.
Pan, Wenqin
Fonarow, Gregg C.
Saver, Jeffrey L.
TI Recent Nationwide Trends in Discharge Statin Treatment of Hospitalized
Patients With Stroke
SO STROKE
LA English
DT Article
DE clinical trials; GWTG; health services; practice patterns; prevention;
statins; stroke; transient ischemic attack; utilization
ID TRANSIENT ISCHEMIC ATTACK; QUALITY-OF-CARE; SEX-DIFFERENCES; GUIDELINES
PROGRAM; UNITED-STATES; REGISTRY; PREVENTION; DISEASE; MANAGEMENT;
INITIATION
AB Background and Purpose-The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial showed statins reduce vascular risk among patients with atherosclerotic stroke or transient ischemic attack. In this study, we assessed recent nationwide trends in discharge statin treatment after acute stroke and the influence of SPARCL on clinical practice.
Methods-Using data from eligible patients with stroke and transient ischemic attack admitted to Get With The Guidelines-Stroke (GWTG-Stroke)-participating hospitals between January 1, 2005, and December 31, 2007, we assessed discharge statin use over time and in relation to dissemination of the SPARCL results.
Results-Among 173 284 patients with ischemic stroke and transient ischemic attack, overall discharge statin treatment was 83.5%. Discharge statin prescription climbed steadily but modestly over the 2-year study period from 75.7% to 84.8% (P<0.001) with a nonsignificant increase during SPARCL reporting but a return to prior levels thereafter. Factors associated with lower discharge statin use in patients without contraindications included female sex and South region.
Conclusions-Discharge statin prescription among hospitalized patients with stroke increased over time, but 1 in 5 patients still leaves the hospital without treatment. Primary drivers of increased use were secular trends and individual/hospital site characteristics. (Stroke. 2010; 41: 1508-1513.)
C1 [Ovbiagele, Bruce; Saver, Jeffrey L.] Ronald Reagan UCLA Med Ctr, Stroke Ctr, Los Angeles, CA USA.
[Ovbiagele, Bruce; Saver, Jeffrey L.] Ronald Reagan UCLA Med Ctr, Dept Neurol, Los Angeles, CA USA.
[Schwamm, Lee H.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Schwamm, Lee H.] Massachusetts Gen Hosp, Stroke Serv, Boston, MA 02114 USA.
[Smith, Eric E.] Univ Calgary, Hotchkiss Brain Inst, Dept Clin Neurosci, Calgary Stroke Program, Calgary, AB, Canada.
[Hernandez, Adrian F.; Olson, DaiWai M.; Pan, Wenqin] Duke Clin Res Inst, Durham, NC USA.
[Fonarow, Gregg C.] Ronald Reagan UCLA Med Ctr, Dept Med, Los Angeles, CA USA.
[Fonarow, Gregg C.] Ronald Reagan UCLA Med Ctr, Div Cardiol, Los Angeles, CA USA.
RP Ovbiagele, B (reprint author), Univ Calif Los Angeles, Stroke Ctr, 710 Westwood Plaza, Los Angeles, CA 90095 USA.
EM Ovibes@mednet.ucla.edu
RI Smith, Eric/C-5443-2012; Hernandez, Adrian F./A-7818-2016;
OI Smith, Eric/0000-0003-3956-1668; Schwamm, Lee/0000-0003-0592-9145;
Hernandez, Adrian F./0000-0003-3387-9616; Saver,
Jeffrey/0000-0001-9141-2251
FU AHA; ASA; Pfizer, Inc, New York, NY; Merck-Schering Plough Partnership
(North Wales, Pa); National Institutes of Health (National Institute of
Neurological Disorders and Stroke) [R01 NS062028]; Canadian Stroke
Network; Heart and Stroke Foundation of Canada; Canadian Institute for
Health Research; Johnson Johnson; Medtronic; Merck
FX The GWTG is funded by the AHA and the ASA. GWTG is also supported in
part by unrestricted educational grants to the AHA by Pfizer, Inc, New
York, NY, and the Merck-Schering Plough Partnership (North Wales, Pa),
who did not participate in the design, analysis, manuscript preparation,
or approval. B.O. and W. P. had full access to all of the data in the
study and take responsibility for the integrity of the data and the
accuracy of the data analysis.; L. H. S. serves as chair of the AHA GWTG
Steering Committee; serves as a consultant to the Research Triangle
Institute, CryoCath, and to the Massachusetts Department of Public
Health; and has provided expert medical opinions in malpractice lawsuits
regarding stroke treatment and prevention. E. E. S. serves as a member
of the GWTG Science Subcommittee and receives research support from the
National Institutes of Health (National Institute of Neurological
Disorders and Stroke R01 NS062028) and the Canadian Stroke Network and
salary support from the Heart and Stroke Foundation of Canada and the
Canadian Institute for Health Research. A. F. H. is a member of the AHA
GWTG analytical center at the Duke Clinical Research Institute and
reports receiving research support from Johnson & Johnson, Medtronic,
and Merck; honoraria from AstraZeneca; and is serving on the speakers'
bureau for Novartis. A. F. H. has made available online a detailed
listing of financial disclosures (www.dcri.duke.edu/research/coi.jsp).
W. P. and D.M.O. are members of the Duke Clinical Research Institute
that serves as the AHA GWTG data coordinating center. G. C. F. serves as
a consultant to Pfizer (modest), Merck (modest), and Schering Plough
(modest); receives speaker honoraria from AstraZeneca (significant),
Pfizer (significant), Merck (significant), Schering Plough
(significant), Bristol Myers Squibb (significant), and Sanofi-Aventis
(significant); and receives research support from the National
Institutes of Health (significant).
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PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
J9 STROKE
JI Stroke
PD JUL
PY 2010
VL 41
IS 7
BP 1508
EP 1513
DI 10.1161/STROKEAHA.109.573618
PG 6
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 617HS
UT WOS:000279272200035
PM 20508182
ER
PT J
AU Reeves, MJ
Parker, C
Fonarow, GC
Smith, EE
Schwamm, LH
AF Reeves, Mathew J.
Parker, Carol
Fonarow, Gregg C.
Smith, Eric E.
Schwamm, Lee H.
TI Development of Stroke Performance Measures Definitions, Methods, and
Current Measures
SO STROKE
LA English
DT Review
DE acute stroke; performance measurement; quality of care
ID QUALITY-OF-CARE; TRANSIENT ISCHEMIC ATTACK; AMERICAN-COLLEGE;
HEALTH-CARE; CARDIOVASCULAR-RADIOLOGY; CARDIOLOGY; GUIDELINES; OUTCOMES;
COUNCIL; INTERVENTION
AB Background and Purpose-In the United States and elsewhere, stroke performance measures have been developed to monitor and improve the quality of care. The process by which these measures are developed, implemented, and evaluated is complex, evolving, and not widely understood. We review the methodological development of stroke performance measures in the United States.
Methods-A literature search identified articles that addressed the development and endorsement of performance measures for stroke care. Emphasis was given to articles specific to acute stroke, but when these were lacking, other cardiovascular diseases were included.
Results-Ten process-based performance measures relevant to acute hospital-based stroke care have now been developed and endorsed. These measures include intravenous thrombolysis, deep vein thrombosis prophylaxis, dysphagia screening, stroke education, and discharge-related medications and assessments. There are currently at least 5 major US-based stroke quality improvement programs implementing stroke measures. Data indicate that rapid improvements in the quality of stroke care can be induced by the systematic collection and evaluation of stroke performance measures. However, current stroke measures are relatively limited, addressing only inpatient care and mostly patients with ischemic stroke.
Conclusions-Stroke quality improvement is still in its early stages, but data suggest that large-scale improvements in stroke care can result from the implementation of stroke performance measures. Performance measures that address multidisciplinary stroke unit care, outpatient-based care, and patient-oriented outcomes such as functional recovery should be considered. Ongoing challenges relevant to stroke quality improvement include the role of public reporting and the need to link better stroke care to improved patient outcomes. (Stroke. 2010; 41: 1573-1578.)
C1 [Reeves, Mathew J.; Parker, Carol] Michigan State Univ, Dept Epidemiol, E Lansing, MI 48824 USA.
[Fonarow, Gregg C.] Univ Calif Los Angeles, Div Cardiol, Los Angeles, CA USA.
[Smith, Eric E.] Univ Calgary, Dept Clin Neurosci, Calgary, AB T2N 1N4, Canada.
[Schwamm, Lee H.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
RP Reeves, MJ (reprint author), Michigan State Univ, Dept Epidemiol, B601 W Fee Hall, E Lansing, MI 48824 USA.
EM reevesm@msu.edu
OI Schwamm, Lee/0000-0003-0592-9145; Smith, Eric/0000-0003-3956-1668
FU Michigan Paul Coverdell Stroke Registry; Agency of Healthcare Research
Quality (AHRQ); National Institutes of Health; Canadian Institutes for
Health Research; Canadian Stroke Network; Hotchkiss Brain Institute
FX M.J.R. serves as a member of the AHA GWTG Quality Improvement and Stroke
Science Subcommittees, receives salary support from the Michigan Paul
Coverdell Stroke Registry, and research funding from the Agency of
Healthcare Research Quality (AHRQ). G. C. F. is a member of the AHA GWTG
Steering Committee; served as a consultant to Pfizer, Merck/Schering
Plough, Bristol Myers Squibb, and Sanofi-Aventis; received speaker
honoraria from Pfizer, Merck, Schering Plough, Bristol Myers Squibb, and
Sanofi-Aventis; and receives research support from the National
Institutes of Health. E. E. S. serves as chair of the AHA GWTG-Stroke
Science Subcommittee and reports research funding from the National
Institutes of Health, Canadian Institutes for Health Research, Canadian
Stroke Network, and Hotchkiss Brain Institute. L. H. S. serves as chair
of the AHA GWTG Steering Committee; serves as a consultant to the
Massachusetts Department of Public Health; and has provided expert
medical opinions in malpractice lawsuits regarding stroke treatment and
prevention.
NR 40
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PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
J9 STROKE
JI Stroke
PD JUL
PY 2010
VL 41
IS 7
BP 1573
EP 1578
DI 10.1161/STROKEAHA.109.577171
PG 6
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 617HS
UT WOS:000279272200047
PM 20489174
ER
PT J
AU Lanthier, S
Poppe, AY
Greenberg, SM
Black, SE
AF Lanthier, S.
Poppe, A. Y.
Greenberg, S. M.
Black, S. E.
TI Immunosuppressive therapy in cerebral amyloid angiopathy with lobar
hyperintensities
SO STROKE
LA English
DT Meeting Abstract
CT 1st Canadian Stroke Congress
CY JUN 07-08, 2010
CL Quebec City, CANADA
C1 [Lanthier, S.; Poppe, A. Y.] CHUM, Notre Dame Hosp, Montreal, PQ, Canada.
[Lanthier, S.; Poppe, A. Y.; Greenberg, S. M.] Univ Montreal, Montreal, PQ, Canada.
[Black, S. E.] Harvard Univ, Harvard Med Sch, Massachusetts Gen Hosp, Ctr Stroke Res, Boston, MA USA.
NR 0
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PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
J9 STROKE
JI Stroke
PD JUL
PY 2010
VL 41
IS 7
BP E481
EP E481
PG 1
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 617HS
UT WOS:000279272200109
ER
PT J
AU Crawford, RS
Albadawi, H
Atkins, MD
Jones, JE
Yoo, HJ
Conrad, MF
Austen, WG
Watkins, MT
AF Crawford, Robert S.
Albadawi, Hassan
Atkins, Marvin D.
Jones, John E.
Yoo, Hyung-Jin
Conrad, Mark F.
Austen, W. Gerald, Jr.
Watkins, Michael T.
TI Postischemic poly (ADP-ribose) polymerase (PARP) inhibition reduces
ischemia reperfusion injury in a hind-limb ischemia model
SO SURGERY
LA English
DT Article
ID SYSTEMIC INFLAMMATORY RESPONSE; SKELETAL-MUSCLE; POLY(ADP-RIBOSE)
POLYMERASE; LIMB ISCHEMIA; POTENT INHIBITOR; MYOCARDIAL-ISCHEMIA;
IN-VITRO; PJ34; DYSFUNCTION; SYNTHETASE
AB Background. Several experiments were designed to determine whether the systemic, postischemic administration of PJ34, which is a poly-adenosine diphosphate (ADP)-ribose polymerase inhibitor, decreased tissue injury and inflammation after hind-limb ischemia reperfusion (I/R)
Methods. C57BL6 mouse limbs were subjected to 1 5 h ischemia followed by 24-h reperfusion The treatment group (PJ) received intraperitoneal PJ34 (30 mg/kg) immediately before reperfusion, as well as 15 mm and 2 h into reperfusion The control group (CG) received lactated Ringer's alone at the same time intervals as PJ34 administration The skeletal muscle levels of adenosine triphosphate (ATP), macrophage inflammatory protein-2 (MIP-2), keratinocyte derived chemokine (KC), and myeloperoxidase (MPO) were measured. Quantitative measurement of skeletal muscle tissue injury was assessed by microscopic analysis of fiber injury
Results. ATP levels were higher in limbs PJ versus CG mice (absolute ATP: 4 7 +/- 0.35 vs 2 3 +/- 0.15-ng/mg tissue, P = .002). The levels of MIP-2, KC, and MPO were lower in PJ versus CG mice (MIP-2 1 4 +/- 0 34 vs 3.67 +/- 0.67-pg/mg protein, P = 014; KC: 4.97 +/- 0.97 vs 12.65 +/- 3 05-pg/mg protein, P = .037; MPO. 46.27 +/- 10 53 vs 107.34 +/- 13 58-ng/mg protein, P = .008). Muscle fiber injury was markedly reduced in PJ versus CG mice (4.25 +/- 1.9% vs 22 68 +/- 3.0% total fibers, P = .0004).
Conclusion. Systemic postischemic administration of PJ34 preserved skeletal muscle energy levels, decreased inflammatory markers. and preserved tissue viability post-I/R. These results support PARP inhibition as a viable treatment for skeletal muscle I/R in a clinically relevant post hoc scenario (Surgery 2010:148.110-8)
C1 [Crawford, Robert S.; Albadawi, Hassan; Atkins, Marvin D.; Jones, John E.; Yoo, Hyung-Jin; Conrad, Mark F.; Watkins, Michael T.] Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, Gen Surg Serv, Boston, MA 02114 USA.
[Austen, W. Gerald, Jr.] Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, Gen Surg Serv, Boston, MA 02114 USA.
[Crawford, Robert S.; Albadawi, Hassan; Atkins, Marvin D.; Jones, John E.; Conrad, Mark F.; Austen, W. Gerald, Jr.; Watkins, Michael T.] Harvard Univ, Sch Med, Boston, MA USA.
RP Watkins, MT (reprint author), Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, Gen Surg Serv, 15 Parkman St,WAC 440, Boston, MA 02114 USA.
FU Pacific Vascular Research Foundation; American Diabetes Association;
Geneen Fund at the Massachusetts General Hospital; National Institutes
of Health [1R01AR055843]
FX Supported by the Pacific Vascular Research Foundation, the American
Diabetes Association, the Geneen Fund at the Massachusetts General
Hospital, and Grant 1R01AR055843 from the National Institutes of Health
NR 39
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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 JUL
PY 2010
VL 148
IS 1
BP 110
EP 118
DI 10.1016/j.surg.2009.12.006
PG 9
WC Surgery
SC Surgery
GA 620JN
UT WOS:000279495800014
PM 20132957
ER
PT J
AU Vagefi, PA
Stangenberg, L
Krings, G
Forcione, DG
Wargo, JA
AF Vagefi, Parsia A.
Stangenberg, Lars
Krings, Gregor
Forcione, David G.
Wargo, Jennifer A.
TI Ocular melanoma metastatic to the pancreas after a 28-year disease-free
interval
SO SURGERY
LA English
DT Editorial Material
ID RESECTION
C1 [Vagefi, Parsia A.; Stangenberg, Lars; Wargo, Jennifer A.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Krings, Gregor] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Forcione, David G.] Harvard Univ, Sch Med, Dept Internal Med, Massachusetts Gen Hosp, Boston, MA USA.
RP Vagefi, PA (reprint author), 55 Fruit St,GRB 425, Boston, MA 02114 USA.
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U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0039-6060
J9 SURGERY
JI Surgery
PD JUL
PY 2010
VL 148
IS 1
BP 151
EP 154
DI 10.1016/j.surg.2009.06.013
PG 4
WC Surgery
SC Surgery
GA 620JN
UT WOS:000279495800020
PM 19744448
ER
PT J
AU Shah, SS
Todkar, JS
Shah, PS
Cummings, DE
AF Shah, Shashank S.
Todkar, Jayashree S.
Shah, Poonam S.
Cummings, David E.
TI Diabetes remission and reduced cardiovascular risk after gastric bypass
in Asian Indians with body mass index < 35 kg/m(2)
SO SURGERY FOR OBESITY AND RELATED DISEASES
LA English
DT Article
DE Gastric bypass; Metabolic surgery; Bariatric surgery; Diabetes;
Mortality; Cardiovascular risk; Ghrelin; Coronary heart disease
ID CORONARY-HEART-DISEASE; BARIATRIC SURGERY; BILIOPANCREATIC DIVERSION;
METABOLIC SYNDROME; ADIPOSE-TISSUE; MELLITUS; MORTALITY; OBESITY;
ANTHROPOMETRY; PARTICIPANTS
AB Background: Roux-en-Y gastric bypass (RYGB) benefits patients with type 2 diabetes mellitus (T2DM) and a body mass index (BMI) >35 kg/m(2); however, its effectiveness in patients with T2DM and a BMI <35 kg/m(2) is unclear. Asian Indians have a high risk of T2DM and cardiovascular disease at relatively low BMI levels. We examined the safety and efficacy of RYGB in Asian Indian patients with T2DM and a BMI of 22-35 kg/m(2) in a tertiary care medical center.
Methods: A total of 15 consecutive patients with T2DM and a BMI of 22-35 kg/m(2) underwent RYGB. The data were prospectively collected before surgery and at 1, 3, 6, and 9 months postoperatively.
Results: Of the 15 patients, 8 were men and 7 were women (age 45.6 +/- 12 years). Their preoperative characteristics were BMI 28.9 +/- 4.0 kg/m(2), body weight 78.7 +/- 12.5 kg, waist circumference 100.2 +/- 6.8 cm, and duration of T2DM 8.7 +/- 5.3 years. At baseline, 80% of subjects required insulin, and 20% controlled their T2DM with oral hypoglycemic medication. The BMI decreased postoperatively by 20%, from 28.9 +/- 4.0 kg/m(2) to 23.0 +/- 3.6 kg/m(2) (P < .001). All antidiabetic medications were discontinued by 1 month after surgery in 80% of the subjects. At 3 months and thereafter, 100% were euglycemic and no longer required diabetes medication. The fasting blood glucose level decreased from 233 +/- 87 mg/dL to 89 +/- 12 mg/dL (P < .001), and the hemoglobin A1c decreased from 10.1% +/- 2.0% to 6.1% +/- 0.6% (P < .001). Their waist circumference, presence of dyslipidemia, and hypertension improved significantly. The predicted 10-year cardiovascular disease risk (calculated using the United Kingdom Prospective Diabetes Study equations) decreased substantially for fatal and nonfatal coronary heart disease and stroke. No mortality, major surgical morbidity, or excessive weight loss occurred.
Conclusion: RYGB safely and effectively eliminated T2DM in Asian Indians with a BMI <35 kg/m(2). Larger, longer term studies are needed to confirm this benefit. (Surg Obes Relat Dis 2010;6:332-339.) (C) 2010 American Society for Metabolic and Bariatric Surgery. All rights reserved.
C1 [Cummings, David E.] Univ Washington, Sch Med, Dept Med, Diabet & Obes Ctr Excellence, Seattle, WA 98195 USA.
[Cummings, David E.] Univ Washington, Sch Med, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98195 USA.
[Shah, Shashank S.; Todkar, Jayashree S.; Shah, Poonam S.] Ruby Hall Clin, Pune, Maharashtra, India.
RP Cummings, DE (reprint author), Univ Washington, Sch Med, Dept Med, Diabet & Obes Ctr Excellence, 815 Mercer St,Room S284, Seattle, WA 98195 USA.
EM davidec@u.washington.edu
FU NIH [DK517498, DK68384, DK66568, DK17047]
FX David Cummings is supported by NIH grants DK517498, DK68384, DK66568,
and DK17047.
NR 31
TC 62
Z9 66
U1 0
U2 5
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 JUL-AUG
PY 2010
VL 6
IS 4
BP 332
EP 338
DI 10.1016/j.soard.2009.08.009
PG 7
WC Surgery
SC Surgery
GA 634WA
UT WOS:000280615400001
PM 19846351
ER
PT J
AU Josbeno, DA
Jakicic, JM
Hergenroeder, A
Eid, GM
AF Josbeno, Deborah A.
Jakicic, John M.
Hergenroeder, Andrea
Eid, George M.
TI Physical activity and physical function changes in obese individuals
after gastric bypass surgery
SO SURGERY FOR OBESITY AND RELATED DISEASES
LA English
DT Article
DE Obesity; Bariatric surgery; Gastric bypass; Physical activity; Physical
function
ID 6-MINUTE WALK TEST; QUALITY-OF-LIFE; LOW-BACK-PAIN; WEIGHT-LOSS;
BARIATRIC SURGERY; HEALTH; WOMEN; EXERCISE; INTERVENTION; RELIABILITY
AB Background: Little is known about the effects of gastric bypass surgery (GBS) on physical activity and physical function. We examined the physical activity, physical function, psychosocial correlates to physical activity participation, and health-related quality of life of patients before and after GBS.
Methods: A total of 20 patients were assessed before and 3 months after GBS. Physical activity was assessed using the 7-day physical activity recall questionnaire and a pedometer worn for 7 days. Physical function was assessed using the 6-minute walk test, Short Physical Performance Battery, and the physical function subscale of the Medical Outcomes Short Form-36 (SF-36). The Physical Activity Self-Efficacy questionnaire, the Physical Activity Barriers and Outcome Expectations questionnaire, the SF-36, and the Numeric Pain Rating Scale were also administered.
Results: Physical activity did not significantly increase from before (191.1 +/- 228.23 min/wk) to after (231.7 +/- 230.04 min/wk) GBS (n = 18); however, the average daily steps did significantly increase (from 4621 +/- 3701 to 7370 +/- 4240 steps/d; n = 11). The scores for the 6-minute walk test (393 +/- 62.08 m to 446 +/- 41.39 m; n = 17), Short Physical Performance Battery (11.2 +/- 1.22 to 11.7 +/- .57; n = 18), physical function subscale of the SF-36 (65 +/- 18.5 to 84.1 +/- 19.9), and the total SF-36 (38.2 +/- 23.58 to 89.7 +/- 15.5; n = 17) increased significantly. The Numeric Pain Rating Scale score decreased significantly for low back (3.5 +/- 1.8 to 1.7 +/- 2.63), knee (2.4 +/- 2.51 to 1.0 +/- 1.43), and foot/ankle (2.3 +/- 2.8 to 0.9 +/- 2.05) pain. No significant changes were found in the Physical Activity Self-Efficacy questionnaire or the Physical Activity Barriers and Outcome Expectations questionnaire.
Conclusion: GBS improves physical function, health-related quality of life, and self-reported pain and results in a modest improvement in physical activity. These are important clinical benefits of surgical weight loss. Long-term follow-up is needed to quantify the ability to sustain or further improve these important clinical outcomes. (Surg Obes Relat Dis 2010;6:361-366.) (C) 2010 American Society for Metabolic and Bariatric Surgery. All rights reserved.
C1 [Josbeno, Deborah A.; Hergenroeder, Andrea] Univ Pittsburgh, Dept Phys Therapy, Pittsburgh, PA 15260 USA.
[Jakicic, John M.] Univ Pittsburgh, Dept Hlth & Phys Act, Pittsburgh, PA USA.
[Eid, George M.] Univ Pittsburgh, Dept Surg, Pittsburgh, PA USA.
[Eid, George M.] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA.
RP Josbeno, DA (reprint author), Univ Pittsburgh, Dept Phys Therapy, Pittsburgh, PA 15260 USA.
NR 30
TC 34
Z9 35
U1 2
U2 13
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 JUL-AUG
PY 2010
VL 6
IS 4
BP 361
EP 366
DI 10.1016/j.soard.2008.08.003
PG 6
WC Surgery
SC Surgery
GA 634WA
UT WOS:000280615400007
PM 18996771
ER
PT J
AU Sogg, S
AF Sogg, Stephanie
TI Comment on: History of substance abuse relates to improved postbariatric
body mass index outcomes
SO SURGERY FOR OBESITY AND RELATED DISEASES
LA English
DT Editorial Material
ID BARIATRIC SURGERY
C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Weight Ctr, Boston, MA 02115 USA.
RP Sogg, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Weight Ctr, Boston, MA 02115 USA.
NR 7
TC 0
Z9 0
U1 1
U2 3
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 JUL-AUG
PY 2010
VL 6
IS 4
BP 421
EP 422
PG 2
WC Surgery
SC Surgery
GA 634WA
UT WOS:000280615400019
PM 20655026
ER
PT J
AU Burstein, HJ
Griggs, JJ
AF Burstein, Harold J.
Griggs, Jennifer J.
TI Adjuvant Hormonal Therapy for Early-Stage Breast Cancer
SO SURGICAL ONCOLOGY CLINICS OF NORTH AMERICA
LA English
DT Article
DE Adjuvant endocrine therapy; Tamoxifen; Aromatase inhibitors; Ovarian
suppression
ID POSTMENOPAUSAL WOMEN; AROMATASE INHIBITORS; PREMENOPAUSAL WOMEN;
RANDOMIZED-TRIAL; ENDOCRINE THERAPY; TAMOXIFEN THERAPY; ZOLEDRONIC ACID;
BIG-1-98 TRIAL; DRUG-THERAPY; BONE LOSS
AB Adjuvant endocrine treatment is an essential component in therapy for hormone receptor positive breast cancer. Among postmenopausal patients, options include tamoxifen, aromatase inhibitors, or a sequence of these agents. Tamoxifen and aromatase inhibitors have distinctive side-effect profiles. Among premenopausal women, tamoxifen remains the standard treatment. The role of ovarian suppression in addition to tamoxifen is under investigation. Questions about the duration of adjuvant endocrine therapy, the use of biomarkers for treatment selection and prognosis, and the management of side effects of adjuvant endocrine therapy remain key areas of investigation.
C1 [Burstein, Harold J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Breast Oncol Ctr, Boston, MA 02115 USA.
[Griggs, Jennifer J.] Univ Michigan, Dept Internal Med, Div Hematol & Oncol, Ann Arbor, MI 48109 USA.
[Griggs, Jennifer J.] Univ Michigan, Dept Hlth Management & Policy, Ann Arbor, MI 48109 USA.
[Griggs, Jennifer J.] Univ Michigan, Ctr Comprehens Canc, Breast Canc Survivorship Program, Ann Arbor, MI 48109 USA.
RP Burstein, HJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Breast Oncol Ctr, 44 Binney St, Boston, MA 02115 USA.
EM hburstein@partners.org
NR 41
TC 10
Z9 10
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 1055-3207
J9 SURG ONCOL CLIN N AM
JI Surg. Oncol. Clin. N. Am.
PD JUL
PY 2010
VL 19
IS 3
BP 639
EP +
DI 10.1016/j.soc.2010.03.006
PG 10
WC Oncology; Surgery
SC Oncology; Surgery
GA 634RL
UT WOS:000280601200015
PM 20620932
ER
PT J
AU Davies, TF
Yin, XM
Latif, R
AF Davies, Terry F.
Yin, Xiaoming
Latif, Rauf
TI The Genetics of the Thyroid Stimulating Hormone Receptor: History and
Relevance
SO THYROID
LA English
DT Article
ID HUMAN THYROTROPIN RECEPTOR; X-CHROMOSOME INACTIVATION; GRAVES-DISEASE;
TSH RECEPTOR; SUSCEPTIBILITY LOCI; MOLECULAR-CLONING;
HASHIMOTOS-THYROIDITIS; FEMALE PREDISPOSITION; ALZHEIMERS-DISEASE;
WHICKHAM SURVEY
AB Background: The thyroid stimulating hormone receptor (TSHR) is the key regulator of thyrocyte function. The gene for the TSHR on chromosome 14q31 has been implicated as coding for the major autoantigen in the autoimmune hyperthyroidism of Graves' disease (GD) to which T cells and autoantibodies are directed.
Summary: The TSHR is a seven-transmembrane domain receptor that undergoes complex posttranslational processing. In this brief review, we look at the genetics of this important autoantigen and its influence on a variety of tissue functions in addition to its role in the induction of GD.
Conclusions: There is convincing evidence that the TSH receptor gene confers increased susceptibility for GD, but not Hashimoto's thyroiditis. GD is associated with polymorphisms in the intron 1 gene region. How such noncoding nucleotide changes influence disease susceptibility remains uncertain, but is likely to involve TSHR splicing variants and/or microRNAs arising from this gene region. Whether such influences are confined to the thyroid gland or whether they influence cell function in the many extrathyroidal sites of TSHR expression remains unknown.
C1 [Davies, Terry F.; Yin, Xiaoming; Latif, Rauf] Mt Sinai Sch Med, Thyroid Res Unit, James J Peters VA Med Ctr, New York, NY 10029 USA.
RP Davies, TF (reprint author), Mt Sinai Sch Med, Thyroid Res Unit, James J Peters VA Med Ctr, Box 1055,1 Gustave L Levy Pl, New York, NY 10029 USA.
EM terry.davies@mssm.edu
FU NIH [DK069713, DK052464]; VA Merit Award
FX Supported in part by NIH grants DK069713 and DK052464, and the VA Merit
Award Program. We thank Yaron Tomer, M. D., and David Greenberg, Ph.D.,
for their ongoing collaboration and support.
NR 89
TC 25
Z9 26
U1 0
U2 8
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1050-7256
J9 THYROID
JI Thyroid
PD JUL
PY 2010
VL 20
IS 7
BP 727
EP 736
DI 10.1089/thy.2010.1638
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 620RS
UT WOS:000279517600007
PM 20578897
ER
PT J
AU Brent, GA
AF Brent, Gregory A.
TI Environmental Exposures and Autoimmune Thyroid Disease
SO THYROID
LA English
DT Article
ID ATOMIC-BOMB SURVIVORS; NATIONAL-HEALTH; UNITED-STATES; IODINE;
HYPOTHYROIDISM; RADIATION; PREVALENCE; NUTRITION; CHERNOBYL;
AUTOANTIBODIES
AB Background: Environmental exposures, ranging from perchlorate in rocket fuel to polychlorinated biphenols, have been shown to influence thyroid function. Although most of these agents are associated with reduced thyroid hormone levels or impaired thyroid hormone action, a number of environmental exposures confer an increased risk of autoimmune thyroid disease.
Summary: Factors that increase autoimmune thyroid disease risk include radiation exposure, both from nuclear fallout and medical radiation, increased iodine intake, as well as several contaminants in the environment that influence the thyroid. Although similar to 70% of the risk for developing autoimmune thyroid disease is attributable to genetic background, environmental triggers are thought to play a role in the development of autoimmune thyroid disease in susceptible individuals.
Conclusions: Understanding the association of environmental agents with thyroid dysfunction can be utilized to reduce the risk to populations. Knowledge of the specific factors that trigger autoimmune thyroid disease and their mode of action, however, may also inform risk reduction in the individual patient. These factors are especially relevant for those at increased risk of autoimmune thyroid disease based on family history.
C1 [Brent, Gregory A.] Univ Calif Los Angeles, David Geffen Sch Med, Endocrinol & Diabet Div,Dept Med, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA.
[Brent, Gregory A.] Univ Calif Los Angeles, David Geffen Sch Med, Endocrinol & Diabet Div,Dept Physiol, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA.
RP Brent, GA (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Endocrinol & Diabet Div,Dept Med, VA Greater Los Angeles Healthcare Syst, 111D,11301 Wilshire Blvd, Los Angeles, CA 90073 USA.
EM gbrent@ucla.edu
FU VA Merit Review funds; NIH [RO1 CA89364]
FX This work was supported by VA Merit Review funds and NIH RO1 CA89364.
NR 48
TC 28
Z9 31
U1 2
U2 9
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1050-7256
J9 THYROID
JI Thyroid
PD JUL
PY 2010
VL 20
IS 7
BP 755
EP 761
DI 10.1089/thy.2010.1636
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 620RS
UT WOS:000279517600010
PM 20578899
ER
PT J
AU Barbesino, G
AF Barbesino, Giuseppe
TI Drugs Affecting Thyroid Function
SO THYROID
LA English
DT Article
ID RENAL-CELL CARCINOMA; CHRONIC HEPATITIS-C; AMIODARONE-ASSOCIATED
THYROTOXICOSIS; SUNITINIB INDUCES HYPOTHYROIDISM; MULTIPLE-SCLEROSIS;
LITHIUM-CARBONATE; GRAVES-DISEASE; IMMUNE RECONSTITUTION; METASTATIC
MELANOMA; DOPPLER SONOGRAPHY
AB Introduction: Over the years, several drugs used in the treatment of nonthyroidal conditions have been shown to affect thyroid function. As novel drugs are introduced, novel interactions are described. The aim of this review is to summarize clinically relevant thyroidal side effects of drugs used for nonthyroidal conditions. Special focus is given to recent developments and to drugs with the largest clinical relevance.
Summary: Thyrosine kinase inhibitors are novel drugs used in the treatment of several neoplasias, including thyroid cancer. Thyroidal side effects are being increasingly detected with these drugs. Some drugs in this category affect thyroid hormone metabolism and therefore only affect patients on thyroid replacement. Others affect the thyroid directly profoundly, causing primary hypothyroidism. Immune modulators used in infectious, inflammatory, and neoplastic conditions also cause hyper- and hypothyroidism, through poorly understood immune or nonimmune mechanisms. The effects of amiodarone on the thyroid have been long recognized. However, given the complexity of these effects, several areas in this field remain problematic, such as the identification of subtypes of hyperthyroidism and the best treatment strategies. Lithium also has important antithyroid effects and it is a commonly prescribed medication. Its antithyroid effects may have clinical utility in selected clinical situations. Other drugs known to affect thyroid hormone absorption, metabolism, and transport are also briefly reviewed.
Conclusions: Several drugs are known to alter thyroid function as a side effect of their primary pharmacological action. Some of these effects have been recognized for decades, but novel thyroid-drug interactions are being recognized as new drugs are developed. It is important for the clinician to be familiar with thyroid-drug interactions, as enhanced surveillance may be necessary in patients undergoing therapies known to affect thyroid function.
C1 Harvard Univ, Sch Med,Thyroid Unit, WANG Ambulatory Care Ctr 740S, Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Barbesino, G (reprint author), Harvard Univ, Sch Med,Thyroid Unit, WANG Ambulatory Care Ctr 740S, Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA.
EM gbarbesino@partners.org
NR 68
TC 51
Z9 53
U1 0
U2 11
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1050-7256
J9 THYROID
JI Thyroid
PD JUL
PY 2010
VL 20
IS 7
BP 763
EP 770
DI 10.1089/thy.2010.1635
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 620RS
UT WOS:000279517600011
PM 20578900
ER
PT J
AU Kemmis, K
AF Kemmis, Karen
TI Common Musculoskeletal Disorders in Older Adults With Diabetes
SO TOPICS IN GERIATRIC REHABILITATION
LA English
DT Article
DE complications; diabetes; musculoskeletal
ID LIMITED JOINT MOBILITY; BONE-MINERAL DENSITY; CALCIFIC SHOULDER
PERIARTHRITIS; ADHESIVE CAPSULITIS; FROZEN-SHOULDER; ARTHROSCOPIC
RELEASE; KNEE OSTEOARTHRITIS; INCREASED RISK; UNITED-STATES; HAND
SYNDROME
AB Diabetes is a disease characterized by chronic hyperglycemia. This can cause microvascular and macrovascular complications. There are several musculoskeletal disorders that occur in people with diabetes. Some are likely directly because of the disease process, others have a higher incidence in those with diabetes, and yet others are likely associated with common etiologies. Rehabilitation professionals should be aware of common musculoskeletal disorders present in those with diabetes and be familiar with the implications of therapy interventions.
C1 SUNY Upstate Med Univ, Phys Med & Rehabil & Joslin Diabet Ctr, Syracuse, NY 13214 USA.
RP Kemmis, K (reprint author), SUNY Upstate Med Univ, Phys Med & Rehabil & Joslin Diabet Ctr, 3229 E Genesee St, Syracuse, NY 13214 USA.
EM kemmisk@upstate.edu
NR 69
TC 3
Z9 3
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0882-7524
J9 TOP GERIATR REHABIL
JI Top. Geriatr. Rehabil.
PD JUL-SEP
PY 2010
VL 26
IS 3
BP 264
EP 272
DI 10.1097/TGR.0b013e3181ef3049
PG 9
WC Gerontology; Rehabilitation
SC Geriatrics & Gerontology; Rehabilitation
GA 632YM
UT WOS:000280466000009
ER
PT J
AU Strasser, DC
Burridge, AB
Falconer, JA
Herrin, J
Uomoto, J
AF Strasser, Dale C.
Burridge, Andrea B.
Falconer, Judith A.
Herrin, Jeph
Uomoto, Jay
TI Measuring Team Process for Quality Improvement
SO TOPICS IN STROKE REHABILITATION
LA English
DT Article
DE patient care teams; process measures; quality of health care; stroke
rehabilitation
ID STROKE REHABILITATION; VETERANS; OUTCOMES; TRIAL
AB Background: Even though team care is pivotal to stroke rehabilitation, we have few tools to measure team process. Process measures of team functioning would benefit stroke rehabilitation outcomes and quality improvement (QI). Objective: To improve measures of team process and evaluate their potential for use in rehabilitation research and QI. Methods: We use item response theory (IRT) to analyze and revise selected scales from the Team Functioning Survey administrated to rehabilitation staff (n=365 at 31 VA hospitals) as part of a national clinical trial (NCT00237757). Revised scales were evaluated for reliability (Cronbach's alpha) and validity (correlations, predictions of patient outcomes). Results: Eight scales (60 items) were selected from the TFS for analyses based on their specificity to rehabilitation and potential utility in process improvement. Factor analyses supported the dropping of 2 scales and the combining of 2 scales. As indicated by the IRT analyses of scale psychometric properties, poor performing scale items were dropped and item response categories modified needed areas for further development were identified. Cronbach's alpha for the resultant best 5 scales was good. Intercorrelations varied among scales but were mostly in the moderate ranges. Two of the scales predicted patient outcomes of mFIM (TM) gain or discharge disposition. Conclusion: The analyses resulted in measures of 5 central components of team functioning: physician support, shared leadership, supervisor team support, teamness, and team effectiveness. IRT enables the scales to be refined and strengthened for use in outcome research and QI. The scales are proposed as another step toward understanding and enhancing team process.
C1 [Strasser, Dale C.] Emory Univ, Sch Med, Dept Rehabil Med, Atlanta, GA 30322 USA.
[Strasser, Dale C.] Atlanta VA Med Ctr, Atlanta, GA USA.
[Falconer, Judith A.] Northwestern Univ, Feinberg Sch Med, Dept Med, Chicago, IL 60611 USA.
[Herrin, Jeph] Yale Univ, Yale Sch Med, Div Cardiol, New Haven, CT USA.
[Uomoto, Jay] VADoD Liaison, Washington, DC USA.
[Uomoto, Jay] US Dept Vet Affairs, TBI, Off Rehabil Serv, Washington, DC USA.
RP Strasser, DC (reprint author), Emory Univ, Sch Med, Dept Rehabil Med, Atlanta, GA 30322 USA.
RI Backscheider Burridge, Andrea/D-9332-2015
OI Backscheider Burridge, Andrea/0000-0001-7502-0047
FU Veterans Administration Rehabilitation Research and Development Service
[B2367R, 03225R]
FX Supported by the Veterans Administration Rehabilitation Research and
Development Service (Merit Review Grants B2367R, 03225R).
NR 23
TC 7
Z9 7
U1 1
U2 11
PU THOMAS LAND PUBLISHERS, INC
PI ST LOUIS
PA 255 JEFFERSON RD, ST LOUIS, MO 63119 USA
SN 1074-9357
J9 TOP STROKE REHABIL
JI Top. Stroke Rehabil.
PD JUL-AUG
PY 2010
VL 17
IS 4
BP 282
EP 293
DI 10.1310/tsr1704-282
PG 12
WC Rehabilitation
SC Rehabilitation
GA 654FD
UT WOS:000282153000007
PM 20826416
ER
PT J
AU Ji, GX
Gu, AH
Zhu, PF
Xia, YK
Zhou, Y
Hu, F
Song, L
Wang, SL
Wang, XR
AF Ji, Guixiang
Gu, Aihua
Zhu, Pengfei
Xia, Yankai
Zhou, Yong
Hu, Fan
Song, Ling
Wang, Shoulin
Wang, Xinru
TI Joint Effects of XRCC1 Polymorphisms and Polycyclic Aromatic
Hydrocarbons Exposure on Sperm DNA Damage and Male Infertility
SO TOXICOLOGICAL SCIENCES
LA English
DT Article
DE infertility; polycyclic hydrocarbons; genetic polymorphisms; XRCC1;
spermatozoa; DNA damage
ID NUCLEOTIDE-EXCISION-REPAIR; COKE-OVEN WORKERS; LUNG-CANCER RISK; MALE
GERM-CELLS; GENETIC POLYMORPHISMS; URINARY METABOLITES; CHINESE
POPULATION; IN-VITRO; ASSOCIATION; 1-HYDROXYPYRENE
AB X-ray repair cross-complementing group 1 (XRCC1) plays a role in repairing polycyclic aromatic hydrocarbons (PAHs)-induced DNA damage. We examined the effects of exposure to PAHs and XRCC1 polymorphism, alone or combined, on sperm DNA integrity and male fertility. A total of 620 idiopathic infertile subjects and 273 fertile controls were recruited in this study. PAHs exposure was indicated by urinary 1-hydroxypyrene level. Genotypes were determined by PCR-RFLP, and sperm DNA damage was detected by Tdt-mediated dUTP nick end labelling assay using flow cytometry. A positive correlation was found between PAHs exposure and sperm DNA damage (beta coefficients = 0.183, p < 0.001), whereas there was no significant association between the XRCC1 polymorphisms and sperm DNA damage. However, when the patients were dichotomized for PAHs exposure, higher sperm DNA damage was found among 399GIn allele carriers compared with the wild-type homozygotes (p = 0.033). Further analysis based on a case-control study revealed the joint effect of XRCC1-399 polymorphism and PAHs exposure on the risk of male infertility (p interaction = 0.041). These findings provided the first evidence about potential joint effects of PAHs exposure and DNA repair gene polymorphisms on male reproductive system and may be helpful in improving our understanding of the etiology of male infertility.
C1 [Ji, Guixiang; Gu, Aihua; Xia, Yankai; Hu, Fan; Song, Ling; Wang, Shoulin; Wang, Xinru] Nanjing Med Univ, Inst Toxicol, Key Lab Reprod Med, Nanjing 210029, Peoples R China.
[Zhu, Pengfei] WuXi Ctr Dis Prevent & Control, Dept Toxicol, Wuxi 214000, Jiangsu, Peoples R China.
[Zhou, Yong] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA.
RP Wang, XR (reprint author), Nanjing Med Univ, Inst Toxicol, Key Lab Reprod Med, Nanjing 210029, Peoples R China.
EM xrwang@njmu.edu.cn
FU National Basic Research Program of China (973 Program) [2009CB941703];
National Natural Science Foundation of China [30930079]; National
Science Foundation of China [30901210]
FX National Basic Research Program of China (973 Program, 2009CB941703);
the Key Project of National Natural Science Foundation of China
(30930079); the National Science Foundation of China (Grant No.
30901210).
NR 42
TC 11
Z9 13
U1 2
U2 13
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1096-6080
J9 TOXICOL SCI
JI Toxicol. Sci.
PD JUL
PY 2010
VL 116
IS 1
BP 92
EP 98
DI 10.1093/toxsci/kfq112
PG 7
WC Toxicology
SC Toxicology
GA 617XZ
UT WOS:000279316500010
PM 20395310
ER
PT J
AU Torres, S
Chodosh, J
Seto, D
Jones, MS
AF Torres, Sarah
Chodosh, James
Seto, Donald
Jones, Morris S.
TI The Revolution in Viral Genomics as Exemplified by the Bioinformatic
Analysis of Human Adenoviruses
SO VIRUSES-BASEL
LA English
DT Review
DE human adenoviruses; genomics; bioinformatics
ID ACUTE RESPIRATORY-DISEASE; NUCLEOTIDE-SEQUENCE; EPIDEMIC
KERATOCONJUNCTIVITIS; COMPUTATIONAL ANALYSIS; VECTOR DEVELOPMENT; HEXON;
DNA; RECOMBINATION; SEROTYPE; GENE
AB Over the past 30 years, genomic and bioinformatic analysis of human adenoviruses has been achieved using a variety of DNA sequencing methods; initially with the use of restriction enzymes and more currently with the use of the GS FLX pyrosequencing technology. Following the conception of DNA sequencing in the 1970s, analysis of adenoviruses has evolved from 100 base pair mRNA fragments to entire genomes. Comparative genomics of adenoviruses made its debut in 1984 when nucleotides and amino acids of coding sequences within the hexon genes of two human adenoviruses (HAdV), HAdV-C2 and HAdV-C5, were compared and analyzed. It was determined that there were three different zones (1-393, 394-1410, 1411-2910) within the hexon gene, of which HAdV-C2 and HAdV-C5 shared zones 1 and 3 with 95% and 89.5% nucleotide identity, respectively. In 1992, HAdV-C5 became the first adenovirus genome to be fully sequenced using the Sanger method. Over the next seven years, whole genome analysis and characterization was completed using bioinformatic tools such as blastn, tblastx, ClustalV and FASTA, in order to determine key proteins in species HAdV-A through HAdV-F. The bioinformatic revolution was initiated with the introduction of a novel species, HAdV-G, that was typed and named by the use of whole genome sequencing and phylogenetics as opposed to traditional serology. HAdV bioinformatics will continue to advance as the latest sequencing technology enables scientists to add to and expand the resource databases. As a result of these advancements, how novel HAdVs are typed has changed. Bioinformatic analysis has become the revolutionary tool that has significantly accelerated the in-depth study of HAdV microevolution through comparative genomics.
C1 [Torres, Sarah; Jones, Morris S.] David Grant USAF Med Ctr, Clin Investigat Facil, Travis AFB, CA 94535 USA.
[Chodosh, James] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol,Howe Lab, Boston, MA 02114 USA.
[Seto, Donald] George Mason Univ, Dept Bioinformat & Computat Biol, Manassas, VA 20110 USA.
RP Jones, MS (reprint author), David Grant USAF Med Ctr, Clin Investigat Facil, Travis AFB, CA 94535 USA.
EM sarah.torres1@travis.af.mil; James_Chodosh@meei.harvard.edu;
dseto@gmu.edu; drmorrisj@yahoo.com
FU U.S. Public Health Service [EY013124]; Research to Prevent Blindness,
NY, NY
FX Supported in part by U.S. Public Health Service grant EY013124 and an
unrestricted grant to the Department of Ophthalmology, Harvard Medical
School, from Research to Prevent Blindness, NY, NY. The views expressed
in this material are those of the authors, and do not reflect the
official policy or position of the U.S. Government, the Department of
Defense, or the Department of the Air Force.
NR 42
TC 5
Z9 7
U1 0
U2 9
PU MDPI AG
PI BASEL
PA KANDERERSTRASSE 25, CH-4057 BASEL, SWITZERLAND
SN 1999-4915
J9 VIRUSES-BASEL
JI Viruses-Basel
PD JUL
PY 2010
VL 2
IS 7
BP 1367
EP 1381
DI 10.3390/v2071367
PG 15
WC Virology
SC Virology
GA 632HS
UT WOS:000280413900002
PM 21994684
ER
PT J
AU Dzik, S
AF Dzik, S.
TI THREE RESPIRATORY GASES AND THE RED CELL: OXYGEN, NITROGEN, AND CARBON
DIOXIDE
SO VOX SANGUINIS
LA English
DT Meeting Abstract
C1 [Dzik, S.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0042-9007
J9 VOX SANG
JI Vox Sang.
PD JUL
PY 2010
VL 99
SU 1
BP 67
EP 67
PG 1
WC Hematology
SC Hematology
GA 625DE
UT WOS:000279872500167
ER
PT J
AU Wagner, D
AF Wagner, D.
TI INFLAMMATION, HEMORRHAGE AND THROMBOCYTOPENIA
SO VOX SANGUINIS
LA English
DT Meeting Abstract
C1 [Wagner, D.] Immune Dis Inst, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0042-9007
J9 VOX SANG
JI Vox Sang.
PD JUL
PY 2010
VL 99
SU 1
BP 72
EP 73
PG 2
WC Hematology
SC Hematology
GA 625DE
UT WOS:000279872500181
ER
PT J
AU Song, GD
Nguyen, DT
Pietramaggiori, G
Scherer, S
Chen, B
Zhan, QA
Ogawa, R
Yannas, IV
Wagers, AJ
Orgill, DP
Murphy, GF
AF Song, Guodong
Nguyen, Dinh T.
Pietramaggiori, Giorgio
Scherer, Saja
Chen, Bin
Zhan, Qian
Ogawa, Rei
Yannas, I. V.
Wagers, Amy J.
Orgill, Dennis P.
Murphy, George F.
TI Use of the parabiotic model in studies of cutaneous wound healing to
define the participation of circulating cells
SO WOUND REPAIR AND REGENERATION
LA English
DT Article
ID MARROW-DERIVED CELLS; ENDOTHELIAL PROGENITOR CELLS; HEMATOPOIETIC
STEM-CELLS; PERIPHERAL-BLOOD; IN-VIVO; SKIN; DIFFERENTIATION;
NEOVASCULARIZATION; POPULATION; PLASTICITY
AB Previous experimental studies to assess the contribution of blood-borne circulating (BBC) cells to cutaneous wound healing have relied on discontinuous pulsing of labeled BBC elements or bone marrow transplant protocols. Such approaches do not allow the examination of stable BBC cells that have matured in a physiologically normal host. We have used a parabiotic murine model for cutaneous wound healing to evaluate the relative contribution of stable populations of peripheral blood cells expressing the green fluorescent protein (GFP) transgene in otherwise normal animals. Circulating cells (mature and immature) expressing the GFP transgene were easily detected and quantified in wounds of GFP- parabiotic twins during all evaluated stages of the healing response. Using multiple antibody probes, the relative contribution of various subsets of BBC cells could be comparatively assessed. In early wounds, some cells expressing mesenchymal epitopes were documented to be of hematopoietic origin, indicating the utility of this model in assessing cell plasticity in the context of tissue regeneration and repair. Application of this approach enables further investigation into the contribution of peripheral blood in normal and abnormal healing responses.
C1 [Song, Guodong; Nguyen, Dinh T.; Chen, Bin; Zhan, Qian; Ogawa, Rei; Murphy, George F.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Program Dermatopathol, Boston, MA 02115 USA.
[Song, Guodong; Nguyen, Dinh T.; Pietramaggiori, Giorgio; Scherer, Saja; Chen, Bin; Ogawa, Rei; Orgill, Dennis P.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Plast Surg, Boston, MA 02115 USA.
[Pietramaggiori, Giorgio; Scherer, Saja; Wagers, Amy J.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Pathol, Boston, MA 02115 USA.
[Yannas, I. V.] MIT, Dept Mech Engn Mat Sci Engn & Biol Engn, Cambridge, MA 02139 USA.
RP Murphy, GF (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Program Dermatopatholgy, 221 Longwood Ave EBRC 401, Boston, MA 02115 USA.
EM gmurphy@rics.bwh.harvard.edu
RI Chen, Bin/I-6677-2013;
OI Murphy, George/0000-0003-3464-793X; Orgill, Dennis/0000-0002-8279-7310
FU NIH [5 T32 HL007627-22]; SPORE; SDRC; NIH/NIDDK [5 P30 DK36836-20]
FX This study was funded by (1) NIH 5 T32 HL007627-22 Physician-Scientist
Training Grant, (2) Brigham and Women's Hospital's Program in
Dermatopathology core grants (SPORE and SDRC), and (3) NIH/NIDDK (5 P30
DK36836-20) to AJW.
NR 33
TC 20
Z9 21
U1 0
U2 5
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1067-1927
J9 WOUND REPAIR REGEN
JI Wound Repair Regen.
PD JUL-AUG
PY 2010
VL 18
IS 4
BP 426
EP 432
DI 10.1111/j.1524-475X.2010.00595.x
PG 7
WC Cell Biology; Dermatology; Medicine, Research & Experimental; Surgery
SC Cell Biology; Dermatology; Research & Experimental Medicine; Surgery
GA 619UB
UT WOS:000279454700084
PM 20546556
ER
PT J
AU Yang, YG
AF Yang, Yong-Guang
TI CD47 in xenograft rejection and tolerance induction
SO XENOTRANSPLANTATION
LA English
DT Article
DE CD47; macrophage; signaling regulatory protein alpha; tolerance;
xenotransplantation
ID INTEGRIN-ASSOCIATED PROTEIN; DONOR-SPECIFIC TRANSFUSION; T-CELL
TOLERANCE; PORCINE ENDOTHELIAL-CELLS; SIGNAL-REGULATORY PROTEIN;
HEMATOPOIETIC STEM-CELLS; HUMAN IMMUNE-SYSTEM; HUMAN NK CELLS; MIXED
CHIMERISM; DENDRITIC CELLS
AB Robust immune responses to xenografts remain a major obstacle to clinical translation of xenotransplantation, which could otherwise be a potential solution to the worldwide shortage of organ donors. The more vigorous xenograft rejection relative to allograft rejection is largely accounted for by the extensive genetic disparities between the donor and recipient. Xenografts activate host immunity not only by expressing immunogenic xenoantigens that provide the targets for immune recognition and rejection, but also by lacking ligands for the host immune inhibitory receptors. This review is focused on recent findings regarding the role of CD47, a ligand of an immune inhibitory receptor SIRP alpha, in xenograft rejection and induction of xenotolerance.
C1 [Yang, Yong-Guang] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA.
RP Yang, YG (reprint author), Columbia Univ, Med Ctr, Columbia Ctr Translat Immunol, 630 W 168th St,PS17-514, New York, NY 10032 USA.
EM yy2324@columbia.edu
FU NIH [RO1 AI064569, PO1 AI045897]; JDRF [1-2005-72]; ROTRF [848155553]
FX The author thanks Dr. Robert Hawley for critical reading of the
manuscript. The work from the author's laboratory discussed in this
review was supported by grants from NIH (RO1 AI064569 and PO1 AI045897),
JDRF (1-2005-72), and ROTRF (#848155553).
NR 82
TC 13
Z9 16
U1 1
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0908-665X
J9 XENOTRANSPLANTATION
JI Xenotransplantation
PD JUL-AUG
PY 2010
VL 17
IS 4
BP 267
EP 273
DI 10.1111/j.1399-3089.2010.00601.x
PG 7
WC Medicine, Research & Experimental; Transplantation
SC Research & Experimental Medicine; Transplantation
GA 640RQ
UT WOS:000281070200003
PM 20723199
ER
PT J
AU Griesemer, A
Liang, F
Hirakata, A
Hirsh, E
Lo, D
Okumi, M
Sykes, M
Yamada, K
Huang, CA
Sachs, DH
AF Griesemer, Adam
Liang, Fan
Hirakata, Atsushi
Hirsh, Erica
Lo, Diana
Okumi, Masayoshi
Sykes, Megan
Yamada, Kazuhiko
Huang, Christene A.
Sachs, David H.
TI Occurrence of specific humoral non-responsiveness to swine antigens
following administration of GalT-KO bone marrow to baboons
SO XENOTRANSPLANTATION
LA English
DT Article
DE bone marrow; chimerism; GalT-Ko; tolerance; xenotransplantation
ID HEMATOPOIETIC-CELL TRANSPLANTATION; NONLETHAL PREPARATIVE REGIMEN;
THROMBOTIC MICROANGIOPATHY; MONOCLONAL-ANTIBODIES; TOLERANCE INDUCTION;
ALLOGRAFT TOLERANCE; NONHUMAN-PRIMATES; NUCLEAR TRANSFER; MIXED
CHIMERISM; MINIATURE SWINE
AB Background:
Hematopoietic chimerism induces transplantation tolerance across allogeneic and xenogeneic barriers, but has been difficult to achieve in the pig-to-primate model. We have now utilized swine with knockout of the gene coding for alpha-1,3-galactosyltransferase (GalT-KO pigs) as bone marrow donors in an attempt to achieve chimerism and tolerance by avoiding the effects of natural antibodies to Gal determinants on pig hematopoietic cells.
Methods:
Baboons (n = 4; Baboons 1 to 4 = B156, B158, B167, and B175, respectively) were splenectomized and conditioned with TBI (150 cGy), thymic irradiation (700 cGy), T cell depletion with rabbit anti-thymocyte globulin (rATG) and rat anti-primate CD2 (LoCD2b), and received FK506 and supportive therapy for 28 days. All animals received GalT-KO bone marrow (1 to 2 x 109 cells/kg) in two fractions on days 0 and 2, and were thereafter monitored for the presence of pig cells by flow cytometry, for porcine progenitor cells by PCR of BM colony-forming units, and for cellular reactivity to pig cells by mixed lymphocyte reaction (MLR). In vitro antibody formation to LoCD2b and rATG was tested by ELISA; antibody reactivity to GalT-KO pig cells was tested by flow cytometry and cytotoxicity assays. Additionally, Baboons 3 and 4 received orthotopic kidney transplants on days 17 and 2, respectively, to test the potential impact of the protocol on renal transplantation.
Results:
None of the animals showed detectable pig cells by flow cytometry for more than 12 h post-BM infusion. However, porcine progenitor cell engraftment, as evidenced by pig-derived colony forming units in the BM, as well as peripheral microchimerism in the thymus, lymph node, and peripheral blood was detected by PCR in baboons 1 and 2 for at least 28 days post-transplant. ELISA results confirmed humoral immunocompetence at time of transplantation as antibody titers to rat (LoCD2b) and rabbit (ATG) increased within 2 weeks. However, no induced antibodies to GalT-KO pig cells or increased donor specific cytotoxicity was detectable by flow cytometry. In contrast, baboons 3 and 4 developed serum antibodies to pig cells as well as to rat and rabbit immunoglobulin by day 14. Retrospective analysis revealed that although all four baboons possessed low levels of antibody-mediated cytotoxicity to GalT-KO cells prior to transplantation, the two baboons (3 and 4) that became sensitized to pig cells (and rejected pig kidneys) had relatively high pre-transplantation titers of anti-non-Gal IgG detectable by flow cytometry, whereas baboons 1 and 2 had undetectable titers.
Conclusions:
Engraftment and specific non-responsiveness to pig cells has been achieved in two of four baboons following GalT-KO pig-to-baboon BMT. Engraftment correlated with absence of preformed anti-non-Gal IgG serum antibodies. These results are encouraging with regard to the possibility of achieving transplantation tolerance across this xenogeneic barrier.
C1 [Sachs, David H.] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Sachs, DH (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Bldg 149-9019,13th St, Boston, MA 02129 USA.
EM david.sachs@tbrc.mgh.harvard.edu
FU NIAID NIH HHS [P01 AI045897-09, R01 AI084657, P01 AI045897]
NR 35
TC 17
Z9 18
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0908-665X
J9 XENOTRANSPLANTATION
JI Xenotransplantation
PD JUL-AUG
PY 2010
VL 17
IS 4
BP 300
EP 312
DI 10.1111/j.1399-3089.2010.00600.x
PG 13
WC Medicine, Research & Experimental; Transplantation
SC Research & Experimental Medicine; Transplantation
GA 640RQ
UT WOS:000281070200006
PM 20723202
ER
PT J
AU Jang, E
Chung, DC
AF Jang, Eunjeong
Chung, Daniel C.
TI Hereditary Colon Cancer: Lynch Syndrome
SO GUT AND LIVER
LA English
DT Review
DE Lynch syndrome; Mismatch repair gene; Microsatellite instability;
Immunohistochemistry; Hereditary nonpolyposis colon cancer; Colon cancer
ID NONPOLYPOSIS COLORECTAL-CANCER; MSH2 MUTATION CARRIERS;
MUIR-TORRE-SYNDROME; REPAIR GENE-MUTATIONS; INHERITED PREDISPOSITION;
GERMLINE EPIMUTATIONS; ENDOMETRIAL CANCER; HMSH2 GENE; RISK; MLH1
AB Lynch syndrome is the most common familial colorectal cancer syndrome. It is linked to germline mutations in one of four DNA mismatch repair (MMR) genes. A comprehensive family history is one important way to identify at-risk individuals. The elucidation of the molecular genetics of this syndrome has made it possible to screen for the disorder with molecular tests. Microsatellite instability and/or immunohistochemistry followed by germline testing for mutations in MMR genes is now a standard approach for clinically suspected cases. Correctly recognizing Lynch syndrome is essential for the application of appropriate screening and surveillance measures. Close surveillance and risk-reducing operations can decrease cancer-related mortality. In addition, counseling is an important component of the management of any family with Lynch syndrome. (Gut Liver 2010;4:151-160)
C1 [Chung, Daniel C.] Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Boston, MA 02114 USA.
[Chung, Daniel C.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Chung, DC (reprint author), Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, 55 Fruit St,GRJ 825, Boston, MA 02114 USA.
EM dchung@partners.org
NR 43
TC 6
Z9 7
U1 1
U2 9
PU EDITORIAL OFFICE GUT & LIVER
PI SEOUL
PA 305 LOTTE GOLD ROSE II, 890-59, DAECHI 4-DONG, GANGNAM-GU, SEOUL,
135-839, SOUTH KOREA
SN 1976-2283
J9 GUT LIVER
JI Gut Liver
PD JUN 30
PY 2010
VL 4
IS 2
BP 151
EP 160
DI 10.5009/gnl.2010.4.2.151
PG 10
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 611WK
UT WOS:000278855200001
PM 20559516
ER
PT J
AU Wyeth, MS
Zhang, NH
Mody, I
Houser, CR
AF Wyeth, Megan S.
Zhang, Nianhui
Mody, Istvan
Houser, Carolyn R.
TI Selective Reduction of Cholecystokinin-Positive Basket Cell Innervation
in a Model of Temporal Lobe Epilepsy
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID HIPPOCAMPAL NETWORK OSCILLATIONS; CB1 CANNABINOID RECEPTOR; CA1
PYRAMIDAL CELLS; GABAERGIC INHIBITION; ENDOCANNABINOID SYSTEM; STATUS
EPILEPTICUS; MOUSE HIPPOCAMPUS; AXON TERMINALS; GABA RELEASE; IN-VIVO
AB Perisomatic inhibition from basket cells plays an important role in regulating pyramidal cell output. Two major subclasses of CA1 basket cells can be identified based on their expression of either cholecystokinin (CCK) or parvalbumin. This study examined their fates in the mouse pilocarpine model of temporal lobe epilepsy. Overall, immunohistochemical labeling of GABAergic boutons in the pyramidal cell layer of CA1 was preserved in the mouse model. However, CCK-labeled boutons in this layer were chronically reduced, whereas parvalbumin-containing boutons were conserved. Immunohistochemistry for cannabinoid receptor 1 (CB(1)), another marker for CCK-containing basket cells, also labeled fewer boutons in pilocarpine-treated mice. Hours after status epilepticus, electron microscopy revealed dark degenerating terminals in the pyramidal cell layer with lingering CCK and CB(1) immunoreactivity. In mice with recurrent seizures, carbachol-induced enhancement of spontaneous IPSCs (sIPSCs) originating from CCK-containing basket cells was accordingly reduced in CA1 pyramidal cells. By suppressing sIPSCs from CCK-expressing basket cells, a CB(1) agonist reverted the stimulatory effects of carbachol in naive mice to levels comparable with those observed in cells from epileptic mice. The agatoxin-sensitive component of CA1 pyramidal cell sIPSCs from parvalbumin-containing interneurons was increased in pilocarpine-treated mice, and miniature IPSCs were reduced, paralleling the decrease in CCK-labeled terminals. Altogether, the findings are consistent with selective reduction in perisomatic CA1 pyramidal cell innervation from CCK-expressing basket cells in mice with spontaneous seizures and a greater reliance on persisting parvalbumin innervation. This differential alteration in inhibition may contribute to the vulnerability of the network to seizure activity.
C1 [Houser, Carolyn R.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA.
[Mody, Istvan] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol & Physiol, Los Angeles, CA 90095 USA.
[Mody, Istvan; Houser, Carolyn R.] Univ Calif Los Angeles, David Geffen Sch Med, Brain Res Inst, Los Angeles, CA 90095 USA.
[Houser, Carolyn R.] Vet Adm Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA 90073 USA.
RP Houser, CR (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, CHS 73-235,10833 Le Conte Ave, Los Angeles, CA 90095 USA.
EM houser@mednet.ucla.edu
FU National Institutes of Health [NS046524, NS002808, NS035985]; Veterans
Affairs Medical Research Funds; University of California
FX This work was supported by National Institutes of Health Grants NS046524
(C. R. H.), NS002808 (I. M.), and NS035985 (I. M.), Veterans Affairs
Medical Research Funds (C. R. H.), and a University of California, Los
Angeles Graduate Research Mentorship Fellowship (M. S. W.). Antibody
9303 raised against cholecystokinin was kindly provided by
CURE/Digestive Diseases Research Center, Antibody/Radioimmunoassay Core,
National Institutes of Health Grant DK41301. We are grateful to Drs. Ken
Mackie and Marco Celio for generously providing antibodies to
cannabinoid receptor 1 and parvalbumin, respectively. We thank Dr.
Zechun Peng, Christine Huang, and Yliana Cetina for skilled help with
tissue preparation and Drs. Vijayalakshmi Santhakumar and Edward Mann
for their assistance with electrophysiology.
NR 71
TC 43
Z9 45
U1 0
U2 2
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 JUN 30
PY 2010
VL 30
IS 26
BP 8993
EP 9006
DI 10.1523/JNEUROSCI.1183-10.2010
PG 14
WC Neurosciences
SC Neurosciences & Neurology
GA 621LY
UT WOS:000279581500031
PM 20592220
ER
PT J
AU Buhlmann, U
Glaesmer, H
Mewes, R
Fama, JM
Wilhelm, S
Brahler, E
Rief, W
AF Buhlmann, Ulrike
Glaesmer, Heide
Mewes, Ricarda
Fama, Jeanne M.
Wilhelm, Sabine
Braehler, Elmar
Rief, Winfried
TI Updates on the prevalence of body dysmorphic disorder: A
population-based survey
SO PSYCHIATRY RESEARCH
LA English
DT Article
DE Appearance concerns; Body image; Prevalence; Nation-wide survey;
Suicidality; Cosmetic surgery; Gender difference
ID OBSESSIVE-COMPULSIVE DISORDER; CLINICAL-FEATURES; IMAGINED UGLINESS;
SAMPLE; SOMATIZATION; THERAPY
AB Body dysmorphic disorder (BDD) is characterised by a preoccupation with perceived defects in one's appearance, which leads to significant distress and/or impairment. Although several studies have investigated the prevalence of BDD, many studies have methodological limitations (e.g., small sample sizes and student populations), and studies on the prevalence of BDD in the general population are limited. In the current study, 2510 individuals participated in a representative German nationwide survey. Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) criteria for BDD and associated characteristics such as suicidality and the prevalence of plastic surgeries were examined using self-report questionnaires. The prevalence of current BDD was 1.8% (N=45). Further, individuals with BDD, relative to individuals without BDD, reported significantly more often a history of cosmetic surgery (15.6% vs. 3.0%), higher rates of suicidal ideation (31.0% vs. 3.5%) and suicide attempts due to appearance concerns (22.2% vs. 2.1%). The current findings are consistent with previous findings, indicating that self-reported BDD is a common disorder associated with significant morbidity. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
C1 [Buhlmann, Ulrike] Humboldt Univ, Dept Clin Psychol, D-12489 Berlin, Germany.
[Glaesmer, Heide; Braehler, Elmar] Univ Leipzig, Dept Med Psychol & Sociol, D-04103 Leipzig, Germany.
[Mewes, Ricarda; Rief, Winfried] Univ Marburg, Dept Psychol, D-35037 Marburg, Germany.
[Fama, Jeanne M.; Wilhelm, Sabine] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Fama, Jeanne M.; Wilhelm, Sabine] Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Buhlmann, U (reprint author), Humboldt Univ, Dept Clin Psychol, Rudower Chaussee 18, D-12489 Berlin, Germany.
EM ulrike.buhlmann@hu-berlin.de
NR 19
TC 90
Z9 90
U1 1
U2 19
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0165-1781
J9 PSYCHIAT RES
JI Psychiatry Res.
PD JUN 30
PY 2010
VL 178
IS 1
BP 171
EP 175
DI 10.1016/j.psychres.2009.05.002
PG 5
WC Psychiatry
SC Psychiatry
GA 620HI
UT WOS:000279489400031
PM 20452057
ER
PT J
AU Lassen, U
Molife, LR
Sorensen, M
Engelholm, SA
Vidal, L
Sinha, R
Penson, RT
Buhl-Jensen, P
Crowley, E
Tjornelund, J
Knoblauch, P
de Bono, JS
AF Lassen, U.
Molife, L. R.
Sorensen, M.
Engelholm, S-A
Vidal, L.
Sinha, R.
Penson, R. T.
Buhl-Jensen, P.
Crowley, E.
Tjornelund, J.
Knoblauch, P.
de Bono, J. S.
TI A phase I study of the safety and pharmacokinetics of the histone
deacetylase inhibitor belinostat administered in combination with
carboplatin and/or paclitaxel in patients with solid tumours
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE HDAC; belinostat; carboplatin; paclitaxel; BelCaP
ID TOPOISOMERASE-II; TRIAL; CANCER; VORINOSTAT; PXD101; ACID
AB BACKGROUND: This phase I study assessed the maximum tolerated dose, dose-limiting toxicity (DLT) and pharmacokinetics of belinostat with carboplatin and paclitaxel and the anti-tumour activity of the combination in solid tumours.
METHODS: Cohorts of three to six patients were treated with escalating doses of belinostat administered intravenously once daily, days 1-5 q21 days; on day 3, carboplatin (area under the curve (AUC) 5) and/or paclitaxel (175 mgm(-2)) were administered 2-3 h after the end of the belinostat infusion.
RESULTS: In all 23 patients received 600-1000 mgm(-2) per day of belinostat with carboplatin and/or paclitaxel. No DLT was observed. The maximal administered dose of belinostat was 1000 mgm(-2) per day for days 1-5, with paclitaxel (175 mgm-2) and carboplatin AUC 5 administered on day 3. Grade III/IV adverse events were (n; %): leucopenia (5; 22%), neutropenia (7; 30%), thrombocytopenia (3; 13%) anaemia (1; 4%), peripheral sensory neuropathy (2; 9%), fatigue (1; 4%), vomiting (1; 4%) and myalgia (1; 4%). The pharmacokinetics of belinostat, paclitaxel and carboplatin were unaltered by the concurrent administration. There were two partial responses (one rectal cancer and one pancreatic cancer). A third patient (mixed mullerian tumour of ovarian origin) showed a complete CA-125 response. In addition, six patients showed a stable disease lasting >= 6 months.
CONCLUSION: The combination was well tolerated, with no evidence of pharmacokinetic interaction. Further evaluation of anti-tumour activity is warranted. British Journal of Cancer (2010) 103, 12-17. doi:10.1038/sj.bjc.6605726 www.bjcancer.com Published online 15 June 2010 (C) 2010 Cancer Research UK
C1 [Lassen, U.; Sorensen, M.; Engelholm, S-A] Univ Hosp, Rigshosp, Dept Oncol, DK-2100 Copenhagen, Denmark.
[Molife, L. R.; Vidal, L.; Sinha, R.; de Bono, J. S.] Royal Marsden Hosp, Inst Canc Res, Drug Dev Unit, Sutton SM2 5PT, Surrey, England.
[Penson, R. T.] Massachusetts Gen Hosp, Dept Haematol Oncol, Boston, MA 02114 USA.
[Buhl-Jensen, P.; Crowley, E.; Tjornelund, J.; Knoblauch, P.] TopoTaget AS, DK-2100 Copenhagen, Denmark.
RP Lassen, U (reprint author), Univ Hosp, Rigshosp, Dept Oncol, DK-2100 Copenhagen, Denmark.
EM ulrik.lassen@rh.regionh.dk
OI Mau-Sorensen, Morten/0000-0003-2235-1250; Lassen,
Ulrik/0000-0002-3865-4574
NR 22
TC 39
Z9 41
U1 0
U2 2
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 JUN 29
PY 2010
VL 103
IS 1
BP 12
EP 17
DI 10.1038/sj.bjc.6605726
PG 6
WC Oncology
SC Oncology
GA 618SA
UT WOS:000279374800003
PM 20588278
ER
PT J
AU Chan, PS
Oetgen, WJ
Buchanan, D
Mitchell, K
Fiocchi, FF
Tang, FM
Jones, PG
Breeding, T
Thrutchley, D
Rumsfeld, JS
Spertus, JA
AF Chan, Paul S.
Oetgen, William J.
Buchanan, Donna
Mitchell, Kristi
Fiocchi, Fran F.
Tang, Fengming
Jones, Philip G.
Breeding, Tracie
Thrutchley, Duane
Rumsfeld, John S.
Spertus, John A.
TI Cardiac Performance Measure Compliance in Outpatients
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
DE performance measure; compliance; quality of care; outpatient
ID ATRIAL-FIBRILLATION; AMERICAN-COLLEGE; QUALITY; CARE; CLASSIFICATION;
IMPROVEMENT; REGISTRY; STROKE
AB Objectives We examined compliance with performance measures for 14,464 patients enrolled from July 2008 through June 2009 into the American College of Cardiology's PINNACLE (Practice Innovation And Clinical Excellence) program to provide initial insights into the quality of outpatient cardiac care.
Background Little is known about the quality of care of outpatients with coronary artery disease (CAD), heart failure, and atrial fibrillation, and whether sex and racial disparities exist in the treatment of outpatients.
Methods The PINNACLE program is the first, national, prospective office-based quality improvement program of cardiac patients designed, in part, to capture, report, and improve outpatient performance measure compliance. We examined the proportion of patients whose care was compliant with established American College of Cardiology, American Heart Association, and American Medical Association-Physician Consortium for Performance Improvement (ACC/AHA/PCPI) performance measures for CAD, heart failure, and atrial fibrillation.
Results There were 14,464 unique patients enrolled from 27 U. S. practices, accounting for 18,021 clinical visits. Of these, 8,132 (56.4%) had CAD, 5,012 (34.7%) had heart failure, and 2,786 (19.3%) had nonvalvular atrial fibrillation. Data from the PINNACLE program were feasibly collected for 24 of 25 ACC/AHA/PCPI performance measures. Compliance with performance measures ranged from being very low (e. g., 13.3% of CAD patients screened for diabetes mellitus) to very high (e. g., 96.7% of heart failure patients with blood pressure assessments), with moderate (70% to 90%) compliance observed for most performance measures. For 3 performance measures, there were small differences in compliance rates by race or sex.
Conclusions For more than 14,000 patients enrolled from 27 practices in the outpatient PINNACLE program, we found that compliance with performance measures was variable, even after accounting for exclusion criteria, suggesting an important opportunity to improve the quality of outpatient care. (J Am Coll Cardiol 2010;56:8-14) (C) 2010 by the American College of Cardiology Foundation
C1 [Chan, Paul S.; Buchanan, Donna; Tang, Fengming; Jones, Philip G.; Breeding, Tracie; Thrutchley, Duane; Spertus, John A.] St Lukes Hosp, Mid Amer Heart Inst, Kansas City, MO 64111 USA.
[Chan, Paul S.; Spertus, John A.] Univ Missouri, Kansas City, MO 64110 USA.
[Oetgen, William J.] Georgetown Univ, Sch Med, Washington, DC USA.
[Mitchell, Kristi; Fiocchi, Fran F.] Amer Coll Cardiol, Washington, DC USA.
[Rumsfeld, John S.] Univ Colorado, Denver Med Ctr, Denver, CO 80202 USA.
[Rumsfeld, John S.] Denver VA Med Ctr, Denver, CO USA.
RP Chan, PS (reprint author), St Lukes Hosp, Mid Amer Heart Inst, 5th Floor,4401 Wornall Rd, Kansas City, MO 64111 USA.
EM pchan@cc-pc.com
RI Max, Mad/E-5238-2010
OI Max, Mad/0000-0001-6966-6829
FU Bristol-Myers Squibb/Sanofi Pharmaceuticals; American College of
Cardiology; American College of Cardiology Foundation; AMA; NHLBI;
Johnson Johnson; Eli Lilly; BMS/Sanofi; Evoheart
FX From the *Mid America Heart Institute and dagger University of Missouri,
Kansas City, Missouri; Georgetown University School of Medicine and the
double dagger American College of Cardiology, Washington, DC; and the
parallel to University of Colorado at Denver Medical Center and Denver
VA Medical Center, Denver, Colorado. Bristol-Myers Squibb/Sanofi
Pharmaceuticals and the American College of Cardiology provide
operational funding for the PINNACLE program. Ms. Fiocchi and Mitchell
are employees of the American College of Cardiology. Drs. Chan and
Spertus and Mr. Jones are affiliated with the Mid America Heart
Institute, which is the major analytic center for the PINNACLE program
and receives funding from the American College of Cardiology for this
role. Dr. Rumsfeld is the Chief Science Officer of the NCDR. Dr. Spertus
is supported by a contract from the American College of Cardiology
Foundation; receives grant support from AMA, NHLBI, Anger, Johnson &
Johnson, Eli Lilly, BMS/Sanofi, and Evoheart; and is a consultant for
United-Healthcare, Anger, and St. Jude Medical.
NR 16
TC 61
Z9 62
U1 0
U2 6
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 JUN 29
PY 2010
VL 56
IS 1
BP 8
EP 14
DI 10.1016/j.jacc.2010.03.043
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 614AV
UT WOS:000279028300002
PM 20620710
ER
PT J
AU Viswanath, K
Ackerson, LK
Sorensen, G
Gupta, PC
AF Viswanath, K.
Ackerson, Leland K.
Sorensen, Glorian
Gupta, Prakash C.
TI Movies and TV Influence Tobacco Use in India: Findings from a National
Survey
SO PLOS ONE
LA English
DT Article
ID YOUTH SMOKING; MORTALITY
AB Background: Exposure to mass media may impact the use of tobacco, a major source of illness and death in India. The objective is to test the association of self-reported tobacco smoking and chewing with frequency of use of four types of mass media: newspapers, radio, television, and movies.
Methodology/Principal Findings: We analyzed data from a sex-stratified nationally-representative cross-sectional survey of 123,768 women and 74,068 men in India. All models controlled for wealth, education, caste, occupation, urbanicity, religion, marital status, and age. In fully-adjusted models, monthly cinema attendance is associated with increased smoking among women (relative risk [RR]: 1.55; 95% confidence interval [CI]: 1.04-2.31) and men (RR: 1.17; 95% CI: 1.12-1.23) and increased tobacco chewing among men (RR: 1.15; 95% CI: 1.11-1.20). Daily television and radio use is associated with higher likelihood of tobacco chewing among men and women, while daily newspaper use is related to lower likelihood of tobacco chewing among women.
Conclusion/Significance: In India, exposure to visual mass media may contribute to increased tobacco consumption in men and women, while newspaper use may suppress the use of tobacco chewing in women. Future studies should investigate the role that different types of media content and media play in influencing other health behaviors.
C1 [Viswanath, K.; Sorensen, Glorian] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA.
[Viswanath, K.; Sorensen, Glorian] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA.
[Ackerson, Leland K.] Univ Massachusetts Lowell, Dept Community Hlth & Sustainabil, Lowell, MA USA.
[Gupta, Prakash C.] Healis Sekhsaria Inst Publ Hlth, Navi Mumbai, India.
RP Viswanath, K (reprint author), Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, 665 Huntington Ave, Boston, MA 02115 USA.
EM vish_viswanath@dfci.harvard.edu
OI Viswanath, Kiron/0000-0003-4640-1910
FU American Legacy Foundation; National Cancer Institute
FX K. Viswanath acknowledges the support of the Dana-Farber Harvard Cancer
Center and the Tobacco Research Network on Disparities (TReND) funded by
the American Legacy Foundation (http://www.legacyforhealth.org/) and the
National Cancer Institute (http://www.cancer.gov/). The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 28
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Z9 11
U1 0
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 JUN 29
PY 2010
VL 5
IS 6
AR e11365
DI 10.1371/journal.pone.0011365
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 618QD
UT WOS:000279369900014
PM 20614005
ER
PT J
AU Zhang, F
Maeder, ML
Unger-Wallace, E
Hoshaw, JP
Reyon, D
Christian, M
Li, XH
Pierick, CJ
Dobbs, D
Peterson, T
Joung, JK
Voytas, DF
AF Zhang, Feng
Maeder, Morgan L.
Unger-Wallace, Erica
Hoshaw, Justin P.
Reyon, Deepak
Christian, Michelle
Li, Xiaohong
Pierick, Christopher J.
Dobbs, Drena
Peterson, Thomas
Joung, J. Keith
Voytas, Daniel F.
TI High frequency targeted mutagenesis in Arabidopsis thaliana using zinc
finger nucleases
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE nonhomologous end-joining; gene knockout; alcohol dehydrogenase;
chalcone synthase
ID POOL ENGINEERING OPEN; TRANSGENIC PLANTS; GENE DISRUPTION; STEM-CELLS;
FLORAL DIP; EXPRESSION; MUTANTS; ARRAYS; TRANSFORMATION; INFORMATION
AB We report here an efficient method for targeted mutagenesis of Arabidopsis genes through regulated expression of zinc finger nucleases (ZFNs)-enzymes engineered to create DNA double-strand breaks at specific target loci. ZFNs recognizing the Arabidopsis ADH1 and TT4 genes were made by Oligomerized Pool ENgineering (OPEN)-a publicly available, selection-based platform that yields high quality zinc finger arrays. The ADH1 and TT4 ZFNs were placed under control of an estrogen-inducible promoter and introduced into Arabidopsis plants by floral-dip transformation. Primary transgenic Arabidopsis seedlings induced to express the ADH1 or TT4 ZFNs exhibited somatic mutation frequencies of 7% or 16%, respectively. The induced mutations were typically insertions or deletions (1-142 bp) that were localized at the ZFN cleavage site and likely derived from imprecise repair of chromosome breaks by nonhomologous end-joining. Mutations were transmitted to the next generation for 69% of primary transgenics expressing the ADH1 ZFNs and 33% of transgenics expressing the TT4 ZFNs. Furthermore, approximate to 20% of the mutant-producing plants were homozygous for mutations at ADH1 or TT4, indicating that both alleles were disrupted. ADH1 and TT4 were chosen as targets for this study because of their selectable or screenable phenotypes (adh1, allyl alcohol resistance; tt4, lack of anthocyanins in the seed coat). However, the high frequency of observed ZFN-induced mutagenesis suggests that targeted mutations can readily be recovered by simply screening progeny of primary transgenic plants by PCR and DNA sequencing. Taken together, our results suggest that it should now be possible to obtain mutations in any Arabidopsis target gene regardless of its mutant phenotype.
C1 [Zhang, Feng; Hoshaw, Justin P.; Christian, Michelle; Li, Xiaohong; Pierick, Christopher J.; Voytas, Daniel F.] Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN 55455 USA.
[Zhang, Feng; Hoshaw, Justin P.; Christian, Michelle; Li, Xiaohong; Pierick, Christopher J.; Voytas, Daniel F.] Univ Minnesota, Ctr Genome Engn, Minneapolis, MN 55455 USA.
[Maeder, Morgan L.; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA 02129 USA.
[Maeder, Morgan L.; Joung, J. Keith] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA 02129 USA.
[Maeder, Morgan L.; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA.
[Reyon, Deepak] Iowa State Univ, Interdept Grad Program Bioinformat & Computat Bio, Ames, IA 50011 USA.
[Unger-Wallace, Erica; Reyon, Deepak; Dobbs, Drena; Peterson, Thomas] Iowa State Univ, Dept Genet Dev & Cell Biol, Ames, IA 50011 USA.
[Joung, J. Keith] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RP Voytas, DF (reprint author), Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN 55455 USA.
EM voytas@umn.edu
RI li, xiaohong/F-1608-2010
FU National Science Foundation [MCB 0209818, DBI 0923827]; National
Institutes of Health [R01 GM069906, R24 GM078369, R21 RR024189];
Massachusetts General Hospital Pathology Service
FX We thank David Wright for assistance in ZFN design, Yi Hou for help with
the Arabidopsis protoplast assay, and Kenichi Tsuda for help with
plasmid construction. The National Science Foundation supported work
carried out by F.Z., J.P.H., M.C., and D.F.V. (MCB 0209818) and D.R. and
D.D. (DBI 0923827). M.L.M. and J.K.J. are supported by National
Institutes of Health Grants R01 GM069906, R24 GM078369, and R21 RR024189
and the Massachusetts General Hospital Pathology Service.
NR 48
TC 148
Z9 167
U1 4
U2 45
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUN 29
PY 2010
VL 107
IS 26
BP 12028
EP 12033
DI 10.1073/pnas.0914991107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 618DT
UT WOS:000279332300067
PM 20508152
ER
PT J
AU Walling, AM
Asch, SM
Lorenz, KA
Roth, CP
Barry, T
Kahn, KL
Wenger, NS
AF Walling, Anne M.
Asch, Steven M.
Lorenz, Karl A.
Roth, Carol P.
Barry, Tod
Kahn, Katherine L.
Wenger, Neil S.
TI The Quality of Care Provided to Hospitalized Patients at the End of Life
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Article; Proceedings Paper
CT 32nd Annual Meeting of the Society-of-General-Internal-Medicine
CY MAY 13-16, 2009
CL Miami, FL
SP Soc Gen Internal Med
ID MEDICAL-CARE; VULNERABLE ELDERS; SUSTAINING TREATMENTS; OLDER PATIENTS;
PREFERENCES; DISCUSSIONS; OUTCOMES; COMMUNITY; SURVIVAL; HOSPICE
AB Background: Patients in American hospitals receive intensive medical treatments. However, when lifesaving treatments are unsuccessful, patients often die in the hospital with distressing symptoms while receiving burdensome care. Systematic measurement of the quality of care planning and symptom palliation is needed.
Methods: Medical records were abstracted using 16 Assessing Care of Vulnerable Elders quality indicators within the domains of end-of-life care and pain management designed to measure the quality of the dying experience for adult decedents (n = 496) hospitalized for at least 3 days between April 2005 and April 2006 at a university medical center recognized for providing intensive care for the seriously ill.
Results: Over half of the patients (mean age, 62 years; 47% were women) were admitted to the hospital with end-stage disease, and 28% were 75 years or older. One-third of the patients required extubation from mechanical ventilation prior to death, and 15% died while receiving cardiopulmonary resuscitation. Overall, patients received recommended care for 70% of applicable indicators (range, 25%-100%). Goals of care were addressed in a timely fashion for patients admitted to the intensive care unit approximately half of the time, whereas pain assessments (94%) and treatments for pain (95%) and dyspnea (87%) were performed with fidelity. Follow-up for distressing symptoms was performed less well than initial assessment, and 29% of patients extubated in anticipation of death had documented dyspnea assessments.
Conclusion: A practical, medical chart-based assessment identified discrete deficiencies in care planning and symptom palliation that can be targeted to improve care for patients dying in the hospital.
C1 [Walling, Anne M.; Kahn, Katherine L.; Wenger, Neil S.] Univ Calif Los Angeles, Div Gen Internal Med & Hlth Serv Res, David Geffen Sch Med, Los Angeles, CA 90024 USA.
[Walling, Anne M.; Wenger, Neil S.] Univ Calif Los Angeles, Hlth Syst Eth Ctr, Los Angeles, CA 90024 USA.
[Barry, Tod] Univ Calif Los Angeles, Ctr Patient Safety & Qual, Los Angeles, CA 90024 USA.
[Asch, Steven M.; Lorenz, Karl A.] Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA.
[Asch, Steven M.; Roth, Carol P.; Kahn, Katherine L.; Wenger, Neil S.] RAND Corp, RAND Hlth, Santa Monica, CA USA.
RP Walling, AM (reprint author), Univ Calif Los Angeles, Div Gen Internal Med, 911 Broxton Plaza, Los Angeles, CA 90024 USA.
EM awalling@mednet.ucla.edu
RI Baolian W, Baolian W/O-6769-2015
FU BHP HRSA HHS [T32 PE19001]; NIA NIH HHS [L30 AG030993, L30 AG030993-01]
NR 43
TC 49
Z9 49
U1 3
U2 10
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0003-9926
J9 ARCH INTERN MED
JI Arch. Intern. Med.
PD JUN 28
PY 2010
VL 170
IS 12
BP 1057
EP 1063
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 616XO
UT WOS:000279245000012
PM 20585072
ER
PT J
AU Bishop, TF
Federman, AD
Keyhani, S
AF Bishop, Tara F.
Federman, Alex D.
Keyhani, Salomeh
TI Physicians' Views on Defensive Medicine: A National Survey
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Letter
C1 [Keyhani, Salomeh] Mt Sinai Sch Med, Dept Hlth Policy, New York, NY 10029 USA.
[Bishop, Tara F.; Federman, Alex D.; Keyhani, Salomeh] Mt Sinai Sch Med, Div Gen Internal Med, New York, NY 10029 USA.
James J Peters Vet Adm Med Ctr, Bronx, NY USA.
RP Keyhani, S (reprint author), Mt Sinai Sch Med, Dept Hlth Policy, 1 Gustave L Levy Pl,Box 1077, New York, NY 10029 USA.
EM salomeh.keyhani@mssm.edu
NR 10
TC 53
Z9 55
U1 1
U2 7
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0003-9926
J9 ARCH INTERN MED
JI Arch. Intern. Med.
PD JUN 28
PY 2010
VL 170
IS 12
BP 1081
EP 1083
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 616XO
UT WOS:000279245000016
PM 20585077
ER
PT J
AU Nagata, T
Uno, H
Perry, MJ
AF Nagata, Takashi
Uno, Hajime
Perry, Melissa J.
TI Clinical consequences of road traffic injuries among the elderly in
Japan
SO BMC PUBLIC HEALTH
LA English
DT Article
ID EMERGENCY; SEVERITY; TRAUMA; PEDESTRIANS; AREA; RISK
AB Background: Road traffic injuries among the elderly have recently become a public health issue; therefore, we investigated the clinical characteristics of such injuries among the elderly in Japan.
Methods: A retrospective study was performed using data from a medium-sized hospital emergency department. Data were extracted from medical records for one year, and patients were categorized into groups ages 18-64, 65-74 and 75+. Variables included demographic characteristics, injury circumstances, and nature of injury. Univariate and bivariate descriptive statistical analyses were performed, and multivariate logistic regression was used to evaluate injury severity and hospital admission by age groups.
Results: A total of 1,656 patients were studied. Patients aged 65+ had more chest wall injury, intracranial injury, lower extremity fracture, and intrathoracic injury than patients aged 18-64.
Conclusions: Injury circumstances and nature of injuries associated with traffic incidents showed different patterns by age groups, particularly among the elderly.
C1 [Nagata, Takashi] Himeno Hosp, Dept Emergency Med, Fukuoka, Japan.
[Nagata, Takashi] Harvard Univ, Sch Publ Hlth, Takemi Program, Dept Int Hlth, Boston, MA 02115 USA.
[Uno, Hajime] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Perry, Melissa J.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA.
RP Nagata, T (reprint author), Himeno Hosp, Dept Emergency Med, Fukuoka, Japan.
EM nagata.takashi@gmail.com
FU Japan Medical Association; Saint Mary's Hospital (SMH)
FX This study was funded by Japan Medical Association and Saint Mary's
Hospital (SMH). We thank Dr. Michio Ide, the former director of SMH for
financial support. We also thank Ms. Keiko Koga at SMH and Danielle
Stockley at Harvard School of Public Health for research assistance. TN
and MP originated and designed the study, interpreted the results, and
commented on drafts of the article. UH carried out the statistical
analysis and calculation, and also gave comments on the manuscript.
NR 30
TC 3
Z9 3
U1 0
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2458
J9 BMC PUBLIC HEALTH
JI BMC Public Health
PD JUN 28
PY 2010
VL 10
AR 375
DI 10.1186/1471-2458-10-375
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 625SE
UT WOS:000279914500001
PM 20584283
ER
PT J
AU Bianchi, MT
Cash, SS
Mietus, J
Peng, CK
Thomas, R
AF Bianchi, Matt T.
Cash, Sydney S.
Mietus, Joseph
Peng, Chung-Kang
Thomas, Robert
TI Obstructive Sleep Apnea Alters Sleep Stage Transition Dynamics
SO PLOS ONE
LA English
DT Article
ID CHRONIC-FATIGUE-SYNDROME; DAYTIME SLEEPINESS; HEART HEALTH; SCALE;
FRAGMENTATION; NEUROBIOLOGY; WAKEFULNESS; DISORDERS; PATTERNS; MODEL
AB Introduction: Enhanced characterization of sleep architecture, compared with routine polysomnographic metrics such as stage percentages and sleep efficiency, may improve the predictive phenotyping of fragmented sleep. One approach involves using stage transition analysis to characterize sleep continuity.
Methods and Principal Findings: We analyzed hypnograms from Sleep Heart Health Study (SHHS) participants using the following stage designations: wake after sleep onset (WASO), non-rapid eye movement (NREM) sleep, and REM sleep. We show that individual patient hypnograms contain insufficient number of bouts to adequately describe the transition kinetics, necessitating pooling of data. We compared a control group of individuals free of medications, obstructive sleep apnea (OSA), medical co-morbidities, or sleepiness (n = 374) with mild (n = 496) or severe OSA (n = 338). WASO, REM sleep, and NREM sleep bout durations exhibited multi-exponential temporal dynamics. The presence of OSA accelerated the "decay'' rate of NREM and REM sleep bouts, resulting in instability manifesting as shorter bouts and increased number of stage transitions. For WASO bouts, previously attributed to a power law process, a multi-exponential decay described the data well. Simulations demonstrated that a multi-exponential process can mimic a power law distribution.
Conclusion and Significance: OSA alters sleep architecture dynamics by decreasing the temporal stability of NREM and REM sleep bouts. Multi-exponential fitting is superior to routine mono-exponential fitting, and may thus provide improved predictive metrics of sleep continuity. However, because a single night of sleep contains insufficient transitions to characterize these dynamics, extended monitoring of sleep, probably at home, would be necessary for individualized clinical application.
C1 [Bianchi, Matt T.; Cash, Sydney S.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Mietus, Joseph; Peng, Chung-Kang] Beth Israel Deaconess Med Ctr, Div Interdisciplinary Med & Biotechnol, Boston, MA 02215 USA.
[Thomas, Robert] Beth Israel Deaconess Med Ctr, Sleep Div, Boston, MA 02215 USA.
RP Bianchi, MT (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
EM mtbianchi@partners.org
RI Peng, Chung-Kang/E-1489-2011
OI Peng, Chung-Kang/0000-0003-3666-9833
FU Department of Neurology, Massachusetts General Hospital; Harvard/MIT
Health Sciences and Technology; Beth Israel Deaconess Medical Center;
Pfizer, Inc.; Merck Co.; [R21HL079248]
FX Fudning: R21HL079248 (RJT); Department of Neurology, Massachusetts
General Hospital, and the Clinical Investigator Training Program:
Harvard/MIT Health Sciences and Technology, Beth Israel Deaconess
Medical Center, in collaboration with Pfizer, Inc. and Merck & Co.
(MTB). This paper represents the work of the authors and not the SHHS.
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 34
TC 39
Z9 39
U1 0
U2 5
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 JUN 28
PY 2010
VL 5
IS 6
AR e11356
DI 10.1371/journal.pone.0011356
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 617DB
UT WOS:000279259900024
PM 20596541
ER
PT J
AU Sahu, N
Morales, JL
Fowell, D
August, A
AF Sahu, Nisebita
Morales, J. Luis
Fowell, Deborah
August, Avery
TI Modeling Susceptibility versus Resistance in Allergic Airway Disease
Reveals Regulation by Tec Kinase Itk
SO PLOS ONE
LA English
DT Article
ID CD4(+) T-CELLS; MICE LACKING; HOUSE-DUST; MURINE MODEL; TYROSINE KINASE;
ASTHMA; ANTIGEN; EXPOSURE; RESPONSES; INFLAMMATION
AB Murine models of allergic asthma have been used to understand the mechanisms of development and pathology in this disease. In addition, knockout mice have contributed significantly to our understanding of the roles of specific molecules and cytokines in these models. However, results can vary significantly depending on the mouse strain used in the model, and in particularly in understanding the effect of specific knockouts. For example, it can be equivocal as to whether specific gene knockouts affect the susceptibility of the mice to developing the disease, or lead to resistance. Here we used a house dust mite model of allergic airway inflammation to examine the response of two strains of mice (C57BL/6 and BALB/c) which differ in their responses in allergic airway inflammation. We demonstrate an algorithm that can facilitate the understanding of the behavior of these models with regards to susceptibility (to allergic airway inflammation) (Saai) or resistance (Raai) in this model. We verify that both C57BL/6 and BALB/c develop disease, but BALB/c mice have higher Saai for development. We then use this approach to show that the absence of the Tec family kinase Itk, which regulates the production of Th2 cytokines, leads to Raai in the C57BL/6 background, but decreases Saai on the BALB/c background. We suggest that the use of such approaches could clarify the behavior of various knockout mice in modeling allergic asthma.
C1 [Sahu, Nisebita; Morales, J. Luis; August, Avery] Penn State Univ, Ctr Mol Immunol & Infect Dis, University Pk, PA 16802 USA.
[Sahu, Nisebita; Morales, J. Luis; August, Avery] Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA.
[Sahu, Nisebita] Penn State Univ, Dept Biochem & Mol Biol, University Pk, PA 16802 USA.
[Fowell, Deborah] Univ Rochester, Sch Med & Dent, Dept Microbiol & Immunol, Rochester, NY 14642 USA.
RP Sahu, N (reprint author), Harvard Univ, Sch Med, Ctr Canc, Massachusetts Gen Hosp,Dept Med, Charlestown, MA USA.
EM averyaugust@cornell.edu
FU National Institutes of Health [AI051626, AI065566, AI073955]; American
Academy of Allergy Asthma and Immunology Strategic Training in Allergy
Research
FX This work was supported by National Institutes of Health grants
AI051626, AI065566 and AI073955 to AA. NS was the recipient of an
American Academy of Allergy Asthma and Immunology Strategic Training in
Allergy Research (ST*AR) Award. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 34
TC 10
Z9 10
U1 0
U2 0
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 JUN 28
PY 2010
VL 5
IS 6
AR e11348
DI 10.1371/journal.pone.0011348
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 617DB
UT WOS:000279259900019
PM 20596543
ER
PT J
AU McCoy, JG
McKenna, JT
Connolly, NP
Poeta, DL
Ling, LM
McCarley, RW
Strecker, RE
AF McCoy, John G.
McKenna, James T.
Connolly, Nina P.
Poeta, Devon L.
Ling, Liming
McCarley, Robert W.
Strecker, Robert E.
TI One week of exposure to intermittent hypoxia impairs attentional
set-shifting in rats
SO BEHAVIOURAL BRAIN RESEARCH
LA English
DT Article
DE Attention; Hypoxia; Sleep apnea syndromes; Discrimination learning;
Animal models
ID OBSTRUCTIVE SLEEP-APNEA; WORKING-MEMORY; COGNITIVE FUNCTION; PREFRONTAL
CORTEX; FRONTAL-CORTEX; DOPAMINE; DEFICITS; HUMANS; MOUSE
AB Intermittent hypoxia (IH), a characteristic of sleep apnea, was modeled in Fischer Brown Norway rats (10 h/day for 7 days) followed by cognitive testing in an attentional set-shifting task. The ability to shift attention from one sensory modality (e.g., odor) to another (e.g., digging medium) was impaired, a finding that could not be attributed to deficits in attention, discrimination, learning, or motor performance. Instead, the deficit is likely to reflect impaired allocation of attentional resources of the working memory system. (C) 2010 Elsevier B.V. All rights reserved.
C1 [McCoy, John G.; McKenna, James T.; Connolly, Nina P.; McCarley, Robert W.; Strecker, Robert E.] VA Boston Healthcare Syst, Brockton, MA 02301 USA.
[McCoy, John G.; McKenna, James T.; Connolly, Nina P.; McCarley, Robert W.; Strecker, Robert E.] Harvard Univ, Sch Med, Neurosci Lab, Brockton, MA 02301 USA.
[McCoy, John G.; Poeta, Devon L.] Stonehill Coll, Dept Psychol, Easton, MA 02357 USA.
[Connolly, Nina P.] Wheaton Coll, Dept Psychol, Norton, MA 02766 USA.
[Ling, Liming] Harvard Univ, Brigham & Womens Hosp, Div Sleep Med, Sch Med, Boston, MA 02115 USA.
RP McCoy, JG (reprint author), VA Boston Healthcare Syst, Res 151-C,940 Belmt St, Brockton, MA 02301 USA.
EM jmccoy1@stonehill.edu
RI McCarley, Robert/N-5562-2014;
OI McCarley, Robert/0000-0001-5705-7495; Poeta, Devon/0000-0002-6286-7182
FU Department of Veteran's Affairs; NIH [HL060292, T32 HL07901, F32
MH070156]
FX This research was supported by the Department of Veteran's Affairs (RES
and RWM), NIH HL060292 (RWM and RES), NIH T32 HL07901 (JTM) and NIH F32
MH070156 (JTM).
NR 31
TC 11
Z9 12
U1 0
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0166-4328
J9 BEHAV BRAIN RES
JI Behav. Brain Res.
PD JUN 26
PY 2010
VL 210
IS 1
BP 123
EP 126
DI 10.1016/j.bbr.2010.01.043
PG 4
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA 597YQ
UT WOS:000277798900016
PM 20122971
ER
PT J
AU Cadwell, K
Patel, KK
Maloney, NS
Liu, TC
Ng, ACY
Storer, CE
Head, RD
Xavier, R
Stappenbeck, TS
Virgin, HW
AF Cadwell, Ken
Patel, Khushbu K.
Maloney, Nicole S.
Liu, Ta-Chiang
Ng, Aylwin C. Y.
Storer, Chad E.
Head, Richard D.
Xavier, Ramnik
Stappenbeck, Thaddeus S.
Virgin, Herbert W.
TI Virus-Plus-Susceptibility Gene Interaction Determines Crohn's Disease
Gene Atg16L1 Phenotypes in Intestine
SO CELL
LA English
DT Article
ID INFLAMMATORY-BOWEL-DISEASE; GENOME-WIDE ASSOCIATION; MURINE NOROVIRUS;
MURINE-NOROVIRUS-1 INFECTION; MONOCLONAL-ANTIBODIES; ULCERATIVE-COLITIS;
INFLUENZA-VIRUS; CELIAC-DISEASE; PANETH CELLS; MOUSE MODEL
AB It is unclear why disease occurs in only a small proportion of persons carrying common risk alleles of disease susceptibility genes. Here we demonstrate that an interaction between a specific virus infection and a mutation in the Crohn's disease susceptibility gene Atg16L1 induces intestinal pathologies in mice. This virus-plus-susceptibility gene interaction generated abnormalities in granule packaging and unique patterns of gene expression in Paneth cells. Further, the response to injury induced by the toxic substance dextran sodium sulfate was fundamentally altered to include pathologies resembling aspects of Crohn's disease. These pathologies triggered by virus-plus-susceptibility gene interaction were dependent on TNF alpha and IFN gamma and were prevented by treatment with broad spectrum antibiotics. Thus, we provide a specific example of how a virus-plus-susceptibility gene interaction can, in combination with additional environmental factors and commensal bacteria, determine the phenotype of hosts carrying common risk alleles for inflammatory disease.
C1 [Cadwell, Ken; Patel, Khushbu K.; Maloney, Nicole S.; Liu, Ta-Chiang; Stappenbeck, Thaddeus S.; Virgin, Herbert W.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
[Virgin, Herbert W.] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA.
[Ng, Aylwin C. Y.; Xavier, Ramnik] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA.
[Ng, Aylwin C. Y.; Xavier, Ramnik] Harvard Univ, Ctr Computat & Integrat Biol, Sch Med, Boston, MA 02114 USA.
[Ng, Aylwin C. Y.; Xavier, Ramnik] MIT, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.
[Ng, Aylwin C. Y.; Xavier, Ramnik] Harvard Univ, Cambridge, MA 02142 USA.
[Storer, Chad E.; Head, Richard D.] Pfizer Global Res & Dev, Inflammat & Immunol Res Unit, St Louis, MO 63017 USA.
[Virgin, Herbert W.] Midwest Reg Ctr Excellence Biodefense & Emerging, St Louis, MO 63110 USA.
RP Stappenbeck, TS (reprint author), Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
EM stappenb@wustl.edu; virgin@wustl.edu
OI Cadwell, Ken/0000-0002-5860-0661
FU Project 5 [U54 AI057160]; Broad Foundation [R01 AI084887]; Damon Runyon
Cancer Research Foundation [DRG-1972-08]; NIH [T32-AI007172]; Pew
Foundation; Washington University Digestive Diseases Research Core
Center [DK52574]; Crohn's and Colitis Foundation of America [DK83756,
DK086502, DK043351]
FX This research was supported by grant U54 AI057160 Project 5 and the
Broad Foundation (K. C., N.M., and H. W. V.), R01 AI084887 (T. S. S. and
H. W. V.), the Lallage Feazel Wall Fellowship DRG-1972-08 from the Damon
Runyon Cancer Research Foundation (K. C.), training grant NIH
T32-AI007172 (N.M.), the Pew Foundation (K. K. P. and T. S. S.),
Washington University Digestive Diseases Research Core Center DK52574,
Pfizer biomedical agreement with Washington University, fellowship award
from the Crohn's and Colitis Foundation of America (A.C.Y.N), and grants
DK83756, DK086502, and DK043351 (R.J.X.). Washington University holds U.
S. patents 7,041,444 B2, 7,264,923, and US 7,455,972 related to growth
and detection of MNV. Washington University and H. W. V. receive income
based on licenses for MNV technology.
NR 71
TC 396
Z9 401
U1 4
U2 33
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD JUN 25
PY 2010
VL 141
IS 7
BP 1135
EP U64
DI 10.1016/j.cell.2010.05.009
PG 18
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 615PV
UT WOS:000279148100011
PM 20602997
ER
PT J
AU Miyazaki-Anzai, S
Levi, M
Kratzer, A
Ting, TC
Lewis, LB
Miyazaki, M
AF Miyazaki-Anzai, Shinobu
Levi, Moshe
Kratzer, Adelheid
Ting, Tabitha C.
Lewis, Linda B.
Miyazaki, Makoto
TI Farnesoid X Receptor Activation Prevents the Development of Vascular
Calcification in ApoE(-/-) Mice With Chronic Kidney Disease
SO CIRCULATION RESEARCH
LA English
DT Article
DE farnesoid X receptor; vascular calcification; chronic kidney disease
ID FXR-MEDIATED REGULATION; BILE-ACID; NUCLEAR RECEPTOR; CELL
CALCIFICATION; GENE-EXPRESSION; METABOLISM; MECHANISMS; ATHEROSCLEROSIS;
INFLAMMATION; DISRUPTION
AB Rationale: Vascular calcification is highly associated with cardiovascular morbidity and mortality, especially in patients with chronic kidney disease. The nuclear receptor farnesoid X receptor (FXR) has been implicated in the control of lipid, carbohydrate and bile acid metabolism in several cell types. Although recent studies have shown that FXR is also expressed in vascular smooth muscle cells, its physiological role in vasculature tissue remains obscure.
Objective: Here, we have examined the role of FXR in vascular calcification.
Methods and Results: The FXR gene, a bile acid nuclear receptor, was highly induced during osteogenic differentiation of bovine calcifying vascular cells (CVCs) and in the aorta of apolipoprotein (Apo) E-/- mice with chronic kidney disease which are common tissue culture and mouse model, respectively, for aortic calcification. FXR activation by a synthetic FXR agonist, 6 alpha-ethyl chenodeoxycholic acid (INT-747) inhibited phosphate induced-mineralization and triglyceride accumulation in CVCs. FXR dominant negative expression augmented mineralization of CVCs and blocked the anticalcific effect of INT-747 whereas VP16FXR that is a constitutively active form reduced mineralization of CVCs. INT-747 treatment also increased phosphorylated c-Jun N-terminal kinase (JNK). SP600125 (specific JNK inhibitor) significantly induced mineralization of CVCs and alkaline phosphatase expression, suggesting that the anticalcific effect of INT-747 is attributable to JNK activation. We also found that INT-747 ameliorates chronic kidney disease induced-vascular calcification in 5/6 nephrectomized ApoE(-/-) mice without affecting the development of atherosclerosis.
Conclusions: These observations provide direct evidence that FXR is a key signaling component in regulation of vascular osteogenic differentiation and, thus representing a promising target for the treatment of vascular calcification. (Circ Res. 2010;106:1807-1817.)
C1 [Miyazaki, Makoto] Univ Colorado Denver, Div Renal Dis & Hypertens, Dept Med, Denver Vet Affairs Med Ctr, Aurora, CO 80045 USA.
[Miyazaki, Makoto] Denver Vet Affairs Med Ctr, Dept Med, Div Endocrinol Diabet & Metab, Denver, CO USA.
Univ Colorado, Boulder, CO 80309 USA.
RP Miyazaki, M (reprint author), Univ Colorado Denver, Div Renal Dis & Hypertens, Dept Med, Denver Vet Affairs Med Ctr, 12700 E 19th Ave,C281, Aurora, CO 80045 USA.
EM Makoto.Miyazaki@ucdenver.edu
OI Levi, Moshe/0000-0002-6225-946X
FU University of Colorado-Denver School of Medicine, Colorado Clinical
Nutrition Research Unit (NIH) [5P30DK048520]; University of Colorado
Health Sciences Center Diabetes and Endocrinology Research Center (NIH)
[P30DK57516]; NIH [U01 DK076134, R01 AG026529]; Veterans Affairs;
Austrian Federal Ministry of Science and Research
FX This work was supported by the University of Colorado-Denver School of
Medicine, Colorado Clinical Nutrition Research Unit (NIH grant
5P30DK048520); University of Colorado Health Sciences Center Diabetes
and Endocrinology Research Center (NIH grant P30DK57516); NIH grants U01
DK076134 and R01 AG026529; and a Veterans Affairs Merit Review grant. A.
K. was supported by an Austrian Federal Ministry of Science and Research
Mobility fellowship (Genomforschung Austria Project G.O.L.D.II, Genomics
of Lipid-associated Disorders II).
NR 46
TC 30
Z9 32
U1 0
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7330
J9 CIRC RES
JI Circ.Res.
PD JUN 25
PY 2010
VL 106
IS 12
BP 1807
EP U55
DI 10.1161/CIRCRESAHA.109.212969
PG 25
WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Hematology
GA 615FC
UT WOS:000279117900005
PM 20431060
ER
PT J
AU Wu, HJ
Ivanov, II
Darce, J
Hattori, K
Shima, T
Umesaki, Y
Littman, DR
Benoist, C
Mathis, D
AF Wu, Hsin-Jung
Ivanov, Ivaylo I.
Darce, Jaime
Hattori, Kimie
Shima, Tatsuichiro
Umesaki, Yoshinori
Littman, Dan R.
Benoist, Christophe
Mathis, Diane
TI Gut-Residing Segmented Filamentous Bacteria Drive Autoimmune Arthritis
via T Helper 17 Cells
SO IMMUNITY
LA English
DT Article
ID MUCOSAL IMMUNE-SYSTEM; RHEUMATOID-ARTHRITIS; TH17 CELLS; INFLAMMATORY
ARTHRITIS; INTESTINAL BACTERIA; COMMENSAL BACTERIA; DENDRITIC CELLS;
MICROBIAL-FLORA; LAMINA PROPRIA; MICE
AB Commensal microbes can have a substantial impact on autoimmune disorders, but the underlying molecular and cellular mechanisms remain largely unexplored. We report that autoimmune arthritis was strongly attenuated in the K/BxN mouse model under germ-free (GF) conditions, accompanied by reductions in serum autoantibody titers, splenic autoantibody-secreting cells, germinal centers, and the splenic T helper 17 (Th17) cell population. Neutralization of interleukin-17 prevented arthritis development in specific-pathogen-free K/BxN mice resulting from a direct effect of this cytokine on B cells to inhibit germinal center formation. The systemic deficiencies of the GF animals reflected a loss of Th17 cells from the small intestinal lamina propria. Introduction of a single gut-residing species, segmented filamentous bacteria, into GF animals reinstated the lamina propria Th17 cell compartment and production of autoantibodies, and arthritis rapidly ensued. Thus, a single commensal microbe, via its ability to promote a specific Th cell subset, can drive an autoimmune disease.
C1 [Wu, Hsin-Jung; Darce, Jaime; Hattori, Kimie; Benoist, Christophe; Mathis, Diane] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Wu, Hsin-Jung; Darce, Jaime; Hattori, Kimie; Benoist, Christophe; Mathis, Diane] Joslin Diabet Ctr, Sect Immunol & Immunogenet, Boston, MA 02215 USA.
[Ivanov, Ivaylo I.; Littman, Dan R.] NYU, Sch Med, Mol Pathogenesis Program, Kimmel Ctr Biol & Med,Skirball Inst, New York, NY 10016 USA.
[Littman, Dan R.] NYU, Sch Med, Howard Hughes Med Inst, Kimmel Ctr Biol & Med,Skirball Inst, New York, NY 10016 USA.
[Shima, Tatsuichiro; Umesaki, Yoshinori] Yakult Cent Inst Microbiol Res, Tokyo 1868650, Japan.
[Benoist, Christophe; Mathis, Diane] Broad Inst, Cambridge, MA 02142 USA.
RP Benoist, C (reprint author), Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
EM cbdm@hms.harvard.edu
FU NIH [P01 AI065858, RC1AI 087266]; Joslin's NIDDK; National Research
Service Award (DFCI/NCI) [T32 CA007386]
FX We thank J. Tocker (Amgen Inc, Seattle, WA) for providing
IL-17R-/- mice; A. Ortiz-Lopez for RT-PCR primers and
assistance with the mouse colonies; M. Kriegel for assistance with part
of the SFB quantitative PCR analysis; K. Leatherbee for microarrays; J.
Lavecchio and G. Buruzula for flow cytometry; and C. Laplace for
assistance with figure preparation. This work was supported by grants
from the NIH to D.M. and C.B. (P01 AI065858) and to D.R.L. (RC1AI
087266) and by Joslin's NIDDK-funded DERC cores. J.D. was funded by
National Research Service Award (DFCI/NCI: T32 CA007386) and I.I.I. by a
Pathway to Independence Award from the NIH (1K99DK085329-01).
NR 59
TC 523
Z9 534
U1 8
U2 58
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-7613
J9 IMMUNITY
JI Immunity
PD JUN 25
PY 2010
VL 32
IS 6
BP 815
EP 827
DI 10.1016/j.immuni.2010.06.001
PG 13
WC Immunology
SC Immunology
GA 618OQ
UT WOS:000279365800012
PM 20620945
ER
PT J
AU Kuchen, S
Resch, W
Yamane, A
Kuo, N
Li, ZY
Chakraborty, T
Wei, L
Laurence, A
Yasuda, T
Peng, SY
Hu-Li, J
Lu, K
Dubois, W
Kitamura, Y
Charles, N
Sun, HW
Muljo, S
Schwartzberg, PL
Paul, WE
O'Shea, J
Rajewsky, K
Casellas, R
AF Kuchen, Stefan
Resch, Wolfgang
Yamane, Arito
Kuo, Nan
Li, Zhiyu
Chakraborty, Tirtha
Wei, Lai
Laurence, Arian
Yasuda, Tomoharu
Peng, Siying
Hu-Li, Jane
Lu, Kristina
Dubois, Wendy
Kitamura, Yoshiaki
Charles, Nicolas
Sun, Hong-wei
Muljo, Stefan
Schwartzberg, Pamela L.
Paul, William E.
O'Shea, John
Rajewsky, Klaus
Casellas, Rafael
TI Regulation of MicroRNA Expression and Abundance during Lymphopoiesis
SO IMMUNITY
LA English
DT Article
ID INDUCED CYTIDINE DEAMINASE; B-CELL DIFFERENTIATION; POSTTRANSCRIPTIONAL
REGULATION; CAENORHABDITIS-ELEGANS; MOUSE OOCYTES; HOST GENES;
STEM-CELLS; SMALL RNAS; C-ELEGANS; T-CELLS
AB Although the cellular concentration of miRNAs is critical to their function, how miRNA expression and abundance are regulated during ontogeny is unclear. We applied miRNA-, mRNA-, and ChIP-Seq to characterize the microRNome during lymphopoiesis within the context of the transcriptome and epigenome. We show that lymphocyte-specific miRNAs are either tightly controlled by polycomb group-mediated H3K27me3 or maintained in a semi-activated epigenetic state prior to full expression. Because of miRNA biogenesis, the cellular concentration of mature miRNAs does not typically reflect transcriptional changes. However, we uncover a subset of miRNAs for which abundance is dictated by miRNA gene expression. We confirm that concentration of 5p and 3p miRNA strands depends largely on free energy properties of miRNA duplexes. Unexpectedly, we also find that miRNA strand accumulation can be developmentally regulated. Our data provide a comprehensive map of immunity's microRNome and reveal the underlying epigenetic and transcriptional forces that shape miRNA homeostasis.
C1 [Resch, Wolfgang; Kitamura, Yoshiaki; Charles, Nicolas] NIAMS, Lab Immune Cell Signaling, NIH, Bethesda, MD 20892 USA.
[Chakraborty, Tirtha; Yasuda, Tomoharu; Peng, Siying; Rajewsky, Klaus] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA.
[Chakraborty, Tirtha; Yasuda, Tomoharu; Peng, Siying; Rajewsky, Klaus] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Hu-Li, Jane; Muljo, Stefan; Paul, William E.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Lu, Kristina; Schwartzberg, Pamela L.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA.
[Dubois, Wendy] NCI, Genet Lab, NIH, Bethesda, MD 20892 USA.
[Casellas, Rafael] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Resch, W (reprint author), NIAMS, Lab Immune Cell Signaling, NIH, Bethesda, MD 20892 USA.
EM wresch@mail.nih.gov; casellar@mail.nih.gov
RI Laurence, Arian/A-8770-2009; Yamane, Arito/A-2959-2013; Wei,
Lai/D-1088-2014; Muljo, Stefan/F-5671-2015; Charles, Nicolas/P-5430-2014
OI Kuchen, Stefan/0000-0003-4899-8132; Laurence, Arian/0000-0003-0942-8292;
Muljo, Stefan/0000-0003-1013-446X; Charles, Nicolas/0000-0002-5416-5834
FU NIAMS-NIH; Swiss Foundation for Grants in Biology and Medicine
FX We thank members of the Casellas lab for discussions; J. Newman and R.
Young for mouse ESCs; J. Simone for cell sorting; G. Gutierrez for
technical assistance with the genome analyzer; B. Wold for the mRNA-seq
protocol; and L. Naldini for the LV-SFFV lentiviral vector. This work
was supported in part by the Intramural Research Program of NIAMS-NIH.
S. K. was supported by the Swiss Foundation for Grants in Biology and
Medicine.
NR 59
TC 167
Z9 179
U1 1
U2 16
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-7613
J9 IMMUNITY
JI Immunity
PD JUN 25
PY 2010
VL 32
IS 6
BP 828
EP 839
DI 10.1016/j.immuni.2010.05.009
PG 12
WC Immunology
SC Immunology
GA 618OQ
UT WOS:000279365800013
PM 20605486
ER
PT J
AU Elo, LL
Jarvenpaa, H
Tuomela, S
Raghav, S
Ahlfors, H
Laurila, K
Gupta, B
Lund, RJ
Tahvanainen, J
Hawkins, RD
Oresic, M
Lahdesmaki, H
Rasool, O
Rao, KV
Aittokallio, T
Lahesmaa, R
AF Elo, Laura L.
Jarvenpaa, Henna
Tuomela, Soile
Raghav, Sunil
Ahlfors, Helena
Laurila, Kirsti
Gupta, Bhawna
Lund, Riikka J.
Tahvanainen, Johanna
Hawkins, R. David
Oresic, Matej
Lahdesmaki, Harri
Rasool, Omid
Rao, Kanury V.
Aittokallio, Tero
Lahesmaa, Riitta
TI Genome-wide Profiling of Interleukin-4 and STAT6 Transcription Factor
Regulation of Human Th2 Cell Programming
SO IMMUNITY
LA English
DT Article
ID IL-1 RECEPTOR ANTAGONIST; T-HELPER-CELLS; GENE-EXPRESSION; CUTTING EDGE;
DEPENDENT TRANSCRIPTION; INDISPENSABLE ROLE; DIFFERENTIATION; PROTEIN;
MECHANISMS; ACTIVATION
AB Dissecting the molecular mechanisms by which T helper (Th) cells differentiate to effector Th2 cells is important for understanding the pathogenesis of immune-mediated diseases, such as asthma and allergy. Because the STAT6 transcription factor is an upstream mediator required for interleukin-4 (IL-4)-induced Th2 cell differentiation, its targets include genes important for this process. Using primary human CD4(+) T cells, and by blocking STAT6 with RNAi, we identified a number of direct and indirect targets of STAT6 with ChIP sequencing. The integration of these data sets with detailed kinetics of IL-4-driven transcriptional changes showed that STAT6 was predominantly needed for the activation of transcription leading to the Th2 cell phenotype. This integrated genome-wide data on IL-4- and STAT6-mediated transcription provide a unique resource for studies on Th cell differentiation and, in particular, for designing interventions of human Th2 cell responses.
C1 [Elo, Laura L.; Jarvenpaa, Henna; Tuomela, Soile; Raghav, Sunil; Ahlfors, Helena; Gupta, Bhawna; Lund, Riikka J.; Tahvanainen, Johanna; Rasool, Omid; Aittokallio, Tero; Lahesmaa, Riitta] Univ Turku, Turku Ctr Biotechnol, FI-20521 Turku, Finland.
[Elo, Laura L.; Jarvenpaa, Henna; Tuomela, Soile; Raghav, Sunil; Ahlfors, Helena; Gupta, Bhawna; Lund, Riikka J.; Tahvanainen, Johanna; Rasool, Omid; Aittokallio, Tero; Lahesmaa, Riitta] Abo Akad Univ, FI-20521 Turku, Finland.
[Elo, Laura L.; Aittokallio, Tero] Univ Turku, Dept Math, Biomath Res Grp, FI-20014 Turku, Finland.
[Jarvenpaa, Henna; Tuomela, Soile] Turku Grad Sch Biomed Sci, FI-20520 Turku, Finland.
[Ahlfors, Helena] Abo Akad Univ, Natl Grad Sch Informat & Struct Biol, FI-20520 Turku, Finland.
[Laurila, Kirsti; Lahdesmaki, Harri] Tampere Univ Technol, Dept Signal Proc, FI-33101 Tampere, Finland.
[Lund, Riikka J.] Univ Sheffield, Dept Biol Sci, Sheffield S10 2TN, S Yorkshire, England.
[Tahvanainen, Johanna] Univ Turku, Drug Discovery Grad Sch, FI-20014 Turku, Finland.
[Hawkins, R. David] Univ Calif San Diego, Ludwig Inst Canc Res, San Diego, CA 92037 USA.
[Oresic, Matej] VTT Tech Res Ctr Finland, FI-02044 Espoo, Finland.
[Lahdesmaki, Harri] Helsinki Univ Technol, Dept Informat & Comp Sci, FI-02015 Helsinki, Finland.
[Rao, Kanury V.] Int Ctr Genet Engn & Biotechnol, New Delhi 110067, India.
[Lahesmaa, Riitta] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA.
RP Lahesmaa, R (reprint author), Univ Turku, Turku Ctr Biotechnol, POB 123, FI-20521 Turku, Finland.
EM riitta.lahesmaa@btk.fi
RI Aittokallio, Tero/B-6583-2009;
OI Aittokallio, Tero/0000-0002-0886-9769; Elo, Laura/0000-0001-5648-4532;
Lund, Riikka/0000-0002-1068-5918; Oresic, Matej/0000-0002-2856-9165
FU Academy of Finland [77773, 203725, 207490, 116639, 115939, 123864,
126063, 127575, 120569]; European Commission [EC-FP7-SYBILLA-201106,
EC-FP7-NANOMMUNE-214281, EC-FP7-DIABIMMUNE-202063]; CIMO/Sitra; Sigrid
Juselius Foundation; Department of Biotechnology, Government of India;
Turku University Hospital
FX We thank the technical personnel for assistance; the staff of the
Finnish Microarray and Sequencing Centre, Turku, Finland for microarray
hybridizations; all voluntary blood donors; the personnel of Turku
University Hospital Department of Obstetrics and Gynaecology, Maternity
Ward (Hospital District of Southwest Finland) for the sample collection;
and A. Rao for the critical reading of the manuscript. The work was
supported by the Academy of Finland (grants 77773, 203725, 207490,
116639, 115939, 123864, 126063, 127575 [L.L.E.], and 120569 [TA.]), the
European Commission Seventh Framework grants (EC-FP7-SYBILLA-201106,
EC-FP7-NANOMMUNE-214281 and EC-FP7-DIABIMMUNE-202063), CIMO/Sitra grant
(S.R. and R.L.), The Sigrid Juselius Foundation (R.L. and K.V.R.), The
Department of Biotechnology, Government of India (K.V.R), and Turku
University Hospital Grant.
NR 70
TC 58
Z9 58
U1 2
U2 13
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-7613
J9 IMMUNITY
JI Immunity
PD JUN 25
PY 2010
VL 32
IS 6
BP 852
EP 862
DI 10.1016/j.immuni.2010.06.011
PG 11
WC Immunology
SC Immunology
GA 618OQ
UT WOS:000279365800015
PM 20620947
ER
PT J
AU Charriere, GM
Ip, WKE
Dejardin, S
Boyer, L
Sokolovska, A
Cappillino, MP
Cherayil, BJ
Podolsky, DK
Kobayashi, KS
Silverman, N
Lacy-Hulbert, A
Stuart, LM
AF Charriere, Guillaume M.
Ip, W. K. Eddie
Dejardin, Stephanie
Boyer, Laurent
Sokolovska, Anna
Cappillino, Michael P.
Cherayil, Bobby J.
Podolsky, Daniel K.
Kobayashi, Koichi S.
Silverman, Neal
Lacy-Hulbert, Adam
Stuart, Lynda M.
TI Identification of Drosophila Yin and PEPT2 as Evolutionarily Conserved
Phagosome-associated Muramyl Dipeptide Transporters
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID INNATE IMMUNE-SYSTEM; TOLL-LIKE RECEPTORS; NF-KAPPA-B; CROHNS-DISEASE;
NOD2; RECOGNITION; ACTIVATION; CELLS; INTERNALIZATION; SUSCEPTIBILITY
AB NOD2 (nucleotide-binding oligomerization domain containing 2) is an important cytosolic pattern recognition receptor that activates NF-kappa B and other immune effector pathways such as autophagy and antigen presentation. Despite its intracellular localization, NOD2 participates in sensing of extracellular microbes such as Staphylococcus aureus. NOD2 ligands similar to the minimal synthetic ligand muramyl dipeptide (MDP) are generated by internalization and processing of bacteria in hydrolytic phagolysosomes. However, how these derived ligands exit this organelle and access the cytosol to activate NOD2 is poorly understood. Here, we address how phagosome-derived NOD2 ligands access the cytosol in human phagocytes. Drawing on data from Drosophila phagosomes, we identify an evolutionarily conserved role of SLC15A transporters, Drosophila Yin and PEPT2, as MDP transporters in fly and human phagocytes, respectively. We show that PEPT2 is highly expressed by human myeloid cells. Ectopic expression of both Yin and PEPT2 increases the sensitivity of NOD2-dependent NF-kappa B activation. Additionally, we show that PEPT2 associates with phagosome membranes. Together, these data identify Drosophila Yin and PEPT2 as evolutionarily conserved phagosome-associated transporters that are likely to be of particular importance in delivery of bacteria-derived ligands generated in phagosomes to cytosolic sensors recruited to the vicinity of these organelles.
C1 [Cherayil, Bobby J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mucosal Immunol Lab, Boston, MA 02144 USA.
[Podolsky, Daniel K.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Kobayashi, Koichi S.] Harvard Univ, Dana Farber Canc Inst, Sch Med, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
[Silverman, Neal] Univ Massachusetts, Sch Med, Dept Med, Div Infect Dis, Worcester, MA 01605 USA.
RP Stuart, LM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Jackson 14,55 Fruit St, Boston, MA 02114 USA.
EM lstuart@partners.org
RI Ip, Eddie/C-3042-2012; Boyer, laurent/F-8921-2015; Charriere,
Guillaume/O-8317-2014;
OI Boyer, laurent/0000-0002-1375-1706; Charriere,
Guillaume/0000-0002-4796-1488; Lacy-Hulbert, Adam/0000-0003-2162-0156;
Silverman, Neal/0000-0002-4259-456X
FU NIAID NIH HHS [R01 AI074958, R01 AI079198, R01 AI079198-02]; NIDDK NIH
HHS [P30 DK040561, P30 DK040561-15, P30 DK043351, R01 DK074738, R01
DK074738-05]
NR 36
TC 16
Z9 16
U1 1
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 JUN 25
PY 2010
VL 285
IS 26
BP 20147
EP 20154
DI 10.1074/jbc.M110.115584
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 613VS
UT WOS:000279012000049
PM 20406817
ER
PT J
AU Gorgun, G
Calabrese, E
Hideshima, T
Ecsedy, J
Perrone, G
Mani, M
Ikeda, H
Bianchi, G
Hu, YG
Cirstea, D
Santo, L
Tai, YT
Nahar, S
Zheng, M
Bandi, M
Carrasco, RD
Raje, N
Munshi, N
Richardson, P
Anderson, KC
AF Goerguen, Guellue
Calabrese, Elisabetta
Hideshima, Teru
Ecsedy, Jeffrey
Perrone, Giulia
Mani, Mala
Ikeda, Hiroshi
Bianchi, Giada
Hu, Yiguo
Cirstea, Diana
Santo, Loredana
Tai, Yu-Tzu
Nahar, Sabikun
Zheng, Mei
Bandi, Madhavi
Carrasco, Ruben D.
Raje, Noopur
Munshi, Nikhil
Richardson, Paul
Anderson, Kenneth C.
TI Anovel Aurora-A kinase inhibitor MLN8237 induces cytotoxicity and
cell-cycle arrest in multiple myeloma
SO BLOOD
LA English
DT Article
ID PROTEIN-KINASE; G2 CHECKPOINT; BONE-MARROW; CANCER; OVEREXPRESSION;
ACTIVATION; TARGETS; AGENTS; EVENT
AB Aurora-A is a mitotic kinase that regulates mitotic spindle formation and segregation. In multiple myeloma (MM), high Aurora-A gene expression has been correlated with centrosome amplification and proliferation; thus, inhibition of Aurora-A in MM may prove to be therapeutically beneficial. Here we assess the in vitro and in vivo anti-MM activity of MLN8237, a small-molecule Aurora-A kinase inhibitor. Treatment of cultured MM cells with MLN8237 results in mitotic spindle abnormalities, mitotic accumulation, as well as inhibition of cell proliferation through apoptosis and senescence. In addition, MLN8237 up-regulates p53 and tumor suppressor genes p21 and p27. Combining MLN8237 with dexamethasone, doxorubicin, or bortezomib induces synergistic/additive anti-MM activity in vitro. In vivo anti-MM activity of MLN8237 was confirmed using a xenograft-murine model of human-MM. Tumor burden was significantly reduced (P = .007) and overall survival was significantly increased (P<.005) in animals treated with 30 mg/kg MLN8237 for 21 days. Induction of apoptosis and cell death by MLN8237 were confirmed in tumor cells excised from treated animals by TdT-mediated dUTP nick end labeling assay. MLN8237 is currently in phase 1 and phase 2 clinical trials in patients with advanced malignancies, and our preclinical results suggest that MLN8237 may be a promising novel targeted therapy in MM. (Blood. 2010;115(25):5202-5213)
C1 [Goerguen, Guellue; Calabrese, Elisabetta; Hideshima, Teru; Perrone, Giulia; Mani, Mala; Ikeda, Hiroshi; Bianchi, Giada; Hu, Yiguo; Cirstea, Diana; Santo, Loredana; Tai, Yu-Tzu; Nahar, Sabikun; Bandi, Madhavi; Carrasco, Ruben D.; Munshi, Nikhil; Richardson, Paul; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Ecsedy, Jeffrey] Millennium Pharmaceut Inc, Cambridge, MA USA.
[Zheng, Mei] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Raje, Noopur] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Munshi, Nikhil] Boston Vet Adm Hlth Care Syst, Boston, MA USA.
RP Gorgun, G (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,M557, Boston, MA 02115 USA.
EM gullu_gorgun@dfci.harvard.edu
FU National Institutes of Health/National Cancer Institute [P50 CA100707,
P01 CA78378, R01 CA50947]
FX This work was supported by the National Institutes of Health/National
Cancer Institute Specialized Program of Research Excellence in Myeloma
(P50 CA100707; K.C.A.), National Institutes of Health/National Cancer
Institute Host-Tumor Cell Interactions in Myeloma (Therapeutic
Applications P01 CA78378; K.C.A.), and National Institutes of
Health/National Cancer Institute Molecular Sequelae of Myeloma-Bone
Marrow Interactions (Therapeutic Applications R01 CA50947; K.C.A.).
NR 44
TC 131
Z9 136
U1 0
U2 5
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD JUN 24
PY 2010
VL 115
IS 25
BP 5202
EP 5213
DI 10.1182/blood-2009-12-259523
PG 12
WC Hematology
SC Hematology
GA 615DP
UT WOS:000279113100013
PM 20382844
ER
PT J
AU Iannacone, M
Moseman, EA
Tonti, E
Bosurgi, L
Junt, T
Henrickson, SE
Whelan, SP
Guidotti, LG
von Andrian, UH
AF Iannacone, Matteo
Moseman, E. Ashley
Tonti, Elena
Bosurgi, Lidia
Junt, Tobias
Henrickson, Sarah E.
Whelan, Sean P.
Guidotti, Luca G.
von Andrian, Ulrich H.
TI Subcapsular sinus macrophages prevent CNS invasion on peripheral
infection with a neurotropic virus
SO NATURE
LA English
DT Article
ID LIPOSOME-MEDIATED DEPLETION; VESICULAR STOMATITIS-VIRUS; IN-VIVO
DEPLETION; CD8(+) T-CELLS; LYMPH-NODES; B-CELLS; DENDRITIC CELLS; MICE;
ACTIVATION; ANTIGEN
AB Lymph nodes (LNs) capture microorganisms that breach the body's external barriers and enter draining lymphatics, limiting the systemic spread of pathogens(1). Recent work has shown that CD11b(+)CD169(+) macrophages, which populate the subcapsular sinus (SCS) of LNs, are critical for the clearance of viruses from the lymph and for initiating antiviral humoral immune responses(2-4). Here we show, using vesicular stomatitis virus (VSV), a relative of rabies virus transmitted by insect bites, that SCS macrophages perform a third vital function: they prevent lymph-borne neurotropic viruses from infecting the central nervous system (CNS). On local depletion of LN macrophages, about 60% of mice developed ascending paralysis and died 7-10 days after subcutaneous infection with a small dose of VSV, whereas macrophage-sufficient animals remained asymptomatic and cleared the virus. VSV gained access to the nervous system through peripheral nerves in macrophage-depleted LNs. In contrast, within macrophage-sufficient LNs VSV replicated preferentially in SCS macrophages but not in adjacent nerves. Removal of SCS macrophages did not compromise adaptive immune responses against VSV, but decreased type I interferon (IFN-I) production within infected LNs. VSV-infected macrophages recruited IFN-I-producing plasmacytoid dendritic cells to the SCS and in addition were a major source of IFN-I themselves. Experiments in bone marrow chimaeric mice revealed that IFN-I must act on both haematopoietic and stromal compartments, including the intranodal nerves, to prevent lethal infection with VSV. These results identify SCS macrophages as crucial gatekeepers to the CNS that prevent fatal viral invasion of the nervous system on peripheral infection.
C1 [Iannacone, Matteo; Moseman, E. Ashley; Tonti, Elena; Bosurgi, Lidia; Henrickson, Sarah E.; von Andrian, Ulrich H.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA.
[Iannacone, Matteo; Moseman, E. Ashley; Tonti, Elena; Bosurgi, Lidia; Henrickson, Sarah E.; von Andrian, Ulrich H.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Iannacone, Matteo; Guidotti, Luca G.] Ist Sci San Raffaele, Dept Immunol Infect Dis & Transplantat, I-20132 Milan, Italy.
[Junt, Tobias] Novartis Inst BioMed Res, CH-4002 Basel, Switzerland.
[Whelan, Sean P.] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA.
RP von Andrian, UH (reprint author), Harvard Univ, Sch Med, Immune Dis Inst, 77 Ave Louis Pasteur, Boston, MA 02115 USA.
EM Matteo_Iannacone@hms.harvard.edu; uva@hms.harvard.edu
RI Iannacone, Matteo/B-3342-2008; von Andrian, Ulrich/A-5775-2008;
OI Guidotti, Luca G./0000-0002-0205-2678; Iannacone,
Matteo/0000-0002-9370-2671
FU National Institutes of Health (NIH) [AI069259, AI072252, AI078897,
AR42689]; Giovanni Armenise-Harvard Foundation; NIH
FX We thank G. Cheng and M. Flynn for technical support; J. Alton for
secretarial assistance; D. Cureton for help and advice with VSV
preparations; H. Leung for help with image quantification; R. M.
Zinkernagel and H. Hengartner for providing tg7 mice; R. Bronson for
help with reading neuropathology; S. Cohen for advice on nerve staining;
N. van Rooijen for clodronate liposomes; and the members of the von
Andrian laboratory for discussion. This work was supported by National
Institutes of Health (NIH) grants AI069259, AI072252, AI078897 and
AR42689 (to U.H.v.A.), the Giovanni Armenise-Harvard Foundation (to
M.I.) and a NIH T32 Training Grant in Hematology (to E.A.M.).
NR 26
TC 121
Z9 121
U1 3
U2 20
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD JUN 24
PY 2010
VL 465
IS 7301
BP 1079
EP U143
DI 10.1038/nature09118
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 614KI
UT WOS:000279056900053
PM 20577213
ER
PT J
AU Ryan, DP
Engelman, JA
Ferrone, CR
Sahani, DV
Lisovsky, M
AF Ryan, David P.
Engelman, Jeffrey A.
Ferrone, Cristina R.
Sahani, Dushyant V.
Lisovsky, Mikhail
TI Case 19-2010: A 35-Year-Old Man with Adenocarcinoma of the Cecum.
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID METASTATIC COLORECTAL-CANCER; INITIAL TREATMENT; CHEMOTHERAPY;
CETUXIMAB; MANAGEMENT; SURGERY
C1 [Ryan, David P.; Engelman, Jeffrey A.] Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA.
[Ferrone, Cristina R.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Sahani, Dushyant V.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Lisovsky, Mikhail] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Ryan, David P.; Engelman, Jeffrey A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Ferrone, Cristina R.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA.
[Sahani, Dushyant V.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA.
[Lisovsky, Mikhail] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Lisovsky, Mikhail] Dartmouth Hitchcock Med Ctr, Dept Pathol, Lebanon, NH 03766 USA.
[Lisovsky, Mikhail] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Hanover, NH 03756 USA.
RP Ryan, DP (reprint author), Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA.
FU NCI NIH HHS [P50 CA127003, P50 CA127003-04, K08 CA120060, K08
CA120060-04, P50 CA127003-03]
NR 22
TC 1
Z9 1
U1 0
U2 1
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JUN 24
PY 2010
VL 362
IS 25
BP 2411
EP 2419
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 614GO
UT WOS:000279043800012
PM 20573930
ER
PT J
AU Olson, KR
Caldwell, A
Nelson, BD
AF Olson, Kristian R.
Caldwell, Aya
Nelson, Brett D.
TI Newborn-Care Training in Developing Countries.
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
C1 [Olson, Kristian R.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Caldwell, Aya] CIMIT Global Hlth Initiat, Boston, MA USA.
[Nelson, Brett D.] MassGen Hosp Children, Boston, MA USA.
RP Olson, KR (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.
EM krolson@partners.org
NR 4
TC 2
Z9 2
U1 0
U2 0
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JUN 24
PY 2010
VL 362
IS 25
BP 2427
EP 2428
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 614GO
UT WOS:000279043800023
PM 20573935
ER
PT J
AU Hawn, MT
AF Hawn, Mary T.
TI Surgical Care Improvement Should Performance Measures Have Performance
Measures
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
ID SITE INFECTIONS; ANTIMICROBIAL-PROPHYLAXIS; ANTIBIOTIC-PROPHYLAXIS;
RISK; SURGERY; TRIAL
C1 [Hawn, Mary T.] Univ Alabama Birmingham, Dept Surg, Birmingham, AL 35294 USA.
[Hawn, Mary T.] Birmingham Vet Affairs Med Ctr, Ctr Surg Med Acute Care Res & Transit, Birmingham, AL USA.
RP Hawn, MT (reprint author), Univ Alabama Birmingham, Dept Surg, 1530 3rd Ave S,KB 429, Birmingham, AL 35294 USA.
EM mhawn@uab.edu
NR 15
TC 23
Z9 23
U1 0
U2 1
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD JUN 23
PY 2010
VL 303
IS 24
BP 2527
EP 2528
DI 10.1001/jama.2010.854
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 613VM
UT WOS:000279010900034
PM 20571022
ER
PT J
AU Lee, BY
Ufberg, PJ
Bailey, RR
Wiringa, AE
Smith, KJ
Nowalk, AJ
Higgins, C
Wateska, AR
Muder, RR
AF Lee, Bruce Y.
Ufberg, Paul J.
Bailey, Rachel R.
Wiringa, Ann E.
Smith, Kenneth J.
Nowalk, Andrew J.
Higgins, Conor
Wateska, Angela R.
Muder, Robert R.
TI The potential economic value of a Staphylococcus aureus vaccine for
neonates
SO VACCINE
LA English
DT Article
DE Staphylococcus aureus; Vaccine; Economics
ID INTENSIVE-CARE-UNIT; LOW-BIRTH-WEIGHT; NOSOCOMIAL-INFECTIONS; DAPTOMYCIN
RESISTANCE; PASSIVE-IMMUNIZATION; SURVEILLANCE; MRSA; EPIDEMIOLOGY;
PREVENTION; PROSPECTS
AB The continuing morbidity and mortality associated with Staphylococcus aureus (S. aureus) infections, especially methicillin-resistant S. aureus (MRSA) infections, have motivated calls to make S. aureus vaccine development a research priority. We developed a decision analytic computer simulation model to determine the potential economic impact of a S. aureus vaccine for neonates. Our results suggest that a S. aureus vaccine for the neonatal population would be strongly cost-effective (and in many situations dominant) over a wide range of vaccine efficacies (down to 10%) for vaccine costs (<=$500), and S. aureus attack rates (>= 1%). (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Lee, Bruce Y.; Ufberg, Paul J.; Bailey, Rachel R.; Wiringa, Ann E.; Smith, Kenneth J.; Higgins, Conor; Wateska, Angela R.] Univ Pittsburgh, Publ Hlth Computat & Operat Res PHICOR, Pittsburgh, PA 15213 USA.
[Lee, Bruce Y.; Ufberg, Paul J.; Bailey, Rachel R.; Wiringa, Ann E.; Higgins, Conor; Wateska, Angela R.] Univ Pittsburgh, Dept Biomed Informat, Pittsburgh, PA 15213 USA.
[Lee, Bruce Y.; Ufberg, Paul J.; Bailey, Rachel R.; Wiringa, Ann E.; Higgins, Conor; Wateska, Angela R.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15213 USA.
[Ufberg, Paul J.] Univ Pittsburgh, Childrens Hosp Pittsburgh, Div Gastroenterol, Pittsburgh, PA 15213 USA.
[Nowalk, Andrew J.] Univ Pittsburgh, Childrens Hosp Pittsburgh, Div Infect Dis, Pittsburgh, PA 15213 USA.
[Muder, Robert R.] Univ Pittsburgh, VA Pittsburgh Hlth Syst, Pittsburgh, PA 15213 USA.
RP Lee, BY (reprint author), Univ Pittsburgh, Publ Hlth Computat & Operat Res PHICOR, 200 Meyran Ave,Suite 200, Pittsburgh, PA 15213 USA.
EM BYL1@pitt.edu
OI Nowalk, Andrew/0000-0002-1374-3167; Smith, Kenneth
J/0000-0001-8088-566X; Slayton, Rachel/0000-0003-4699-8040
FU Bill and Melinda Gates Foundation; National Institute of General Medical
Sciences Models of Infectious Disease Agent Study (MIDAS)
[1U54GM088491-0109]; Pennsylvania Department of Health; Vaccine Modeling
Initiative (VMI)
FX Supported by the National Institute of General Medical Sciences Models
of Infectious Disease Agent Study (MIDAS) through grant
1U54GM088491-0109, the Pennsylvania Department of Health, and the
Vaccine Modeling Initiative (VMI), funded by the Bill and Melinda Gates
Foundation. The funder had no role in the study design, data collection
and analysis, decision to publish, or preparation of the manuscript.
NR 62
TC 8
Z9 8
U1 0
U2 3
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
J9 VACCINE
JI Vaccine
PD JUN 23
PY 2010
VL 28
IS 29
BP 4653
EP 4660
DI 10.1016/j.vaccine.2010.04.069
PG 8
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 625AO
UT WOS:000279863900018
PM 20472028
ER
PT J
AU Tormos, JR
Taylor, AB
Daubner, SC
Hart, PJ
Fitzpatrick, PF
AF Tormos, Jose R.
Taylor, Alexander B.
Daubner, S. Colette
Hart, P. John
Fitzpatrick, Paul F.
TI Identification of a Hypothetical Protein from Podospora anserina as a
Nitroalkane Oxidase
SO BIOCHEMISTRY
LA English
DT Article
ID ACYL-COA DEHYDROGENASES; FAD-CONTAINING FORM; FUSARIUM-OXYSPORUM;
SUBSTRATE-SPECIFICITY; CRYSTAL-STRUCTURES; HYDRIDE TRANSFER; MECHANISM;
OXIDATION; PH; CATALYSIS
AB The flavoprotein nitroalkane oxidase (NAO) from Fusarium oxysporum catalyzes the oxidation of primary and secondary nitroalkanes to their respective aldehydes and ketones. Structurally, the enzyme is a member of the acyl-CoA dehydrogenase superfamily. To date no enzymes other than that from F. oxysporum have been annotated as NAOs. To identify additional potential NAOs, the available database was searched for enzymes in which the active site residues Asp402, Ara409, and Ser276 were conserved. Of the several fungal enzymes identified in this fashion, PODANSg2158 from Podospora anserina was selected for expression and characterization. The recombinant enzyme is a flavoprotein with activity on nitroalkanes comparable to the F. oxysporum NAO, although the substrate specificity is somewhat different. Asp399, Arg406, and Ser273 in PODANSg2158 correspond to the active site triad in F. oxysporum NAO. The k(cat)/K(M)-pH profile with nitroethane shows a pK(a) of 5.9 that is assigned to Asp399 as the active site base. Mutation of Asp399 to asparagine decreases the k(cat)/K(M) value for nitroethane over 2 orders of magnitude. The R406K and S373A mutations decrease this kinetic parameter by 64- and 3-fold, respectively. The structure of PODANSg2158 has been determined at a resolution of 2.0 angstrom, confirming its identification as an NAO.
C1 [Tormos, Jose R.; Taylor, Alexander B.; Hart, P. John; Fitzpatrick, Paul F.] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA.
[Daubner, S. Colette] St Marys Univ, Dept Biol, San Antonio, TX 78228 USA.
[Hart, P. John] S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Dept Vet Affairs, Audie Murphy Div, San Antonio, TX 78229 USA.
[Fitzpatrick, Paul F.] Univ Texas San Antonio, Dept Chem, San Antonio, TX 78249 USA.
RP Fitzpatrick, PF (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA.
EM Fitzpatrick@biochem.uthscsa.edu
FU NIH [GM 058698]; Robert A. Welch Foundation [AQ-1399]; National Center
for Research Resources at the National Institutes of Health [RR-15301];
U.S. Department of Energy, Office of Basic Energy Sciences
[W-31-109-ENG-38]
FX This work was supported in part by NIH Grant GM 058698 to P.F.F and
Robert A. Welch Foundation Grant AQ-1399 to P.J.H.; This work is based
upon research conducted at the Northeastern Collaborative Access Team
beamlines of the Advanced Photon Source, supported by award RR-15301
from the National Center for Research Resources at the National
Institutes of Health. Use of the Advanced Photon Source is supported by
the U.S. Department of Energy, Office of Basic Energy Sciences, under
Contract No. W-31-109-ENG-38. We thank Dr. Jonathan P. Schuermann at the
Advanced Photon Source for collecting the X-ray diffraction data.
Support for the X-ray Crystallography Core Laboratory by the UTHSC-SA
Executive Research Committee and the San Antonio Cancer Institute is
also gratefully acknowledged.
NR 36
TC 6
Z9 6
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD JUN 22
PY 2010
VL 49
IS 24
BP 5035
EP 5041
DI 10.1021/bi100610e
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 609VA
UT WOS:000278684400012
PM 20481475
ER
PT J
AU Espitia, CM
Zhao, WG
Saldarriaga, O
Osorio, Y
Harrison, LM
Cappello, M
Travi, BL
Melby, PC
AF Espitia, Claudia M.
Zhao, Weiguo
Saldarriaga, Omar
Osorio, Yaneth
Harrison, Lisa M.
Cappello, Michael
Travi, Bruno L.
Melby, Peter C.
TI Duplex real-time reverse transcriptase PCR to determine cytokine mRNA
expression in a hamster model of New World cutaneous leishmaniasis
SO BMC IMMUNOLOGY
LA English
DT Article
ID FEVER VIRUS-INFECTION; GOLDEN SYRIAN-HAMSTER; MESOCRICETUS-AURATUS;
T-CELLS; VISCERAL LEISHMANIASIS; QUANTITATIVE PCR; IMMUNE-RESPONSE;
MAJOR INFECTION; GENE-EXPRESSION; DENDRITIC CELLS
AB Background: The Syrian hamster, Mesocricetus auratus, has distinct immunological features and is uniquely susceptible to intracellular pathogens. Studies in hamsters are limited by the relative unavailability of tools to conduct immunological studies. To address this limitation we developed duplex real-time reverse transcriptase (RT) PCR assays for the relative quantification of the mRNAs of hamster cytokines, chemokines, and related immune response molecules.
Results: Real-time RT-PCR primers and probes were synthesized for analysis of interleukin (IL)-4, IFN-gamma, TNF-alpha, IL-10, IL-12p40, TGF-beta, IL-13, IL-21, chemokine ligand (CCL) 22, CCL17, Chemokine (C-C motif) receptor 4 and FoxP3 expression. Standard curves and validation experiments were performed for each real-time RT-PCR assay, allowing us to use the comparative Ct (2-(Delta Delta Ct)) method to calculate changes in gene expression. Application of the real-time RT PCR assays to a biological model was demonstrated by comparing mRNA expression in skin and lymph node tissues between uninfected and Leishmania panamensis infected hamsters.
Conclusions: The duplex real-time RT PCR assays provide a powerful approach for the quantification of cytokine transcription in hamsters, and their application to a model of cutaneous leishmaniasis suggests that a balanced type 1 and type 2 cytokine response contributes to the chronic, nonprogressive course of disease. These new molecular tools will further facilitate investigation into the mechanisms of disease in the hamster, not only for models of leishmaniasis, but also for other viral, bacterial, fungal, and parasitic infections.
C1 [Espitia, Claudia M.; Zhao, Weiguo; Saldarriaga, Omar; Osorio, Yaneth; Travi, Bruno L.; Melby, Peter C.] S Texas Vet Hlth Care Syst, Dept Vet Affairs Med Ctr, Res Serv, San Antonio, TX USA.
[Espitia, Claudia M.; Zhao, Weiguo; Saldarriaga, Omar; Osorio, Yaneth; Travi, Bruno L.; Melby, Peter C.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA.
[Harrison, Lisa M.; Cappello, Michael] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA.
[Melby, Peter C.] Univ Texas Hlth Sci Ctr San Antonio, Dept Microbiol & Immunol, San Antonio, TX 78229 USA.
RP Melby, PC (reprint author), S Texas Vet Hlth Care Syst, Dept Vet Affairs Med Ctr, Res Serv, 7400 Merton Minter, San Antonio, TX USA.
EM melby@uthscsa.edu
FU National Institutes of Health [AI61624, AI058980]; U.S. Department of
Veterans Affairs
FX This work was supported by the funding from the National Institutes of
Health (AI61624) and the U.S. Department of Veterans Affairs to PCM, and
NIH grant AI058980 to MC. Special thanks to Lourdes Arteaga and Alheli
Rodriguez for technical assistance.
NR 47
TC 15
Z9 15
U1 0
U2 5
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2172
J9 BMC IMMUNOL
JI BMC Immunol.
PD JUN 22
PY 2010
VL 11
AR 31
DI 10.1186/1471-2172-11-31
PG 12
WC Immunology
SC Immunology
GA 632DV
UT WOS:000280401800001
PM 20569429
ER
PT J
AU Morrow, DA
AF Morrow, David A.
TI Cardiovascular Risk Prediction in Patients With Stable and Unstable
Coronary Heart Disease
SO CIRCULATION
LA English
DT Article
DE angina; atherosclerosis; myocardial infarction; prevention; prognosis
ID ACUTE MYOCARDIAL-INFARCTION; C-REACTIVE PROTEIN; BRAIN NATRIURETIC
PEPTIDE; PROGNOSTIC VALUE; ST-SEGMENT; ARTERY-DISEASE; SCIENTIFIC
STATEMENT; FOLLOW-UP; ASSOCIATION COUNCIL; PRACTICE GUIDELINES
C1 [Morrow, David A.] Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Dept Med, Boston, MA 02115 USA.
[Morrow, David A.] Harvard Univ, Sch Med, Boston, MA 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 AstraZeneca; Beckman Coulter; Biosite; Bristol-Myers Squibb; CV
Therapeutics; Daiichi Sankyo; Eli Lilly; GlaxoSmithKline; Merck;
Nanosphere; Novartis; Ortho-Clinical Diagnostics; Pfizer; Roche;
Sanofi-Aventis; Schering-Plough; Siemens; Singulex
FX The TIMI Study Group has received research grant support from
AstraZeneca, Beckman Coulter, Biosite, Bristol-Myers Squibb, CV
Therapeutics, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Merck,
Nanosphere, Novartis, Ortho-Clinical Diagnostics, Pfizer, Roche,
Sanofi-Aventis, Schering-Plough, Siemens, and Singulex. In the past 2
years, Dr Morrow has received honoraria from Eli Lilly and Co and
Sanofi-Aventis. He has served as a consultant for AstraZeneca, Beckman
Coulter, Boeringher Ingelheim, Critical Diagnostics, CV Therapeutics,
Genentech, Gilead, Ikaria, Heartscape, Menarini, OrthoClinical
Diagnostics, Roche, Schering-Plough, and Siemens.
NR 82
TC 37
Z9 37
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD JUN 22
PY 2010
VL 121
IS 24
BP 2681
EP 2691
DI 10.1161/CIRCULATIONAHA.109.852749
PG 11
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 613MY
UT WOS:000278984600012
PM 20566966
ER
PT J
AU Newton-Cheh, C
Smith, JG
AF Newton-Cheh, Christopher
Smith, J. Gustav
TI What Can Human Genetics Teach Us About the Causes of Cardiovascular
Disease?
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Editorial Material
DE cholesterol; genetics; LDL; Mendelian randomization; myocardial
infarction
ID CORONARY-HEART-DISEASE; HIGH-DENSITY-LIPOPROTEIN; C-REACTIVE PROTEIN;
MENDELIAN RANDOMIZATION; MYOCARDIAL-INFARCTION; COMMON VARIANTS; RISK;
ASSOCIATION; CHOLESTEROL; CONTRIBUTE
C1 [Newton-Cheh, Christopher] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Human Genet Res,Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Newton-Cheh, Christopher; Smith, J. Gustav] Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA.
[Newton-Cheh, Christopher; Smith, J. Gustav] MIT, Cambridge, MA 02139 USA.
[Smith, J. Gustav] Lund Univ, Dept Cardiol, Lund, Sweden.
RP Newton-Cheh, C (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Human Genet Res,Cardiovasc Res Ctr, 185 Cambridge St,CPZN 5-242, Boston, MA 02114 USA.
EM cnewtoncheh@chgr.mgh.harvard.edu
NR 19
TC 4
Z9 4
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 JUN 22
PY 2010
VL 55
IS 25
BP 2843
EP 2845
DI 10.1016/j.jacc.2009.11.097
PG 3
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 610ZF
UT WOS:000278779300009
PM 20579541
ER
PT J
AU Pejchal, R
Walker, LM
Stanfield, RL
Phogat, SK
Koff, WC
Poignard, P
Burton, DR
Wilson, IA
AF Pejchal, Robert
Walker, Laura M.
Stanfield, Robyn L.
Phogat, Sanjay K.
Koff, Wayne C.
Poignard, Pascal
Burton, Dennis R.
Wilson, Ian A.
TI Structure and function of broadly reactive antibody PG16 reveal an H3
subdomain that mediates potent neutralization of HIV-1
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE neutralizing antibody; PG9; sulfotyrosine; gp120; Env
ID IMMUNODEFICIENCY-VIRUS TYPE-1; HUMAN MONOCLONAL-ANTIBODY; PROXIMAL
EXTERNAL REGION; RECOMBINANT GLYCOPROTEIN-120 VACCINE; ENVELOPE
GLYCOPROTEIN; TYROSINE SULFATION; CHIMERIC VIRUS; BINDING SITE; GP120;
GP41
AB Development of an effective vaccine against HIV-1 will likely require elicitation of broad and potent neutralizing antibodies against the trimeric surface envelope glycoprotein (Env). Monoclonal antibodies (mAbs) PG9 and PG16 neutralize similar to 80% of HIV-1 isolates across all clades with extraordinary potency and target novel epitopes preferentially expressed on Env trimers. As these neutralization properties are ideal for a vaccine-elicited antibody response to HIV-1, their structural basis was investigated. The crystal structure of the antigen-binding fragment (Fab) of PG16 at 2.5 angstrom resolution revealed its unusually long, 28-residue, complementarity determining region (CDR) H3 forms a unique, stable subdomain that towers above the antibody surface. A 7-residue "specificity loop" on the "hammerhead" subdomain was identified that, when transplanted from PG16 to PG9 and vice versa, accounted for differences in the. ne specificity and neutralization of these two mAbs. The PG16 electron density maps also revealed that a CDR H3 tyrosine was sulfated, which was confirmed for both PG9 (doubly) and PG16 (singly) by mass spectral analysis. We further showed that tyrosine sulfation plays a role in binding and neutralization. An N-linked glycan modi. cation is observed in the variable light chain, but not required for antigen recognition. Further, the crystal structure of the PG9 light chain at 3.0 angstrom facilitated homology modeling to support the presence of these unusual features in PG9. Thus, PG9 and PG16 use unique structural features to mediate potent neutralization of HIV-1 that may be of utility in antibody engineering and for high-affinity recognition of a variety of therapeutic targets.
C1 [Walker, Laura M.; Poignard, Pascal; Burton, Dennis R.] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.
[Pejchal, Robert; Stanfield, Robyn L.; Wilson, Ian A.] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA.
[Poignard, Pascal; Burton, Dennis R.; Wilson, Ian A.] Scripps Res Inst, Int AIDS Vaccine Initiat Neutralizing Antibody Ct, La Jolla, CA 92037 USA.
[Wilson, Ian A.] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA.
[Phogat, Sanjay K.; Koff, Wayne C.] Int AIDS Vaccine Initiat, New York, NY 10038 USA.
[Burton, Dennis R.] Massachusetts Gen Hosp, MIT, Ragon Inst, Boston, MA 02114 USA.
[Burton, Dennis R.] Harvard Univ, Boston, MA 02114 USA.
RP Burton, DR (reprint author), Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.
EM burton@scripps.edu; wilson@scripps.edu
RI poignard, pascal/N-6678-2013
FU National Institutes of Health Grants [AI84817, AI33292]; National
Institutes of Health/National Institute of Allergy and Infectious
Diseases National Research Service [AI74372]; International AIDS Vaccine
Initiative Neutralizing Antibody Center; Scripps Research Institute
[20640-MB]
FX We thank the staff at General Medicine and Cancer Institutes
Collaborative Access Team at the Advanced Photon Source and X. Dai for
assistance with data collection, D. Marciano and H. Tien of the Joint
Center for Structural Genomics for assistance with the International
AIDS Vaccine Initiative/The Scripps Research Institute/Joint Center for
Structural Genomics CrystalMation robot, R. Stefanko for technical help,
J. Binley (Torrey Pines Institute for Molecular Studies, San Diego) for
the gift of E51 IgG, H. Gobind Khorana (Massachusetts Institute of
Technology, Cambridge, MA) for the gift of HEK 293S cells, and Peter D.
Kwong and Richard Lerner for helpful discussions. Monoclonal antibodies
PG9 and PG16 were provided for initial experiments by Theraclone
Sciences. This work was supported by National Institutes of Health
Grants AI84817 (to I. A. W. and R. L. S.) and AI33292 (to D. R. B.), by
National Institutes of Health/National Institute of Allergy and
Infectious Diseases National Research Service Award fellowship AI74372
(to R. P.), and by the International AIDS Vaccine Initiative
Neutralizing Antibody Center. This is manuscript 20640-MB from The
Scripps Research Institute.
NR 49
TC 108
Z9 109
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 JUN 22
PY 2010
VL 107
IS 25
BP 11483
EP 11488
DI 10.1073/pnas.1004600107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 614KS
UT WOS:000279058000060
PM 20534513
ER
PT J
AU Wiedemeyer, WR
Dunn, IF
Quayle, SN
Zhang, JH
Chheda, MG
Dunn, GP
Zhuang, L
Rosenbluh, J
Chen, SJ
Xiao, YH
Shapiro, GI
Hahn, WC
Chin, L
AF Wiedemeyer, W. Ruprecht
Dunn, Ian F.
Quayle, Steven N.
Zhang, Jianhua
Chheda, Milan G.
Dunn, Gavin P.
Zhuang, Li
Rosenbluh, Joseph
Chen, Shujuan
Xiao, Yonghong
Shapiro, Geoffrey I.
Hahn, William C.
Chin, Lynda
TI Pattern of retinoblastoma pathway inactivation dictates response to
CDK4/6 inhibition in GBM
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE cyclin-dependent kinase inhibitor; INK4C; PD0332991; targeted therapy
ID CELL-LINES; GLIOBLASTOMA-MULTIFORME; KINASE 4/6; CANCER; AMPLIFICATION;
XENOGRAFTS; P18(INK4C); RECEPTOR; GROWTH; GLIOMA
AB Glioblastoma multiforme (GBM) is a fatal primary brain tumor harboring myriad genetic and epigenetic alterations. The recent multidimensional analysis of the GBM genome has provided a more complete view of the landscape of such alterations and their linked pathways. This effort has demonstrated that certain pathways are universally altered, but that the specific genetic events altered within each pathway can vary for each particular patient's tumor. With this atlas of genetic and epigenetic events, it now becomes feasible to assess how the patterns of mutations in a pathway influence response to drugs that are targeting such pathways. This issue is particularly important for GBM because, in contrast to other tumor types, molecularly targeted therapies have failed to alter overall survival substantially. Here, we combined functional genetic screens and comprehensive genomic analyses to identify CDK6 as a GBM oncogene that is required for proliferation and viability in a subset of GBM cell lines and tumors. Using an available small molecule targeting cyclin-dependent kinases (CDKs) 4 and 6, we sought to determine if the specific pattern of retinoblastoma pathway inactivation dictated the response to CDK4/6 inhibitor therapy. We showed that codeletion of CDKN2A and CDKN2C serves as a strong predictor of sensitivity to a selective inhibitor of CDK4/6. Thus, genome-informed drug sensitivity studies identify a subset of GBMs likely to respond to CDK4/6 inhibition. More generally, these observations demonstrate that the integration of genomic, functional and pharmacologic data can be exploited to inform the development of targeted therapy directed against specific cancer pathways.
C1 [Wiedemeyer, W. Ruprecht; Dunn, Ian F.; Quayle, Steven N.; Chheda, Milan G.; Dunn, Gavin P.; Zhuang, Li; Rosenbluh, Joseph; Chen, Shujuan; Shapiro, Geoffrey I.; Hahn, William C.; Chin, Lynda] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Dunn, Ian F.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA.
[Wiedemeyer, W. Ruprecht; Quayle, Steven N.; Zhang, Jianhua; Zhuang, Li; Chen, Shujuan; Xiao, Yonghong; Chin, Lynda] Belfer Inst Appl Canc Sci, Boston, MA 02115 USA.
[Dunn, Ian F.; Chheda, Milan G.; Dunn, Gavin P.; Rosenbluh, Joseph; Hahn, William C.; Chin, Lynda] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA.
[Dunn, Ian F.; Chheda, Milan G.; Dunn, Gavin P.; Rosenbluh, Joseph; Hahn, William C.; Chin, Lynda] Harvard & Massachusetts Inst Technol, Broad Inst, Cambridge, MA 02142 USA.
[Shapiro, Geoffrey I.; Hahn, William C.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Chin, Lynda] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA.
RP Hahn, WC (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
EM william_hahn@dfci.harvard.edu; lynda_chin@dfci.harvard.edu
FU NINDS NIH HHS [K08 NS062907]
NR 21
TC 75
Z9 79
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 JUN 22
PY 2010
VL 107
IS 25
BP 11501
EP 11506
DI 10.1073/pnas.1001613107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 614KS
UT WOS:000279058000063
PM 20534551
ER
PT J
AU Sun, WJ
Powell, M
O'Dwyer, PJ
Catalano, P
Ansari, RH
Benson, AB
AF Sun, Weijing
Powell, Mark
O'Dwyer, Peter J.
Catalano, Paul
Ansari, Rafat H.
Benson, Al B., III
TI Phase II Study of Sorafenib in Combination With Docetaxel and Cisplatin
in the Treatment of Metastatic or Advanced Gastric and Gastroesophageal
Junction Adenocarcinoma: ECOG 5203
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID RENAL-CELL CARCINOMA; MULTIKINASE INHIBITOR; 1ST-LINE THERAPY;
LUNG-CANCER; TRIAL; FLUOROURACIL; ANGIOGENESIS; EPIRUBICIN; TARGETS;
VEGF
AB Purpose
The combination of sorafenib with chemotherapy is well-tolerated and is associated with encouraging response rates in several malignances. Both docetaxel and cisplatin are active in gastric cancer. A phase II study was conducted to determine the efficacy and toxicity of combined sorafenib, docetaxel, and cisplatin in patients with metastatic or advanced adenocarcinoma of stomach or gastroesophageal junction (GEJ).
Patients and Methods
Forty-four chemotherapy-naive patients with Eastern Cooperative Oncology Group performance status 0 or 1, of whom 80% had metastatic disease and two thirds had poorly differentiated gastric or GEJ adenocarcinoma, were enrolled. The treatment regimen was sorafenib 400 mg orally twice a day for 21 days, docetaxel 75 mg/m(2) intravenously on day 1, and cisplatin 75 mg/m(2) intravenously on day 1, repeated every 21 days. The primary end point was response rate to the combination. Toxicity, overall survival, and progression-free survival were assessed as secondary end points.
Results
Eighteen of the 44 eligible and treated patients showed partial responses (41%; 90% CI, 28% to 54%). The median progression-free survival was 5.8 months (90% CI, 5.4 to 7.4 months). The median overall survival was 13.6 months (90% CI, 8.6 to 16.1 month). The major toxicity of this regimen was neutropenia, which reached grade 3 to 4 in 64% of patients. One patient experienced hemorrhage at the tumor site.
Conclusion
The combination of sorafenib, docetaxel, and cisplatin has an encouraging efficacy profile with tolerable toxicity. Additional studies of sorafenib with chemotherapy are warranted in gastric cancer.
C1 [Sun, Weijing] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Mem Hosp S Bend, South Bend, IN USA.
Northwestern Univ, Chicago, IL 60611 USA.
RP Sun, WJ (reprint author), Univ Penn, Abramson Canc Ctr, 16 Penn Tower,3400 Spruce St, Philadelphia, PA 19104 USA.
EM weijing.sun@uphs.upenn.edu
FU National Cancer Institute [CA23318, CA66636, CA21115, CA15488, CA17145];
Bayer/Onyx
FX Supported in part by Public Health Service Grants No. CA23318, CA66636,
CA21115, CA15488, and CA17145 from the National Cancer Institute.;
Employment or Leadership Position: None Consultant or Advisory Role:
None Stock Ownership: None Honoraria: Weijing Sun, Bayer/Onyx; Al B.
Benson III, Bayer/Onyx Research Funding: Peter J. O'Dwyer, Bayer/Onyx
Expert Testimony: None Other Remuneration: None
NR 22
TC 108
Z9 116
U1 0
U2 3
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JUN 20
PY 2010
VL 28
IS 18
BP 2947
EP 2951
DI 10.1200/JCO.2009.27.7988
PG 5
WC Oncology
SC Oncology
GA 612FW
UT WOS:000278883200005
PM 20458043
ER
PT J
AU Colleoni, M
Cole, BF
Viale, G
Regan, MM
Price, KN
Maiorano, E
Mastropasqua, MG
Crivellari, D
Gelber, RD
Goldhirsch, A
Coates, AS
Gusterson, BA
AF Colleoni, Marco
Cole, Bernard F.
Viale, Giuseppe
Regan, Meredith M.
Price, Karen N.
Maiorano, Eugenio
Mastropasqua, Mauro G.
Crivellari, Diana
Gelber, Richard D.
Goldhirsch, Aron
Coates, Alan S.
Gusterson, Barry A.
TI Classical Cyclophosphamide, Methotrexate, and Fluorouracil Chemotherapy
Is More Effective in Triple-Negative, Node-Negative Breast Cancer:
Results From Two Randomized Trials of Adjuvant Chemoendocrine Therapy
for Node-Negative Breast Cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID HORMONE-RECEPTOR STATUS; PREDICTIVE-VALUE; EXPRESSION; HER2; DOCETAXEL;
ESTROGEN; RESPONSIVENESS; DURATION; SUBTYPES; UPDATE
AB Purpose
Retrospective studies suggest that primary breast cancers lacking estrogen receptor (ER) and progesterone receptor (PR) and not overexpressing human epidermal growth factor receptor 2 (HER2; triple-negative tumors) are particularly sensitive to DNA-damaging chemotherapy with alkylating agents.
Patients and Methods
Patients enrolled in International Breast Cancer Study Group Trials VIII and IX with node-negative, operable breast cancer and centrally assessed ER, PR, and HER2 were included (n = 2,257). The trials compared three or six courses of adjuvant classical cyclophosphamide, methotrexate, and fluorouracil (CMF) with or without endocrine therapy versus endocrine therapy alone. We explored patterns of recurrence by treatment according to three immunohistochemically defined tumor subtypes: triple negative, HER2 positive and endocrine receptor absent, and endocrine receptor present.
Results
Patients with triple-negative tumors (303 patients; 13%) were significantly more likely to have tumors > 2 cm and grade 3 compared with those in the HER2-positive, endocrine receptor absent, and endocrine receptor-present subtypes. No clear chemotherapy benefit was observed in endocrine receptor-present disease (hazard ratio [HR], 0.90; 95% CI, 0.74 to 1.11). A statistically significantly greater benefit for chemotherapy versus no chemotherapy was observed in triple-negative breast cancer (HR, 0.46; 95% CI, 0.29 to 0.73; interaction P = .009 v endocrine receptor-present disease). The magnitude of the chemotherapy effect was lower in HER2-positive endocrine receptor-absent disease (HR, 0.58; 95% CI, 0.29 to 1.17; interaction P = .24 v endocrine receptor-present disease).
Conclusion
The magnitude of benefit of CMF chemotherapy is largest in patients with triple-negative, node-negative breast cancer.
C1 [Colleoni, Marco] Univ Milan, European Inst Oncol, Res Unit Med Senol, Dept Med, I-20141 Milan, Italy.
Univ Milan, Div Pathol & Lab Med, European Inst Oncol, I-20141 Milan, Italy.
Univ Bari, Dept Pathol Anat, Bari, Italy.
Ctr Riferimento Oncol, I-33081 Aviano, Italy.
Univ Vermont, Dept Math & Stat, Coll Engn & Math Sci, Burlington, VT 05405 USA.
Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst,Dept Biostat & Computat Bio, Frontier Sci & Technol Res Fdn,Int Brest Canc Stu, Boston, MA 02115 USA.
Oncol Inst So Switzerland, Bellinzona, Switzerland.
Int Breast Canc Study Grp, Bern, Switzerland.
Univ Sydney, Sydney, NSW 2006, Australia.
Univ Glasgow, Fac Med, Div Canc Sci & Mol Pathol, Glasgow, Lanark, Scotland.
RP Colleoni, M (reprint author), Univ Milan, European Inst Oncol, Res Unit Med Senol, Dept Med, Via Ripamonti 435, I-20141 Milan, Italy.
EM marco.colleoni@ieo.it
RI Maiorano, Eugenio/F-1382-2015
FU Swiss Group for Clinical Cancer Research; Cancer Research
Switzerland/Oncosuisse; Frontier Science and Technology Research
Foundation; Cancer Council Australia; Australian New Zealand Breast
Cancer Trials Group; National Cancer Institute, National Institutes of
Health, Bethesda, MD [CA-75362]; Swedish Cancer Society; Foundation for
Clinical Research of Eastern Switzerland; National Health and Medical
Research Council of Australia; Breakthrough Breast Cancer
FX Supported in part by the Swiss Group for Clinical Cancer Research;
Cancer Research Switzerland/Oncosuisse; Frontier Science and Technology
Research Foundation; The Cancer Council Australia; Australian New
Zealand Breast Cancer Trials Group; Grant No. CA-75362 from the National
Cancer Institute, National Institutes of Health, Bethesda, MD; Swedish
Cancer Society; Foundation for Clinical Research of Eastern Switzerland;
grants from the National Health and Medical Research Council of
Australia; and Breakthrough Breast Cancer (B. A. G.).
NR 40
TC 70
Z9 72
U1 1
U2 7
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 JUN 20
PY 2010
VL 28
IS 18
BP 2966
EP 2973
DI 10.1200/JCO.2009.25.9549
PG 8
WC Oncology
SC Oncology
GA 612FW
UT WOS:000278883200008
PM 20458051
ER
PT J
AU Gururangan, S
Chi, SN
Poussaint, TY
Onar-Thomas, A
Gilbertson, RJ
Vajapeyam, S
Friedman, HS
Packer, RJ
Rood, BN
Boyett, JM
Kun, LE
AF Gururangan, Sridharan
Chi, Susan N.
Poussaint, Tina Young
Onar-Thomas, Arzu
Gilbertson, Richard J.
Vajapeyam, Sridhar
Friedman, Henry S.
Packer, Roger J.
Rood, Brian N.
Boyett, James M.
Kun, Larry E.
TI Lack of Efficacy of Bevacizumab Plus Irinotecan in Children With
Recurrent Malignant Glioma and Diffuse Brainstem Glioma: A Pediatric
Brain Tumor Consortium Study
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; NERVOUS-SYSTEM TUMORS; PHASE-II TRIAL;
ONCOLOGY-GROUP; THERAPY; ANGIOGENESIS; CANCER; TEMOZOLOMIDE; VEGF;
GLIOBLASTOMA
AB Purpose
A phase II study of bevacizumab (BVZ) plus irinotecan (CPT-11) was conducted in children with recurrent malignant glioma (MG) and intrinsic brainstem glioma (BSG).
Patients and Methods
Eligible patients received two doses of BVZ intravenously (10 mg/kg) 2 weeks apart and then BVZ plus CPT-11 every 2 weeks until progressive disease, unacceptable toxicity, or a maximum of 2 years of therapy. Correlative studies included diffusion weighted and T1 dynamic contrast enhanced permeability imaging, BVZ pharmacokinetics, and estimation of vascular endothelial growth factor receptor 2 (VEGFR-2) phosphorylation in peripheral blood mononuclear cells (PBMC) after single-agent BVZ.
Results
Thirty-one evaluable patients received a median of two courses of BVZ plus CPT-11 (range, 1 to 19). No sustained responses were observed in either stratum. Median time to progression for all 34 eligible patients enrolled was 127 days for MG and 71 days for BSG. Progression-free survival rates at 6 months were 41.8% and 9.7% for MG and BSG, respectively. Toxicities related to BVZ included grade 1 to 3 fatigue in seven patients, grade 1 to 2 hypertension in seven patients, grade 1 CNS hemorrhage in four patients, and grade 4 CNS ischemia in two patients. The mean diffusion ratio decreased after two doses of BVZ in patients with MG only. Vascular permeability parameters did not change significantly after therapy in either stratum. Inhibition of VEGFR-2 phosphorylation in PBMC was detected in eight of 11 patients after BVZ exposure.
Conclusion
BVZ plus CPT-11 was well-tolerated but had minimal efficacy in children with recurrent malignant glioma and brainstem glioma.
C1 [Gururangan, Sridharan] Duke Univ, Med Ctr, Preston Robert Tisch Brain Tumor Ctr, MRCP UK, Durham, NC 27710 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Childrens Hosp Boston, Boston, MA USA.
St Jude Childrens Hosp, Memphis, TN 38105 USA.
Operat & Biostat Ctr Pediat Brain Tumor Consortiu, Memphis, TN USA.
Childrens Natl Med Ctr, Washington, DC 20010 USA.
RP Gururangan, S (reprint author), Duke Univ, Med Ctr, Preston Robert Tisch Brain Tumor Ctr, MRCP UK, Box 3624, Durham, NC 27710 USA.
EM gurur002@mc.duke.edu
FU Pediatric Brain Tumor Consortium [U01CA81457]; National Center for
Research Resources [M01RR00188]; American Lebanese Syrian Associated
Charities
FX Supported by Pediatric Brain Tumor Consortium Grant No. U01CA81457,
National Center for Research Resources Grant No. M01RR00188, and the
American Lebanese Syrian Associated Charities.
NR 32
TC 80
Z9 80
U1 0
U2 2
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JUN 20
PY 2010
VL 28
IS 18
BP 3069
EP 3075
DI 10.1200/JCO.2009.26.8789
PG 7
WC Oncology
SC Oncology
GA 612FW
UT WOS:000278883200023
PM 20479404
ER
PT J
AU Sequist, LV
Besse, B
Lynch, TJ
Miller, VA
Wong, KK
Gitlitz, B
Eaton, K
Zacharchuk, C
Freyman, A
Powell, C
Ananthakrishnan, R
Quinn, S
Soria, JC
AF Sequist, Lecia V.
Besse, Benjamin
Lynch, Thomas J.
Miller, Vincent A.
Wong, Kwok K.
Gitlitz, Barbara
Eaton, Keith
Zacharchuk, Charles
Freyman, Amy
Powell, Christine
Ananthakrishnan, Revathi
Quinn, Susan
Soria, Jean-Charles
TI Neratinib, an Irreversible Pan-ErbB Receptor Tyrosine Kinase Inhibitor:
Results of a Phase II Trial in Patients With Advanced Non-Small-Cell
Lung Cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID GROWTH-FACTOR-RECEPTOR; MOLECULAR PREDICTORS; ACQUIRED-RESISTANCE;
ANTITUMOR-ACTIVITY; KRAS MUTATIONS; EGFR MUTATIONS; GENE-MUTATIONS;
BREAST-CANCER; SOLID TUMORS; GEFITINIB
AB Purpose
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have had a significant impact on non-small-cell lung cancer (NSCLC) outcomes, particularly for patients with EGFR mutations. Resistance emerges after 9 to 12 months, primarily mediated by the T790M resistance mutation. We studied neratinib, an irreversible pan-ErbB TKI that may overcome T790M.
Patients and Methods
Patients with advanced NSCLC underwent EGFR sequencing of available tumor tissue at enrollment. Those with <= 12 weeks of prior TKI therapy were placed in arm A if they were EGFR mutation positive or arm B if they were wild-type. Arm C included TKI-naOve patients with adenocarcinoma and light smoking histories (<= 20 pack-years). All patients received daily oral neratinib, initially at 320 mg but subsequently reduced to 240 mg because of excessive diarrhea. The primary end point was objective response rate (RR).
Results
One-hundred sixty-seven patients were treated: 91 in arm A, 48 in arm B, and 28 in arm C. Diarrhea was the most common toxicity; grade 3 incidence was 50% at 320 mg but improved to 25% after dose reduction. The RR was 3% in arm A and zero in arms B and C. No patients with known T790M responded. Notably, three of four patients with an exon 18 G719X EGFR mutation had a partial response and the fourth had stable disease lasting 40 weeks.
Conclusion
Neratinib had low activity in patients with prior benefit from TKIs and in TKI-naOve patients, potentially because of insufficient bioavailability from diarrhea-imposed dose limitation. Responses were seen in patients with the rare G719X EGFR mutation, highlighting the importance of obtaining comprehensive genetic information on trials of targeted agents.
C1 [Sequist, Lecia V.] Harvard Univ, Sch Med, MGH Canc Ctr, Boston, MA 02114 USA.
Dana Farber Canc Ctr, Boston, MA USA.
Wyeth, Cambridge, MA USA.
Inst Gustave Roussy, Villejuif, France.
Yale Canc Ctr, New Haven, CT USA.
Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
Univ So Calif, Los Angeles, CA USA.
Univ Washington, Seattle, WA 98195 USA.
RP Sequist, LV (reprint author), Harvard Univ, Sch Med, MGH Canc Ctr, 55 Fruit St,POB 212, Boston, MA 02114 USA.
EM LVSequist@partners.org
NR 43
TC 218
Z9 231
U1 3
U2 19
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JUN 20
PY 2010
VL 28
IS 18
BP 3076
EP 3083
DI 10.1200/JCO.2009.27.9414
PG 8
WC Oncology
SC Oncology
GA 612FW
UT WOS:000278883200024
PM 20479403
ER
PT J
AU Bang, Y
Kwak, EL
Shaw, AT
Camidge, DR
Iafrate, AJ
Maki, RG
Solomon, BJ
Ou, SI
Salgia, R
Clark, JW
AF Bang, Y.
Kwak, E. L.
Shaw, A. T.
Camidge, D. R.
Iafrate, A. J.
Maki, R. G.
Solomon, B. J.
Ou, S. I.
Salgia, R.
Clark, J. W.
TI Clinical activity of the oral ALK inhibitor PF-02341066 in ALK-positive
patients with non-small cell lung cancer (NSCLC)
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Seoul Natl Univ Hosp, Dept Internal Med, Seoul 110744, South Korea.
Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
Univ Colorado Denver, Aurora, CO USA.
Massachusetts Gen Hosp, Translat Res Lab, Boston, MA 02114 USA.
Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
Peter MacCallum Canc Ctr, Melbourne, Vic, Australia.
Canc Trials Australia, Melbourne, Vic, Australia.
Univ Calif Irvine, Irvine Med Ctr, Chao Family Comprehens Canc Ctr, Orange, CA 92668 USA.
Univ Chicago, Dept Med, Chicago, IL 60637 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 29
Z9 39
U1 0
U2 4
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 JUN 20
PY 2010
VL 28
IS 18
SU S
MA 3
PG 1
WC Oncology
SC Oncology
GA V31JV
UT WOS:000208880800003
PM 27937460
ER
PT J
AU Fidias, P
Ciuleanu, TA
Gladkov, O
Manikhas, GM
Bondarenko, IN
Pluzanska, A
Ramlau, R
Lynch, TJ
AF Fidias, P.
Ciuleanu, T. A.
Gladkov, O.
Manikhas, G. M.
Bondarenko, I. N.
Pluzanska, A.
Ramlau, R.
Lynch, T. J.
TI A randomized, open-label, phase III trial of NOV-002 in combination with
paclitaxel (P) and carboplatin (C) versus paclitaxel and carboplatin
alone for the treatment of advanced non-small cell lung cancer (NSCLC)
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
Inst Oncol Cluj Napoca, Cluj Napoca, Romania.
Reg Oncol Ctr, Chelyabinsk, Russia.
City Clin Oncol Ctr, St Petersburg, Russia.
City Clin Hosp, Dnepropetrovsk, Ukraine.
Klin Chemioterapii Nowotworow AM, Lodz, Poland.
Wielkopolskie Ctr Chorob Pluc & Gruzlicy, Poznan, Poland.
Yale Canc Ctr, New Haven, CT USA.
Smilow Canc Hosp, New Haven, CT USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
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 JUN 20
PY 2010
VL 28
IS 18
SU S
MA LBA7007
PG 1
WC Oncology
SC Oncology
GA V31JV
UT WOS:000208880800037
PM 27937471
ER
PT J
AU Fizazi, K
Carducci, MA
Smith, MR
Damiao, R
Brown, JE
Karsh, L
Milecki, P
Wang, H
Dansey, RD
Goessl, CD
AF Fizazi, K.
Carducci, M. A.
Smith, M. R.
Damiao, R.
Brown, J. E.
Karsh, L.
Milecki, P.
Wang, H.
Dansey, R. D.
Goessl, C. D.
TI A randomized phase III trial of denosumab versus zoledronic acid in
patients with bone metastases from castration-resistant prostate cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Inst Gustave Roussy, Villejuif, France.
Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
Hosp Univ Pedro Ernesto, Rio De Janeiro, Brazil.
Canc Res UK Clin Ctr, Leeds, W Yorkshire, England.
Urol Ctr Colorado, Denver, CO USA.
Wielkopolskie Ctr Onkol, Poznan, Poland.
Amgen Inc, Thousand Oaks, CA USA.
NR 0
TC 6
Z9 6
U1 0
U2 0
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 JUN 20
PY 2010
VL 28
IS 18
SU S
MA LBA4507
PG 1
WC Oncology
SC Oncology
GA V31JV
UT WOS:000208880800023
PM 27937469
ER
PT J
AU Karp, DD
Lee, SJ
Wright, GLS
Johnson, DH
Johnston, MR
Goodman, GE
Clamon, GH
Okawara, GS
Marks, R
Ruckdeschel, JC
AF Karp, D. D.
Lee, S. J.
Wright, G. L. Shaw
Johnson, D. H.
Johnston, M. R.
Goodman, G. E.
Clamon, G. H.
Okawara, G. S.
Marks, R.
Ruckdeschel, J. C.
CA MDACC Thoracic Chemoprevention Res
TI A phase III, intergroup, randomized, double-blind, chemoprevention trial
of selenium (Se) supplementation in resected stage I non-small cell lung
cancer (NSCLC)
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Florida Canc Inst, Hudson, FL USA.
Vanderbilt Univ, Med Ctr, Nashville, TN USA.
Queen Elizabeth 2 Hlth Sci Ctr, Halifax, NS, Canada.
Swedish Med Ctr Canc Inst, Seattle, WA USA.
Univ Iowa Hosp & Clin, Iowa City, IA 52242 USA.
McMaster Univ, Hamilton, ON, Canada.
Mayo Clin Rochester, Rochester, MN USA.
Nevada Canc Inst, Las Vegas, NV USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
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 JUN 20
PY 2010
VL 28
IS 18
SU S
MA CRA7004
PG 1
WC Oncology
SC Oncology
GA V31JV
UT WOS:000208880800011
PM 27937462
ER
PT J
AU Kelly, WK
Halabi, S
Carducci, MA
George, DJ
Mahoney, JF
Stadler, WM
Morris, MJ
Kantoff, PW
Monk, JP
Small, EJ
AF Kelly, W. K.
Halabi, S.
Carducci, M. A.
George, D. J.
Mahoney, J. F.
Stadler, W. M.
Morris, M. J.
Kantoff, P. W.
Monk, J. P., III
Small, E. J.
CA Canc Leukemia Grp
TI A randomized, double-blind, placebo-controlled phase III trial comparing
docetaxel, prednisone, and placebo with docetaxel, prednisone, and
bevacizumab in men with metastatic castration-resistant prostate cancer
(mCRPC): Survival results of CALGB 90401
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Yale Univ, Sch Med, New Haven, CT USA.
Duke Univ, Med Ctr, Durham, NC USA.
Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
Carolinas Hematol Oncol Associates, Charlotte, NC USA.
Univ Chicago, Chicago, IL 60637 USA.
Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Ohio State Univ, Columbus, OH 43210 USA.
Univ Calif San Francisco, San Francisco, CA 94143 USA.
NR 0
TC 24
Z9 24
U1 1
U2 3
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 JUN 20
PY 2010
VL 28
IS 18
SU S
MA LBA4511
PG 1
WC Oncology
SC Oncology
GA V31JV
UT WOS:000208880800024
PM 27937476
ER
PT J
AU O'Day, S
Hodi, FS
McDermott, DF
Weber, RW
Sosman, JA
Haanen, JB
Zhu, X
Yellin, MJ
Hoos, A
Urba, WJ
AF O'Day, S.
Hodi, F. S.
McDermott, D. F.
Weber, R. W.
Sosman, J. A.
Haanen, J. B.
Zhu, X.
Yellin, M. J.
Hoos, A.
Urba, W. J.
TI A phase III, randomized, double-blind, multicenter study comparing
monotherapy with ipilimumab or gp100 peptide vaccine and the combination
in patients with previously treated, unresectable stage III or IV
melanoma
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Angeles Clin & Res Inst, Los Angeles, CA USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
St Marys Hosp, San Francisco, CA USA.
Vanderbilt Univ, Med Ctr, Nashville, TN USA.
Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Amsterdam, Netherlands.
Medarex Inc, Bloomsbury, NJ USA.
Bristol Myers Squibb Co, Wallingford, CT 06492 USA.
Earle A Chiles Res Inst, Portland, OR USA.
NR 0
TC 5
Z9 5
U1 0
U2 1
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 JUN 20
PY 2010
VL 28
IS 18
SU S
MA 4
PG 1
WC Oncology
SC Oncology
GA V31JV
UT WOS:000208880800004
PM 27937457
ER
PT J
AU Schiller, JH
Akerley, WL
Brugger, W
Ferrari, D
Garmey, EG
Gerber, DE
Orlov, SV
Ramlau, R
Von Pawel, J
Sequist, LV
AF Schiller, J. H.
Akerley, W. L.
Brugger, W.
Ferrari, D.
Garmey, E. G.
Gerber, D. E.
Orlov, S. V.
Ramlau, R.
Von Pawel, J.
Sequist, L. V.
TI Results from ARQ 197-209: A global randomized placebo-controlled phase
II clinical trial of erlotinib plus ARQ 197 versus erlotinib plus
placebo in previously treated EGFR inhibitor-naive patients with locally
advanced or metastatic non-small cell lung cancer (NSCLC)
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
Univ Utah, Huntsman Canc Inst, Intermt Canc Care Program, Salt Lake City, UT USA.
Schwarzwald Baar Clin, Villingen Schwenningen, Germany.
Arqule Inc, Woburn, MA USA.
St Petersburg Pavlov State Med Univ, St Petersburg, Russia.
Wielkopolskie Ctr Chorob Pluc & Gruzlicy, Poznan, Poland.
Asklepios Klinikum Gauting, Munich, Germany.
Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
NR 0
TC 7
Z9 7
U1 0
U2 0
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 JUN 20
PY 2010
VL 28
IS 18
SU S
MA LBA7502
PG 1
WC Oncology
SC Oncology
GA V31JV
UT WOS:000208880800039
PM 27937470
ER
PT J
AU Yock, TI
Yeap, BY
Ebb, D
MacDonald, SM
Pulsifer, MB
Marcus, KC
Tarbell, N
AF Yock, T. I.
Yeap, B. Y.
Ebb, D.
MacDonald, S. M.
Pulsifer, M. B.
Marcus, K. C.
Tarbell, N.
TI A phase II trial of proton radiotherapy for medulloblastoma: Preliminary
results
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
Childrens Hosp Med Ctr, Boston, MA USA.
Harvard Univ, Sch Med, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 JUN 20
PY 2010
VL 28
IS 18
SU S
MA CRA9507
PG 1
WC Oncology
SC Oncology
GA V31JV
UT WOS:000208880800013
PM 27937463
ER
PT J
AU Rempel, H
Sun, B
Calosing, C
Pillai, SK
Pulliam, L
AF Rempel, Hans
Sun, Bing
Calosing, Cyrus
Pillai, Satish K.
Pulliam, Lynn
TI Interferon-alpha drives monocyte gene expression in chronic unsuppressed
HIV-1 infection
SO AIDS
LA English
DT Article
DE gene expression; HIV-1; IFN-alpha; lipopolysaccharide; monocyte
ID PLASMACYTOID DENDRITIC CELLS; I INTERFERON; HIV-1-INFECTED PATIENTS;
MICROBIAL TRANSLOCATION; DISEASE PROGRESSION; IMMUNE ACTIVATION; AIDS
PATIENTS; IFN-ALPHA; LIPOPOLYSACCHARIDE; SIALOADHESIN
AB Objectives: HIV-1 infection dysregulates the innate immune system and alters leukocyte-gene expression. The objectives were two fold: to characterize the impact of HIV-1 infection on peripheral monocyte gene expression and to identify the predominant factor(s) responsible for altered gene expression.
Design and methods: In a cross-sectional study (n = 55), CD14(+) monocytes were isolated from 11 HIV-1 seronegative controls, 22 HIV-1 seropositive individuals with low-viral loads (LVL) and 22 HIV-1 seropositive individuals with high-viral loads (HVL). Monocyte gene expression data were collected for control, LVL and HVL individuals using high-density microarrays. We evaluated three HIV-1 disease-related peripheral factors, interferon (IFN)-alpha, IFN-gamma and lipopolysaccharide (LPS) as candidates causing monocyte dysregulation, by comparing gene expression profiles between study individuals and monocytes treated with these factors in vitro. Plasma from HIV-1 positive individuals was quantified for LPS and soluble CD14.
Results: Monocytes from HIV-1-infected individuals with viral loads above 10 000 RNA copies/ml (HVL) displayed an activated phenotype. Characterization of gene expression revealed an ongoing immune response to viral infection including inflammation and chemotaxis. Gene expression analysis of in-vitro-treated HIV-1 seronegative monocytes with IFN-alpha, IFN-gamma or LPS demonstrated that IFN-alpha most accurately recapitulated the HIV-1 HVL profile. No LPS-induced gene expression signature was detected even in HIV-1 individuals with the highest LPS and sCD14 levels.
Conclusion: Monocyte gene expression in individuals with HIV-1 viremia is predominantly due to IFN-alpha, whereas individuals with LVL have a nonactivated phenotype. In monocytes, there was no discernible expression profile linked to LPS exposure. (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins
C1 [Rempel, Hans; Sun, Bing; Calosing, Cyrus; Pulliam, Lynn] San Francisco VA Med Ctr, Dept Lab Med, San Francisco, CA USA.
[Pillai, Satish K.; Pulliam, Lynn] San Francisco VA Med Ctr, Dept Med, San Francisco, CA USA.
[Pillai, Satish K.; Pulliam, Lynn] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Pulliam, Lynn] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA.
RP Pulliam, L (reprint author), San Francisco VA Med Ctr, Dept Lab Med, San Francisco, CA USA.
EM Lynn.Pulliam@ucsf.edu
FU National Institutes of Health (NIMH) [R01MH073478]
FX The authors thank Sandy Charles RN, Linda Adams RN and Harry Lampiris MD
for recruiting individuals into this study and collecting clinical
information. This research was supported by a grant from the National
Institutes of Health (NIMH) R01MH073478.
NR 37
TC 35
Z9 35
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
EI 1473-5571
J9 AIDS
JI Aids
PD JUN 19
PY 2010
VL 24
IS 10
BP 1415
EP 1423
DI 10.1097/QAD.0b013e32833ac623
PG 9
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 609DX
UT WOS:000278636400003
PM 20495440
ER
PT J
AU Yang, KL
Moldovan, GL
D'Andrea, AD
AF Yang, Kailin
Moldovan, George-Lucian
D'Andrea, Alan D.
TI RAD18-dependent Recruitment of SNM1A to DNA Repair Complexes by a
Ubiquitin-binding Zinc Finger
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID FANCONI-ANEMIA PATHWAY; HOMOLOGOUS RECOMBINATION; TRANSLESION SYNTHESIS;
POLYMERASE-ETA; PCNA; PROTEIN; DAMAGE; RAD18; CELLS; FAMILY
AB SNM1A is a member of the SNM1 family of nucleases required for cellular processing of interstrand DNA crosslinks (ICLs). Little is known about the molecular function of SNM1A, in terms of its recruitment to ICL lesions or its DNA damage processing activity. Here we show that SNM1A contains a functional PIP box (PCNA-interacting protein box) and a UBZ (ubiquitin binding zinc finger), required for assembly of SNM1A into nuclear focus. Moreover, RAD18-dependent monoubiquitination of PCNA is required for Mitomycin C and Ultraviolet Light inducible SNM1A nuclear focus assembly. Taken together, our results identify a novel RAD18-PCNA(Ub)-SNM1A pathway required for nuclear focus formation and ICL resistance.
C1 [D'Andrea, Alan D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA.
[Yang, Kailin] Harvard Univ, Sch Med, Biol & Biomed Sci Program, Leder Human Biol Program, Boston, MA 02115 USA.
RP D'Andrea, AD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA.
EM alan_dandrea@dfci.harvard.edu
RI Yang, Kailin/D-7966-2013; Yang, Kailin/L-2205-2013;
OI Yang, Kailin/0000-0001-5968-6738; George-Lucian,
Moldovan/0000-0003-3825-149X
FU National Institutes of Health [R01DK43889, R01HL52725, P01CA092584]
FX This work was supported, in whole or in part, by National Institutes of
Health Grants R01DK43889, R01HL52725, and P01CA092584 (to A. D. D.).
NR 34
TC 30
Z9 30
U1 0
U2 1
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUN 18
PY 2010
VL 285
IS 25
BP 19085
EP 19091
DI 10.1074/jbc.M109.100032
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 610JG
UT WOS:000278727800018
PM 20385554
ER
PT J
AU Deshpande, AS
Fang, PA
Simmer, JP
Margolis, HC
Beniash, E
AF Deshpande, Atul S.
Fang, Ping-An
Simmer, James P.
Margolis, Henry C.
Beniash, Elia
TI Amelogenin-Collagen Interactions Regulate Calcium Phosphate
Mineralization in Vitro
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID DENTIN-ENAMEL JUNCTION; DENTINOENAMEL JUNCTION; HUMAN TEETH;
MECHANICAL-PROPERTIES; PORCINE AMELOGENIN; HYDROXYAPATITE CRYSTALS;
IMPERFECTA PHENOTYPE; SECONDARY STRUCTURE; BONE SIALOPROTEIN; PROTEIN
AB Collagen and amelogenin are two major extracellular organic matrix proteins of dentin and enamel, the mineralized tissues comprising a tooth crown. They both are present at the dentin-enamel boundary (DEB), a remarkably robust interface holding dentin and enamel together. It is believed that interactions of dentin and enamel protein assemblies regulate growth and structural organization of mineral crystals at the DEB, leading to a continuum at the molecular level between dentin and enamel organic and mineral phases. To gain insight into the mechanisms of the DEB formation and structural basis of its mechanical resiliency we have studied the interactions between collagen fibrils, amelogenin assemblies, and forming mineral in vitro, using electron microscopy. Our data indicate that collagen fibrils guide assembly of amelogenin into elongated chain or filament-like structures oriented along the long axes of the fibrils. We also show that the interactions between collagen fibrils and amelogenin-calcium phosphate mineral complexes lead to oriented deposition of elongated amorphous mineral particles along the fibril axes, triggering mineralization of the bulk of collagen fibril. The resulting structure was similar to the mineralized collagen fibrils found at the DEB, with arrays of smaller well organized crystals inside the collagen fibrils and bundles of larger crystals on the outside of the fibrils. These data suggest that interactions between collagen and amelogenin might play an important role in the formation of the DEB providing structural continuity between dentin and enamel.
C1 [Beniash, Elia] Univ Pittsburgh, Sch Dent Med, Dept Oral Biol, Ctr Craniofacial Regenerat, Pittsburgh, PA 15261 USA.
[Simmer, James P.] Univ Michigan, Dept Biol & Mat Sci, Sch Dent, Ann Arbor, MI 48109 USA.
[Margolis, Henry C.] Forsyth Inst, Dept Biomineralizat, Boston, MA 02115 USA.
RP Beniash, E (reprint author), Univ Pittsburgh, Sch Dent Med, Dept Oral Biol, Ctr Craniofacial Regenerat, 589 Salk Hall,3501 Terrace St, Pittsburgh, PA 15261 USA.
EM ebeniash@pitt.edu
RI Deshpande, Atul/B-2993-2008; Fang, PINGAN/A-2461-2009
FU National Institutes of Health NIDCR [DE016703]; UPSOM Department of
Structural Biology [SAP 4100031302]
FX This work was supported, in whole or in part, by National Institutes of
Health NIDCR Grant DE016703 (to E.B.).; We thank Dr. Peijun Zhang for
her help in the analysis of the tomographic data. Electron microscopy
studies were conducted at the Center for Biological Imaging, the
Department of Structural Biology at the University of Pittsburgh and the
Department of Materials Science and Engineering, Carnegie Mellon
University, Pittsburgh. Support for electron tomography studies was
provided by Dr. James Conway of the UPSOM Department of Structural
Biology, including Commonwealth of Pennsylvania Grant SAP 4100031302,
with assistance from Drs. Peijun Zhang and Alexander Makhov.
NR 65
TC 24
Z9 26
U1 4
U2 12
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 JUN 18
PY 2010
VL 285
IS 25
BP 19277
EP 19287
DI 10.1074/jbc.M109.079939
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 610JG
UT WOS:000278727800037
PM 20404336
ER
PT J
AU Pai, S
Ledoux, WR
AF Pai, Shruti
Ledoux, William R.
TI The compressive mechanical properties of diabetic and non-diabetic
plantar soft tissue
SO JOURNAL OF BIOMECHANICS
LA English
DT Article
DE Foot; Diabetic; Subcutaneous; Soft tissue; Viscoelastic
ID HEEL-PAD; FAT PADS; FOOT; MELLITUS; SOLE; BIOMECHANICS; INDENTATION;
STIFFNESS; HISTOLOGY; LOCATION
AB Diabetic subjects are at an increased risk of developing plantar ulcers. Knowledge of the physiologic compressive properties of the plantar soft tissue is critical to understanding the possible mechanisms of ulcer formation and improving treatment options. The purpose of this study was to determine the compressive mechanical properties of the plantar soft tissue in both diabetic and non-diabetic specimens from six relevant locations beneath the foot, namely the hallux (big toe), first, third, and fifth metatarsal heads, lateral midfoot, and calcaneus (heel). Cylindrical specimens (1.905 cm diameter) from these locations were excised and separated from the skin and bone from 4 diabetic and 4 non-diabetic age-matched, elderly, fresh-frozen cadaveric feet. Specimens were then subjected to biomechanically realistic strains of similar to 50% in compression using triangle wave tests conducted at five frequencies ranging from 1 to 10 Hz to determine tissue modulus, energy loss, and strain rate dependence. Diabetic vs. non-diabetic results across all specimens, locations, and testing frequencies demonstrated altered mechanical properties with significantly increased modulus (1146.7 vs. 593.0 kPa) but no change in energy loss (68.5 vs. 67.9%). All tissue demonstrated strain rate dependence and tissue beneath the calcaneus was found to have decreased modulus and energy loss compared to other areas. The results of this study could be used to generate material properties for all areas of the plantar soft tissue in diabetic or non-diabetic feet, with implications for foot computational modeling efforts and potentially for pressure alleviating footwear that could reduce plantar ulcer incidence. Published by Elsevier Ltd.
C1 [Pai, Shruti; Ledoux, William R.] VA RR&D Ctr Excellence Limb Loss Prevent & Prosth, Seattle, WA 98108 USA.
[Pai, Shruti; Ledoux, William R.] Univ Washington, Dept Mech Engn, Seattle, WA 98195 USA.
[Ledoux, William R.] Univ Washington, Dept Orthopaed & Sports Med, Seattle, WA 98195 USA.
RP Ledoux, WR (reprint author), VA Puget Sound, MS 151,1660 S Columbian Way, Seattle, WA 98108 USA.
EM wrledoux@u.washington.edu
RI Ledoux, William/K-6815-2015
OI Ledoux, William/0000-0003-4982-7714
FU National institutes of Health [1R01 DK75633-03]; Department of Veterans
Affairs [A4843C]
FX This study was supported by the National institutes of Health grant 1R01
DK75633-03 and the Department of Veterans Affairs, RR&D Service grant
A4843C. The authors would also like to thank Jane Shofer, M.S. for the
statistical analysis, Michael Fassbind, M.S. for equipment design, and
Paul Vawter for assisting with data analysis.
NR 39
TC 31
Z9 31
U1 2
U2 16
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 JUN 18
PY 2010
VL 43
IS 9
BP 1754
EP 1760
DI 10.1016/j.jbiomech.2010.02.021
PG 7
WC Biophysics; Engineering, Biomedical
SC Biophysics; Engineering
GA 619ZJ
UT WOS:000279468500016
PM 20207359
ER
PT J
AU Kennedy, J
Katsuta, H
Jung, MH
Marselli, L
Goldfine, AB
Balis, UJ
Sgroi, D
Bonner-Weir, S
Weir, GC
AF Kennedy, Jeffrey
Katsuta, Hitoshi
Jung, Min-Ho
Marselli, Lorella
Goldfine, Allison B.
Balis, Ulysses J.
Sgroi, Dennis
Bonner-Weir, Susan
Weir, Gordon C.
TI Protective Unfolded Protein Response in Human Pancreatic Beta Cells
Transplanted into Mice
SO PLOS ONE
LA English
DT Article
ID ENDOPLASMIC-RETICULUM STRESS; ACTIVATING TRANSCRIPTION FACTOR-3; LASER
CAPTURE MICRODISSECTION; ISLET AMYLOID POLYPEPTIDE; ER STRESS;
DIABETES-MELLITUS; OXIDATIVE STRESS; GENE-EXPRESSION; KINASE IRE1;
PATHWAY
C1 [Kennedy, Jeffrey; Katsuta, Hitoshi; Jung, Min-Ho; Marselli, Lorella; Goldfine, Allison B.; Bonner-Weir, Susan; Weir, Gordon C.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Cell Biol & Regenerat Med,Res Div, Boston, MA 02115 USA.
[Kennedy, Jeffrey; Katsuta, Hitoshi; Jung, Min-Ho; Marselli, Lorella; Goldfine, Allison B.; Bonner-Weir, Susan; Weir, Gordon C.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
[Balis, Ulysses J.; Sgroi, Dennis] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Pathol Unit, Boston, MA 02115 USA.
RP Kennedy, J (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Cell Biol & Regenerat Med,Res Div, Boston, MA 02115 USA.
EM gordon.weir@joslin.harvard.edu
OI Bonner-Weir, Susan/0000-0003-4682-0656
FU American Diabetes Association; Juvenile Diabetes Research Foundation;
National Institutes of Health [RO1 DK66056, P30 DK36836]; Diabetes
Research and Wellness Foundation
FX This study was supported by grants from the American Diabetes
Association, the Juvenile Diabetes Research Foundation, the National
Institutes of Health (RO1 DK66056 and P30 DK36836 - the Advanced
Microscopy, Bioinformatics, and Genomics Cores of Joslin Diabetes and
Endocrinology Research Center), and the Diabetes Research and Wellness
Foundation. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 42
TC 18
Z9 20
U1 0
U2 2
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 JUN 18
PY 2010
VL 5
IS 6
AR e11211
DI 10.1371/journal.pone.0011211
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 613KE
UT WOS:000278977200014
PM 20585452
ER
PT J
AU Najafi-Shoushtari, SH
Kristo, F
Li, YX
Shioda, T
Cohen, DE
Gerszten, RE
Naar, AM
AF Najafi-Shoushtari, S. Hani
Kristo, Fjoralba
Li, Yingxia
Shioda, Toshi
Cohen, David E.
Gerszten, Robert E.
Naeaer, Anders M.
TI MicroRNA-33 and the SREBP Host Genes Cooperate to Control Cholesterol
Homeostasis
SO SCIENCE
LA English
DT Article
ID IN-VIVO; INTRONIC MICRORNAS; METABOLISM; ABCA1; ATHEROSCLEROSIS;
COEXPRESSION; MECHANISM; TRANSPORT; EFFLUX; LIVER
AB Proper coordination of cholesterol biosynthesis and trafficking is essential to human health. The sterol regulatory element-binding proteins (SREBPs) are key transcription regulators of genes involved in cholesterol biosynthesis and uptake. We show here that microRNAs (miR-33a/b) embedded within introns of the SREBP genes target the adenosine triphosphate-binding cassette transporter A1 (ABCA1), an important regulator of high-density lipoprotein (HDL) synthesis and reverse cholesterol transport, for posttranscriptional repression. Antisense inhibition of miR-33 in mouse and human cell lines causes up-regulation of ABCA1 expression and increased cholesterol efflux, and injection of mice on a western-type diet with locked nucleic acid-antisense oligonucleotides results in elevated plasma HDL. Our findings indicate that miR-33 acts in concert with the SREBP host genes to control cholesterol homeostasis and suggest that miR-33 may represent a therapeutic target for ameliorating cardiometabolic diseases.
C1 [Najafi-Shoushtari, S. Hani; Shioda, Toshi; Naeaer, Anders M.] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA.
[Najafi-Shoushtari, S. Hani; Naeaer, Anders M.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
[Kristo, Fjoralba; Gerszten, Robert E.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA.
[Li, Yingxia; Cohen, David E.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Gastroenterol, Boston, MA 02115 USA.
[Gerszten, Robert E.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA.
RP Naar, AM (reprint author), Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA.
EM naar@helix.mgh.harvard.edu
OI Najafi-Shoushtari, Hani/0000-0002-7562-4083; Kristo,
Fjoralba/0000-0002-8045-9756
FU NIH [R01GM071449, R21DK084459, R01DK56626, R01DK48873, P30 DK34854];
American Heart Association; Fondation Leducq; Massachusetts Biomedical
Research Corporation
FX We thank S. Vasudevan and A. Walker for critical reading of the
manuscript and K. Coser for technical assistance. This work was
supported by the following funding sources: NIH R01GM071449 and
R21DK084459 (A.M.N.), R01DK56626, R01DK48873, and P30 DK34854 (D. E.
C.), American Heart Association Established Investigator Award (R. E.
G.), the Fondation Leducq (R. E. G.), and Massachusetts Biomedical
Research Corporation Tosteson Fellowship Award (S.H.N.-S.). A.M.N. and
Massachusetts General Hospital have filed a patent application relating
to the therapeutic use of antisense oligonucleotides directed against
miR-33.
NR 29
TC 407
Z9 434
U1 4
U2 50
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
EI 1095-9203
J9 SCIENCE
JI Science
PD JUN 18
PY 2010
VL 328
IS 5985
BP 1566
EP 1569
DI 10.1126/science.1189123
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 611XW
UT WOS:000278859200049
PM 20466882
ER
PT J
AU Rayner, KJ
Suarez, Y
Davalos, A
Parathath, S
Fitzgerald, ML
Tamehiro, N
Fisher, EA
Moore, KJ
Fernandez-Hernando, C
AF Rayner, Katey J.
Suarez, Yajaira
Davalos, Alberto
Parathath, Saj
Fitzgerald, Michael L.
Tamehiro, Norimasa
Fisher, Edward A.
Moore, Kathryn J.
Fernandez-Hernando, Carlos
TI MiR-33 Contributes to the Regulation of Cholesterol Homeostasis
SO SCIENCE
LA English
DT Article
ID CASSETTE TRANSPORTER 1; TANGIER-DISEASE; CELLULAR CHOLESTEROL;
LIPID-METABOLISM; IN-VIVO; HDL; MUTATIONS
AB Cholesterol metabolism is tightly regulated at the cellular level. Here we show that miR-33, an intronic microRNA (miRNA) located within the gene encoding sterol-regulatory element-binding factor-2 (SREBF-2), a transcriptional regulator of cholesterol synthesis, modulates the expression of genes involved in cellular cholesterol transport. In mouse and human cells, miR-33 inhibits the expression of the adenosine triphosphate-binding cassette (ABC) transporter, ABCA1, thereby attenuating cholesterol efflux to apolipoprotein A1. In mouse macrophages, miR-33 also targets ABCG1, reducing cholesterol efflux to nascent high-density lipoprotein (HDL). Lentiviral delivery of miR-33 to mice represses ABCA1 expression in the liver, reducing circulating HDL levels. Conversely, silencing of miR-33 in vivo increases hepatic expression of ABCA1 and plasma HDL levels. Thus, miR-33 appears to regulate both HDL biogenesis in the liver and cellular cholesterol efflux.
C1 [Rayner, Katey J.; Suarez, Yajaira; Davalos, Alberto; Parathath, Saj; Fisher, Edward A.; Moore, Kathryn J.; Fernandez-Hernando, Carlos] NYU, Sch Med, Dept Med, New York, NY 10016 USA.
[Rayner, Katey J.; Suarez, Yajaira; Davalos, Alberto; Parathath, Saj; Fisher, Edward A.; Moore, Kathryn J.; Fernandez-Hernando, Carlos] NYU, Sch Med, Dept Cell Biol, Leon H Charney Div Cardiol, New York, NY 10016 USA.
[Rayner, Katey J.; Suarez, Yajaira; Davalos, Alberto; Parathath, Saj; Fisher, Edward A.; Moore, Kathryn J.; Fernandez-Hernando, Carlos] NYU, Sch Med, Marc & Ruti Bell Vasc Biol & Dis Program, New York, NY 10016 USA.
[Rayner, Katey J.; Fitzgerald, Michael L.; Tamehiro, Norimasa; Moore, Kathryn J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA.
RP Moore, KJ (reprint author), NYU, Sch Med, Dept Med, New York, NY 10016 USA.
EM kathryn.moore@nyumc.org; carlos.fernandez-hernando@nyumc.org
RI Rayner, Katey/K-8914-2012;
OI Davalos, Alberto/0000-0001-5709-6443; Moore,
kathryn/0000-0003-2505-2547; Fisher, Edward/0000-0001-9802-143X
FU American Heart Association [SDG-0835585D, SDG-0835481N, 09GRNT2260352];
NIH [R01AG02055, R01HL074136, R01HL084312, 1P30HL101270-01]; Heart and
Stroke Foundation of Canada
FX We thank E. Hernando-Monje for assisting with lentiviral experiments and
M. Freeman and L. Stuart for discussions. This work was supported by the
American Heart Association (grant SDG-0835585D to C. F.-H., grant
SDG-0835481N to Y.S., and grant 09GRNT2260352 to M. L. F.); NIH (grant
R01AG02055 to K.J.M., grant R01HL074136 to M. L. F., grant R01HL084312
to E. A. F., and grant 1P30HL101270-01 to C. F.-H.); and the Heart and
Stroke Foundation of Canada (K.J.R.). The authors (C. F.-H. and K.J.M)
and New York University School of Medicine are preparing a patent
application relating to the use of miR-33 as a therapeutic.
NR 14
TC 505
Z9 548
U1 10
U2 90
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 JUN 18
PY 2010
VL 328
IS 5985
BP 1570
EP 1573
DI 10.1126/science.1189862
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 611XW
UT WOS:000278859200050
PM 20466885
ER
PT J
AU Grisariu, S
Avni, B
Batchelor, TT
van den Bent, MJ
Bokstein, F
Schiff, D
Kuittinen, O
Chamberlain, MC
Roth, P
Nemets, A
Shalom, E
Ben-Yehuda, D
Siegal, T
AF Grisariu, Sigal
Avni, Batia
Batchelor, Tracy T.
van den Bent, Martin J.
Bokstein, Felix
Schiff, David
Kuittinen, Outi
Chamberlain, Marc C.
Roth, Patrick
Nemets, Anatoly
Shalom, Edna
Ben-Yehuda, Dina
Siegal, Tali
TI Neurolymphomatosis: an International Primary CNS Lymphoma Collaborative
Group report
SO BLOOD
LA English
DT Article
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; PET-CT; MALIGNANT-LYMPHOMA; CRANIAL
NERVES; TRIGEMINAL REGION; CASE ILLUSTRATION; CELL LYMPHOMA;
CAUDA-EQUINA; FDG PET; PLEXUS
AB Neurolymphomatosis (NL) is a rare clinical entity. The International Primary CNS Lymphoma Collaborative Group retrospectively analyzed 50 patients assembled from 12 centers in 5 countries over a 16-year period. NL was related to non-Hodgkin lymphoma in 90% and to acute leukemia in 10%. It occurred as the initial manifestation of malignancy in 26% of cases. The affected neural structures included peripheral nerves (60%), spinal nerve roots (48%), cranial nerves (46%), and plexus (40%) with multiple site involvement in 58%. Imaging studies often suggested the diagnosis with 77% positive magnetic resonance imaging, and 84% (16 of 19) positive computed tomography-positron emission tomography studies. Cerebrospinal fluid cytology was positive in 40%, and nerve biopsy confirmed the diagnosis in 23 of 26 (88%). Treatment in 47 patients included systemic chemotherapy (70%), intra-cerebrospinal fluid chemotherapy (49%), and radiotherapy (34%). Response to treatment was observed in 46%. The median overall survival was 10 months, with 12- and 36-month survival proportions of 46% and 24%, respectively. NL is a challenging diagnosis, but contemporary imaging techniques frequently detect the relevant neural invasion. An aggressive multimodality therapy can prevent neurologic deterioration and is associated with a prolonged survival in a subset of patients. (Blood. 2010;115(24):5005-5011)
C1 [Grisariu, Sigal; Avni, Batia; Shalom, Edna; Ben-Yehuda, Dina; Siegal, Tali] Hadassah Hebrew Univ Med Ctr, Gaffin Ctr Neurooncol, IL-91120 Jerusalem, Israel.
[Grisariu, Sigal; Avni, Batia; Shalom, Edna; Ben-Yehuda, Dina; Siegal, Tali] Hadassah Hebrew Univ Med Ctr, Dept Hematol, IL-91120 Jerusalem, Israel.
[Batchelor, Tracy T.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
[van den Bent, Martin J.] Erasmus Univ, Med Ctr, Neurooncol Unit, Dr Daniel Den Hoed Canc Ctr, Rotterdam, Netherlands.
[Bokstein, Felix] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Dept Oncol, IL-69978 Tel Aviv, Israel.
[Schiff, David] Univ Virginia, Neurooncol Ctr, Charlottesville, VA USA.
[Kuittinen, Outi] Oulu Univ Hosp, Dept Oncol, Oulu, Finland.
[Chamberlain, Marc C.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA.
[Roth, Patrick] Univ Zurich Hosp, Dept Neurol, CH-8091 Zurich, Switzerland.
[Nemets, Anatoly] Barzilai Govt Hosp, Dept Hematol, Ashqelon, Israel.
RP Siegal, T (reprint author), Hadassah Hebrew Univ Med Ctr, Gaffin Ctr Neurooncol, POB 12000, IL-91120 Jerusalem, Israel.
EM siegal@hadassah.org.il
FU NCI NIH HHS [R13 CA124293]
NR 41
TC 74
Z9 81
U1 3
U2 5
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 JUN 17
PY 2010
VL 115
IS 24
BP 5005
EP 5011
DI 10.1182/blood-2009-12-258210
PG 7
WC Hematology
SC Hematology
GA 612HW
UT WOS:000278888900008
PM 20368468
ER
PT J
AU Shapiro, RL
Hughes, MD
Ogwu, A
Kitch, D
Lockman, S
Moffat, C
Makhema, J
Moyo, S
Thior, I
McIntosh, K
van Widenfelt, E
Leidner, J
Powis, K
Asmelash, A
Tumbare, E
Zwerski, S
Sharma, U
Handelsman, E
Mburu, K
Jayeoba, O
Moko, E
Souda, S
Lubega, E
Akhtar, M
Wester, C
Tuomola, R
Snowden, W
Martinez-Tristani, M
Mazhani, L
Essex, M
AF Shapiro, R. L.
Hughes, M. D.
Ogwu, A.
Kitch, D.
Lockman, S.
Moffat, C.
Makhema, J.
Moyo, S.
Thior, I.
McIntosh, K.
van Widenfelt, E.
Leidner, J.
Powis, K.
Asmelash, A.
Tumbare, E.
Zwerski, S.
Sharma, U.
Handelsman, E.
Mburu, K.
Jayeoba, O.
Moko, E.
Souda, S.
Lubega, E.
Akhtar, M.
Wester, C.
Tuomola, R.
Snowden, W.
Martinez-Tristani, M.
Mazhani, L.
Essex, M.
TI Antiretroviral Regimens in Pregnancy and Breast-Feeding in Botswana
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID MOTHER-TO-CHILD; HIV-INFECTED WOMEN; LOW-BIRTH-WEIGHT; RANDOMIZED-TRIAL;
PREMATURE DELIVERY; LOPINAVIR EXPOSURE; EQUIVALENCE TRIAL; PRETERM
DELIVERY; INCREASED RISK; COTE-DIVOIRE
AB Background
The most effective highly active antiretroviral therapy (HAART) to prevent mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) in pregnancy and its efficacy during breast-feeding are unknown.
Methods
We randomly assigned 560 HIV-1-infected pregnant women (CD4+ count, >= 200 cells per cubic millimeter) to receive coformulated abacavir, zidovudine, and lamivudine (the nucleoside reverse-transcriptase inhibitor [NRTI] group) or lopinavir-ritonavir plus zidovudine-lamivudine (the protease-inhibitor group) from 26 to 34 weeks' gestation through planned weaning by 6 months post partum. A total of 170 women with CD4+ counts of less than 200 cells per cubic millimeter received nevirapine plus zidovu-dine-lamivudine (the observational group). Infants received single-dose nevirapine and 4 weeks of zidovudine.
Results
The rate of virologic suppression to less than 400 copies per milliliter was high and did not differ significantly among the three groups at delivery (96% in the NRTI group, 93% in the protease-inhibitor group, and 94% in the observational group) or throughout the breast-feeding period (92% in the NRTI group, 93% in the protease-inhibitor group, and 95% in the observational group). By 6 months of age, 8 of 709 live-born infants (1.1%) were infected (95% confidence interval [CI], 0.5 to 2.2): 6 were infected in utero (4 in the NRTI group, 1 in the protease-inhibitor group, and 1 in the observational group), and 2 were infected during the breast-feeding period (in the NRTI group). Treatment-limiting adverse events occurred in 2% of women in the NRTI group, 2% of women in the protease-inhibitor group, and 11% of women in the observational group.
Conclusions
All regimens of HAART from pregnancy through 6 months post partum resulted in high rates of virologic suppression, with an overall rate of mother-to-child transmission of 1.1%. (ClinicalTrials.gov number, NCT00270296.)
C1 [Shapiro, R. L.] Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA.
[Shapiro, R. L.; Lockman, S.; Thior, I.; McIntosh, K.; Leidner, J.; Essex, M.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA.
[Hughes, M. D.; Kitch, D.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Lockman, S.] Brigham & Womens Hosp, Infect Dis Unit, Boston, MA 02115 USA.
[Tuomola, R.] Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA.
[McIntosh, K.] Childrens Hosp, Div Infect Dis, Boston, MA 02115 USA.
[Powis, K.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Powis, K.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA.
[Ogwu, A.; Moffat, C.; Makhema, J.; Moyo, S.; Thior, I.; van Widenfelt, E.; Asmelash, A.; Tumbare, E.; Mburu, K.; Jayeoba, O.; Moko, E.; Souda, S.; Lubega, E.; Akhtar, M.; Wester, C.] Botswana Harvard AIDS Inst, Gaborone, Botswana.
[Mazhani, L.] Botswana Minist Hlth, Gaborone, Botswana.
[Zwerski, S.; Sharma, U.; Handelsman, E.] NIAID, NIH, Bethesda, MD 20892 USA.
[Snowden, W.] GlaxoSmithKline Inc, Greenford, Middx, England.
[Martinez-Tristani, M.] Abbott Virol, Abbott Pk, IL USA.
RP Shapiro, RL (reprint author), Beth Israel Deaconess Med Ctr, Div Infect Dis, 110 Francis St,Suite GB, Boston, MA 02215 USA.
EM rshapiro@hsph.harvard.edu
FU National Institute of Allergy and Infectious Diseases [U01-AI066454];
Fogarty International Cente [D43 TW00004]
FX Supported by a grant (U01-AI066454) from the National Institute of
Allergy and Infectious Diseases and by a grant (D43 TW00004) from the
Fogarty International Center, which supported several of the trainees
who were involved in this study.
NR 44
TC 250
Z9 255
U1 0
U2 15
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 JUN 17
PY 2010
VL 362
IS 24
BP 2282
EP 2294
DI 10.1056/NEJMoa0907736
PG 13
WC Medicine, General & Internal
SC General & Internal Medicine
GA 611LJ
UT WOS:000278816300007
PM 20554983
ER
PT J
AU Garg, HG
Mrabat, H
Yu, LY
Freeman, C
Li, BYZ
Zhang, FM
Linhardt, RJ
Hales, CA
AF Garg, Hari G.
Mrabat, Hicham
Yu, Lunyin
Freeman, Craig
Li, Boyangzi
Zhang, Fuming
Linhardt, Robert J.
Hales, Charles A.
TI Effect of carboxyl-reduced heparin on the growth inhibition of bovine
pulmonary artery smooth muscle cells
SO CARBOHYDRATE RESEARCH
LA English
DT Article
DE Cell proliferation; Heparin; Carboxyl-reduced heparin
ID MOLECULAR-WEIGHT; IDURONIC ACID; PROLIFERATION; SULFATE;
GLYCOSAMINOGLYCANS; HYPOXIA; RATS
AB Heparin (HP) inhibits the proliferation of bovine pulmonary artery smooth muscle cells (BPASMC's), among other cell types in vitro. In order to develop a potential therapeutic agent to reverse vascular remodeling, we are involved in deciphering the relationship between the native HP structure and its anti-proliferative potency. We have previously reported the influence of the molecular size and the effects of various O-sulfo and N-acetyl groups of HP on growth-inhibitory activity. In this study, to understand the influence of carboxyl groups in the HP structure required for endogenous activity, a chemically modified derivative of native HP was prepared by converting the carboxyl groups of hexuronic acid residues in HP to primary hydroxyl groups. This modification procedure involves the treatment of HP with N-(3-dimethylaminopropyl)-N-ethylcarbodiimide followed by reduction with NaBH(4) to yield carboxyl-reduced heparin (CR-HP). When compared to the antiproliferative potency of native HP on cultured BPASMC's at three dose levels (1, 10, and 100 mu g/mL), the CR-HP showed significantly less potency at all the doses. These results suggest that hexuronic acid residues in both major and variable sequences in HP are essential for the antiproliferative properties of native HP. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Garg, Hari G.; Mrabat, Hicham; Yu, Lunyin; Hales, Charles A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Pulm Crit Care Unit, Boston, MA 02114 USA.
[Freeman, Craig] Australian Natl Univ, John Curtin Sch Med Res, Program Immunol, Canberra, ACT 2601, Australia.
[Li, Boyangzi; Zhang, Fuming; Linhardt, Robert J.] Rensselaer Polytech Inst, Dept Chem & Chem Biol, Ctr Biotechnol & Interdisciplinary Studies, Troy, NY 12180 USA.
[Li, Boyangzi; Zhang, Fuming; Linhardt, Robert J.] Rensselaer Polytech Inst, Dept Biol, Ctr Biotechnol & Interdisciplinary Studies, Troy, NY 12180 USA.
[Li, Boyangzi; Zhang, Fuming; Linhardt, Robert J.] Rensselaer Polytech Inst, Dept Biol & Chem Engn, Ctr Biotechnol & Interdisciplinary Studies, Troy, NY 12180 USA.
RP Garg, HG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Pulm Crit Care Unit, Boston, MA 02114 USA.
EM Hgarg@partners.org
RI Li, Boyangzi/B-4813-2012
FU National Institute of Health [HL039150, HL62244, GM38060]
FX This work was supported by National Institute of Health Grant HL039150
to Charles A. Hales and HL62244 and GM38060 to Robert J. Linhardt.
NR 25
TC 2
Z9 4
U1 0
U2 2
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0008-6215
J9 CARBOHYD RES
JI Carbohydr. Res.
PD JUN 16
PY 2010
VL 345
IS 9
BP 1084
EP 1087
DI 10.1016/j.carres.2010.03.026
PG 4
WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic
SC Biochemistry & Molecular Biology; Chemistry
GA 618RK
UT WOS:000279373200002
PM 20399420
ER
PT J
AU Han, HS
Devaraj, NK
Lee, J
Hilderbrand, SA
Weissleder, R
Bawendi, MG
AF Han, Hee-Sun
Devaraj, Neal K.
Lee, Jungmin
Hilderbrand, Scott A.
Weissleder, Ralph
Bawendi, Moungi G.
TI Development of a Bioorthogonal and Highly Efficient Conjugation Method
for Quantum Dots Using Tetrazine-Norbornene Cycloaddition
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID FREE CLICK CHEMISTRY; GOLD NANOPARTICLES
AB We present a bioorthogonal and modular conjugation method for efficient coupling of organic dyes and biomolecules to quantum dots (QDs) using a norbornene-tetrazine cycloaddition. The use of noncoordinating functional groups combined with the rapid rate of the cycloaddition leads to highly efficient conjugation. We have applied this method to the in situ targeting of norbornene-coated QDs to live cancer cells labeled with tetrazine-modified proteins.
C1 [Han, Hee-Sun; Lee, Jungmin; Bawendi, Moungi G.] MIT, Dept Chem, Cambridge, MA 02139 USA.
[Devaraj, Neal K.; Hilderbrand, Scott A.; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA.
RP Bawendi, MG (reprint author), MIT, Dept Chem, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM mgb@mit.edu
RI Devaraj, Neal/B-4712-2014
FU NIH [5-U54-CA119349-05, 5R01CA126642-02, U01-HL080731, T32-CA79443]; MIT
DCIF [CHE-980806, DBI-9729592]; Samsung
FX This work was supported by the NIH through Grants 5-U54-CA119349-05
(M.G.B., R.W.), 5R01CA126642-02 (M.G.B.), U01-HL080731 (R.W.), and
T32-CA79443 (N.K.D.) and by the MIT DCIF (CHE-980806, DBI-9729592) via
the use of its shared user facilities. H.-S.H. was supported by the
Samsung Scholarship.
NR 13
TC 117
Z9 118
U1 5
U2 103
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 JUN 16
PY 2010
VL 132
IS 23
BP 7838
EP +
DI 10.1021/ja101677r
PG 3
WC Chemistry, Multidisciplinary
SC Chemistry
GA 610FS
UT WOS:000278717700008
PM 20481508
ER
PT J
AU Hackler, EA
Byun, NE
Jones, CK
Williams, JM
Baheza, R
Sengupta, S
Grier, MD
Avison, M
Conn, PJ
Gore, JC
AF Hackler, E. A.
Byun, N. E.
Jones, C. K.
Williams, J. M.
Baheza, R.
Sengupta, S.
Grier, M. D.
Avison, M.
Conn, P. J.
Gore, J. C.
TI SELECTIVE POTENTIATION OF THE METABOTROPIC GLUTAMATE RECEPTOR SUBTYPE 2
BLOCKS PHENCYCLIDINE-INDUCED ACTIVATION HYPERLOCOMOTION AND BRAIN
SO NEUROSCIENCE
LA English
DT Article
DE mGluR2; BINA; phMRI; BOLD; antipsychotic; schizophrenia
ID POSITIVE ALLOSTERIC MODULATOR; INDUCED LOCOMOTOR-ACTIVITY;
PHARMACOLOGICAL MRI; ANIMAL-MODELS; ANTIPSYCHOTIC ACTIVITY; STEREOTYPED
BEHAVIOR; GLUCOSE-UTILIZATION; COMPONENT ANALYSIS; NMDA ANTAGONIST;
MESSENGER-RNA
AB Previous preclinical and clinical studies have demonstrated the efficacy of group II metabotropic glutamate receptor (mGluR) agonists as potential antipsychotics. Recent studies utilizing mGluR2-, mGluR3-, and double knockout mice support that the antipsychotic effects of those compounds are mediated by mGluR2. Indeed, biphenyl indanone-A (BINA), an allosteric potentiator of mGluR2, is effective in experimental models of psychosis, blocking phencyclidine (PCP)-induced hyperlocomotion and prepulse inhibition deficits in mice. In this study, we administered the NMDA receptor antagonist PCP (5.6 mg/kg i.p.) to rats, an established animal model predictive of schizophrenia. Here, we show that BINA (32 mg/kg i.p.) attenuated PCP-induced locomotor activity in rats. Using behaviorally relevant doses of BINA and PCP, we performed pharmacological magnetic resonance imaging (phMRI) to assess the specific brain regions that underlie the psychotomimetic effects of PCP, and examined how BINA modulated the PCP-induced functional changes in vivo. In anesthetized rats, acute administration of PCP produced robust, sustained blood oxygenation level-dependent (BOLD) activation in specific cortical, limbic, thalamic, and striatal regions. Pretreatment with BINA suppressed the amplitude of the BOLD response to PCP in the prefrontal cortex, caudaute-putamen, nucleus accumbens, and mediodorsal thalamus. Our results show key brain structures underlying PCP-induced behaviors in a preclinical model of schizophrenia, and, importantly, its reversal by potentiation of mGluR2 by BINA, revealing specific brain regions functionally involved in its pharmacological action. Finally, our findings bolster the growing body of evidence that mGluR2 is a viable target for the treatment of schizophrenia. (C) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.
C1 [Byun, N. E.] Vanderbilt Univ, Inst Imaging Sci, AA Med Ctr N 3101, Nashville, TN 37232 USA.
[Hackler, E. A.; Byun, N. E.; Williams, J. M.; Avison, M.; Gore, J. C.] Vanderbilt Univ, Med Ctr, Dept Radiol & Radiol Sci, Nashville, TN 37232 USA.
[Jones, C. K.] Tennessee Valley Healthcare Syst, US Dept Vet Affairs, Nashville, TN 37212 USA.
[Jones, C. K.; Grier, M. D.; Avison, M.; Conn, P. J.] Vanderbilt Univ, Med Ctr, Dept Pharmacol, Nashville, TN 37232 USA.
[Jones, C. K.; Conn, P. J.] Vanderbilt Univ, Med Ctr, Vanderbilt Program Drug Discovery, Nashville, TN 37232 USA.
[Sengupta, S.; Gore, J. C.] Vanderbilt Univ, Dept Biomed Engn, Nashville, TN 37232 USA.
[Gore, J. C.] Vanderbilt Univ, Dept Phys, Nashville, TN 37232 USA.
[Gore, J. C.] Vanderbilt Univ, Med Ctr, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA.
RP Byun, NE (reprint author), Vanderbilt Univ, Inst Imaging Sci, AA Med Ctr N 3101, 1161 21st Ave S, Nashville, TN 37232 USA.
EM nellie.byun@vanderbilt.edu
RI Conn, Peter/D-7848-2012
FU National Institutes of Health; NIBIB; NIMH
FX This work was supported by grants from the National Institutes of
Health, NIBIB and NIMH. Vanderbilt is a site in the National Institutes
of Health-Supported Molecular Libraries Probe Center Network. We would
like to thank Jarred True of the Vanderbilt University Institute of
Imaging Science for his technical support and assistance.
NR 70
TC 33
Z9 33
U1 0
U2 3
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0306-4522
J9 NEUROSCIENCE
JI Neuroscience
PD JUN 16
PY 2010
VL 168
IS 1
BP 209
EP 218
DI 10.1016/j.neuroscience.2010.02.057
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 601ER
UT WOS:000278041500020
PM 20350588
ER
PT J
AU Kulik, A
Singh, JP
Levin, R
Avorn, J
Choudhry, NK
AF Kulik, Alexander
Singh, Jagmeet P.
Levin, Raisa
Avorn, Jerry
Choudhry, Niteesh K.
TI Association Between Statin Use and the Incidence of Atrial Fibrillation
Following Hospitalization for Coronary Artery Disease
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID BYPASS GRAFT-SURGERY; C-REACTIVE PROTEIN; PREOPERATIVE STATINS;
CARDIAC-SURGERY; PREVENTION; THERAPY; RISK; ATORVASTATIN; METAANALYSIS;
ARRHYTHMIAS
AB Mounting evidence suggests that statins possess antiarrhythmic properties and inhibit atrial fibrillation (AF). The goal of this study was to evaluate the relation between statin use and new-onset AF in a large cohort of patients with coronary artery disease. We identified all Medicare beneficiaries >= 65 years old who had been hospitalized for acute myocardial infarction or coronary revascularization from 1995 to 2004 and participated in 1 of 2 government-sponsored medication benefit programs. Patients with a history of AF before and during hospitalization were excluded. This yielded a cohort of 29,088. The incidence of new AF was compared between patients who were (n = 8,450) and were not (n = 20,638) prescribed statins within 1 month of hospital discharge after their cardiac event. New-onset AFs within 5 and 10 years were 32.6% and 51.2%, respectively, in patients who received statins compared to 38.3% and 58.0% in patients who did not receive statins (unadjusted hazard ratio 0.82, 95% confidence interval 0.78 to 0.86). Multivariable analysis controlling for demographic and clinical confounders indicated that statin use independently decreased the risk of developing new-onset AF compared to nonusers (adjusted hazard ratio 0.90, 95% confidence interval 0.85 to 0.94). Adjustment for propensity-score and health-seeking behaviors yielded nearly identical results. In conclusion, statin therapy initiated within 1 month after hospital discharge is independently associated with a decrease in the risk of new-onset AF after myocardial infarction or coronary revascularization. These findings lend support to the antiarrhythmic effects of statins and suggest another benefit for their use in patients with coronary artery disease. (C) 2010 Elsevier Inc. All rights reserved. (Am J Cardiol 2010;105:1655-1660)
C1 [Levin, Raisa; Avorn, Jerry; Choudhry, Niteesh K.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA.
[Kulik, Alexander] Boca Raton Community Hosp, Lynn Heart Inst, Div Cardiothorac Surg, Boca Raton, FL USA.
[Singh, Jagmeet P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02115 USA.
RP Choudhry, NK (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA.
EM nchoudhry@partners.org
NR 27
TC 19
Z9 22
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 JUN 15
PY 2010
VL 105
IS 12
BP 1655
EP 1660
DI 10.1016/j.amjcard.2010.01.341
PG 6
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 618TH
UT WOS:000279378100002
PM 20538110
ER
PT J
AU Don, CW
Witzke, C
Cubeddu, RJ
Herrero-Garibi, J
Pomerantsev, E
Caldera, AE
McCarty, D
Inglessis, I
Palacios, IF
AF Don, Creighton W.
Witzke, Christian
Cubeddu, Roberto J.
Herrero-Garibi, Jesus
Pomerantsev, Eugene
Caldera, Angel E.
McCarty, David
Inglessis, Ignacio
Palacios, Igor F.
TI Comparison of Procedural and In-Hospital Outcomes of Percutaneous
Balloon Aortic Valvuloplasty in Patients > 80 Years Versus Patients <=
80 Years
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID LONG-TERM SURVIVAL; ELDERLY-PATIENTS; FOLLOW-UP; STENOSIS; REGISTRY; AGE
AB Percutaneous balloon aortic valvuloplasty (PBAV) is a procedure used for palliation, bridging to surgery, and as an integral step in the procedure for percutaneous aortic valve replacement. Older patients with severe aortic stenosis are thought to have greater risk for adverse perioperative events than younger patients. The aim of this study was to evaluate the outcomes of patients aged >80 years and those aged <= 80 years who underwent PBAV to identify factors associated with adverse clinical outcomes. This was a retrospective study of 111 consecutive patients with severe symptomatic aortic stenosis who underwent retrograde PBAV at Massachusetts General Hospital from December 2004 to December 2008. Forty-nine patients (44%) were men, and the mean age for the whole group was 82 +/- 8 years. Patients were divided into 2 age groups: those aged >80 years (n = 73) and those aged <= 80 years (n = 38). Procedural outcomes, complications, and in-hospital adverse events were compared. Multivariate logistic regression was used for the adjusted analysis. Nearly 90% of patients were in New York Heart Association class III or IV. Patients aged >80 years had lower baseline ejection fractions (43.5% vs 56.1%, p <0.01) and smaller aortic valve areas (059 vs 0.73 cm(2), p <0.01). Although the 2 age groups had a similar percentage of aortic valve area increase (55.5% vs 45.2%, p = 0.28), those aged >80 years had smaller post-PBAV aortic valve areas (0.89 vs 1.02 cm(2), p <0.05). Overall, in-hospital mortality was 8.1%, with no significant differences between the groups. Advanced age was not an independent predictor of in-hospital death, myocardial infarction, stroke, cardiac arrest, or tamponade; however, patients aged >80 years had a significantly higher incidence of intra-procedural emergent intubation and cardiopulmonary resuscitation compared to the younger group. New York Heart Association class was the only independent predictor of worse in-hospital outcomes. In conclusion, compared to younger patients, those aged >80 years had less favorable preprocedural characteristics for PBAV but similar overall in-hospital clinical outcomes. Patients aged >80 years had significantly higher incidence of emergent intubation and cardiopulmonary resuscitation during PBAV. (C) 2010 Elsevier Inc. All rights reserved. (Am J Cardiol 2010;105:1815-1820)
C1 [Don, Creighton W.; Witzke, Christian; Cubeddu, Roberto J.; Herrero-Garibi, Jesus; Pomerantsev, Eugene; Caldera, Angel E.; McCarty, David; Inglessis, Ignacio; Palacios, Igor F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA.
[Don, Creighton W.] Univ Washington, Med Ctr, Div Cardiol, Seattle, WA 98195 USA.
[Cubeddu, Roberto J.] Aventura Hosp & Med Ctr, Div Cardiol, Miami, FL USA.
RP Don, CW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA.
EM cwdon@u.washington.edu
NR 16
TC 14
Z9 14
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 JUN 15
PY 2010
VL 105
IS 12
BP 1815
EP 1820
DI 10.1016/j.amjcard.2010.01.366
PG 6
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 618TH
UT WOS:000279378100028
PM 20538136
ER
PT J
AU Wear, J
McPherson, TB
Kolling, WM
AF Wear, Jennifer
McPherson, Timothy B.
Kolling, William M.
TI Stability of sodium bicarbonate solutions in polyolefin bags
SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY
LA English
DT Article
DE Alkalinizing agents; Concentration; Containers; Dextrose; Diluents;
Hydrogen ion concentration; Injections; Polyolefin; Refrigeration;
Sodium bicarbonate; Stability; Storage; Temperature; Water for Injection
ID OVERDOSE; MANAGEMENT
AB Purpose. The stability of sodium bicarbonate solutions in sterile water for injection or 5% dextrose injection stored at 21-24 degrees C or 2-4 degrees C was evaluated.
Methods. Sodium bicarbonate injection was obtained in 50-mL vials of 8.4% (1 meq/mL). A total of 50, 100, or 150 meq of sodium bicarbonate was added to each 1-L polyolefin bag of either sterile water for injection or 5% dextrose injection. All solutions were prepared in a laminar-airflow hood using aseptic technique. Bags were punctured once to remove headspace air and once for the addition of each 50 meq of sodium bicarbonate. Six replicates of each test solution were prepared. The solutions were stored at 21-24 degrees C and 2-4 degrees C. Control solutions (50 and 150 meq) were similarly prepared in triplicate. Control solutions were sparged with either nitrogen gas or oxygen gas before storage. Sodium bicarbonate stability was assessed by measuring solution pH. Bicarbonate content was measured utilizing titration. Both pH and bicarbonate concentrations were measured immediately upon preparation and on days 3, 5, and 7 for both test and control solutions.
Results. All 95% confidence interval values for sample solution pH remained within 7.0-8.5 for seven days at 2-4 degrees C.
Conclusion. Sodium bicarbonate solutions of 50, 100, and 150 meq in sterile water for injection or 5% dextrose injection were stable for up to seven days when refrigerated. The 50-meq solution was stable for up to 48 hours when stored at room temperature, and the 100- and 150-meq solutions were stable for up to 30 hours when stored at room temperature.
C1 [McPherson, Timothy B.; Kolling, William M.] So Illinois Univ, Sch Pharm, Edwardsville, IL 62026 USA.
[Wear, Jennifer] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA.
RP McPherson, TB (reprint author), So Illinois Univ, Sch Pharm, Campus Box 2000, Edwardsville, IL 62026 USA.
EM tmcpher@siue.edu
NR 16
TC 2
Z9 2
U1 0
U2 0
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 JUN 15
PY 2010
VL 67
IS 12
BP 1026
EP 1029
DI 10.2146/ajhp090301
PG 4
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 609VG
UT WOS:000278685100017
PM 20516474
ER
PT J
AU Cartin-Ceba, R
Bajwa, EK
AF Cartin-Ceba, Rodrigo
Bajwa, Ednan K.
TI 24-Hour On-Site Intensivist in the Intensive Care Unit: Yes
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Editorial Material
ID SATISFACTION; IMPACT
C1 [Cartin-Ceba, Rodrigo] Mayo Clin, Div Pulm Crit Care Med, Rochester, MN 55905 USA.
[Bajwa, Ednan K.] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA.
[Bajwa, Ednan K.] Harvard Univ, Sch Med, Boston, MA USA.
RP Cartin-Ceba, R (reprint author), Mayo Clin, Div Pulm Crit Care Med, Rochester, MN 55905 USA.
FU NHLBI NIH HHS [K23 HL087934]
NR 11
TC 12
Z9 12
U1 0
U2 0
PU AMER THORACIC SOC
PI NEW YORK
PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA
SN 1073-449X
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PD JUN 15
PY 2010
VL 181
IS 12
BP 1279
EP 1280
DI 10.1164/rccm.201004-0676ED
PG 2
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 615UB
UT WOS:000279162000001
PM 20558637
ER
PT J
AU Jones, SF
Gaggar, A
AF Jones, Shirley Fong
Gaggar, Amit
TI Is There a Doctor in the House? The Downside of 24/7 Attending Coverage
in Academic Intensive Care Units
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Editorial Material
ID MORTALITY; PROGRAMS
C1 [Jones, Shirley Fong] Scott & White Mem Hosp & Clin, Texas A&M Hlth Sci Ctr, Dept Internal Med, Temple, TX 76508 USA.
[Gaggar, Amit] Univ Alabama, Dept Internal Med, Birmingham, AL USA.
[Gaggar, Amit] Birmingham VA Med Ctr, Birmingham, AL USA.
RP Jones, SF (reprint author), Scott & White Mem Hosp & Clin, Texas A&M Hlth Sci Ctr, Dept Internal Med, Temple, TX 76508 USA.
NR 7
TC 12
Z9 12
U1 0
U2 0
PU AMER THORACIC SOC
PI NEW YORK
PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA
SN 1073-449X
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PD JUN 15
PY 2010
VL 181
IS 12
BP 1280
EP 1281
DI 10.1164/rccm.201005-0681ED
PG 2
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 615UB
UT WOS:000279162000002
PM 20558638
ER
PT J
AU Ziemer, DC
Kolm, P
Weintraub, WS
Vaccarino, V
Rhee, MK
Twombly, JG
Narayan, V
Koch, DD
Phillips, LS
AF Ziemer, David C.
Kolm, Paul
Weintraub, William S.
Vaccarino, Viola
Rhee, Mary K.
Twombly, Jennifer G.
Narayan, Venkat
Koch, David D.
Phillips, Lawrence S.
TI Glucose-Independent, Black-White Differences in Hemoglobin A(1c) Levels
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Article
ID DEPENDENT DIABETES-MELLITUS; MEAN BLOOD-GLUCOSE; HEALTH-CARE ACCESS;
GLYCEMIC CONTROL; GLYCATED HEMOGLOBIN; ETHNIC DISPARITIES; MICROVASCULAR
COMPLICATIONS; GLYCOSYLATED HEMOGLOBIN; BIOLOGICAL VARIATION; RACIAL
DISPARITIES
AB Background: A previous study of participants with prediabetes found that hemoglobin A(1c) (HbA(1c)) levels differed between black and white participants with no differences in glucose concentration.
Objective: To determine whether black-white differences in HbA(1c) level are present in other populations and across the full spectrum of glycemia.
Design: Cross-sectional, retrospective.
Setting: Outpatient.
Participants: 1581 non-Hispanic black and white participants between 18 and 87 years of age without known diabetes in the SIGT (Screening for Impaired Glucose Tolerance) study and 1967 non-Hispanic black and white participants older than 40 years without known diabetes in the NHANES III (Third National Health and Nutrition Examination Survey).
Measurements: HbA(1c) levels, anthropometry, and plasma glucose levels during oral glucose tolerance testing.
Results: Hemoglobin A(1c) levels were higher in black than in white participants with normal glucose tolerance (0.13 percentage point [P < 0.001] in the SIGT sample and 0.21 percentage point [P < 0.001] in the NHANES III sample), prediabetes (0.26 percentage point [P < 0.001] and 0.30 percentage point [P < 0.001], respectively), or diabetes (0.47 percentage point [P < 0.020] and 0.47 percentage point [P < 0.013], respectively) after adjustment for plasma glucose levels and other characteristics known to correlate with HbA(1c) levels.
Limitation: The mechanism for the differences is unknown.
Conclusion: Black persons have higher HbA(1c) levels than white persons across the full spectrum of glycemia, and the differences increase as glucose intolerance worsens. These findings could limit the use of HbA(1c) to screen for glucose intolerance, indicate the risk for complications, measure quality of care, and evaluate disparities in health.
C1 [Ziemer, David C.] Emory Univ, Sch Med, Div Endocrinol, Atlanta, GA 30303 USA.
Med Ctr, US Dept Vet Affairs, Atlanta, GA USA.
Christiana Care Hlth Syst, Newark, DE USA.
RP Ziemer, DC (reprint author), Emory Univ, Sch Med, Div Endocrinol, 49 Jesse Hill Jr Dr SE, Atlanta, GA 30303 USA.
FU National Institutes of Health and National Center for Research Resources
[DK07298, DK062668, RR017643, DK066204, RR00039]; U.S. Department of
Veterans Affairs Health Services Research and Development Service [SHP
08-144, IIR 07-138]
FX By the National Institutes of Health and National Center for Research
Resources (awards DK07298, DK062668, RR017643, DK066204, and RR00039)
and U.S. Department of Veterans Affairs Health Services Research and
Development Service (awards SHP 08-144 and IIR 07-138).
NR 51
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PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
EI 1539-3704
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD JUN 15
PY 2010
VL 152
IS 12
BP 770
EP +
DI 10.7326/0003-4819-152-12-201006150-00004
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 611OP
UT WOS:000278827700002
PM 20547905
ER
PT J
AU Iezzoni, LI
Ronan, LJ
AF Iezzoni, Lisa I.
Ronan, Laurence J.
TI Disability Legacy of the Haitian Earthquake
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Editorial Material
ID AMPUTATION
C1 [Iezzoni, Lisa I.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Iezzoni, LI (reprint author), Massachusetts Gen Hosp, Mongan Inst Hlth Policy, 50 Staniford St,Room 901B, Boston, MA 02114 USA.
EM liezzoni@partners.org
NR 14
TC 17
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U1 0
U2 3
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
EI 1539-3704
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD JUN 15
PY 2010
VL 152
IS 12
BP 812
EP 814
DI 10.7326/0003-4819-152-12-201006150-00234
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 611OP
UT WOS:000278827700008
PM 20231547
ER
PT J
AU Rosell, DR
Thompson, JL
Slifstein, M
Xu, XY
Frankle, WG
New, AS
Goodman, M
Weinstein, SR
Laruelle, M
Abi-Dargham, A
Siever, LJ
AF Rosell, Daniel R.
Thompson, Judy L.
Slifstein, Mark
Xu, Xiaoyan
Frankle, W. Gordon
New, Antonia S.
Goodman, Marianne
Weinstein, Shauna R.
Laruelle, Marc
Abi-Dargham, Anissa
Siever, Larry J.
TI Increased Serotonin 2A Receptor Availability in the Orbitofrontal Cortex
of Physically Aggressive Personality Disordered Patients
SO BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE Aggression; intermittent explosive disorder; orbitofrontal cortex;
personality disorder; positron emission tomography; serotonin
ID INTERMITTENT EXPLOSIVE DISORDER; POSITRON-EMISSION-TOMOGRAPHY;
PLACEBO-CONTROLLED TRIAL; PRIMATE CEREBRAL-CORTEX; IMPULSIVE AGGRESSION;
5-HT2A RECEPTORS; ABNORMAL AGGRESSION; RAT-BRAIN; LEARNED HELPLESSNESS;
PREFRONTAL CORTEX
AB Background: Impulsive physical aggression is a common and problematic feature of many personality disorders. The serotonergic system is known to be involved in the pathophysiology of aggression, and multiple lines of evidence have implicated the serotonin 2A receptor (5-HT(2A)R). We sought to examine the role of the 5-HT(2A)R in impulsive aggression specifically in the orbitofrontal cortex (OFC), given that our own studies and an extensive literature indicate that serotonergic disturbances in the OFC are linked to aggression. We have previously hypothesized that increased 5-HT(2A)R function in the OFC is a state phenomenon that promotes impulsive aggression.
Methods: Serotonin 2A receptor availability was measured with positron emission tomography and the selective 5-HT(2A)R antagonist radioligand [(11)C]MDL100907 in two groups of impulsively aggressive personality disordered patients-14 with current physical aggression, and 15 without current physical aggression-and 25 healthy control subjects. Clinical ratings of various symptom dimensions were also obtained.
Results: Orbitofrontal 5-HT(2A)R availability was greater in patients with current physical aggression compared with patients without current physical aggression and healthy control subjects; no differences in OFC 5-HT(2A)R availability were observed between patients without current physical aggression and healthy control subjects. No significant differences in 5-HT(2A)R availability were observed in other brain regions examined. Among both groups of impulsively aggressive personality disordered patients combined, OFC 5-HT(2A)R availability was correlated, specifically, with a state measure of impulsive aggression.
Conclusions: These findings are consistent with our previously described model in which impulsive aggression is related to dynamic changes in 5-HT(2A)R function in the OFC.
C1 [Rosell, Daniel R.; New, Antonia S.; Goodman, Marianne; Weinstein, Shauna R.; Siever, Larry J.] James J Peters Vet Affairs Med Ctr, Bronx, NY USA.
[Rosell, Daniel R.; New, Antonia S.; Goodman, Marianne; Weinstein, Shauna R.; Siever, Larry J.] Mt Sinai Sch Med, New York, NY USA.
[Thompson, Judy L.; Slifstein, Mark; Xu, Xiaoyan; Abi-Dargham, Anissa] Columbia Univ, Med Ctr, New York, NY 10027 USA.
[Thompson, Judy L.; Slifstein, Mark; Xu, Xiaoyan; Abi-Dargham, Anissa] New York State Psychiat Inst & Hosp, New York, NY 10032 USA.
[Frankle, W. Gordon] Univ Pittsburgh, Western Psychiat Inst & Clin, Pittsburgh, PA 15213 USA.
[Laruelle, Marc] Univ London Imperial Coll Sci Technol & Med, London, England.
RP Siever, LJ (reprint author), James J Peters Dept Vet Affairs, Med Ctr, 130 W Kingsbridge Rd,Room 6A-44, Bronx, NY 10468 USA.
EM larry.siever@va.gov
OI Frankle, William/0000-0003-0356-4197
FU National Institute of Mental Health [MH063875]; Veterans Affairs Merit
Review [7609-028]; Veterans Affairs VISN 3 Mental Illness Research,
Education and Clinical Center; Office of Academic Affiliations; Mental
Illness Research and Treatment, Department of Veterans Affairs; National
Center for Research Resources (NCRR) [MO1-RR-00071]; Intracellular
Therapies, Inc.; GlaxoSmithKline, Inc.; Bristol-Meyers Squibb, Inc.;
Sepracor Inc.
FX This research was supported by Grant MH063875 from the National
Institute of Mental Health and by a Veterans Affairs Merit Review Grant
(7609-028) to us and by the Veterans Affairs VISN 3 Mental Illness
Research, Education and Clinical Center. Writing of this manuscript was
supported by the Office of Academic Affiliations, Advanced Fellowship
Program in Mental Illness Research and Treatment, Department of Veterans
Affairs. This publication was made possible by Grant MO1-RR-00071 from
the National Center for Research Resources (NCRR), a component of the
National Institutes of Health (Nth). Its contents are solely the
responsibility of the authors and do not necessarily represent the
official views of NCRR or NIH.; Dr. Slifstein reports the following:
Grant Support: Intracellular Therapies, Inc.; Consulting:
GlaxoSmithKline, Inc., Amgen, Inc. Dr. Frankle reports the following:
Consulting: Ono Pharma, USA, Inc.; Sepracor, Inc.; Speaking Fees:
Bristol-Meyers Squibb, Inc.; Research Support: GlaxoSmithKline, Inc.;
and Sepracor Inc. Dr. Laruelle is a full time employee of
GlaxoSmithKline, Inc. Dr. Abi-Dargham reports the following: Grant
support: GlaxoSmithKline, Inc.; compensation received from BMS-Otsuka
for consulting and speaking engagements. The other authors report no
biomedical financial interests or potential conflicts of interest.
NR 57
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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 JUN 15
PY 2010
VL 67
IS 12
BP 1154
EP 1162
DI 10.1016/j.biopsych.2010.03.013
PG 9
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 616JQ
UT WOS:000279205800006
PM 20434136
ER
PT J
AU Haas, JS
Brawarsky, P
Iyer, A
Fitzmaurice, GM
Neville, BA
Earle, C
Kaplan, CP
AF Haas, Jennifer S.
Brawarsky, Phyllis
Iyer, Aarthi
Fitzmaurice, Garrett M.
Neville, Bridget A.
Earle, Craig
Kaplan, Celia Patricia
TI Association of Local Capacity for Endoscopy With Individual Use of
Colorectal Cancer Screening and Stage at Diagnosis
SO CANCER
LA English
DT Article
DE colorectal cancer; screening; disparities; regional variation
ID UNITED-STATES; MEDICARE REIMBURSEMENT; AVERAGE-RISK; TASK-FORCE;
COLONOSCOPY; POPULATION; SURVEILLANCE; DISPARITIES; TESTS; BENEFICIARIES
AB BACKGROUND: Limited capacity for endoscopy in areas in which African Americans and Hispanics live may be a reason for persistent disparities in colorectal cancer (CRC) screening and stage at diagnosis. METHODS: The authors linked data from the National Health Interview Survey on the use of CRC screening and data from Surveillance, Epidemiology, and End Results-Medicare on CRC stage with measures of county capacity for colonoscopy and sigmoidoscopy (endoscopy) derived from Medicare claims. RESULTS: Hispanics lived in counties with less capacity for endoscopy than African Americans or whites (for National Health Interview Survey, an average of 1224, 1569, and 1628 procedures per 100,000 individuals aged >= 50 years, respectively). Individual use of CRC screening increased modestly as county capacity increased. For example, as the number of endoscopies per 100,000 residents increased by 750, the odds of being screened increased by 4%. Disparities in screening were mitigated or diminished by adjustment for area endoscopy capacity, racial/ethnic composition, and socioeconomic status. Similarly, among individuals with CRC, those who lived in counties with less endoscopy capacity were marginally less likely to be diagnosed at an early stage. Adjustment for area characteristics diminished disparities in stage for Hispanics compared with whites but not African Americans. CONCLUSIONS: Increasing the use of CRC screening may require interventions to improve capacity for endoscopy in some areas. The characteristics of the area where an individual resides may in part mediate disparities in CRC screening use for both African Americans and Hispanics, and disparities in cancer stage for Hispanics. Cancer 2010;116:2922-31. (C) 2010 American Cancer Society.
C1 [Haas, Jennifer S.; Brawarsky, Phyllis; Iyer, Aarthi] Brigham & Womens Hosp, Div Gen Med & Primary Care, Dept Med, Boston, MA 02120 USA.
[Haas, Jennifer S.; Brawarsky, Phyllis; Iyer, Aarthi; Fitzmaurice, Garrett M.] Harvard Univ, Sch Med, Boston, MA USA.
[Fitzmaurice, Garrett M.] McLean Hosp, Lab Psychiat Biostat, Boston, MA USA.
[Neville, Bridget A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Earle, Craig] Canc Care Ontario, Hlth Serv Res Program, Toronto, ON, Canada.
[Earle, Craig] Ontario Inst Canc Res, Toronto, ON, Canada.
[Kaplan, Celia Patricia] Univ Calif San Francisco, Dept Med, Div Gen Internal Med, Med Effectiveness Res Ctr, San Francisco, CA 94143 USA.
RP Haas, JS (reprint author), Brigham & Womens Hosp, Div Gen Med & Primary Care, Dept Med, 1620 Tremont St, Boston, MA 02120 USA.
EM jhaas@partners.org
FU American Cancer Society [RSGT CPHPS-114979]; National Cancer Institute
[R01 CA112451]
FX Supported by grants from the American Cancer Society (RSGT CPHPS-114979)
and the National Cancer Institute (R01 CA112451).
NR 42
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U1 1
U2 4
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0008-543X
J9 CANCER-AM CANCER SOC
JI Cancer
PD JUN 15
PY 2010
VL 116
IS 12
BP 2922
EP 2931
DI 10.1002/cncr.25093
PG 10
WC Oncology
SC Oncology
GA 609OH
UT WOS:000278665900013
PM 20564398
ER
PT J
AU Yeh, JM
Hur, C
Kuntz, KM
Ezzati, M
Goldie, SJ
AF Yeh, Jennifer M.
Hur, Chin
Kuntz, Karen M.
Ezzati, Majid
Goldie, Sue J.
TI Cost-Effectiveness of Treatment and Endoscopic Surveillance of
Precancerous Lesions to Prevent Gastric Cancer
SO CANCER
LA English
DT Article
DE gastric cancer; surveillance; secondary prevention; cost-effectiveness;
outcomes research
ID GASTROESOPHAGEAL-REFLUX DISEASE; POPULATION-BASED COHORT; FOLLOW-UP;
INTESTINAL METAPLASIA; MUCOSAL RESECTION; HELICOBACTER-PYLORI;
HIGH-RISK; GASTROINTESTINAL-ENDOSCOPY; PRENEOPLASTIC LESIONS; EPITHELIAL
DYSPLASIA
AB BACKGROUND: Although surveillance for Barrett esophagus and other gastrointestinal precancerous conditions is recommended, no analogous guidelines exist for gastric lesions. The objective of this study was to estimate the clinical benefits and cost-effectiveness of treatment and endoscopic surveillance to prevent gastric cancer. METHODS: The authors developed a state-transition decision model for a cohort of US men with a recent incidental diagnosis of gastric precancerous lesions (dysplasia, intestinal metaplasia, or atrophy). Strategies included 1) no surveillance or treatment and 2) referral for surveillance and treatment, and varied by surveillance frequency (none, every 10 years, every 5 years, or every year) and treatment modality for dysplastic and cancerous lesions (surgery or endoscopic mucosa) resection [EMR]). The term "post-treatment surveillance" was restricted to surveillance of individuals after treatment. Data were based on published literature and databases. Outcomes included lifetime gastric cancer risk, quality-adjusted life expectancy, lifetime costs, and incremental cost-effectiveness ratios. RESULTS: For a cohort of men with dysplasia aged 50 years, the lifetime gastric cancer risk was 5.9%. EMR with annual surveillance reduced the lifetime cancer risk by 90% and cost $39,800 per quality-adjusted life year (QALY). Addition of post-treatment surveillance every 10 years provided little incremental benefit (similar to 5%) but cost >$1 million per QALY. Results were most sensitive to surgical risks and the proportion of lesions completely removed with EMR. For intestinal metaplasia, surveillance every 10 years reduced lifetime cancer risk by 61% and cost $544,500 per QALY. CONCLUSIONS: EMR with surveillance every 1 to 5 years for gastric dysplasia was promising for secondary cancer prevention and had a cost-effectiveness ratio that would be considered attractive in the United States. Endoscopic surveillance of less advanced lesions did not appear to be cost-effective, except possibly for immigrants from high-risk countries. Cancer 2010;116:2941-53. (C) 2010 American Cancer Society.
C1 [Yeh, Jennifer M.; Goldie, Sue J.] Harvard Univ, Sch Publ Hlth, Ctr Hlth Decis Sci, Boston, MA 02115 USA.
[Hur, Chin] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA.
[Kuntz, Karen M.] Univ Minnesota, Sch Publ Hlth, Div Hlth Policy & Management, Minneapolis, MN USA.
[Ezzati, Majid] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Dept Global Hlth & Populat, Boston, MA 02115 USA.
RP Yeh, JM (reprint author), Harvard Univ, Sch Publ Hlth, Ctr Hlth Decis Sci, 718 Huntington Ave,2nd Floor, Boston, MA 02115 USA.
EM jyeh@hsph.harvard.edu
OI Hur, Chin/0000-0002-2819-7576
FU National Cancer Institute [R25-CA057711]
FX Dr. Yeh was funded by the National Cancer Institute (R25-CA057711).
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PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0008-543X
J9 CANCER-AM CANCER SOC
JI Cancer
PD JUN 15
PY 2010
VL 116
IS 12
BP 2941
EP 2953
DI 10.1002/cncr.25030
PG 13
WC Oncology
SC Oncology
GA 609OH
UT WOS:000278665900015
PM 20564399
ER
PT J
AU Carretero, J
Shimamura, T
Rikova, K
Jackson, AL
Wilkerson, MD
Borgman, CL
Buttarazzi, MS
Sanofsky, BA
McNamara, KL
Brandstetter, KA
Walton, ZE
Gu, TL
Silva, JC
Crosby, K
Shapiro, GI
Maira, SM
Ji, HB
Castrillon, DH
Kim, CF
Garcia-Echeverria, C
Bardeesy, N
Sharpless, NE
Hayes, ND
Kim, WY
Engelman, JA
Wong, KK
AF Carretero, Julian
Shimamura, Takeshi
Rikova, Klarisa
Jackson, Autumn L.
Wilkerson, Matthew D.
Borgman, Christa L.
Buttarazzi, Matthew S.
Sanofsky, Benjamin A.
McNamara, Kate L.
Brandstetter, Kathleyn A.
Walton, Zandra E.
Gu, Ting-Lei
Silva, Jeffrey C.
Crosby, Katherine
Shapiro, Geoffrey I.
Maira, Sauveur-Michel
Ji, Hongbin
Castrillon, Diego H.
Kim, Carla F.
Garcia-Echeverria, Carlos
Bardeesy, Nabeel
Sharpless, Norman E.
Hayes, Neil D.
Kim, William Y.
Engelman, Jeffrey A.
Wong, Kwok-Kin
TI Integrative Genomic and Proteomic Analyses Identify Targets for
Lkb1-Deficient Metastatic Lung Tumors
SO CANCER CELL
LA English
DT Article
ID EPITHELIAL-MESENCHYMAL TRANSITION; ONCOGENIC K-RAS; KINASE INHIBITOR;
CANCER-CELLS; EXPRESSION PROFILES; GENE; SRC; TUMORIGENESIS; SUPPRESSOR;
MUTATIONS
AB In mice, Lkb1 deletion and activation of KraS(G12D) results in lung tumors with a high penetrance of lymph node and distant metastases. We analyzed these primary and metastatic de novo lung cancers with integrated genomic and proteomic profiles, and have identified gene and phosphoprotein signatures associated with Lkb1 loss and progression to invasive and metastatic lung tumors. These studies revealed that SRC is activated in Lkb1-deficient primary and metastatic lung tumors, and that the combined inhibition of SRC, PI3K, and MEK1/2 resulted in synergistic tumor regression. These studies demonstrate that integrated genomic and proteomic analyses can be used to identify signaling pathways that may be targeted for treatment.
C1 [Carretero, Julian; Shimamura, Takeshi; Borgman, Christa L.; Buttarazzi, Matthew S.; Sanofsky, Benjamin A.; McNamara, Kate L.; Brandstetter, Kathleyn A.; Walton, Zandra E.; Shapiro, Geoffrey I.; Wong, Kwok-Kin] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Carretero, Julian] Univ Valencia, Fac Med & Odontol, Dept Physiol, Valencia 46010, Spain.
[Shimamura, Takeshi; Shapiro, Geoffrey I.; Wong, Kwok-Kin] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA.
[Rikova, Klarisa; Gu, Ting-Lei; Silva, Jeffrey C.; Crosby, Katherine] Cell Signaling Technol Inc, Danvers, MA 01923 USA.
[Jackson, Autumn L.; Wilkerson, Matthew D.; Sharpless, Norman E.; Hayes, Neil D.; Kim, William Y.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
[Sharpless, Norman E.; Kim, William Y.] Univ N Carolina, Dept Med & Genet, Chapel Hill, NC 27599 USA.
[Buttarazzi, Matthew S.; Sanofsky, Benjamin A.; McNamara, Kate L.; Brandstetter, Kathleyn A.; Walton, Zandra E.; Wong, Kwok-Kin] Dana Farber Harvard Canc Ctr, Ludwig Ctr, Boston, MA 02115 USA.
[Maira, Sauveur-Michel; Garcia-Echeverria, Carlos] Novartis Inst Biomed Res, Oncol Dis Area, CH-4002 Basel, Switzerland.
[Ji, Hongbin] Chinese Acad Sci, Mol Cell Biol Lab, Inst Biochem & Cell Biol, Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China.
[Castrillon, Diego H.] Univ Texas SW Med Ctr Dallas, Dept Pathol, Dallas, TX 75390 USA.
[Kim, Carla F.] Childrens Hosp, Boston, MA 02115 USA.
[Bardeesy, Nabeel; Engelman, Jeffrey A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
RP Wong, KK (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA.
EM kwong1@partners.org
RI Carretero, Julian/N-5214-2014;
OI Carretero, Julian/0000-0001-7269-8506; Hayes, D.
Neil/0000-0001-6203-7771; wong, kwok kin/0000-0001-6323-235X
FU DF/HCC [P50 CA127003]; Dana-Farber-Harvard Cancer Center Lung Cancer
Specialized Program of Research Excellence (SPORE) [P50 CA090578,
U01CA141576, R01 AG2400401, R01 CA122794, R01 CA140594, 1RC2CA147940-01,
CA120060, R01CA137008]; American Association for Cancer Research; V
Foundation; American Cancer Society [RSG-06-102-01-CCE]; Ellison
Foundation Scholar; Novartis
FX J.C. was a fellow of Spanish Ministry of Science and Innovation (MICINN)
and Spanish Association against Cancer (AECC). T.S. was supported by the
DF/HCC Claudia Adams Barr Program in Innovative Basic Cancer Research.
K.-K.W. and J.A.E. are founders of Gatekeeper Therapeutics. This work
was supported by Dana-Farber-Harvard Cancer Center Lung Cancer
Specialized Program of Research Excellence (SPORE) grant P50 CA090578
(J.A.E. and K.-K.W.); U01CA141576 (K.-K.W., D.C., N.S. and N.B.) R01
AG2400401 (K.-K.W.), R01 CA122794 (K.-K.W.), R01 CA140594 (J.A.E. and
K.-K.W.), 1RC2CA147940-01 (J.A.E. and K.-K.W.), K08 grant CA120060
(J.A.E.), R01CA137008 (J.A.E.), DF/HCC Gastrointestinal Cancer SPORE P50
CA127003 (J.A.E.); American Association for Cancer Research (J.A.E.); V
Foundation (J.A.E.); American Cancer Society RSG-06-102-01-CCE (J.A.E.);
and Ellison Foundation Scholar (J.A.E.). K.R., K.C., J.C.S. and T.-L.G.
are employees of Cell Signaling Technology. C.G.-E. and S.-M.M. are
employees of Novartis Institutes for Biochemical Research. J.A.E.
receives research funding from Novartis. We thank H. Voelker for help in
preparation of this manuscript.
NR 45
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U1 1
U2 15
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1535-6108
J9 CANCER CELL
JI Cancer Cell
PD JUN 15
PY 2010
VL 17
IS 6
BP 547
EP 559
DI 10.1016/j.ccr.2010.04.026
PG 13
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 613BY
UT WOS:000278952300007
PM 20541700
ER
PT J
AU Mullally, A
Lane, SW
Ball, B
Megerdichian, C
Okabe, R
Al-Shahrour, F
Paktinat, M
Haydu, JE
Housman, E
Lord, AM
Wernig, G
Kharas, MG
Mercher, T
Kutok, JL
Gilliland, DG
Ebert, BL
AF Mullally, Ann
Lane, Steven W.
Ball, Brian
Megerdichian, Christine
Okabe, Rachel
Al-Shahrour, Fatima
Paktinat, Mahnaz
Haydu, J. Erika
Housman, Elizabeth
Lord, Allegra M.
Wernig, Gerlinde
Kharas, Michael G.
Mercher, Thomas
Kutok, Jeffery L.
Gilliland, D. Gary
Ebert, Benjamin L.
TI Physiological Jak2V617F Expression Causes a Lethal Myeloproliferative
Neoplasm with Differential Effects on Hematopoietic Stem and Progenitor
Cells
SO CANCER CELL
LA English
DT Article
ID CHRONIC MYELOMONOCYTIC LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; TYROSINE
KINASE JAK2; VERA-LIKE DISEASE; POLYCYTHEMIA-VERA; IN-VIVO; ESSENTIAL
THROMBOCYTHEMIA; MYELODYSPLASTIC-SYNDROMES; CONDITIONAL EXPRESSION;
ACTIVATING MUTATION
AB We report a Jak2V617F knockin mouse myeloproliferative neoplasm (MPN) model resembling human polycythemia vera (PV). The MPN is serially transplantable and we demonstrate that the hematopoietic stem cell (HSC) compartment has the unique capacity for disease initiation but does not have a significant selective competitive advantage over wild-type HSCs. In contrast, myeloid progenitor populations are expanded and skewed toward the erythroid lineage, but cannot transplant the disease. Treatment with a JAK2 kinase inhibitor ameliorated the MPN phenotype, but did not eliminate the disease-initiating population. These findings provide insights into the consequences of JAK2 activation on HSC differentiation and function and have the potential to inform therapeutic approaches to JAK2V617F-positive MPN.
C1 [Mullally, Ann; Ebert, Benjamin L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Mullally, Ann; Lane, Steven W.; Ball, Brian; Megerdichian, Christine; Okabe, Rachel; Al-Shahrour, Fatima; Paktinat, Mahnaz; Haydu, J. Erika; Housman, Elizabeth; Lord, Allegra M.; Kharas, Michael G.; Gilliland, D. Gary; Ebert, Benjamin L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Hematol,Dept Med, Boston, MA 02115 USA.
[Kutok, Jeffery L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Lane, Steven W.] Univ Queensland, Brisbane, Qld 4006, Australia.
[Al-Shahrour, Fatima; Ebert, Benjamin L.] Broad Inst, Cambridge, MA 02142 USA.
[Wernig, Gerlinde] Stanford Univ, Dept Pathol, Stanford, CA 94305 USA.
[Mercher, Thomas] Univ Paris 05, Hop Necker, INSERM, U985, F-75015 Paris, France.
[Gilliland, D. Gary] Merck & Co Inc, N Wales, PA 19454 USA.
RP Ebert, BL (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA.
EM bebert@partners.org
RI Lane, Steven/C-3215-2012; Mercher, Thomas/J-2446-2014
OI Lane, Steven/0000-0002-8050-6209; Mercher, Thomas/0000-0003-1552-087X
FU NIH [P30 DK49216]; NIDDK Centers of Excellence in Hematology; TargeGen
Inc. (San Diego, CA, USA) [TG101348]; Myeloproliferative Disorders
Foundation (Chicago, IL); NIH/NHLBI [R01 HL082950, T32HL0763]; NIH/NCI
[P01 CA 66996-11]; Jeanne D. Housman Fund; GlaxoSmithKline
FX We gratefully acknowledge transgenic core facilities supported by NIH
P30 DK49216, NIDDK Centers of Excellence in Hematology for generating
chimeric mice, and TargeGen Inc. (San Diego, CA, USA) for supplying
TG101348. We warmly thank Drs. Ross Levine and Demetrios Kalaitzidis for
critically reviewing the manuscript and all members of the Gilliland and
Ebert laboratories for their insights and collegiality.; This work was
supported with funding from the Myeloproliferative Disorders Foundation
(Chicago, IL), R01 HL082950 (NIH/NHLBI), and P01 CA 66996-11 (NIH/NCI).
A.M. has received T32HL0763 funding (NIH/NHLBI) and support from the
Jeanne D. Housman Fund for Research on Myeloproliferative Disorders and
is a 2010 ASH Scholar recipient.; Authorship contributions are as
follows. A.M., S.W.L., D.G.G., and B.L.E. designed experiments. A.M.,
S.W.L., B.B., C.M., R.O., and F.A.-S. performed experiments and analyzed
data. A.M. wrote the manuscript with assistance from S.W.L. All authors
provided critical review of the manuscript.; Conflict-of-interest
disclosure: B.L.E. has received research support from GlaxoSmithKline.
D.G.G. is now an employee of Merck.
NR 58
TC 128
Z9 130
U1 1
U2 6
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1535-6108
J9 CANCER CELL
JI Cancer Cell
PD JUN 15
PY 2010
VL 17
IS 6
BP 584
EP 596
DI 10.1016/j.ccr.2010.05.015
PG 13
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 613BY
UT WOS:000278952300010
PM 20541703
ER
PT J
AU Mateos, MV
Cibeira, MT
Richardson, PG
Prosper, F
Oriol, A
de la Rubia, J
Lahuerta, JJ
Garcia-Sanz, R
Extremera, S
Szyldergemajn, S
Corrado, C
Singer, H
Mitsiades, CS
Anderson, KC
Blade, J
San Miguel, J
AF Victoria Mateos, Maria
Teresa Cibeira, Maria
Richardson, Paul G.
Prosper, Felipe
Oriol, Albert
de la Rubia, Javier
Jose Lahuerta, Juan
Garcia-Sanz, Ramon
Extremera, Sonia
Szyldergemajn, Sergio
Corrado, Claudia
Singer, Harald
Mitsiades, Constantine S.
Anderson, Kenneth C.
Blade, Joan
San Miguel, Jesus
TI Phase II Clinical and Pharmacokinetic Study of Plitidepsin 3-Hour
Infusion Every Two Weeks Alone or with Dexamethasone in Relapsed and
Refractory Multiple Myeloma
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID PRACTICE GUIDELINES; MARINE ORIGIN; IN-VITRO; APLIDINE; CELLS;
ACTIVATION; THERAPY; JNK; BORTEZOMIB; MANAGEMENT
AB Purpose: This trial evaluated the antitumor activity and safety of the marine-derived cyclodepsipeptide plitidepsin in patients with relapsed/refractory multiple myeloma.
Experimental Design: This was a prospective, multicenter, open-label, single-arm, phase II trial with plitidepsin at 5 mg/m(2) as a 3-hour i.v. infusion every two weeks. The protocol was amended to allow patients with suboptimal response to single-agent plitidepsin to add 20 mg/day on days 1 to 4 of oral dexamethasone every two weeks.
Results: Fifty-one patients started treatment with plitidepsin and 47 were evaluable for efficacy. The overall response rate ( complete response plus partial response plus minimal response) was 13% with plitidepsin alone and 22% in the cohort of patients with the addition of dexamethasone ( n = 19, 18 evaluable). Both plitidepsin alone and with dexamethasone were feasible and well tolerated. Anemia ( 29%) and thrombocytopenia ( 18%) were the most frequent grade 3/4 hematologic toxicities. Fatigue ( 16%), muscular toxicity ( 6%), and transient alanine aminotransferase/aspartate aminotransferase ( 27%) and creatine phosphokinase ( 23%) increases were the most relevant nonhematologic side effects. A prolonged plasma half-life was observed in responding patients as compared with nonresponding patients ( P = 0.009).
Conclusions: Single-agent plitidepsin has limited but reproducible activity in relapsed/refractory multiple myeloma patients. Activity observed after dexamethasone addition merits further study. Both regimens were well tolerated in this heavily pretreated population. Clin Cancer Res; 16( 12); 3260-9. (C)2010 AACR.
C1 [Victoria Mateos, Maria; Garcia-Sanz, Ramon; San Miguel, Jesus] Hosp Univ Salamanca, Salamanca, Spain.
[Teresa Cibeira, Maria; Blade, Joan] Hosp Clin Barcelona, Barcelona, Spain.
[Richardson, Paul G.; Mitsiades, Constantine S.; Anderson, Kenneth C.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Prosper, Felipe] Univ Navarra Clin, Pamplona, Spain.
[Oriol, Albert] Hosp Badalona Germans Trias & Pujol, Badalona, Spain.
[de la Rubia, Javier] Hosp Univ La Fe, Valencia, Spain.
[Jose Lahuerta, Juan] Hosp Univ 12 Octubre, Madrid, Spain.
[Extremera, Sonia; Szyldergemajn, Sergio; Corrado, Claudia; Singer, Harald] Pharma Mar, Colmenar Viejo, Madrid, Spain.
RP Mateos, MV (reprint author), Univ Salamanca, Dept Hematol, Paseo San Vicente 58-182, Salamanca 37007, Spain.
EM mvmateos@usal.es
RI Garcia-Sanz, Ramon/B-7986-2017;
OI Garcia-Sanz, Ramon/0000-0003-4120-2787; Prosper,
Felipe/0000-0001-6115-8790; SAN MIGUEL, JESUS/0000-0002-9183-4857
NR 36
TC 31
Z9 32
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD JUN 15
PY 2010
VL 16
IS 12
BP 3260
EP 3269
DI 10.1158/1078-0432.CCR-10-0469
PG 10
WC Oncology
SC Oncology
GA 610QN
UT WOS:000278749400021
PM 20530693
ER
PT J
AU Baddley, JW
Andes, DR
Marr, KA
Kontoyiannis, DP
Alexander, BD
Kauffman, CA
Oster, RA
Anaissie, EJ
Walsh, TJ
Schuster, MG
Wingard, JR
Patterson, TF
Ito, JI
Williams, OD
Chiller, T
Pappas, PG
AF Baddley, John W.
Andes, David R.
Marr, Kieren A.
Kontoyiannis, Dimitrios P.
Alexander, Barbara D.
Kauffman, Carol A.
Oster, Robert A.
Anaissie, Elias J.
Walsh, Thomas J.
Schuster, Mindy G.
Wingard, John R.
Patterson, Thomas F.
Ito, James I.
Williams, O. Dale
Chiller, Tom
Pappas, Peter G.
CA Transplant Associated Infect Surve
TI Factors Associated with Mortality in Transplant Patients with Invasive
Aspergillosis
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
ID STEM-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; LIPOSOMAL
AMPHOTERICIN-B; PROGNOSTIC-FACTORS; FUNGAL-INFECTIONS; IMMUNOCOMPROMISED
PATIENTS; HEMATOLOGIC MALIGNANCIES; ATTRIBUTABLE MORTALITY; PRIMARY
THERAPY; EPIDEMIOLOGY
AB Background. Invasive aspergillosis (IA) is an important cause of morbidity and mortality in hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT) recipients. The purpose of this study was to evaluate factors associated with mortality in transplant patients with IA.
Methods. Transplant patients from 23 US centers were enrolled from March 2001 to October 2005 as part of the Transplant Associated Infection Surveillance Network. IA cases were identified prospectively in this cohort through March 2006, and data were collected. Factors associated with 12-week all-cause mortality were determined by logistic regression analysis and Cox proportional hazards regression.
Results. Six-hundred forty-two cases of proven or probable IA were evaluated, of which 317 (49.4%) died by the study endpoint. All-cause mortality was greater in HSCT patients (239 [57.5%] of 415) than in SOT patients (78 [34.4%] of 227;). Independent poor prognostic factors P < .001 in HSCT patients were neutropenia, renal insufficiency, hepatic insufficiency, early-onset IA, proven IA, and methylprednisolone use. In contrast, white race was associated with decreased risk of death. Among SOT patients, hepatic insufficiency, malnutrition, and central nervous system disease were poor prognostic indicators, whereas prednisone use was associated with decreased risk of death. Among HSCT or SOT patients who received antifungal therapy, use of an amphotericin B preparation as part of initial therapy was associated with increased risk of death.
Conclusions. There are multiple variables associated with survival in transplant patients with IA. Understanding these prognostic factors may assist in the development of treatment algorithms and clinical trials.
C1 [Baddley, John W.] Univ Alabama, Dept Med, Div Infect Dis, Birmingham, AL 35294 USA.
[Baddley, John W.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA.
[Andes, David R.] Univ Wisconsin, Madison, WI USA.
[Marr, Kieren A.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Walsh, Thomas J.] NCI, Bethesda, MD 20892 USA.
[Kontoyiannis, Dimitrios P.] Univ Texas MD Anderson Canc Res Ctr, Houston, TX USA.
[Patterson, Thomas F.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Patterson, Thomas F.] S Texas Vet Hlth Care Syst, San Antonio, TX USA.
[Alexander, Barbara D.] Duke Univ, Med Ctr, Durham, NC USA.
[Kauffman, Carol A.] Univ Michigan, Ann Arbor, MI 48109 USA.
[Kauffman, Carol A.] Vet Affairs Hlth Care Syst, Ann Arbor, MI USA.
[Anaissie, Elias J.] Univ Arkansas, Dept Med, Div Infect Dis, Little Rock, AR 72204 USA.
[Schuster, Mindy G.] Univ Penn, Philadelphia, PA 19104 USA.
[Wingard, John R.] Univ Florida, Gainesville, FL USA.
[Ito, James I.] City Hope Natl Med Ctr, Duarte, CA 91010 USA.
[Chiller, Tom] Ctr Dis Control & Prevent, Div Mycot Dis, Atlanta, GA USA.
RP Baddley, JW (reprint author), Univ Alabama, Dept Med, Div Infect Dis, 1900 Univ Blvd,229 Tinsley Harrison Tower, Birmingham, AL 35294 USA.
EM jbaddley@uab.edu
FU NIAID NIH HHS [K24 AI072522, K23 AI064613, K23 AI064613-05, K23AI064613]
NR 28
TC 117
Z9 120
U1 1
U2 9
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD JUN 15
PY 2010
VL 50
IS 12
BP 1559
EP 1567
DI 10.1086/652768
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 598BF
UT WOS:000277806200002
PM 20450350
ER
PT J
AU Lipsky, BA
Byren, I
Hoey, CT
AF Lipsky, Benjamin A.
Byren, Ivor
Hoey, Christopher T.
TI Treatment of Bacterial Prostatitis
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
ID PELVIC PAIN SYNDROME; DOUBLE-BLIND TRIAL; TISSUE CONCENTRATIONS; SYMPTOM
INDEX; ANTIBIOTIC-THERAPY; ESCHERICHIA-COLI; ADENOMA TISSUE; SEMINAL
FLUID; MEN; LEVOFLOXACIN
AB Prostatitis is characterized by voiding symptoms and genitourinary pain and is sometimes associated with sexual dysfunction. Up to 25% of men receive a diagnosis of prostatitis in their lifetime, but ! 10% have a proven bacterial infection. The causes and treatment of nonbacterial prostatitis are largely unknown, but bacterial prostatitis is caused by infection with uropathogens, especially gram-negative bacilli, although infection is sometimes due to gram-positive and atypical microorganisms. Acute bacterial prostatitis is easily diagnosed (by abrupt urogential and often systemic symptoms, along with bacteriuria) and treated (by systemic antibiotic therapy). Chronic bacterial prostatitis is characterized by prolonged or recurrent symptoms and relapsing bacteriuria; diagnosis traditionally requires comparing urinary specimens obtained before with specimens obtained after prostatic massage. Treating chronic bacterial prostatitis requires prolonged therapy with an antibiotic that penetrates the prostate (ie, one with high lipid solubility, a low degree of ionization, high dissociation constant, low protein binding, and small molecular size). We review recent pharmacological and clinical data on treating bacterial prostatitis.
C1 [Lipsky, Benjamin A.] VA Puget Sound Hlth Care Syst, Primary Care Clin S 111 PCC, Gen Internal Med Serv, Seattle, WA 98108 USA.
[Hoey, Christopher T.] VA Puget Sound Hlth Care Syst, Serv Pharm, Seattle, WA 98108 USA.
[Lipsky, Benjamin A.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA.
[Byren, Ivor] John Radcliffe Hosp, Dept Infect Dis, Oxford OX3 9DU, England.
[Byren, Ivor] Univ Oxford, Oxford, England.
RP Lipsky, BA (reprint author), VA Puget Sound Hlth Care Syst, Primary Care Clin S 111 PCC, Gen Internal Med Serv, 1660 S Columbian Way, Seattle, WA 98108 USA.
EM balipsky@uw.edu
OI Lipsky, Benjamin A./0000-0001-9886-5114
FU Merck; Pfizer; Nordic Pharma
FX Potential conflicts of interest. B. A. L. has received research funding
from Merck and Pfizer and has served as a consultant to Pfizer,
Ortho-McNeil, Cubist, and Wyeth-Ayerst. I. B. has received honoraria for
serving on advisory boards from Pfizer and has received lecture fees
from Pfizer and Nordic Pharma. C. T. H.: no conflicts.
NR 102
TC 47
Z9 57
U1 3
U2 8
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD JUN 15
PY 2010
VL 50
IS 12
BP 1641
EP 1652
DI 10.1086/652861
PG 12
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 598BF
UT WOS:000277806200015
PM 20459324
ER
PT J
AU Friedlander, AH
AF Friedlander, Arthur H.
TI Oral Cavity Staphylococci Are a Potential Source of Prosthetic Joint
Infection
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Letter
ID MICROFLORA; AGE
C1 [Friedlander, Arthur H.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA.
[Friedlander, Arthur H.] UCLA Med Ctr, Hosp Dent Serv, Los Angeles, CA USA.
[Friedlander, Arthur H.] UCLA Dent Sch, Los Angeles, CA USA.
RP Friedlander, AH (reprint author), VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA.
EM arthur.friedlander@med.va.gov
NR 11
TC 5
Z9 5
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD JUN 15
PY 2010
VL 50
IS 12
BP 1682
EP 1683
DI 10.1086/653003
PG 2
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 598BF
UT WOS:000277806200020
PM 20482262
ER
PT J
AU Lipinski, MM
Hoffman, G
Ng, A
Zhou, W
Py, BF
Hsu, E
Liu, XX
Eisenberg, J
Liu, J
Blenis, J
Xavier, RJ
Yuan, JY
AF Lipinski, Marta M.
Hoffman, Greg
Ng, Aylwin
Zhou, Wen
Py, Benedicte F.
Hsu, Emily
Liu, Xuxin
Eisenberg, Jason
Liu, Jun
Blenis, John
Xavier, Ramnik J.
Yuan, Junying
TI A Genome-Wide siRNA Screen Reveals Multiple mTORC1 Independent Signaling
Pathways Regulating Autophagy under Normal Nutritional Conditions
SO DEVELOPMENTAL CELL
LA English
DT Article
ID ENDOPLASMIC-RETICULUM STRESS; PROTEIN; IDENTIFICATION; TUMORIGENESIS;
ACTIVATION; BECLIN-1; CANCER; ASSAYS; CELLS; MICE
AB Autophagy is a cellular catabolic mechanism that plays an essential function in protecting multicellular eukaryotes from neurodegeneration, cancer, and other diseases. However, we still know very little about mechanisms regulating autophagy under normal homeostatic conditions when nutrients are not limiting. In a genome-wide human siRNA screen, we demonstrate that under normal nutrient conditions upregulation of autophagy requires the type III PI3 kinase, but not inhibition of mTORC1, the essential negative regulator of starvation-induced autophagy. We show that a group of growth factors and cytokines inhibit the type III PI3 kinase through multiple pathways, including the MAPK-ERK1/2, Stat3, Akt/Foxo3, and CXCR4/GPCR, which are all known to positively regulate cell growth and proliferation. Our study suggests that the type III PI3 kinase integrates diverse signals to regulate cellular levels of autophagy, and that autophagy and cell proliferation may represent two alternative cell fates that are regulated in a mutually exclusive manner.
C1 [Lipinski, Marta M.; Hoffman, Greg; Zhou, Wen; Py, Benedicte F.; Hsu, Emily; Blenis, John; Yuan, Junying] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
[Ng, Aylwin; Eisenberg, Jason; Xavier, Ramnik J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA.
[Liu, Xuxin; Liu, Jun] Harvard Univ, Dept Stat, Cambridge, MA 02138 USA.
RP Yuan, JY (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, 240 Longwood Ave, Boston, MA 02115 USA.
EM junying_yuan@hms.harvard.edu
RI Py, Benedicte/M-6129-2014;
OI Lipinski, Marta/0000-0002-7537-9014
FU NIH [R37 AG012859, P01 AG027916, AI062773, DK043351, R01 GM051405, R21
NS059428]; Helen Hay Whitney Foundation; LAM Foundation; Crohn's and
Colitis Foundation of America; CCIB Development Fund; NSF [DMS-0706989]
FX We thank N. Mizushima and N. Gray for reagents, C. Yi for critical
reading of the manuscript, and the members of the Yuan lab and the
ICCB-Longwood for help during this work. This work was supported in part
by NIH grants R37 AG012859 and P01 AG027916 to J.Y., AI062773 and
DK043351 to R.J.X., R01 GM051405 and R21 NS059428 to J.B., and NSF grant
DMS-0706989 to J.L. G.H. is supported by fellowships from the Helen Hay
Whitney Foundation and the LAM Foundation, A.N. by the Crohn's and
Colitis Foundation of America, and J.E. by CCIB Development Fund.
NR 31
TC 112
Z9 118
U1 0
U2 11
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1534-5807
J9 DEV CELL
JI Dev. Cell
PD JUN 15
PY 2010
VL 18
IS 6
BP 1041
EP 1052
DI 10.1016/j.devcel.2010.05.005
PG 12
WC Cell Biology; Developmental Biology
SC Cell Biology; Developmental Biology
GA 618OT
UT WOS:000279366200018
PM 20627085
ER
PT J
AU van Riggelen, J
Muller, J
Otto, T
Beuger, V
Yetil, A
Choi, PS
Kosan, C
Moroy, T
Felsher, DW
Eilers, M
AF van Riggelen, Jan
Mueller, Judith
Otto, Tobias
Beuger, Vincent
Yetil, Alper
Choi, Peter S.
Kosan, Christian
Moeroey, Tarik
Felsher, Dean W.
Eilers, Martin
TI The interaction between Myc and Miz1 is required to antagonize TGF
beta-dependent autocrine signaling during lymphoma formation and
maintenance
SO GENES & DEVELOPMENT
LA English
DT Article
DE Myc; Miz1; senescence; TGF beta; lymphoma; T-cell
ID ONCOGENE-INDUCED SENESCENCE; CELLULAR SENESCENCE; INHIBITOR P15(INK4B);
CDK INHIBITOR; N-MYC; TUMOR; TUMORIGENESIS; RAS; DIFFERENTIATION;
PHOSPHORYLATION
AB The Myc protein suppresses the transcription of several cyclin-dependent kinase inhibitors (CKIs) via binding to Miz1; whether this interaction is important for Myc's ability to induce or maintain tumorigenesis is not known. Here we show that the oncogenic potential of a point mutant of Myc (MycV394D) that is selectively deficient in binding to Miz1 is greatly attenuated. Binding of Myc to Miz1 is continuously required to repress CKI expression and inhibit accumulation of trimethylated histone H3 at Lys 9 (H3K9triMe), a hallmark of cellular senescence, in T-cell lymphomas. Lymphomas that arise express high amounts of transforming growth factor beta-2 (TGF beta-2) and TGF beta-3. Upon Myc suppression, TGF beta signaling is required to induce CKI expression and cellular senescence and suppress tumor recurrence. Binding of Myc to Miz1 is required to antagonize growth suppression and induction of senescence by TGF beta. We demonstrate that, since lymphomas express high levels of TGF beta, they are poised to elicit an autocrine program of senescence upon Myc inactivation, demonstrating that TGF beta is a key factor that establishes oncogene addiction of T-cell lymphomas.
C1 [Mueller, Judith; Beuger, Vincent; Eilers, Martin] Univ Wurzburg, Theodor Boveri Inst, Bioctr, D-97074 Wurzburg, Germany.
[Otto, Tobias] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Beuger, Vincent] TaconicArtemis GmbH, D-51063 Cologne, Germany.
[Kosan, Christian; Moeroey, Tarik] Univ Montreal, Inst Rech Clin Montreal, Montreal, PQ H2W 1R7, Canada.
[van Riggelen, Jan; Yetil, Alper; Choi, Peter S.; Felsher, Dean W.] Stanford Univ, Sch Med, Dept Med, Div Oncol, Stanford, CA 94304 USA.
[van Riggelen, Jan; Yetil, Alper; Choi, Peter S.; Felsher, Dean W.] Stanford Univ, Sch Med, Dept Pathol, Div Oncol, Stanford, CA 94304 USA.
RP Eilers, M (reprint author), Univ Wurzburg, Theodor Boveri Inst, Bioctr, D-97074 Wurzburg, Germany.
EM dfelsher@stanford.edu; martin.eilers@biozentrum.uni-wuerzburg.de
RI Moroy, Tarik/D-9923-2011; Kosan, Christian/C-1213-2017;
OI Kosan, Christian/0000-0002-8387-3653; Eilers, Martin/0000-0002-0376-6533
FU Deutsche Forschungsgemeinschaft; Sander-Stiftung; Lymphoma Research
Foundation; NIH; Leukemia and Lymphoma Society; Burroughs Wellcome Fund
FX We thank Anton Berns for the gift of cdkn2b-/- mice. This
study was supported by grants from the Deutsche Forschungsgemeinschaft
via Transregio 17 ("Ras-dependent pathways in human cancer") and from
the Sander-Stiftung to M. E. J.v.R. was supported by the Lymphoma
Research Foundation. D. W. F. is supported by grants from the NIH, the
Leukemia and Lymphoma Society, and the Burroughs Wellcome Fund.
NR 47
TC 57
Z9 57
U1 0
U2 6
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI WOODBURY
PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA
SN 0890-9369
J9 GENE DEV
JI Genes Dev.
PD JUN 15
PY 2010
VL 24
IS 12
BP 1281
EP 1294
DI 10.1101/gad.585710
PG 14
WC Cell Biology; Developmental Biology; Genetics & Heredity
SC Cell Biology; Developmental Biology; Genetics & Heredity
GA 610YX
UT WOS:000278778200008
PM 20551174
ER
PT J
AU Firestein, R
Shima, K
Nosho, K
Irahara, N
Baba, Y
Bojarski, E
Giovannucci, EL
Hahn, WC
Fuchs, CS
Ogino, S
AF Firestein, Ron
Shima, Kaori
Nosho, Katsuhiko
Irahara, Natsumi
Baba, Yoshifumi
Bojarski, Emeric
Giovannucci, Edward L.
Hahn, William C.
Fuchs, Charles S.
Ogino, Shuji
TI CDK8 expression in 470 colorectal cancers in relation to beta-catenin
activation, other molecular alterations and patient survival
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE colon cancer; CDK8; prognosis; CTNNB1; FASN
ID ISLAND METHYLATOR PHENOTYPE; FATTY-ACID SYNTHASE; POPULATION-BASED
SAMPLE; HORMONE REPLACEMENT THERAPY; MICROSATELLITE INSTABILITY;
COLON-CANCER; DISEASE PROGRESSION; MEDIATOR COMPLEX; BRAF MUTATION; CIMP
AB Alterations in the Wnt/beta-catenin pathway define a key event in the pathogenesis of colon cancer. We have recently shown that CDK8, the gene encoding a cyclin-dependent kinase (CDK) component of the Mediator complex, acts as a colon cancer oncogene that is necessary for beta-catenin activity. Here, we tested the hypothesis that colorectal cancers with CDK8 expression have distinct clinical, prognostic and molecular attributes. Among 470 colorectal cancers identified in 2 prospective cohort studies, CDK8 expression was detected in 329 (70%) tumors by immunohistochemistry. Cox proportional hazards model and backward stepwise elimination were used to compute hazard ratio (HR) of deaths according to CDK8 status, initially adjusted for various patient and molecular features, including beta-catenin, p53, p21, p27 (CDK inhibitors), cyclin D1, fatty acid synthase (FASN), cyclooxygenase-2 (COX-2), microsatellite instability (MSI), CpG island methylator phenotype (CIMP), LINE-1 methylation, and mutations in KRAS, BRAF and PIK3CA. CDK8 expression in colorectal cancer was independently associated with beta-catenin activation (p = 0.0002), female gender (p < 0.0001) and FASN overexpression (p = 0.0003). Among colon cancer patients, CDK8 expression significantly increased colon cancer-specific mortality in both univariate analysis [HR 1.70; 95% confidence interval (CI), 1.03-2.83; p = 0.039] and multivariate analysis (adjusted HR 2.05; 95% CI, 1.18-3.56; p = 0.011) that was adjusted for potential confounders including beta-catenin, COX-2, FASN, LINE-1 hypomethylation, CIMP and MSI. CDK8 expression was unrelated with clinical outcome among rectal cancer patients. These data support a potential link between CDK8 and beta-catenin, and suggest that CDK8 may identify a subset of colon cancer patients with a poor prognosis.
C1 [Firestein, Ron; Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Firestein, Ron; Shima, Kaori; Nosho, Katsuhiko; Irahara, Natsumi; Baba, Yoshifumi; Bojarski, Emeric; Giovannucci, Edward L.; Hahn, William C.; Fuchs, Charles S.; Ogino, Shuji] Harvard Univ, Sch Med, Boston, MA USA.
[Firestein, Ron; Shima, Kaori; Nosho, Katsuhiko; Irahara, Natsumi; Baba, Yoshifumi; Bojarski, Emeric; Hahn, William C.; Fuchs, Charles S.; Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Firestein, Ron; Hahn, William C.] MIT, Broad Inst, Cambridge, MA 02139 USA.
[Firestein, Ron; Hahn, William C.] Harvard Univ, Cambridge, MA 02138 USA.
[Giovannucci, Edward L.; Fuchs, Charles S.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA.
[Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
RP Firestein, R (reprint author), Genentech Inc, Dept Pathol, 1 DNA Way, San Francisco, CA 94080 USA.
EM firestein.ron@gene.com; shuji_ogino@dfci.harvard.edu
FU U.S. National Institute of Health [P01 CA87969, P01 CA55075, P50
CA127003, R33 CA128625, K07 CA122826, K08 CA134836]; Bennett Family Fund
for Targeted Therapies Research; Entertainment Industry Foundation
National Colorectal Cancer Research Alliance; Japan Society for
Promotion of Science
FX Grant sponsor: U.S. National Institute of Health; Grant numbers: P01
CA87969, P01 CA55075, P50 CA127003, R33 CA128625, K07 CA122826, K08
CA134836; Grant sponsors: Bennett Family Fund for Targeted Therapies
Research, Entertainment Industry Foundation National Colorectal Cancer
Research Alliance, Japan Society for Promotion of Science
NR 50
TC 40
Z9 44
U1 0
U2 5
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD JUN 15
PY 2010
VL 126
IS 12
BP 2863
EP 2873
DI 10.1002/ijc.24908
PG 11
WC Oncology
SC Oncology
GA 594QA
UT WOS:000277551100011
PM 19790197
ER
PT J
AU Becker, K
Poon, C
Zeidler, M
Wang, TS
AF Becker, Kendra
Poon, Charles
Zeidler, Michelle
Wang, Tisha
TI An Unusual Cause of Delirium
SO JOURNAL OF CLINICAL SLEEP MEDICINE
LA English
DT Editorial Material
DE Central sleep apnea; obstructive sleep apnea; delirium; congestive heart
failure; Cheyne-Stokes
ID HEART-FAILURE; SLEEP-APNEA
AB Sleep disordered breathing (SDB) including obstructive sleep apnea (OSA), central sleep apnea (CSA), and Cheyne-Stokes breathing is common in patients with congestive heart failure (CHF). In a study of 81 males with an ejection fraction (EF) < 45%, 51% of patients had documented SDB with the majority of cases representing CSA.(1) Studies suggest that SDB is an independent risk factor for increased morbidity and mortality in the setting of CHF.(2) Like OSA, CSA frequently presents with nighttime awakenings, nocturnal hypoxia, and daytime somnolence, but only OSA has been reported to present with delirium. We present a patient with clear manifestations of CSA with frank delirium that improved only after BPAP therapy.
C1 [Becker, Kendra] VA Greater Los Angeles Healthcare Syst, Sleep Med Dept 111Q, Los Angeles, CA 90073 USA.
[Becker, Kendra; Poon, Charles] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA.
[Becker, Kendra; Poon, Charles] Olive View UCLA Med Ctr, Sylmar, CA 91342 USA.
[Zeidler, Michelle; Wang, Tisha] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
RP Becker, K (reprint author), VA Greater Los Angeles Healthcare Syst, Sleep Med Dept 111Q, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA.
EM kendrabecker@gmail.com
NR 6
TC 3
Z9 3
U1 0
U2 1
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 JUN 15
PY 2010
VL 6
IS 3
BP 290
EP 291
PG 2
WC Clinical Neurology
SC Neurosciences & Neurology
GA 611BU
UT WOS:000278786300012
PM 20572424
ER
PT J
AU Varthaman, A
Khallou-Laschet, J
Clement, M
Fornasa, G
Kim, HJ
Gaston, AT
Dussiot, M
Caligiuri, G
Herbelin, A
Kaveri, S
Cantor, H
Nicoletti, A
AF Varthaman, Aditi
Khallou-Laschet, Jamila
Clement, Marc
Fornasa, Giulia
Kim, Hye-Jung
Gaston, Anh-Thu
Dussiot, Michael
Caligiuri, Giuseppina
Herbelin, Andre
Kaveri, Srinivas
Cantor, Harvey
Nicoletti, Antonino
TI Control of T Cell Reactivation by Regulatory Qa-1-Restricted CD8(+) T
Cells
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID MOLECULE; RECEPTOR; PEPTIDE; QA-1(B); ANTIGEN; TCR
AB Administration of attenuated pathogenic T cell clones, a procedure known as T cell vaccination, induces CD8(+) T cells specific for peptides derived from the V beta-chain of the TCR presented by the MHC class Ib molecule, Qa-1 expressed on the vaccine cells. These regulatory CD8(+) T cells have the capacity to control the activation of endogenous T cells expressing the same TCR V beta-chain as the vaccinating cells. We hypothesized that vaccination with NKT cells could also induce Qa-1-restricted CD8(+) T cells that would control NKT cell activation. We tested this hypothesis in a murine model of Con A-induced hepatitis that is induced by NKT cells. Vaccination with NKT cells effectively induced protective Qa-1-restricted CD8(+) T cells that prevented hepatitis. Surprisingly, upon vaccination with T cells expressing V beta-chains irrelevant to NKT cells, we discovered that the specificity of vaccine-induced Qa-1-restricted CD8(+) T cells was not limited to the V beta-chain of the vaccinating cells. We further show that these regulatory Qa-1-restricted CD8(+) T cells arise spontaneously upon polyclonal activation of T cells in the absence of deliberate T cell vaccination. These experiments provide new insight into a CD8(+) T cell compartment that regulates the immediate reactivation of conventional T cells and NKT cells. The Journal of Immunology, 2010, 184: 6585-6591.
C1 [Varthaman, Aditi; Khallou-Laschet, Jamila; Clement, Marc; Fornasa, Giulia; Gaston, Anh-Thu; Dussiot, Michael; Caligiuri, Giuseppina; Nicoletti, Antonino] Bichat Claude Bernard Hosp, INSERM, U698, F-75877 Paris 18, France.
[Varthaman, Aditi; Khallou-Laschet, Jamila; Clement, Marc; Fornasa, Giulia; Gaston, Anh-Thu; Dussiot, Michael; Caligiuri, Giuseppina; Nicoletti, Antonino] Univ Denis Diderot Paris 7, Hop Bichat Claude Bernard, Paris, France.
[Varthaman, Aditi; Khallou-Laschet, Jamila; Clement, Marc; Fornasa, Giulia; Gaston, Anh-Thu; Dussiot, Michael; Caligiuri, Giuseppina; Kaveri, Srinivas; Nicoletti, Antonino] Univ Paris 06, INSERM, U872, Ctr Rech Cordeliers,Equipe 16, Paris, France.
[Herbelin, Andre] Univ Paris 05, Hop Necker Enfants Malad, Fac Med, CNRS,Unite Mixte Rech 8147, Paris, France.
[Kim, Hye-Jung; Cantor, Harvey] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
[Cantor, Harvey] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RP Nicoletti, A (reprint author), Bichat Claude Bernard Hosp, INSERM, U698, 46 Rue Henri Huchard, F-75877 Paris 18, France.
EM antonino.nicoletti@inserm.fr
RI Caligiuri, Giuseppina/G-4810-2015; Nicoletti, Antonino/A-9460-2015;
Herbelin, Andre/D-3096-2017
OI Caligiuri, Giuseppina/0000-0003-4973-2205; Nicoletti,
Antonino/0000-0002-2623-0897;
FU Institut National de la Sante et de la Recherche Medicale; Fondation de
France
FX This work was supported by the Institut National de la Sante et de la
Recherche Medicale and the Fondation de France.
NR 12
TC 14
Z9 14
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 JUN 15
PY 2010
VL 184
IS 12
BP 6585
EP 6591
DI 10.4049/jimmunol.0903109
PG 7
WC Immunology
SC Immunology
GA 607PB
UT WOS:000278516700004
PM 20488793
ER
PT J
AU Onoe, T
Kalscheuer, H
Chittenden, M
Zhao, GL
Yang, YG
Sykes, M
AF Onoe, Takashi
Kalscheuer, Hannes
Chittenden, Meredith
Zhao, Guiling
Yang, Yong-Guang
Sykes, Megan
TI Homeostatic Expansion and Phenotypic Conversion of Human T Cells Depend
on Peripheral Interactions with APCs
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID SCID-HU MOUSE; IN-VIVO; PROLIFERATION; LYMPHOPENIA; NAIVE; MICE; MODEL;
TRANSPLANTATION; AUTOIMMUNITY; REGENERATION
AB Immune recovery in lymphopenic hosts depends largely on homeostatic peripheral expansion, especially when thymopoiesis is insufficient, as is often the case in human adults. Although it has been well studied in mice, the study of homeostatic peripheral expansion of human T cells has been limited by the lack of an appropriate in vivo model. In this study, we use T cell-deficient humanized mice and an adoptive transfer approach to demonstrate that two distinct proliferative responses of autologous T cells occur in vivo in a lymphopenic setting. Human naive CD4 and CD8 T cells that undergo rapid proliferation acquire a memory-like phenotype and the ability to rapidly produce IFN-gamma, whereas those undergoing slow proliferation retain naive phenotypic and functional characteristics. Recovery of both populations depends on the extent of human non-T cell chimerism in the periphery of recipient humanized mice. Furthermore, memory conversion of CD4 and CD8 T cells correlates with the level of human CD14(+) and CD19(+) chimerism in recipient mice, respectively, suggesting that different types of APCs support memory conversion of CD4 and CD8 T cells. Because lymphopenia affects clinical outcomes, this model, which will allow detailed investigation of the effects of lymphopenia in patients, is of clinical significance. The Journal of Immunology, 2010, 184: 6756-6765.
C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA.
Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA.
RP Sykes, M (reprint author), Columbia Univ, Med Ctr, Columbia Ctr Translat Immunol, 630 W 168th St,PH 17-111, New York, NY 10032 USA.
EM megan.sykes@columbia.edu
FU National Institutes of Health [P01 AI045897]; Japan Society for the
Promotion of Science
FX This work was supported by National Institutes of Health Grant P01
AI045897. T.O. was supported in part by a Postdoctoral Fellowship for
Research Abroad of the Japan Society for the Promotion of Science.
NR 26
TC 21
Z9 21
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 JUN 15
PY 2010
VL 184
IS 12
BP 6756
EP 6765
DI 10.4049/jimmunol.0901711
PG 10
WC Immunology
SC Immunology
GA 607PB
UT WOS:000278516700022
PM 20483739
ER
PT J
AU Ip, WKE
Sokolovska, A
Charriere, GM
Boyer, L
Dejardin, S
Cappillino, MP
Yantosca, LM
Takahashi, K
Moore, KJ
Lacy-Hulbert, A
Stuart, LM
AF Ip, W. K. Eddie
Sokolovska, Anna
Charriere, Guillaume M.
Boyer, Laurent
Dejardin, Stephanie
Cappillino, Michael P.
Yantosca, L. Michael
Takahashi, Kazue
Moore, Kathryn J.
Lacy-Hulbert, Adam
Stuart, Lynda M.
TI Phagocytosis and Phagosome Acidification Are Required for Pathogen
Processing and MyD88-Dependent Responses to Staphylococcus aureus
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID TOLL-LIKE RECEPTORS; PATTERN-RECOGNITION; DENDRITIC CELLS; MECHANISMS;
MATURATION; PEPTIDOGLYCAN; MACROPHAGES; RESISTANT; PROCEEDS; IMMUNITY
AB Innate immunity is vital for protection from microbes and is mediated by humoral effectors, such as cytokines, and cellular immune defenses, including phagocytic cells (e. g., macrophages). After internalization by phagocytes, microbes are delivered into a phagosome, a complex intracellular organelle with a well-established and important role in microbial killing. However, the role of this organelle in cytokine responses and microbial sensing is less well defined. In this study, we assess the role of the phagosome in innate immune sensing and demonstrate the critical interdependence of phagocytosis and pattern recognition receptor signaling during response to the Gram-positive bacteria Staphylococcus aureus. We show that phagocytosis is essential to initiate an optimal MyD88-dependent response to Staphylococcus aureus. Prior to TLR-dependent cytokine production, bacteria must be engulfed and delivered into acidic phagosomes where acid-activated host enzymes digest the internalized bacteria to liberate otherwise cryptic bacterial-derived ligands that initiate responses from the vacuole. Importantly, in macrophages in which phagosome acidification is perturbed, the impaired response to S. aureus can be rescued by the addition of lysostaphin, a bacterial endopeptidase active at neutral pH that can substitute for the acid-activated host enzymes. Together, these observations delineate the interdependence of phagocytosis with pattern recognition receptor signaling and suggest that therapeutics to augment functions and signaling from the vacuole may be useful strategies to increase host responses to S. aureus. The Journal of Immunology, 2010, 184: 7071-7081.
C1 [Moore, Kathryn J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lipid Metab Unit, Boston, MA 02144 USA.
RP Stuart, LM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Jackson 14,55 Fruit St, Boston, MA 02114 USA.
EM lstuart@partners.org
RI Ip, Eddie/C-3042-2012; Boyer, laurent/F-8921-2015; Charriere,
Guillaume/O-8317-2014;
OI Boyer, laurent/0000-0002-1375-1706; Charriere,
Guillaume/0000-0002-4796-1488; Lacy-Hulbert, Adam/0000-0003-2162-0156;
Moore, kathryn/0000-0003-2505-2547
FU Massachusetts General Hospital for Children; Massachusetts General
Hospital Executive Committee on Research; National Institutes of Health,
National Institute of Allergy and Infectious Diseases
FX This work was supported by Massachusetts General Hospital for Children
startup and grants from the Massachusetts General Hospital Executive
Committee on Research and the National Institutes of Health, National
Institute of Allergy and Infectious Diseases (to L. M. S.).
NR 33
TC 53
Z9 53
U1 1
U2 6
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD JUN 15
PY 2010
VL 184
IS 12
BP 7071
EP 7081
DI 10.4049/jimmunol.1000110
PG 11
WC Immunology
SC Immunology
GA 607PB
UT WOS:000278516700056
PM 20483752
ER
PT J
AU Kalayjian, RC
Machekano, RN
Rizk, N
Robbins, GK
Gandhi, RT
Rodriguez, BA
Pollard, RB
Lederman, MM
Landay, A
AF Kalayjian, Robert C.
Machekano, Rhoderick N.
Rizk, Nesrine
Robbins, Gregory K.
Gandhi, Rajesh T.
Rodriguez, Benigno A.
Pollard, Richard B.
Lederman, Michael M.
Landay, Alan
TI Pretreatment Levels of Soluble Cellular Receptors and Interleukin-6 Are
Associated with HIV Disease Progression in Subjects Treated with Highly
Active Antiretroviral Therapy
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID TUMOR-NECROSIS-FACTOR; IMMUNODEFICIENCY-VIRUS TYPE-1; IMMUNE ACTIVATION;
SEX-DIFFERENCES; PLASMA-LEVELS; VIRAL LOAD; INFECTION; AIDS; MARKERS;
EXPRESSION
AB Background. To identify inflammatory pathways that may contribute to the pathogenesis of human immunodeficiency virus (HIV) disease, we explored associations between AIDS or death and different inflammatory markers, including selected soluble tumor necrosis factor superfamily receptors (sTNFRs) and ligands, interleukin (IL)-6, and CD8 T cell activation, in individuals treated with highly active antiretroviral therapy (HAART).
Methods. A case-control study of subjects in AIDS Clinical Trials Group (ACTG) protocols 384 and 5015, who were matched according to the CD4 cell count and plasma viral load at baseline, was performed using conditional logistic regression.
Results. Higher pretreatment concentrations of sTNFR-1, sCD27, sCD40L, and plasma IL-6 were associated with a new AIDS-defining illness or death in separate models adjusted for age, sex, hemoglobin, and the latest CD4 cell counts. In additional models that excluded case patients with opportunistic infections, sTNFR-1, sCD27, and sCD40L were each associated with a new AIDS-defining malignancy or death that developed at a median of 51 weeks after initiation of HAART, by which time the majority of subjects had a CD4 cell count of >200 cells/cm(3) and had achieved a plasma viral load of <50 copies/mL.
Conclusion. These data are compatible with a model in which these soluble inflammatory markers identify pathways that may contribute to the pathogenesis of HIV disease progression, pathways that might not be a direct consequence of ongoing HIV type 1 replication.
C1 [Kalayjian, Robert C.] Metrohlth Med Ctr, Div Infect Dis, Cleveland, OH 44109 USA.
[Rodriguez, Benigno A.; Lederman, Michael M.] Case Western Reserve Univ, Sch Med, Univ Hosp, Case Med Ctr, Cleveland, OH USA.
[Robbins, Gregory K.; Gandhi, Rajesh T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
[Pollard, Richard B.] Univ Calif Davis, Med Ctr, Sacramento, CA 95817 USA.
[Landay, Alan] Rush Med Coll, Chicago, IL 60612 USA.
RP Kalayjian, RC (reprint author), Metrohlth Med Ctr, Div Infect Dis, 2500 MetroHealth Dr, Cleveland, OH 44109 USA.
EM rkalayjian@metrohealth.org
RI Robbins, Gregory/F-7988-2011; Rodriguez, Benigno/C-3365-2009
OI Rodriguez, Benigno/0000-0001-9736-7957
FU National Institutes of Health [AI 69501, AI 36219, AI 68636, AI069472, 5
RO1 AI066992-04, AI U01 68635, AI062435]; Abbott Laboratories;
Agouron/Pfizer; Brystol-Myers Squibb; Glaxo-SmithKline; Triangle
Pharmaceuticals; National Institutes of Allergy and Infectious Diseases;
National Institutes of Aging
FX Financial support: The National Institutes of Allergy and Infectious
Diseases, the National Institutes of Aging, and the National Institutes
of Health (grants AI 69501, AI 36219, AI 68636, AI069472, 5 RO1
AI066992-04, AI U01 68635, and AI062435); Abbott Laboratories;
Agouron/Pfizer; Brystol-Myers Squibb; Glaxo-SmithKline; and Triangle
Pharmaceuticals.
NR 50
TC 63
Z9 63
U1 0
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD JUN 15
PY 2010
VL 201
IS 12
BP 1796
EP 1805
DI 10.1086/652750
PG 10
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 596LZ
UT WOS:000277687900004
PM 20446847
ER
PT J
AU Yang, CW
Chen, L
Li, CQ
Lynch, MC
Brisken, C
Schmidt, EV
AF Yang, Chuanwei
Chen, Li
Li, Cuiqi
Lynch, Mary C.
Brisken, Cathrin
Schmidt, Emmett V.
TI Cyclin D1 Enhances the Response to Estrogen and Progesterone by
Regulating Progesterone Receptor Expression
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID BREAST-CANCER CELLS; MAMMARY-GLAND DEVELOPMENT; TRANSGENIC MICE;
BETA-CATENIN; TRANSCRIPTIONAL ACTIVITY; BINDING-SITES; GENE; PROMOTER;
GROWTH; ALPHA
AB Estrogen and progesterone are the defining hormones of normal female development, and both play critical roles in breast carcinogenesis. Cyclin D1 is a breast cancer oncogene whose amplification is linked to poor prognosis in estrogen and progesterone receptor-positive breast cancers. Here we report that cyclin D1 regulates progesterone receptor expression, consequently enhancing responses to estrogen and progesterone. Estrogen treatment of cyclin D1 transgenic mice increased progesterone receptor expression and induced mammary hyperplasias that were stimulated by progesterone and blocked by a progesterone antagonist. Progesterone receptor levels decreased in cyclin D1 knockout mice. Cyclin D1 regulated progesterone receptor expression through a novel estrogen-and cyclin D1-responsive enhancer in DNA encoding part of the 3' untranslated region of the progesterone receptor gene. Small inhibitory RNAs for cyclin D1 decreased progesterone receptor expression and estrogen receptor binding to the 3' enhancer region in human breast cancer cells. Since estrogen and progesterone regulate cyclin D1, our results suggest that cyclin D1's participation in a feed-forward loop could contribute to increased breast cancer risks associated with estrogen and progesterone combinations. Additionally, its regulation of the progesterone receptor identifies a novel role for cyclin D1 in ovarian hormone control of breast development and breast carcinogenesis.
C1 [Yang, Chuanwei; Chen, Li; Li, Cuiqi; Lynch, Mary C.; Schmidt, Emmett V.] Massachusetts Gen Hosp, Canc Res Ctr, Boston, MA 02114 USA.
[Brisken, Cathrin] Swiss Inst Expt Canc Res, CH-1066 Epalinges Sur Lausanne, Switzerland.
RP Schmidt, EV (reprint author), Massachusetts Gen Hosp, Canc Res Ctr, 55 Fruit St,GRJ 9th Floor, Boston, MA 02114 USA.
EM schmidt@helix.mgh.harvard.edu
FU National Cancer Institute of the National Institutes of Health [RO1
CA69069]; Harvard Breast Cancer SPORE [P50 CA89393]; [R01 CA112021];
[U01 AI07033]
FX For this work, C. Yang, L. Chen, and E. V. Schmidt were supported by a
grant from the National Cancer Institute of the National Institutes of
Health (grant RO1 CA69069). C. Yang received additional support from
grant R01 CA112021, and both E. V. Schmidt and L. Chen received support
from grant U01 AI07033. C. Li was supported by the Harvard Breast Cancer
SPORE grant P50 CA89393.
NR 52
TC 16
Z9 18
U1 0
U2 4
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 JUN 15
PY 2010
VL 30
IS 12
BP 3111
EP 3125
DI 10.1128/MCB.01398-09
PG 15
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 600OZ
UT WOS:000277997900023
PM 20404095
ER
PT J
AU O'Brien, JL
O'Keefe, KM
LaViolette, PS
DeLuca, AN
Blacker, D
Dickerson, BC
Sperling, RA
AF O'Brien, J. L.
O'Keefe, K. M.
LaViolette, P. S.
DeLuca, A. N.
Blacker, D.
Dickerson, B. C.
Sperling, R. A.
TI Longitudinal fMRI in elderly reveals loss of hippocampal activation with
clinical decline
SO NEUROLOGY
LA English
DT Article
ID MILD COGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE; FUNCTIONAL MRI;
OLDER-ADULTS; RISK; NEURODEGENERATION; PATTERNS; BRAIN; MCI
AB Background: Previous cross-sectional fMRI studies in subjects with prodromal Alzheimer disease (AD) have reported variable results, ranging from hypoactivation, similar to patients with AD, to paradoxically increased activation or hyperactivation compared to cognitively normal older individuals. We have hypothesized that subjects in early phases of prodromal AD may experience a period of hippocampal hyperactivation, followed by loss of hippocampal activation as the disease progresses.
Methods: We studied 51 older individuals without dementia (Clinical Dementia Rating [CDR] at baseline of 0, n = 21, and 0.5, n = 30) with longitudinal clinical and neuropsychological assessments, as well as fMRI during a face-name associative memory paradigm. Whole brain and region-of-interest analyses were applied to the longitudinal fMRI data.
Results: Subjects classified as CDR 0 at baseline showed no difference in fMRI activity over 2 years, whereas those who were CDR 0.5 at baseline demonstrated a decrease in fMRI activity in the right hippocampus (p < 0.001). Dividing the subjects on the basis of their clinical and neuropsychological change over the 2 years, we found that subjects with more rapid decline demonstrated both the highest hippocampal activation at baseline, and the greatest loss of hippocampal activation. These findings remained significant after accounting for age, hippocampal volume, and APOE 4 carrier status.
Conclusions: Clinical decline is associated with loss of hippocampal activation in older subjects. Longitudinal fMRI provides a reliable indicator of brain activation over time, and may prove useful in identifying functional brain changes associated with cognitive decline on the trajectory toward clinical Alzheimer disease. Neurology (R) 2010;74:1969-1976
C1 [O'Brien, J. L.; O'Keefe, K. M.; DeLuca, A. N.; Sperling, R. A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurol,Ctr Alzheimer Res & Treatment, Boston, MA 02115 USA.
[LaViolette, P. S.; Blacker, D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
[Dickerson, B. C.; Sperling, R. A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02115 USA.
[LaViolette, P. S.; Dickerson, B. C.; Sperling, R. A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02115 USA.
RP Sperling, RA (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurol,Ctr Alzheimer Res & Treatment, 221 Longwood Ave, Boston, MA 02115 USA.
EM reisa@rics.bwh.harvard.edu
FU National Institute on Aging [AG-027435]; Alzheimer's Association; NIH
[T32 MH017119, 4 R37 MH060009-09, 5 P50 AG005134-25, 2 R01 AG007370-15,
1 R01AG029411-0-1, R01 NS062028, U01 AG032984, NIA R01 AG29411];
Fidelity Foundation; Elan Corporation; Wyeth; Bristol-Myers Squibb; NIH
(NIA) [R01 AG027435, R01 AG29411, P50 AG005134-25]
FX Supported by the National Institute on Aging AG-027435 and the
Alzheimer's Association.; Ms. O'Brien has received research support from
the NIH (T32 MH017119 [trainee]). Ms. O'Keefe, Nit. LaViolette, and Ms.
DeLuca report no disclosures. Dr. Blacker serves on the editorial boards
of the American Journal of Geriatric Psychiatry and Experimental
Gerontology: and receives research support from the NIH (4 R37
MH060009-09 [Co-PI], 5 P50 AG005134-25 [Co-PI of Core], 2 R01
AG007370-15 [PI of-subcontract], 1 R01AG029411-01 [Co-I], R01 NS062028
[PI], and U01 AG032984 [PI of subcontract]), the Fidelity Foundation,
and the Alzheimer's Association. Dr. Dickerson receives research support
from the NIH (NIA R01 AG29411 [PI]). Dr. Sperling has served on a
scientific advisory board for Archimedes Pharma Ltd (formerly Link
Pharmaceuticals); serves on the editorial board of Alzheimer:, Disease
and Associated Disorders; has received speaker honoraria from Pfizer
Inc; has served as a consultant for Elan Corporation, Wyeth,
Bristol-Myers Squibb, and Bayer; her husband has served as a consultant
for GE Healthcare. She receives research support from Elan Corporation,
Wyeth, Bristol-Myers Squibb, the NIH (NIA R01 AG027435 [PI]; NIA R01
AG29411 [Co-I]; P50 AG005134-25 [PI-Project I]), and from the
Alzheimer's Association,
NR 32
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Z9 108
U1 2
U2 14
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD JUN 15
PY 2010
VL 74
IS 24
BP 1969
EP 1976
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA 617LH
UT WOS:000279281700009
PM 20463288
ER
PT J
AU Buckner, RL
AF Buckner, Randy L.
TI Human functional connectivity: New tools, unresolved questions
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Editorial Material
ID BRAIN NETWORKS
C1 [Buckner, Randy L.] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA.
[Buckner, Randy L.] Massachusetts Gen Hosp, Charlestown, MA 02129 USA.
RP Buckner, RL (reprint author), Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA.
EM randy_buckner@harvard.edu
FU Howard Hughes Medical Institute
NR 15
TC 38
Z9 39
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 JUN 15
PY 2010
VL 107
IS 24
BP 10769
EP 10770
DI 10.1073/pnas.1005987107
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 611IC
UT WOS:000278807400001
PM 20547869
ER
PT J
AU Ulanet, DB
Ludwig, DL
Kahn, CR
Hanahan, D
AF Ulanet, Danielle B.
Ludwig, Dale L.
Kahn, C. Ronald
Hanahan, Douglas
TI Insulin receptor functionally enhances multistage tumor progression and
conveys intrinsic resistance to IGF-1R targeted therapy
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE multistage tumorigenesis; pancreatic neuroendocrine tumor; insulin
receptor isoform A
ID GROWTH-FACTOR-I; HUMAN-BREAST-CANCER; ONCOGENE-INDUCED TUMORIGENESIS;
COLORECTAL-CANCER; MONOCLONAL-ANTIBODY; METABOLIC SYNDROME; HYBRID
RECEPTORS; MOUSE MODELS; CELL-LINES; 2ND SIGNAL
AB The type 1 insulin-like growth factor receptor (IGF-1R) tyrosine kinase is an important mediator of the protumorigenic effects of IGF-I/II, and inhibitors of IGF-1R signaling are currently being tested in clinical cancer trials aiming to assess the utility of this receptor as a therapeutic target. Despite mounting evidence that the highly homologous insulin receptor (IR) can also convey protumorigenic signals, its direct role in cancer progression has not been genetically defined in vivo, and it remains unclear whether such a role for IR signaling could compromise the efficacy of selective IGF-1R targeting strategies. A transgenic mouse model of pancreatic neuroendocrine carcinogenesis engages the IGF signaling pathway, as revealed by its dependence on IGF-II and by accelerated malignant progression upon IGF-1R overexpression. Surprisingly, preclinical trials with an inhibitory monoclonal antibody to IGF-1R did not significantly impact tumor growth, prompting us to investigate the involvement of IR. The levels of IR were found to be significantly up-regulated during multistep progression from hyperplastic lesions to islet tumors. Its functional involvement was revealed by genetic disruption of the IR gene in the oncogene-expressing pancreatic beta cells, which resulted in reduced tumor burden accompanied by increased apoptosis. Notably, the IR knockout tumors now exhibited sensitivity to anti-IGF1R therapy; similarly, high IR to IGF-1R ratios demonstrably conveyed resistance to IGF-1R inhibition in human breast cancer cells. The results predict that elevated IR signaling before and after treatment will respectively manifest intrinsic and adaptive resistance to anti-IGF-1R therapies.
C1 [Ulanet, Danielle B.; Hanahan, Douglas] Univ Calif San Francisco, Ctr Diabet, San Francisco, CA 94143 USA.
[Hanahan, Douglas] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA.
[Hanahan, Douglas] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA.
[Ludwig, Dale L.] ImClone Syst, New York, NY 10014 USA.
[Kahn, C. Ronald] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA.
RP Hanahan, D (reprint author), Swiss Fed Inst Technol, Swiss Inst Expt Canc Res, CH-1015 Lausanne, Switzerland.
EM dh@epfl.ch
FU A.P. Giannini Foundation for Medical Research; National Cancer Institute
FX We thank Ehud Drori, Marina Vayner, Susan Cacacho, and Annie Wang for
technical assistance; the University of California, San Francisco (UCSF)
Diabetes and Endocrinology Research Center Islet Production Facility
Core (for islet isolations) and Microscopy and Imaging Core (for use of
their brightfield microscope and histology equipment); the UCSF Cancer
Center Genome Analysis Core (for Taqman analysis); Peter Olson (UCSF)
for contributing useful reagents; Olivier Nolan-Stevaux for helpful
discussions and suggestions for the manuscript; and Rohit Kulkarni
(Joslin Diabetes Center, Boston, MA) for providing the IRlox mice used
in this study. This research was supported by the A.P. Giannini
Foundation for Medical Research (D.B.U), and by a grant from the
National Cancer Institute (D.H.).
NR 69
TC 118
Z9 125
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 JUN 15
PY 2010
VL 107
IS 24
BP 10791
EP 10798
DI 10.1073/pnas.0914076107
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 611IC
UT WOS:000278807400006
PM 20457905
ER
PT J
AU Lee, SH
Poulogiannis, G
Pyne, S
Jia, SD
Zou, LH
Signoretti, S
Loda, M
Cantley, LC
Roberts, TM
AF Lee, Sang Hyun
Poulogiannis, George
Pyne, Saumyadipta
Jia, Shidong
Zou, Lihua
Signoretti, Sabina
Loda, Massimo
Cantley, Lewis Clayton
Roberts, Thomas M.
TI A constitutively activated form of the p110 beta isoform of PI3-kinase
induces prostatic intraepithelial neoplasia in mice
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID NF-KAPPA-B; PHOSPHOINOSITIDE 3-OH KINASE; TUMOR-SUPPRESSOR GENE;
PHOSPHATIDYLINOSITOL 3-KINASES; EMBRYONIC LETHALITY; IN-VITRO; CANCER;
PTEN; EXPRESSION; AKT
AB Recent work has shown that ablation of p110 beta, but not p110 alpha, markedly impairs tumorigenesis driven by loss of phosphatase and tensin homolog (PTEN) in the mouse prostate. Other laboratories have reported complementary data in human prostate tumor lines, suggesting that p110 beta activation is necessary for tumorigenesis driven by PTEN loss. Given the multiple functions of PTEN, we wondered if p110 beta activation also is sufficient for tumorigenesis. Here, we report that transgenic expression of a constitutively activated p110 beta allele in the prostate drives prostate intraepithelial neoplasia formation. The resulting lesions are similar to, but are clearly distinct from, the ones arising from PTEN loss or Akt activation. Array analyses of transcription in multiple murine prostate tumor models featuring PI3K/AKT pathway activation allowed construction of a pathway signature that may be useful in predicting the prognosis of human prostate tumors.
C1 [Poulogiannis, George; Cantley, Lewis Clayton] Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02115 USA.
[Lee, Sang Hyun; Jia, Shidong; Zou, Lihua; Roberts, Thomas M.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Pyne, Saumyadipta; Signoretti, Sabina; Loda, Massimo] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
RP Cantley, LC (reprint author), Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02115 USA.
EM lewis_cantley@hms.harvard.edu; thomas_roberts@dfci.harvard.edu
RI Zou, Lihua/E-6748-2010; Cantley, Lewis/D-1800-2014
OI Cantley, Lewis/0000-0002-1298-7653
FU National Institutes of Health [P01CA089021]; Prostate Cancer Foundation;
Linda and Arthur Gelb Center for Translational Research;
Dana-Farber/Harvard Cancer Center Prostate Specialized Programs of
Research Excellence
FX We thank Dr. J. S. Lee (University of Texas MD Anderson Cancer Center,
Houston) for helpful discussions, Dr. A. Upadhyaya (University of South
Florida, Tampa, FL) for helpful comments on the manuscript, Dr. W.
Sellers (Novartis Phamaceuticals, Cambridge, MA) for the Akt TG mouse,
Dr. R. Shivadasani (Dana-Farber Cancer Institute) for reviewing slides,
and Dr. E. Li (Novartis Pharmaceuticals) and J. Horner (Dana-Farber
Cancer Institute, Boston) for creating the TG mice. This work was
supported in part by grants from the National Institutes of Health
(including Grant P01CA089021 to T.M.R., L.C.C., and M.L.), the Prostate
Cancer Foundation (to M.L.), the Linda and Arthur Gelb Center for
Translational Research (to M.L.), and the Dana-Farber/Harvard Cancer
Center Prostate Specialized Programs of Research Excellence (to T.M.R.,
L.C.C., and M.L.).
NR 49
TC 33
Z9 35
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 JUN 15
PY 2010
VL 107
IS 24
BP 11002
EP 11007
DI 10.1073/pnas.1005642107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 611IC
UT WOS:000278807400042
PM 20534477
ER
PT J
AU Holt, SK
Kwon, EM
Lin, DW
Ostrander, EA
Stanford, JL
AF Holt, Sarah K.
Kwon, Erika M.
Lin, Daniel W.
Ostrander, Elaine A.
Stanford, Janet L.
TI Association of Hepsin Gene Variants with Prostate Cancer Risk and
Prognosis
SO PROSTATE
LA English
DT Article
DE prostate neoplasm; single nucleotide polymorphism; Hepsin; case-control
ID SINGLE-NUCLEOTIDE POLYMORPHISMS; LINKAGE DISEQUILIBRIUM; AGGRESSIVENESS
LOCI; LAMININ-332; PROGRESSION; SUBSTRATE; SCAN
AB BACKGROUND. Hepsin (HPN) is one of the most consistently overexpressed genes in prostate cancer and there is some evidence supporting an association between HPN gene variants and prostate cancer risk. We report results from a population-based case control genetic association study for six tagging single nucleotide polymorphisms (tagSNPs) in the HPN gene.
METHODS. Prostate cancer risk was estimated using adjusted unconditional logistic regression in 1,401 incident prostate cancer cases diagnosed in 1993 through 1996 or 2002 through 2005 and 1,351 age-matched controls. Risks of disease recurrence/progression and prostate cancer-specific mortality were estimated using Cox proportional hazards (PH) regression in 437 cases with long-term follow-up.
RESULTS. There were 135 recurrence/progression events and 57 cases who died of prostate cancer. Contrary to some earlier studies, we found no evidence of altered risk of developing prostate cancer overall or when clinical measures of tumor aggressiveness were considered for any of the tagSNPs, assessed either individually or by haplotypes. There was no evidence of altered risks of tumor recurrence/progression or prostate cancer death associated with variants in the HPN gene.
CONCLUSIONS. Germline genetic variation of HPN does not seem to contribute to risk of prostate cancer or prognosis. Prostate 70: 1012-1019, 2010. (c) 2010 Wiley-Liss, Inc.
C1 [Holt, Sarah K.; Lin, Daniel W.; Stanford, Janet L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
[Kwon, Erika M.; Ostrander, Elaine A.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA.
[Kwon, Erika M.] Johns Hopkins Univ, Sch Med, Program Human Genet & Mol Biol, Baltimore, MD USA.
[Lin, Daniel W.] Vet Affairs Puget Sound Hlth Care Syst, Dept Urol, Seattle, WA USA.
[Lin, Daniel W.] Univ Washington, Dept Urol, Seattle, WA 98195 USA.
[Stanford, Janet L.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
RP Holt, SK (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Mailstop M4-A402,POB 19024, Seattle, WA 98109 USA.
EM skholt@fhcrc.org
OI Ostrander, Elaine/0000-0001-6075-9738
FU National Cancer Institute [RO1-CA56678, RO1-CA092579, RO1-CA082554,
P50-CA097186]; Fred Hutchinson Cancer Research Center; National Human
Genome Research Institute
FX Grant sponsor: National Cancer Institute; Grant numbers: RO1-CA56678,
RO1-CA092579, RO1-CA082554, P50-CA097186; Grant sponsor: Fred Hutchinson
Cancer Research Center; Grant sponsor: Intramural Program of the
National Human Genome Research Institute.
NR 21
TC 15
Z9 15
U1 0
U2 0
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 JUN 15
PY 2010
VL 70
IS 9
BP 1012
EP 1019
DI 10.1002/pros.21135
PG 8
WC Endocrinology & Metabolism; Urology & Nephrology
SC Endocrinology & Metabolism; Urology & Nephrology
GA 607IO
UT WOS:000278494300009
PM 20166135
ER
PT J
AU Zhang, P
Lader, AS
Etcheverry, MA
Cantiello, HF
AF Zhang, Peng
Lader, Alan S.
Etcheverry, Martin A.
Cantiello, Horacio F.
TI Crotoxin potentiates L-type calcium currents and modulates the action
potential of neonatal rat cardiomyocytes
SO TOXICON
LA English
DT Article
DE Snake venom; Phospholipase A(2); L-type Ca(2+) channels; Cardiac
electrical activity; Cardiotoxicity
ID SOUTH-AMERICAN RATTLESNAKE; MUSCARINIC TOXINS; BETA-BUNGAROTOXIN;
SKELETAL-MUSCLE; SNAKE-VENOMS; GREEN MAMBA; HEART; COMPONENTS;
RECEPTORS; CELLS
AB Crotoxin (CTX), the major component of the venom from the South American rattlesnake (Crotalus durissus terrificus) has diverse toxic effects, including pre-synaptic neurotoxicity. Among these, the effect of CTX in the heart is the least understood. In this study, we explored the effect(s) of CTX on the electrophysiological activity of neonatal rat cardiomyocytes (NRCM). By using patch, voltage-, and current-clamping techniques, we found that, in NRCM, CTX strongly potentiates L-type Ca(2+) currents, an important contributor to the cardiac action potential (AP) and excitation-contraction (EC) coupling. External addition of CTX produced a rapid increase in L-type Ca(2+) currents. Addition of verapamil (10 mu M) an L-type Ca(2+) channel blocker, completely blocked the CTX-induced increase in the currents. A detailed kinetic analysis of AP in NRCM revealed that CTX caused both an elongation of AP duration (APD) and an increase of its amplitude, while a decrease of firing frequency. In addition, increasing concentrations of CTX completely blocked the AP as well as the beating of NRCM. The data indicate that CTX is a potent modulator of L-type Ca(2+) currents, which provides a possible mechanistic correlation for the cardiotoxicity of the toxin, and may offer potential clinical implications in the control of cardiac function. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Zhang, Peng; Lader, Alan S.; Cantiello, Horacio F.] Massachusetts Gen Hosp, Dept Med, Div Nephrol, Charlestown, MA 02129 USA.
[Etcheverry, Martin A.] Ventech Res, Cambridge, MA USA.
[Cantiello, Horacio F.] UBA CONICET, Lab Canales Ion, ININCA, Buenos Aires, DF, Argentina.
RP Cantiello, HF (reprint author), Massachusetts Gen Hosp E, 149 13th St, Charlestown, MA 02129 USA.
EM cantiello@helix.mgh.harvard.edu
NR 37
TC 6
Z9 6
U1 0
U2 2
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0041-0101
J9 TOXICON
JI Toxicon
PD JUN 15
PY 2010
VL 55
IS 7
BP 1236
EP 1243
DI 10.1016/j.toxicon.2010.01.008
PG 8
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA 599AJ
UT WOS:000277881900004
PM 20122949
ER
PT J
AU Duran-Struuck, R
Cho, PS
Teague, AGS
Fishman, B
Fishman, AS
Hanekamp, JS
Moran, SG
Wikiel, KJ
Ferguson, KK
Lo, DP
Duggan, M
Arn, JS
Billiter, B
Horner, B
Houser, S
Yeap, BY
Westmoreland, SV
Spitzer, TR
McMorrow, IM
Sachs, DH
Bronson, RT
Huang, CA
AF Duran-Struuck, Raimon
Cho, Patricia S.
Teague, Alexander G. S.
Fishman, Brian
Fishman, Aaron S.
Hanekamp, John S.
Moran, Shannon G.
Wikiel, Krzysztof J.
Ferguson, Kelly K.
Lo, Diana P.
Duggan, Michael
Arn, J. Scott
Billiter, Bob
Horner, Ben
Houser, Stuart
Yeap, Beow Yong
Westmoreland, Susan V.
Spitzer, Thomas R.
McMorrow, Isabel M.
Sachs, David H.
Bronson, Roderick T.
Huang, Christene A.
TI Myelogenous leukemia in adult inbred MHC-defined miniature swine: A
model for human myeloid leukemias
SO VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY
LA English
DT Article
DE Myelogenous leukemia; Miniature swine; MGH histocompatible swine;
Immunophenotyping
ID MAJOR HISTOCOMPATIBILITY COMPLEX; LARGE-ANIMAL MODEL;
MONOCLONAL-ANTIBODIES; DIFFERENTIATION ANTIGENS; CD WORKSHOP; PORCINE;
CELLS; PIGS; ULTRASTRUCTURE; LYMPHOSARCOMA
AB This manuscript reports on five cases of spontaneous myelogenous leukemia, similar to human disease, occurring within highly inbred, histocompatible sublines of Massachusetts General Hospital (MGH) MHC-defined miniature swine. In cases where a neoplasm was suspected based on clinical observations, samples were obtained for complete blood count, peripheral blood smear, and flow cytometric analysis. Animals confirmed to have neoplasms were euthanized and underwent necropsy. Histological samples were obtained from abnormal tissues and suspect lesions. The phenotype of the malignancies was assessed by flow cytometric analysis of processed peripheral blood mononuclear cells and affected tissues. Five cases of spontaneous myeloid leukemia were identified in adult animals older than 30 months of age. All animals presented with symptoms of weight loss, lethargy, and marked leukocytosis. At autopsy, all animals had systemic disease involvement and presented with severe hepatosplenomegaly. Three of the five myelogenous leukemias have successfully been expanded in vitro. The clustered incidence of disease in this closed herd suggests that genetic factors may be contributing to disease development. Myelogenous leukemia cell lines established from inbred sublines of MGH MHC-defined miniature swine have the potential to be utilized as a model to evaluate therapies of human leukemia. (C) 2009 Elsevier B.V. All rights reserved.
C1 [Duran-Struuck, Raimon] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr,Dept Surg, Boston, MA 02129 USA.
[Yeap, Beow Yong] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA.
[Spitzer, Thomas R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
[Westmoreland, Susan V.] Harvard Univ, New England Primate Res Ctr, Sch Med, Boston, MA 02129 USA.
RP Duran-Struuck, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr,Dept Surg, 149 13th St, Boston, MA 02129 USA.
EM raimon.duran-struuck@tbrc.mgh.harvard.edu
OI Ferguson, Kelly/0000-0001-8467-3250
FU National Center for Research Resources [K01RR024466]; National Cancer
Institute [1P01CA111519-01-A1]
FX The project described was supported by Award Number K01RR024466 (RDS)
from the National Center for Research Resources, and the
1P01CA111519-01-A1 (CAR) from the National Cancer Institute.
NR 46
TC 8
Z9 8
U1 0
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-2427
J9 VET IMMUNOL IMMUNOP
JI Vet. Immunol. Immunopathol.
PD JUN 15
PY 2010
VL 135
IS 3-4
BP 243
EP 256
DI 10.1016/j.vetimm.2009.12.005
PG 14
WC Immunology; Veterinary Sciences
SC Immunology; Veterinary Sciences
GA 604RO
UT WOS:000278296400009
PM 20079939
ER
PT J
AU Johansen, KL
AF Johansen, Kirsten L.
TI Chronic Kidney Disease in Elderly Individuals
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Editorial Material
ID CARDIOVASCULAR-DISEASE; MORTALITY RISK; AGE; PREVALENCE; OUTCOMES; EGFR;
CKD
C1 [Johansen, Kirsten L.] San Francisco VA Med Ctr, Nephrol Sect, San Francisco, CA 94121 USA.
[Johansen, Kirsten L.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
RP Johansen, KL (reprint author), San Francisco VA Med Ctr, Nephrol Sect, 4150 Clement St,POB 111J, San Francisco, CA 94121 USA.
EM kirsten.johansen@ucsf.edu
NR 14
TC 2
Z9 2
U1 0
U2 0
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 JUN 14
PY 2010
VL 170
IS 11
BP 926
EP 927
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 610YA
UT WOS:000278775100001
PM 20548002
ER
PT J
AU O'Hare, AM
Hailpern, SM
Pavkov, ME
Rios-Burrows, N
Gupta, I
Maynard, C
Todd-Stenberg, J
Rodriguez, RA
Hemmelgarn, BR
Saran, R
Williams, DE
AF O'Hare, Ann M.
Hailpern, Susan M.
Pavkov, Meda E.
Rios-Burrows, Nilka
Gupta, Indra
Maynard, Charles
Todd-Stenberg, Jeff
Rodriguez, Rudolph A.
Hemmelgarn, Brenda R.
Saran, Rajiv
Williams, Desmond E.
TI Prognostic Implications of the Urinary Albumin to Creatinine Ratio in
Veterans of Different Ages With Diabetes
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Article
ID CHRONIC KIDNEY-DISEASE; GLOMERULAR-FILTRATION-RATE; ALL-CAUSE MORTALITY;
CARDIOVASCULAR MORTALITY; NONDIABETIC INDIVIDUALS; RISK-FACTORS;
MICROALBUMINURIA; POPULATION; DEATH; OUTCOMES
AB Background: Albuminuria is associated with an increased risk of death independent of level of renal function. Whether this association is similar for adults of all ages is not known.
Methods: We examined the association between the albumin to creatinine ratio (ACR) and all-cause mortality after stratification by estimated glomerular filtration rate (eGFR) and age group in 94 934 veterans with diabetes mellitus. Cohort members had at least 1 ACR recorded in the Veterans Affairs Health Care System between October 1, 2002, and September 30, 2003, and were followed up for death through October 15, 2009.
Results: From the youngest to the oldest age group, the prevalence of an eGFR less than 60 mL/min/1.73 m(2) ranged from 11% to 41%; microalbuminuria (ACR 30299 mg/g) ranged from 19% to 28%; and macroalbuminuria (ACR >= 300 mg/g) ranged from 3.2% to 3.7%. Of patients with an eGFR less than 60 mL/min/1.73 m(2), 72% of those younger than 65 years, 74% of those 65 to 74 years old, and 59% of those 75 years and older had an eGFR of 45 to 59 mL/min/1.73 m(2). In all age groups, less than 35% of these patients had albuminuria (ie, ACR >= 30 mg/g). In patients 75 years and older, the ACR was independently associated with an increased risk of death at all levels of eGFR after adjusting for potential confounders. In younger age groups, this association was present at higher levels of eGFRs but seemed to be attenuated at lower levels.
Conclusion: The ACR is independently associated with mortality at all levels of eGFR in older adults with diabetes and may be particularly helpful for risk stratification in the large group with moderate reductions in eGFR.
C1 [O'Hare, Ann M.; Rodriguez, Rudolph A.] Vet Affairs Puget Sound Healthcare Syst, Dept Med, Seattle, WA USA.
[O'Hare, Ann M.; Gupta, Indra; Maynard, Charles; Todd-Stenberg, Jeff] Vet Affairs Puget Sound Healthcare Syst, Hlth Serv Res & Dev Ctr Excellence, Seattle, WA USA.
[O'Hare, Ann M.; Rodriguez, Rudolph A.] Univ Washington, Dept Med, Seattle, WA USA.
[Hailpern, Susan M.; Pavkov, Meda E.; Rios-Burrows, Nilka; Williams, Desmond E.] Ctr Dis Control & Prevent, Div Diabet Translat, Atlanta, GA USA.
[Hemmelgarn, Brenda R.] Univ Calgary, Dept Med, Calgary, AB, Canada.
[Saran, Rajiv] Univ Michigan, Ann Arbor, MI 48109 USA.
RP O'Hare, AM (reprint author), VA Puget Sound Med Ctr, Div Nephrol, Primary & Specialty Med Serv Line, Nephrol & Renal Dialysis Unit, Bldg 100,Room 5B113,1660 S Columbian Way, Seattle, WA 98108 USA.
EM ann.ohare@va.gov
RI Hemmelgarn, Brenda/I-6894-2012; Maynard, Charles/N-3906-2015
OI Maynard, Charles/0000-0002-1644-7814
FU National Institute on Aging; Japanese Society for Footcare; UpToDate;
Centers for Disease Control and Prevention; VA Puget Sound Health Care
System
FX Financial Disclosure: Dr O'Hare receives research support from the
National Institute on Aging and has received royalties from UpToDate and
speaker fees from the Japanese Society for Footcare in the past year.;
Funding/Support: This work was supported by an Interagency Agreement
between the Centers for Disease Control and Prevention and the VA Puget
Sound Health Care System.
NR 29
TC 31
Z9 34
U1 1
U2 1
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0003-9926
J9 ARCH INTERN MED
JI Arch. Intern. Med.
PD JUN 14
PY 2010
VL 170
IS 11
BP 930
EP 936
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 610YA
UT WOS:000278775100005
PM 20548004
ER
PT J
AU Kerlikowske, K
AF Kerlikowske, Karla
TI A Call for Evidence of Benefits Outweighing Harms Before Implementing
New Technologies
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Editorial Material
ID COMPUTER-AIDED DETECTION; SCREENING MAMMOGRAPHY; BREAST-CANCER;
PERFORMANCE
C1 [Kerlikowske, Karla] Univ Calif San Francisco, Gen Internal Med Sect, Dept Vet Affairs, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94121 USA.
[Kerlikowske, Karla] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94121 USA.
[Kerlikowske, Karla] Univ Calif San Francisco, Dept Med, San Francisco, CA 94121 USA.
RP Kerlikowske, K (reprint author), Univ Calif San Francisco, Gen Internal Med Sect, Dept Vet Affairs, San Francisco Vet Affairs Med Ctr, 111A1,4150 Clement St, San Francisco, CA 94121 USA.
EM karla.kerlikowske@ucsf.edu
FU NCI NIH HHS [U01CA63740, P50 CA58207]
NR 14
TC 4
Z9 5
U1 0
U2 0
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 JUN 14
PY 2010
VL 170
IS 11
BP 990
EP 991
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 610YA
UT WOS:000278775100015
PM 20548014
ER
PT J
AU Schmittdiel, JA
Steers, N
Duru, OK
Ettner, SL
Brown, AF
Fung, V
Hsu, J
Quiter, E
Tseng, CW
Mangione, CM
AF Schmittdiel, Julie A.
Steers, Neil
Duru, O. Kenrik
Ettner, Susan L.
Brown, Arleen F.
Fung, Vicki
Hsu, John
Quiter, Elaine
Tseng, Chien-Wen
Mangione, Carol M.
TI Patient-provider communication regarding drug costsin Medicare Part D
beneficiaries with diabetes: a TRIAD Study
SO BMC HEALTH SERVICES RESEARCH
LA English
DT Article
ID OF-POCKET COSTS; PRESCRIPTION DRUGS; NATIONAL-SURVEY; COVERAGE; SENIORS;
BENEFIT; RESPONSIBILITY; NONADHERENCE; GUIDE; PLAN
AB Background: Little is known about drug cost communications of Medicare Part D beneficiaries with chronic conditions such as diabetes. The purpose of this study is to assess Medicare Part D beneficiaries with diabetes' levels of communication with physicians regarding prescription drug costs; the perceived importance of these communications; levels of prescription drug switching due to cost; and self-reported cost-related medication non-adherence.
Methods: Data were obtained from a cross-sectional survey (58% response rate) of 1,458 Medicare beneficiaries with diabetes who entered the coverage gap in 2006; adjusted percentages of patients with communication issues were obtained from multivariate regression analyses adjusting for patient demographics and clinical characteristics.
Results: Fewer than half of patients reported discussing the cost of medications with their physicians, while over 75% reported that such communications were important. Forty-eight percent reported their physician had switched to a less expensive medication due to costs. Minorities, females, and older adults had significantly lower levels of communication with their physicians regarding drug costs than white, male, and younger patients respectively. Patients with < $25 K annual household income were more likely than higher income patients to have talked about prescription drug costs with doctors, and to report cost-related non-adherence (27% vs. 17%, p < .001).
Conclusions: Medicare Part D beneficiaries with diabetes who entered the coverage gap have low levels of communication with physicians about drug costs, despite the high perceived importance of such communication. Understanding patient and plan-level characteristics differences in communication and use of cost-cutting strategies can inform interventions to help patients manage prescription drug costs.
C1 [Schmittdiel, Julie A.; Fung, Vicki; Mangione, Carol M.] Kaiser Permanente, Div Res, Oakland, CA USA.
[Steers, Neil; Duru, O. Kenrik; Ettner, Susan L.; Brown, Arleen F.; Quiter, Elaine; Mangione, Carol M.] Univ Calif Los Angeles, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA USA.
[Hsu, John] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA.
[Tseng, Chien-Wen] Family Med & Community Hlth, Pacific Hlth Res Inst, Honolulu, HI USA.
RP Schmittdiel, JA (reprint author), Kaiser Permanente, Div Res, Oakland, CA USA.
EM Julie.A.Schmittdiel@kp.org
FU Centers for Disease Control [U58/CCU923527-04-1]; Agency for Healthcare
Research and Quality; National Institute of Aging [R01HS013902-01,
AG029316-01]; Office of Research in Women [K12HD052163]; UCLA Resource
Center for Minority Aging Research (NIA) [2P30AG021684-06]
FX This project was funded by Centers for Disease Control, Contract no.
U58/CCU923527-04-1; the Agency for Healthcare Research and Quality and
the National Institute of Aging (R01HS013902-01) and NIA
(R01-AG029316-01), by the Office of Research in Women's Health Building
Interdisciplinary Careers in Women's Health K12 Career Development Award
(K12HD052163), and by the UCLA Resource Center for Minority Aging
Research (NIA # 2P30AG021684-06).
NR 25
TC 9
Z9 9
U1 2
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1472-6963
J9 BMC HEALTH SERV RES
JI BMC Health Serv. Res.
PD JUN 14
PY 2010
VL 10
AR 164
DI 10.1186/1472-6963-10-164
PG 7
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA 625GR
UT WOS:000279883600002
PM 20546616
ER
PT J
AU Stankovic, KM
Adachi, O
Tsuji, K
Kristiansen, AG
Adams, JC
Rosen, V
McKenna, MJ
AF Stankovic, Konstantina M.
Adachi, Osamu
Tsuji, Kunikazu
Kristiansen, Arthur G.
Adams, Joe C.
Rosen, Vicki
McKenna, Michael J.
TI Differences in gene expression between the otic capsule and other bones
SO HEARING RESEARCH
LA English
DT Article
DE Otic capsule; opg; Bmpr1b; Otosclerosis
ID CHICKEN INNER-EAR; MORPHOGENETIC PROTEINS; CLASS DISCOVERY;
MESSENGER-RNA; MOUSE LIMB; OTOSCLEROSIS; ASSOCIATION; PATTERNS; COL1A1;
NOGGIN
AB Our long term goal is to understand the molecular pathology of otosclerosis and to develop better forms of therapy. Toward this goal, the current study focused on characterizing the molecular factors responsible for the unique biological features of the otic capsule: its minimal rate of remodeling, and lack of healing capacity when fractured. We compared expression levels of 62 genes involved in bone metabolism between the adult murine otic capsule and the tibia and parietal bones; the latter exemplify bones formed by endochondral and intramembranous ossification, respectively. Gene expression levels were measured using real-time quantitative RT-PCR and analyzed using tools of bioinformatics. Expression patterns of key genes were verified with in situ hybridization. The molecular profile of the otic capsule was distinctly different from that of the tibia and parietal bone. Genes found to be most characteristic of the otic capsule were: osteoprotegerin (opg), bone morphogenetic protein receptor 1b (bmpr1b) and bone morphogenetic protein 3 (bmp3). Expression levels were high for opg and bmpr1b, and minimal for bmp3 within the otic capsule. We concluded that opg and bmpr1b likely play important roles in inhibition of remodeling within the otic capsule. (C) 2010 Elsevier B.V. All rights reserved.
C1 [Stankovic, Konstantina M.; Adachi, Osamu; Kristiansen, Arthur G.; Adams, Joe C.; McKenna, Michael J.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA.
[Stankovic, Konstantina M.; Adachi, Osamu; Kristiansen, Arthur G.; Adams, Joe C.; McKenna, Michael J.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA.
[Stankovic, Konstantina M.; Adachi, Osamu; Adams, Joe C.; McKenna, Michael J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA.
[Tsuji, Kunikazu; Rosen, Vicki] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA.
RP Stankovic, KM (reprint author), Massachusetts Eye & Ear Infirm Otolaryngol, 243 Charles St, Boston, MA 02114 USA.
EM konstantina_stankovic@meei.harvard.edu; osamu_adachi@meei.harvard.edu;
kunikazu_tsuji@hsdm.harvard.edu; kris@epl.meei.harvard.edu;
jca@meei.harvard.edu; vicki_rosen@hsdm.harvard.edu;
michael_mckenna@meei.harvard.edu
FU NIDCD [5RO1 DCO3401-06]; American Otological Association; Massachusetts
Life Sciences Center
FX We thank Dr. Saumil Merchant for helpful comments on earlier versions of
the manuscript. This work was supported by NIDCD Grant 5RO1 DCO3401-06
(M.J.M.), American Otological Association (K.M.S.), Massachusetts Life
Sciences Center (K.M.S.) and Mr. Lakshmi Mittal (M.J.M.).
NR 52
TC 15
Z9 15
U1 3
U2 7
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0378-5955
J9 HEARING RES
JI Hear. Res.
PD JUN 14
PY 2010
VL 265
IS 1-2
BP 83
EP 89
DI 10.1016/j.heares.2010.02.006
PG 7
WC Audiology & Speech-Language Pathology; Neurosciences;
Otorhinolaryngology
SC Audiology & Speech-Language Pathology; Neurosciences & Neurology;
Otorhinolaryngology
GA 614XB
UT WOS:000279092000012
PM 20146935
ER
PT J
AU Greenstein, RJ
Su, LY
Brown, ST
AF Greenstein, Robert J.
Su, Liya
Brown, Sheldon T.
TI The Thioamides Methimazole and Thiourea Inhibit Growth of M. avium
Subspecies paratuberculosis in Culture
SO PLOS ONE
LA English
DT Article
ID CROHNS-DISEASE; MYCOBACTERIUM-LEPRAE; ANTITHYROID DRUGS; GRAVES-DISEASE;
HASHIMOTOS-THYROIDITIS; LEPROSY; MECHANISM; TUBERCULOSIS;
HYPERTHYROIDISM; MULTIPLICATION
AB Background: Thyrotoxicosis is conceptualized as an "autoimmune'' disease with no accepted infectious etiology. There are increasingly compelling data that another "autoimmune'' affliction, Crohn disease, may be caused by Mycobacterium avium subspecies paratuberculosis (MAP). Like M. tb, MAP is systemic. We hypothesized that some cases of thyrotoxicosis may be initiated by a MAP infection. Because other thioamides treat tuberculosis, leprosy and M. avium complex, we hypothesized that a mode of action of some thioamide anti-thyrotoxicosis medications may include MAP growth inhibition.
Methods: The effect of the thioamides, thiourea, methimazole and 6-propo-2-thiouracil (6-PTU) were studied in radiometric Bactec (R) culture, on ten strains of three mycobacterial species (six of MAP, two of M. avium and two of M. tb. complex). Data are presented as "cumulative growth index,'' (cGI) or "percent decrease in cumulative GI'' (%-Delta cGI).
Principal Findings: Methimazole was the most effective thioamide at inhibiting MAP growth. At 128 mu g/ml: MAP UCF-4; 65%-Delta cGI & MAP ATCC 19698; 90%-Delta cGI. Thiourea inhibited MAP "Ben'' maximally; 70%-Delta cGI. Neither methimazole nor thiourea inhibited M. avium or M. tb. at the doses tested. 6-PTU has no inhibition on any strain studied, although a structurally analogous control, 5-PTU, was the most inhibitory thioamide tested.
Significance: We show inhibition of MAP growth by the thioamides, thiourea and methimazole in culture. These data are compatible with the hypothesis that these thioamides may have anti-prokaryotic in addition to their well-established eukaryotic actions in thyrotoxic individuals.
C1 [Greenstein, Robert J.] James J Peters VA Med Ctr, Dept Surg, Bronx, NY USA.
[Greenstein, Robert J.; Su, Liya] James J Peters VA Med Ctr, Lab Mol Surg Res, Bronx, NY USA.
[Brown, Sheldon T.] James J Peters VA Med Ctr, Dept Med, Bronx, NY USA.
[Brown, Sheldon T.] Mt Sinai Sch Med, New York, NY USA.
RP Greenstein, RJ (reprint author), James J Peters VA Med Ctr, Dept Surg, Bronx, NY USA.
EM BGAxis@aol.com
FU Bronx Veterans Medical Research Foundation, Inc. at the James J. Peters
VAMC Bronx NY
FX The authors thank Becton-Dickinson for providing the Bactec (R) vials.
Becton-Dickinson had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript. No
other extramural funds were obtained. This material is the result of
work supported with resources and the use of facilities at the James J.
Peters VAMC Bronx NY. Other than the JJP VAMC Bronx Research and
Development Committee reviewing, and approving, our submitted research
protocol the James J. Peters VAMC Bronx NY had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript. This study was supported by the Bronx Veterans Medical
Research Foundation, Inc. at the James J. Peters VAMC Bronx NY. The
Bronx Veterans Medical Research Foundation, Inc. had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 39
TC 4
Z9 4
U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 14
PY 2010
VL 5
IS 6
AR e11099
DI 10.1371/journal.pone.0011099
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 610NX
UT WOS:000278741100013
PM 20559419
ER
PT J
AU Halling-Brown, M
Pappalardo, F
Rapin, N
Zhang, P
Alemani, D
Emerson, A
Castiglione, F
Duroux, P
Pennisi, M
Miotto, O
Churchill, D
Rossi, E
Moss, DS
Sansom, CE
Bernaschi, M
Lefranc, MP
Brunak, S
Lund, O
Motta, S
Lollini, PL
Murgo, A
Palladini, A
Basford, KE
Brusic, V
Shepherd, AJ
AF Halling-Brown, Mark
Pappalardo, Francesco
Rapin, Nicolas
Zhang, Ping
Alemani, Davide
Emerson, Andrew
Castiglione, Filippo
Duroux, Patrice
Pennisi, Marzio
Miotto, Olivo
Churchill, Daniel
Rossi, Elda
Moss, David S.
Sansom, Clare E.
Bernaschi, Massimo
Lefranc, Marie-Paule
Brunak, Soren
Lund, Ole
Motta, Santo
Lollini, Pier-Luigi
Murgo, Annalisa
Palladini, Arianna
Basford, Kaye E.
Brusic, Vladimir
Shepherd, Adrian J.
TI ImmunoGrid: towards agent-based simulations of the human immune system
at a natural scale
SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY A-MATHEMATICAL PHYSICAL
AND ENGINEERING SCIENCES
LA English
DT Article; Proceedings Paper
CT 4th International Congress on Computational Bioengineering/1st European
Symposium on Biomedical Integrative Research
CY SEP 16-18, 2009
CL Bertinoro, ITALY
DE systems biology; agent-based simulation; immunoinformatics; Grid
computing; vaccine discovery
ID IMGT-ONTOLOGY; MODELS; VACCINE; INFECTION; IMMUNOGENETICS; OPTIMIZATION;
PREDICTIONS; CHALLENGES; EVOLUTION; DISCOVERY
AB The ultimate aim of the EU-funded ImmunoGrid project is to develop a natural-scale model of the human immune system-that is, one that reflects both the diversity and the relative proportions of the molecules and cells that comprise it-together with the grid infrastructure necessary to apply this model to specific applications in the field of immunology. These objectives present the ImmunoGrid Consortium with formidable challenges in terms of complexity of the immune system, our partial understanding about how the immune system works, the lack of reliable data and the scale of computational resources required.
In this paper, we explain the key challenges and the approaches adopted to overcome them. We also consider wider implications for the present ambitious plans to develop natural-scale, integrated models of the human body that can make contributions to personalized health care, such as the European Virtual Physiological Human initiative.
Finally, we ask a key question: How long will it take us to resolve these challenges and when can we expect to have fully functional models that will deliver health-care benefits in the form of personalized care solutions and improved disease prevention?
C1 [Halling-Brown, Mark; Moss, David S.; Sansom, Clare E.; Shepherd, Adrian J.] Univ London Birkbeck Coll, Inst Struct & Mol Biol, Dept Biol Sci, London WC1E 7HX, England.
[Pappalardo, Francesco; Pennisi, Marzio; Motta, Santo] Univ Catania, Dept Math & Comp Sci, Catania, Italy.
[Rapin, Nicolas; Brunak, Soren; Lund, Ole] Danish Tech Univ, Ctr Biol Sequence Anal, Lyngby, Denmark.
[Zhang, Ping] Bond Univ, Fac Hlth Sci & Med, Robina, Qld, Australia.
[Alemani, Davide; Basford, Kaye E.; Brusic, Vladimir] Univ Queensland, Sch Land Crop & Food Sci, Brisbane, Qld, Australia.
[Emerson, Andrew; Rossi, Elda] CINECA, High Performance Syst Div, Casalecchio Di Reno, Italy.
[Castiglione, Filippo; Bernaschi, Massimo] CNR, Italian Natl Res Council, Inst Appl Comp, Rome, Italy.
[Duroux, Patrice; Lefranc, Marie-Paule] CNRS, Inst Genet Humaine, Immunogenet Mol Lab, Montpellier, France.
[Miotto, Olivo] Natl Univ Singapore, Inst Syst Sci, Singapore 117548, Singapore.
[Churchill, Daniel] Univ Hong Kong, Div Informat & Technol Studies, Pokfulam, Hong Kong, Peoples R China.
[Lollini, Pier-Luigi; Murgo, Annalisa; Palladini, Arianna] Univ Bologna, Sect Canc Res, I-40126 Bologna, Italy.
[Brusic, Vladimir] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA.
RP Shepherd, AJ (reprint author), Univ London Birkbeck Coll, Inst Struct & Mol Biol, Dept Biol Sci, Malet St, London WC1E 7HX, England.
EM a.shepherd@mail.cryst.bbk.ac.uk
RI Zhang, Ping/E-5306-2010; Basford, Kaye/G-5837-2010; Alemani,
Davide/A-6102-2011; Palladini, Arianna/A-8994-2013; Pappalardo,
Francesco/C-5832-2011; Lund, Ole/F-4437-2014; Castiglione,
Filippo/B-1366-2010; Pennisi, Marzio/G-4618-2015;
OI Rapin, Nicolas/0000-0001-5208-8874; Motta, Santo/0000-0003-3533-2972;
Pappalardo, Francesco/0000-0003-1668-3320; Lund,
Ole/0000-0003-1108-0491; Castiglione, Filippo/0000-0002-1442-3552;
Pennisi, Marzio/0000-0003-0231-7653; Miotto, Olivo/0000-0001-8060-6771;
Lollini, Pier Luigi/0000-0003-1702-4108
NR 45
TC 19
Z9 20
U1 1
U2 11
PU ROYAL SOC
PI LONDON
PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND
SN 1364-503X
J9 PHILOS T R SOC A
JI Philos. Trans. R. Soc. A-Math. Phys. Eng. Sci.
PD JUN 13
PY 2010
VL 368
IS 1920
BP 2799
EP 2815
DI 10.1098/rsta.2010.0067
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 590EN
UT WOS:000277207300012
PM 20439274
ER
PT J
AU Colak, D
Chishti, MA
Al-Bakheet, AB
Al-Qahtani, A
Shoukri, MM
Goyns, MH
Ozand, PT
Quackenbush, J
Park, BH
Kaya, N
AF Colak, Dilek
Chishti, Muhammad A.
Al-Bakheet, Al-Bandary
Al-Qahtani, Ahmed
Shoukri, Mohamed M.
Goyns, Malcolm H.
Ozand, Pinar T.
Quackenbush, John
Park, Ben H.
Kaya, Namik
TI Integrative and comparative genomics analysis of early hepatocellular
carcinoma differentiated from liver regeneration in young and old
SO MOLECULAR CANCER
LA English
DT Article
ID GENE-EXPRESSION PATTERNS; DIPEPTIDYL PEPTIDASE-IV; SQUAMOUS-CELL
CARCINOMA; HUMAN BREAST-TUMORS; COLORECTAL-CANCER; TARGET GENES;
OSTEOSARCOMA PROGRESSION; HOMOZYGOUS DELETIONS; FUNCTIONAL GENOMICS;
LUMICAN EXPRESSION
AB Background: Hepatocellular carcinoma (HCC) is the third-leading cause of cancer-related deaths worldwide. It is often diagnosed at an advanced stage, and hence typically has a poor prognosis. To identify distinct molecular mechanisms for early HCC we developed a rat model of liver regeneration post-hepatectomy, as well as liver cells undergoing malignant transformation and compared them to normal liver using a microarray approach. Subsequently, we performed cross-species comparative analysis coupled with copy number alterations (CNA) of independent early human HCC microarray studies to facilitate the identification of critical regulatory modules conserved across species.
Results: We identified 35 signature genes conserved across species, and shared among different types of early human HCCs. Over 70% of signature genes were cancer-related, and more than 50% of the conserved genes were mapped to human genomic CNA regions. Functional annotation revealed genes already implicated in HCC, as well as novel genes which were not previously reported in liver tumors. A subset of differentially expressed genes was validated using quantitative RT-PCR. Concordance was also confirmed for a significant number of genes and pathways in five independent validation microarray datasets. Our results indicated alterations in a number of cancer related pathways, including p53, p38 MAPK, ERK/MAPK, PI3K/AKT, and TGF-beta signaling pathways, and potential critical regulatory role of MYC, ERBB2, HNF4A, and SMAD3 for early HCC transformation.
Conclusions: The integrative analysis of transcriptional deregulation, genomic CNA and comparative cross species analysis brings new insights into the molecular profile of early hepatoma formation. This approach may lead to robust biomarkers for the detection of early human HCC.
C1 [Colak, Dilek; Shoukri, Mohamed M.] King Faisal Specialist Hosp & Res Ctr, Dept Biostat Epidemiol & Sci Comp, Riyadh 11211, Saudi Arabia.
[Chishti, Muhammad A.] King Saud Univ, Dept Med Biochem, Obes Res Ctr, Riyadh, Saudi Arabia.
[Al-Bakheet, Al-Bandary; Kaya, Namik] King Faisal Specialist Hosp & Res Ctr, Dept Genet, Riyadh 11211, Saudi Arabia.
[Al-Qahtani, Ahmed] King Faisal Specialist Hosp & Res Ctr, Dept Biol & Med Res, Riyadh 11211, Saudi Arabia.
[Al-Qahtani, Ahmed] King Saud Univ, Coll Med, Liver Res Ctr, Riyadh 11461, Saudi Arabia.
[Goyns, Malcolm H.] Immorgene Concepts Ltd, Stockton On Tees, England.
[Ozand, Pinar T.] Duzen Labs, Istanbul, Turkey.
[Quackenbush, John] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Park, Ben H.] Johns Hopkins Univ, Sch Med, Dept Oncol, Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD 21205 USA.
RP Colak, D (reprint author), King Faisal Specialist Hosp & Res Ctr, Dept Biostat Epidemiol & Sci Comp, Riyadh 11211, Saudi Arabia.
EM dcolakkaya@kfshrc.edu.sa; nkaya@kfshrc.edu.sa
FU King Faisal Specialist Hospital and Research Center
FX We thank Maqbool Ahmad for providing help in RNA isolation, and Bedri
Karakas for critically reading the manuscript. We would like to thank to
King Faisal Specialist Hospital and Research Center for the financial
support.
NR 103
TC 13
Z9 15
U1 1
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1476-4598
J9 MOL CANCER
JI Mol. Cancer
PD JUN 12
PY 2010
VL 9
AR 146
DI 10.1186/1476-4598-9-146
PG 19
WC Biochemistry & Molecular Biology; Oncology
SC Biochemistry & Molecular Biology; Oncology
GA 629HU
UT WOS:000280187500001
PM 20540791
ER
PT J
AU Price, AL
Kryukov, GV
de Bakker, PIW
Purcell, SM
Staples, J
Wei, LJ
Sunyaev, SR
AF Price, Alkes L.
Kryukov, Gregory V.
de Bakker, Paul I. W.
Purcell, Shaun M.
Staples, Jeff
Wei, Lee-Jen
Sunyaev, Shamil R.
TI Pooled Association Tests for Rare Variants in Exon-Resequencing Studies
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID COMPLEX DISEASES; CONTRIBUTE; MUTATIONS; ALLELES; CAPTURE; SERVER;
GENES; HDL
AB Deep sequencing will soon generate comprehensive sequence information in large disease samples. Although the power to detect association with an individual rare variant is limited, pooling variants by gene or pathway into a composite test provides an alternative strategy for identifying susceptibility genes. We describe a statistical method for detecting association of multiple rare variants in protein-coding genes with a quantitative or dichotomous trait. The approach is based on the regression of phenotypic values on individuals' genotype scores subject to a variable allele-frequency threshold, incorporating computational predictions of the functional effects of missense variants. Statistical significance is assessed by permutation testing with variable thresholds. We used a rigorous population-genetics simulation framework to evaluate the power of the method, and we applied the method to empirical sequencing data from three disease studies.
C1 [Price, Alkes L.; Kryukov, Gregory V.; de Bakker, Paul I. W.; Purcell, Shaun M.; Staples, Jeff; Sunyaev, Shamil R.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA 02142 USA.
[Price, Alkes L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Price, Alkes L.; Wei, Lee-Jen] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Kryukov, Gregory V.; de Bakker, Paul I. W.; Staples, Jeff; Sunyaev, Shamil R.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Genet,Dept Med, Boston, MA 02115 USA.
[Purcell, Shaun M.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
RP Sunyaev, SR (reprint author), Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA 02142 USA.
EM ssunyaev@rics.bwh.harvard.edu
RI Kryukov, Gregory/A-9592-2008; Sincan, Murat /A-3794-2010; de Bakker,
Paul/B-8730-2009;
OI de Bakker, Paul/0000-0001-7735-7858; Kryukov,
Gregory/0000-0002-6131-9483
FU NIH [R01 MH084676, R01 GM078598]
FX We are grateful to J. Cohen for sharing data from 14 and to
L. Pennacchio for sharing data from 11. This work was funded
by NIH grants R01 MH084676 and R01 GM078598.
NR 19
TC 373
Z9 382
U1 1
U2 12
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD JUN 11
PY 2010
VL 86
IS 6
BP 832
EP 838
DI 10.1016/j.ajhg.2010.04.005
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA 613AT
UT WOS:000278948900001
PM 20471002
ER
PT J
AU Yang, YZ
Yang, YQ
Liang, B
Liu, JQ
Li, J
Grunnet, M
Olesen, SP
Rasmussen, HB
Ellinor, PT
Gao, LJ
Lin, XP
Li, L
Wang, L
Xiao, JJ
Liu, Y
Liu, Y
Zhang, SL
Liang, DD
Peng, LY
Jespersen, T
Chen, YH
AF Yang, Yanzong
Yang, Yiqing
Liang, Bo
Liu, Jinqiu
Li, Jun
Grunnet, Morten
Olesen, Soren-Peter
Rasmussen, Hanne B.
Ellinor, Patrick T.
Gao, Lianjun
Lin, Xiaoping
Li, Li
Wang, Lei
Xiao, Junjie
Liu, Yi
Liu, Ying
Zhang, Shulong
Liang, Dandan
Peng, Luying
Jespersen, Thomas
Chen, Yi-Han
TI Identification of a Kir3.4 Mutation in Congenital Long QT Syndrome
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID K+ CHANNEL SUBUNIT; G-PROTEIN; CARDIAC-ARRHYTHMIA; VENTRICULAR MYOCYTES;
ATRIAL-FIBRILLATION; POTASSIUM CHANNELS; I-KACH; EXPRESSION; ACTIVATION;
ACETYLCHOLINE
AB Congenital long QT syndrome (LQTS) is a hereditary disorder that leads to sudden cardiac death secondary to fatal cardiac arrhythmias. Although many genes for LQTS have been described, the etiology remains unknown in 30%-40% of cases. In the present study, a large Chinese family (four generations, 49 individuals) with autosomal-dominant LQTS was clinically evaluated. Genome-wide linkage analysis was performed by using polymorphic microsatellite markers to map the genetic locus, and positional candidate genes were screened by sequencing for mutations. The expression pattern and functional characteristics of the mutated protein were investigated by western blotting and patch-clamp electrophysiology. The genetic locus of the LQTS-associated gene was mapped to chromosome 11q23.3-24.3. A heterozygous mutation (Kir3.4-Gly387Arg) was identified in the G protein-coupled, inwardly rectifying potassium channel subunit Kir3.4, encoded by the KCNJ5 gene. The Kir3.4-Gly387Arg mutation was present in all nine affected family members and absent in 528 ethnically matched controls. Western blotting of human cardiac tissue demonstrated significant Kir3.4 expression levels in the cardiac ventricles. Heterologous expression studies with Kir3.4-Gly387Arg revealed a loss-of-function electrophysiological phenotype resulting from reduced plasma membrane expression. Our findings suggest a role for Kir3.4 in the etiology of LQTS.
C1 [Yang, Yanzong; Yang, Yiqing; Li, Jun; Lin, Xiaoping; Li, Li; Wang, Lei; Xiao, Junjie; Liu, Yi; Liu, Ying; Liang, Dandan; Peng, Luying; Chen, Yi-Han] Tongji Univ, Sch Med, Minist Educ, East Hosp,Key Lab Arrhythmias, Shanghai 200120, Peoples R China.
[Yang, Yanzong; Liu, Jinqiu; Gao, Lianjun; Zhang, Shulong] Dalian Med Univ, Affiliated Hosp 1, Dept Cardiol, Dalian 116011, Peoples R China.
[Yang, Yanzong; Liu, Jinqiu; Gao, Lianjun; Zhang, Shulong] Minist Hlth, Training Ctr Intervent Therapy Arrhythmias, Dalian 116011, Peoples R China.
[Yang, Yiqing; Lin, Xiaoping; Wang, Lei; Chen, Yi-Han] Tongji Univ, Sch Med, Dept Cardiol, East Hosp, Shanghai 200120, Peoples R China.
[Yang, Yiqing; Li, Jun; Lin, Xiaoping; Li, Li; Wang, Lei; Xiao, Junjie; Liang, Dandan; Peng, Luying; Chen, Yi-Han] Tongji Univ, Inst Med Genet, Shanghai 200120, Peoples R China.
[Liang, Bo; Grunnet, Morten; Olesen, Soren-Peter; Rasmussen, Hanne B.; Jespersen, Thomas] Danish Natl Res Fdn, Ctr Cardiac Arrhythmia, DK-2200 Copenhagen, Denmark.
[Liang, Bo; Grunnet, Morten; Olesen, Soren-Peter; Rasmussen, Hanne B.; Jespersen, Thomas] Univ Copenhagen, Fac Hlth Sci, Dept Biomed Sci, DK-2200 Copenhagen, Denmark.
[Grunnet, Morten; Olesen, Soren-Peter] NeuroSearch AS, DK-2750 Ballerup, Denmark.
[Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA.
RP Chen, YH (reprint author), Tongji Univ, Sch Med, Minist Educ, East Hosp,Key Lab Arrhythmias, Shanghai 200120, Peoples R China.
EM yihanchen@hotmail.com
RI Jespersen, Thomas/G-4860-2011; Olesen, Soren-Peter/B-9621-2012; Liang,
Bo/C-7210-2012; Rasmussen, Hanne /N-9652-2016
OI Rasmussen, Hanne /0000-0002-2218-5646
FU "973" Program Fund of China [2007CB512100]; "863" Program Fund of China
[2007AA02Z438]; Program Fund for Shanghai Subject Chief Scientists;
Ministry of Education of China; National Science Fund of China
[30425016, 30330290]; Shanghai Pujiang Program Fund [07114058]; Danish
National Research Foundation; Danish National Research Council; Lundbeck
Foundation; National Institutes of Health [HL092577, DA027021]
FX We thank Yunfu Sun, Emelia J. Benjamin, and Kui Hong for their helpful
comments. This work was supported by the "973" Program Fund of China
(2007CB512100), the "863" Program Fund of China (2007AA02Z438), the
Program Fund for Shanghai Subject Chief Scientists, the Program Fund for
Innovative Research Teams by the Ministry of Education of China, the
National Science Fund of China (30425016 and 30330290 to Y.-H.C.), the
Shanghai Pujiang Program Fund (07114058 to L.P.), the Danish National
Research Foundation (to S.-P.O.), the Danish National Research Council
(to B.L. and M.G.), the Lundbeck Foundation (to T.J.), and the National
Institutes of Health (HL092577 and DA027021 to P.T.E.).
NR 42
TC 79
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U1 1
U2 18
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD JUN 11
PY 2010
VL 86
IS 6
BP 872
EP 880
DI 10.1016/j.ajhg.2010.04.017
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA 613AT
UT WOS:000278948900005
PM 20560207
ER
PT J
AU Biffi, A
Anderson, CD
Nalls, MA
Rahman, R
Sonni, A
Cortellini, L
Rost, NS
Matarin, M
Hernandez, DG
Plourde, A
de Bakker, PIW
Ross, OA
Greenberg, SM
Furie, KL
Meschia, JF
Singleton, AB
Saxena, R
Rosand, J
AF Biffi, Alessandro
Anderson, Christopher D.
Nalls, Michael A.
Rahman, Rosanna
Sonni, Akshata
Cortellini, Lynelle
Rost, Natalia S.
Matarin, Mar
Hernandez, Dena G.
Plourde, Anna
de Bakker, Paul I. W.
Ross, Owen A.
Greenberg, Steven M.
Furie, Karen L.
Meschia, James F.
Singleton, Andrew B.
Saxena, Richa
Rosand, Jonathan
TI Principal-Component Analysis for Assessment of Population Stratification
in Mitochondrial Medical Genetics
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; DNA; DISEASE; RISK; METAANALYSIS; DIVERSITY
AB Although inherited mitochondrial genetic variation can cause human disease, no validated methods exist for control of confounding due to mitochondrial population stratification (PS). We sought to identify a reliable method for PS assessment in mitochondrial medical genetics. We analyzed mitochondria' SNP data from 1513 European American individuals concomitantly genotyped with the use of a previously validated panel of 144 mitochondrial markers as well as the Affymetrix 6.0 (n = 432), Illumina 610-Quad (n = 458), or Illumina 660 (n = 623) platforms. Additional analyses were performed in 938 participants in the Human Genome Diversity Panel (HGDP) (Illumina 650). We compared the following methods for controlling for PS: haplogroup-stratified analyses, mitochondrial principal-component analysis (PCA), and combined autosomal-mitochondrial PCA. We computed mitochondria' genomic inflation factors (mtGIFs) and test statistics for simulated case-control and continuous phenotypes (10,000 simulations each) with varying degrees of correlation with mitochondria' ancestry. Results were then compared across adjustment methods. We also calculated power for discovery of true associations under each method, using a simulation approach. Mitochondria! PCA recapitulated haplogroup information, but haplogroup-stratified analyses were inferior to mitochondria' PCA in controlling for PS. Correlation between nuclear and mitochondria' principal components (PCs) was very limited. Adjustment for nuclear PCs had no effect on mitochondria' analysis of simulated phenotypes. Mitochondria! PCA performed with the use of data from commercially available genome-wide arrays correlated strongly with PCA performed with the use of an exhaustive mitochondria' marker panel. Finally, we demonstrate, through simulation, no loss in power for detection of true associations with the use of mitochondria' PCA.
C1 [Biffi, Alessandro; Anderson, Christopher D.; Rahman, Rosanna; Sonni, Akshata; Cortellini, Lynelle; Rost, Natalia S.; Plourde, Anna; Saxena, Richa; Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Biffi, Alessandro; Anderson, Christopher D.; Rahman, Rosanna; Sonni, Akshata; Cortellini, Lynelle; Rost, Natalia S.; Plourde, Anna; Greenberg, Steven M.; Furie, Karen L.; Rosand, Jonathan] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Biffi, Alessandro; Anderson, Christopher D.; Rahman, Rosanna; Sonni, Akshata; Cortellini, Lynelle; Rost, Natalia S.; Plourde, Anna; de Bakker, Paul I. W.; Saxena, Richa; Rosand, Jonathan] 7 Cambridge Ctr, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02139 USA.
[Nalls, Michael A.; Matarin, Mar; Hernandez, Dena G.; Singleton, Andrew B.] NIA, Neurogenet Lab, Intramural Res Program, Bethesda, MD 20892 USA.
[Matarin, Mar] UCL Inst Neurol, Dept Clin & Expt Epilepsy, London WC1N 3BG, England.
[Hernandez, Dena G.] UCL, Inst Neurol, Dept Mol Neurosci, London WC1E 6BT, England.
[Hernandez, Dena G.] UCL, Inst Neurol, Reta Lila Weston Labs, London WC1E 6BT, England.
[de Bakker, Paul I. W.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Genet, Boston, MA 02115 USA.
[Ross, Owen A.; Meschia, James F.] Mayo Clin Jacksonville, Dept Neurol, Jacksonville, FL 32224 USA.
RP Rosand, J (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
EM jrosand@partners.org
RI Singleton, Andrew/C-3010-2009; Ross, Owen/D-7573-2013; de Bakker,
Paul/B-8730-2009; Matarin, Mar/F-1771-2016;
OI de Bakker, Paul/0000-0001-7735-7858; Matarin, Mar/0000-0002-4717-5735;
Anderson, Christopher/0000-0002-0053-2002
FU American Heart Association / Bugher Foundation Centers for Stroke
Prevention Research [0775010N]; Deane Institute for Integrative Study of
Atrial Fibrillation and Stroke; Myron and Jane Hanley Award in Stroke
Research; Marriott Disease Risk and Regenerative Medicine Initiative
Award in Individualized Medicine; National Institute for Neurologic
Disorders and Stroke [R01NS052585, R01NS059727, 5K23NS042720,
5P50NS051343]; Fulbright Foundation; American Association of University
Women; National Center for Research Resources [U54 RR020278]; NIH
National Institute on Aging [Z01 AG000954-06]
FX This study was funded by the American Heart Association / Bugher
Foundation Centers for Stroke Prevention Research (0775010N), the Deane
Institute for Integrative Study of Atrial Fibrillation and Stroke, the
Myron and Jane Hanley Award in Stroke Research, the Marriott Disease
Risk and Regenerative Medicine Initiative Award in Individualized
Medicine, the National Institute for Neurologic Disorders and Stroke
(R01NS052585, R01NS059727, 5K23NS042720, 5P50NS051343), the Fulbright
Foundation, the American Association of University Women, and the
National Center for Research Resources (U54 RR020278). This research was
supported in part by the Intramural Research Program of the NIH National
Institute on Aging (Z01 AG000954-06).
NR 29
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U1 3
U2 6
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD JUN 11
PY 2010
VL 86
IS 6
BP 904
EP 917
DI 10.1016/j.ajhg.2010.05.005
PG 14
WC Genetics & Heredity
SC Genetics & Heredity
GA 613AT
UT WOS:000278948900008
PM 20537299
ER
PT J
AU Levy, C
Khaled, M
Robinson, KC
Veguilla, RA
Chen, PH
Yokoyama, S
Makino, E
Lu, J
Larue, L
Beermann, F
Chin, L
Bosenberg, M
Song, JS
Fisher, DE
AF Levy, Carmit
Khaled, Mehdi
Robinson, Kathleen C.
Veguilla, Rosa A.
Chen, Po-Hao
Yokoyama, Satoru
Makino, Eiichi
Lu, Jun
Larue, Lionel
Beermann, Friedrich
Chin, Lynda
Bosenberg, Marcus
Song, Jun. S.
Fisher, David E.
TI Lineage-Specific Transcriptional Regulation of DICER by MITF in
Melanocytes
SO CELL
LA English
DT Article
ID POSTTRANSCRIPTIONAL REGULATION; MALIGNANT-MELANOMA; HUMAN CANCERS;
CELL-DEATH; BCL-2-DEFICIENT MICE; MICRORNA BIOGENESIS; BCL-2 DEFICIENCY;
MASTER REGULATOR; EXPRESSION; GENE
AB DICER is a central regulator of microRNA maturation. However, little is known about mechanisms regulating its expression in development or disease. While profiling miRNA expression in differentiating melanocytes, two populations were observed: some upregulated at the pre-miRNA stage, and others upregulated as mature miRNAs (with stable pre-miRNA levels). Conversion of pre-miRNAs to fully processed miRNAs appeared to be dependent upon stimulation of DICER expression-an event found to occur via direct transcriptional targeting of DICER by the melanocyte master transcriptional regulator MITF. MITF binds and activates a conserved regulatory element upstream of DICER's transcriptional start site upon melanocyte differentiation. Targeted KO of DICER is lethal to melanocytes, at least partly via DICER-dependent processing of the pre-miRNA-17 similar to 92 cluster thus targeting BIM, a known proapoptotic regulator of melanocyte survival. These observations highlight a central mechanism underlying lineage-specific miRNA regulation which could exist for other cell types during development.
C1 [Levy, Carmit; Khaled, Mehdi; Robinson, Kathleen C.; Veguilla, Rosa A.; Yokoyama, Satoru; Makino, Eiichi; Fisher, David E.] Harvard Univ, Sch Med, Dept Dermatol, Cutaneous Biol Res Ctr,Mass Gen Hosp, Boston, MA 02115 USA.
[Chen, Po-Hao] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Lu, Jun] Broad Inst, Cambridge, MA 02141 USA.
[Lu, Jun] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Lu, Jun] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA.
[Larue, Lionel] UMR CNRS 146, Inst Curie, F-91405 Orsay, France.
[Beermann, Friedrich] Swiss Inst Expt Canc Res, EPFL SV ISREC, CH-1015 Lausanne, Switzerland.
[Chin, Lynda] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Bosenberg, Marcus] Yale Univ, Sch Med, Dept Dermatol, New Haven, CT 06510 USA.
[Song, Jun. S.] Inst Adv Study, Simons Ctr Syst Biol, Princeton, NJ 08540 USA.
RP Fisher, DE (reprint author), Harvard Univ, Sch Med, Dept Dermatol, Cutaneous Biol Res Ctr,Mass Gen Hosp, Boston, MA 02115 USA.
EM dfisher3@partners.org
RI khaled, mehdi/C-4854-2012; Larue, Lionel/F-7355-2013; Larue,
Lionel/I-6532-2016
FU Martin A. and Helen Chooljian Membership; NIH; Melanoma Research
Alliance; Doris Duke Charitable Foundation; Adelson Medical Research
Foundation; Israel-US Binational Science Foundation
FX The authors gratefully acknowledge help from Dr. Rod Bronson with mouse
pathology; Dr. Carl Novina for useful discussions; Dr. Ian Jackson for
Dct-LacZ transgenic mice; Dr. T. Kunisada for K14-SCF transgenic mice;
Dr. Clifford J. Tabin for Dicer Floxed mice; Dr. Ruth Halaban for 501mel
melanoma cells; Maja Janas, Ana Hernandez, Dr. Jacob Hanna, and members
of the Fisher lab for help with numerous aspects of this work. JSS was
supported in part by the Martin A. and Helen Chooljian Membership.
D.E.F. gratefully acknowledges grant support from NIH, The Melanoma
Research Alliance, The Doris Duke Charitable Foundation, The Adelson
Medical Research Foundation, and the Israel-US Binational Science
Foundation.
NR 79
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U1 0
U2 11
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD JUN 11
PY 2010
VL 141
IS 6
BP 994
EP 1005
DI 10.1016/j.cell.2010.05.004
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 608XH
UT WOS:000278618800014
PM 20550935
ER
PT J
AU Zraika, S
Aston-Mourney, K
Marek, P
Hull, RL
Green, PS
Udayasankar, J
Subramanian, SL
Raleigh, DP
Kahn, SE
AF Zraika, Sakeneh
Aston-Mourney, Kathryn
Marek, Peter
Hull, Rebecca L.
Green, Pattie S.
Udayasankar, Jayalakshmi
Subramanian, Shoba L.
Raleigh, Daniel P.
Kahn, Steven E.
TI Neprilysin Impedes Islet Amyloid Formation by Inhibition of Fibril
Formation Rather Than Peptide Degradation
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID INSULIN-DEGRADING ENZYME; NEUTRAL ENDOPEPTIDASE; DIABETES-MELLITUS;
POLYPEPTIDE IAPP; IN-VITRO; TRANSGENIC MICE; MOUSE ISLETS; A-BETA; CELL;
SECRETION
AB Deposition of islet amyloid polypeptide (IAPP) as islet amyloid in type 2 diabetes contributes to loss of beta-cell function and mass, yet the mechanism for its occurrence is unclear. Neprilysin is a metallopeptidase known to degrade amyloid in Alzheimer disease. We previously demonstrated neprilysin to be present in pancreatic islets and now sought to determine whether it plays a role in degrading islet amyloid. We used an in vitro model where cultured human IAPP (hIAPP) transgenic mouse islets develop amyloid and thereby have increased beta-cell apoptosis. Islet neprilysin activity was inhibited or up-regulated using a specific inhibitor or adenovirus encoding neprilysin, respectively. Following neprilysin inhibition, islet amyloid deposition and beta-cell apoptosis increased by 54 and 75%, respectively, whereas when neprilysin was up-regulated islet amyloid deposition and beta-cell apoptosis both decreased by 79%. To determine if neprilysin modulated amyloid deposition by cleaving hIAPP, analysis of hIAPP incubated with neprilysin was performed by mass spectrometry, which failed to demonstrate neprilysin-induced cleavage. Rather, neprilysin may act by reducing hIAPP fibrillogenesis, which we showed to be the case by fluorescence-based thioflavin T binding studies and electron microscopy. In summary, neprilysin decreases islet amyloid deposition by inhibiting hIAPP fibril formation, rather than degrading hIAPP. These findings suggest that targeting the role of neprilysin in IAPP fibril assembly, in addition to IAPP cleavage by other peptidases, may provide a novel approach to reduce and/or prevent islet amyloid deposition in type 2 diabetes.
C1 [Zraika, Sakeneh; Aston-Mourney, Kathryn; Hull, Rebecca L.; Green, Pattie S.; Udayasankar, Jayalakshmi; Subramanian, Shoba L.; Kahn, Steven E.] Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Seattle, WA 98108 USA.
[Zraika, Sakeneh; Aston-Mourney, Kathryn; Hull, Rebecca L.; Green, Pattie S.; Udayasankar, Jayalakshmi; Subramanian, Shoba L.; Kahn, Steven E.] Univ Washington, Seattle, WA 98108 USA.
[Marek, Peter; Raleigh, Daniel P.] SUNY Stony Brook, Dept Chem, Stony Brook, NY 11794 USA.
RP Zraika, S (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Dept Med, 1660 S Columbian Way 151, Seattle, WA 98108 USA.
EM zraikas@u.washington.edu
OI Aston-Mourney, Kathryn/0000-0003-1412-6715; Hull,
Rebecca/0000-0001-9690-4087
FU National Institutes of Health [DK-080945, DK-074404, GM-078114]; Dept.
of Veterans Affairs, Virginia; NIH [DK-017047]
FX This work was supported, in whole or in part, by National Institutes of
Health Grants DK-080945 (to S. Z.), DK-074404 (to R. L. H.), and
GM-078114 (to D. P. R.). This work was also supported by the Dept. of
Veterans Affairs, Virginia Affairs Puget Sound Health Care System,
Seattle, WA. Mass spectrometry work was performed at the University of
Washington's Diabetes Endocrinology Research Center Mass Spectrometry
Core, which is supported by NIH Grant DK-017047.
NR 44
TC 17
Z9 17
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 JUN 11
PY 2010
VL 285
IS 24
BP 18177
EP 18183
DI 10.1074/jbc.M109.082032
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 606UN
UT WOS:000278453900008
PM 20400513
ER
PT J
AU Miedlich, SU
Zalutskaya, A
Zhu, ED
Demay, MB
AF Miedlich, Susanne U.
Zalutskaya, Alena
Zhu, Eric D.
Demay, Marie B.
TI Phosphate-induced Apoptosis of Hypertrophic Chondrocytes Is Associated
with a Decrease in Mitochondrial Membrane Potential and Is Dependent
upon Erk1/2 Phosphorylation
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID HORMONE-RELATED PEPTIDE; SIGNALING PATHWAY; RICKETS; MATURATION; MICE;
MINERALIZATION; EXPRESSION
AB Growth plate abnormalities, associated with impaired hypertrophic chondrocyte apoptosis, are observed in humans and animals with abnormalities of vitamin D action and renal phosphate reabsorption. Low circulating phosphate levels impair hypertrophic chondrocyte apoptosis, whereas treatment of these cells with phosphate activates the mitochondrial apoptotic pathway. Because phosphate-mediated apoptosis of chondrocytes is differentiation-dependent, studies were performed to identify factors that contribute to hypertrophic chondrocyte apoptosis. An increase in the percentage of cells with low mitochondrial membrane potential, evaluated by JC-1 fluorescence, was observed during hypertrophic differentiation of primary murine chondrocytes in culture. This percentage was further increased by treatment of hypertrophic, but not proliferative, chondrocytes with phosphate. Phosphate-mediated apoptosis was observed as early as 30 min post-treatment and was dependent upon Erk1/2 phosphorylation. Inhibition of Erk1/2 phosphorylation in vivo confirmed an important role for this signaling pathway in regulating hypertrophic chondrocyte apoptosis in growing mice. Murine embryonic metatarsals cultured under phosphate-restricted conditions demonstrated a 2.5-fold increase in parathyroid hormone-related protein mRNA expression accompanied by a marked attenuation in phospho-Erk immunoreactivity in hypertrophic chondrocytes. Thus, these investigations point to an important role for phosphate in regulating mitochondrial membrane potential in hypertrophic chondrocytes and growth plate maturation by the parathyroid hormone-related protein signaling pathway.
C1 [Miedlich, Susanne U.; Zalutskaya, Alena; Zhu, Eric D.; Demay, Marie B.] Harvard Univ, Endocrine Unit, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Demay, MB (reprint author), Harvard Univ, Endocrine Unit, Sch Med, Massachusetts Gen Hosp, 50 Blossom St,Thier 11, Boston, MA 02114 USA.
EM demay@helix.mgh.harvard.edu
FU National Institutes of Health [R01 DK46974, P50 AR054086, T32 DK007028]
FX This work was supported, in whole or in part, by National Institutes of
Health Grants R01 DK46974, P50 AR054086, and T32 DK007028.
NR 22
TC 33
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U1 0
U2 2
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUN 11
PY 2010
VL 285
IS 24
BP 18270
EP 18275
DI 10.1074/jbc.M109.098616
PG 6
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 606UN
UT WOS:000278453900019
PM 20404333
ER
PT J
AU Xu, C
Liu, Y
Wang, P
Fan, WH
Rue, TC
Upton, MP
Houck, JR
Lohavanichbutr, P
Doody, DR
Futran, ND
Zhao, LP
Schwartz, SM
Chen, C
Mendez, E
AF Xu, Chang
Liu, Yan
Wang, Pei
Fan, Wenhong
Rue, Tessa C.
Upton, Melissa P.
Houck, John R.
Lohavanichbutr, Pawadee
Doody, David R.
Futran, Neal D.
Zhao, Lue Ping
Schwartz, Stephen M.
Chen, Chu
Mendez, Eduardo
TI Integrative analysis of DNA copy number and gene expression in
metastatic oral squamous cell carcinoma identifies genes associated with
poor survival
SO MOLECULAR CANCER
LA English
DT Article
ID LYMPH-NODE METASTASIS; CLINICOPATHOLOGICAL FEATURES; ANALYSIS REVEALS;
LUNG-CANCER; BREAST; HEAD; PROFILES; GENOME; HETEROZYGOSITY; TUMORS
AB Background: Lymphotropism in oral squamous cell carcinoma (OSCC) is one of the most important prognostic factors of 5-year survival. In an effort to identify genes that may be responsible for the initiation of OSCC lymphotropism, we examined DNA copy number gains and losses and corresponding gene expression changes from tumor cells in metastatic lymph nodes of patients with OSCC.
Results: We performed integrative analysis of DNA copy number alterations (CNA) and corresponding mRNA expression from OSCC cells isolated from metastatic lymph nodes of 20 patients using Affymetrix 250 K Nsp I SNP and U133 Plus 2.0 arrays, respectively. Overall, genome CNA accounted for expression changes in 31% of the transcripts studied. Genome region 11q13.2-11q13.3 shows the highest correlation between DNA CNA and expression. With a false discovery rate < 1%, 530 transcripts (461 genes) demonstrated a correlation between CNA and expression. Among these, we found two subsets that were significantly associated with OSCC (n = 122) when compared to controls, and with survival (n = 27), as tested using an independent dataset with genome-wide expression profiles for 148 primary OSCC and 45 normal oral mucosa. We fit Cox models to calculate a principal component analysis-derived risk-score for these two gene sets ('122-' or '27-transcript PC'). The models combining the 122- or 27-transcript PC with stage outperformed the model using stage alone in terms of the Area Under the Curve (AUC = 0.82 or 0.86 vs. 0.72, with p = 0.044 or 0.011, respectively).
Conclusions: Genes exhibiting CNA-correlated expression may have biological impact on carcinogenesis and cancer progression in OSCC. Determination of copy number-associated transcripts associated with clinical outcomes in tumor cells with an aggressive phenotype (i.e., cells metastasized to the lymph nodes) can help prioritize candidate transcripts from high-throughput data for further studies.
C1 [Xu, Chang; Futran, Neal D.; Chen, Chu; Mendez, Eduardo] Univ Washington, Dept Otolaryngol Head & Neck Surg, Seattle, WA 98195 USA.
[Liu, Yan; Fan, Wenhong; Zhao, Lue Ping] Fred Hutchinson Canc Res Ctr, Program Biostat & Biomath, Div Publ Hlth Sci, Seattle, WA 98109 USA.
[Wang, Pei] Fred Hutchinson Canc Res Ctr, Program Canc Prevent & Biostat, Div Publ Hlth Sci, Seattle, WA 98109 USA.
[Rue, Tessa C.; Zhao, Lue Ping] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Upton, Melissa P.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA.
[Houck, John R.; Lohavanichbutr, Pawadee; Doody, David R.; Schwartz, Stephen M.; Chen, Chu; Mendez, Eduardo] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, Seattle, WA 98109 USA.
[Schwartz, Stephen M.; Chen, Chu] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Mendez, Eduardo] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA.
[Mendez, Eduardo] VA Puget Sound Hlth Care Syst, Surg & Perioperat Care Serv, Seattle, WA 98108 USA.
RP Mendez, E (reprint author), Univ Washington, Dept Otolaryngol Head & Neck Surg, Seattle, WA 98195 USA.
EM edmendez@u.washington.edu
FU National Center for Research Resources, National Institutes of Health
(NIH) [5KL2RR025015-03]; Robert Wood Johnson Foundation; Howard Hughes
Medical Institute; National Cancer Institute, NIH [R01CA095419];
Institute of Translational Health Sciences, University of Washington,
National Center for Research Resources, NIH [UL1RR025014]; Department of
Otolaryngology - Head and Neck Surgery, University of Washington
FX This work was supported in part by grants 5KL2RR025015-03 from National
Center for Research Resources, National Institutes of Health (NIH); Amos
Medical Faculty Development Program Award from The Robert Wood Johnson
Foundation; Early Physician-Scientist Career Development Award from the
Howard Hughes Medical Institute; R01CA095419 from the National Cancer
Institute, NIH; Small Grants Translational Research Projects Award from
the Institute of Translational Health Sciences, University of Washington
supported by grant UL1RR025014 from the National Center for Research
Resources, NIH; center funds from the Department of Otolaryngology -
Head and Neck Surgery, University of Washington; and by resources from
and use of facilities at the VA Puget Sound Health Care System, Fred
Hutchinson Cancer Research Center, University of Washington Medical
Center and Harborview Medical Center, Seattle, Washington.
NR 37
TC 27
Z9 27
U1 1
U2 5
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1476-4598
J9 MOL CANCER
JI Mol. Cancer
PD JUN 11
PY 2010
VL 9
AR 143
DI 10.1186/1476-4598-9-143
PG 12
WC Biochemistry & Molecular Biology; Oncology
SC Biochemistry & Molecular Biology; Oncology
GA 617LA
UT WOS:000279281000001
PM 20537188
ER
PT J
AU van Gils, JM
Stewart, MC
Rayner, KJ
Fernandes, LR
McDonald, TO
O'Brien, KD
Moore, KJ
AF van Gils, J. M.
Stewart, M. C.
Rayner, K. J.
Fernandes, L. R.
McDonald, T. O.
O'Brien, K. D.
Moore, K. J.
TI THE GUIDANCE CUE NETRIN-1 PROMOTES ATHEROSCLEROSIS
SO ATHEROSCLEROSIS SUPPLEMENTS
LA English
DT Meeting Abstract
CT 78th Congress of the European-Atherosclerosis-Society
CY JUN 20-23, 2010
CL Hamburg, GERMANY
SP European Atherosclerosis Soc
C1 [van Gils, J. M.; Rayner, K. J.; Moore, K. J.] NYU, Langone Med Ctr, New York, NY USA.
[Stewart, M. C.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Fernandes, L. R.] Univ Fed Minas Gerais, Belo Horizonte, MG, Brazil.
[McDonald, T. O.; O'Brien, K. D.] Univ Washington, Seattle, WA 98195 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 1567-5688
J9 ATHEROSCLEROSIS SUPP
JI Atheroscler. Suppl.
PD JUN 10
PY 2010
VL 11
IS 2
MA L3
BP 14
EP 14
PG 1
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 613IJ
UT WOS:000278972300063
ER
PT J
AU Krobot, KJ
Siebert, U
AF Krobot, K. J.
Siebert, U.
TI FIRST APPLICATION OF RISK ADVANCEMENT PERIODS TO LIPID RATIOS
SO ATHEROSCLEROSIS SUPPLEMENTS
LA English
DT Meeting Abstract
CT 78th Congress of the European-Atherosclerosis-Society
CY JUN 20-23, 2010
CL Hamburg, GERMANY
SP European Atherosclerosis Soc
C1 [Siebert, U.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Cambridge, MA 02138 USA.
[Siebert, U.] Harvard Univ, Sch Publ Hlth, Ctr Hlth Decis Sci, Dept Hlth Policy & Management, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 1567-5688
J9 ATHEROSCLEROSIS SUPP
JI Atheroscler. Suppl.
PD JUN 10
PY 2010
VL 11
IS 2
MA P116
BP 40
EP 41
PG 2
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 613IJ
UT WOS:000278972300183
ER
PT J
AU Wong, MC
van Diepen, JA
Hu, L
Guigas, B
de Boer, HC
Romijn, JA
Havekes, LM
Shoelson, SE
Voshol, PJ
Tamsma, JT
Rensen, PCN
Hiemstra, PS
Berbee, JFP
AF Wong, M. -C.
van Diepen, J. A.
Hu, L.
Guigas, B.
de Boer, H. C.
Romijn, J. A.
Havekes, L. M.
Shoelson, S. E.
Voshol, P. J.
Tamsma, J. T.
Rensen, P. C. N.
Hiemstra, P. S.
Berbee, J. F. P.
TI LIVER-SPECIFIC IKK-beta ACTIVATION SEVERELY AGGRAVATES ATHEROSCLEROSIS
DEVELOPMENT IN APOE*3-LEIDEN MICE
SO ATHEROSCLEROSIS SUPPLEMENTS
LA English
DT Meeting Abstract
CT 78th Congress of the European-Atherosclerosis-Society
CY JUN 20-23, 2010
CL Hamburg, GERMANY
SP European Atherosclerosis Soc
C1 [Havekes, L. M.] Leiden Univ, Ctr Med, Leiden, Netherlands.
[Havekes, L. M.] TNO, Gaubius Lab, Leiden, Netherlands.
[Shoelson, S. E.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 1567-5688
J9 ATHEROSCLEROSIS SUPP
JI Atheroscler. Suppl.
PD JUN 10
PY 2010
VL 11
IS 2
MA P408
BP 103
EP 103
PG 1
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 613IJ
UT WOS:000278972300475
ER
PT J
AU Fayad, Z
Farkouh, M
Tawakol, A
Rudd, J
Woodward, M
Yang, L
Bucerius, J
Calcagno, C
Burgess, T
Pozza, J
Mani, V
Kallend, D
AF Fayad, Z.
Farkouh, M.
Tawakol, A.
Rudd, J.
Woodward, M.
Yang, L.
Bucerius, J.
Calcagno, C.
Burgess, T.
Pozza, J.
Mani, V.
Kallend, D.
TI FDG-PET/CT AND MRI EVALUATION OF THE EFFECT OF DALCETRAPIB ON
ATHEROSCLEROTIC PLAQUE PROGRESSION/REGRESSION: DESIGN OF THE DAL-PLAQUE
STUDY
SO ATHEROSCLEROSIS SUPPLEMENTS
LA English
DT Meeting Abstract
CT 78th Congress of the European-Atherosclerosis-Society
CY JUN 20-23, 2010
CL Hamburg, GERMANY
SP European Atherosclerosis Soc
C1 [Fayad, Z.; Farkouh, M.; Woodward, M.; Yang, L.; Bucerius, J.; Calcagno, C.; Mani, V.] Mt Sinai Med Ctr, New York, NY 10029 USA.
[Tawakol, A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Rudd, J.] Addenbrookes Hosp, Cambridge, England.
[Burgess, T.; Pozza, J.] Hoffmann La Roche Inc, Nutley, NJ 07110 USA.
[Kallend, D.] F Hoffmann La Roche & Co Ltd, CH-4002 Basel, Switzerland.
RI Mani, Venkatesh/B-8939-2011
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 1567-5688
J9 ATHEROSCLEROSIS SUPP
JI Atheroscler. Suppl.
PD JUN 10
PY 2010
VL 11
IS 2
MA MS387
BP 188
EP 188
PG 1
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 613RW
UT WOS:000278998800388
ER
PT J
AU Shao, LJ
Sun, Y
Zhang, ZH
Feng, W
Gao, YX
Cai, ZL
Wang, ZZ
Look, AT
Wu, WS
AF Shao, Lijian
Sun, Yan
Zhang, Zhonghui
Feng, Wei
Gao, Yongxing
Cai, Zailong
Wang, Zack Z.
Look, A. Thomas
Wu, Wen-Shu
TI Deletion of proapoptotic Puma selectively protects hematopoietic stem
and progenitor cells against high-dose radiation
SO BLOOD
LA English
DT Article
ID COLORECTAL-CANCER CELLS; BH3-ONLY PROTEINS PUMA; GENE-EXPRESSION; BCL-2
FAMILY; APOPTOTIC PATHWAYS; GAMMA-RADIATION; DNA-DAMAGE; P53; MICE;
DEATH
AB Bone marrow injury is a major adverse side effect of radiation and chemotherapy. Attempts to limit such damage are warranted, but their success requires a better understanding of how radiation and anticancer drugs harm the bone marrow. Here, we report one pivotal role of the BH3-only protein Puma in the radiosensitivity of hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs). Puma deficiency in mice confers resistance to high-dose radiation in a hematopoietic cell-autonomous manner. Unexpectedly, loss of one Puma allele is sufficient to confer mice radioresistance. Interestingly, null mutation in Puma protects both primitive and differentiated hematopoietic cells from damage caused by low-dose radiation but selectively protects HSCs and HPCs against high-dose radiation, thereby accelerating hematopoietic regeneration. Consistent with these findings, Puma is required for radiation-induced apoptosis in HSCs and HPCs, and Puma is selectively induced by irradiation in primitive hematopoietic cells, and this induction is impaired in Puma-heterozygous cells. Together, our data indicate that selective targeting of p53 downstream apoptotic targets may represent a novel strategy to protecting HSCs and HPCs in patients undergoing intensive cancer radiotherapy and chemotherapy. (Blood. 2010;115(23):4707-4714)
C1 [Shao, Lijian; Sun, Yan; Zhang, Zhonghui; Feng, Wei; Gao, Yongxing; Wang, Zack Z.; Wu, Wen-Shu] Maine Med Ctr, Res Inst, COBRE Stem Biol & Regenerat Med, Ctr Mol Med, Scarborough, ME 04074 USA.
[Cai, Zailong] Second Mil Med Univ, Changhai Hosp, Clin Res Ctr, Shanghai, Peoples R China.
[Look, A. Thomas] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
RP Wu, WS (reprint author), Maine Med Ctr, Res Inst, COBRE Stem Biol & Regenerat Med, Ctr Mol Med, 81 Res Dr, Scarborough, ME 04074 USA.
EM wuw@mmc.org
RI Wu, Wen-Shu/I-1258-2014
OI Wu, Wen-Shu/0000-0002-0225-2522
FU National Institutes of Health from the National Center for Research
Resources [P20 RR018789]; National Institute of Diabetes and Digestive
and Kidney Diseases [K01DK078180]
FX This work was supported in part by National Institutes of Health from
the National Center for Research Resources (grant P20 RR018789). W. S. W
was supported by a K01 award from the National Institute of Diabetes and
Digestive and Kidney Diseases (K01DK078180).
NR 33
TC 43
Z9 52
U1 1
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 JUN 10
PY 2010
VL 115
IS 23
BP 4707
EP 4714
DI 10.1182/blood-2009-10-248872
PG 8
WC Hematology
SC Hematology
GA 609DS
UT WOS:000278635900017
PM 20360471
ER
PT J
AU Wang, SS
Abdou, AM
Morton, LM
Thomas, R
Cerhan, JR
Gao, XJ
Cozen, W
Rothman, N
Davis, S
Severson, RK
Bernstein, L
Hartge, P
Carrington, M
AF Wang, Sophia S.
Abdou, Amr M.
Morton, Lindsay M.
Thomas, Rasmi
Cerhan, James R.
Gao, Xiaojiang
Cozen, Wendy
Rothman, Nathaniel
Davis, Scott
Severson, Richard K.
Bernstein, Leslie
Hartge, Patricia
Carrington, Mary
TI Human leukocyte antigen class I and II alleles in non-Hodgkin lymphoma
etiology
SO BLOOD
LA English
DT Article
ID CHRONIC HEPATITIS-B; NECROSIS-FACTOR TNF; HETEROZYGOTE ADVANTAGE;
INTERLYMPH-CONSORTIUM; GENETIC-VARIANTS; RISK; HLA; ASSOCIATION;
SUSCEPTIBILITY; POLYMORPHISMS
AB Genome-wide association and candidate gene studies implicate different genetic variants within the 6p21 chromosomal region with different non-Hodgkin lymphoma (NHL) subtypes. Complementing these efforts, we conducted human leukocyte antigen (HLA) class I and class II genotyping among 610 NHL cases and 555 controls of non-Hispanic white descent from a US multicenter study. Allele-disease associations were assessed by logistic regression for NHL and its subtypes. Statistically significant associations between HLA and NHL subtypes include HLA-DRB1*0101 for follicular lymphoma (odds ratio [OR] = 2.14, P < .001), HLA-DRB1*0401 for diffuse large B-cell lymphoma (DLBCL; OR = 0.45, P = .006), and HLA-DRB1*13 and follicular lymphoma (OR = 0.48, P = .008). We further observed significant heterozygote advantage for HLA class I alleles and NHL, and particularly DLBCL (P trend = .01 for elevated risk with increasing number of homozygous alleles). Our results support a role for HLA in the etiology of NHL and its subtypes. (Blood. 2010;115(23):4820-4823)
C1 [Wang, Sophia S.] City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Div Canc Etiol, Duarte, CA 91010 USA.
[Abdou, Amr M.; Thomas, Rasmi; Gao, Xiaojiang; Carrington, Mary] NCI Frederick, Canc & Inflammat Program, Expt Immunol Lab, SAIC Frederick Inc, Frederick, MD USA.
[Morton, Lindsay M.; Rothman, Nathaniel; Hartge, Patricia] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
[Cerhan, James R.] Mayo Clin, Coll Med, Rochester, MN USA.
[Cozen, Wendy] Univ So Calif, Norris Comprehens Canc Ctr, Los Angeles, CA USA.
[Davis, Scott] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Davis, Scott] Univ Washington, Seattle, WA 98195 USA.
[Severson, Richard K.] Wayne State Univ, Dept Family Med & Publ Hlth Sci, Detroit, MI USA.
[Severson, Richard K.] Karmanos Canc Inst, Detroit, MI USA.
[Carrington, Mary] MIT, Massachusetts Gen Hosp, Ragon Inst, Boston, MA USA.
[Carrington, Mary] Harvard Univ, Boston, MA 02115 USA.
RP Wang, SS (reprint author), City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Div Canc Etiol, Duarte, CA 91010 USA.
EM sowang@coh.org
RI Morton, Lindsay/B-5234-2015;
OI Morton, Lindsay/0000-0001-9767-2310; Abdou, Amr/0000-0002-3373-2406;
Cerhan, James/0000-0002-7482-178X
FU NIH (National Cancer Institute [NCI]) [HHSN261200800001E]; Public Health
Service (PHS) [N01-PC-65064, N01-PC-67008, N01-PC-67009, N01-PC-67010,
N02-PC-71105]; NIH, NCI, Center for Cancer Research
FX The NCI-SEER study was supported by the Intramural Research Program of
the NIH (National Cancer Institute [NCI]), and by Public Health Service
(PHS) contracts N01-PC-65064, N01-PC-67008, N01-PC-67009, N01-PC-67010,
and N02-PC-71105. HLA typing for the study was funded in part with
federal funds from the NCI, NIH, under contract no. HHSN261200800001E
and in part by the Intramural Research Program of the NIH, NCI, Center
for Cancer Research.
NR 20
TC 37
Z9 41
U1 0
U2 2
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD JUN 10
PY 2010
VL 115
IS 23
BP 4820
EP 4823
DI 10.1182/blood-2010-01-266775
PG 4
WC Hematology
SC Hematology
GA 609DS
UT WOS:000278635900029
PM 20385791
ER
PT J
AU Batchelor, TT
Duda, DG
di Tomaso, E
Ancukiewicz, M
Plotkin, SR
Gerstner, E
Eichler, AF
Drappatz, J
Hochberg, FH
Benner, T
Louis, DN
Cohen, KS
Chea, H
Exarhopoulos, A
Loeffler, JS
Moses, MA
Ivy, P
Sorensen, AG
Wen, PY
Jain, RK
AF Batchelor, Tracy T.
Duda, Dan G.
di Tomaso, Emmanuelle
Ancukiewicz, Marek
Plotkin, Scott R.
Gerstner, Elizabeth
Eichler, April F.
Drappatz, Jan
Hochberg, Fred H.
Benner, Thomas
Louis, David N.
Cohen, Kenneth S.
Chea, Houng
Exarhopoulos, Alexis
Loeffler, Jay S.
Moses, Marsha A.
Ivy, Percy
Sorensen, A. Gregory
Wen, Patrick Y.
Jain, Rakesh K.
TI Phase II Study of Cediranib, an Oral Pan-Vascular Endothelial Growth
Factor Receptor Tyrosine Kinase Inhibitor, in Patients With Recurrent
Glioblastoma
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID ANTIANGIOGENIC THERAPY; BRAIN-TUMORS; COLORECTAL-CANCER; RESPONSE
CRITERIA; MALIGNANT GLIOMA; CLINICAL-TRIALS; ANGIOGENESIS;
NORMALIZATION; BEVACIZUMAB; PROGRESSION
AB Purpose
Glioblastoma is an incurable solid tumor characterized by increased expression of vascular endothelial growth factor (VEGF). We performed a phase II study of cediranib in patients with recurrent glioblastoma.
Methods
Cediranib, an oral pan-VEGF receptor tyrosine kinase inhibitor, was administered (45 mg/d) until progression or unacceptable toxicity to patients with recurrent glioblastoma. The primary end point was the proportion of patients alive and progression free at 6 months (APF6). We performed magnetic resonance imaging (MRI) and plasma and urinary biomarker evaluations at multiple time points.
Results
Thirty-one patients with recurrent glioblastoma were accrued. APF6 after cediranib was 25.8%. Radiographic partial responses were observed by MRI in 17 (56.7%) of 30 evaluable patients using three-dimensional measurements and in eight (27%) of 30 evaluable patients using two-dimensional measurements. For the 15 patients who entered the study taking corticosteroids, the dose was reduced (n = 10) or discontinued (n = 5). Toxicities were manageable. Grade 3/4 toxicities included hypertension (four of 31; 12.9%); diarrhea (two of 31; 6.4%); and fatigue (six of 31; 19.4%). Fifteen (48.4%) of 31 patients required at least one dose reduction and 15 patients required temporary drug interruptions due to toxicity. Drug interruptions were not associated with outcome. Changes in plasma placental growth factor, basic fibroblast growth factor, matrix metalloproteinase (MMP) -2, soluble VEGF receptor 1, stromal cell-derived factor-1 alpha, and soluble Tek/Tie2 receptor and in urinary MMP-9/neutrophil gelatinase-associated lipocalin activity after cediranib were associated with radiographic response or survival.
Conclusion
Cediranib monotherapy for recurrent glioblastoma is associated with encouraging proportions of radiographic response, 6-month progression-free survival, and a steroid-sparing effect with manageable toxicity. We identified early changes in circulating molecules as potential biomarkers of response to cediranib. The efficacy of cediranib and the predictive value of these candidate biomarkers will be explored in prospective trials. J Clin Oncol 28:2817-2823. (C) 2010 by American Society of Clinical Oncology
C1 [Batchelor, Tracy T.] Massachusetts Gen Hosp, Ctr Canc, Stephen E & Catherine Pappas Ctr Neurooncol, Boston, MA 02114 USA.
Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
Massachusetts Gen Hosp, Ctr Regenerat Med, Dept Pathol, Boston, MA 02114 USA.
Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA.
Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA USA.
Harvard Univ, Childrens Hosp, Sch Med, Vasc Biol Program, Boston, MA 02115 USA.
MIT, AA Martinos Ctr Biomed Imaging, Div Hlth Sci & Technol, Charlestown, MA USA.
Massachusetts Gen Hosp, Charlestown, MA USA.
NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
RP Batchelor, TT (reprint author), Massachusetts Gen Hosp, Ctr Canc, Stephen E & Catherine Pappas Ctr Neurooncol, Yawkey 9E,55 Fruit St, Boston, MA 02114 USA.
EM tbatchelor@partners.org
FU National Institutes of Health [R21-CA117079, K24-CA125440, R01-CA129371,
P01-CA80124, R01-CA115767, M01-RR-01066, P41-RR014075, R01-CA118764,
P01-CA455481]; Federal Share/National Cancer Institute Proton Beam
Program Income [1UL1RR025758-01]; Harvard Clinical and Translational
Science Center, National Center for Research Resources; Montesi Family
Research Fund; Simches Fund for Brain Tumor Research
FX Supported by Grants No. R21-CA117079, K24-CA125440, R01-CA129371,
P01-CA80124, R01-CA115767, M01-RR-01066, P41-RR014075, R01-CA118764, and
P01-CA455481 from the National Institutes of Health; by grants from the
Federal Share/National Cancer Institute Proton Beam Program Income; by
Grant No. 1UL1RR025758-01 from the Harvard Clinical and Translational
Science Center, National Center for Research Resources; and by gifts
from the Montesi Family Research Fund and the Simches Fund for Brain
Tumor Research.
NR 43
TC 272
Z9 277
U1 1
U2 20
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JUN 10
PY 2010
VL 28
IS 17
BP 2817
EP 2823
DI 10.1200/JCO.2009.26.3988
PG 7
WC Oncology
SC Oncology
GA 608AA
UT WOS:000278548000003
PM 20458050
ER
PT J
AU Gyurkocza, B
Storb, R
Storer, BE
Chauncey, TR
Lange, T
Shizuru, JA
Langston, AA
Pulsipher, MA
Bredeson, CN
Maziarz, RT
Bruno, B
Petersen, FB
Maris, MB
Agura, E
Yeager, A
Bethge, W
Sahebi, F
Appelbaum, FR
Maloney, DG
Sandmaier, BM
AF Gyurkocza, Boglarka
Storb, Rainer
Storer, Barry E.
Chauncey, Thomas R.
Lange, Thoralf
Shizuru, Judith A.
Langston, Amelia A.
Pulsipher, Michael A.
Bredeson, Christopher N.
Maziarz, Richard T.
Bruno, Benedetto
Petersen, Finn B.
Maris, Michael B.
Agura, Edward
Yeager, Andrew
Bethge, Wolfgang
Sahebi, Firoozeh
Appelbaum, Frederick R.
Maloney, David G.
Sandmaier, Brenda M.
TI Nonmyeloablative Allogeneic Hematopoietic Cell Transplantation in
Patients With Acute Myeloid Leukemia
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID TOTAL-BODY IRRADIATION; ACUTE MYELOGENOUS LEUKEMIA;
SOUTHWEST-ONCOLOGY-GROUP; VERSUS-HOST-DISEASE; BONE-MARROW GRAFTS;
MYELODYSPLASTIC SYNDROME; UNRELATED DONORS; OLDER PATIENTS; POSTGRAFTING
IMMUNOSUPPRESSION; HEMATOLOGIC MALIGNANCIES
AB Purpose
Allogeneic hematopoietic cell transplantation (HCT) after high-dose conditioning regimens imposes prohibitively high risks of morbidity and mortality for patients with high-risk acute myeloid leukemia (AML) who are older or have comorbid conditions. Here, we examined outcomes after nonmyeloablative allogeneic HCT in such patients.
Patients and Methods
Two hundred seventy-four patients (median age, 60 years) with de novo or secondary AML underwent allogeneic HCT from related (n = 118) or unrelated donors (n = 156) after conditioning with 2 Gy of total-body irradiation (TBI) with or without fludarabine. A calcineurin inhibitor and mycophenolate mofetil were used for postgrafting immunosuppression.
Results
With a median follow-up of 38 months in surviving patients, the estimated overall survival at 5 years was 33%. The estimated 5-year relapse/progression and nonrelapse mortality rates were 42% and 26%, respectively. The cumulative incidences of grades 2, 3, and 4 acute graft-versus-host disease (GVHD) were 38%, 9%, and 5%, respectively. The cumulative incidence of chronic GVHD at 5 years was 44%. Patients in first and second complete remission had better survival rates than patients with more advanced disease (37% and 34% v 18%, respectively). Patients with HLA-matched related or unrelated donors had similar survivals. Unfavorable cytogenetic risk status was associated with increased relapse and subsequent mortality. Chronic GVHD was associated with lower relapse risk.
Conclusion
Allogeneic HCT from related or unrelated donors after conditioning with low-dose TBI and fludarabine, relying almost exclusively on graft-versus-leukemia effects, can result in long-term remissions in older or medically infirm patients with AML.
C1 [Sandmaier, Brenda M.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA.
Univ Washington, Sch Med, Seattle, WA 98195 USA.
Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA.
Stanford Univ, Stanford, CA 94305 USA.
City Hope Kaiser Permanente Med Grp, Duarte, CA USA.
Emory Univ, Atlanta, GA 30322 USA.
Univ Utah, Latter Day St Hosp, Salt Lake City, UT 84143 USA.
Med Coll Wisconsin, Milwaukee, WI 53226 USA.
Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
Rocky Mt Canc Ctr, Denver, CO USA.
Baylor Univ, Dallas, TX USA.
Univ Arizona, Tucson, AZ USA.
Univ Leipzig, Leipzig, Germany.
Univ Tubingen, Tubingen, Germany.
Univ Turin, Turin, Italy.
RP Sandmaier, BM (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,Mail Stop D1-100,POB 19024, Seattle, WA 98109 USA.
EM bsandmai@fhcrc.org
OI Gyurkocza, Boglarka/0000-0002-2933-2119
FU National Institutes of Health, Bethesda, MD [CA78902, HL36444, CA18029,
CA15704, CA106177]
FX Supported by Grants No. CA78902, HL36444, CA18029, CA15704, and CA106177
from the National Institutes of Health, Bethesda, MD.
NR 45
TC 114
Z9 114
U1 0
U2 2
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JUN 10
PY 2010
VL 28
IS 17
BP 2859
EP 2867
DI 10.1200/JCO.2009.27.1460
PG 9
WC Oncology
SC Oncology
GA 608AA
UT WOS:000278548000009
PM 20439626
ER
PT J
AU Yeh, RW
Sidney, S
Chandra, M
Sorel, M
Selby, JV
Go, AS
AF Yeh, Robert W.
Sidney, Stephen
Chandra, Malini
Sorel, Michael
Selby, Joseph V.
Go, Alan S.
TI Population Trends in the Incidence and Outcomes of Acute Myocardial
Infarction.
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID CORONARY-HEART-DISEASE; CONVERTING-ENZYME-INHIBITOR; ST-SEGMENT
ELEVATION; CARDIOVASCULAR-DISEASE; UNITED-STATES; CHOLESTEROL LEVELS;
TEMPORAL TRENDS; MEDICAL-CARE; US ADULTS; MORTALITY
AB Background: Few studies have characterized recent population trends in the incidence and outcomes of myocardial infarction.
Methods: We identified patients 30 years of age or older in a large, diverse, community-based population who were hospitalized for incident myocardial infarction between 1999 and 2008. Age- and sex-adjusted incidence rates were calculated for myocardial infarction overall and separately for ST-segment elevation and non-ST-segment elevation myocardial infarction. Patient characteristics, outpatient medications, and cardiac biomarker levels during hospitalization were identified from health plan databases, and 30-day mortality was ascertained from administrative databases, state death data, and Social Security Administration files.
Results: We identified 46,086 hospitalizations for myocardial infarctions during 18,691,131 person-years of follow-up from 1999 to 2008. The age- and sex-adjusted incidence of myocardial infarction increased from 274 cases per 100,000 person-years in 1999 to 287 cases per 100,000 person-years in 2000, and it decreased each year thereafter, to 208 cases per 100,000 person-years in 2008, representing a 24% relative decrease over the study period. The age- and sex-adjusted incidence of ST-segment elevation myocardial infarction decreased throughout the study period (from 133 cases per 100,000 person-years in 1999 to 50 cases per 100,000 person-years in 2008, P<0.001 for linear trend). Thirty-day mortality was significantly lower in 2008 than in 1999 (adjusted odds ratio, 0.76; 95% confidence interval, 0.65 to 0.89).
Conclusions: Within a large community-based population, the incidence of myocardial infarction decreased significantly after 2000, and the incidence of ST-segment elevation myocardial infarction decreased markedly after 1999. Reductions in short-term case fatality rates for myocardial infarction appear to be driven, in part, by a decrease in the incidence of ST-segment elevation myocardial infarction and a lower rate of death after non-ST-segment elevation myocardial infarction.
N Engl J Med 2010;362:2155-65.
C1 [Sidney, Stephen; Chandra, Malini; Sorel, Michael; Selby, Joseph V.; Go, Alan S.] Kaiser Permanente No Calif, Div Res, Oakland, CA 94612 USA.
[Yeh, Robert W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiol Div, Boston, MA USA.
[Sidney, Stephen; Selby, Joseph V.; Go, Alan S.] Permanente Med Grp Inc, Oakland, CA USA.
[Go, Alan S.] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA.
[Go, Alan S.] Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94143 USA.
[Go, Alan S.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
RP Go, AS (reprint author), Kaiser Permanente No Calif, Div Res, 2000 Broadway St,3rd Fl, Oakland, CA 94612 USA.
EM alan.s.go@kp.org
FU Permanente Medical Group; Schering-Plough Future Leaders in
Cardiovascular Medical Research
FX Supported by research funding from the Permanente Medical Group and by a
Schering-Plough Future Leaders in Cardiovascular Medical Research grant.
NR 56
TC 533
Z9 559
U1 2
U2 39
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JUN 10
PY 2010
VL 362
IS 23
BP 2155
EP 2165
DI 10.1056/NEJMoa0908610
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA 608AL
UT WOS:000278551500004
PM 20558366
ER
PT J
AU Tarsy, D
Sweadner, KJ
Song, PC
AF Tarsy, Daniel
Sweadner, Kathleen J.
Song, Phillip C.
TI A Woman with Flexion of the Left Hand and Foot and Difficulty Speaking
Rapid-onset dystonia-parkinsonism due to a mutation in the ATP1A3 gene.
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID CHROMOSOME 19Q13; FAMILY; RDP; HETEROGENEITY; LINKAGE
C1 [Tarsy, Daniel] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA.
[Sweadner, Kathleen J.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA.
[Song, Phillip C.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA.
[Tarsy, Daniel] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA.
[Sweadner, Kathleen J.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA.
[Song, Phillip C.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA.
RP Tarsy, D (reprint author), Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA.
FU NINDS NIH HHS [R01 NS058949]
NR 24
TC 10
Z9 10
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 JUN 10
PY 2010
VL 362
IS 23
BP 2213
EP 2219
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 608AL
UT WOS:000278551500012
PM 20558373
ER
PT J
AU Wang, HY
Wang, Q
Pape, UJ
Shen, BR
Huang, JH
Wu, B
Li, X
AF Wang, Haiyun
Wang, Qi
Pape, Utz J.
Shen, Bairong
Huang, Jianhua
Wu, Bin
Li, Xia
TI Systematic investigation of global coordination among mRNA and protein
in cellular society
SO BMC GENOMICS
LA English
DT Article
ID SACCHAROMYCES-CEREVISIAE; EXPRESSION PROFILES; GENE; CLASSIFICATION;
CANCER; PREDICTION; MICROARRAY; TRANSCRIPT; PROTEOMICS; DISCOVERY
AB Background: Cell functions depend on molecules organized in the cellular society. Two basic components are mRNA molecules and proteins. The interactions within and between those two components are crucial for carrying out sophisticated cell functions. The interplay can be analyzed by comparing expression levels of mRNA and proteins. This is critical for understanding the molecular interactions, (post-) transcriptional regulations and conservation of co-expression between mRNAs and proteins. By using high-throughput transcriptome and proteome data, this study aims to systematically investigate the general picture of such expression correlations. We analyze four groups of correlations: (i) transcript levels of different genes, (ii) protein levels of different genes, (iii) mRNA levels with protein levels of different genes and (iv) mRNA levels with protein levels of same genes. This helps to obtain global insights into the stability and variability of co-expression and correlation of mRNA and protein levels.
Results: Analysis of the simultaneous co-expression of mRNAs and proteins yields mainly weak correlations. Therefore we introduce the concept of time-delayed co-expression patterns. Based on a time-course dataset, we obtain a high fraction of time-delayed correlations. In group (i), 67% of different transcripts are significantly correlated. At the protein level (ii), 68% of different proteins are significantly correlated. Comparison of the different molecular levels results in a 74% fraction of correlated transcript and protein levels of different genes (iii) and 56% for the same genes (iv). Furthermore, a higher fraction of protein levels (simultaneously 20% and short time-delayed 29%) is correlated than at the transcript level (10% and 18% respectively). Analysis of the dynamics of the correlation shows that correlation at the transcript level is largely passed to the protein level. In contrast, specific co-expression patterns are changed in multiple ways.
Conclusions: Our analysis reveals that the regulation of transcription and translation contains a time-delayed component. The correlation at the protein level is more synchronous or delayed by shorter time than those at the transcript level. This supports the hypothesis that a higher degree of direct physical interactions require a higher synchronicity between the interacting partners. The conservation of correlation between the transcript level (i) and the protein level (ii) sheds light on the processes underlying transcription, translation and regulation. A future investigation of the conditions of conservation will give comprehensive insights in the complexity of the regulatory mechanisms.
C1 [Wang, Haiyun; Shen, Bairong; Li, Xia] Tongji Univ, Sch Life Sci & Technol, Shanghai 200092, Peoples R China.
[Wang, Qi; Huang, Jianhua; Wu, Bin] Fudan Univ, Huashan Hosp, Shanghai 200040, Peoples R China.
[Pape, Utz J.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Pape, Utz J.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Pape, Utz J.] Immune Dis Inst, Dept Pathol, Boston, MA 02115 USA.
[Pape, Utz J.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Shen, Bairong] Soochow Univ, Ctr Syst Biol, Suzhou 215006, Peoples R China.
[Li, Xia] Harbin Med Coll, Coll Bioinformat Sci & Technol, Harbin 150086, Peoples R China.
[Shen, Bairong] Univ Tampere, Inst Med Technol, Tampere 33014, Finland.
RP Wang, HY (reprint author), Tongji Univ, Sch Life Sci & Technol, Shanghai 200092, Peoples R China.
EM wanghaiyun@tongji.edu.cn; profli@126.com
RI Shen, Bairong/E-6431-2012
OI Shen, Bairong/0000-0003-2899-1531
FU 973 Program of China [2007CB947002, 2008CB517302]
FX This work was supported in part by the 973 Program of China
(2007CB947002, 2008CB517302). We are very grateful to Scott Taing for
manuscript modification and suggestion. We also greatly thank Yong Zhang
and X. Shirley Liu for all help and support of this work.
NR 23
TC 20
Z9 20
U1 1
U2 6
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2164
J9 BMC GENOMICS
JI BMC Genomics
PD JUN 9
PY 2010
VL 11
AR 364
DI 10.1186/1471-2164-11-364
PG 9
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA 625CB
UT WOS:000279868600001
PM 20529381
ER
PT J
AU Blumenthal, KJ
Larkin, ME
Winning, G
Nathan, DM
Grant, RW
AF Blumenthal, Karen J.
Larkin, Mary E.
Winning, Gail
Nathan, David M.
Grant, Richard W.
TI Changes in glycemic control from 1996 to 2006 among adults with type 2
diabetes: a longitudinal cohort study
SO BMC HEALTH SERVICES RESEARCH
LA English
DT Article
ID DENSITY-LIPOPROTEIN CHOLESTEROL; COMPLICATIONS; PROGRESSION; MELLITUS;
PLASMA; RISK
AB Background: Our objectives were to examine temporal changes in HbA1c and lipid levels over a 10-year period and to identify predictors of metabolic control in a longitudinal patient cohort.
Methods: We identified all adults within our hospital network with T2DM who had HbA1c's measured in both 1996 and 2006 (longitudinal cohort). For patients with no data in 2006, we used hospital and social security records to distinguish patients lost to follow-up from those who died after 1996. We compared characteristics of the 3 baseline cohorts (longitudinal, lost to f/u, died) and examined metabolic trends in the longitudinal cohort.
Results: Of the 4944 patients with HbA1c measured in 1996, 1772 (36%) had an HbA1c measured in 2006, 1296 (26%) were lost to follow-up, and 1876 (38%) had died by 2006. In the longitudinal cohort, mean HbA1c decreased by 0.4 +/- 1.8% over the ten-year span (from 8.2% +/- 1.7% to 7.8% +/- 1.4%) and mean total cholesterol decreased by 49.3 (+/- 46.5) mg/dL. In a multivariate model, independent predictors of HbA1c decline included older age (OR 1.41 per decade, 95% CI: 1.3-1.6, p < 0.001), baseline HbA1c (OR 2.9 per 1% increment, 2.6 - 3.2, p < 0.001), and speaking English (OR 2.1, 1.4-3.1, p < 0.001).
Conclusions: Despite having had diabetes for an additional 10 years, patients in our longitudinal cohort had better glycemic and cholesterol control in 2006 than 1996. Greatest improvements occurred in patients with the highest levels in the baseline year.
C1 [Blumenthal, Karen J.; Larkin, Mary E.; Winning, Gail; Nathan, David M.; Grant, Richard W.] Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA.
[Grant, Richard W.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA.
[Nathan, David M.; Grant, Richard W.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
RP Grant, RW (reprint author), Massachusetts Gen Hosp, Ctr Diabet, 50 Staniford St, Boston, MA 02114 USA.
EM rgrant@partners.org
OI Grant, Richard/0000-0002-6164-8025
FU NIDDK [K23 DK067452]; Earl Charlton Fund for Innovative Diabetes
Research
FX Dr. Grant was supported by NIDDK Career Development Award (K23
DK067452). Dr. Nathan, Karen Blumenthal, Mary Larkin and Gail Winning
were supported in part by the Earl Charlton Fund for Innovative Diabetes
Research.
NR 18
TC 7
Z9 7
U1 0
U2 0
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1472-6963
J9 BMC HEALTH SERV RES
JI BMC Health Serv. Res.
PD JUN 9
PY 2010
VL 10
AR 158
DI 10.1186/1472-6963-10-158
PG 6
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA 625GL
UT WOS:000279883000001
PM 20534158
ER
PT J
AU Pitman, RK
AF Pitman, Roger K.
TI Posttraumatic Stress Disorder and Dementia What Is the Origin of the
Association?
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
ID INTELLIGENCE; RISK
C1 [Pitman, Roger K.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Pitman, Roger K.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
RP Pitman, RK (reprint author), MGH East,120 2nd Ave, Charlestown, MA 02129 USA.
EM roger_pitman@hms.harvard.edu
NR 10
TC 8
Z9 8
U1 0
U2 1
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD JUN 9
PY 2010
VL 303
IS 22
BP 2287
EP 2288
DI 10.1001/jama.2010.767
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 607IY
UT WOS:000278496800028
PM 20540170
ER
PT J
AU Devore, S
Delgutte, B
AF Devore, Sasha
Delgutte, Bertrand
TI Effects of Reverberation on the Directional Sensitivity of Auditory
Neurons across the Tonotopic Axis: Influences of Interaural Time and
Level Differences
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID SUPERIOR OLIVARY COMPLEX; HIGH-FREQUENCY NEURONS; INFERIOR COLLICULUS
NEURONS; AMPLITUDE-MODULATED TONES; SOUND LOCALIZATION; TEMPORAL
DISPARITIES; BINAURAL INTERACTION; CHANGING FREQUENCY; NEURAL
SENSITIVITY; CONVERGENT INPUT
AB In reverberant environments, acoustic reflections interfere with the direct sound arriving at a listener's ears, distorting the binaural cues for sound localization. We investigated the effects of reverberation on the directional sensitivity of single neurons in the inferior colliculus (IC) of unanesthetized rabbits. We find that reverberation degrades the directional sensitivity of single neurons, although the amount of degradation depends on the characteristic frequency (CF) and the type of binaural cues available. When interaural time differences (ITDs) are the only available directional cue, low-CF cells sensitive to ITDs in the waveform fine time structure maintain better directional sensitivity in reverberation than high-CF cells sensitive to ITDs in the envelope induced by cochlear filtering. Conversely, when both ITD and interaural level difference (ILD) cues are available, directional sensitivity in reverberation is comparable throughout the tonotopic axis of the IC. This result suggests that, at high frequencies, ILDs provide better directional information than envelope ITDs, emphasizing the importance of the ILD-processing pathway for sound localization
C1 [Devore, Sasha; Delgutte, Bertrand] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA.
[Devore, Sasha; Delgutte, Bertrand] Harvard Massachusetts Inst Technol Speech & Heari, Cambridge, MA 02139 USA.
[Devore, Sasha; Delgutte, Bertrand] MIT, Elect Res Lab, Cambridge, MA 02139 USA.
RP Devore, S (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA.
EM sashad@alum.mit.edu
OI , /0000-0003-1349-9608
FU National Institutes of Health [R01 DC002258, P30 DC005209]; Helen Carr
Peake fund
FX This work was supported by National Institutes of Health Grants R01
DC002258 and P30 DC005209 (B. D.) and the Helen Carr Peake fund (S. D.).
We thank Laurel Carney and Shigeyuki Kuwada for help with the awake
rabbit preparation, Ken Hancock for software support, and Melissa Wood
for technical assistance. We also thank Shigeyuki Kuwada, Christopher
Moore, and Barbara Shinn-Cunningham for reading a previous version of
the manuscript.
NR 46
TC 28
Z9 28
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 JUN 9
PY 2010
VL 30
IS 23
BP 7826
EP 7837
DI 10.1523/JNEUROSCI.5517-09.2010
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA 608LY
UT WOS:000278586900009
PM 20534831
ER
PT J
AU Kastman, EK
Willette, AA
Coe, CL
Bendlin, BB
Kosmatka, KJ
McLaren, DG
Xu, GF
Canu, E
Field, AS
Alexander, AL
Voytko, ML
Beasley, TM
Colman, RJ
Weindruch, RH
Johnson, SC
AF Kastman, Erik K.
Willette, Auriel A.
Coe, Christopher L.
Bendlin, Barbara B.
Kosmatka, Kris J.
McLaren, Donald G.
Xu, Guofan
Canu, Elisa
Field, Aaron S.
Alexander, Andrew L.
Voytko, Mary Lou
Beasley, T. Mark
Colman, Ricki J.
Weindruch, Richard H.
Johnson, Sterling C.
TI A Calorie-Restricted Diet Decreases Brain Iron Accumulation and
Preserves Motor Performance in Old Rhesus Monkeys
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID VOXEL-BASED MORPHOMETRY; TRANSVERSE RELAXATION RATES;
PARKINSONS-DISEASE; ALZHEIMERS-DISEASE; SUBSTANTIA-NIGRA;
NONHUMAN-PRIMATES; OXIDATIVE DAMAGE; HEME OXYGENASE-1; SKELETAL-MUSCLE;
RANDOM-FIELD
AB Caloric restriction (CR) reduces the pathological effects of aging and extends the lifespan in many species, including nonhuman primates, although the effect on the brain is less well characterized. We used two common indicators of aging, motor performance speed and brain iron deposition measured in vivo using MRI, to determine the potential effect of CR on elderly rhesus macaques eating restricted (n = 24; 13 males, 11 females) and standard diets (n = 17; 8 males, 9 females). Both the CR and control monkeys showed age-related increases in iron concentrations in globus pallidus (GP) and substantia nigra (SN), although the CR group had significantly less iron deposition in the GP, SN, red nucleus, and temporal cortex. A diet X age interaction revealed that CR modified age-related brain changes, evidenced as attenuation in the rate of iron accumulation in basal ganglia and parietal, temporal, and perirhinal cortex. Additionally, control monkeys had significantly slower fine motor performance on the Movement Assessment Panel, which was negatively correlated with iron accumulation in left SN and parietal lobe, although CR animals did not show this relationship. Our observations suggest that the CR-induced benefit of reduced iron deposition and preserved motor function may indicate neural protection similar to effects described previously in aging rodent and primate species.
C1 [Kastman, Erik K.; Bendlin, Barbara B.; Kosmatka, Kris J.; McLaren, Donald G.; Xu, Guofan; Canu, Elisa; Weindruch, Richard H.; Johnson, Sterling C.] William S Middleton Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Madison, WI 53705 USA.
[Kastman, Erik K.; Willette, Auriel A.; Bendlin, Barbara B.; Kosmatka, Kris J.; McLaren, Donald G.; Xu, Guofan; Canu, Elisa; Weindruch, Richard H.; Johnson, Sterling C.] Univ Wisconsin, Sch Med & Publ Hlth, Wisconsin Alzheimers Dis Res Ctr, Madison, WI 53705 USA.
[Willette, Auriel A.; Coe, Christopher L.] Univ Wisconsin, Dept Psychol, Harlow Primate Lab, Madison, WI 53715 USA.
[Willette, Auriel A.; Coe, Christopher L.; Alexander, Andrew L.; Johnson, Sterling C.] Univ Wisconsin, Waisman Imaging Ctr, Madison, WI 53705 USA.
[McLaren, Donald G.] Univ Wisconsin, Neurosci Training Program, Madison, WI 53706 USA.
[Field, Aaron S.] Univ Wisconsin, Dept Radiol, Madison, WI 53792 USA.
[Voytko, Mary Lou] Wake Forest Univ, Bowman Gray Sch Med, Dept Neurobiol & Anat, Winston Salem, NC 27157 USA.
[Voytko, Mary Lou] Wake Forest Univ, Bowman Gray Sch Med, Interdisciplinary Neurosci Program, Winston Salem, NC 27157 USA.
[Beasley, T. Mark; Colman, Ricki J.] Univ Alabama, Dept Biostat, Birmingham, AL 35294 USA.
[Weindruch, Richard H.; Johnson, Sterling C.] Wisconsin Natl Primate Res Ctr, Madison, WI 53792 USA.
RP Johnson, SC (reprint author), D4225 Vet Adm Hosp, Ctr Geriatr Res Educ & Clin, 2500 Overlook Terrace, Madison, WI 53705 USA.
EM scj@medicine.wisc.edu
RI McLaren, Donald/G-9906-2011; Kastman, Erik/N-6645-2016; Canu,
Elisa/K-1423-2016
OI Kastman, Erik/0000-0001-7221-9042; Bendlin, Barbara/0000-0002-0580-9875;
Canu, Elisa/0000-0001-5804-3378
FU National Institutes of Health [P01 AG11915, P51 RR000167]; Institute of
Aging [AG000213]; Research Facilities Improvement Program [RR15459-01,
RR020141-01]
FX This work was supported by funding from the National Institutes of
Health to the WNPRC (Grants P01 AG11915 and P51 RR000167) and Institute
of Aging Grant AG000213. This research was conducted in part at a
facility constructed with support from Research Facilities Improvement
Program (Grants RR15459-01 and RR020141-01). The project also benefited
from resources and facilities at the William S. Middleton Memorial
Veterans Hospital. We gratefully acknowledge the excellent technical
assistance provided by R. Fisher; S. Baum; J. Smith; J. Adriansjach; C.
Armstrong; the Waisman Center; and the Animal Care, Veterinary and
Pathology Staff of the WNPRC. We thank Dr. Craig Atwood for critical
comments on the manuscript.
NR 80
TC 28
Z9 28
U1 2
U2 4
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 JUN 9
PY 2010
VL 30
IS 23
BP 7940
EP 7947
DI 10.1523/JNEUROSCI.0835-10.2010
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA 608LY
UT WOS:000278586900020
PM 20534842
ER
PT J
AU Putrino, D
Brown, EN
Mastaglia, FL
Ghosh, S
AF Putrino, David
Brown, Emery N.
Mastaglia, Frank L.
Ghosh, Soumya
TI Differential Involvement of Excitatory and Inhibitory Neurons of Cat
Motor Cortex in Coincident Spike Activity Related to Behavioral Context
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID FIELD POTENTIAL OSCILLATIONS; CROSS-CORRELATION ANALYSIS; SPATIAL
WORKING-MEMORY; SYNAPTIC INTERACTION; VOLUNTARY MOVEMENTS; NONPYRAMIDAL
CELLS; CORTICAL-NEURONS; IN-VIVO; MONKEY; SYNCHRONIZATION
AB To assess temporal associations in spike activity between pairs of neurons in the primary motor cortex (MI) related to different behaviors, we compared the incidence of coincident spiking activity of task-related (TR) and non-task-related (NTR) neurons during a skilled motor task and sitting quietly in adult cats (Felis domestica). Chronically implanted microwires were used to record spike activity of MI neurons in four animals (two male and two female) trained to perform a skilled reaching task or sit quietly. Neurons were identified as TR if spike activity was modulated during the task (and NTR if not). Based on spike characteristics, they were also classified as either regular-spiking (RS, putatively excitatory) or fast-spiking (FS, putatively inhibitory) neurons. Temporal associations in the activities of simultaneously recorded neurons were evaluated using shuffle-corrected cross-correlograms. Pairs of NTR and TR neurons showed associations in their firing patterns over wide areas of MI (representing forelimb and hindlimb movements) during quiet sitting, more commonly involving RS neurons. During skilled task performance, however, significantly coincident firing was seen almost exclusively between TR neurons in a smaller part of MI (representing forelimb movements), involving mainly FS neurons. The findings of this study show evidence for widespread interactions in MI when the animal sits quietly, which changes to a more specific and restricted pattern of interactions during task performance. Different populations of excitatory and inhibitory neurons appear to be synchronized during skilled movement and quiet sitting.
C1 [Mastaglia, Frank L.; Ghosh, Soumya] Univ Western Australia, QEII Med Ctr, Ctr Neuromuscular & Neurol Disorders, Nedlands, WA 6009, Australia.
[Putrino, David; Brown, Emery N.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA.
[Putrino, David; Brown, Emery N.] Harvard Univ, MIT, Div Hlth Sci & Technol, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA.
RP Ghosh, S (reprint author), Univ Western Australia, QEII Med Ctr, Ctr Neuromuscular & Neurol Disorders, A Block,4th Floor, Nedlands, WA 6009, Australia.
EM sghosh@cyllene.uwa.edu.au
OI Putrino, David/0000-0002-2232-3324
FU National Institutes of Health [DP1-OD003646, R01-DA015644]; Australian
Neuromuscular Research Institute
FX D. P. received salary support from the National Institutes of Health
under the Grants DP1-OD003646 (E.N.B.) and R01-DA015644 (E.N.B.) while
writing this manuscript. We thank the Australian Neuromuscular Research
Institute for support and the staff of Animal House in A Block, QEII
Medical Centre, for help with animals.
NR 46
TC 9
Z9 9
U1 0
U2 1
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 JUN 9
PY 2010
VL 30
IS 23
BP 8048
EP 8056
DI 10.1523/JNEUROSCI.0770-10.2010
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA 608LY
UT WOS:000278586900031
PM 20534853
ER
PT J
AU Garraway, LA
Hahn, WC
AF Garraway, Levi A.
Hahn, William C.
TI On or Off Target: Mutations, Models, and Predictions
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID MELANOMA; CANCER; RESISTANCE; SORAFENIB; GENE
AB In a series of articles published in February 2010, The New York Times chronicled, from a personal perspective, the rollercoaster experience of those associated with clinical trials of a RAF inhibitor for the treatment of melanoma. In this issue of Science Translational Medicine, Whittaker et al. describe research that reconciles some of the bewildering aspects of the discovery and development of drugs that inhibit such protein kinase targets in cancer.
C1 [Garraway, Levi A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
Broad Inst Harvard & MIT, Cambridge, MA 02142 USA.
RP Garraway, LA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA.
EM Levi_Garraway@dfci.harvard.edu; William_Hahn@dfci.harvard.edu
NR 9
TC 1
Z9 1
U1 3
U2 3
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD JUN 9
PY 2010
VL 2
IS 35
AR 35ps28
DI 10.1126/scitranslmed.3001263
PG 3
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 735OL
UT WOS:000288426700002
PM 20538617
ER
PT J
AU Paraiso, KHT
Fedorenko, IV
Cantini, LP
Munko, AC
Hall, M
Sondak, VK
Messina, JL
Flaherty, KT
Smalley, KSM
AF Paraiso, K. H. T.
Fedorenko, I. V.
Cantini, L. P.
Munko, A. C.
Hall, M.
Sondak, V. K.
Messina, J. L.
Flaherty, K. T.
Smalley, K. S. M.
TI Recovery of phospho-ERK activity allows melanoma cells to escape from
BRAF inhibitor therapy
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE melanoma; BRAF; resistance; therapy
ID HEDGEHOG PATHWAY INHIBITOR; B-RAF; MALIGNANT-MELANOMA; MEK INHIBITOR;
RESISTANCE; KINASE; GROWTH; EXPRESSION; APOPTOSIS; TUMOR
AB BACKGROUND: Resistance to BRAF inhibitors is an emerging problem in the melanoma field. Strategies to prevent and overcome resistance are urgently required.
METHODS: The dynamics of cell signalling, BrdU incorporation and cell-cycle entry after BRAF inhibition was measured using flow cytometry and western blot. The ability of combined BRAF/MEK inhibition to prevent the emergence of resistance was demonstrated by apoptosis and colony formation assays and in 3D organotypic cell culture.
RESULTS: BRAF inhibition led to a rapid recovery of phospho-ERK (pERK) signalling. Although most of the cells remained growth arrested in the presence of drug, a minor population of cells retained their proliferative potential and escaped from BRAF inhibitor therapy. A function for the rebound pERK signalling in therapy escape was demonstrated by the ability of combined BRAF/MEK inhibition to enhance the levels of apoptosis and abrogate the onset of resistance.
CONCLUSION: Combined BRAF/MEK inhibition may be one strategy to prevent the emergence of drug resistance in BRAF-V600E-mutated melanomas. British Journal of Cancer (2010) 102, 1724-1730. doi: 10.1038/sj.bjc.6605714 www.bjcancer.com (C) 2010 Cancer Research UK
C1 [Paraiso, K. H. T.; Fedorenko, I. V.; Cantini, L. P.; Munko, A. C.; Smalley, K. S. M.] H Lee Moffitt Canc Ctr & Res Inst, Dept Mol Oncol, Tampa, FL 33612 USA.
[Hall, M.; Sondak, V. K.; Smalley, K. S. M.] H Lee Moffitt Canc Ctr & Res Inst, Dept Cutaneous Oncol, Tampa, FL 33612 USA.
[Messina, J. L.] Univ S Florida, Coll Med, Dept Pathol & Cell Biol, Tampa, FL 33612 USA.
[Flaherty, K. T.] Massachusetts Gen Hosp, Div Hematol Oncol, Dept Med, Ctr Canc, Boston, MA 02114 USA.
[Smalley, K. S. M.] H Lee Moffitt Canc Ctr & Res Inst, Dept Integrated Math Oncol, Tampa, FL 33612 USA.
RP Smalley, KSM (reprint author), H Lee Moffitt Canc Ctr & Res Inst, Dept Mol Oncol, 12902 Magnolia Dr, Tampa, FL 33612 USA.
EM keiran.smalley@moffitt.org
RI Smalley, Keiran/A-1320-2007; Fedorenko, Inna/G-9016-2015
OI Smalley, Keiran/0000-0002-4121-8335; Fedorenko, Inna/0000-0002-6796-9145
FU Melanoma Research Foundation; Bankhead-Coley Research Program of the
State of Florida [09BN-14]; American Cancer Society [93-032-13]; Donald
A Adam Comprehensive Melanoma Research Center (Moffitt Cancer Center);
NIH/National Cancer Institute [U54 CA143970-01]
FX We thank Gideon Bollag at Plexxikon Inc. for providing the PLX4720. This
study was supported by the Melanoma Research Foundation, the
Bankhead-Coley Research Program of the State of Florida (09BN-14), an
Institutional Research Grant from the American Cancer Society 93-032-13,
a Career Development Award from the Donald A Adam Comprehensive Melanoma
Research Center (Moffitt Cancer Center) and the NIH/National Cancer
Institute PSOC grant U54 CA143970-01.
NR 29
TC 149
Z9 151
U1 0
U2 5
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 JUN 8
PY 2010
VL 102
IS 12
BP 1724
EP 1730
DI 10.1038/sj.bjc.6605714
PG 7
WC Oncology
SC Oncology
GA 608NQ
UT WOS:000278591400007
PM 20531415
ER
PT J
AU Nahrendorf, M
Pittet, MJ
Swirski, FK
AF Nahrendorf, Matthias
Pittet, Mikael J.
Swirski, Filip K.
TI Monocytes: Protagonists of Infarct Inflammation and Repair After
Myocardial Infarction
SO CIRCULATION
LA English
DT Article
DE monocyte; atherosclerosis; myocardial infarction; heart failure; wound
healing; remodeling
ID PROINFLAMMATORY CD14(+)CD16(+)DR(++) MONOCYTES; RECEPTOR-DEFICIENT MICE;
HUMAN PERIPHERAL-BLOOD; DENDRITIC CELLS; BONE-MARROW; CHEMOATTRACTANT
PROTEIN-1; IN-VIVO; REDUCES ATHEROSCLEROSIS; LY-6C(HI) MONOCYTES;
BACTERIAL-INFECTION
C1 [Nahrendorf, Matthias] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Nahrendorf, M (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St, Boston, MA 02114 USA.
EM mnahrendorf@mgh.harvard.edu
FU National Institutes of Health [R01HL095629, R01HL096576]; American Heart
Association [SDG0835623D, R01HL095612]
FX This work was funded in part by grants from the National Institutes of
Health (R01HL095629 and R01HL096576) and American Heart Association
(SDG0835623D) to Dr Nahrendorf and Dr Swirski (R01HL095612).
NR 100
TC 236
Z9 244
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 JUN 8
PY 2010
VL 121
IS 22
BP 2437
EP 2445
DI 10.1161/CIRCULATIONAHA.109.916346
PG 9
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 607KW
UT WOS:000278503600008
PM 20530020
ER
PT J
AU Goldfine, AB
Fonseca, V
AF Goldfine, Allison B.
Fonseca, Vivian
TI Management of Diabetes Mellitus in Patients With Cardiovascular Disease
in the Bypass Angioplasty Revascularization Investigation 2 Diabetes
(BARI 2D) Trial
SO CIRCULATION
LA English
DT Editorial Material
DE coronary disease; diabetes mellitus; insulin; revascularization
ID GLUCOSE CONTROL; HEART; RISK; COMPLICATIONS; CONTROVERSY; RESISTANCE;
MORTALITY
C1 [Goldfine, Allison B.] Joslin Diabet Ctr, Sect Clin Res, Boston, MA 02215 USA.
[Goldfine, Allison B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Fonseca, Vivian] Tulane Univ, Hlth Sci Ctr, Endocrinol Sect, New Orleans, LA 70118 USA.
RP Goldfine, AB (reprint author), Joslin Diabet Ctr, Sect Clin Res, 1 Joslin Pl, Boston, MA 02215 USA.
EM Allison.Goldfine@Joslin.Harvard.Edu
NR 19
TC 12
Z9 12
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 JUN 8
PY 2010
VL 121
IS 22
BP 2447
EP 2449
DI 10.1161/CIRCULATIONAHA.109.925883
PG 3
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 607KW
UT WOS:000278503600010
PM 20530022
ER
PT J
AU Vago, H
Toth, A
Apor, A
Maurovich-Horvat, P
Toth, M
Merkely, B
AF Vago, Hajnalka
Toth, Attila
Apor, Astrid
Maurovich-Horvat, Pal
Toth, Miklos
Merkely, Bela
TI Cardiac Contusion in a Professional Soccer Player Visualization of Acute
and Late Pathological Changes in the Myocardium With Magnetic Resonance
Imaging
SO CIRCULATION
LA English
DT Editorial Material
C1 [Vago, Hajnalka; Toth, Attila; Apor, Astrid; Merkely, Bela] Semmelweis Univ, Ctr Heart, H-1122 Budapest, Hungary.
[Toth, Miklos] Semmelweis Univ, Dept Hlth Sci & Sport Med, H-1122 Budapest, Hungary.
[Maurovich-Horvat, Pal] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp,Cardiac MR PET CT Program, Boston, MA 02115 USA.
RP Merkely, B (reprint author), Semmelweis Univ, Ctr Heart, 68 Varosmajor St, H-1122 Budapest, Hungary.
EM merkely.bela@kardio.sote.hu
OI Maurovich-Horvat, Pal/0000-0003-0885-736X
NR 2
TC 10
Z9 11
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 JUN 8
PY 2010
VL 121
IS 22
BP 2456
EP 2461
DI 10.1161/CIRCULATIONAHA.109.917724
PG 6
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 607KW
UT WOS:000278503600013
PM 20530025
ER
PT J
AU Rudd, JHF
Narula, J
Strauss, HW
Virmani, R
Machac, J
Klimas, M
Tahara, N
Fuster, V
Warburton, EA
Fayad, ZA
Tawakol, AA
AF Rudd, James H. F.
Narula, Jagat
Strauss, H. William
Virmani, Renu
Machac, Josef
Klimas, Mike
Tahara, Nobuhiro
Fuster, Valentin
Warburton, Elizabeth A.
Fayad, Zahi A.
Tawakol, Ahmed A.
TI Imaging Atherosclerotic Plaque Inflammation by Fluorodeoxyglucose With
Positron Emission Tomography
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Review
DE atherosclerosis; imaging; positron emission tomography
ID APOLIPOPROTEIN E-DEFICIENT; VASCULAR F-18-FDG UPTAKE; VULNERABLE PLAQUE;
IN-VIVO; FDG-PET; HIGH-FAT; CAROTID ATHEROSCLEROSIS; INTRAPLAQUE
HEMORRHAGE; NOFDG ACCUMULATION; CORONARY-ARTERIES
AB Inflammation is a determinant of atherosclerotic plaque rupture, the event leading to most myocardial infarctions and strokes. Although conventional imaging techniques identify the site and severity of luminal stenosis, the inflammatory status of the plaque is not addressed. Positron emission tomography imaging of atherosclerosis using the metabolic marker fluorodeoxyglucose allows quantification of arterial inflammation across multiple vessels. This review sets out the background and current and potential future applications of this emerging biomarker of cardiovascular risk, along with its limitations. (J Am Coll Cardiol 2010;55:2527-35) (C) 2010 by the American College of Cardiology Foundation
C1 [Rudd, James H. F.; Warburton, Elizabeth A.] Univ Cambridge, Div Cardiovasc Med, Cambridge CB2 2QQ, England.
[Narula, Jagat] Long Beach Mem Hosp Med Ctr, Irvine, CA USA.
[Narula, Jagat] Univ Calif Irvine, Irvine, CA USA.
[Strauss, H. William] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Virmani, Renu] CVPath Inst Inc, Gaithersburg, MD USA.
[Machac, Josef] Mt Sinai Sch Med, Div Nucl Med, New York, NY USA.
[Fuster, Valentin; Fayad, Zahi A.] Mt Sinai Sch Med, Translat & Mol Imaging Inst, New York, NY USA.
[Klimas, Mike] Merck Res Labs, West Point, PA USA.
[Tahara, Nobuhiro] Kurume Univ, Sch Med, Dept Med, Kurume, Fukuoka 830, Japan.
[Tawakol, Ahmed A.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
RP Rudd, JHF (reprint author), Univ Cambridge, Addenbrookes Hosp, Div Cardiovasc Med, ACCI, Box 110,Hills Rd, Cambridge CB2 2QQ, England.
EM jhfr2@cam.ac.uk
RI Fuster, Valentin/H-4319-2015;
OI Fuster, Valentin/0000-0002-9043-9986; Rudd, James/0000-0003-2243-3117
FU NIHR Cambridge Biomedical Center; British Heart Foundation;
GlaxoSmithKline; VIA Pharmaceuticals; WebMD
FX From the *Division of Cardiovascular Medicine, University of Cambridge,
Cambridge, England; +Long Beach Memorial Hospital and University of
California, Irvine, California; Memorial Sloan-Kettering Cancer Center,
New York, New York; CVPath Institute, Inc., Gaithersburg, Maryland;
parallel to Division of Nuclear Medicine, Translational and Molecular
Imaging Institute, Mount Sinai School of Medicine, New York, New York;
#Merck Research Laboratories, West Point, Pennsylvania; **Department of
Medicine, Kurume University School of Medicine, Kurume City, Japan; and
the ++Department of Medicine, Massachusetts General Hospital, Boston,
Massachusetts. Work described in this article was supported by the NIHR
Cambridge Biomedical Center and the British Heart Foundation. Dr. Rudd
is an advisory board member for Roche and BG Medicine, has received
research funding from GlaxoSmithKline, has received consulting fees from
VIA Pharmaceuticals, and has received fees from WebMD for providing
conference coverage on their website. Dr. Machac has relationships with
Phillips, GE Healthcare, and Bristol-Myers Squibb. Dr. Klimas is an
employee of Merck and Co. Dr. Fuster is the Chair of the HRP Study with
BG Medicine. Joseph L. Wu, MD, PhD, served as Guest Editor for this
paper.
NR 93
TC 113
Z9 115
U1 1
U2 14
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 JUN 8
PY 2010
VL 55
IS 23
BP 2527
EP 2535
DI 10.1016/j.jacc.2009.12.061
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 603QJ
UT WOS:000278222800001
PM 20513592
ER
PT J
AU Wijdicks, EFM
Varelas, PN
Gronseth, GS
Greer, DM
AF Wijdicks, Eelco F. M.
Varelas, Panayiotis N.
Gronseth, Gary S.
Greer, David M.
TI Evidence-based guideline update: Determining brain death in adults
Report of the Quality Standards Subcommittee of the American Academy of
Neurology
SO NEUROLOGY
LA English
DT Article
ID GUILLAIN-BARRE-SYNDROME; COMPUTED TOMOGRAPHIC ANGIOGRAPHY; STEM DEATH;
MR-ANGIOGRAPHY; CT ANGIOGRAPHY; DIAGNOSIS; PATIENT; INJURY; MOVEMENTS;
REFLEXES
AB Objective: To provide an update of the 1995 American Academy of Neurology guideline with regard to the following questions: Are there patients who fulfill the clinical criteria of brain death who recover neurologic function? What is an adequate observation period to ensure that cessation of neurologic function is permanent? Are complex motor movements that falsely suggest retained brain function sometimes observed in brain death? What is the comparative safety of techniques for determining apnea? Are there new ancillary tests that accurately identify patients with brain death?
Methods: A systematic literature search was conducted and included a review of MEDLINE and EMBASE from January 1996 to May 2009. Studies were limited to adults ( aged 18 years and older).
Results and recommendations: In adults, there are no published reports of recovery of neurologic function after a diagnosis of brain death using the criteria reviewed in the 1995 American Academy of Neurology practice parameter. Complex-spontaneous motor movements and false-positive triggering of the ventilator may occur in patients who are brain dead. There is insufficient evidence to determine the minimally acceptable observation period to ensure that neurologic functions have ceased irreversibly. Apneic oxygenation diffusion to determine apnea is safe, but there is insufficient evidence to determine the comparative safety of techniques used for apnea testing. There is insufficient evidence to determine if newer ancillary tests accurately confirm the cessation of function of the entire brain. Neurology (R) 2010;74:1911-1918
C1 [Wijdicks, Eelco F. M.] Mayo Clin, Div Crit Care Neurol, Rochester, MN USA.
[Varelas, Panayiotis N.] Henry Ford Hosp, Dept Neurol, Detroit, MI 48202 USA.
[Gronseth, Gary S.] Univ Kansas, Med Ctr, Dept Neurol, Kansas City, KS USA.
[Greer, David M.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
RP Wijdicks, EFM (reprint author), Amer Acad Neurol, 1080 Montreal Ave, St Paul, MN 55116 USA.
EM guidelines@aan.com
NR 39
TC 238
Z9 246
U1 0
U2 21
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD JUN 8
PY 2010
VL 74
IS 23
BP 1911
EP 1918
DI 10.1212/WNL.0b013e3181e242a8
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA 607KU
UT WOS:000278503300012
PM 20530327
ER
PT J
AU Nucera, C
Porrello, A
Antonello, ZA
Mekel, M
Nehs, MA
Giordano, TJ
Gerald, D
Benjamin, LE
Priolo, C
Puxeddu, E
Finn, S
Jarzab, B
Hodin, RA
Pontecorvi, A
Nose, V
Lawler, J
Parangi, S
AF Nucera, Carmelo
Porrello, Alessandro
Antonello, Zeus Andrea
Mekel, Michal
Nehs, Matthew A.
Giordano, Thomas J.
Gerald, Damien
Benjamin, Laura E.
Priolo, Carmen
Puxeddu, Efisio
Finn, Stephen
Jarzab, Barbara
Hodin, Richard A.
Pontecorvi, Alfredo
Nose, Vania
Lawler, Jack
Parangi, Sareh
TI B-Raf(V600E) and thrombospondin-1 promote thyroid cancer progression
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE extracellular matrix; metastasis; papillary thyroid cancer; tumor
microenvironment; cell invasion
ID GENE-EXPRESSION; ALPHA-3-BETA-1 INTEGRIN; BREAST-CANCER; GROWTH-FACTOR;
CARCINOMA; BRAF; MUTATION; METASTASIS; PROFILES; MELANOMA
AB Although B-Raf(V600E) is the most common somatic mutation in papillary thyroid carcinoma (PTC), how it induces tumor aggressiveness is not fully understood. Using gene set enrichment analysis and in vitro and in vivo functional studies, we identified and validated a B-Raf(V600E) gene set signature associated with tumor progression in PTCs. An independent cohort of B-Raf(V600E)-positive PTCs showed significantly higher expression levels of many extracellular matrix genes compared with controls. We performed extensive in vitro and in vivo validations on thrombospondin-1 (TSP-1), because it has been previously shown to be important in the regulation of tumor angiogenesis and metastasis and is present in abundance in tumor stroma. Knockdown of B-Raf(V600E) resulted in TSP-1 down-regulation and a reduction of adhesion and migration/invasion of human thyroid cancer cells. Knockdown of TSP-1 resulted in a similar phenotype. B-Raf(V600E) cells in which either B-Raf(V600E) or TSP-1 were knocked down were implanted orthotopically into the thyroids of immunocompromised mice, resulting in significant reduction in tumor size and fewer pulmonary metastases from the primary carcinoma as compared with the control cells. Treatment of orthotopic thyroid tumors, initiated 1 week after tumor cell implantation with PLX4720, an orally available selective inhibitor of B-Raf(V600E), caused a significant tumor growth delay and decreased distant metastases, without evidence of toxicity. In conclusion, B-Raf(V600E) plays an important role in PTC progression through genes (i.e., TSP-1) important in tumor invasion and metastasis. Testing of a patient's thyroid cancer for B-Raf(V600E) will yield important information about potential tumor aggressiveness and also allow for future use of targeted therapies with selective B-Raf(V600E) inhibitors, such as PLX4720.
C1 [Nucera, Carmelo; Mekel, Michal; Nehs, Matthew A.; Hodin, Richard A.; Parangi, Sareh] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Thyroid Canc Res Lab,Endocrine Surg Unit, Boston, MA 02114 USA.
[Nucera, Carmelo; Antonello, Zeus Andrea; Lawler, Jack] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Canc Biol & Angiogenesis,Dept Pathol, Boston, MA 02115 USA.
[Porrello, Alessandro] Duke Univ, Inst Genome Sci & Policy, Durham, NC 27710 USA.
[Giordano, Thomas J.] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA.
[Priolo, Carmen; Finn, Stephen] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Puxeddu, Efisio] Univ Perugia, Dept Med, Endocrinol Unit, I-06126 Perugia, Italy.
[Jarzab, Barbara] Maria Sklodowska Curie Mem Canc Ctr & Inst Oncol, Dept Nucl Med & Endocrine Oncol, PL-44100 Gliwice, Poland.
[Pontecorvi, Alfredo] Catholic Univ, Med Sch A Gemelli, Endocrinol Unit, I-00168 Rome, Italy.
[Nose, Vania] Harvard Univ, Dept Pathol, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
RP Parangi, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Thyroid Canc Res Lab,Endocrine Surg Unit, Boston, MA 02114 USA.
EM sparangi@partners.org
RI Puxeddu, Efisio/I-8188-2012;
OI Giordano, Thomas/0000-0003-0641-8873; Finn, Stephen/0000-0002-8628-5814
FU PhD Fellowship in Experimental Endocrinology and Metabolic Diseases,
Italy; National Institutes of Health [CA130895]; Massachusetts General
Hospital Faculty; Polsky Family Fund; American Thyroid Association
FX We thank Dr. Yutaka Kawami (Keio University, Japan) for kindly providing
the vectors HIV-U6; Dr. W. C. Hahn [Harvard Medical School (HMS)] for
providing BJ cells and pLKO and pBABE constructs; Mr. Mark Duquette and
James Lawler for technical assistance; Drs. Shou-Ching Shih,
Michelangelo Fiorentino, Amrik Singh, and Peter Sadow for help with the
real-time RT-PCR experiments, Ariol instrument SL-50, anti-tag-cmyc
antibody, and MMP-9 and VEGF immunohistochemistry, respectively; Drs.
Gideon Bollag and Paul Lin (Plexxikon) for providing PLX4720 and for
technical assistance; and Dr. PierPaolo Pandolfi (HMS) for helpful
suggestions. C.N. was a recipient of a PhD Fellowship in Experimental
Endocrinology and Metabolic Diseases funded from Italy and carried out
at HMS. This study was funded through National Institutes of Health
Grant CA130895 (to S. P. and J.L.) and from the Massachusetts General
Hospital Faculty Development Fund, Polsky Family Fund, and American
Thyroid Association (S. P.).
NR 30
TC 89
Z9 91
U1 1
U2 8
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 JUN 8
PY 2010
VL 107
IS 23
BP 10649
EP 10654
DI 10.1073/pnas.1004934107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 608AH
UT WOS:000278549300058
PM 20498063
ER
PT J
AU Hock, H
AF Hock, Hanno
TI Some hematopoietic stem cells are more equal than others
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Review
ID SELF-RENEWAL CAPACITY; MULTIPOTENT PROGENITORS; BONE-MARROW;
RECONSTITUTION; HOMEOSTASIS; MECHANISM; EXPANSION; MICE
AB Hematopoietic stem cells (HSCs) save lives in routine clinical practice every day, as they are the key element in transplantation-based therapies for hematologic malignancies. The success of clinical stem cell transplantation critically relies on the ability of stem cells to reconstitute the hematopoietic system for many decades after the administration of the powerful chemotherapy and/or irradiation that is required to eradicate malignant cells, but also irreversibly ablates patients' own blood forming capacity. Surprisingly, despite enormous efforts and continuous progress in the field, our understanding of the basic biology of HSCs is still rather incomplete. Several recent studies substantially refine our understanding of the cells at the very top of the hematopoietic hierarchy, and suggest that we may need to revise the criteria we typically use to identify and define HSCs.
C1 [Hock, Hanno] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02114 USA.
[Hock, Hanno] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med, Boston, MA 02114 USA.
[Hock, Hanno] Harvard Stem Cell Inst, Boston, MA 02114 USA.
RP Hock, H (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02114 USA.
EM Hock.Hanno@mgh.harvard.edu
FU National Cancer Institute [R01CA122726]
FX This work was supported by National Cancer Institute grant R01CA122726.
NR 29
TC 14
Z9 14
U1 0
U2 3
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 JUN 7
PY 2010
VL 207
IS 6
BP 1127
EP 1130
DI 10.1084/jem.20100950
PG 4
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 608AV
UT WOS:000278554200001
PM 20513745
ER
PT J
AU Westerberg, LS
Meelu, P
Baptista, M
Eston, MA
Adamovich, DA
Cotta-de-Almeida, V
Seed, B
Rosen, MK
Vandenberghe, P
Thrasher, AJ
Klein, C
Alt, FW
Snapper, SB
AF Westerberg, Lisa S.
Meelu, Parool
Baptista, Marisa
Eston, Michelle A.
Adamovich, David A.
Cotta-de-Almeida, Vinicius
Seed, Brian
Rosen, Michael K.
Vandenberghe, Peter
Thrasher, Adrian J.
Klein, Christoph
Alt, Frederick W.
Snapper, Scott B.
TI Activating WASP mutations associated with X-linked neutropenia result in
enhanced actin polymerization, altered cytoskeletal responses, and
genomic instability in lymphocytes
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID WISKOTT-ALDRICH-SYNDROME; SEVERE CONGENITAL NEUTROPENIA; SYNDROME
PROTEIN; N-WASP; DEFICIENCY LEADS; STEM-CELLS; GENE; HOMEOSTASIS;
MIGRATION; DEFECTS
AB X-linked neutropenia (XLN) is caused by activating mutations in the Wiskott-Aldrich syndrome protein ( WASP) that result in aberrant autoinhibition. Although patients with XLN appear to have only defects in myeloid lineages, we hypothesized that activating mutations of WASP are likely to affect the immune system more broadly. We generated mouse models to assess the role of activating WASP mutations associated with XLN (XLN-WASP) in lymphocytes. XLN-WASP is expressed stably in B and T cells and induces a marked increase in polymerized actin. XLN-WASP-expressing B and T cells migrate toward chemokines but fail to adhere normally. In marked contrast to WASP-deficient cells, XLN-WASP-expressing T cells proliferate normally in response to cell-surface receptor activation. However, XLN-WASP-expressing B cells fail to proliferate and secrete lower amounts of antibodies. Moreover, XLN-WASP expression in lymphocytes results in modestly increased apoptosis associated with increased genomic instability. These data indicate that there are unique requirements for the presence and activation status of WASP in B and T cells and that WASP-activating mutations interfere with lymphocyte cell survival and genomic stability.
C1 [Westerberg, Lisa S.; Meelu, Parool; Eston, Michelle A.; Adamovich, David A.; Cotta-de-Almeida, Vinicius; Snapper, Scott B.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
[Westerberg, Lisa S.; Meelu, Parool; Eston, Michelle A.; Adamovich, David A.; Cotta-de-Almeida, Vinicius; Snapper, Scott B.] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA.
[Seed, Brian] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA.
[Westerberg, Lisa S.; Meelu, Parool; Eston, Michelle A.; Adamovich, David A.; Cotta-de-Almeida, Vinicius; Snapper, Scott B.] Harvard Univ, Sch Med, Immune Dis Inst, Childrens Hosp Boston,Dept Med, Boston, MA 02115 USA.
[Seed, Brian; Alt, Frederick W.] Harvard Univ, Sch Med, Immune Dis Inst, Childrens Hosp Boston,Dept Genet, Boston, MA 02115 USA.
[Alt, Frederick W.] Harvard Univ, Sch Med, Immune Dis Inst, Childrens Hosp Boston,Howard Hughes Med Inst, Boston, MA 02115 USA.
[Westerberg, Lisa S.; Baptista, Marisa] Karolinska Inst, Dept Med, Unit Clin Allergy Res, S-17176 Stockholm, Sweden.
[Cotta-de-Almeida, Vinicius] Fundacao Oswaldo Cruz, Inst Oswaldo Cruz, BR-21045900 Rio De Janeiro, Brazil.
[Rosen, Michael K.] Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX 75390 USA.
[Rosen, Michael K.] Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA.
[Vandenberghe, Peter] Univ Hosp Leuven, Ctr Human Genet, B-3000 Louvain, Belgium.
[Vandenberghe, Peter] Univ Hosp Leuven, Dept Hematol, B-3000 Louvain, Belgium.
Univ Louvain, B-3000 Louvain, Belgium.
[Thrasher, Adrian J.] UCL, UCL Inst Child Hlth, Mol Immunol Unit, London WC1N 1EH, England.
[Klein, Christoph] Hannover Med Sch, Dept Pediat Hematol & Oncol, D-30625 Hannover, Germany.
RP Snapper, SB (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
EM ssnapper@hms.harvard.edu
RI Cotta-de-Almeida, Vinicius/G-3939-2012;
OI Vandenberghe, Peter/0000-0003-4719-1935; Westerberg,
Lisa/0000-0003-2943-2192
FU Wenner-Gren foundation; Wellcome Trust; National Institutes of Health
(NIH) [HL59561]; United States Immunodeficiency Network-NIH [AI30070];
Fonds voor Wetenschappelijk Onderzoek-Vlaanderen
FX This work was supported by a postdoctoral fellowship from the
Wenner-Gren foundation to L.S. Westerberg, by Wellcome Trust grants to
A.J. Thrasher, and by National Institutes of Health (NIH) grant HL59561
to S. B. Snapper and United States Immunodeficiency Network-NIH grant
AI30070 to L.S. Westerberg and S.B. Snapper. P. Vandenberghe is a senior
clinical investigator for Fonds voor Wetenschappelijk
Onderzoek-Vlaanderen.
NR 33
TC 23
Z9 23
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 JUN 7
PY 2010
VL 207
IS 6
BP 1145
EP 1152
DI 10.1084/jem.20091245
PG 8
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 608AV
UT WOS:000278554200004
PM 20513746
ER
PT J
AU Duy, C
Yu, JJ
Nahar, R
Swaminathan, S
Kweon, SM
Polo, JM
Valls, E
Klemm, L
Shojaee, S
Cerchietti, L
Schuh, W
Jack, HM
Hurtz, C
Ramezani-Rad, P
Herzog, S
Jumaa, H
Koeffler, HP
de Alboran, IM
Melnick, AM
Ye, BH
Muschen, M
AF Duy, Cihangir
Yu, J. Jessica
Nahar, Rahul
Swaminathan, Srividya
Kweon, Soo-Mi
Polo, Jose M.
Valls, Ester
Klemm, Lars
Shojaee, Seyedmehdi
Cerchietti, Leandro
Schuh, Wolfgang
Jaeck, Hans-Martin
Hurtz, Christian
Ramezani-Rad, Parham
Herzog, Sebastian
Jumaa, Hassan
Koeffler, H. Phillip
Moreno de Alboran, Ignacio
Melnick, Ari M.
Ye, B. Hilda
Mueschen, Markus
TI BCL6 is critical for the development of a diverse primary B cell
repertoire
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID GERMINAL-CENTER FORMATION; PRE-B; TRANSCRIPTIONAL REPRESSION; CYCLE
ARREST; GENE; EXPRESSION; RECEPTOR; PROLIFERATION; INHIBITOR; LEUKEMIA
AB BCL6 protects germinal center ( GC) B cells against DNA damage-induced apoptosis during somatic hypermutation and class-switch recombination. Although expression of BCL6 was not found in early IL-7-dependent B cell precursors, we report that IL-7R alpha-Stat5 signaling negatively regulates BCL6. Upon productive V(H)-DJ(H) gene rearrangement and expression of a. heavy chain, however, activation of pre-B cell receptor signaling strongly induces BCL6 expression, whereas IL-7R alpha-Stat5 signaling is attenuated. At the transition from IL-7-dependent to -independent stages of B cell development, BCL6 is activated, reaches expression levels resembling those in GC B cells, and protects pre-B cells from DNA damage-induced apoptosis during immunoglobulin (Ig) light chain gene recombination. In the absence of BCL6, DNA breaks during Ig light chain gene rearrangement lead to excessive up-regulation of Arf and p53. As a consequence, the pool of new bone marrow immature B cells is markedly reduced in size and clonal diversity. We conclude that negative regulation of Arf by BCL6 is required for pre-B cell self-renewal and the formation of a diverse polyclonal B cell repertoire.
C1 [Duy, Cihangir; Nahar, Rahul; Swaminathan, Srividya; Kweon, Soo-Mi; Klemm, Lars; Shojaee, Seyedmehdi; Hurtz, Christian; Ramezani-Rad, Parham; Mueschen, Markus] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA.
[Duy, Cihangir; Nahar, Rahul; Swaminathan, Srividya; Kweon, Soo-Mi; Klemm, Lars; Shojaee, Seyedmehdi; Hurtz, Christian; Ramezani-Rad, Parham; Mueschen, Markus] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Leukemia & Lymphoma Program, Los Angeles, CA 90027 USA.
[Duy, Cihangir] Univ Dusseldorf, D-40225 Dusseldorf, Germany.
[Yu, J. Jessica; Ye, B. Hilda] Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10461 USA.
[Polo, Jose M.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
[Polo, Jose M.] Harvard Stem Cell Inst, Boston, MA 02114 USA.
[Valls, Ester; Cerchietti, Leandro; Melnick, Ari M.] Weill Cornell Med Coll, Dept Med, New York, NY 10065 USA.
[Valls, Ester; Cerchietti, Leandro; Melnick, Ari M.] Weill Cornell Med Coll, Dept Pharmacol, New York, NY 10065 USA.
[Schuh, Wolfgang; Jaeck, Hans-Martin] Univ Erlangen Nurnberg, Nikolaus Fiebiger Ctr Mol Med, Div Mol Immunol, D-91054 Erlangen, Germany.
[Herzog, Sebastian; Jumaa, Hassan] Max Planck Inst Immunobiol, D-79108 Freiburg, Germany.
[Koeffler, H. Phillip] Natl Univ Singapore, Cedars Sinai Med Ctr, Singapore 119077, Singapore.
[Koeffler, H. Phillip] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Moreno de Alboran, Ignacio] Ctr Nacl Biotecnol, Madrid 28049, Spain.
RP Muschen, M (reprint author), Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA.
EM mmuschen@chla.usc.edu
OI Jack, Hans-Martin/0000-0002-6332-8463; Cerchietti,
Leandro/0000-0003-0608-1350
FU National Institutes of Health/National Cancer Institute [R01CA104348,
5R01CA085573, R01CA137060, R01CA139032, R21CA152497]; Leukemia and
Lymphoma Society [6132-09, 6097-10]; V Foundation for Cancer Research;
William Laurence and Blanche Hughes Foundation; Stand Up to
Cancer-American Association for Cancer Research Innovative Research
[IRG00909]; Deutsche Forschungsgemeinschaft [MU1616/5-1]
FX This work was supported by grants from the National Institutes of
Health/National Cancer Institute (R01CA104348 to A.M. Melnick,
5R01CA085573 to B.H. Ye, and R01CA137060, R01CA139032, and R21CA152497
to M. Muschen), Translational Research Program grants from the Leukemia
and Lymphoma Society (6132-09 and 6097-10), the V Foundation for Cancer
Research (M. Muschen), the William Laurence and Blanche Hughes
Foundation and a Stand Up to Cancer-American Association for Cancer
Research Innovative Research Grant (IRG00909 to M. Muschen), and a grant
from the Deutsche Forschungsgemeinschaft (MU1616/5-1). A.M. Melnick and
M. Muschen are Scholars of the Leukemia and Lymphoma Society.
NR 44
TC 58
Z9 59
U1 0
U2 3
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 JUN 7
PY 2010
VL 207
IS 6
BP 1209
EP 1221
DI 10.1084/jem.20091299
PG 13
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 608AV
UT WOS:000278554200010
PM 20498019
ER
PT J
AU Forrest, GN
Kopack, AM
Perencevich, EN
AF Forrest, Graeme N.
Kopack, Angela M.
Perencevich, Eli N.
TI Statins in Candidemia: clinical outcomes from a matched cohort study
SO BMC INFECTIOUS DISEASES
LA English
DT Article
ID POPULATION-BASED COHORT; FLUCONAZOLE THERAPY; SEVERE SEPSIS; MORTALITY;
HOSPITALIZATION; CANDIDAEMIA; INFECTIONS; PROTECTION; CYTOKINES;
ALBICANS
AB Background: HMG CoA reductase inhibitors (statins) in patients with bacteremic sepsis have shown significant survival benefits in several studies. There is no data on the effect of statins in candidemic patients, however in-vitro models suggest that statins interfere with ergesterol formation in the wall of yeasts.
Methods: This retrospective matched-cohort study from 1/2003 to 12/2006 evaluated the effects of statins on patients with candidemia within intensive care units. Statin-users had candidemia as a cause of their systemic inflammatory response and were on statins throughout their antifungal therapy, while non-statin users were matched based on age +/-5 years and co-morbid factors. Primary analysis was 30-day survival or discharge using bivariable comparisons. Multivariable comparisons were completed using conditional logistic regression. All variables with a p-value less than 0.10 in the bivariable comparisons were considered for inclusion in the conditional logistic model.
Results: There were 15 statin-users and 30 non-statin users that met inclusion criteria, all with similar demographics and co-morbid conditions except the statin group had more coronary artery disease (P < 0.01) and peripheral vascular disease (P = 0.03) and lower median APCAHE II scores (14.6 vs 17, p = 0.03). There were no differences in duration of candidemia, antifungal therapy or Candida species between the groups. Statins were associated with lower mortality on bivariable (OR 0.09, 95% Cl 0.11-0.75, p = 0.03) and multivariable (OR 0.22, 95% Cl 0.02-2.4, p = 0.21) analyses compared to controls; although, in the latter the protective effect lacked statistical signficance.
Conclusion: In our small, single-center matched-cohort study, statins may provide a survival benefit in candidemia, however further studies are warranted to validate and further explore this association.
C1 [Forrest, Graeme N.] Oregon Hlth & Sci Univ, Div Infect Dis, Portland, OR 97239 USA.
[Forrest, Graeme N.] Portland VA Med Ctr, Portland, OR 97239 USA.
[Kopack, Angela M.] Infect Dis Associates, Ellicott City, MD 21201 USA.
[Perencevich, Eli N.] Univ Iowa, Carver Coll Med, Iowa City VA Med Ctr, Iowa City, IA 52242 USA.
RP Forrest, GN (reprint author), Oregon Hlth & Sci Univ, Div Infect Dis, 3701 SW US Vet Hosp Rd,P3-ID, Portland, OR 97239 USA.
EM forrestg@ohsu.edu
NR 30
TC 14
Z9 16
U1 0
U2 0
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2334
J9 BMC INFECT DIS
JI BMC Infect. Dis.
PD JUN 4
PY 2010
VL 10
AR 152
DI 10.1186/1471-2334-10-152
PG 8
WC Infectious Diseases
SC Infectious Diseases
GA 625LK
UT WOS:000279896600002
PM 20525374
ER
PT J
AU Buecker, C
Chen, HH
Polo, JM
Daheron, L
Bu, L
Barakat, TS
Okwieka, P
Porter, A
Gribnau, J
Hochedlinger, K
Geijsen, N
AF Buecker, Christa
Chen, Hsu-Hsin
Polo, Jose Maria
Daheron, Laurence
Bu, Lei
Barakat, Tahsin Stefan
Okwieka, Patricia
Porter, Andrew
Gribnau, Joost
Hochedlinger, Konrad
Geijsen, Niels
TI A Murine ESC-like State Facilitates Transgenesis and Homologous
Recombination in Human Pluripotent Stem Cells
SO CELL STEM CELL
LA English
DT Article
ID HUMAN BLASTOCYSTS; MOUSE EMBRYOS; GROUND-STATE; SELF-RENEWAL;
METHYLATION; CHROMATIN; EPIBLAST; LINES; DIFFERENTIATION; GENERATION
AB Murine pluripotent stem cells can exist in two functionally distinct states, LIF-dependent embryonic stem cells (ESCs) and bFGF-dependent epiblast stem cells (EpiSCs). However, human pluripotent cells so far seemed to assume only an epiblast-like state. Here we demonstrate that human iPSC reprogramming in the presence of LIF yields human stem cells that display morphological, molecular, and functional properties of murine ESCs. We termed these hLR5 iPSCs because they require the expression of five ectopic reprogramming factors, Oct4, Sox2, Klf4, cMyc, and Nanog, to maintain this more naive state. The cells are "metastable" and upon ectopic factor withdrawal they revert to standard human iPSCs. Finally, we demonstrate that the hLR5 state facilitates gene targeting, and as such provides a powerful tool for the generation of recombinant human pluripotent stem cell lines.
C1 [Buecker, Christa; Chen, Hsu-Hsin; Polo, Jose Maria; Daheron, Laurence; Okwieka, Patricia; Hochedlinger, Konrad; Geijsen, Niels] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med, Boston, MA 02114 USA.
[Polo, Jose Maria; Hochedlinger, Konrad] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02114 USA.
[Bu, Lei] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Buecker, Christa; Chen, Hsu-Hsin; Polo, Jose Maria; Daheron, Laurence; Bu, Lei; Hochedlinger, Konrad; Geijsen, Niels] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
[Hochedlinger, Konrad] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
[Barakat, Tahsin Stefan; Gribnau, Joost] Univ Med Ctr, Erasmus MC, Dept Reprod & Dev, NL-3000 CA Rotterdam, Netherlands.
[Porter, Andrew] Univ London Imperial Coll Sci Technol & Med, Gene Therapy Grp, Dept Haematol, London W12 0NN, England.
[Geijsen, Niels] Hubrecht Inst Dev Biol & Stem Cell Res, NL-3584 CT Utrecht, Netherlands.
RP Geijsen, N (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med, Boston, MA 02114 USA.
EM ngeijsen@mgh.harvard.edu
RI Bu, Lei/F-4461-2011;
OI Buecker, Christa/0000-0003-3055-2642; Barakat,
Stefan/0000-0003-1231-1562; Polo, Jose M/0000-0002-2531-778X
FU NIH; Dutch Science Organization (NWO); Gottlieb Daimler- and Karl
Benz-Foundation; National Science Council (Taiwan, ROC)
FX The authors thank Tim Ahfeldt, Nimet Maherali, and Chad Cowan for
providing human iPSCs, Laura Prickett-Rice and Kat Folz-Donahue at the
HSCI/MGH Flow Cytometry Core facility cell sorting; and Jason West and
Meredith Bryden for technical support. This work was supported by grants
from the NIH and a grant from the Dutch Science Organization (NWO). C.B.
was supported by the Gottlieb Daimler- and Karl Benz-Foundation. H.-H.C.
was supported by the National Science Council (Taiwan, ROC).
NR 36
TC 126
Z9 131
U1 1
U2 8
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1934-5909
J9 CELL STEM CELL
JI Cell Stem Cell
PD JUN 4
PY 2010
VL 6
IS 6
BP 535
EP 546
DI 10.1016/j.stem.2010.05.003
PG 12
WC Cell & Tissue Engineering; Cell Biology
SC Cell Biology
GA 611SB
UT WOS:000278840700014
PM 20569691
ER
PT J
AU Aiden, AP
Rivera, MN
Rheinbay, E
Ku, MC
Coffman, EJ
Truong, TT
Vargas, SO
Lander, ES
Haber, DA
Bernstein, BE
AF Aiden, Aviva Presser
Rivera, Miguel N.
Rheinbay, Esther
Ku, Manching
Coffman, Erik J.
Truong, Thanh T.
Vargas, Sara O.
Lander, Eric S.
Haber, Daniel A.
Bernstein, Bradley E.
TI Wilms Tumor Chromatin Profiles Highlight Stem Cell Properties and a
Renal Developmental Network
SO CELL STEM CELL
LA English
DT Article
ID WOLF-HIRSCHHORN-SYNDROME; MICE LACKING GDNF; GENE-EXPRESSION; KIDNEY
DEVELOPMENT; HUMAN CANCER; MAMMALIAN KIDNEY; NONCODING RNAS; GENOME;
METHYLATION; LOCUS
AB Wilms tumor is the most common pediatric kidney cancer. To identify transcriptional and epigenetic mechanisms that drive this disease, we compared genome-wide chromatin profiles of Wilms tumors, embryonic stem cells (ESCs), and normal kidney. Wilms tumors prominently exhibit large active chromatin domains previously observed in ESCs. In the cancer, these domains frequently correspond to genes that are critical for kidney development and expressed in the renal stem cell compartment. Wilms cells also express "embryonic" chromatin regulators and maintain stem cell-like p16 silencing. Finally, Wilms and ESCs both exhibit "bivalent" chromatin modifications at silent promoters that may be poised for activation. In Wilms tumor, bivalent promoters correlate to genes expressed in specific kidney compartments and point to a kidney-specific differentiation program arrested at an early-progenitor stage. We suggest that Wilms cells share a transcriptional and epigenetic landscape with a normal renal stem cell, which is inherently susceptible to transformation and may represent a cell of origin for this disease.
C1 [Aiden, Aviva Presser; Rivera, Miguel N.; Rheinbay, Esther; Ku, Manching; Truong, Thanh T.; Lander, Eric S.; Haber, Daniel A.; Bernstein, Bradley E.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA.
[Aiden, Aviva Presser] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
[Rivera, Miguel N.; Rheinbay, Esther; Ku, Manching; Truong, Thanh T.; Bernstein, Bradley E.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Rivera, Miguel N.; Rheinbay, Esther; Ku, Manching; Truong, Thanh T.; Bernstein, Bradley E.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Rivera, Miguel N.; Rheinbay, Esther; Ku, Manching; Coffman, Erik J.; Truong, Thanh T.; Haber, Daniel A.; Bernstein, Bradley E.] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA.
[Rheinbay, Esther; Ku, Manching; Truong, Thanh T.; Bernstein, Bradley E.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA.
[Rivera, Miguel N.; Rheinbay, Esther; Ku, Manching; Coffman, Erik J.; Truong, Thanh T.; Haber, Daniel A.; Bernstein, Bradley E.] Boston Univ, Howard Hughes Med Inst, Boston, MA 02115 USA.
[Rheinbay, Esther] Boston Univ, Bioinformat Program, Boston, MA 02115 USA.
[Rheinbay, Esther] Boston Univ, Dept Biomed Engn, Boston, MA 02115 USA.
[Vargas, Sara O.] Childrens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Vargas, Sara O.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Lander, Eric S.] MIT, Dept Biol, Cambridge, MA 02142 USA.
RP Bernstein, BE (reprint author), Broad Inst Harvard & MIT, Cambridge, MA 02142 USA.
EM bernstein.bradley@mgh.harvard.edu
FU National Defense Science and Engineering; NIDDK [K08DK080175]; Burroughs
Wellcome Fund; Howard Hughes Medical Institute; MGH; Croucher
Foundation; National Cancer Institute [R37CA058596, P50CA101942];
National Human Genome Research Institute
FX We thank Mazhar Adli, Alexa Burger, Chuck Epstein, and Noam Shoresh for
helpful discussions and Erez Lieberman-Aiden for editing the manuscript.
A.P.A. was supported by a National Defense Science and Engineering
Graduate Fellowship. M.N.R. is supported by awards from the NIDDK
(K08DK080175), the Burroughs Wellcome Fund, the Howard Hughes Medical
Institute, and MGH. M.K. was supported by a fellowship from the Croucher
Foundation. D.A.H. is an Investigator of the Howard Hughes Medical
Institute and is also supported by grants from the National Cancer
Institute (R37CA058596 and P50CA101942). B.E.B. is a Charles E. Culpeper
Medical Scholar and an Early Career Scientist of the Howard Hughes
Medical Institute. This research was supported by funds from the
National Human Genome Research Institute, the National Cancer Institute,
and the Burroughs Wellcome Fund.
NR 70
TC 45
Z9 46
U1 0
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1934-5909
J9 CELL STEM CELL
JI Cell Stem Cell
PD JUN 4
PY 2010
VL 6
IS 6
BP 591
EP 602
DI 10.1016/j.stem.2010.03.016
PG 12
WC Cell & Tissue Engineering; Cell Biology
SC Cell Biology
GA 611SB
UT WOS:000278840700019
PM 20569696
ER
PT J
AU Zeng, M
Kikuchi, H
Pino, MS
Chung, DC
AF Zeng, Min
Kikuchi, Hirotoshi
Pino, Maria S.
Chung, Daniel C.
TI Hypoxia Activates the K-Ras Proto-Oncogene to Stimulate Angiogenesis and
Inhibit Apoptosis in Colon Cancer Cells
SO PLOS ONE
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; SIGNALING PATHWAYS; UP-REGULATION;
EXPRESSION; ERK1/2; AKT; PROLIFERATION; INTERLEUKIN-8; METABOLISM;
INDUCTION
AB The KRAS proto-oncogene plays a key role in the development of many human tumors and is commonly activated by somatic mutation or signaling through specific growth factor receptors. However, the interaction between the micro-environment and K-ras activity has not been defined. Hypoxia invariably develops as tumors outgrow their supply of oxygen. A series of well-orchestrated cellular adaptations occur that stimulate angiogenesis and enhance survival of the tumor in hypoxic conditions. Our previous studies demonstrated that mutant KRAS alleles can interact with hypoxia to induce vascular endothelial growth factor (VEGF) in colon cancer. We sought to determine whether similar hypoxic responses are also present in tumors without a KRAS mutation. Hypoxia consistently increased the levels of activated, GTP-bound K-ras in colon cancer cell lines with a wild-type KRAS gene, and this depended upon the activation of c-Src. Inhibition of c-Src by PP2 treatment or siRNA knockdown blocked the hypoxic activation of K-ras. This activation of K-ras did not depend upon EGFR and resulted in the phosphorylation of Akt and induction of VEGF expression. In addition, activation of K-ras significantly blocked apoptosis in hypoxic conditions. These studies reveal a unique adaptive mechanism in hypoxia that activates K-ras signaling in the absence of a mutant KRAS oncogene.
C1 [Zeng, Min; Kikuchi, Hirotoshi; Pino, Maria S.; Chung, Daniel C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit,Dept Med, Boston, MA 02115 USA.
RP Zeng, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit,Dept Med, Boston, MA 02115 USA.
EM dchung@partners.org
FU National Institutes of Health [CA92594]; Kate J. and Dorothy L. Clapp
Fund
FX This work was funded by National Institutes of Health grant CA92594;
Kate J. and Dorothy L. Clapp Fund. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 26
TC 20
Z9 21
U1 1
U2 2
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 JUN 4
PY 2010
VL 5
IS 6
AR e10966
DI 10.1371/journal.pone.0010966
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 605XA
UT WOS:000278380500011
PM 20532039
ER
PT J
AU Reeves, RK
Gillis, J
Wong, FE
Yu, Y
Connole, M
Johnson, RP
AF Reeves, R. Keith
Gillis, Jacqueline
Wong, Fay E.
Yu, Yi
Connole, Michelle
Johnson, R. Paul
TI CD16(-) natural killer cells: enrichment in mucosal and secondary
lymphoid tissues and altered function during chronic SIV infection
SO BLOOD
LA English
DT Article
ID SIMIAN IMMUNODEFICIENCY VIRUS; ACUTE HIV-1 INFECTION; RHESUS MACAQUES;
NK CELL; T-LYMPHOCYTES; HLA-B; EXPRESSION; ACTIVATION; INNATE; SUBSET
AB Natural killer (NK) cells contribute to control of HIV/SIV infection. We defined macaque NK-cell subsets based on expression of CD56 and CD16 and found their distribution to be highly disparate. CD16(+) NK cells predominated in peripheral blood, whereas most mucosal NK cells were CD56(+), and lymph nodes contained both CD56(+) and CD16(-)CD56(-) (double-negative [DN]) subsets. Functional profiles were also distinct among subsets CD16(+) NK cells expressed high levels of cytolytic molecules, and CD56(+) NK cells were predominantly cytokine-secreting cells, whereas DN NK possessed both functions. In macaques chronically infected with SIV, circulating CD16(+) and DN NK cells were expanded in number and, although markers of cytoxicity increased, cytokine secretion decreased. Notably, CD56(+) NK cells in SIV-infected animals up-regulated perforin, granzyme B, and CD107a. In contrast, the lymph node homing molecules CD62 ligand (CD62L) and C-C chemokine receptor type 7 (CCR7), which are expressed primarily on CD56(+) and DN NK cells, were significantly down-regulated on NK cells from infected animals. These data demonstrate that SIV infection drives a shift in NK-cell function characterized by decreased cytokine production, expanded cytotoxicity, and trafficking away from secondary lymphoid organs, suggesting that the NK-cell repertoire is not only heterogeneous but also plastic. (Blood. 2010; 115(22): 4439-4446)
C1 [Reeves, R. Keith; Gillis, Jacqueline; Wong, Fay E.; Yu, Yi; Connole, Michelle; Johnson, R. Paul] Harvard Univ, Sch Med, Div Immunol, New England Primate Res Ctr, Southborough, MA 01772 USA.
[Johnson, R. Paul] Massachusetts Gen Hosp, Ragon Inst, MIT, Boston, MA 02114 USA.
[Johnson, R. Paul] Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA.
[Johnson, R. Paul] Harvard Univ, Boston, MA 02115 USA.
RP Johnson, RP (reprint author), Harvard Univ, Sch Med, Div Immunol, New England Primate Res Ctr, 1 Pine Hill Dr,Southborough Campus, Southborough, MA 01772 USA.
EM paul_johnson@hms.harvard.edu
FU National Institutes of Health [AI062412, AI071306, RR00168]; Center for
HIV/AIDS Vaccine Immunology/HIV Vaccine Trials Network Early Career
Investigator [U19AI 067854-04]
FX This work was supported through National Institutes of Health grants
AI062412, AI071306, and RR00168, and a Center for HIV/AIDS Vaccine
Immunology/HIV Vaccine Trials Network Early Career Investigator award,
grant number U19AI 067854-04 (R. K. R.).
NR 50
TC 59
Z9 60
U1 0
U2 3
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD JUN 3
PY 2010
VL 115
IS 22
BP 4439
EP 4446
DI 10.1182/blood-2010-01-265595
PG 8
WC Hematology
SC Hematology
GA 605UN
UT WOS:000278372600021
PM 20339088
ER
PT J
AU Kumar, R
Shah, P
Swiatlo, E
Burgess, SC
Lawrence, ML
Nanduri, B
AF Kumar, Ranjit
Shah, Pratik
Swiatlo, Edwin
Burgess, Shane C.
Lawrence, Mark L.
Nanduri, Bindu
TI Identification of novel non-coding small RNAs from Streptococcus
pneumoniae TIGR4 using high-resolution genome tiling arrays
SO BMC GENOMICS
LA English
DT Article
ID BACILLUS-SUBTILIS; ESCHERICHIA-COLI; GENE-EXPRESSION; SOLUBLE-RNAS;
PSEUDOMONAS-AERUGINOSA; MICROARRAY DATA; ENCODING GENES; MESSENGER-RNA;
OPERON; PREDICTION
AB Background: The identification of non-coding transcripts in human, mouse, and Escherichia coli has revealed their widespread occurrence and functional importance in both eukaryotic and prokaryotic life. In prokaryotes, studies have shown that non-coding transcripts participate in a broad range of cellular functions like gene regulation, stress and virulence. However, very little is known about non-coding transcripts in Streptococcus pneumoniae (pneumococcus), an obligate human respiratory pathogen responsible for significant worldwide morbidity and mortality. Tiling microarrays enable genome wide mRNA profiling as well as identification of novel transcripts at a high-resolution.
Results: Here, we describe a high-resolution transcription map of the S. pneumoniae clinical isolate TIGR4 using genomic tiling arrays. Our results indicate that approximately 66% of the genome is expressed under our experimental conditions. We identified a total of 50 non-coding small RNAs (sRNAs) from the intergenic regions, of which 36 had no predicted function. Half of the identified sRNA sequences were found to be unique to S. pneumoniae genome. We identified eight overrepresented sequence motifs among sRNA sequences that correspond to sRNAs in different functional categories. Tiling arrays also identified approximately 202 operon structures in the genome.
Conclusions: In summary, the pneumococcal operon structures and novel sRNAs identified in this study enhance our understanding of the complexity and extent of the pneumococcal 'expressed' genome. Furthermore, the results of this study open up new avenues of research for understanding the complex RNA regulatory network governing S. pneumoniae physiology and virulence.
C1 [Kumar, Ranjit; Burgess, Shane C.; Lawrence, Mark L.; Nanduri, Bindu] Mississippi State Univ, Coll Vet Med, Dept Basic Sci, Mississippi State, MS 39762 USA.
[Kumar, Ranjit; Burgess, Shane C.; Lawrence, Mark L.; Nanduri, Bindu] Mississippi State Univ, Inst Digital Biol, Mississippi State, MS 39762 USA.
[Burgess, Shane C.] Mississippi State Univ, Mississippi Agr & Forestry Expt Stn, Mississippi State, MS 39762 USA.
[Burgess, Shane C.] Mississippi State Univ, MSU Life Sci & Biotechnol Inst, Mississippi State, MS 39762 USA.
[Swiatlo, Edwin] Vet Affairs Med Ctr, Res Serv 151, Jackson, MS 39216 USA.
[Shah, Pratik] Univ Mississippi, Med Ctr, Dept Microbiol, Jackson, MS 39216 USA.
[Shah, Pratik] Massachusetts Gen Hosp, Dept Mol Biol & Microbiol, Boston, MA 02114 USA.
[Shah, Pratik] Massachusetts Gen Hosp, Dept Mol Genet, Boston, MA 02114 USA.
[Shah, Pratik] Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Nanduri, B (reprint author), Mississippi State Univ, Coll Vet Med, Dept Basic Sci, Mississippi State, MS 39762 USA.
EM bnanduri@cvm.msstate.edu
OI Shah, Pratik/0000-0002-1255-9325
FU National Science Foundation (Mississippi) [EPSCoR-0903787]
FX This project was partially supported by a grant from the National
Science Foundation (Mississippi EPSCoR-0903787). We acknowledge Allen
Shack and Dusan Kunec from College of Veterinary Medicine, Mississippi
State University for technical help in conducting RT-PCR. We acknowledge
Tony Arick and Life Sciences and Biotechnology Institute, Mississippi
State University for hosting S. pneumoniae GBrowse. We acknowledge the
Department of Basic Sciences, College of Veterinary Medicine, and the
Life Sciences and Biotechnology Institute, Mississippi State University
for assistance with the article-processing charges of this manuscript.
Approved for publication as Journal Article by the Mississippi
Agricultural and Forestry Experiment Station, Mississippi State
University.
NR 73
TC 35
Z9 36
U1 0
U2 6
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2164
J9 BMC GENOMICS
JI BMC Genomics
PD JUN 3
PY 2010
VL 11
AR 350
DI 10.1186/1471-2164-11-350
PG 19
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA 625BX
UT WOS:000279868100001
PM 20525227
ER
PT J
AU Swain, SM
Jeong, JH
Geyer, CE
Costantino, JP
Pajon, ER
Fehrenbacher, L
Atkins, JN
Polikoff, J
Vogel, VG
Erban, JK
Rastogi, P
Livingston, RB
Perez, EA
Mamounas, EP
Land, SR
Ganz, PA
Wolmark, N
AF Swain, Sandra M.
Jeong, Jong-Hyeon
Geyer, Charles E., Jr.
Costantino, Joseph P.
Pajon, Eduardo R.
Fehrenbacher, Louis
Atkins, James N.
Polikoff, Jonathan
Vogel, Victor G.
Erban, John K.
Rastogi, Priya
Livingston, Robert B.
Perez, Edith A.
Mamounas, Eleftherios P.
Land, Stephanie R.
Ganz, Patricia A.
Wolmark, Norman
TI Longer Therapy, Iatrogenic Amenorrhea, and Survival in Early Breast
Cancer
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID PHASE-III TRIAL; ADJUVANT CHEMOTHERAPY; PREMENOPAUSAL WOMEN;
DOXORUBICIN; DOCETAXEL; CYCLOPHOSPHAMIDE; RECURRENCE; OUTCOMES; TESTS;
RISK
AB BACKGROUND
Chemotherapy regimens that combine anthracyclines and taxanes result in improved disease-free and overall survival among women with operable lymph-node-positive breast cancer. The effectiveness of concurrent versus sequential regimens is not known.
METHODS
We randomly assigned 5351 patients with operable, node-positive, early-stage breast cancer to receive four cycles of doxorubicin and cyclophosphamide followed by four cycles of docetaxel (sequential ACT); four cycles of doxorubicin and docetaxel (doxorubicin-docetaxel); or four cycles of doxorubicin, cyclophosphamide, and docetaxel (con-current ACT). The primary aims were to examine whether concurrent ACT was more effective than sequential ACT and whether the doxorubicin-docetaxel regimen would be as effective as the concurrent-ACT regimen. The secondary aims were to assess toxic effects and to correlate amenorrhea with outcomes in premenopausal women.
RESULTS
At a median follow-up of 73 months, overall survival was improved in the sequential-ACT group (8-year overall survival, 83%) as compared with the doxorubicin-docetaxel group (overall survival, 79%; hazard ratio for death, 0.83; P=0.03) and the concurrent-ACT group (overall survival, 79%; hazard ratio, 0.86; P=0.09). Disease-free survival was improved in the sequential-ACT group (8-year disease-free survival, 74%) as compared with the doxorubicin-docetaxel group (disease-free survival, 69%; hazard ratio for recurrence, a second malignant condition, or death, 0.80; P=0.001) and the concurrent-ACT group (disease-free survival, 69%; hazard ratio, 0.83; P=0.01). The doxorubicin-docetaxel regimen showed noninferiority to the concurrent-ACT regimen for overall survival (hazard ratio, 0.96; 95% confidence interval, 0.82 to 1.14). Overall survival was improved in patients with amenorrhea for 6 months or more across all treatment groups, independently of estrogen-receptor status.
CONCLUSIONS
Sequential ACT improved disease-free survival as compared with doxorubicin-docetaxel or concurrent ACT, and it improved overall survival as compared with doxorubicin-docetaxel. Amenorrhea was associated with improved survival regardless of the treatment and estrogen-receptor status. (ClinicalTrials.gov number, NCT00003782.)
C1 [Swain, Sandra M.] Washington Hosp Ctr, Washington Canc Inst, Washington, DC 20010 USA.
[Jeong, Jong-Hyeon; Costantino, Joseph P.; Land, Stephanie R.] Univ Pittsburgh, NSABP Biostat Ctr, Pittsburgh, PA USA.
[Jeong, Jong-Hyeon; Costantino, Joseph P.; Land, Stephanie R.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA.
[Geyer, Charles E., Jr.; Wolmark, Norman] Allegheny Gen Hosp, Pittsburgh, PA 15212 USA.
[Vogel, Victor G.; Rastogi, Priya] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA.
[Pajon, Eduardo R.] Colorado Canc Res Program, Denver, CO USA.
[Fehrenbacher, Louis] Kaiser Permanente No Calif, Vallejo, CA USA.
[Atkins, James N.] SE Canc Control Consortium, Clin Canc Oncol Program, Goldsboro, NC USA.
[Polikoff, Jonathan] So Calif Kaiser Permanente, San Diego, CA USA.
[Vogel, Victor G.] Amer Canc Soc, Atlanta, GA 30329 USA.
[Erban, John K.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
[Erban, John K.] Harvard Univ, Sch Med, Boston, MA USA.
[Erban, John K.] Eastern Cooperat Oncol Grp, Philadelphia, PA USA.
[Livingston, Robert B.] Univ Arizona, Arizona Canc Ctr, Tucson, AZ USA.
[Livingston, Robert B.] SW Oncol Grp, Ann Arbor, MI USA.
[Perez, Edith A.] Mayo Clin, Jacksonville, FL USA.
[Perez, Edith A.] N Cent Canc Treatment Grp, Rochester, MN USA.
[Mamounas, Eleftherios P.] Aultman Hlth Fdn, Canton, OH USA.
[Ganz, Patricia A.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Sch Med & Publ Hlth, Los Angeles, CA 90024 USA.
RP Swain, SM (reprint author), Washington Hosp Ctr, Washington Canc Inst, 110 Irving St NW, Washington, DC 20010 USA.
EM sandra.m.swain@medstar.net
OI Jeong, Jong/0000-0003-0596-2201
FU National Cancer Institute, National Institutes of Health, Department of
Health and Human Services [U10-CA-37377, U10-CA-69974, U10-CA-12027,
U10-CA-69651, CA07190, CA2115, CA-25224, CA-32102, CA-13612, CA-58348,
CA-45808]; Sanofi-Aventis; Rhone-Poulenc-Rhorer; Genentech;
Bristol-Myers Squibb; Susan G. Komen for the Cure Foundation, Living in
Pink, and Safeway; Eisai; GlaxoSmithKline; Pfizer; Onyx; Novartis;
Roche; Abraxis; BiPar; Wyeth; NSABP; Kaiser Permanente; Eastern
Cooperative Oncology Group; Lance Armstrong Foundation; Breast Cancer
Research Foundation
FX Supported by Public Health Service grants (U10-CA-37377, U10-CA-69974,
U10-CA-12027, and U10-CA-69651 to the National Surgical Adjuvant Breast
and Bowel Project; CA07190 to Dr. Erban; CA2115 to the Eastern
Cooperative Oncology Group; CA-25224 to the North Central Cancer
Treatment Group; and CA-32102, CA-13612, CA-58348, and CA-45808 to the
Southwest Oncology Group) from the National Cancer Institute, National
Institutes of Health, Department of Health and Human Services; and by
Sanofi-Aventis.; Dr. Swain reports receiving consulting fees from
Rhone-Poulenc-Rhorer, grant support from Genentech, Sanofi-Aventis,
Bristol-Myers Squibb, the Susan G. Komen for the Cure Foundation, Living
in Pink, and Safeway, donations to the Washington Hospital Center
Foundation from Genentech, Sanofi-Aventis, and Eisai, in-kind travel
fees from Sanofi-Aventis, and grants to her institution (Medstar
Research Institute) from Genentech, GlaxoSmithKline, Pfizer, Onyx,
Novartis, Roche, Abraxis, BiPar, and Wyeth. Dr. Pajon reports receiving
travel fees from the NSABP, which also provided fees to cover the
clinical research associates and data managers; and owning stocks with
his spouse in Gilead, Abbott, and Bristol-Myers Squibb. Dr. Fehrenbacher
reports receiving grants and travel fees from Kaiser Permanente. Dr.
Vogel reports receiving grants to the University of Pittsburgh from
Sanofi-Aventis. Dr. Erban reports receiving grants from the Eastern
Cooperative Oncology Group. Dr. Mamounas reports receiving consulting
and lecture fees and serving on an advisory board for Sanofi-Aventis.
Dr. Ganz reports receiving research support from the Lance Armstrong
Foundation and the Breast Cancer Research Foundation. Drs. Geyer and
Wolmark report receiving funding from Sanofi-Aventis for work performed
by the NSABP to cover costs for non-standard of care procedures required
by the study. No other potential conflict of interest relevant to this
article was reported.
NR 24
TC 147
Z9 151
U1 0
U2 11
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 JUN 3
PY 2010
VL 362
IS 22
BP 2053
EP 2065
DI 10.1056/NEJMoa0909638
PG 13
WC Medicine, General & Internal
SC General & Internal Medicine
GA 603XU
UT WOS:000278242200005
PM 20519679
ER
PT J
AU Follett, KA
Weaver, FM
Stern, M
Hur, K
Harris, CL
Luo, P
Marks, WJ
Rothlind, J
Sagher, O
Moy, C
Pahwa, R
Burchiel, K
Hogarth, P
Lai, EC
Duda, JE
Holloway, K
Samii, A
Horn, S
Bronstein, JM
Stoner, G
Starr, PA
Simpson, R
Baltuch, G
De Salles, A
Huang, GD
Reda, DJ
AF Follett, Kenneth A.
Weaver, Frances M.
Stern, Matthew
Hur, Kwan
Harris, Crystal L.
Luo, Ping
Marks, William J., Jr.
Rothlind, Johannes
Sagher, Oren
Moy, Claudia
Pahwa, Rajesh
Burchiel, Kim
Hogarth, Penelope
Lai, Eugene C.
Duda, John E.
Holloway, Kathryn
Samii, Ali
Horn, Stacy
Bronstein, Jeff M.
Stoner, Gatana
Starr, Philip A.
Simpson, Richard
Baltuch, Gordon
De Salles, Antonio
Huang, Grant D.
Reda, Domenic J.
CA CSP 468 Study Grp
TI Pallidal versus Subthalamic Deep-Brain Stimulation for Parkinson's
Disease
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID QUALITY-OF-LIFE; GLOBUS-PALLIDUS; FOLLOW-UP; MOTOR FLUCTUATIONS;
NUCLEUS; TRIAL; VALIDATION; EFFICACY
AB BACKGROUND
Deep-brain stimulation is the surgical procedure of choice for patients with advanced Parkinson's disease. The globus pallidus interna and the subthalamic nucleus are accepted targets for this procedure. We compared 24-month outcomes for patients who had undergone bilateral stimulation of the globus pallidus interna (pallidal stimulation) or subthalamic nucleus (subthalamic stimulation).
METHODS
At seven Veterans Affairs and six university hospitals, we randomly assigned 299 patients with idiopathic Parkinson's disease to undergo either pallidal stimulation (152 patients) or subthalamic stimulation (147 patients). The primary outcome was the change in motor function, as blindly assessed on the Unified Parkinson's Disease Rating Scale, part III (UPDRS-III), while patients were receiving stimulation but not receiving antiparkinsonian medication. Secondary outcomes included self-reported function, quality of life, neurocognitive function, and adverse events.
RESULTS
Mean changes in the primary outcome did not differ significantly between the two study groups (P=0.50). There was also no significant difference in self-reported function. Patients undergoing subthalamic stimulation required a lower dose of dopaminergic agents than did those undergoing pallidal stimulation (P=0.02). One component of processing speed (visuomotor) declined more after subthalamic stimulation than after pallidal stimulation (P=0.03). The level of depression worsened after subthalamic stimulation and improved after pallidal stimulation (P=0.02). Serious adverse events occurred in 51% of patients undergoing pallidal stimulation and in 56% of those undergoing subthalamic stimulation, with no significant between-group differences at 24 months.
CONCLUSIONS
Patients with Parkinson's disease had similar improvement in motor function after either pallidal or subthalamic stimulation. Nonmotor factors may reasonably be included in the selection of surgical target for deep-brain stimulation. (ClinicalTrials.gov numbers, NCT00056563 and NCT01076452.)
C1 [Weaver, Frances M.] Hines Vet Affairs Hosp, Ctr Management Complex Chron Care, Hines, IL 60141 USA.
[Follett, Kenneth A.] Iowa City Vet Affairs Med Ctr, Iowa City, IA USA.
[Stoner, Gatana] Univ Iowa Hlth Care, Iowa City, IA USA.
[Follett, Kenneth A.] Univ Nebraska Med Ctr, Omaha, NE USA.
[Hur, Kwan; Luo, Ping; Reda, Domenic J.] Hines Vet Affairs Hosp, Cooperat Studies Coordinating Ctr, Hines, IL 60141 USA.
[Weaver, Frances M.] Loyola Univ, Stritch Sch Med, Maywood, IL 60153 USA.
[Stern, Matthew; Horn, Stacy; Baltuch, Gordon] Univ Penn Hlth Syst, Philadelphia, PA USA.
[Stern, Matthew; Duda, John E.; Baltuch, Gordon] Philadelphia VA Med Ctr, Philadelphia, PA USA.
[Harris, Crystal L.] VA Cooperat Studies Program, Clin Res Pharm, Albuquerque, NM USA.
[Marks, William J., Jr.; Rothlind, Johannes; Starr, Philip A.] San Francisco VA Med Ctr, San Francisco, CA USA.
[Marks, William J., Jr.; Rothlind, Johannes; Starr, Philip A.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Sagher, Oren] Univ Michigan, Med Ctr, Ann Arbor, MI USA.
[Moy, Claudia] NINDS, Rockville, MD USA.
[Pahwa, Rajesh] Univ Kansas, Med Ctr, Kansas City, MO USA.
[Burchiel, Kim] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Burchiel, Kim; Hogarth, Penelope] Portland VA Med Ctr, Portland, OR USA.
[Lai, Eugene C.; Simpson, Richard] Michael E DeBakey VA Med Ctr, Houston, TX USA.
[Lai, Eugene C.; Simpson, Richard] Baylor Coll Med, Houston, TX 77030 USA.
[Hur, Kwan] Richmond VA Med Ctr, Richmond, VA USA.
[Samii, Ali] VA Puget Sound Hlth Care Syst, Seattle, WA USA.
[Bronstein, Jeff M.; De Salles, Antonio] Univ Calif Los Angeles, W Los Angeles VA Med Ctr, Los Angeles, CA USA.
[Bronstein, Jeff M.; De Salles, Antonio] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Huang, Grant D.] US Dept Vet Affairs, Cooperat Studies Program, Cent Off, Washington, DC USA.
RP Weaver, FM (reprint author), Hines Vet Affairs Hosp, Ctr Management Complex Chron Care, 5000 S 5th Ave,151H, Hines, IL 60141 USA.
EM frances.weaver@va.gov
FU Department of Veterans Affairs Office of Research and Development;
National Institute of Neurological Disorders and Stroke; Medtronic;
Novartis; Teva; Schering-Plough; Boehringer Ingelheim; Vernalis; Ipsen;
Ceregene; Sofamor Danek; Schering-Plough Research Institute; Samueli
Institute; Ipsen Pharmaceuticals; Teva Pharmaceuticals; Boston
Scientific; SurgiVision
FX Supported by the Cooperative Studies Program of the Department of
Veterans Affairs Office of Research and Development, the National
Institute of Neurological Disorders and Stroke, and Medtronic.; Dr.
Stern reports receiving consulting fees from Novartis, Teva,
Schering-Plough, Boehringer Ingelheim, Vernalis, and Ipsen and lecture
fees from Novartis and having an equity interest in Adamis; Dr. Harris,
having an equity interest in Johnson & Johnson; Dr. Marks, receiving
consulting and lecture fees from Medtronic and grant support from
Boehringer Ingelheim and Ceregene; Dr. Pahwa, receiving consulting and
lecture fees from Medtronic; Dr. Burchiel, having an equity interest in
Medtronic and receiving grant support from Medtronic and Sofamor Danek;
Dr. Hogarth, receiving grant support from Schering-Plough Research
Institute; Dr. Lai, receiving grant support from Medtronic; Dr. Duda,
receiving consulting fees from Boehringer Ingelheim and grant support
from the Samueli Institute; Dr. Holloway, receiving consulting fees and
grant support from Medtronic; Dr. Samii, receiving lecture fees from
Ipsen Pharmaceuticals, Boehringer Ingelheim, and Teva Pharmaceuticals;
Dr. Starr, receiving consulting fees from Medtronic and Boston
Scientific and grant support from SurgiVision; Dr. Simpson, receiving
consulting and lecture fees from Medtronic; and Dr. De Salles, receiving
fellowship support from Medtronic. No other potential conflict of
interest relevant to this article was reported.
NR 25
TC 411
Z9 421
U1 6
U2 52
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 JUN 3
PY 2010
VL 362
IS 22
BP 2077
EP 2091
DI 10.1056/NEJMoa0907083
PG 15
WC Medicine, General & Internal
SC General & Internal Medicine
GA 603XU
UT WOS:000278242200007
PM 20519680
ER
PT J
AU van Eekelen, M
Sasportas, LS
Kasmieh, R
Yip, S
Figueiredo, JL
Louis, DN
Weissleder, R
Shah, K
AF van Eekelen, M.
Sasportas, L. S.
Kasmieh, R.
Yip, S.
Figueiredo, J-L
Louis, D. N.
Weissleder, R.
Shah, K.
TI Human stem cells expressing novel TSP-1 variant have anti-angiogenic
effect on brain tumors
SO ONCOGENE
LA English
DT Article
DE brain tumor; glioma; human neural stem cells; TSP-1; endothelial cells;
angiogenesis; in vivo imaging
ID IN-VIVO; MALIGNANT GLIOMA; CANCER-THERAPY; GROWTH; ABT-510; APOPTOSIS;
TRAIL; MODEL; ENDOSTATIN; INHIBITOR
AB Novel therapeutic agents combined with innovative modes of delivery and non-invasive imaging of drug delivery, pharmacokinetics and efficacy are crucial in developing effective clinical anticancer therapies. In this study, we have created and characterized multiple novel variants of anti-angiogenic protein thrombospondin (aaTSP-1) that comprises unique regions of three type-I-repeats of TSP-1 and used engineered human neural stem cells (hNSC) to provide sustained on-site delivery of secretable aaTSP-1 to tumor-vasculature. We show that hNSC-aaTSP-1 has anti-angiogenic effect on human brain and dermal microvascular endothelial cells co-cultured with established glioma cells and CD133+ glioma-initiating cells. Using human glioma cells and hNSC engineered with different combinations of fluorescent and bioluminescent marker proteins and employing multi-modality imaging techniques, we show that aaTSP-1 targets the vascular-component of gliomas and a single administration of hNSC-aaTSP-1 markedly reduces tumor vessel-density that results in inhibition of tumor-progression and increased survival in mice bearing highly malignant human gliomas. We also show that therapeutic hNSC do not proliferate and remain in an un-differentiated state in the brains of glioma-bearing mice. This study provides a platform for accelerated development of future cell-based therapies for cancer. Oncogene (2010) 29, 3185-3195; doi: 10.1038/onc.2010.75; published online 22 March 2010
C1 [van Eekelen, M.; Sasportas, L. S.; Kasmieh, R.; Shah, K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Neurotherapy & Imaging Lab, Boston, MA USA.
[van Eekelen, M.; Sasportas, L. S.; Kasmieh, R.; Figueiredo, J-L; Weissleder, R.; Shah, K.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Louis, D. N.; Shah, K.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Yip, S.; Louis, D. N.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Yip, S.; Louis, D. N.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA.
[Figueiredo, J-L; Weissleder, R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA USA.
RP Shah, K (reprint author), Harvard Univ, Mol Neurotherapy & Imaging Lab, Massachusetts Gen Hosp, Dept Radiol & Neurol,Med Sch, Rm 5403,149,13th St, Charlestown, MA 02129 USA.
EM kshah@helix.mgh.harvard.edu
RI van Eekelen, Mark/A-6225-2010
FU American Cancer Society; Goldhirsh foundation; Alliance for Cancer Gene
Therapy [P50 CA86355, R21CA131980]
FX This work was supported by American Cancer Society (KS), Goldhirsh
foundation (KS), Alliance for Cancer Gene Therapy (KS), P50 CA86355 (KS,
RW), R21CA131980 (KS). We thank Dr Rainer Koehler for his help with
intravital microscopy and Dr Claudio Vinegoni for his help with
processing images. We also thank Dr Jack Lawler (Beth Israel Deaconess
Hospital, Boston) for providing us with TSP-1 cDNA construct and Dr Paul
van Bergen en Henegouwen (Utrecht University, The Netherlands) for his
constructive comments.
NR 37
TC 28
Z9 28
U1 0
U2 11
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD JUN 3
PY 2010
VL 29
IS 22
BP 3185
EP 3195
DI 10.1038/onc.2010.75
PG 11
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA 605BA
UT WOS:000278321100002
PM 20305695
ER
PT J
AU Bueno, H
Ross, JS
Wang, Y
Chen, J
Vidan, MT
Normand, SLT
Curtis, JP
Drye, EE
Lichtman, JH
Keenan, PS
Kosiborod, M
Krumholz, HM
AF Bueno, Hector
Ross, Joseph S.
Wang, Yun
Chen, Jersey
Vidan, Maria T.
Normand, Sharon-Lise T.
Curtis, Jeptha P.
Drye, Elizabeth E.
Lichtman, Judith H.
Keenan, Patricia S.
Kosiborod, Mikhail
Krumholz, Harlan M.
TI Trends in Length of Stay and Short-term Outcomes Among Medicare Patients
Hospitalized for Heart Failure, 1993-2006
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID READMISSION RATES; TEMPORAL TRENDS; MORTALITY; SURVIVAL; CARE;
PERFORMANCE; MODEL
AB Context Whether decreases in the length of stay during the past decade for patients with heart failure (HF) may be associated with changes in outcomes is unknown.
Objective To describe the temporal changes in length of stay, discharge disposition, and short-term outcomes among older patients hospitalized for HF.
Design, Setting, and Participants An observational study of 6 955 461 Medicare fee-for-service hospitalizations for HF between 1993 and 2006, with a 30-day follow-up.
Main Outcome Measures Length of hospital stay, in-patient and 30-day mortality, and 30-day readmission rates.
Results Between 1993 and 2006, mean length of stay decreased from 8.81 days (95% confidence interval [CI], 8.79-8.83 days) to 6.33 days (95% CI, 6.32-6.34 days). In-hospital mortality decreased from 8.5% (95% CI, 8.4%-8.6%) in 1993 to 4.3% (95% CI, 4.2%-4.4%) in 2006, whereas 30-day mortality decreased from 12.8% (95% CI, 12.8%-12.9%) to 10.7% (95% CI, 10.7%-10.8%). Discharges to home or under home care service decreased from 74.0% to 66.9% and discharges to skilled nursing facilities increased from 13.0% to 19.9%. Thirty-day readmission rates increased from 17.2% (95% CI, 17.1%-17.3%) to 20.1% (95% CI, 20.0%-20.2%; all P<.001). Consistent with the unadjusted analyses, the 2005-2006 risk-adjusted 30-day mortality risk ratio was 0.92 (95% CI, 0.91-0.93) compared with 1993-1994, and the 30-day readmission risk ratio was 1.11 (95% CI, 1.10-1.11).
Conclusion For patients admitted with HF during the past 14 years, reductions in length of stay and in-hospital mortality, less marked reductions in 30-day mortality, and changes in discharge disposition accompanied by increases in 30-day readmission rates were observed. JAMA. 2010; 303(21): 2141-2147
C1 [Bueno, Hector] Hosp Gen Univ Gregorio Maranon, Dept Cardiol, Madrid, Spain.
[Vidan, Maria T.] Hosp Gen Univ Gregorio Maranon, Serv Geriatr Med, Madrid, Spain.
[Ross, Joseph S.] Mt Sinai Sch Med, Dept Geriatr & Palliat Med, New York, NY USA.
[Ross, Joseph S.] James J Peters VA Med Ctr, HSR&D Res Enhancement Award Program, Bronx, NY USA.
[Ross, Joseph S.] James J Peters VA Med Ctr, Ctr Geriatr Res Educ & Clin, Bronx, NY USA.
[Wang, Yun; Chen, Jersey; Curtis, Jeptha P.; Drye, Elizabeth E.; Krumholz, Harlan M.] Yale New Haven Med Ctr, Ctr Outcomes Res & Evaluat, New Haven, CT 06504 USA.
[Krumholz, Harlan M.] Yale Univ, Sch Med, Dept Internal Med, Sch Publ Hlth, New Haven, CT 06510 USA.
[Krumholz, Harlan M.] Yale Univ, Sch Med, Sch Publ Hlth, Robert Wood Johnson Clin Scholars Program, New Haven, CT 06510 USA.
[Lichtman, Judith H.] Yale Univ, Sch Med, Sch Publ Hlth, Sect Chron Dis Epidemiol, New Haven, CT 06510 USA.
[Keenan, Patricia S.; Krumholz, Harlan M.] Yale Univ, Sch Med, Sch Publ Hlth, Sect Hlth Policy & Adm, New Haven, CT 06510 USA.
[Normand, Sharon-Lise T.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
[Normand, Sharon-Lise T.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Kosiborod, Mikhail] Univ Missouri, St Lukes Hosp, Mid Amer Heart Inst, Kansas City, MO USA.
[Kosiborod, Mikhail] Univ Missouri, Dept Med, Kansas City, MO USA.
RP Krumholz, HM (reprint author), Yale Univ, Sch Med, Dept Internal Med, Sch Publ Hlth, 1 Church St,Ste 200, New Haven, CT 06510 USA.
EM harlan.krumholz@yale.edu
RI BUENO, HECTOR/I-3910-2015
OI BUENO, HECTOR/0000-0003-0277-7596
FU Centers for Medicare & Medicaid Services, US Department of Health and
Human Services [HHSM-500-2005-CO001C]; Centers for Disease Control and
Prevention [K01 DP000085-05]; Fondo de Investigacion Sanitaria del
Instituto de Salud Carlos III, Spain [BA08/90010, BA08/90012]; National
Institute on Aging [K08 AG032886]; American Federation for Aging
Research; American Heart Association; Almirall; Bayer; Bristol-Myers
Squibb; Sanofi-Aventis; Astra-Zeneca; Pfizer; Centers for Medicare &
Medicaid Services
FX The analyses upon which this publication is based were performed under
contract HHSM-500-2005-CO001C, entitled "Utilization and Quality Control
Quality Improvement Organization for the State (commonwealth) of
Colorado," which was funded by the Centers for Medicare & Medicaid
Services, an agency of the US Department of Health and Human Services.
This work was also funded by grant K01 DP000085-05 from the Centers for
Disease Control and Prevention. Drs Bueno and Vidan were supported in
part by grants BA08/90010 and BA08/90012, respectively, from the Fondo
de Investigacion Sanitaria del Instituto de Salud Carlos III, Spain,
while at the Center for Outcomes Research and Evaluation, Yale-New Haven
Hospital, where they participated in the development of this study. Dr
Ross is supported by grant K08 AG032886 from the National Institute on
Aging and by the American Federation for Aging Research through the Paul
B. Beeson Career Development Award Program. Dr Kosiborod is supported by
the American Heart Association Career Development Award in
Implementation Research.; Dr Bueno reported having received consulting
fees from Almirall, Bayer, Bristol-Myers Squibb, and Sanofi-Aventis, and
research grants from Astra-Zeneca, Bristol-Myers Squibb, and Pfizer. Drs
Wang, Chen, Normand, Curtis, Drye, Keenan, and Krumholz reported that
they develop and maintain performance measures under contract with the
Centers for Medicare & Medicaid Services. Dr Kosiborod reported serving
on the advisory board of Sanofi-Aventis and receiving speaking honoraria
from the Vascular Biology Working Group and DiaVed Inc. Dr Krumholz
reported chairing a scientific advisory board for United Healthcare. Drs
Ross, Vidan, and Lichtman did not report any disclosures.
NR 27
TC 257
Z9 262
U1 0
U2 10
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD JUN 2
PY 2010
VL 303
IS 21
BP 2141
EP 2147
DI 10.1001/jama.2010.748
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 603BE
UT WOS:000278182100022
PM 20516414
ER
PT J
AU Marso, SP
Amin, AP
House, JA
Kennedy, KF
Spertus, JA
Rao, SV
Cohen, DJ
Messenger, JC
Rumsfeld, JS
AF Marso, Steven P.
Amin, Amit P.
House, John A.
Kennedy, Kevin F.
Spertus, John A.
Rao, Sunil V.
Cohen, David J.
Messenger, John C.
Rumsfeld, John S.
CA Natl Cardiovasc Data Registry
TI Association Between Use of Bleeding Avoidance Strategies and Risk of
Periprocedural Bleeding Among Patients Undergoing Percutaneous Coronary
Intervention
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID ACUTE MYOCARDIAL-INFARCTION; GLYCOPROTEIN IIB/IIIA INHIBITION; EARLY
INVASIVE MANAGEMENT; VASCULAR CLOSURE DEVICES; PROPENSITY SCORE;
CARDIAC-CATHETERIZATION; ECONOMIC-EVALUATION; REPLACE-2 TRIAL; ACUITY
TRIAL; BIVALIRUDIN
AB Context Bleeding complications with percutaneous coronary intervention (PCI) are associated with adverse patient outcomes. The association between the use of bleeding avoidance strategies and post-PCI bleeding as a function of a patient's preprocedural risk of bleeding is unknown.
Objective To describe the use of 2 bleeding avoidance strategies, vascular closure devices and bivalirudin, and associated post-PCI bleeding rates in a nationally representative PCI population.
Design, Setting, and Patients Analysis of data from 1 522 935 patients undergoing PCI procedures performed at 955 US hospitals participating in the National Cardiovascular Data Registry (NCDR) CathPCI Registry from January 1, 2004, through September 30, 2008.
Main Outcome Measure Periprocedural bleeding.
Results Bleeding occurred in 30 654 patients (2%). Manual compression, vascular closure devices, bivalirudin, or vascular closure devices plus bivalirudin were used in 35%, 24%, 23%, and 18% of patients, respectively. Bleeding events were reported in 2.8% of patients who received manual compression, compared with 2.1%, 1.6%, and 0.9% of patients receiving vascular closure devices, bivalirudin, and both strategies, respectively (P<.001). Bleeding rates differed by preprocedural risk assessed with the NCDR bleeding risk model (low risk, 0.72%; intermediate risk, 1.73%; high risk, 4.69%). In high-risk patients, use of both strategies was associated with lower bleeding rates (manual compression, 6.1%; vascular closure devices, 4.6%; bivalirudin, 3.8%; vascular closure devices plus bivalirudin, 2.3%; P<.001). This association persisted following adjustment using a propensity-matched and site-controlled model. Use of both strategies was used least often in high-risk patients (14.4% vs 21.0% in low-risk patients, P<.001).
Conclusions In a large national PCI registry, vascular closure devices and bivalirudin were associated with significantly lower bleeding rates, particularly among patients at greatest risk for bleeding. However, these strategies were less often used among higher-risk patients. JAMA. 2010; 303(21): 2156-2164
C1 [Marso, Steven P.; Amin, Amit P.; House, John A.; Kennedy, Kevin F.; Spertus, John A.; Cohen, David J.] Univ Missouri, St Lukes Mid Amer Heart Inst, Kansas City, MO 64111 USA.
[Rao, Sunil V.] Duke Clin Res Inst, Durham, NC USA.
[Messenger, John C.; Rumsfeld, John S.] Univ Colorado, Denver, CO 80202 USA.
[Messenger, John C.; Rumsfeld, John S.] Denver VA Med Ctr, Denver, CO USA.
RP Marso, SP (reprint author), Univ Missouri, St Lukes Mid Amer Heart Inst, 4401 Wornall Rd, Kansas City, MO 64111 USA.
EM smarso@saint-lukes.org
FU American Diabetes Association; Amylin Pharmaceuticals; Boston
Scientific; Medicines Company; Volcano Corporation; Terumo Corporation;
National Institutes of Health; American College of Cardiology
Foundation; American Heart Association; Amgen; Lilly; Bristol-Myers
Squibb/Sanofi-Aventis; EvaHeart; Cordis Corporation; Atherotech; Roche
Diagnostics; Momenta Pharmaceuticals; Portola Pharmaceuticals;
Schering-Plough; Eli Lilly; Daichi Sankyo; Pfizer; Medtronic;
Sanofi-Aventis; Society for Cardiac Angiography and Interventions
FX Dr Marso reported receiving research support from the American Diabetes
Association, Amylin Pharmaceuticals, Boston Scientific, The Medicines
Company, Volcano Corporation, and Terumo Corporation and serving as a
consultant for Abbott Vascular, NovoNordisk, Volcano Corporation, and
The Medicines Company. Mr House reported receiving consulting fees from
Volcano Corporation. Dr Spertus reported receiving research funding from
the National Institutes of Health, American College of Cardiology
Foundation, American Heart Association, Amgen, Lilly, Bristol-Myers
Squibb/Sanofi-Aventis, EvaHeart, and Cordis Corporation; receiving
in-kind research support from Atherotech and Roche Diagnostics; serving
as a consultant for United Healthcare, St Jude Medical, and Amgen;
serving as a copyright holder of the Seattle Angina Questionnaire, the
Kansas City Cardiomyopathy Questionnaire, and the Peripheral Artery
Questionnaire; having equity ownership in Health Outcomes Sciences; and
holding a patent on the PRISM technology, which executes multivariable
models at the point of clinical care. Dr Rao reported receiving research
support from Momenta Pharmaceuticals, Portola Pharmaceuticals, and
Cordis Corporation and serving as a consultant for Bristol-Myers Squibb,
Sanofi-Aventis, The Medicines Company, AstraZeneca, and Terumo
Corporation. Dr Cohen reported receiving research support from The
Medicines Company, Schering-Plough, Eli Lilly, and Daichi Sankyo;
serving as a consultant for Schering-Plough and Eli Lilly; and receiving
speaking honoraria from The Medicines Company, Eli Lilly, and St Jude
Medical. Dr Messenger reported receiving research support from Pfizer,
Medtronic, and Sanofi-Aventis. Dr Rumsfeld reported receiving salary
support for the position of chief science officer for the NCDR. No other
authors reported financial disclosures.; The views expressed in this
article represent those of the authors and do not necessarily represent
the American College of Cardiology Foundation or the Society for Cardiac
Angiography and Interventions, which cosponsor the National
Cardiovascular Data Registry.
NR 49
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Z9 163
U1 2
U2 10
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD JUN 2
PY 2010
VL 303
IS 21
BP 2156
EP 2164
DI 10.1001/jama.2010.708
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 603BE
UT WOS:000278182100024
PM 20516416
ER
PT J
AU Bhatt, DL
AF Bhatt, Deepak L.
TI Advancing the Care of Cardiac Patients Using Registry Data Going Where
Randomized Clinical Trials Dare Not
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
ID ACUTE CORONARY SYNDROMES; ELEVATION MYOCARDIAL-INFARCTION; OUTCOMES;
ATHEROTHROMBOSIS; ANGIOPLASTY; ASSOCIATION; PERFORMANCE; OUTPATIENTS;
QUALITY
C1 [Bhatt, Deepak L.] VA Boston Healthcare Syst, Boston, MA 02132 USA.
[Bhatt, Deepak L.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA.
RP Bhatt, DL (reprint author), VA Boston Healthcare Syst, 1400 VFW Pkwy, Boston, MA 02132 USA.
EM dlbhattmd@post.harvard.edu
NR 15
TC 20
Z9 20
U1 0
U2 2
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD JUN 2
PY 2010
VL 303
IS 21
BP 2188
EP 2189
DI 10.1001/jama.2010.743
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 603BE
UT WOS:000278182100030
PM 20516422
ER
PT J
AU Buran, BN
Strenzke, N
Neef, A
Gundelfinger, ED
Moser, T
Liberman, MC
AF Buran, Bradley N.
Strenzke, Nicola
Neef, Andreas
Gundelfinger, Eckart D.
Moser, Tobias
Liberman, M. Charles
TI Onset Coding Is Degraded in Auditory Nerve Fibers from Mutant Mice
Lacking Synaptic Ribbons
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID INNER HAIR-CELLS; SUPERIOR OLIVARY COMPLEX; ZONE PROTEIN BASSOON; SOUND
LOCALIZATION; CA(V)1.3 CHANNELS; RESPONSE PROPERTIES; TEMPORAL
PRECISION; CALCIUM-DEPENDENCE; AFFERENT SYNAPSE; KINETIC-ANALYSIS
AB Synaptic ribbons, found at the presynaptic membrane of sensory cells in both ear and eye, have been implicated in the vesicle-pool dynamics of synaptic transmission. To elucidate ribbon function, we characterized the response properties of single auditory nerve fibers in mice lacking Bassoon, a scaffolding protein involved in anchoring ribbons to the membrane. In bassoon mutants, immunohistochemistry showed that fewer than 3% of the hair cells' afferent synapses retained anchored ribbons. Auditory nerve fibers from mutants had normal threshold, dynamic range, and postonset adaptation in response to tone bursts, and they were able to phase lock with normal precision to amplitude-modulated tones. However, spontaneous and sound-evoked discharge rates were reduced, and the reliability of spikes, particularly at stimulus onset, was significantly degraded as shown by an increased variance of first-spike latencies. Modeling based on in vitro studies of normal and mutant hair cells links these findings to reduced release rates at the synapse. The degradation of response reliability in these mutants suggests that the ribbon and/or Bassoon normally facilitate high rates of exocytosis and that its absence significantly compromises the temporal resolving power of the auditory system.
C1 [Buran, Bradley N.; Strenzke, Nicola; Liberman, M. Charles] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA.
[Buran, Bradley N.; Liberman, M. Charles] MIT, Harvard Mit Div Hlth Sci & Technol, Program Speech & Hearing Biosci & Technol, Cambridge, MA 02139 USA.
[Neef, Andreas] Univ Gottingen, Bernstein Ctr Computat Neurosci, D-37073 Gottingen, Germany.
[Gundelfinger, Eckart D.] Leibniz Inst Neurobiol, Dept Neurochem & Mol Biol, D-39118 Magdeburg, Germany.
[Moser, Tobias] Univ Gottingen, Dept Otolaryngol, InnerEarLab, D-37075 Gottingen, Germany.
[Moser, Tobias] Univ Gottingen, Ctr Mol Physiol Brain, D-37075 Gottingen, Germany.
RP Buran, BN (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA.
EM bburan@alum.mit.edu
RI Moser, Tobias/L-5068-2014
OI Moser, Tobias/0000-0001-7145-0533
FU National Institute of Deafness and Other Communication Disorders [R01
DC00188 and P30 DC05209]; Jack Kent Cooke graduate fellowship; German
Research Foundation; Federal Ministry for Education and Research (BMBF);
Bernstein Center for Computational Neuroscience Gottingen; European
Commission; Deutsche Forschungsgemeinschaft [SFB 779/B9]; Bernstein
Center for Computational Neuroscience, Gottingen
FX This work was supported by the National Institute of Deafness and Other
Communication Disorders Grants R01 DC00188 and P30 DC05209 to M.C.L.; a
Jack Kent Cooke graduate fellowship to B.N.B.; a fellowship of the
German Research Foundation to N.S.; grants of the German Research
Foundation (Center for Molecular Physiology of the Brain), the Federal
Ministry for Education and Research (BMBF), Bernstein Center for
Computational Neuroscience Gottingen), and the European Commission
(Eurohear) to T.M.; and Deutsche Forschungsgemeinschaft SFB 779/B9 to
E.D.G.A.N. is a Bernstein Fellow of the Bernstein Center for
Computational Neuroscience, Gottingen. The guidance of thesis committee
members J.J. Guinan, W.F. Sewell, and D. Vetter as well as the technical
assistance of L.W. Dodds are gratefully acknowledged. We thank D.
Khimich for initial contribution to the project and N. Chapochnikov for
discussion and suggestions for data analysis.
NR 79
TC 91
Z9 92
U1 1
U2 8
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 JUN 2
PY 2010
VL 30
IS 22
BP 7587
EP 7597
DI 10.1523/JNEUROSCI.0389-10.2010
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA 604OK
UT WOS:000278288200016
PM 20519533
ER
PT J
AU Gore, JL
Litwin, MS
Lai, J
Yano, EM
Madison, R
Setodji, C
Adams, JL
Saigal, CS
AF Gore, John L.
Litwin, Mark S.
Lai, Julie
Yano, Elizabeth M.
Madison, Rodger
Setodji, Claude
Adams, John L.
Saigal, Christopher S.
CA Urologic Dis Amer Project
TI Use of Radical Cystectomy for Patients With Invasive Bladder Cancer
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID HEALTH-SERVICES RESEARCH; INSTRUMENTAL VARIABLES; UTILIZATION PROJECT;
OUTCOMES RESEARCH; CARE UTILIZATION; MORTALITY; SURVIVAL;
REGIONALIZATION; ACCESS; BREAST
AB Evidence-based guidelines recommend radical cystectomy for patients with muscle-invasive bladder cancer. However, many patients receive alternate therapies, such as chemotherapy or radiation. We examined factors that are associated with the use of radical cystectomy for invasive bladder cancer and compared the survival outcomes of patients with invasive bladder cancer by the treatment they received.
From linked Surveillance, Epidemiology, and End Results-Medicare data, we identified a cohort of 3262 Medicare beneficiaries aged 66 years or older at diagnosis with stage II muscle-invasive bladder cancer from January 1, 1992, through December 31, 2002. We examined the use of radical cystectomy with multilevel multivariable models and survival after diagnosis with the use of instrumental variable analyses. All statistical tests were two-sided.
A total of 21% of the study subjects underwent radical cystectomy. Older age at diagnosis and higher comorbidity were associated with decreased odds of receiving cystectomy (for those >= 80 vs 66-69 years old, odds ratio [OR] = 0.10, 95% confidence interval [CI] = 0.07 to 0.14; for Charlson comorbidity index of 3 vs 0-1, OR = 0.25, 95% CI = 0.14 to 0.45). Long travel distance to an available surgeon was associated with decreased odds of receiving cystectomy (for > 50 vs 0-4 miles travel distance to an available surgeon, OR = 0.60, 95% CI = 0.37 to 0.98). Overall survival was better for those who underwent cystectomy compared with those who underwent alternative treatments (for chemotherapy and/or radiation vs cystectomy, hazard ratio of death = 1.5, 95% CI = 1.3 to 1.8; for surveillance vs cystectomy, hazard ratio of death = 1.9, 95% CI = 1.6 to 2.3; 5-year adjusted survival: 42.2% [95% CI = 39.1% to 45.4%] for cystectomy; 20.7% [95% CI = 18.7% to 22.8%] for chemotherapy and/or radiation; 14.5% [95% CI = 13.0% to 16.2%] for surveillance).
Guideline-recommended care with radical cystectomy is underused for patients with muscle-invasive bladder cancer. Many bladder cancer patients whose survival outcomes might benefit with surgery are receiving alternative less salubrious treatments.
C1 [Gore, John L.] Univ Washington, Dept Urol, Sch Med, Seattle, WA 98195 USA.
[Gore, John L.; Litwin, Mark S.; Saigal, Christopher S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA 90095 USA.
[Gore, John L.; Litwin, Mark S.; Lai, Julie; Madison, Rodger; Setodji, Claude; Adams, John L.; Saigal, Christopher S.] RAND Corp, Santa Monica, CA USA.
[Yano, Elizabeth M.] VA Greater Los Angeles HSR&D Ctr Excellence, Los Angeles, CA USA.
RP Gore, JL (reprint author), Univ Washington, Dept Urol, Sch Med, 1959 NE Pacific St,Box 356510, Seattle, WA 98195 USA.
EM jlgore@u.washington.edu
OI Gore, John/0000-0002-2847-5062
FU California Department of Public Health [103885]; National Cancer
Institute [N01-PC-35136, N01-PC-35139, N02-PC-15105]; Centers for
Disease Control and Prevention [U55/CCR921930-02]; UCLA Robert Wood
Johnson Clinical Scholars Program; National Institute of Diabetes and
Digestive and Kidney Diseases [N01-DK-7-0003]
FX Collection of the California cancer incidence data used in this study
was supported by the California Department of Public Health as part of
the statewide cancer reporting program mandated by California Health and
Safety Code Section 103885; National Cancer Institute's Surveillance,
Epidemiology, and End Results (SEER) Program under contract N01-PC-35136
awarded to the Northern California Cancer Center, contract N01-PC-35139
awarded to the University of Southern California, and contract
N02-PC-15105 awarded to the Public Health Institute; Centers for Disease
Control and Prevention's National Program of Cancer Registries, under
agreement #U55/CCR921930-02 awarded to the Public Health Institute. This
work was supported by the UCLA Robert Wood Johnson Clinical Scholars
Program and the National Institute of Diabetes and Digestive and Kidney
Diseases N01-DK-7-0003 (Principal investigator: M.S.L.).
NR 52
TC 89
Z9 93
U1 1
U2 3
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 J NATL CANCER I
JI J. Natl. Cancer Inst.
PD JUN 2
PY 2010
VL 102
IS 11
BP 802
EP 811
DI 10.1093/jnci/djq121
PG 10
WC Oncology
SC Oncology
GA 606QA
UT WOS:000278440900009
PM 20400716
ER
PT J
AU von Knoch, F
Choi, HR
Zurakowski, D
Nelson, SB
Rubash, HE
Malchau, H
AF von Knoch, Fabian
Choi, Ho-Rim
Zurakowski, David
Nelson, Sandra B.
Rubash, Harry E.
Malchau, Henrik
TI Can implant retention be recommended for treatment of infected TKA?
SO SWISS MEDICAL WEEKLY
LA English
DT Meeting Abstract
C1 [von Knoch, Fabian; Malchau, Henrik] Schulthess Clin, Hip & Knee Reconstruct Unit, Zurich, Switzerland.
[von Knoch, Fabian; Choi, Ho-Rim; Rubash, Harry E.] Massachusetts Gen Hosp, Arthroplasty Serv, Boston, MA 02114 USA.
[von Knoch, Fabian; Choi, Ho-Rim; Rubash, Harry E.] Harvard Univ, Sch Med, Boston, MA USA.
[Zurakowski, David] Childrens Hosp, Dept Anesthesiol, Boston, MA 02115 USA.
[Zurakowski, David] Childrens Hosp, Dept Surg, Boston, MA 02115 USA.
[Nelson, Sandra B.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU E M H SWISS MEDICAL PUBLISHERS LTD
PI MUTTENZ
PA FARNSBURGERSTR 8, CH-4132 MUTTENZ, SWITZERLAND
SN 1424-7860
J9 SWISS MED WKLY
JI Swiss Med. Wkly.
PD JUN 2
PY 2010
VL 140
IS 23-24
SU 181
BP 20S
EP 21S
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 623SJ
UT WOS:000279763200077
ER
PT J
AU von Knoch, F
Choi, HR
Zurakowski, D
Kandil, A
Vezeridis, P
Moore, S
Jibodh, S
Malchau, H
AF von Knoch, Fabian
Choi, Ho-Rim
Zurakowski, David
Kandil, Abdurrahman
Vezeridis, Peter
Moore, Slade
Jibodh, Stefan
Malchau, Henrik
TI Treatment of periprosthetic infection after total hip arthroplasty: is
implant retention a viable option?
SO SWISS MEDICAL WEEKLY
LA English
DT Meeting Abstract
C1 [von Knoch, Fabian] Schulthess Clin, Hip & Knee Reconstruct Unit, Zurich, Switzerland.
[von Knoch, Fabian; Choi, Ho-Rim; Kandil, Abdurrahman; Vezeridis, Peter; Moore, Slade; Jibodh, Stefan; Malchau, Henrik] Massachusetts Gen Hosp, Arthroplasty Serv, Boston, MA 02114 USA.
[von Knoch, Fabian; Choi, Ho-Rim; Kandil, Abdurrahman; Vezeridis, Peter; Moore, Slade; Jibodh, Stefan; Malchau, Henrik] Harvard Univ, Sch Med, Boston, MA USA.
[Zurakowski, David] Childrens Hosp, Dept Anesthesiol, Boston, MA 02115 USA.
[Zurakowski, David] Childrens Hosp, Dept Surg, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU E M H SWISS MEDICAL PUBLISHERS LTD
PI MUTTENZ
PA FARNSBURGERSTR 8, CH-4132 MUTTENZ, SWITZERLAND
SN 1424-7860
J9 SWISS MED WKLY
JI Swiss Med. Wkly.
PD JUN 2
PY 2010
VL 140
IS 23-24
SU 181
BP 25S
EP 25S
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 623SJ
UT WOS:000279763200093
ER
PT J
AU van Vlerken, LE
Duan, ZF
Little, SR
Seiden, MV
Amiji, MM
AF van Vlerken, Lilian E.
Duan, Zhenfeng
Little, Steven R.
Seiden, Michael V.
Amiji, Mansoor M.
TI Augmentation of Therapeutic Efficacy in Drug-Resistant Tumor Models
Using Ceramide Coadministration in Temporal-Controlled Polymer-Blend
Nanoparticle Delivery Systems
SO AAPS JOURNAL
LA English
DT Article
DE combination therapy; intracellular ceramide modulation; multidrug
resistance; temporal-controlled polymeric nanoparticle delivery
ID POLY(BETA-AMINO ESTER) NANOPARTICLES; PH-SENSITIVE SYSTEM;
MULTIDRUG-RESISTANCE; HYDROPHOBIC DRUGS; TARGETED DELIVERY;
OVARIAN-CANCER; GLUCOSYLCERAMIDE; ACCUMULATION; MODULATION; CELLS
AB The development of multidrug resistance (MDR) is a major hindrance to cancer eradication as it renders tumors unresponsive to most chemotherapeutic treatments and is associated with cancer resurgence. This study describes a novel mechanism to overcome MDR through a polymer-blend nanoparticle platform that delivers a combination therapy of C6-ceramide (CER), a synthetic analog of an endogenously occurring apoptotic modulator, together with the chemotherapeutic drug paclitaxel (PTX), in a single formulation. The PTX/CER combination therapy circumvents another cellular mechanism whereby MDR develops, by lowering the threshold for apoptotic signaling. In vivo studies in a resistant subcutaneous SKOV3 human ovarian and in an orthotopic MCF7 human breast adenocarcinoma xenograft showed that the PTX and CER nanoparticle combination therapy reduced the final tumor volume at least twofold over treatment with the standard PTX therapy alone. The study also revealed that the cotherapy accomplished this enhanced efficacy by generating an enhancement in apoptotic signaling in both tumor types. Additionally, acute evaluation of safety with the combination therapy did not show significant changes in body weight, white blood cell counts, or liver enzyme levels. The temporal-controlled nanoparticle delivery system presented in this study allows for a simultaneous delivery of PTX + CER in breast and ovarian tumor model drug, leading to a modulation of the apoptotic threshold. This strategy has tremendous potential for effective treatment of refractory disease in cancer patients.
C1 [van Vlerken, Lilian E.; Amiji, Mansoor M.] Northeastern Univ, Dept Pharmaceut Sci, Sch Pharm, Boston, MA 02115 USA.
[Duan, Zhenfeng] Massachusetts Gen Hosp, Dept Orthoped Surg, Boston, MA 02114 USA.
[Little, Steven R.] Univ Pittsburgh, Dept Chem Engn, Pittsburgh, PA 15260 USA.
[Little, Steven R.] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA 15260 USA.
[Little, Steven R.] Univ Pittsburgh, Dept Immunol, Pittsburgh, PA 15260 USA.
[Little, Steven R.] Univ Pittsburgh, McGowan Inst Regenerat Med, Pittsburgh, PA 15260 USA.
[Seiden, Michael V.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
RP Amiji, MM (reprint author), Northeastern Univ, Dept Pharmaceut Sci, Sch Pharm, 360 Huntington Ave, Boston, MA 02115 USA.
EM m.amiji@neu.edu
RI Amiji, Mansoor/A-4365-2014;
OI Amiji, Mansoor/0000-0001-6170-881X; Little, Steven/0000-0002-7000-3931
FU National Cancer Institute's Alliance in Nanotechnology for Cancer
[R01-CA119617]; National Science Foundation
FX This project was supported by the National Cancer Institute's Alliance
in Nanotechnology for Cancer Platform Partnership grant (R01-CA119617).
Lilian E. van Vlerken was a fellow in the IGERT Nanomedical Science and
Technology doctoral training program, which is jointly funded by the
National Cancer Institute and the National Science Foundation. We deeply
appreciate the assistance from Dr. Bo Rueda's group at the Mass General
Hospital in the development of MCF7TR tumor model.
NR 21
TC 26
Z9 27
U1 1
U2 7
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1550-7416
J9 AAPS J
JI AAPS J.
PD JUN
PY 2010
VL 12
IS 2
BP 171
EP 180
DI 10.1208/s12248-010-9174-4
PG 10
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 574FX
UT WOS:000275975700007
PM 20143195
ER
PT J
AU Souza, FF
Jagganathan, J
Ramayia, N
Johnston, C
Jackman, D
Van den Abbeele, A
Ros, PR
AF Souza, Frederico F.
Jagganathan, Jyothi
Ramayia, Nikhil
Johnston, Ciaran
Jackman, David
Van den Abbeele, Annick
Ros, Pablo R.
TI Recurrent malignant peritoneal mesothelioma: radiological manifestations
SO ABDOMINAL IMAGING
LA English
DT Article
DE Malignant peritoneal mesothelioma; Recurrence; CT; Ascites; Omental
disease
ID PLEURAL MESOTHELIOMA; CT FINDINGS
AB To describe the CT imaging findings of recurrent malignant peritoneal mesothelioma in patients who underwent debulking surgery.
The history, clinical and laboratory data, and imaging studies of 13 patients with histologically proven diagnosis of Malignant Peritoneal Mesothelioma (MPM) and their recurrence following cytoreductive surgery were reviewed. CT studies were reviewed for presence of ascites, peritoneal, mesenteric and omental involvement, presence of solid abdominal viscera involvement, gastrointestinal involvement, presence and location of enlarged lymph nodes and extra abdominal sites of involvement.
The most common finding at recurrence was ascites (n = 6). Peritoneal thickening was seen in five patients, infiltration of the peritoneum resembling omental caking was seen in one patient, and low density implants mimicking pseudomyxoma peritonei was seen in another patient. None of the peritoneal implants showed calcification. Three patients had large discrete soft tissue masses in the omentum and/or peritoneum. Multifocal serosal implants were seen in four patients; one had low grade small bowel obstruction which was managed conservatively. Three patients had evidence of intrathoracic disease seen as soft tissue pericardial mass and malignant pleural effusions.
CT findings of recurrent MPM resemble primary MPM, metastatic or granulomatous diseases. Radiologist should be aware of its appearance and forms of recurrence which may be seen at extra abdominal sites.
C1 [Souza, Frederico F.; Ros, Pablo R.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA.
[Souza, Frederico F.; Jagganathan, Jyothi; Ramayia, Nikhil; Johnston, Ciaran; Van den Abbeele, Annick; Ros, Pablo R.] Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA.
[Jackman, David] Dana Farber Canc Inst, Dept Oncol, Boston, MA 02115 USA.
RP Souza, FF (reprint author), Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA.
EM ffsouza@partners.org
NR 16
TC 6
Z9 8
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0942-8925
J9 ABDOM IMAGING
JI Abdom. Imaging
PD JUN
PY 2010
VL 35
IS 3
BP 315
EP 321
DI 10.1007/s00261-009-9512-0
PG 7
WC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical
Imaging
SC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical
Imaging
GA 611IV
UT WOS:000278809700010
PM 19319590
ER
PT J
AU Kabrhel, C
Courtney, DM
Camargo, CA
Plewa, MC
Nordenholz, KE
Moore, CL
Richman, PB
Smithline, HA
Beam, DM
Kline, JA
AF Kabrhel, Christopher
Courtney, D. Mark
Camargo, Carlos A., Jr.
Plewa, Michael C.
Nordenholz, Kristen E.
Moore, Christopher L.
Richman, Peter B.
Smithline, Howard A.
Beam, Daren M.
Kline, Jeffrey A.
TI Factors Associated With Positive D-dimer Results in Patients Evaluated
for Pulmonary Embolism
SO ACADEMIC EMERGENCY MEDICINE
LA English
DT Article; Proceedings Paper
CT Annual Meeting of the Society-for-Academic-Emergency-Medicine
CY MAY 13-17, 2009
CL New Orleans, LA
SP Soc Acad Emergency Med
DE D-dimer; pulmonary embolism; venous thromboembolism; testing
ID VENOUS THROMBOEMBOLISM; SEATED IMMOBILITY; NORMAL-PREGNANCY;
RISK-FACTORS; WOMEN; COAGULABILITY; ANGIOGRAPHY; THROMBOSIS; DIAGNOSIS;
OBESITY
AB Objectives: Available D-dimer assays have low specificity and may increase radiographic testing for pulmonary embolism (PE). To help clinicians better target testing, this study sought to quantify the effect of risk factors for a positive quantitative D-dimer in patients evaluated for PE.
Methods: This was a prospective, multicenter, observational study. Emergency department (ED) patients evaluated for PE with a quantitative D-dimer were eligible for inclusion. The main outcome of interest was a positive D-dimer. Odds ratio (ORs) and 95% confidence intervals (CIs) were determined by multivariable logistic regression. Adjusted estimates of relative risk were also calculated.
Results: A total of 4,346 patients had D-dimer testing, of whom 2,930 (67%) were women. A total of 2,500 (57%) were white, 1,474 (34%) were black or African American, 238 (6%) were Hispanic, and 144 (3%) were of other race or ethnicity. The mean (+/- SD) age was 48 (+/- 17) years. Overall, 1,903(44%) D-dimers were positive. Model fit was adequate (c-statistic = 0.739, Hosmer and Lemeshow p-value = 0.13). Significant positive predictors of D-dimer positive included female sex; increasing age; black (vs. white) race; cocaine use; general, limb, or neurologic immobility; hemoptysis; hemodialysis; active malignancy; rheumatoid arthritis; lupus; sickle cell disease; prior venous thromboembolism (VTE; not under treatment); pregnancy and postpartum state; and abdominal, chest, orthopedic, or other surgery. Warfarin use was protective. In contrast, several variables known to be associated with PE were not associated with positive D-dimer results: body mass index (BMI), estrogen use, family history of PE, (inactive) malignancy, thrombophilia, trauma within 4 weeks, travel, and prior VTE (under treatment).
Conclusions: Many factors are associated with a positive D-dimer test. The effect of these factors on the usefulness of the test should be considered prior to ordering a D-dimer. ACADEMIC EMERGENCY MEDICINE 2010; 17:589-597 (C) 2010 by the Society for Academic Emergency Medicine
C1 [Kabrhel, Christopher; Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02115 USA.
[Courtney, D. Mark] Northwestern Univ, Med Ctr, Dept Emergency Med, Chicago, IL 60611 USA.
[Plewa, Michael C.] St Vincent Mercy Med Ctr, Dept Emergency Med, Toledo, OH USA.
[Nordenholz, Kristen E.] Univ Colorado, Dept Surg, Div Emergency Med, Denver, CO 80202 USA.
[Moore, Christopher L.] Yale Univ, Med Ctr, Dept Emergency Med, New Haven, CT USA.
[Richman, Peter B.] Mayo Clin Arizona, Dept Emergency Med, Scottsdale, AZ USA.
[Smithline, Howard A.] Baystate Med Ctr, Dept Emergency Med, Springfield, MA USA.
[Beam, Daren M.] E Carolina Univ, Sch Med, Greenville, NC USA.
[Kline, Jeffrey A.] Carolinas Med Ctr, Dept Emergency Med, Charlotte, NC 28203 USA.
RP Kabrhel, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02115 USA.
EM ckabrhel@partners.org
OI Kabrhel, Christopher/0000-0002-8699-7176
FU NHLBI NIH HHS [R42 HL074415, 2R42 HL074415-02A1]
NR 24
TC 40
Z9 45
U1 0
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1069-6563
J9 ACAD EMERG MED
JI Acad. Emerg. Med.
PD JUN
PY 2010
VL 17
IS 6
BP 589
EP 597
DI 10.1111/j.1553-2712.2010.00765.x
PG 9
WC Emergency Medicine
SC Emergency Medicine
GA 605IX
UT WOS:000278342300009
PM 20624138
ER
PT J
AU Delgado, MK
Ginde, AA
Pallin, DJ
Camargo, CA
AF Delgado, M. Kit
Ginde, Adit A.
Pallin, Daniel J.
Camargo, Carlos A., Jr.
TI Multicenter Study of Preferences for Health Education in the Emergency
Department Population
SO ACADEMIC EMERGENCY MEDICINE
LA English
DT Article
DE health education; health promotion; preventive services; patient
preferences; emergency department
ID CLINICAL PREVENTIVE SERVICES; RANDOMIZED CONTROLLED-TRIAL; BRIEF
INTERVENTION; PATIENT EDUCATION; CARE; MEDICINE; PROGRAM;
RECOMMENDATIONS; ADOLESCENTS; INFORMATION
AB Objectives: Emergency departments (EDs) are increasingly proposed as high-yield venues for providing preventive health education to a population at risk for unhealthy behaviors and unmet primary care needs. This study sought to determine the preferred health education topics and teaching modality among ED patients and visitors.
Methods: For two 24-hour periods, patients aged 18 years and older presenting to four Boston EDs were consecutively enrolled, and waiting room visitors were surveyed every 3 hours. The survey assessed interest in 28 health conditions and topics, which were further classified into nine composite health education categories. Also assessed was the participants' preferred teaching modality.
Results: Among 1,321 eligible subjects, 1,010 (76%) completed the survey, of whom 56% were patients and 44% were visitors. Among the health conditions, respondents were most interested in learning about stress and depression (32%). Among the health topics, respondents were most interested in exercise and nutrition (43%). With regard to learning modality, 34% of subjects chose brochures/book, 25% video, 24% speaking with an expert, 14% using a computer, and 3% another mode of learning (e.g., a class). Speaking with an expert was the overall preferred modality for those with less than high school education and Hispanics, as well as those interested in HIV screening, youth violence, and stroke. Video was the preferred modality for those interested in learning more about depression, alcohol, drugs, firearm safety, and smoke detectors.
Conclusions: Emergency department patients and visitors were most interested in health education on stress, depression, exercise, and nutrition, compared to topics more commonly targeted to the ED population such as substance abuse, sexual health (including HIV testing), and injury prevention. Despite many recent innovations in health education, most ED patients and visitors in our study preferred the traditional form of books and brochures. Future ED health education efforts may be optimized by taking into account the learning preferences of the target ED population. ACADEMIC EMERGENCY MEDICINE 2010; 17:652-658 (C) 2010 by the Society for Academic Emergency Medicine
C1 [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02115 USA.
[Delgado, M. Kit] Stanford Univ, Sch Med, Ctr Primary Care & Outcomes Res, Palo Alto, CA 94304 USA.
[Delgado, M. Kit] Stanford Univ, Sch Med, Div Emergency Med, Palo Alto, CA 94304 USA.
[Ginde, Adit A.] Univ Colorado Denver, Sch Med, Dept Emergency Med, Aurora, CO USA.
[Pallin, Daniel J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Emergency Med, Boston, MA 02115 USA.
RP Camargo, CA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02115 USA.
EM ccamargo@partners.org
RI Pallin, Daniel/H-6382-2013; Vila, Vanessa/B-4982-2014; Siry,
Bonnie/D-7189-2017
OI Pallin, Daniel/0000-0002-8517-9702;
FU AHRQ [T32 HS00028]
FX The authors thank Drs. Jeff Collins (Chelsea HealthCare Center) and
Richard Larson (Faulkner Hospital) for their participation and also
Karen Bos, Gabrielle Hunter, and Dr. Sunghye Kim of the EMNet
Coordinating Center for their important logistical contributions. Dr.
Delgado was supported by AHRQ training grant T32 HS00028 to the Center
for Primary Care and Outcomes Research, Stanford University.
NR 34
TC 10
Z9 10
U1 0
U2 7
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1069-6563
J9 ACAD EMERG MED
JI Acad. Emerg. Med.
PD JUN
PY 2010
VL 17
IS 6
BP 652
EP 658
DI 10.1111/j.1553-2712.2010.00764.x
PG 7
WC Emergency Medicine
SC Emergency Medicine
GA 605IX
UT WOS:000278342300019
ER
PT J
AU Wakeman, SE
AF Wakeman, Sarah E.
TI Sitting With Sorrow
SO ACADEMIC MEDICINE
LA English
DT Editorial Material
C1 Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA.
RP Wakeman, SE (reprint author), Massachusetts Gen Hosp, Dept Internal Med, 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 1040-2446
J9 ACAD MED
JI Acad. Med.
PD JUN
PY 2010
VL 85
IS 6
BP 987
EP 987
DI 10.1097/ACM.0b013e3181db2dbe
PG 1
WC Education, Scientific Disciplines; Health Care Sciences & Services
SC Education & Educational Research; Health Care Sciences & Services
GA 618SZ
UT WOS:000279377300018
PM 20505398
ER
PT J
AU Sheridan, JT
Fine, E
Pribbenow, CM
Handelsman, J
Carnes, M
AF Sheridan, Jennifer T.
Fine, Eve
Pribbenow, Christine Maidl
Handelsman, Jo
Carnes, Molly
TI Searching for Excellence & Diversity: Increasing the Hiring of Women
Faculty at One Academic Medical Center
SO ACADEMIC MEDICINE
LA English
DT Article
ID DECISION-MAKING; GENDER; GLASS; LEADERSHIP; FEMALE; HEALTH; IMPACT;
MODEL
AB One opportunity to realize the diversity goals of academic health centers comes at the time of hiring new faculty. To improve the effectiveness of search committees in increasing the gender diversity of faculty hires, the authors created and implemented a training workshop for faculty search committees designed to improve the hiring process and increase the diversity of faculty hires at the University of Wisconsin-Madison. They describe the workshops, which they presented in the School of Medicine and Public Health between 2004 and 2007, and they compare the subsequent hiring of women faculty in participating and nonparticipating departments and the self-reported experience of new faculty within the hiring process. Attendance at the workshop correlates with improved hiring of women faculty and with a better hiring experience for faculty recruits, especially women. The authors articulate successful elements of workshop implementation for other medical schools seeking to increase gender diversity on their faculties. Acad Med. 2010;85:999-1007.
C1 [Sheridan, Jennifer T.; Fine, Eve; Pribbenow, Christine Maidl; Handelsman, Jo; Carnes, Molly] Univ Wisconsin, WISELI, Madison, WI 53706 USA.
[Pribbenow, Christine Maidl] Univ Wisconsin, Wisconsin Ctr Educ Res, Madison, WI 53706 USA.
[Handelsman, Jo] Yale Univ, Howard Hughes Med Inst, New Haven, CT 06511 USA.
[Carnes, Molly] Univ Wisconsin, Ctr Womens Hlth Res, Madison, WI 53706 USA.
[Carnes, Molly] William S Middleton Mem Vet Adm Med Ctr, Women Vet Hlth Program, Madison, WI USA.
RP Sheridan, JT (reprint author), Univ Wisconsin, WISELI, 2107 Mech Engn Bldg,1513 Univ Ave, Madison, WI 53706 USA.
EM sheridan@engr.wisc.edu
FU National Science Foundation (NSF) [0123666, 0619979]
FX This research was funded with support from the National Science
Foundation (NSF #0123666 and #0619979).
NR 68
TC 12
Z9 12
U1 0
U2 5
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 JUN
PY 2010
VL 85
IS 6
BP 999
EP 1007
DI 10.1097/ACM.0b013e3181dbf75a
PG 9
WC Education, Scientific Disciplines; Health Care Sciences & Services
SC Education & Educational Research; Health Care Sciences & Services
GA 618SZ
UT WOS:000279377300021
PM 20505400
ER
PT J
AU Tondo, L
Vazquez, G
Baldessarini, RJ
AF Tondo, L.
Vazquez, G.
Baldessarini, R. J.
TI Mania associated with antidepressant treatment: comprehensive
meta-analytic review
SO ACTA PSYCHIATRICA SCANDINAVICA
LA English
DT Review
DE antidepressants; bipolar disorder; major depression; mania;
meta-analysis
ID BIPOLAR DEPRESSED-PATIENTS; SEROTONIN REUPTAKE INHIBITORS; TREATMENT
ENHANCEMENT PROGRAM; DISORDER STEP-BD; DOUBLE-BLIND; LITHIUM-CARBONATE;
UNIPOLAR DEPRESSION; MOOD-STABILIZERS; ANTI-DEPRESSANTS; CONTROLLED
TRIAL
AB Objective:
To review available data pertaining to risk of mania-hypomania among bipolar (BPD) and major depressive disorder (MDD) patients with vs. without exposure to antidepressant drugs (ADs) and consider effects of mood stabilizers.
Method:
Computerized searching yielded 73 reports (109 trials, 114 521 adult patients); 35 were suitable for random effects meta-analysis, and multivariate-regression modeling included all available trials to test for effects of trial design, AD type, and mood-stabilizer use.
Results:
The overall risk of mania with/without ADs averaged 12.5%/7.5%. The AD-associated mania was more frequent in BPD than MDD patients, but increased more in MDD cases. Tricyclic antidepressants were riskier than serotonin-reuptake inhibitors (SRIs); data for other types of ADs were inconclusive. Mood stabilizers had minor effects probably confounded by their preferential use in mania-prone patients.
Conclusion:
Use of ADs in adults with BPD or MDD was highly prevalent and moderately increased the risk of mania overall, with little protection by mood stabilizers.
C1 [Tondo, L.; Baldessarini, R. J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
[Tondo, L.; Baldessarini, R. J.] Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA.
[Tondo, L.; Baldessarini, R. J.] Massachusetts Gen Hosp, McLean Div, Boston, MA 02114 USA.
[Tondo, L.] Univ Cagliari, Dept Psychol, Cagliari, Sardinia, Italy.
[Tondo, L.] Lucio Bini Mood Disorders Res Ctr, Cagliari, Sardinia, Italy.
[Vazquez, G.] Univ Palermo, Dept Neurosci, Buenos Aires, DF, Argentina.
RP Tondo, L (reprint author), McLean Hosp, MRC 3,115 Mill St, Belmont, MA 02178 USA.
EM ltondo@mclean.harvard.edu
FU NARSAD; Centro Bini Private Donors Mood Research Fund; Bruce J. Anderson
Foundation; McLean Private Donors Neuropsychopharmacology & Bipolar
Disorder Research Fund
FX This study was supported in part by awards from NARSAD and the Centro
Bini Private Donors Mood Research Fund (LT), by grants from the Bruce J.
Anderson Foundation and by the McLean Private Donors
Neuropsychopharmacology & Bipolar Disorder Research Fund (RJB). The
authors thank Roy Perlis, M.D. of Massachusetts General Hospital and
Nassir Ghaemi, M.D. of Tufts University School of Medicine for valuable
advice, and Christian Teter, Pharm.D., and Aimee Mertz, pre-Pharm.D. of
the Bouve College of Health Sciences, Northeastern University and McLean
Hospital for bibliographic advice and assistance.
NR 113
TC 97
Z9 99
U1 1
U2 10
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 JUN
PY 2010
VL 121
IS 6
BP 404
EP 414
DI 10.1111/j.1600-0447.2009.01514.x
PG 11
WC Psychiatry
SC Psychiatry
GA 591RE
UT WOS:000277319700002
PM 19958306
ER
PT J
AU Tondo, L
Lepri, B
Cruz, N
Baldessarini, RJ
AF Tondo, L.
Lepri, B.
Cruz, N.
Baldessarini, R. J.
TI Age at onset in 3014 Sardinian bipolar and major depressive disorder
patients
SO ACTA PSYCHIATRICA SCANDINAVICA
LA English
DT Article
DE bipolar I and II disorders; major depressive disorder onset age
ID OF-ONSET; ANTIDEPRESSANT TREATMENT; FAMILY-HISTORY; CASE REGISTRY;
ILLNESS; PERSONALITY; COMORBIDITY; RECURRENT; PATTERNS; EPISODE
AB Objective:
To test if onset age in major affective illnesses is younger in bipolar disorder (BPD) than unipolar-major depressive disorder (UP-MDD), and is a useful measure.
Method:
We evaluated onset-age for DSM-IV-TR major illnesses in 3014 adults (18.5% BP-I, 12.5% BP-II, 69.0% UP-MDD; 64% women) at a mood-disorders center.
Results:
Median and interquartile range (IQR) onset-age ranked: BP-I = 24 (19-32) < BP-II = 29 (20-40) < UP-MDD = 32 (23-47) years (P < 0.0001), and has remained stable since the 1970s. In BP-I patients, onset was latest for hypomania, and depression presented earlier than in BP-II or UP-MDD cases. Factors associated with younger onset included: i) being unmarried, ii) more education, iii) BPD-diagnosis, iv) family-history, v) being employed, vi) ever-suicidal, vii) substance-abuse and viii) ever-hospitalized. Onset-age distinguished BP-I from UP-MDD depressive onsets with weak sensitivity and specificity.
Conclusion:
Onset age was younger among BPD than MDD patients, and very early onset may distinguish BPD vs. UP-MDD with depressive-onset.
C1 [Tondo, L.; Cruz, N.; Baldessarini, R. J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
[Tondo, L.; Cruz, N.; Baldessarini, R. J.] Massachusetts Gen Hosp, Int Consortium Psychot & Mood Disorders Res, McLean Div, Boston, MA 02114 USA.
[Tondo, L.] Univ Cagliari, Dept Psychol, Sardinia, Italy.
[Tondo, L.; Lepri, B.] Lucio Bini Mood Disorder Res Ctr, Cagliari, Sardinia, Italy.
[Cruz, N.] Univ Barcelona, Dept Psychiat, E-08007 Barcelona, Spain.
RP Baldessarini, RJ (reprint author), McLean Hosp, Mailman Res Ctr, 115 Mill St, Belmont, MA 02178 USA.
EM rjb@mclean.org
FU Centro Bini Private Donors Research Fund; Bruce J. Anderson Foundation;
McLean Private Donors Psychotic and Mood Disorders Research Fund;
University of Barcelona
FX Supported by the Centro Bini Private Donors Research Fund (LT, BL), a
grant from the Bruce J. Anderson Foundation and by the McLean Private
Donors Psychotic and Mood Disorders Research Fund (RJB), and by a
Research Fellowship from the University of Barcelona (NC).
NR 38
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U1 3
U2 4
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 JUN
PY 2010
VL 121
IS 6
BP 446
EP 452
DI 10.1111/j.1600-0447.2009.01523.x
PG 7
WC Psychiatry
SC Psychiatry
GA 591RE
UT WOS:000277319700007
PM 20040069
ER
PT J
AU Morris, DW
Trivedi, MH
Husain, MM
Fava, M
Budhwar, N
Wisniewski, SR
Miyahara, S
Gollan, JK
Davis, LL
Daly, EJ
Rush, AJ
AF Morris, D. W.
Trivedi, M. H.
Husain, M. M.
Fava, M.
Budhwar, N.
Wisniewski, S. R.
Miyahara, S.
Gollan, J. K.
Davis, L. L.
Daly, E. J.
Rush, A. J.
TI Indicators of pretreatment suicidal ideation in adults with major
depressive disorder
SO ACTA PSYCHIATRICA SCANDINAVICA
LA English
DT Article
DE suicidal ideation; suicide; depression; major depressive disorder; mood
disorder
ID RISK; ANTIDEPRESSANTS; QUESTIONNAIRE; COMORBIDITY; HISTORY; SCALE
AB Objective:
In order to evaluate the presence of treatment emergent suicidal ideation (SI), it becomes necessary to identify those patients with SI at the onset of treatment. The purpose of this report is to identify sociodemographic and clinical features that are associated with SI in major depressive disorder (MDD) patients prior to treatment with a selective serotonin reuptake inhibitor.
Method:
This multisite study enrolled 265 out-patients with non-psychotic MDD. Sociodemographic and clinical features of participants with and without SI were compared post hoc.
Results:
Social phobia, bulimia nervosa, number of past depressive episodes, and race were independently associated with SI by one or more SI measure.
Conclusion:
Concurrent social phobia and bulimia nervosa may be potential risk factors for SI in patients with non-psychotic MDD. Additionally, patients with more than one past depressive episode may also be at increased risk of SI.
C1 [Morris, D. W.] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Mood Disorders Program, Dallas, TX 75390 USA.
[Fava, M.] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA.
[Budhwar, N.] Univ Texas SW Med Ctr Dallas, Dept Family & Community Med, Dallas, TX 75390 USA.
[Wisniewski, S. R.; Miyahara, S.] Univ Pittsburgh, Grad Sch Publ Hlth, Epidemiol Data Ctr, Pittsburgh, PA USA.
[Gollan, J. K.] Northwestern Univ, Asher Ctr Study & Treatment Depress Disorders, Feinberg Sch Med, Chicago, IL 60611 USA.
[Davis, L. L.] Univ Alabama, VA Med Ctr, Tuscaloosa, AL USA.
[Rush, A. J.] Duke Natl Univ Singapore, Singapore, Singapore.
RP Morris, DW (reprint author), Univ Texas SW Med Ctr Dallas, Dept Psychiat, Mood Disorders Program, 6363 Forest Pk Rd,Suite 13-354, Dallas, TX 75390 USA.
EM davidw.morris@utsouthwestern.edu
OI Wisniewski, Stephen/0000-0002-3877-9860; Rush,
Augustus/0000-0003-2004-2382
FU National Institute of Mental Health [N01MH90003]
FX This project was funded by the National Institute of Mental Health under
Contract N01MH90003 to UT Southwestern Medical Center at Dallas (PI,
Trivedi MH). The content of this publication does not necessarily
reflect the views or policies of the Department of Health and Human
Services, nor does mention of trade names, commercial products, or
organizations imply endorsement by the U.S. Government.The NIMH approved
of the design of the overall study and reviewed its conduct, but
performed no role in the collection, management, and interpretation of
the data analyzed in this manuscript, nor in the preparation, review, or
approval of the manuscript.
NR 16
TC 10
Z9 10
U1 0
U2 0
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 JUN
PY 2010
VL 121
IS 6
BP 480
EP 484
DI 10.1111/j.1600-0447.2009.01516.x
PG 5
WC Psychiatry
SC Psychiatry
GA 591RE
UT WOS:000277319700011
PM 19958307
ER
PT J
AU O'Neill, ED
Wilding, JPH
Kahn, CR
Van Remmen, H
McArdle, A
Jackson, MJ
Close, GL
AF O'Neill, Elaine D.
Wilding, John P. H.
Kahn, C. Ronald
Van Remmen, Holly
McArdle, Anne
Jackson, Malcolm J.
Close, Graeme L.
TI Absence of insulin signalling in skeletal muscle is associated with
reduced muscle mass and function: evidence for decreased protein
synthesis and not increased degradation
SO AGE
LA English
DT Article
DE Ageing; ROS; Muscle
ID OXIDATIVE STRESS; METABOLIC SYNDROME; CONTRACTILE ACTIVITY; IN-VIVO;
MICE; ATROPHY; MECHANISMS; RESISTANCE; EXERCISE; AUTOPHAGY
AB Loss of skeletal muscle mass and function is observed in many insulin-resistant disease states such as diabetes, cancer cachexia, renal failure and ageing although the mechanisms for this remain unclear. We hypothesised that impaired insulin signalling results in reduced muscle mass and function and that this decrease in muscle mass and function is due to both increased production of atrogenes and aberrant reactive oxygen species (ROS) generation. Maximum tetanic force of the extensor digitorum longus of muscle insulin receptor knockout (MIRKO) and lox/lox control mice was measured in situ. Muscles were removed for the measurement of mass, histological examination and ROS production. Activation of insulin signalling pathways, markers of muscle atrophy and indices of protein synthesis were determined in a separate group of MIRKO and lox/lox mice 15 min following treatment with insulin. Muscles from MIRKO mice had 36% lower maximum tetanic force generation compared with muscles of lox/lox mice. Muscle fibres of MIRKO mice were significantly smaller than those of lox/lox mice with no apparent structural abnormalities. Muscles from MIRKO mice demonstrated absent phosphorylation of AKT in response to exogenous insulin along with a failure to phosphorylate ribosomal S6 compared with lox/lox mice. Atrogin-1 and MuRF1 relative mRNA expression in muscles from MIRKO mice were decreased compared with muscles from lox/lox mice following insulin treatment. There were no differences in markers of reactive oxygen species damage between muscles from MIRKO mice and lox/lox mice. These data support the hypothesis that the absence of insulin signalling contributes to reduced muscle mass and function though decreased protein synthesis rather than proteasomal atrophic pathways.
C1 [O'Neill, Elaine D.; Wilding, John P. H.; McArdle, Anne; Jackson, Malcolm J.] Univ Liverpool, Sch Clin Sci, Liverpool L69 3GA, Merseyside, England.
[Kahn, C. Ronald] Harvard Univ, Sch Med, Dept Med, Joslin Diabet Ctr, Boston, MA 02215 USA.
[Van Remmen, Holly] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA.
RP Close, GL (reprint author), Liverpool John Moores Univ, Res Inst Sport & Exercise Sci, Liverpool L3 2ET, Merseyside, England.
EM g.l.close@ljmu.ac.uk
RI Close, graeme/I-7287-2012; Wilding, John/A-7106-2008;
OI Wilding, John/0000-0003-2839-8404; Jackson, Malcolm/0000-0003-3683-8297
FU Nathan Shock Center for Excellence in Basic Biology of Aging [AG 13319]
FX The authors would like to thank Dr. Anna Kayani and Dr. Lea Zibrik from
the Pathophysiology group at The University of Liverpool for their
assistance with the PCR, Dr. Daniel Cuthbertson for his assistance in
the preparation of the manuscript, Research into Ageing for their
continued financial support and the Oxidative Stress Core of the Nathan
Shock Center for Excellence in Basic Biology of Aging, Grant, AG 13319
(HVR).
NR 42
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U1 3
U2 8
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0161-9152
J9 AGE
JI Age
PD JUN
PY 2010
VL 32
IS 2
BP 209
EP 222
DI 10.1007/s11357-009-9125-0
PG 14
WC Geriatrics & Gerontology
SC Geriatrics & Gerontology
GA 590BL
UT WOS:000277198300008
PM 20431988
ER
PT J
AU Jensen, DK
Lal, A
AF Jensen, Danielle K.
Lal, Ashish
TI Micromanaging senescence
SO AGING-US
LA English
DT Article
ID CELL-PROLIFERATION; BINDING; HUR
C1 [Lal, Ashish] Harvard Univ, Childrens Hosp Boston, Sch Med, Immune Dis Inst, Boston, MA 02115 USA.
Harvard Univ, Childrens Hosp Boston, Sch Med, Program Cellular & Mol Med, Boston, MA 02115 USA.
RP Lal, A (reprint author), Harvard Univ, Childrens Hosp Boston, Sch Med, Immune Dis Inst, Boston, MA 02115 USA.
EM alal@idi.harvard.edu
NR 8
TC 2
Z9 2
U1 0
U2 0
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1945-4589
J9 AGING-US
JI Aging-US
PD JUN
PY 2010
VL 2
IS 6
BP 322
EP 323
PG 2
WC Cell Biology
SC Cell Biology
GA 636ID
UT WOS:000280724300004
PM 20603523
ER
PT J
AU Bogart, LM
Howerton, D
Lange, J
Setodji, CM
Becker, K
Klein, DJ
Asch, SM
AF Bogart, Laura M.
Howerton, Devery
Lange, James
Setodji, Claude Messan
Becker, Kirsten
Klein, David J.
Asch, Steven M.
TI Provider-related Barriers to Rapid HIV Testing in US Urban Non-profit
Community Clinics, Community-based Organizations (CBOs) and Hospitals
SO AIDS AND BEHAVIOR
LA English
DT Article
DE Rapid HIV testing; Provider barriers; Hospitals; Community clinics;
Community-based organizations
ID UNITED-STATES; OF-CARE; RANDOMIZED-TRIAL; EXPERIENCE; ROUTINE; LABOR;
METAANALYSIS; FLUID; IMPLEMENTATION; PREVENTION
AB We examined provider-reported barriers to rapid HIV testing in U.S. urban non-profit community clinics, community-based organizations (CBOs), and hospitals. 12 primary metropolitan statistical areas (PMSAs; three per region) were sampled randomly, with sampling weights proportional to AIDS case reports. Across PMSAs, all 671 hospitals and a random sample of 738 clinics/CBOs were telephoned for a survey on rapid HIV test availability. Of the 671 hospitals, 172 hospitals were randomly selected for barriers questions, for which 158 laboratory and 136 department staff were eligible and interviewed in 2005. Of the 738 clinics/CBOs, 276 were randomly selected for barriers questions, 206 were reached, and 118 were eligible and interviewed in 2005-2006. In multivariate models, barriers regarding translation of administrative/quality assurance policies into practice were significantly associated with rapid HIV testing availability. For greater rapid testing diffusion, policies are needed to reduce administrative barriers and provide quality assurance training to non-laboratory staff.
C1 [Bogart, Laura M.; Setodji, Claude Messan; Becker, Kirsten; Klein, David J.; Asch, Steven M.] RAND Corp, Santa Monica, CA 90407 USA.
[Howerton, Devery; Lange, James] Ctr Dis Control & Prevent, Lab Practice Evaluat & Genom Branch, Atlanta, GA USA.
[Asch, Steven M.] VA Greater Los Angeles Healthcare Network, Los Angeles, CA USA.
[Asch, Steven M.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
RP Bogart, LM (reprint author), RAND Corp, 1776 Main St,POB 2138, Santa Monica, CA 90407 USA.
EM lbogart@rand.org
FU PHS HHS [U65/CCU924523-01]
NR 61
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U1 2
U2 4
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1090-7165
J9 AIDS BEHAV
JI AIDS Behav.
PD JUN
PY 2010
VL 14
IS 3
BP 697
EP 707
DI 10.1007/s10461-008-9456-3
PG 11
WC Public, Environmental & Occupational Health; Social Sciences, Biomedical
SC Public, Environmental & Occupational Health; Biomedical Social Sciences
GA 592VU
UT WOS:000277410500023
PM 18770022
ER
PT J
AU Pearline, RV
Tucker, JD
Yuan, LF
Bu, J
Yin, YP
Chen, XS
Cohen, MS
AF Pearline, Rachel V.
Tucker, Joseph D.
Yuan, Liu-Feng
Bu, Jin
Yin, Yue-Ping
Chen, Xiang-Sheng
Cohen, Myron S.
TI Sexually Transmitted Infections Among Individuals Over Fifty Years of
Age in China
SO AIDS PATIENT CARE AND STDS
LA English
DT Letter
ID SYPHILIS; HIV
C1 [Yuan, Liu-Feng; Bu, Jin; Yin, Yue-Ping; Chen, Xiang-Sheng] Chinese Acad Med Sci, Natl Ctr STD Control, Nanjing, Peoples R China.
[Yuan, Liu-Feng; Bu, Jin; Yin, Yue-Ping; Chen, Xiang-Sheng] Peking Union Med Coll, Inst Dermatol, Nanjing, Peoples R China.
[Cohen, Myron S.] Univ N Carolina, Sch Med, Chapel Hill, NC USA.
[Pearline, Rachel V.] Tulane Univ, Sch Med, New Orleans, LA 70112 USA.
[Tucker, Joseph D.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Tucker, Joseph D.] Harvard Univ, Sch Med, Boston, MA USA.
RP Chen, XS (reprint author), China CDC, Natl Ctr STD Control, 12 Jiangwangmiao Rd, Nanjing 210042, Jiangsu, Peoples R China.
EM chenxs@ncstdlc.org
FU FIC NIH HHS [D43 TW01039]
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U1 0
U2 1
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1087-2914
J9 AIDS PATIENT CARE ST
JI Aids Patient Care STDS
PD JUN
PY 2010
VL 24
IS 6
BP 345
EP 347
DI 10.1089/apc.2009.0323
PG 3
WC Public, Environmental & Occupational Health; Infectious Diseases
SC Public, Environmental & Occupational Health; Infectious Diseases
GA 614CN
UT WOS:000279032800001
PM 20515416
ER
PT J
AU Baillargeon, J
Giordano, TP
Harzke, AJ
Spaulding, AC
Wu, ZH
Grady, JJ
Baillargeon, G
Paar, DP
AF Baillargeon, Jacques
Giordano, Thomas P.
Harzke, Amy Jo
Spaulding, Anne C.
Wu, Z. Helen
Grady, James J.
Baillargeon, Gwen
Paar, David P.
TI Predictors of Reincarceration and Disease Progression Among Released
HIV-Infected Inmates
SO AIDS PATIENT CARE AND STDS
LA English
DT Article
ID US CORRECTIONAL FACILITIES; ANTIRETROVIRAL THERAPY;
PSYCHIATRIC-DISORDERS; HEALTH-SERVICES; PRISON RELEASE; CARE; COMMUNITY;
INCARCERATION; ADHERENCE; WOMEN
AB We conducted a retrospective cohort study to determine the 3-year reincarceration rate of all HIV-infected inmates (n = 1917) released from the Texas prison system between January 2004 and March 2006. We also analyzed postrelease changes in HIV clinical status in the subgroup of inmates who were subsequently reincarcerated and had either CD4 lymphocyte counts (n = 119) or plasma HIV RNA levels (n = 122) recorded in their electronic medical record at both release and reincarceration. Multivariable analyses were performed to assess predictors of reincarceration and clinical changes in HIV status. Only 20% of all HIV-infected inmates were reincarcerated within 3 years of release. Female inmates (hazard ratio [HR] 0.63; 95% confidence interval [CI], 0.47, 0.84) and inmates taking antiretroviral therapy at the time of release (HR 0.31; 95% CI, 0.25, 0.39) were at decreased risk of reincarceration. African Americans (HR 1.58; 95% CI, 1.22, 2.05), inmates with a major psychiatric disorder (HR 1.82; 95% CI, 1.41, 2.34), and inmates released on parole (HR 2.86; 95% CI, 2.31, 3.55) were at increased risk of reincarceration. A subgroup of reincarcerated inmates had a mean decrease in CD4 cell count of 79.4 lymphocytes per microliter (p<0.0003) and a mean increase in viral load of 1.5 log(10) copies per milliliter (p<0.0001) in the period between release and reincarceration. Our findings, although substantially limited by selection bias, highlight the importance of developing discharge planning programs to improve linkage to community-based HIV care and reduce recidivism among released HIV-infected inmates.
C1 [Baillargeon, Jacques; Harzke, Amy Jo; Grady, James J.; Paar, David P.] Univ Texas Med Branch, Dept Prevent Med & Community Hlth, Galveston, TX 77555 USA.
[Baillargeon, Jacques; Harzke, Amy Jo; Baillargeon, Gwen] Univ Texas Med Branch, Community Hlth Serv, Galveston, TX 77555 USA.
[Giordano, Thomas P.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA.
[Giordano, Thomas P.] Michael E DeBakey VA Med Ctr Hlth Serv, Res & Dev Ctr Excellence, Houston, TX USA.
[Spaulding, Anne C.] Emory Univ, Dept Med, Atlanta, GA 30322 USA.
[Wu, Z. Helen] Univ Texas Med Branch, Dept Obstet & Gynecol, Galveston, TX 77555 USA.
[Paar, David P.] Univ Texas Med Branch, Dept Med, Galveston, TX 77555 USA.
RP Baillargeon, J (reprint author), Univ Texas Med Branch, Dept Prevent Med & Community Hlth, 301 Univ Blvd,Mail Route 1007, Galveston, TX 77555 USA.
EM jbaillar@utmb.edu
FU National Institute on Drug Abuse [R03-DA023870-02]; National Institutes
of Health [K01-DA-21814]
FX This study was supported by a grant from the National Institute on Drug
Abuse # R03-DA023870-02. Dr. Wu's participation was also supported by
National Institutes of Health grant K01-DA-21814. The authors thank Mr.
Leonard Pechacek for assistance in editing the manuscript and Ms. DeeAnn
Novakosky for data management assistance. The research described herein
was coordinated in part by the Texas Department of Criminal Justice
(TDCJ) research agreement # 542-MR07. The contents of this manuscript
reflect the views of the authors and not necessarily those of the TDCJ
or the Department of Veterans Affairs.
NR 36
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U1 1
U2 7
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1087-2914
J9 AIDS PATIENT CARE ST
JI Aids Patient Care STDS
PD JUN
PY 2010
VL 24
IS 6
BP 389
EP 394
DI 10.1089/apc.2009.0303
PG 6
WC Public, Environmental & Occupational Health; Infectious Diseases
SC Public, Environmental & Occupational Health; Infectious Diseases
GA 614CN
UT WOS:000279032800008
PM 20565323
ER
PT J
AU Froehlich, JC
Federoff, D
Rasmussen, DD
AF Froehlich, J. C.
Federoff, D.
Rasmussen, D. D.
TI PRAZOSIN, AN A(1)-ADRENERGIC RECEPTOR ANTAGONIST, MAINTAINS CONTINUED
SUPPRESSION OF ALCOHOL DRINKING DURING PROLONGED ADMINISTRATION
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 33rd Annual Meeting of the Research-Society-on-Alcoholism
CY JUN 26-30, 2010
CL San Antonio, TX
SP Res Soc Alcoholism
C1 [Froehlich, J. C.; Federoff, D.] Indiana Univ Sch Med, Indianapolis, IN 46202 USA.
[Rasmussen, D. D.] Univ Washington, Seattle, WA 98195 USA.
[Rasmussen, D. D.] VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2010
VL 34
IS 6
SU 2
BP 19A
EP 19A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 601ZJ
UT WOS:000278107200034
ER
PT J
AU Rasmussen, DD
Kincaid, CL
AF Rasmussen, D. D.
Kincaid, C. L.
TI PROTRACTED ABSTINENCE FOLLOWING CHRONIC ETHANOL: INCREASED LOCUS
COERULEUS TYROSINE HYDROXYLASE GENE EXPRESSION IS REVERSED BY MELATONIN
TREATMENT IN RATS
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 33rd Annual Meeting of the Research-Society-on-Alcoholism
CY JUN 26-30, 2010
CL San Antonio, TX
SP Res Soc Alcoholism
C1 Univ Washington, Seattle, WA 98108 USA.
VA Puget Sound Hlth Care Syst, VISN Mental Illness Res Educ & Clin Ctr 20, Seattle, WA 98108 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 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2010
VL 34
IS 6
SU 2
BP 19A
EP 19A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 601ZJ
UT WOS:000278107200035
ER
PT J
AU Durazzo, TC
Gazdzinski, S
Mon, A
Wang, J
Meyerhoff, DJ
AF Durazzo, T. C.
Gazdzinski, S.
Mon, A.
Wang, J.
Meyerhoff, D. J.
TI N-ACETYLASPARTATE LEVELS IN THE BRAIN REWARD SYSTEM DIFFERENTIATE
SMOKING AND NON-SMOKING ALCOHOL DEPENDENT INDIVIDUALS DURING EARLY
ABSTINENCE
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 33rd Annual Meeting of the Research-Society-on-Alcoholism
CY JUN 26-30, 2010
CL San Antonio, TX
SP Res Soc Alcoholism
C1 [Durazzo, T. C.; Gazdzinski, S.; Mon, A.; Wang, J.; Meyerhoff, D. J.] Univ Calif San Francisco, San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis, San Francisco, CA 94143 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 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2010
VL 34
IS 6
SU 2
BP 24A
EP 24A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 601ZJ
UT WOS:000278107200054
ER
PT J
AU Leite-Morris, KA
Frank, LE
AF Leite-Morris, K. A.
Frank, L. E.
TI MICROINJECTION OF GABA A RECEPTOR AGONIST INTO THE VENTRAL TEGMENTAL
AREA INHIBITS ETHANOL'S MOTIVATED BEHAVIOR IN LONG TERM BINGE DRINKING
RATS
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 33rd Annual Meeting of the Research-Society-on-Alcoholism
CY JUN 26-30, 2010
CL San Antonio, TX
SP Res Soc Alcoholism
C1 Boston Univ, Sch Med, Div Psychiat, Boston, MA 02130 USA.
Boston Univ, Sch Med, Dept Pharmacol & Expt Therapeut, Boston, MA 02130 USA.
VA Boston Healthcare Syst, Res Serv, Boston, MA 02130 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 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2010
VL 34
IS 6
SU 2
BP 38A
EP 38A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 601ZJ
UT WOS:000278107200111
ER
PT J
AU Walter, NAR
Denmark, DL
Buck, KJ
AF Walter, N. A. R.
Denmark, D. L.
Buck, K. J.
TI FINE-MAPPING MULTIPLE TRANS-REGULATION EVENTS ON MOUSE DISTAL CHROMOSOME
1 POTENTIALLY INVOLVED IN ETHANOL SENSITIVITY AND WITHDRAWAL
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 33rd Annual Meeting of the Research-Society-on-Alcoholism
CY JUN 26-30, 2010
CL San Antonio, TX
SP Res Soc Alcoholism
C1 Oregon Hlth & Sci Univ, Portland, OR 97239 USA.
Portland VA Med Ctr, Portland, OR 97239 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 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2010
VL 34
IS 6
SU 2
BP 131A
EP 131A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 601ZJ
UT WOS:000278107200485
ER
PT J
AU Chen, S
Charness, ME
AF Chen, S.
Charness, M. E.
TI ETHANOL MODULATES DENDRITE MORPHOGENESIS OF CEREBELLAR GRANULE NEURONS
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 33rd Annual Meeting of the Research-Society-on-Alcoholism
CY JUN 26-30, 2010
CL San Antonio, TX
SP Res Soc Alcoholism
C1 Harvard Univ, Sch Med, Dept Neurol, W Roxbury, MA 02132 USA.
VA Boston Healthcare Syst, W Roxbury, MA 02132 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 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2010
VL 34
IS 6
SU 2
BP 159A
EP 159A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 601ZJ
UT WOS:000278107200595
ER
PT J
AU Kelly, JF
Dow, SJ
Yeterian, JD
AF Kelly, J. F.
Dow, S. J.
Yeterian, J. D.
TI CAN AA PARTICIPATION POTENTIATE AND EXTEND THE BENEFITS OF ADOLESCENT
OUTPATIENT TREATMENT? A LAGGED ANALYSIS OF PREDICTORS AND EFFECTS
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 33rd Annual Meeting of the Research-Society-on-Alcoholism
CY JUN 26-30, 2010
CL San Antonio, TX
SP Res Soc Alcoholism
C1 [Kelly, J. F.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[Kelly, J. F.; Dow, S. J.; Yeterian, J. D.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2010
VL 34
IS 6
SU 2
BP 173A
EP 173A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 601ZJ
UT WOS:000278107200650
ER
PT J
AU Batki, SL
Dimmock, JA
Meszaros, ZS
Ploutz-Snyder, R
Cavallerano, M
Leontieva, L
Carey, KB
Maisto, SA
Canfield, K
AF Batki, S. L.
Dimmock, J. A.
Meszaros, Z. S.
Ploutz-Snyder, R.
Cavallerano, M.
Leontieva, L.
Carey, K. B.
Maisto, S. A.
Canfield, K.
TI EXTENDED-RELEASE NALTREXONE FOR ALCOHOL DEPENDENCE IN PATIENTS WITH
SERIOUS MENTAL ILLNESS
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 33rd Annual Meeting of the Research-Society-on-Alcoholism
CY JUN 26-30, 2010
CL San Antonio, TX
SP Res Soc Alcoholism
C1 San Francisco VA Med Ctr, UCSF Dept Psychiat, San Francisco, CA 94121 USA.
SUNY Upstate Med Univ, Syracuse, NY 13210 USA.
Syracuse Univ, Syracuse, NY 13210 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2010
VL 34
IS 6
SU 2
BP 176A
EP 176A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 601ZJ
UT WOS:000278107200661
ER
PT J
AU Myrick, H
Li, X
Randall, P
Henderson, S
Anton, R
AF Myrick, H.
Li, X.
Randall, P.
Henderson, S.
Anton, R.
TI THE EFFECT OF VARENICLINE ON CUE-INDUCED BRAIN ACTIVATION AND DRINKING
PARAMETERS IN ALCOHOLICS
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 33rd Annual Meeting of the Research-Society-on-Alcoholism
CY JUN 26-30, 2010
CL San Antonio, TX
SP Res Soc Alcoholism
C1 [Myrick, H.; Li, X.; Randall, P.; Henderson, S.; Anton, R.] Med Univ S Carolina, Alcohol Res Ctr, Dept Psychiat, Ralph H Johnson VAMC, Charleston, SC 29425 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2010
VL 34
IS 6
SU 2
BP 177A
EP 177A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 601ZJ
UT WOS:000278107200668
ER
PT J
AU Lapham, GT
Rubinsky, AD
Hawkins, EJ
Kivlahan, DR
Bradley, KA
AF Lapham, G. T.
Rubinsky, A. D.
Hawkins, E. J.
Kivlahan, D. R.
Bradley, K. A.
TI TRAJECTORIES OF ALCOHOL SCREENING SCORES OVER TIME
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 33rd Annual Meeting of the Research-Society-on-Alcoholism
CY JUN 26-30, 2010
CL San Antonio, TX
SP Res Soc Alcoholism
C1 [Lapham, G. T.; Rubinsky, A. D.; Hawkins, E. J.; Kivlahan, D. R.; Bradley, K. A.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA 98101 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 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2010
VL 34
IS 6
SU 2
BP 180A
EP 180A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 601ZJ
UT WOS:000278107200678
ER
PT J
AU Dou, X
Wilkemyer, MF
Menkari, CE
Charness, ME
AF Dou, X.
Wilkemyer, M. F.
Menkari, C. E.
Charness, M. E.
TI L1 SENSITIVITY TO ETHANOL IS MODULATED BY THE MAPK SIGNALING PATHWAY
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 33rd Annual Meeting of the Research-Society-on-Alcoholism
CY JUN 26-30, 2010
CL San Antonio, TX
SP Res Soc Alcoholism
C1 [Dou, X.; Wilkemyer, M. F.; Menkari, C. E.; Charness, M. E.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, W Roxbury, MA 02132 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 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2010
VL 34
IS 6
SU 2
BP 209A
EP 209A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 601ZJ
UT WOS:000278107200795
ER
PT J
AU Kelly, JF
Dow, SJ
Westerhoff, C
AF Kelly, J. F.
Dow, S. J.
Westerhoff, C.
TI DOES OUR CHOICE OF SUBSTANCE-RELATED TERMINOLOGY INFLUENCE PERCEPTIONS
OF TREATMENT NEED? AN EMPIRICAL INVESTIGATION WITH TWO COMMONLY USED
TERMS
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 33rd Annual Meeting of the Research-Society-on-Alcoholism
CY JUN 26-30, 2010
CL San Antonio, TX
SP Res Soc Alcoholism
C1 [Kelly, J. F.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[Kelly, J. F.; Dow, S. J.; Westerhoff, C.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2010
VL 34
IS 6
SU 2
BP 232A
EP 232A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 601ZJ
UT WOS:000278107200888
ER
PT J
AU Das, J
Pany, S
Shanmugasundararaj, S
Miller, KW
AF Das, J.
Pany, S.
Shanmugasundararaj, S.
Miller, K. W.
TI ALCOHOL BINDING SITE(S) IN PROTEIN KINASE C EPSILON
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 33rd Annual Meeting of the Research-Society-on-Alcoholism
CY JUN 26-30, 2010
CL San Antonio, TX
SP Res Soc Alcoholism
C1 [Das, J.; Pany, S.; Shanmugasundararaj, S.; Miller, K. W.] Univ Houston, Dept Pharmacol & Pharmaceut Sci, Houston, TX 77204 USA.
[Das, J.; Pany, S.; Shanmugasundararaj, S.; Miller, K. W.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2010
VL 34
IS 6
SU 2
SI SI
BP 247A
EP 247A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 777RF
UT WOS:000291641500013
ER
PT J
AU Myrick, H
AF Myrick, H.
TI NEUROIMAGING PREDICTORS OF RESPONSE TO ARIPIPRAZOLE AND VARENICLINE
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 33rd Annual Meeting of the Research-Society-on-Alcoholism
CY JUN 26-30, 2010
CL San Antonio, TX
SP Res Soc Alcoholism
C1 [Myrick, H.] Med Univ S Carolina, Alcohol Res Ctr, Charleston, SC 29425 USA.
[Myrick, H.] Ralph H Johnson VAMC, Mental Hlth Serv Line, Charleston, SC 29425 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2010
VL 34
IS 6
SU 2
SI SI
BP 264A
EP 264A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 777RF
UT WOS:000291641500079
ER
PT J
AU Kelly, JF
Stout, RL
Magill, M
Tonigan, JS
Pagano, M
AF Kelly, J. F.
Stout, R. L.
Magill, M.
Tonigan, J. S.
Pagano, M.
TI GOD GRANT ME PATIENCE, AND GRANT IT RIGHT NOW! SPIRITUALITY, ALCOHOLICS
ANONYMOUS, AND ALCOHOL TREATMENT OUTCOME
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 33rd Annual Meeting of the Research-Society-on-Alcoholism
CY JUN 26-30, 2010
CL San Antonio, TX
SP Res Soc Alcoholism
C1 [Kelly, J. F.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Kelly, J. F.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[Stout, R. L.] Decis Sci Inst, Atlanta, GA USA.
[Magill, M.] Brown Univ, Providence, RI 02912 USA.
[Tonigan, J. S.] Univ New Mexico, CAASA, Albuquerque, NM 87131 USA.
[Pagano, M.] Case Western Reserve, Cleveland, OH USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2010
VL 34
IS 6
SU 2
SI SI
BP 269A
EP 269A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 777RF
UT WOS:000291641500099
ER
PT J
AU Sherwood, MW
Morrow, DA
Scirica, BM
Jiang, ST
Bode, C
Rifai, N
Gerszten, RE
Gibson, CM
Cannon, CP
Braunwald, E
Sabatine, MS
AF Sherwood, Matthew W.
Morrow, David A.
Scirica, Benjamin M.
Jiang, Songtao
Bode, Christoph
Rifai, Nader
Gerszten, Robert E.
Gibson, C. Michael
Cannon, Christopher P.
Braunwald, Eugene
Sabatine, Marc S.
TI Early dynamic risk stratification with baseline troponin levels and
90-minute ST-segment resolution to predict 30-day cardiovascular
mortality in ST-segment elevation myocardial infarction: Analysis from
CLopidogrel as Adjunctive ReperfusIon TherapY (CLARITY) - Thrombolysis
in Myocardial Infarction (TIMI) 28
SO AMERICAN HEART JOURNAL
LA English
DT Article
ID ACUTE CORONARY SYNDROMES; PROGNOSTIC-SIGNIFICANCE; FIBRINOLYTIC THERAPY;
ADMISSION; TRIAL; RECLASSIFICATION; INTERVENTION; EFFICACY; INSIGHTS;
ABILITY
AB Background Troponin is the preferred biomarker for risk stratification in non-ST elevation ACS. The incremental prognostic use of the initial magnitude of troponin elevation and its value in conjunction with ST-segment resolution (STRes) in ST elevation myocardial infarction (STEMI) is less well defined.
Methods Troponin T (TnT) was measured in 1,250 patients at presentation undergoing fibrinolysis for STEMI in CLARITY-TIMI 28. ST-segment resolution was measured at 90 minutes. Multivariable logistic regression was used to examine the independent association between TnT levels, STRes, and 30-day cardiovascular (CV) mortality.
Results Patients were classified into undetectable TnT at baseline (n=594), detectable but below the median of 0.12 ng/mL (n=330), and above the median (n=326). Rates of 30-day CV death were 1.5%, 4.5%, and 9.5%, respectively (P<.0001). Compared with those with undetectable levels and adjusting for baseline factors, the odds ratios for 30-day CV death were 4.56 (1.72-12.08, P=.002) and 5.81 (2.29-14.73, P=.0002) for those below and above the median, respectively. When combined with STRes, there was a significant gradient of risk, and in a multivariable model both baseline TnT (P=.004) and STRes (P=.003) were significant predictors of 30-day CV death. The addition of TnT and STRes to clinical risk factors significantly improved the C-statistic (from 0.86 to 0.90, P=.02) and the integrated discriminative improvement (7.1% increase) (P=.0009).
Conclusions Baseline TnT and 90-minute STRes are independent predictors of 30-day CV death in patients with STEMI. Use of these 2 simple, readily available tools can aid clinicians in early risk stratification. (Am Heart J 2010; 159: 964-971.e1.)
C1 [Sherwood, Matthew W.; Morrow, David A.; Scirica, Benjamin M.; Cannon, Christopher P.; Braunwald, Eugene; Sabatine, Marc S.] Brigham & Womens Hosp, Div Cardiovasc Med, TIMI Study Grp, Boston, MA 02115 USA.
[Sherwood, Matthew W.; Morrow, David A.; Scirica, Benjamin M.; Rifai, Nader; Gerszten, Robert E.; Gibson, C. Michael; Cannon, Christopher P.; Braunwald, Eugene; Sabatine, Marc S.] Harvard Univ, Sch Med, Boston, MA USA.
[Jiang, Songtao] Harvard Clin Res Inst, Boston, MA USA.
[Bode, Christoph] Univ Freiburg, Dept Cardiol, Freiburg, Germany.
[Rifai, Nader] Childrens Hosp, Dept Lab Med, Boston, MA 02115 USA.
[Gerszten, Robert E.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA.
[Gerszten, Robert E.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Gibson, C. Michael] Beth Israel Deaconess Med Ctr, TIMI Study Grp, Boston, MA 02215 USA.
[Gibson, C. Michael] Beth Israel Deaconess Med Ctr, Div Cardiol, Boston, MA 02215 USA.
RP Sabatine, MS (reprint author), Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA.
EM msabatine@partners.org
FU NHLBI NIH HHS [U01 HL081341, U01 HL081341-04]
NR 21
TC 9
Z9 9
U1 1
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-8703
EI 1097-5330
J9 AM HEART J
JI Am. Heart J.
PD JUN
PY 2010
VL 159
IS 6
BP 964
EP U3
DI 10.1016/j.ahj.2010.03.005
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 607UU
UT WOS:000278533200006
PM 20569707
ER
PT J
AU Liu, EJ
Meigs, JB
Pittas, AG
Economos, CD
McKeown, NM
Booth, SL
Jacques, PF
AF Liu, Enju
Meigs, James B.
Pittas, Anastassios G.
Economos, Christina D.
McKeown, Nicola M.
Booth, Sarah L.
Jacques, Paul F.
TI Predicted 25-hydroxyvitamin D score and incident type 2 diabetes in the
Framingham Offspring Study
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID VITAMIN-D STATUS; FOOD FREQUENCY QUESTIONNAIRE; INSULIN-SECRETION; D
DEFICIENCY; SERUM 25-HYDROXYVITAMIN-D; METABOLIC SYNDROME; D
SUPPLEMENTATION; CALCIUM; HEALTH; GLUCOSE
AB Background: Accumulating evidence suggests that vitamin D is involved in the development of type 2 diabetes (T2D).
Objective: Our objective was to examine the relation between vitamin D status and incidence of T2D.
Design: We used a subsample of 1972 Framingham Offspring Study participants to develop a regression model to predict plasma 25-hydroxyvitamin D [25(OH)D] concentrations from age, sex, body mass index, month of blood sampling, total vitamin D intake, smoking status, and total energy intake. Using this model, we calculated the predicted 25(OH)D score for each nondiabetic participant at the cohort's fifth examination to assess the association between the predicted 25(OH)D score and incidence of T2D by using Cox proportional hazards models.
Results: A total of 133 T2D cases were identified over a 7-y average follow-up. In comparison with individuals in the lowest tertile of the predicted 25(OH)D score at baseline, those in the highest tertile had a 40% lower incidence of T2D after adjustment for age, sex, waist circumference, parental history of T2D, hypertension, low HDL cholesterol, elevated triglycerides, impaired fasting glucose, and Dietary Guidelines for Americans Adherence Index score (hazard ratio: 0.60: 95% CI: 0.37, 0.97; P for trend = 0.03).
Conclusions: Our findings suggest that higher vitamin D status is associated with decreased risk of T2D. Maintaining optimal 25(OH)D status may be a strategy to prevent the development of T2D. Am J Clin Nutr 2010;91:1627-33.
C1 [Jacques, Paul F.] Tufts Univ, Program Epidemiol, Human Nutr Res Ctr Aging, Jean Mayer US Dept Agr, Boston, MA 02111 USA.
[Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA.
[Meigs, James B.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Meigs, James B.] Harvard Univ, Sch Med, Boston, MA USA.
[Pittas, Anastassios G.] Tufts Med Ctr, Div Endocrinol Diabet & Metab, Boston, MA USA.
[Economos, Christina D.; McKeown, Nicola M.; Booth, Sarah L.; Jacques, Paul F.] Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA.
RP Jacques, PF (reprint author), Tufts Univ, Program Epidemiol, Human Nutr Res Ctr Aging, Jean Mayer US Dept Agr, 711 Washington St, Boston, MA 02111 USA.
EM paul.jacques@tufts.edu
RI liu, enju/B-2136-2010; liu, enju/F-4062-2010
FU US Department of Agriculture [58-1950-7-707]; National Institute of
Aging [AG 14759]; Framingham Heart Study of the National Heart, Lung,
and Blood Institute of the National Institutes of Health [N01-HC-25195];
American Diabetes Association; NIDDK [K24 DK080140, R01DK076092,
R21DK078867]; Beverage Institute for Health and Wellness
FX Supported in part by the US Department of Agriculture, under agreement
no. 58-1950-7-707, National Institute of Aging (AG 14759). and the
Framingham Heart Study of the National Heart, Lung, and Blood Institute
of the National Institutes of Health (contract no. N01-HC-25195); and by
an American Diabetes Association Career Development Award (JBM), NIDDK
K24 DK080140 (JBM), R01DK076092 and R21DK078867 (AGP), and the Beverage
Institute for Health and Wellness (CDE).
NR 47
TC 68
Z9 73
U1 0
U2 5
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 JUN
PY 2010
VL 91
IS 6
BP 1627
EP 1633
DI 10.3945/ajcn.2009.28441
PG 7
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 598MP
UT WOS:000277841700012
PM 20392893
ER
PT J
AU Grisson, R
Kim, JY
Brodsky, V
Kamis, IK
Singh, B
Belkziz, SM
Batra, S
Myers, HJ
Demyanov, A
Dighe, AS
AF Grisson, Ricky
Kim, Ji Yeon
Brodsky, Victor
Kamis, Irina K.
Singh, Balaji
Belkziz, Sidi M.
Batra, Shalini
Myers, Harold J.
Demyanov, Alexander
Dighe, Anand S.
TI A Novel Class of Laboratory Middleware Promoting Information Flow and
Improving Computerized Provider Order Entry
SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY
LA English
DT Article
DE Informatics; Management; Administration; Order entry
AB A central duty of the laboratory is to inform clinicians about the availability and usefulness of laboratory testing. In this report, we describe a new class of laboratory middleware that connects the traditional clinical laboratory information system with the rest of the enterprise, facilitating information flow about testing services. We demonstrate the value of this approach in efficiently supporting an inpatient order entry application. We also show that order entry monitoring and iterative middleware updates can enhance ordering efficiency and promote improved ordering practices. Furthermore, we demonstrate the value of algorithmic approaches to improve the accuracy and completeness of laboratory test searches. We conclude with a discussion of design recommendations for middleware applications and discuss the potential role of middleware as a sharable, centralized repository of laboratory test information.
C1 [Grisson, Ricky; Kim, Ji Yeon; Brodsky, Victor; Dighe, Anand S.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Kamis, Irina K.; Singh, Balaji; Belkziz, Sidi M.; Batra, Shalini; Myers, Harold J.; Demyanov, Alexander] Partners HealthCare Syst, Informat Syst, Charlestown, MA USA.
RP Dighe, AS (reprint author), Massachusetts Gen Hosp, Dept Pathol, Bigelow Bldg,Room 510,55 Fruit St, Boston, MA 02114 USA.
NR 11
TC 6
Z9 6
U1 0
U2 0
PU AMER SOC CLINICAL PATHOLOGY
PI CHICAGO
PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA
SN 0002-9173
J9 AM J CLIN PATHOL
JI Am. J. Clin. Pathol.
PD JUN
PY 2010
VL 133
IS 6
BP 860
EP 869
DI 10.1309/AJCPCVT30YEMRKRY
PG 10
WC Pathology
SC Pathology
GA 598OE
UT WOS:000277846700006
PM 20472843
ER
PT J
AU Sholl, LM
Xiao, Y
Joshi, V
Yeap, BY
Cioffredi, LA
Jackman, DM
Lee, C
Janne, PA
Lindeman, NI
AF Sholl, Lynette M.
Xiao, Yun
Joshi, Victoria
Yeap, Beow Y.
Cioffredi, Leigh-Anne
Jackman, David M.
Lee, Charles
Jaenne, Pasi A.
Lindeman, Neal I.
TI EGFR Mutation Is a Better Predictor of Response to Tyrosine Kinase
Inhibitors in Non-Small Cell Lung Carcinoma Than FISH, CISH, and
Immunohistochemistry
SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY
LA English
DT Article
DE EGFR; Non-small cell lung carcinoma; Mutation; Fluorescence in situ
hybridization; Chromogenic in situ hybridization; Immunohistochemistry;
Erlotinib
ID GROWTH-FACTOR-RECEPTOR; GENE COPY NUMBER; CHEMOTHERAPY-NAIVE PATIENTS;
IN-SITU-HYBRIDIZATION; PHASE-II; CLINICAL-TRIALS; CANCER PATIENTS;
BRONCHIOLOALVEOLAR-CARCINOMA; GEFITINIB SENSITIVITY; PROTEIN EXPRESSION
AB About 10% of patients with non small cell lung carcinoma (NSCLC) respond to epidermal growth factor receptor (EGFR)-targeted tyrosine kinase inhibitors (TKIs). More than 75% of "responders" have activating mutations in EGFR. However, mutation analysis is not widely available, and proposed alternatives (in situ hybridization and immunohistochemical analysis) have shown inconsistent associations with outcome. Fluorescence in situ hybridization (FISH), chromogenic in situ hybridization (CISH), immunohistochemical analysis, and DNA sequencing were compared in this study of 40 NSCLC samples from TKI-treated patients. Response rates were 12 of 19 in EGFR-mutant vs I of 20 EGFR wild-type tumors (P = .0001), 7 of 19 FISH+ vs 4 of 17 FISH- tumors (not significant [NS]), 5 of 16 CISH+ vs 6 of 21 CISH- tumors (NS), and 3 of 9 immunohistochemically positive vs 7 of 22 immunohistochemically negative tumors (NS). EGFR mutation was associated with improved progression-free survival (P = .0004). Increased copy number (FISH or CISH) and protein expression (immunohistochemical) did not independently predict outcome. Thus, EGFR sequence analysis was the only method useful for predicting response and progression-free survival following TKI therapy in NSCLC.
C1 [Sholl, Lynette M.; Xiao, Yun; Lee, Charles; Lindeman, Neal I.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Joshi, Victoria] Harvard Univ, Mol Med Lab, Boston, MA 02115 USA.
[Yeap, Beow Y.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Cioffredi, Leigh-Anne; Jackman, David M.; Jaenne, Pasi A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
RP Sholl, LM (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA.
FU National Institutes of Health, Bethesda, MD [R01 CA114465]; Pfizer, New
York, NY
FX Supported by grant R01 CA114465 from National Institutes of Health,
Bethesda, MD (Dr Janne).; Dr Jackman is a paid member of the advisory
board for Genentech, South San Francisco, CA, and has received honoraria
from Roche, South San Francisco, CA. Dr Janne has received research
support from Pfizer, New York, NY, is a consultant for AVEO
Pharmaceuticals, Cambridge, MA, and Boehringer Ingelheim, Ridgefield,
CT, and has other affiliations with Genzyme, Cambridge, MA.
NR 41
TC 69
Z9 70
U1 0
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 JUN
PY 2010
VL 133
IS 6
BP 922
EP 934
DI 10.1309/AJCPST1CTHZS3PSZ
PG 13
WC Pathology
SC Pathology
GA 598OE
UT WOS:000277846700014
PM 20472851
ER
PT J
AU Greendale, GA
Wight, RG
Huang, MH
Avis, N
Gold, EB
Joffe, H
Seeman, T
Vuge, M
Karlamangla, AS
AF Greendale, Gail A.
Wight, Richard G.
Huang, Mei-Hua
Avis, Nancy
Gold, Ellen B.
Joffe, Hadine
Seeman, Teresa
Vuge, Marike
Karlamangla, Arun S.
TI Menopause-associated Symptoms and Cognitive Performance: Results From
the Study of Women's Health Across the Nation
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE cohort studies; longitudinal studies; memory; menopause
ID MULTIETHNIC COMMUNITY; POSTMENOPAUSAL WOMEN; DEPRESSIVE SYMPTOMS;
MIDLIFE WOMEN; HOT FLASHES; ESTROGEN THERAPY; HORMONE-THERAPY; SLEEP
QUALITY; VERBAL MEMORY; TRANSITION
AB A long-standing, but unproven hypothesis is that menopause symptoms cause cognitive difficulties during the menopause transition. This 6-year longitudinal cohort study of 1,903 midlife US women (2000-2006) asked whether symptoms negatively affect cognitive performance during the menopause transition and whether they are responsible for the negative effect of perimenopause on cognitive processing speed. Major exposures were depressive, anxiety, sleep disturbance, and vasomotor symptoms and menopause transition stages. Outcomes were longitudinal performance in 3 domains: processing speed (Symbol Digit Modalities Test (SDMT)), verbal memory (East Boston Memory Test), and working memory (Digit Span Backward). Adjustment for demographics showed that women with concurrent depressive symptoms scored 1 point lower on the SDMT (P < 0.05). On the East Boston Memory Test, the rate of learning among women with anxiety symptoms tested previously was 0.09 smaller per occasion (P = 0.03), 53% of the mean learning rate. The SDMT learning rate was 1.00 point smaller during late perimenopause than during premenopause (P = 0.04); further adjustment for symptoms did not attenuate this negative effect. Depressive and anxiety symptoms had a small, negative effect on processing speed. The authors found that depressive, anxiety, sleep disturbance, and vasomotor symptoms did not account for the transient decrement in SDMT learning observed during late perimenopause.
C1 [Greendale, Gail A.; Huang, Mei-Hua; Seeman, Teresa; Karlamangla, Arun S.] Univ Calif Los Angeles, David Geffen Sch Med, Div Geriatr, Los Angeles, CA 90095 USA.
[Wight, Richard G.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Community Hlth Sci, Los Angeles, CA 90024 USA.
[Avis, Nancy] Wake Forest Univ, Sch Med, Dept Social Sci & Hlth Policy, Winston Salem, NC 27109 USA.
[Gold, Ellen B.] Univ Calif Davis, Sch Med, Dept Publ Hlth Sci, Davis, CA 95616 USA.
[Joffe, Hadine] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
[Vuge, Marike] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA.
RP Greendale, GA (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Geriatr, 10945 Le Conte Ave,Suite 2339, Los Angeles, CA 90095 USA.
EM ggreenda@mednet.ucla.edu
FU National Institutes of Health (NIH); Department of Health and Human
Services, through the National Institute on Aging (NIA); National
Institute of Nursing Research (NINR); NIH Office of Research on Women's
Health (ORWH) [NR004061, AG012505, AG012535, AG012531, AG012539,
AG012546, AG012553, AG012554, AG012495]
FX SWAN receives grant support from the National Institutes of Health
(NIH), Department of Health and Human Services, through the National
Institute on Aging (NIA), the National Institute of Nursing Research
(NINR), and the NIH Office of Research on Women's Health (ORWH) (grants
NR004061; AG012505, AG012535, AG012531, AG012539, AG012546, AG012553,
AG012554, AG012495).
NR 52
TC 37
Z9 38
U1 3
U2 11
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
EI 1476-6256
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD JUN 1
PY 2010
VL 171
IS 11
BP 1214
EP 1224
DI 10.1093/aje/kwq067
PG 11
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 603QH
UT WOS:000278222600007
PM 20442205
ER
PT J
AU Littman, AJ
Jacobson, IG
Powell, T
Boyko, EJ
Smith, TC
AF Littman, A. J.
Jacobson, I. G.
Powell, T.
Boyko, E. J.
Smith, T. C.
CA Millennium Cohort
TI WEIGHT CHANGE FOLLOWING SEPARATION FROM THE MILITARY
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT 43rd Annual Meeting of the Society-for-Epidemiologic-Research
CY JUN 23-26, 2010
CL Anaheim, CA
SP Soc Epidemiol Res
C1 [Littman, A. J.; Jacobson, I. G.; Powell, T.; Boyko, E. J.; Smith, T. C.; Millennium Cohort] VA Puget Sound Hlth Care Syst, Seattle, WA USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD JUN 1
PY 2010
VL 171
SU 11
BP S77
EP S77
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 603QO
UT WOS:000278223300306
ER
PT J
AU Ioannou, GN
AF Ioannou, George N.
TI Cholelithiasis, Cholecystectomy, and Liver Disease
SO AMERICAN JOURNAL OF GASTROENTEROLOGY
LA English
DT Article
ID SERUM ALANINE AMINOTRANSFERASE; UNITED-STATES POPULATION; NONALCOHOLIC
STEATOHEPATITIS; DIETARY-CHOLESTEROL; GALLSTONE DISEASE; PREVALENCE;
CIRRHOSIS; HOMEOSTASIS; FIBROSIS; MICE
AB OBJECTIVES: Cholelithiasis and fatty liver disease share some important risk factors, such as central obesity, insulin resistance, and diabetes. We sought to determine whether persons with cholelithiasis or a history of cholecystectomy were more likely to have elevated serum liver enzymes or to develop cirrhosis.
METHODS: We used cohort data from the first National Health and Nutrition Examination Survey (NHANES), to determine whether persons with a self-reported history of cholecystectomy at baseline (n = 466) had a higher incidence of hospitalization or death due to cirrhosis than persons without a history of cholecystectomy (n = 8,691) during up to 21 years of follow-up. We also used cross-sectional data from the third NHANES conducted between the years 1988 and 1994 to determine whether persons with cholelithiasis (n = 833) or previous cholecystectomy (n = 709), as determined by ultrasonography, were more likely to have elevated serum alanine aminotransferase (ALT) or gamma-glutamyl transferase (GGT) than persons without cholecystectomy or cholelithiasis (n = 8,027).
RESULTS: Persons with previous cholecystectomy were two times more likely to be hospitalized for or die of cirrhosis (adjusted hazard ratio 2.1, 95% confidence interval (CI) 1.1-4.0) and were more likely to have elevated serum ALT (adjusted odds ratio 1.8, 95 % CI 1.3-2.5) or GGT (adjusted odds ratio 1.7, 95 % CI 1.1-2.6) than persons without cholecystectomy. We did not identify an independent association between cholelithiasis and serum ALT or GGT levels.
CONCLUSIONS: Cholecystectomy is a predictor of the development cirrhosis and is associated with elevated serum liver enzymes. Cholelithiasis is not independently associated with serum liver enzyme levels; whether cholelithiasis is associated with the development of cirrhosis remains to be determined.
C1 [Ioannou, George N.] Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Div Gastroenterol, Seattle, WA 98108 USA.
[Ioannou, George N.] Univ Washington, Seattle, WA 98108 USA.
[Ioannou, George N.] Vet Affairs Puget Sound Hlth Care Syst, Res Enhancement Award Program, Seattle, WA 98108 USA.
RP Ioannou, GN (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Div Gastroenterol, S-111 Gastro,1660 S Columbian Way, Seattle, WA 98108 USA.
EM georgei@medicine.washington.edu
FU Veterans Affairs Research Enhancement Award Program (REAP)
FX This project was supported by a Veterans Affairs Research Enhancement
Award Program (REAP).
NR 27
TC 15
Z9 15
U1 2
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 JUN
PY 2010
VL 105
IS 6
BP 1364
EP 1373
DI 10.1038/ajg.2009.737
PG 10
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 607OU
UT WOS:000278515700026
PM 20068558
ER
PT J
AU Marcum, ZA
Handler, SM
Wright, R
Hanlon, JT
AF Marcum, Zachary A.
Handler, Steven M.
Wright, Rollin
Hanlon, Joseph T.
TI Interventions to Improve Suboptimal Prescribing in Nursing Homes: A
Narrative Review
SO AMERICAN JOURNAL OF GERIATRIC PHARMACOTHERAPY
LA English
DT Review
DE drug utilization; prescribing; nursing home; long-term care; geriatrics
ID RANDOMIZED CONTROLLED-TRIAL; TERM-CARE FACILITIES; CLINICAL
DECISION-SUPPORT; MULTIFACETED INTERVENTION; EDUCATIONAL-PROGRAM;
ELDERLY-PEOPLE; DRUG-THERAPY; ORDER ENTRY; RESIDENTS; GUIDELINES
AB Background: Appropriate medication prescribing for nursing home residents remains a challenge.
Objective: The purpose of this study was to conduct a narrative review of the published literature describing randomized controlled trials that used interventions to improve suboptimal prescribing in nursing homes.
Methods: The PubMed, International Pharmaceutical Abstracts, and EMBASE databases were searched for articles published in the English language between January 1975 and December 2009, using the terms drug utilization, pharmaceutical services, aged, long-term care, nursing homes, prescribing, geriatrics, and randomized controlled trial. A manual search of the reference lists of identified articles and the authors' files, book chapters, and recent review articles was also conducted. Abstracts and posters from meetings were not included in the search. Studies were included if they: (1) had a randomized controlled design; (2) had a process measure outcome for quality of prescribing or a distal outcome measure for medication-related adverse patient events; and (3) involved nursing home residents.
Results: Eighteen studies met the inclusion criteria for this review. Seven of those studies described educational approaches using various interventions (eg, outreach visits) and measured suboptimal prescribing in different manners (eg, adherence to guidelines). Two studies described computerized decision-support systems to measure the intervention's impact on adverse drug events (ADEs) and appropriate drug orders. Five studies described clinical pharmacist activities, most commonly involving a medication review, and used various measures of suboptimal prescribing, including a measure of medication appropriateness and the total number of medications prescribed. Two studies each described multidisciplinary and multifaceted approaches that included heterogeneous interventions and measures of prescribing. Most (15/18; 83.3%) of these studies reported statistically significant improvements in >= 1 aspect of suboptimal prescribing. Only 3 of the studies reported significant improvements in distal health outcomes, and only 3 measured ADEs or adverse drug reactions.
Conclusions: Mixed results were reported for a variety of approaches used to improve suboptimal prescribing. However, the heterogeneity of the study interventions and the various measures of suboptimal prescribing used in these studies does not allow for an authoritative conclusion based on the currently available literature. (Am J Geriatr Pharmacother. 2010;8:183-200) (C) 2010 Excerpta Medica Inc.
C1 [Marcum, Zachary A.; Handler, Steven M.; Wright, Rollin; Hanlon, Joseph T.] Univ Pittsburgh, Sch Med, Dept Geriatr Med, Pittsburgh, PA 15213 USA.
[Handler, Steven M.] Univ Pittsburgh, Sch Med, Dept Biomed Informat, Pittsburgh, PA 15213 USA.
[Hanlon, Joseph T.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15213 USA.
[Hanlon, Joseph T.] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15213 USA.
[Handler, Steven M.; Hanlon, Joseph T.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA.
[Handler, Steven M.; Hanlon, Joseph T.] Vet Affairs Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA.
RP Marcum, ZA (reprint author), Univ Pittsburgh, Sch Med, Dept Med, Div Geriatr Med, Kaufman Med Bldg,Suite 500,3471 5th Ave, Pittsburgh, PA 15213 USA.
EM zam12@pitt.edu
OI Handler, Steven/0000-0002-3940-3224
FU National Institute of Aging [R01AG027017, P30AG024827, T32AG021885,
K07AG033174, R01AG034056]; National Institute of Mental Health [R34
MH082682]; National Institute of Nursing [R01 NR010135]; Agency for
Healthcare [R01 HS017695]; Veterans Affairs Health Services
[IIR-06-062]; National Institutes of Health [K12 RR023267]
FX This study was supported by National Institute of Aging grants
(R01AG027017, P30AG024827, T32AG021885, K07AG033174, and R01AG034056), a
National Institute of Mental Health grant (R34 MH082682), a National
Institute of Nursing Research grant (R01 NR010135), an Agency for
Healthcare Research and Quality grant (R01 HS017695), a Veterans Affairs
Health Services Research grant (IIR-06-062), and a National Institutes
of Health Roadmap Multidisciplinary Clinical Research Career Development
Award Grant (K12 RR023267). The authors have indicated that they have no
other conflicts of interest regarding the content of this article.
NR 40
TC 29
Z9 32
U1 4
U2 11
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 JUN
PY 2010
VL 8
IS 3
BP 183
EP 200
DI 10.1016/j.amjopharm.2010.05.004
PG 18
WC Geriatrics & Gerontology; Pharmacology & Pharmacy
SC Geriatrics & Gerontology; Pharmacology & Pharmacy
GA 621KU
UT WOS:000279578200001
PM 20624609
ER
PT J
AU Rodriguez, KL
Hanlon, JT
Perera, S
Jaffe, EJ
Sevick, MA
AF Rodriguez, Keri L.
Hanlon, Joseph T.
Perera, Subashan
Jaffe, Emily J.
Sevick, Mary Ann
TI A Cross-Sectional Analysis of the Prevalence of Undertreatment of
Nonpain Symptoms and Factors Associated With Undertreatment in Older
Nursing Home Hospice/Palliative Care Patients
SO AMERICAN JOURNAL OF GERIATRIC PHARMACOTHERAPY
LA English
DT Article
DE long-term care; nursing homes; palliative care; hospice care; aged
ID PALLIATIVE-CARE; TERMINALLY-ILL; HOSPICE CARE; LIFE; PAIN; MANAGEMENT;
NETHERLANDS; NATIONWIDE; DISEASES; DEATH
AB Background: Approximately 25% of all US deaths occur in the long-term care setting, and this figure is projected to rise to 40% by the year 2040. Currently, there is limited information on nonpain symptoms and their appropriate treatment in this setting at the end of life.
Objective: This study evaluated the prevalence of undertreatment of nonpain symptoms and factors associated with undertreatment in older nursing home hospice/palliative care patients.
Methods: This study used a cross-sectional sample of older (>= 65 years) hospice/palliative care patients to represent all patients from the 2004 National Nursing Home Survey (NNHS) funded by the Centers for Disease Control and Prevention. Nonpain symptoms were determined from facility staff, who used the medical records to answer questions about the residents. Data on medication use were derived from medication administration records. Under-treatment was defined as the omission of a necessary medication for a specific nonpain symptom and was evaluated as a dichotomous variable (yes = the nonpain symptom was not treated with a medication; no = the nonpain symptom was treated with a medication). Cross-sectional bivariate analyses were conducted using chi(2) and regression coefficient tests to determine factors potentially associated with undertreatment of nonpain symptoms.
Results: The cross-sectional sample included 303 older nursing home hospice/palliative care patients from among the 33,413 (weighted) patients from the 2004 NNHS. Overall, most of the patients were white (91.4% [277/303]) and female (71.9% [218/303]), and nearly half were aged >= 85 years (47.9% [145/303]). One or more nonpain symptoms occurred in 82 patients (22.0% weighted). The most common nonpain symptoms (weighted percentages) were constipation/fecal impaction in 35 patients (8.8%), cough in 34 patients (9.2%), nausea/vomiting in 26 patients (7.2%), fever in 11 patients (3.1%), and diarrhea in 9 patients (1.9%). Medication undertreatment of any of the above symptoms was seen in 47 of 82 patients (60.0% weighted), ranging from a low of 26.4% for constipation/fecal impaction to a high of 88.0% for nausea/vomiting. Undertreated patients had significantly more problems with bed mobility (n [weighted %], 43 [92.3%] vs 21 [67.2%]; P = 0.013), mood (21 [44.7%] vs 7 [19.7%]; P = 0.017), and pressure ulcers (12 [25.7%] vs 2 [6.1%]; P = 0.023) than did treated patients. The undertreated group also had a significantly greater number of secondary diagnoses (weighted mean [SD], 6.5 [0.7] vs 5.2 [0.5]; P = 0.004) but had a shorter length of stay in hospice/palliative care (120.5 [20.1] vs 219.4 [51.8] days; P < 0.001) or in the nursing home (552.0 [96.5] vs 1285.4 [268.3] days; P = 0.001).
Conclusions: The prevalence of nonpain symptoms was low (22.0% weighted) in older nursing home hospice/palliative care patients. However, medication undertreatment of nonpain symptoms was seen in more than half of these patients. Future quality-improvement initiatives for nursing home hospice/palliative care patients arc needed beyond the management of pain symptoms. (Am J Geriatr Pharmacother. 2010;8:225-232) (C) 2010 Excerpta Medica Inc.
C1 [Rodriguez, Keri L.; Hanlon, Joseph T.; Sevick, Mary Ann] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15206 USA.
[Perera, Subashan] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA.
[Rodriguez, Keri L.; Hanlon, Joseph T.; Sevick, Mary Ann] Vet Affairs Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA 15206 USA.
[Sevick, Mary Ann] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Behav & Community Hlth Sci, Pittsburgh, PA 15261 USA.
[Jaffe, Emily J.] Univ Pittsburgh, Sect Palliat Care & Med Eth, Pittsburgh, PA 15261 USA.
[Rodriguez, Keri L.; Sevick, Mary Ann] Univ Pittsburgh, Sch Med, Dept Med, Div Gen Internal Med, Pittsburgh, PA 15261 USA.
[Hanlon, Joseph T.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15261 USA.
[Hanlon, Joseph T.] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15261 USA.
[Hanlon, Joseph T.; Perera, Subashan] Univ Pittsburgh, Sch Med, Dept Med, Div Geriatr Med, Pittsburgh, PA 15261 USA.
RP Rodriguez, KL (reprint author), Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, 7180 Highland Dr,Bldg 2,Room 4083E 151C-H, Pittsburgh, PA 15206 USA.
EM keri.rodriguez@va.gov
RI Perera, Subashan/D-7603-2014
FU National Institute of Aging [R01 AG027017, P30 AG024827, T32 AG021885,
K07 AG033174, R01 AG034056]; National Institute of Mental Health [R34
MH082682]; National Institute of Nursing [R01 NR010135]; Agency for
Healthcare [R01 HS017695]; VA Health Services [IIR-06-062]
FX There was no funding for this study. Dr. Hanlon was supported by the
following: National Institute of Aging grants (R01 AG027017, P30
AG024827, T32 AG021885, K07 AG033174, and R01 AG034056), a National
Institute of Mental Health grant (R34 MH082682), a National Institute of
Nursing Research grant (R01 NR010135), an Agency for Healthcare Research
and Quality grant (R01 HS017695), and a VA Health Services Research
grant (IIR-06-062). The authors have indicated that they have no other
conflicts of interest regarding the content of this article.
NR 32
TC 15
Z9 15
U1 0
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 JUN
PY 2010
VL 8
IS 3
BP 225
EP 232
DI 10.1016/j.amjopharm.2010.05.002
PG 8
WC Geriatrics & Gerontology; Pharmacology & Pharmacy
SC Geriatrics & Gerontology; Pharmacology & Pharmacy
GA 621KU
UT WOS:000279578200004
PM 20624612
ER
PT J
AU Khor, B
Van Cott, EM
AF Khor, Bernard
Van Cott, Elizabeth M.
TI Laboratory tests for protein C deficiency
SO AMERICAN JOURNAL OF HEMATOLOGY
LA English
DT Article
ID VENOUS THROMBOSIS; ANTITHROMBIN-III; INCREASED RISK; PLASMA-LEVELS;
THROMBOPHILIA; COAGULATION; PREGNANCY; ASSAY; AGE; PLASMINOGEN
AB Hereditary protein C deficiency is a hypercoagulable state associated with an increased risk for venous thrombosis. The recommended initial test for protein C is an activity (functional) assay, which may be clotting time based or chromogenic. The advantages and disadvantages of the various testing options are presented. The causes of acquired protein C deficiency are much more common than hereditary deficiency. Therefore, this article describes the appropriate steps to take when protein C activity is low, to confirm or exclude a hereditary deficiency. The causes of falsely normal results are also described, including lupus anticoagulants and direct thrombin inhibitors. Am. J. Hematol. 85:440-442, 2010. (C) 2010 Wiley-Liss, Inc.
C1 [Van Cott, Elizabeth M.] Massachusetts Gen Hosp, Dept Pathol, Coagulat Lab, Boston, MA 02114 USA.
RP Van Cott, EM (reprint author), Massachusetts Gen Hosp, Dept Pathol, Coagulat Lab, Gray Jackson 235,55 Fruit St, Boston, MA 02114 USA.
OI Khor, Bernard/0000-0003-4689-5092
NR 33
TC 18
Z9 18
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0361-8609
J9 AM J HEMATOL
JI Am. J. Hematol.
PD JUN
PY 2010
VL 85
IS 6
BP 440
EP 442
DI 10.1002/ajh.21679
PG 3
WC Hematology
SC Hematology
GA 605MT
UT WOS:000278352400010
PM 20309856
ER
PT J
AU Young, BA
AF Young, Bessie Ann
TI The Interaction of Race, Poverty, and CKD
SO AMERICAN JOURNAL OF KIDNEY DISEASES
LA English
DT Editorial Material
ID STAGE RENAL-DISEASE; CHRONIC KIDNEY-DISEASE; NEIGHBORHOOD
SOCIOECONOMIC-STATUS; ATHEROSCLEROSIS RISK; UNITED-STATES; EXPLANATORY
FACTORS; HEALTH DISPARITIES; RACIAL-DIFFERENCES; AFRICAN-AMERICANS;
EXCESS RISK
C1 Univ Washington, VA Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Seattle, WA 98101 USA.
RP Young, BA (reprint author), Univ Washington, VA Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Metropolitan Pk W,1100 Olive Way,Ste 1400, Seattle, WA 98101 USA.
EM youngb@u.washington.edu
FU NIDDK NIH HHS [R01 DK079745, R01 DK079745-01, R01 DK079745-03]
NR 42
TC 8
Z9 9
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 0272-6386
EI 1523-6838
J9 AM J KIDNEY DIS
JI Am. J. Kidney Dis.
PD JUN
PY 2010
VL 55
IS 6
BP 977
EP 980
DI 10.1053/j.ajkd.2010.04.008
PG 4
WC Urology & Nephrology
SC Urology & Nephrology
GA 601CU
UT WOS:000278036400003
PM 20497834
ER
PT J
AU Post, JB
AF Post, James B.
TI Thrombocytopenia Associated With Use of a Biocompatible Hemodialysis
Membrane: A Case Report
SO AMERICAN JOURNAL OF KIDNEY DISEASES
LA English
DT Article
DE Hemodialysis; thrombocytopenia; thrombosis
ID PLATELET-ACTIVATING FACTOR; COMPLEMENT ACTIVATION; DIALYZER
AB Biocompatibility of a dialyzer membrane has been defined largely by the degree to which it activates complement. Modifications of the cellulose membrane and the development of synthetic membranes have minimized the activation of complement and its associated complications. However, less is known about the blood-dialyzer membrane interactions that may occur in membranes made of the same synthetic polymer. A patient is described who developed dialysis-associated thrombocytopenia using a Fresenius Medical Care Optiflux polysulfone membrane (F-160) that significantly improved when switched to the polysulfone Asahi REXEED 25S membrane (AR-25S). A comparison of postdialysis D-dimer level suggests that the F-160 membrane activated the coagulation pathway to a greater extent than the AR-25S. Subtle differences between the internal surfaces of the membranes that are manufacturer specific may be responsible for exposing this patient's unique predisposition to thrombosis and thrombocytopenia. Despite the advances in membrane biocompatibility, differences may exist among membranes made of the same synthetic polymer. Am J Kidney Dis 55:e25-e28. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. This is a US Government Work. There are no restrictions on its use.
C1 [Post, James B.] James J Peters VA Med Ctr, Bronx, NY 10468 USA.
[Post, James B.] Mt Sinai Sch Med, Dept Med, New York, NY USA.
RP Post, JB (reprint author), James J Peters VA Med Ctr, 4C-12 Outpatient Renal Practice,130 W Kingsbridge, Bronx, NY 10468 USA.
EM james.post@va.gov
FU Veterans Administration Rehabilitation Research and Development [B5050W]
FX Support: This study was supported by Veterans Administration
Rehabilitation Research and Development Career Development Award
CDA2-#B5050W.
NR 15
TC 12
Z9 13
U1 1
U2 5
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0272-6386
J9 AM J KIDNEY DIS
JI Am. J. Kidney Dis.
PD JUN
PY 2010
VL 55
IS 6
BP E25
EP E28
DI 10.1053/j.ajkd.2009.10.059
PG 4
WC Urology & Nephrology
SC Urology & Nephrology
GA 601CU
UT WOS:000278036400028
PM 20110145
ER
PT J
AU Qidwai, K
Pearson, DM
Patel, GS
Pober, BR
Immken, LL
Cheung, SW
Scott, DA
AF Qidwai, Kanwal
Pearson, David M.
Patel, Gayle Simpson
Pober, Barbara R.
Immken, LaDonna L.
Cheung, Sau Wai
Scott, Daryl A.
TI Deletions of Xp Provide Evidence for the Role of Holocytochrome C-Type
Synthase (HCCS) in Congenital Diaphragmatic Hernia
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A
LA English
DT Letter
ID LINEAR SKIN DEFECTS; MLS SYNDROME; MICROPHTHALMIA; GENE; MUTATIONS;
FETUS
C1 [Pearson, David M.; Cheung, Sau Wai; Scott, Daryl A.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
[Patel, Gayle Simpson; Immken, LaDonna L.] Specially Children, Austin, TX USA.
[Pober, Barbara R.] MassGen Hosp Children, Dept Pediat, Boston, MA USA.
[Pober, Barbara R.] Childrens Hosp, Dept Surg, Boston, MA 02115 USA.
RP Scott, DA (reprint author), R813,1 Baylor Plaza,BCM 227, Houston, TX 77030 USA.
EM dscott@bcm.edu
FU NICHD NIH HHS [K08 HD-050583, K08 HD050583, K08 HD050583-05, R01
HD064667]
NR 17
TC 5
Z9 5
U1 0
U2 1
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1552-4825
J9 AM J MED GENET A
JI Am. J. Med. Genet. A
PD JUN
PY 2010
VL 152A
IS 6
BP 1588
EP 1590
DI 10.1002/ajmg.a.33410
PG 3
WC Genetics & Heredity
SC Genetics & Heredity
GA 610RJ
UT WOS:000278752000038
PM 20503342
ER
PT J
AU Ching, MSL
Shen, YP
Tan, WH
Jeste, SS
Morrow, EM
Chen, XL
Mukaddes, NM
Yoo, SY
Hanson, E
Hundley, R
Austin, C
Becker, RE
Berry, GT
Driscoll, K
Engle, EC
Friedman, S
Gusella, JF
Hisama, FM
Irons, MB
Lafiosca, T
LeClair, E
Miller, DT
Neessen, M
Picker, JD
Rappaport, L
Rooney, CM
Sarco, DP
Stoler, JM
Walsh, CA
Wolff, RR
Zhang, T
Nasir, RH
Wu, BL
AF Ching, Michael S. L.
Shen, Yiping
Tan, Wen-Hann
Jeste, Shafali S.
Morrow, Eric M.
Chen, Xiaoli
Mukaddes, Nahit M.
Yoo, Seung-Yun
Hanson, Ellen
Hundley, Rachel
Austin, Christina
Becker, Ronald E.
Berry, Gerard T.
Driscoll, Katherine
Engle, Elizabeth C.
Friedman, Sandra
Gusella, James F.
Hisama, Fuki M.
Irons, Mira B.
Lafiosca, Tina
LeClair, Elaine
Miller, David T.
Neessen, Michael
Picker, Jonathan D.
Rappaport, Leonard
Rooney, Cynthia M.
Sarco, Dean P.
Stoler, Joan M.
Walsh, Christopher A.
Wolff, Robert R.
Zhang, Ting
Nasir, Ramzi H.
Wu, Bai-Lin
CA Childrens Hosp Boston Genotype Phe
TI Deletions of NRXN1 (Neurexin-1) Predispose to a Wide Spectrum of
Developmental Disorders
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS
LA English
DT Article
DE NRXN1 (neurexin-1); developmental disorders; array CGH; NRXN1 exonic
deletions; CNV
ID ALPHA-NEUREXINS; STRUCTURAL VARIANTS; NICOTINE DEPENDENCE; CA2+
CHANNELS; AUTISM; GENES; SCHIZOPHRENIA; ASSOCIATION; NEUROLIGINS;
COMPLEX
AB Research has implicated mutations in the gene for neurexin-1 (NRXN1) in a variety of conditions including autism, schizophrenia, and nicotine dependence. To our knowledge, there have been no published reports describing the breadth of the phenotype associated with mutations in NRXN1. We present a medical record review of subjects with deletions involving exonic sequences of NRXN1. We ascertained cases from 3,540 individuals referred clinically for comparative genomic hybridization testing from March 2007 to January 2009. Twelve subjects were identified with exonic deletions. The phenotype of individuals with NRXN1 deletion is variable and includes autism spectrum disorders, mental retardation, language delays, and hypotonia. There was a statistically significant increase in NRXN1 deletion in our clinical sample compared to control populations described in the literature (P=8.9 x 10(-7)). Three additional subjects with NRXN1 deletions and autism were identified through the Homozygosity Mapping Collaborative for Autism, and this deletion segregated with the phenotype. Our study indicates that deletions of NRXN1 predispose to a wide spectrum of developmental disorders. (C) 2010 Wiley-Liss, Inc.
C1 [Nasir, Ramzi H.] Harvard Univ, Sch Med, Div Dev Med, Childrens Hosp Boston, Boston, MA 02115 USA.
[Gusella, James F.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Shen, Yiping; Gusella, James F.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Tan, Wen-Hann; Yoo, Seung-Yun; Austin, Christina; Berry, Gerard T.; Hisama, Fuki M.; Irons, Mira B.; Miller, David T.; Picker, Jonathan D.; Stoler, Joan M.; Walsh, Christopher A.] Childrens Hosp Boston, Div Genet, Boston, MA USA.
[Jeste, Shafali S.; Engle, Elizabeth C.; Rooney, Cynthia M.; Sarco, Dean P.; Wolff, Robert R.] Childrens Hosp Boston, Dept Neurol, Boston, MA USA.
[Morrow, Eric M.] Brown Univ, Dept Mol Biol Cell Biol & Biochem, Providence, RI 02912 USA.
[Shen, Yiping; Chen, Xiaoli; Miller, David T.; Wu, Bai-Lin] Childrens Hosp Boston, Dept Lab Med, Boston, MA USA.
[Chen, Xiaoli; Zhang, Ting] Capital Inst Pediat, Dept Mol Immunol, Beijing, Peoples R China.
[Mukaddes, Nahit M.] Istanbul Univ, Istanbul Fac Med, Dept Child Psychiat, Istanbul, Turkey.
[Engle, Elizabeth C.] Childrens Hosp Boston, Howard Hughes Med Inst, Boston, MA USA.
[Engle, Elizabeth C.; Walsh, Christopher A.] Childrens Hosp Boston, Manton Ctr Orphan Dis Res, Boston, MA USA.
[Engle, Elizabeth C.] Childrens Hosp Boston, Dept Ophthalmol, Boston, MA USA.
[Walsh, Christopher A.] Beth Israel Deaconess Med Ctr, Howard Hughes Med Inst, Boston, MA 02215 USA.
[Wu, Bai-Lin] Fudan Univ, Childrens Hosp, Shanghai 200433, Peoples R China.
[Wu, Bai-Lin] Fudan Univ, Inst Biomed Sci, Shanghai 200433, Peoples R China.
RP Nasir, RH (reprint author), Harvard Univ, Sch Med, Div Dev Med, Childrens Hosp Boston, 300 Longwood Ave, Boston, MA 02115 USA.
EM ramzi.nasir@childrens.harvard.edu; bai-lin.wu@childrens.harvard.edu
RI Morrow, Eric/J-2767-2013;
OI Ching, Michael/0000-0002-5213-062X; Berry, Gerard/0000-0001-5299-3313
FU Nancy Lurie Marks Family Foundation; Simons Foundation; Autism Speaks;
NIH [5K23MH080954-02, 1R01MH083565]; Children's Tumor Foundation;
Harvard Medical School; Burroughs Wellcome Fund; Fudan University
FX The authors gratefully acknowledge the assistance by our colleagues from
the DNA Diagnostics Lab: Va Lip, Xiaoming Sheng, Ann Reinhard, Hong
Fang, Sly Tang, Hong Shao, Haitao Zhu, Sam Tang, and Andrew Cheng for
technical support of array CGH; Christopher A. Walsh Lab: Danielle
Gleason and Daniel Rakiec for technical support and Robert Sean Hill for
bioinformatics support. We are further grateful for the support from the
Nancy Lurie Marks Family Foundation (C.A.W.), the Simons Foundation
(C.A.W. and J.F.G.), Autism Speaks (J.F.G.), and the NIH
(5K23MH080954-02 to E.M.M. and 1R01MH083565 to C.A.W). E.C.E. and C.A.W.
are Investigators of the Howard Hughes Medical Institute. Y.S. holds a
Young Investigator Award from the Children's Tumor Foundation and
Catalyst Award from Harvard Medical School, E.M.M. holds a Career Award
for Medical Scientists from the Burroughs Wellcome Fund, B.L.W. holds a
Fudan Scholar Research Award from Fudan University.
NR 51
TC 145
Z9 146
U1 3
U2 19
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 JUN
PY 2010
VL 153B
IS 4
BP 937
EP 947
DI 10.1002/ajmg.b.31063
PG 11
WC Genetics & Heredity; Psychiatry
SC Genetics & Heredity; Psychiatry
GA 604AT
UT WOS:000278250400009
PM 20468056
ER
PT J
AU Ko, CW
Dominitz, JA
Green, P
Kreuter, W
Baldwin, LM
AF Ko, Cynthia W.
Dominitz, Jason A.
Green, Pam
Kreuter, William
Baldwin, Laura-Mae
TI Specialty Differences in Polyp Detection, Removal, and Biopsy during
Colonoscopy
SO AMERICAN JOURNAL OF MEDICINE
LA English
DT Article
DE Colonic polyp; Colonoscopy; Colorectal neoplasms
ID MEDICARE CLAIMS DATA; COLORECTAL-CANCER; FAMILY PHYSICIAN; SENSITIVITY;
RISK
AB BACKGROUND: Colonoscopy is a technically complex procedure commonly performed to detect and remove colorectal pathology. This study examined the influence of provider characteristics on polyp detection, polyp removal, and diagnostic biopsy rates.
METHODS: We conducted a retrospective cross-sectional study using a 20% sample of 2003 Medicare claims. Primary outcome measures were use of diagnostic biopsy, polyp detection, and polyp removal. We used generalized estimating equations to identify independent predictors of the outcomes, adjusting for patient and provider characteristics.
RESULTS: Among 328,167 outpatient colonoscopies, polyp detection and removal rates were significantly lower for nongastroenterologists than gastroenterologists, with adjusted relative risk for polyp detection between 0.80 (95% confidence interval [CI], 0.77-0.83) for general surgeons and 0.93 (95% CI, 0.89-0.98) for internists. Compared with gastroenterologists, diagnostic biopsy was significantly less likely for general (relative risk [RR] 0.69; 95% CI, 0.65-0.74) or colorectal surgeons (RR 0.58; 95% CI, 0.52-0.65). The likelihood of polyp detection and removal was higher for physicians in the middle 2 quartiles of annual colonoscopy volume, but similar for physicians in the highest and lowest volume quartiles. Polyp detection and removal were significantly less likely for examinations in ambulatory surgery centers or offices than hospital outpatient settings, while diagnostic biopsy was significantly less likely in office settings.
CONCLUSIONS: Physician specialty, annual colonoscopy volume, and site of service are significant predictors of polyp detection, polyp removal, and diagnostic biopsy. These findings may have important implications for the effectiveness of colonoscopy. (C) 2010 Elsevier Inc. All rights reserved. . The American Journal of Medicine (2010) 123, 528-535
C1 [Ko, Cynthia W.] Univ Washington, Div Gastroenterol, Dept Med, Seattle, WA 98195 USA.
[Dominitz, Jason A.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA.
[Green, Pam; Baldwin, Laura-Mae] Univ Washington, Dept Family Med, Seattle, WA 98195 USA.
[Kreuter, William] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA.
RP Ko, CW (reprint author), Univ Washington, Div Gastroenterol, Dept Med, Box 356424, Seattle, WA 98195 USA.
EM cwko@u.washington.edu
OI Dominitz, Jason/0000-0002-8070-7086
FU American College of Gastroenterology; American Society for
Gastrointestinal Endoscopy; VA Puget Sound Health Care System, Seattle,
Washington
FX Funding: This work was funded by the American College of
Gastroenterology. Dr. Dominitz was supported by the American Society for
Gastrointestinal Endoscopy Endoscopic Research Career Development Award.
This material is the result of work supported in part by resources from
the VA Puget Sound Health Care System, Seattle, Washington. The views
and opinions of authors expressed herein do not necessarily state or
reflect those of the United States Government or the Department of
Veterans Affairs.
NR 27
TC 25
Z9 25
U1 2
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9343
J9 AM J MED
JI Am. J. Med.
PD JUN
PY 2010
VL 123
IS 6
BP 528
EP 535
DI 10.1016/j.amjmed.2010.01.016
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 607DX
UT WOS:000278480100014
PM 20569759
ER
PT J
AU Brastianos, PK
Streiff, M
AF Brastianos, Priscilla Kaliopi
Streiff, Michael
TI The Underdiagnosis of Pulmonary Hypertension in Myelofibrosis Reply
SO AMERICAN JOURNAL OF MEDICINE
LA English
DT Letter
C1 [Brastianos, Priscilla Kaliopi] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Streiff, Michael] Johns Hopkins Med Inst, Dept Med, Baltimore, MD 21205 USA.
RP Brastianos, PK (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, 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 0002-9343
J9 AM J MED
JI Am. J. Med.
PD JUN
PY 2010
VL 123
IS 6
BP E14
EP E14
DI 10.1016/j.amjmed.2010.03.009
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 607DX
UT WOS:000278480100029
ER
PT J
AU Burns, SM
Hough, S
Boyd, BL
Hill, J
AF Burns, Shaun Michael
Hough, Sigmund
Boyd, Briana L.
Hill, Justin
TI Men's Adjustment to Spinal Cord Injury: The Unique Contributions of
Conformity to Masculine Gender Norms
SO AMERICAN JOURNAL OF MENS HEALTH
LA English
DT Article
DE depression; gender; masculinity; social support; spinal cord injury;
treatment interventions; Web-based research
ID QUALITY-OF-LIFE; PROSTATE-CANCER; SOCIAL SUPPORT; UNMITIGATED AGENCY;
FUNCTIONAL STATUS; SEXUAL ACTIVITIES; HEALTH-STATUS; SATISFACTION;
DEPRESSION; PEOPLE
AB Men constitute 82% of the approximately 250,000 people in the United States living with a spinal cord injury. Unfortunately, however, little is known about the impact of men's adherence to gender norms on their adjustment to such injuries. The present investigation examined the utility of masculine norms in explaining variance in depression beyond that accounted for by commonly identified predictors of men's adjustment following spinal cord injury. As hypothesized, results suggested that men's adherence to masculine norms accounted for unique variance in their depression scores beyond that contributed by social support, environmental barriers/access, and erectile functioning. Respondents who adhered to norms stressing the primacy of men's work demonstrated lower rates of depression, whereas those who conformed to norms for self-reliance demonstrated higher depression scores. The authors discuss future research directions and potential psychotherapeutic strategies for working with men with spinal cord injuries.
C1 [Burns, Shaun Michael] Harvard Univ, Sch Med, VA Boston Healthcare Syst, W Roxbury, MA 02132 USA.
[Boyd, Briana L.] Hartford Hosp, Hartford, CT 06115 USA.
RP Burns, SM (reprint author), Harvard Univ, Sch Med, VA Boston Healthcare Syst, 1400 VFW Pkwy, W Roxbury, MA 02132 USA.
EM shaun.burns@va.gov
NR 51
TC 6
Z9 6
U1 1
U2 6
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1557-9883
J9 AM J MENS HEALTH
JI Am. J. Mens Health
PD JUN
PY 2010
VL 4
IS 2
BP 157
EP 166
DI 10.1177/1557988309332690
PG 10
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 603FO
UT WOS:000278194300008
PM 19477753
ER
PT J
AU Londono, D
Cadavid, D
AF Londono, Diana
Cadavid, Diego
TI Bacterial Lipoproteins Can Disseminate from the Periphery to Inflame the
Brain
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID RELAPSING-FEVER BORRELIOSIS; BLOOD-BRAIN; PERSISTENT INFECTION;
NEUROTROPIC STRAIN; GENE-EXPRESSION; SURFACE PROTEIN; NERVOUS-SYSTEM;
BURGDORFERI; SPIROCHETE; TURICATAE
AB The current view is that bacteria need to enter the brain to cause inflammation. However, in mice infected with the spirochete Borrelia turicatae, we observed widespread cerebral inflammation despite a paucity of spirochetes in the brain parenchyma at times of high bacteremia. Here we studied the possibility that bacterial lipoproteins may be capable of disseminating from the periphery across the blood-brain barrier to inflame the brain. For this we injected normal and infected mice intraperitoneally with lanthanide-labeled variable outer membrane lipoproteins of B. turicatae and measured their localization in blood, various peripheral organs, and whole and capillary-depleted brain protein extracts at various times. Lanthanide-labeled nonlipidated lipoproteins of B. turicatae and mouse albumin were used as controls. Brain inflammation was measured by TaqMan RT-PCR amplification of genes known to be upregulated in response to borrelial infection. The results showed that the two lipoproteins we studied, LVsp1 and LVsp2, were capable of inflaming the brain after intraperitoneal injection to different degrees: LVsp1 was better than LVsp2 and Bt1 spirochetes at moving from blood to brain. The dissemination of LVsp1 from the periphery to the brain occurred under normal conditions and significantly increased with infection. In contrast, LVsp2 disseminated better to peripheral organs. We conclude that some bacterial lipoproteins can disseminate from the periphery to inflame the brain. (Am J Pathol 2010, 176.2848-2857; DOI: 10.2353/ajpath.2010.091235)
C1 [Cadavid, Diego] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA.
Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Neurol & Neurosci, Newark, NJ 07103 USA.
Univ Med & Dent New Jersey, New Jersey Med Sch, Ctr Emerging Pathogens, Newark, NJ 07103 USA.
RP Cadavid, D (reprint author), Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, 149 13th St,Room 8301, Charlestown, MA 02129 USA.
EM dcadavid@partners.org
FU NIH [R21 NS053997, R21 NS057545-02]
FX Supported by NIH grants R21 NS053997 and R21 NS057545-02 to D.C.
NR 39
TC 8
Z9 8
U1 0
U2 1
PU AMER SOC INVESTIGATIVE PATHOLOGY, INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA
SN 0002-9440
J9 AM J PATHOL
JI Am. J. Pathol.
PD JUN
PY 2010
VL 176
IS 6
BP 2848
EP 2857
DI 10.2353/ajpath.2010.091235
PG 10
WC Pathology
SC Pathology
GA 609WU
UT WOS:000278689700027
PM 20431027
ER
PT J
AU Lew, HL
Pogoda, TK
Hsu, PT
Cohen, S
Amick, MM
Baker, E
Meterko, M
Vanderploeg, RD
AF Lew, Henry L.
Pogoda, Terri K.
Hsu, Pei-Te
Cohen, Sara
Amick, Melissa M.
Baker, Errol
Meterko, Mark
Vanderploeg, Rodney D.
TI Impact of the "Polytrauma Clinical Triad" on Sleep Disturbance in a
Department of Veterans Affairs Outpatient Rehabilitation Setting
SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION
LA English
DT Article
DE Traumatic Brain Injury; Post Traumatic Stress Disorder; Pain; Sleep
ID TRAUMATIC BRAIN-INJURY; POSTTRAUMATIC-STRESS-DISORDER; HEAD-INJURY;
IRAQ-WAR; MANAGEMENT; COMPLAINTS; SYMPTOMS; PREVALENCE; HEADACHES;
INSOMNIA
AB Objective: There is a high prevalence of Operation Enduring Freedom/Operation Iraqi Freedom veterans returning with the "polytrauma clinical triad" of pain, posttraumatic stress disorder, and traumatic brain injury. This study examined the effect of the polytrauma clinical triad on sleep disturbance, defined as difficulty falling or staying asleep, a common problem in Operation Enduring Freedom/Operation Iraqi Freedom veterans.
Design: A chart review was conducted for 200 Operation Enduring Freedom/Operation Iraqi Freedom veterans evaluated at a polytrauma outpatient clinic. Data that were abstracted included a sleep disturbance severity index, diagnoses of posttraumatic stress disorder and traumatic brain injury, and reported problems of pain.
Results: Sleep disturbance was highly prevalent (93.5%) in this sample, in which the majority of traumatic brain injury diagnoses were mild. In the multiple regression analysis, posttraumatic stress disorder, pain, the interaction of traumatic brain injury and posttraumatic stress disorder, and the interaction of posttraumatic stress disorder and pain significantly accounted for sleep disturbance. As a separate independent variable, traumatic brain injury was not associated with sleep disturbance.
Conclusions: Our preliminary results showed that posttraumatic stress disorder and pain significantly contributed to sleep disturbance. When traumatic brain injury or pain coexisted with posttraumatic stress disorder, sleep problems worsened. In this clinical population, where the majority of traumatic brain injury diagnoses tend to be in the mild category, traumatic brain injury alone did not predict sleep disturbance. Through increased awareness of pain, posttraumatic stress disorder, and traumatic brain injury, clinicians can work collaboratively to maximize rehabilitation outcomes.
C1 [Lew, Henry L.] DVBIC, Richmond, VA USA.
[Lew, Henry L.] Virginia Commonwealth Univ, Dept PM&R, Sch Med, Richmond, VA USA.
[Lew, Henry L.; Hsu, Pei-Te; Cohen, Sara] Harvard Univ, Sch Med, Dept PM&R, Boston, MA USA.
[Pogoda, Terri K.; Cohen, Sara; Amick, Melissa M.] VA Boston Healthcare Syst, Polytrauma & Traumat Brain Injury Ctr, Boston, MA USA.
[Pogoda, Terri K.; Baker, Errol; Meterko, Mark] VA Boston Healthcare Syst, Ctr Org Leadership & Management Res, Boston, MA USA.
[Pogoda, Terri K.; Meterko, Mark] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA.
[Hsu, Pei-Te] Kaohsiung Vet Gen Hosp, Dept Rehabil, Kaohsiung, Taiwan.
[Vanderploeg, Rodney D.] James A Haley Vet Affairs Med Ctr, Dept Mental Hlth & Behav Sci, Tampa, FL USA.
[Vanderploeg, Rodney D.] Vet Brain Injury Ctr, Tampa, FL USA.
[Vanderploeg, Rodney D.] Univ S Florida, Dept Psychiat & Behav Med, Tampa, FL USA.
[Vanderploeg, Rodney D.] Univ S Florida, Dept Psychol, Tampa, FL USA.
RP Lew, HL (reprint author), DVBIC, Richmond, VA USA.
NR 37
TC 44
Z9 44
U1 2
U2 9
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 JUN
PY 2010
VL 89
IS 6
BP 437
EP 445
DI 10.1097/PHM.0b013e3181ddd301
PG 9
WC Rehabilitation; Sport Sciences
SC Rehabilitation; Sport Sciences
GA 605GY
UT WOS:000278337100001
PM 20489391
ER
PT J
AU Scremin, OU
Figoni, SF
Norman, K
Scremin, AME
Kunkel, CF
Opava-Rutter, D
Schmitter, ED
Bert, A
Mandelkern, M
AF Scremin, Oscar U.
Figoni, Stephen F.
Norman, Keith
Scremin, A. M. Erika
Kunkel, Charles F.
Opava-Rutter, Dorene
Schmitter, Eric D.
Bert, Alberto
Mandelkern, Mark
TI Preamputation Evaluation of Lower-Limb Skeletal Muscle Perfusion with
H-2 O-15 Positron Emission Tomography
SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION
LA English
DT Article
DE Amputation; Positron Emission Tomography; Ischemia; Peripheral Vascular
Diseases
ID CEREBRAL-BLOOD-FLOW; ARTERIAL INPUT FUNCTION; LOWER-EXTREMITY;
GLUCOSE-UPTAKE; HEART-DISEASE; PET; HUMANS; SKIN; (H2O)-O-15; EXERCISE
AB Objective: To establish whether muscle blood flow (MBF) measurements with O-15-water positron emission tomography could reliably identify patients with critical limb ischemia and detect and quantify a distal deficit in skeletal MBF in these cases.
Design: O-15-water positron emission tomography scans were performed at rest or during unloaded ankle plantar and dorsiflexion exercise of the diseased leg in 17 subjects with leg ischemia or on a randomly selected leg of 18 age-matched healthy control subjects. TcPO2 was evaluated with Novametrix monitors and perfusion of skin topically heated to 44 degrees C and adjacent nonheated areas with a Moor Instruments laser Doppler imaging scanner.
Results: The enhancement of MBF induced by exercise was significantly lower in ischemic than in normal legs, and the sensitivity and specificity of this phenomenon were similar to those of laser Doppler imaging or TcPO2 in identifying ischemia subjects. In addition, the exercise MBF deficit was predominant at the distal-leg levels, indicating the ability of the technique to help determine the correct level of amputation.
Conclusions: Skeletal MBF of legs with severe ischemia can be detected accurately with O-15-water positron emission tomography and could add valuable information about viability of skeletal muscle in the residual limb when deciding the level of an amputation.
C1 [Scremin, Oscar U.; Figoni, Stephen F.; Scremin, A. M. Erika; Kunkel, Charles F.; Opava-Rutter, Dorene] VA Greater Los Angeles Healthcare Syst, Dept Phys Med & Rehabil, Los Angeles, CA 90073 USA.
[Scremin, Oscar U.; Norman, Keith] VA Greater Los Angeles Healthcare Syst, Dept Res, Los Angeles, CA 90073 USA.
[Mandelkern, Mark] VA Greater Los Angeles Healthcare Syst, Dept Nucl Med, Los Angeles, CA 90073 USA.
[Scremin, Oscar U.] Univ Calif Los Angeles, Dept Physiol, Los Angeles, CA 90024 USA.
[Scremin, A. M. Erika; Kunkel, Charles F.; Bert, Alberto] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA.
[Schmitter, Eric D.] Univ Calif Los Angeles, Dept Surg, David Geffen Sch Med, Los Angeles, CA 90024 USA.
[Mandelkern, Mark] Univ Calif Irvine, Dept Phys, Irvine, CA 92717 USA.
RP Scremin, OU (reprint author), VA Greater Los Angeles Healthcare Syst, Dept Phys Med & Rehabil, 11301 Wilshire Blvd,Bldg 115,Room 319, Los Angeles, CA 90073 USA.
OI Bert, Alberto/0000-0001-8391-7508
FU VA Rehabilitation Research and Development Awards [A2196PA, A2860R];
Senior Research Career Scientist Award [B2541SA]
FX Supported by VA Rehabilitation Research and Development Awards A2196PA
and A2860R and a Senior Research Career Scientist Award (B2541SA; to
O.U.S). Part of this work was presented as a poster in the American
Academy of Physical Medicine and Rehabilitation 67th Annual Assembly and
Technical Exhibition in Honolulu, HI, November 9-12, 2006. Financial
disclosure statements have been obtained, and no conflicts of interest
have been reported by the authors or by any individuals in control of
the content of this article.
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U2 0
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 JUN
PY 2010
VL 89
IS 6
BP 473
EP 486
DI 10.1097/PHM.0b013e3181d89b08
PG 14
WC Rehabilitation; Sport Sciences
SC Rehabilitation; Sport Sciences
GA 605GY
UT WOS:000278337100005
PM 20357647
ER
PT J
AU Brose, SW
Weber, DJ
Salatin, BA
Grindle, GG
Wang, H
Vazquez, JJ
Cooper, RA
AF Brose, Steven W.
Weber, Douglas J.
Salatin, Ben A.
Grindle, Garret G.
Wang, Hongwu
Vazquez, Juan J.
Cooper, Rory A.
TI The Role of Assistive Robotics in the Lives of Persons with Disability
SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION
LA English
DT Review
DE Robotics; Rehabilitation; Assistive Devices; Disabled Persons
ID NONHOLONOMIC MOBILE ROBOT; ENERGY-EXPENDITURE; POWER WHEELCHAIR; SENSORY
FEEDBACK; PROSTHETIC ARM; REHABILITATION; SYSTEM; TETRAPLEGIA;
PERSPECTIVE; INTERFACES
AB Robotic assistive devices are used increasingly to improve the independence and quality of life of persons with disabilities. Devices as varied as robotic feeders, smart-powered wheelchairs, independent mobile robots, and socially assistive robots are becoming more clinically relevant. There is a growing importance for the rehabilitation professional to be aware of available systems and ongoing research efforts. The aim of this article is to describe the advances in assistive robotics that are relevant to professionals serving persons with disabilities. This review breaks down relevant advances into categories of Assistive Robotic Systems, User Interfaces and Control Systems, Sensory and Feedback Systems, and User Perspectives. An understanding of the direction that assistive robotics is taking is important for the clinician and researcher alike; this review is intended to address this need.
C1 [Salatin, Ben A.; Grindle, Garret G.; Wang, Hongwu; Vazquez, Juan J.; Cooper, Rory A.] VA Pittsburgh Healthcare Syst, Human Engn Res Labs, VA Ctr Excellence, Pittsburgh, PA 15206 USA.
[Brose, Steven W.; Weber, Douglas J.; Cooper, Rory A.] Univ Pittsburgh, Dept Phys Med & Rehabil, Med Ctr, Pittsburgh, PA 15260 USA.
[Salatin, Ben A.; Grindle, Garret G.; Wang, Hongwu; Vazquez, Juan J.; Cooper, Rory A.] Univ Pittsburgh, Dept Rehabil Sci & Technol, Sch Hlth & Rehabil Sci, Pittsburgh, PA USA.
RP Cooper, RA (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs, VA Ctr Excellence, 7180 Highland Dr,Bldg 4,2nd Floor E,151R-1, Pittsburgh, PA 15206 USA.
RI Weber, Douglas/E-7554-2011; Wang, Hongwu/J-6133-2013
OI Wang, Hongwu/0000-0002-6567-9144
FU National Science Foundation Quality of Life Technology Engineering
Research Center [EEC-0540865]; VA Center of Excellence for Wheelchairs
and Associated Rehabilitation [B6789C]; National Science Foundation
Integrative Graduate Education and Research Traineeship [DGE0333420];
Paralyzed Veterans of America
FX Supported by the National Science Foundation Quality of Life Technology
Engineering Research Center (grant no. EEC-0540865), VA Center of
Excellence for Wheelchairs and Associated Rehabilitation (grant no.
B6789C), the National Science Foundation Integrative Graduate Education
and Research Traineeship, Interdisciplinary Research Training in
Assistive Technology (grant no. DGE0333420), and the Paralyzed Veterans
of America. Financial disclosure statements have been obtained, and no
conflicts of interest have been reported by the authors or by any
individuals in control of the content of this article.
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PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0894-9115
EI 1537-7385
J9 AM J PHYS MED REHAB
JI Am. J. Phys. Med. Rehabil.
PD JUN
PY 2010
VL 89
IS 6
BP 509
EP 521
DI 10.1097/PHM.0b013e3181cf569b
PG 13
WC Rehabilitation; Sport Sciences
SC Rehabilitation; Sport Sciences
GA 605GY
UT WOS:000278337100009
PM 20134305
ER
PT J
AU Da Silva, N
Pisitkun, T
Belleannee, C
Miller, LR
Nelson, R
Knepper, MA
Brown, D
Breton, S
AF Da Silva, Nicolas
Pisitkun, Trairak
Belleannee, Clemence
Miller, Lance R.
Nelson, Raoul
Knepper, Mark A.
Brown, Dennis
Breton, Sylvie
TI Proteomic analysis of V-ATPase-rich cells harvested from the kidney and
epididymis by fluorescence-activated cell sorting
SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
LA English
DT Article
DE intercalated cells; mass spectrometry; proteome; proton secretion; clear
cells
ID MALE REPRODUCTIVE-TRACT; VACUOLAR H+-ATPASE; POLARIZED EPITHELIAL-CELLS;
B2 SUBUNIT ISOFORM; PROTON PUMP ATPASE; RAT EPIDIDYMIS; INTERCALATED
CELLS; CLEAR CELLS; LUMINAL ACIDIFICATION; CONNECTING TUBULE
AB Da Silva N, Pisitkun T, Belleannee C, Miller LR, Nelson R, Knepper MA, Brown D, Breton S. Proteomic analysis of V-ATPase-rich cells harvested from the kidney and epididymis by fluorescence activated cell sorting. Am J Physiol Cell Physiol 298: C1326-C1342, 2010. First published February 24, 2010; doi:10.1152/ajpcell.00552.2009.-Proton-transporting cells are located in several tissues where they acidify the extracellular environment. These cells express the vacuolar H(+)-ATPase (V-ATPase) B1 subunit (ATP6V1B1) in their plasma membrane. We provide here a comprehensive catalog of the proteins that are expressed in these cells, after their isolation by enzymatic digestion and fluorescence-activated cell sorting (FACS) from transgenic B1-enhanced green fluorescent protein (EGFP) mice. In these mice, type A and B intercalated cells and connecting segment cells of the kidney, and narrow and clear cells of the epididymis, which all express ATP6V1B1, also express EGFP, while all other cell types are negative. The proteome of renal and epididymal EGFP-positive (EGFP(+)) cells was identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and compared with their respective EGFP-negative (EGFP(-)) cell populations. A total of 2,297 and 1,564 proteins were detected in EGFP(+) cells from the kidney and epididymis, respectively. Out of these proteins, 202 and 178 were enriched by a factor greater than 1.5 in EGFP(+) cells compared with EGFP(-) cells, in the kidney and epididymis respectively, and included subunits of the V-ATPase (B1, a4, and A). In addition, several proteins involved in intracellular trafficking, signaling, and cytoskeletal dynamics were identified. A novel common protein that was enriched in renal and epididymal EGFP(+) cells is the progesterone receptor, which might be a potential candidate for the regulation of V-ATPase-dependent proton transport. These proteomic databases provide a framework for comprehensive future analysis of the common and distinct functions of V-ATPase-B1-expressing cells in the kidney and epididymis.
C1 [Da Silva, Nicolas; Belleannee, Clemence; Brown, Dennis; Breton, Sylvie] Massachusetts Gen Hosp, Div Nephrol, Program Membrane Biol, Ctr Syst Biol, Boston, MA 02114 USA.
[Da Silva, Nicolas; Belleannee, Clemence; Brown, Dennis; Breton, Sylvie] Harvard Univ, Sch Med, Boston, MA USA.
[Pisitkun, Trairak; Miller, Lance R.; Knepper, Mark A.] NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA.
[Miller, Lance R.; Nelson, Raoul] Univ Utah, Sch Med, Dept Pediat, Salt Lake City, UT USA.
RP Breton, S (reprint author), MGH Program Membrane Biol, 185 Cambridge St,CPZN 8-204, Boston, MA 02114 USA.
EM Breton.Sylvie@mgh.harvard.edu
OI Pisitkun, Trairak/0000-0001-6677-2271
FU National Institutes of Health [HD-40793, DK-38452, DK-42956]; NHLBI
Project [HL-001285]; American Physiological Society; Boston Area
Diabetes and Endocrinology Research Center [DK-57521]; Center for the
Study of Inflammatory Bowel Disease [DK-43341]
FX This work was supported by National Institutes of Health Grants HD-40793
(to S. Breton), DK-38452 (to S. Breton and D. Brown), and DK-42956 (to
D. Brown) as well as the intramural research budget of NHLBI Project
HL-001285 (to M. A. Knepper). N. Da Silva was supported by a research
career enhancement award from the American Physiological Society. The
Microscopy Core facility of the MGH Program in Membrane Biology receives
support from the Boston Area Diabetes and Endocrinology Research Center
(DK-57521) and the Center for the Study of Inflammatory Bowel Disease
(DK-43341).
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U2 2
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0363-6143
J9 AM J PHYSIOL-CELL PH
JI Am. J. Physiol.-Cell Physiol.
PD JUN
PY 2010
VL 298
IS 6
BP C1326
EP C1342
DI 10.1152/ajpcell.00552.2009
PG 17
WC Cell Biology; Physiology
SC Cell Biology; Physiology
GA 599YD
UT WOS:000277949300010
PM 20181927
ER
PT J
AU Heneghan, JF
Akhavein, A
Salas, MJ
Shmukler, BE
Karniski, LP
Vandorpe, DH
Alper, SL
AF Heneghan, John F.
Akhavein, Arash
Salas, Maria J.
Shmukler, Boris E.
Karniski, Lawrence P.
Vandorpe, David H.
Alper, Seth L.
TI Regulated transport of sulfate and oxalate by SLC26A2/DTDST
SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
LA English
DT Article
DE chondrodysplasia; nephrolithiasis; oxalosis; anion exchange; Xenopus
oocyte
ID CONGENITAL CHLORIDE DIARRHEA; XENOPUS-LAEVIS OOCYTE; ANION-EXCHANGER;
DTDST GENE; CHONDRODYSPLASIA PHENOTYPE; INTESTINAL TRANSPORT;
INTRACELLULAR PH; ION-TRANSPORT; MUTATIONS; SLC26A6
AB Heneghan JF, Akhavein A, Salas MJ, Shmukler BE, Karniski LP, Vandorpe DH, Alper SL. Regulated transport of sulfate and oxalate by SLC26A2/DTDST. Am J Physiol Cell Physiol 298: C1363-C1375, 2010. First Published March 10, 2010; doi:10.1152/ajpcell.00004.2010.-Nephrolithiasis in the Slc26a6(-/-) mouse is accompanied by 50-75% reduction in intestinal oxalate secretion with unchanged intestinal oxalate absorption. The molecular identities of enterocyte pathways for oxalate absorption and for Slc26a6-independent oxalate secretion remain undefined. The reported intestinal expression of SO(4)(2-) transporter SLC26A2 prompted us to characterize transport of oxalate and other anions by human SLC26A2 and mouse Slc26a2 expressed in Xenopus oocytes. We found that hSLC26A2- mediated [(14)C]oxalate uptake (K(1/2) of 0.65 +/- 0.08 mM) was cis-inhibited by external SO(4)(2-) (K(1/2) of 3.1 mM). hSLC26A2-mediated bidirectional oxalate/SO(4)(2-) exchange exhibited extracellular SO(4)(2-) K(1/2) of 1.58 +/- 0.44 mM for exchange with intracellular [(14)C]oxalate, and extracellular oxalate K(1/2) of 0.14 +/- 0.11 mM for exchange with intracellular 35SO(4)(2-). Influx rates and K(1/2) values for mSlc26a2 were similar. hSLC26A2- mediated oxalate/Cl(-) exchange and bidirectional SO(4)(2-)/Cl(-) exchange were not detectably electrogenic. Both SLC26A2 orthologs exhibited nonsaturable extracellular Cl(-) dependence for efflux of intracellular [(14)C]oxalate, (35)SO(4)(2-), or (36)Cl(-). Rate constants for (36)Cl(-) efflux into extracellular Cl(-), SO(4)(2-), and oxalate were uniformly 10-fold lower than for oppositely directed exchange. Acidic extracellular pH (pH(o)) inhibited all modes of hSLC26A2-mediated anion exchange. In contrast, acidic intracellular pH (pH(i)) selectively activated exchange of extracellular Cl(-) for intracellular (35)SO(4)(2-) but not for intracellular (36)Cl(-) or [(14)C]oxalate. Protein kinase C inhibited hSLC26A2 by reducing its surface abundance. Diastrophic dysplasia mutants R279W and A386V of hSLC26A2 exhibited similar reductions in uptake of both 35SO(4)(2-) and [(14)C]oxalate. A386V surface abundance was reduced, but R279W surface abundance was at wild-type levels.
C1 [Heneghan, John F.; Akhavein, Arash; Salas, Maria J.; Shmukler, Boris E.; Vandorpe, David H.; Alper, Seth L.] Beth Israel Deaconess Med Ctr, Div Renal, Boston, MA 02215 USA.
[Heneghan, John F.; Akhavein, Arash; Salas, Maria J.; Shmukler, Boris E.; Vandorpe, David H.; Alper, Seth L.] Beth Israel Deaconess Med Ctr, Mol & Vasc Med Unit, Boston, MA 02215 USA.
[Heneghan, John F.; Shmukler, Boris E.; Vandorpe, David H.; Alper, Seth L.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Karniski, Lawrence P.] Univ Iowa, Dept Med, Iowa City, IA 52242 USA.
RP Alper, SL (reprint author), E RW763 Beth Israel Deaconess Med Ctr, 330 Brookline Ave, Boston, MA 02215 USA.
EM salper@bidmc.harvard.edu
FU National Institutes of Health [DK-07094, DK-07477, R01DK-43495]; Harvard
Digestive Diseases Center [P30DK-34854]
FX This work was supported by National Institutes of Health T32 Grants
DK-07094 and DK-07477 (to J. F. Heneghan), R01DK-43495 (to S. L. Alper),
and by P30DK-34854 (Harvard Digestive Diseases Center to to S. L.
Alper).
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PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0363-6143
J9 AM J PHYSIOL-CELL PH
JI Am. J. Physiol.-Cell Physiol.
PD JUN
PY 2010
VL 298
IS 6
BP C1363
EP C1375
DI 10.1152/ajpcell.00004.2010
PG 13
WC Cell Biology; Physiology
SC Cell Biology; Physiology
GA 599YD
UT WOS:000277949300013
PM 20219950
ER
PT J
AU Witczak, CA
Jessen, N
Warro, DM
Toyoda, T
Fujii, N
Anderson, ME
Hirshman, MF
Goodyear, LJ
AF Witczak, Carol A.
Jessen, Niels
Warro, Daniel M.
Toyoda, Taro
Fujii, Nobuharu
Anderson, Mark E.
Hirshman, Michael F.
Goodyear, Laurie J.
TI CaMKII regulates contraction- but not insulin-induced glucose uptake in
mouse skeletal muscle
SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
LA English
DT Article
DE Ca2+/calmodulin-dependent protein kinase II; Ca2+ signaling; exercise;
metabolism
ID PROTEIN-KINASE-II; GLUT4 TRANSLOCATION; TRANSPORT; PHOSPHORYLATION;
ACTIVATION; EXERCISE; CALCIUM; RAT; IDENTIFICATION; STIMULATION
AB Witczak CA, Jessen N, Warro DM, Toyoda T, Fujii N, Anderson ME, Hirshman MF, Goodyear LJ. CaMKII regulates contraction- but not insulin-induced glucose uptake in mouse skeletal muscle. Am J Physiol Endocrinol Metab 298: E1150-E1160, 2010. First published March 9, 2010; doi:10.1152/ajpendo.00659.2009.-Studies using chemical inhibitors have suggested that the Ca2+-sensitive serine/threonine kinase Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a key regulator of both insulin-and contraction-stimulated glucose uptake in skeletal muscle. However, due to nonspecificity of these inhibitors, the specific role that CaMKII may play in the regulation of glucose uptake is not known. We sought to determine whether specific inhibition of CaMKII impairs insulin- and/or contraction- induced glucose uptake in mouse skeletal muscle. Expression vectors containing green fluorescent protein conjugated to a CaMKII inhibitory (KKALHRQEAVDCL) or control (KKALHAQERVDCL) peptide were transfected into tibialis anterior muscles by in vivo electroporation. After 1 wk, muscles were assessed for peptide expression, CaMK activity, insulin-and contraction-induced 2-[H-3]deoxyglucose uptake, glycogen concentrations, and changes in intracellular signaling proteins. Expression of the CaMKII inhibitory peptide decreased muscle CaMK activity similar to 35% compared with control peptide. Insulin-induced glucose uptake was not changed in muscles expressing the inhibitory peptide. In contrast, expression of the inhibitory peptide significantly decreased contraction-induced muscle glucose uptake (similar to 30%). Contraction-induced decreases in muscle glycogen were not altered by the inhibitory peptide. The CaMKII inhibitory peptide did not alter expression of the glucose transporter GLUT4 and did not impair contraction-induced increases in the phosphorylation of AMP-activated protein kinase (Thr(172)) or TBC1D1/TBC1D4 on phospho-Akt substrate sites. These results demonstrate that CaMKII does not regulate insulin-stimulated glucose uptake in skeletal muscle. However, CaMKII plays a critical role in the regulation of contraction-induced glucose uptake in mouse skeletal muscle.
C1 [Witczak, Carol A.] Brigham & Womens Hosp, Div Res, Integrat Physiol & Metab Sect, Joslin Diabet Ctr,Dept Med, Boston, MA 02215 USA.
[Witczak, Carol A.; Jessen, Niels; Warro, Daniel M.; Toyoda, Taro; Fujii, Nobuharu; Hirshman, Michael F.; Goodyear, Laurie J.] Harvard Univ, Sch Med, Boston, MA USA.
[Anderson, Mark E.] Univ Iowa, Dept Internal Med, Carver Coll Med, Div Cardiovasc Med, Iowa City, IA 52242 USA.
RP Witczak, CA (reprint author), Brigham & Womens Hosp, Div Res, Integrat Physiol & Metab Sect, Joslin Diabet Ctr,Dept Med, Rm 520,1 Joslin Pl, Boston, MA 02215 USA.
EM carol.witczak@joslin.harvard.edu
RI Jessen, Niels/E-1731-2011; Fujii, Nobuharu/J-2724-2014;
OI Fujii, Nobuharu/0000-0002-0974-3033; Jessen, Niels/0000-0001-5613-7274
FU National Institutes of Health [R01-AR-42238, R-01-AR-45670,
F-32-AR-051663, K99-AR-056298]; Joslin Diabetes Center [T-32-DK-07260];
American Diabetes Association; Danish Agency for Science Technology and
Innovation [271-07-0719]; Nakatomi Foundation (Japan); Naito Foundation
(Japan); Japan Society for the Promotion of Science [KAKENHI 21240063]
FX This work was supported by grants from the National Institutes of Health
to L. J. Goodyear (R01-AR-42238, R-01-AR-45670), C. A. Witczak
(F-32-AR-051663 and K99-AR-056298), and the Joslin Diabetes Center
(T-32-DK-07260). Additional funds to support this work were provided by
an American Diabetes Association mentor-based fellowship to L. J.
Goodyear, the Danish Agency for Science Technology and Innovation to N.
Jessen (Grant no. 271-07-0719), the Nakatomi Foundation (Japan) and the
Naito Foundation (Japan) to T. Toyoda, and the Japan Society for the
Promotion of Science (Grant no. KAKENHI 21240063) to N. Fujii.
NR 44
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U2 9
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0193-1849
EI 1522-1555
J9 AM J PHYSIOL-ENDOC M
JI Am. J. Physiol.-Endocrinol. Metab.
PD JUN
PY 2010
VL 298
IS 6
BP E1150
EP E1160
DI 10.1152/ajpendo.00659.2009
PG 11
WC Endocrinology & Metabolism; Physiology
SC Endocrinology & Metabolism; Physiology
GA 595NH
UT WOS:000277617400006
PM 20215576
ER
PT J
AU Lu, FX
Fernandes, SM
Davis, AE
AF Lu, Fengxin
Fernandes, Stacey M.
Davis, Alvin E., III
TI The role of the complement and contact systems in the dextran sulfate
sodium-induced colitis model: the effect of C1 inhibitor in inflammatory
bowel disease
SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
LA English
DT Article
DE C3; bradykinin; colon; leukocyte infiltration
ID CROHNS-DISEASE; ULCERATIVE-COLITIS; LEUKOCYTE ADHESION; KININ SYSTEM;
ACTIVATION; RECEPTORS; PLASMA; COLON; RAT; MECHANISMS
AB Lu F, Fernandes SM, Davis AE 3rd. The role of the complement and contact systems in the dextran sulfate sodium-induced colitis model: the effect of C1 inhibitor in inflammatory bowel disease. Am J Physiol Gastrointest Liver Physiol 298: G878-G883, 2010. First published March 25, 2010; doi: 10.1152/ajpgi.00400.2009.-The complement and contact systems may be involved in the pathophysiological process of inflammatory bowel disease (IBD). C1 inhibitor (C1INH) is the most important inhibitor of both the complement and contact systems. We evaluated the role of these systems and the effect of both active and inactive forms of C1INH (iC1INH) in dextran sulfate sodium (DSS)-induced colitis mouse model. Three percent DSS was used in drinking water to induce colitis in complement C3-deficient (C3(-/-)) mice, bradykinin type 2 receptor deficient (Bk(2)R(-/-) ) mice, and C57BL/6 mice. After ten days DSS exposure, C3(-/-) mice exhibited markedly less weight loss than wild-type (WT) mice (12 +/- 3.3% vs. 30 +/- 1.2%, P < 0.05) and developed a milder disease-activity index (DAI), histological score, colon shortening, and myeloperoxidase (MPO) elevation (P < 0.05, respectively). The Bk2R(-/-) mice were not protected from the disease. Seven-day treatment with either native C1INH or iC1INH reduced the severity of the disease in WT mice, as indicated by decreased weight loss (15 +/- 1.8%, 14 +/- 2.1% vs. 30 +/- 1.2%, P < 0.05, respectively), DAI, intestinal tissue damage, and MPO elevation compared with untreated WT DSS control mice (P < 0.05, respectively). These findings suggest that complement plays a role in the development of DSS-induced colitis and that blockade of the complement system might be useful for the acute phase of IBD treatment. C1INH, however, leads to an amelioration of DSS-induced colitis via a mechanism that does not involve the inhibition of complement or contact system activation but does result in significant suppression of leukocyte infiltration.
C1 [Lu, Fengxin; Fernandes, Stacey M.; Davis, Alvin E., III] Harvard Univ, Immune Dis Inst, Sch Med, Boston, MA USA.
RP Lu, FX (reprint author), 97 Gerry Rd, Chestnut Hill, MA 02467 USA.
EM fengxinlu@gmail.com
NR 43
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U2 0
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0193-1857
J9 AM J PHYSIOL-GASTR L
JI Am. J. Physiol.-Gastroint. Liver Physiol.
PD JUN
PY 2010
VL 298
IS 6
BP G878
EP G883
DI 10.1152/ajpgi.00400.2009
PG 6
WC Gastroenterology & Hepatology; Physiology
SC Gastroenterology & Hepatology; Physiology
GA 598CE
UT WOS:000277809200009
PM 20338925
ER
PT J
AU Said, HM
Mee, L
Sekar, VT
Ashokkumar, B
Pandol, SJ
AF Said, Hamid M.
Mee, Lisa
Sekar, V. Thillai
Ashokkumar, Balasubramaniem
Pandol, Stephen J.
TI Mechanism and regulation of folate uptake by pancreatic acinar cells:
effect of chronic alcohol consumption
SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
LA English
DT Article
DE RFC; PCFT; transporter; pancreas; chronic alcohol use
ID FUNCTIONAL-CHARACTERIZATION; ETHANOL-CONSUMPTION; MAMMALIAN-CELLS; RATS;
DEFICIENCY; SECRETION; IDENTIFICATION; TRANSPORTER; METABOLISM; PROMOTER
AB Said HM, Mee L, Sekar VT, Ashokkumar B, Pandol SJ. Mechanism and regulation of folate uptake by pancreatic acinar cells: effect of chronic alcohol consumption. Am J Physiol Gastrointest Liver Physiol 298: G985-G993, 2010. First published April 1, 2010; doi:10.1152/ajpgi.00068.2010.-Folate plays an essential role in one-carbon metabolism, and a relationship exists between methyl group metabolism and pancreatic exocrine function. Little, however, is known about the mechanism(s) and regulation of folate uptake by pancreatic acinar cells and the effect of chronic alcohol use on the process. We addressed these issues using the rat-derived pancreatic acinar cell line AR42J and freshly isolated primary rat pancreatic acinar cells as models. We found [(3)H] folic acid uptake to be 1) temperature and pH dependent with a higher uptake at acidic than at neutral/alkaline pH; 2) saturable as a function of substrate concentration at both buffer pH 7.4 and 6.0; 3) inhibited by folate structural analogs and by anion transport inhibitors at both buffer pH 7.4 and 6.0; 4) trans-stimulated by unlabeled folate; 5) adaptively regulated by the prevailing extracellular folate level, and 6) inhibited by modulators of the cAMP/PKA-mediated pathway. Both the reduced folate carrier (RFC) and the proton-coupled folate transporter (PCFT) were found to be expressed in AR42J and in primary pancreatic acinar cells, as well as in native human pancreas with expression of RFC being higher than PCFT. Chronic alcohol feeding of rats (4 wk; 36% of calories from ethanol) led to a significant decrease in folate uptake by freshly isolated primary pancreatic acinar cells compared with cells from pair-fed controls; this effect was associated with a parallel decrease in the level of expression of RFC and PCFT. These studies reveal that folate uptake by pancreatic acinar cells is via a regulated carrier-mediated process which may involve RFC and PCFT. In addition, chronic alcohol feeding leads to a marked inhibition in folate uptake by pancreatic acinar cells, an effect that is associated with reduction in level of expression of RFC and PCFT.
C1 [Said, Hamid M.] Vet Adm Med Ctr, Dept Med Res, Long Beach, CA 90822 USA.
[Said, Hamid M.; Mee, Lisa; Sekar, V. Thillai; Ashokkumar, Balasubramaniem] Univ Calif Irvine, Dept Med, Irvine, CA 92717 USA.
[Said, Hamid M.; Mee, Lisa; Sekar, V. Thillai; Ashokkumar, Balasubramaniem] Univ Calif Irvine, Dept Physiol Biophys, Irvine, CA USA.
[Pandol, Stephen J.] Vet Affairs Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA.
[Pandol, Stephen J.] Univ Calif Los Angeles, Los Angeles, CA USA.
RP Said, HM (reprint author), VA Med Ctr 151, Long Beach, CA 90822 USA.
EM hmsaid@uci.edu
FU National Institutes of Health [AA018071, DK56061]; Southern California
Research Center for Alcoholic Liver and Pancreatic Diseases
[P50-AA11999]; Department of Veterans Affairs
FX This study was supported by grants from the National Institutes of
Health (AA018071 and DK56061 to H. M. Said; and the Southern California
Research Center for Alcoholic Liver and Pancreatic Diseases P50-AA11999)
and the Department of Veterans Affairs.
NR 30
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Z9 15
U1 0
U2 1
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0193-1857
J9 AM J PHYSIOL-GASTR L
JI Am. J. Physiol.-Gastroint. Liver Physiol.
PD JUN
PY 2010
VL 298
IS 6
BP G985
EP G993
DI 10.1152/ajpgi.00068.2010
PG 9
WC Gastroenterology & Hepatology; Physiology
SC Gastroenterology & Hepatology; Physiology
GA 598CE
UT WOS:000277809200021
PM 20360131
ER
PT J
AU Lorentz, CU
Alston, EN
Belcik, T
Lindner, JR
Giraud, GD
Habecker, BA
AF Lorentz, Christina U.
Alston, Eric N.
Belcik, Todd
Lindner, Jonathan R.
Giraud, George D.
Habecker, Beth A.
TI Heterogeneous ventricular sympathetic innervation, altered
beta-adrenergic receptor expression, and rhythm instability in mice
lacking the p75 neurotrophin receptor
SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
LA English
DT Article
DE sympathetic innervation; nerve growth factor; semaphorin 3a; ventricular
arrhythmias
ID NERVE GROWTH-FACTOR; SUDDEN CARDIAC DEATH; SUPERIOR CERVICAL-GANGLIA;
TYROSINE-HYDROXYLASE; MYOCARDIAL-INFARCTION; CHOLINERGIC NEURONS;
CIRCADIAN VARIATION; TARGET INNERVATION; SEMAPHORIN-III; HEART-FAILURE
AB Lorentz CU, Alston EN, Belcik T, Lindner JR, Giraud GD, Habecker BA. Heterogeneous ventricular sympathetic innervation, altered beta-adrenergic receptor expression, and rhythm instability in mice lacking the p75 neurotrophin receptor. Am J Physiol Heart Circ Physiol 298: H1652-H1660, 2010. First published February 26, 2010; doi:10.1152/ajpheart.01128.2009.-Sympathetic nerves stimulate cardiac function through the release of norepinephrine and the activation of cardiac beta(1)-adrenergic receptors. The sympathetic innervation of the heart is sculpted during development by chemoattractive factors including nerve growth factor (NGF) and the chemorepulsive factor semaphorin 3a. NGF acts through the TrkA receptor and the p75 neurotrophin receptor (p75(NTR)) in sympathetic neurons. NGF stimulates sympathetic axon extension into the heart through TrkA, but p75(NTR) modulates multiple coreceptors that can either stimulate or inhibit axon outgrowth. In mice lacking p75(NTR), the sympathetic innervation density in target tissues ranges from denervation to hyperinnervation. Recent studies have revealed significant changes in the sympathetic innervation density of p75(NTR)-deficient (p75(NTR-/-)) atria between early postnatal development and adulthood. We examined the innervation of adult p75(NTR-/-) ventricles and discovered that the sub-endocardium of the p75(NTR-/-) left ventricle was essentially devoid of sympathetic nerve fibers, whereas the innervation density of the subepicardium was normal. This phenotype is similar to that seen in mice overexpressing semaphorin 3a, and we found that sympathetic axons lacking p75(NTR) are more sensitive to semaphorin 3a in vitro than control neurons. The lack of subendocardial innervation was associated with decreased dP/dt, altered cardiac beta(1)-adrenergic receptor expression and sensitivity, and a significant increase in spontaneous ventricular arrhythmias. The lack of p75(NTR) also resulted in increased tyrosine hydroxylase content in cardiac sympathetic neurons and elevated norepinephrine in the right ventricle, where innervation density was normal.
C1 [Lorentz, Christina U.; Alston, Eric N.; Habecker, Beth A.] Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97239 USA.
[Belcik, Todd; Lindner, Jonathan R.; Giraud, George D.] Oregon Hlth & Sci Univ, Div Cardiovasc Med, Portland, OR 97239 USA.
[Giraud, George D.] Portland VA Med Ctr, Dept Hosp & Specialty Med, Portland, OR USA.
RP Habecker, BA (reprint author), Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA.
EM habecker@ohsu.edu
FU American Heart Association [0715669Z, 09PRE2110052, 0555553Z]; National
Heart, Lung, and Blood Institute [HL-093056]
FX This work was supported by American Heart Association Grants 0715669Z
and 09PRE2110052 (to C. U. Lorentz) and 0555553Z (to B. A. Habecker) and
National Heart, Lung, and Blood Institute Grant HL-093056 (to B. A.
Habecker).
NR 63
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U2 2
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0363-6135
J9 AM J PHYSIOL-HEART C
JI Am. J. Physiol.-Heart Circul. Physiol.
PD JUN
PY 2010
VL 298
IS 6
BP H1652
EP H1660
DI 10.1152/ajpheart.01128.2009
PG 9
WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Physiology
GA 598UB
UT WOS:000277863100005
PM 20190098
ER
PT J
AU Pettinati, HM
Oslin, DW
Kampman, KM
Dundon, WD
Xie, H
Gallis, TL
Dackis, CA
O'Brien, CP
AF Pettinati, Helen M.
Oslin, David W.
Kampman, Kyle M.
Dundon, William D.
Xie, Hu
Gallis, Thea L.
Dackis, Charles A.
O'Brien, Charles P.
TI A Double-Blind, Placebo-Controlled Trial Combining Sertraline and
Naltrexone for Treating Co-Occurring Depression and Alcohol Dependence
SO AMERICAN JOURNAL OF PSYCHIATRY
LA English
DT Article
ID MAJOR DEPRESSION; USE DISORDERS; COMORBIDITY; DRINKING; DRINKERS;
OUTCOMES; ABUSE
AB Objective: Empirical evidence has only weakly supported antidepressant treatment for patients with co-occurring depression and alcohol dependence. While some studies have demonstrated that antidepressants reduce depressive symptoms in individuals with depression and alcohol dependence, most studies have not found antidepressant treatment helpful in reducing excessive drinking in these patients. The authors provide results from a double-blind, placebo-controlled trial that evaluated the efficacy of combining approved medications for depression (sertraline) and alcohol dependence (naltrexone) in treating patients with both disorders.
Method: A total of 170 depressed alcohol-dependent patients were randomly assigned to receive 14 weeks of treatment with sertraline (200 mg/day [N=40]), naltrexone (100 mg/day [N=49]), the combination of sertraline plus naltrexone (N=42), or double placebo (N=39) while receiving weekly cognitive-behavioral therapy.
Results: The sertraline plus naltrexone combination produced a higher alcohol abstinence rate (53.7%) and demonstrated a longer delay before relapse to heavy drinking (median delay=98 days) than the naltrexone (abstinence rate: 21.3%; delay=29 days), sertraline (abstinence rate: 27.5%; delay=23 days), and placebo (abstinence rate: 23.1%; delay=26 days) groups. The number of patients in the medication combination group not depressed by the end of treatment (83.3%) approached significance when compared with patients in the other treatment groups. The serious adverse event rate was 25.9%, with fewer reported with the medication combination (11.9%) than the other treatments.
Conclusion: More depressed alcohol-dependent patients receiving the sertraline plus naltrexone combination achieved abstinence from alcohol, had delayed relapse to heavy drinking, reported fewer serious adverse events, and tended to not be depressed by the end of treatment. (Am J Psychiatry 2010;167:668-675)
C1 Univ Penn, Ctr Studies Addict, Dept Psychiat, Sch Med, Philadelphia, PA 19104 USA.
Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA.
RP Pettinati, HM (reprint author), Univ Penn, Treatment Res Ctr, 3900 Chestnut St, Philadelphia, PA 19104 USA.
EM pettinati_h@mail.trc.upenn.edu
FU National Institute on Alcohol Abuse and Alcoholism [R01-AA09544-10];
Pfizer Inc. U.S. Pharmaceuticals Group
FX Supported by the National Institute on Alcohol Abuse and Alcoholism
grant R01-AA09544-10 (principal investigator, Dr. Pettinati) and Pfizer
Inc. U.S. Pharmaceuticals Group, who donated sertraline and matching
placebo. These agencies had no role in the design, conduct, or reporting
of this study.
NR 31
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U1 4
U2 12
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 0002-953X
EI 1535-7228
J9 AM J PSYCHIAT
JI Am. J. Psychiat.
PD JUN
PY 2010
VL 167
IS 6
BP 668
EP 675
PG 8
WC Psychiatry
SC Psychiatry
GA 604HG
UT WOS:000278269500011
PM 20231324
ER
PT J
AU Gardner, DM
Murphy, AL
O'Donnell, H
Centorrino, F
Baldessarini, RJ
AF Gardner, David M.
Murphy, Andrea L.
O'Donnell, Heather
Centorrino, Franca
Baldessarini, Ross J.
TI International Consensus Study of Antipsychotic Dosing
SO AMERICAN JOURNAL OF PSYCHIATRY
LA English
DT Article
ID ATYPICAL ANTIPSYCHOTICS; 2ND-GENERATION ANTIPSYCHOTICS; SCHIZOPHRENIA;
DRUGS; OCCUPANCY; MEDICATIONS; RISPERIDONE
AB Objective: Potency equivalents for antipsychotic drugs are required to guide clinical dosing and for designing and interpreting research studies. Available dosing guidelines are limited by the methods and data from which they were generated.
Method: With a two-step Delphi method, the authors surveyed a diverse group of international clinical and research experts, seeking consensus regarding antipsychotic dosing. The authors determined median clinical dosing equivalents and recommended starting, target range, and maximum doses for 61 drugs, adjusted for selected clinical circumstances.
Results: Participants (N=43) from 18 countries provided dosing recommendations regarding treatment of psychotic disorders for 37 oral agents and 14 short-acting and 10 long-acting parenteral agents. With olanzapine 20 mg/day as reference, estimated clinical equivalency ratios of oral agents ranged from 0.025 for sulpiride to 10.0 for trifluperidol. Seventeen patient and treatment characteristics, including age, hepatic and renal function, illness stage and severity, sex, and diagnosis, were associated with dosing modifications.
Conclusion: In the absence of adequate prospective, randomized drug-drug comparisons, the present findings provide broad, international, expert consensus-based recommendations for most clinically employed antipsychotic drugs. They can support clinical practice, trial design, and interpretation of comparative antipsychotic trials. (Am J Psychiatry 2010; 167:686-693)
C1 [Gardner, David M.] Dalhousie Univ, Dept Psychiat, QEII HSC, Coll Pharm, Halifax, NS B3H 2E2, Canada.
Dalhousie Univ, Sch Nursing, Halifax, NS B3H 2E2, Canada.
Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
Massachusetts Gen Hosp, Int Bipolar & Psychot Disorders Res Consortium, McLean Div, Boston, MA 02114 USA.
RP Gardner, DM (reprint author), Dalhousie Univ, Dept Psychiat, QEII HSC, Coll Pharm, Abbie Lane Bldg,7517,5909 Vet Mem Lane, Halifax, NS B3H 2E2, Canada.
EM david.gardner@dal.ca
FU Department of Psychiatry Research Fund, Dalhousie University; Bruce J.
Anderson Foundation; McLean Private Donors Psychopharmacology Research
Fund
FX Supported by the Department of Psychiatry Research Fund, Dalhousie
University (to Dr. Gardner), a grant from the Bruce J. Anderson
Foundation, and by the McLean Private Donors Psychopharmacology Research
Fund (to Dr. Baldessarini).
NR 35
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Z9 351
U1 1
U2 13
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 0002-953X
J9 AM J PSYCHIAT
JI Am. J. Psychiat.
PD JUN
PY 2010
VL 167
IS 6
BP 686
EP 693
PG 8
WC Psychiatry
SC Psychiatry
GA 604HG
UT WOS:000278269500013
PM 20360319
ER
PT J
AU Keyhani, S
Wang, S
Hebert, P
Carpenter, D
Anderson, G
AF Keyhani, Salomeh
Wang, Steven
Hebert, Paul
Carpenter, Daniel
Anderson, Gerard
TI US Pharmaceutical Innovation in an International Context
SO AMERICAN JOURNAL OF PUBLIC HEALTH
LA English
DT Article
ID DRUG BENEFIT; MEDICINES; PRICE; EXPENDITURE; INDUSTRY
AB Objectives. We explored whether the United States, which does not regulate pharmaceutical prices, is responsible for the development of a disproportionate share of the new molecular entities (NMEs; a drug that does not contain an active moiety previously approved by the Food and Drug Administration) produced worldwide.
Methods. We collected data on NMEs approved between 1992 and 2004 and assigned each NME to an inventor country. We examined the relation between the proportion of total NMEs developed in each country and the proportion of total prescription drug spending and gross domestic product (GDP) of each country represented.
Results. The United States accounted for 42% of prescription drug spending and 40% of the total GDP among innovator countries and was responsible for the development of 43.7% of the NMEs. The United Kingdom, Switzerland, and a few other countries innovated proportionally more than their contribution to GDP or prescription drug spending, whereas Japan, South Korea, and a few other countries innovated less.
Conclusions. Higher prescription drug spending in the United States does not disproportionately privilege domestic innovation, and many countries with drug price regulation were significant contributors to pharmaceutical innovation. (Am J Public Health. 2010;100:1075-1080. doi:10.2105/AJPH.2009.178491)
C1 [Keyhani, Salomeh] Mt Sinai Sch Med, Dept Hlth Policy, New York, NY 10128 USA.
[Keyhani, Salomeh] James J Peters VA Med Ctr, New York, NY USA.
[Wang, Steven] Yale Univ, Sch Med, Dept Radiol, New Haven, CT 06510 USA.
[Hebert, Paul] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Devel, Seattle, WA USA.
[Hebert, Paul] Univ Washington, Sch Publ Hlth & Community Med, Dept Hlth Serv, Seattle, WA 98195 USA.
[Carpenter, Daniel] Harvard Univ, Fac Arts & Sci, Dept Govt, Cambridge, MA 02138 USA.
[Anderson, Gerard] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD USA.
RP Keyhani, S (reprint author), Mt Sinai Sch Med, Dept Hlth Policy, 1 Gustave L Levy Pl,Box 1077, New York, NY 10128 USA.
EM salomeh.keyhani@mountsinai.org
FU VA HSRD
FX This project was not supported by any direct funds. S. Keyhani is funded
by a VA HSRD Career Development Award.
NR 27
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U1 2
U2 13
PU AMER PUBLIC HEALTH ASSOC INC
PI WASHINGTON
PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA
SN 0090-0036
J9 AM J PUBLIC HEALTH
JI Am. J. Public Health
PD JUN
PY 2010
VL 100
IS 6
BP 1075
EP 1080
DI 10.2105/AJPH.2009.178491
PG 6
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 596YT
UT WOS:000277722500029
PM 20403883
ER
PT J
AU Uppot, RN
Harisinghani, MG
Gervais, DA
AF Uppot, Raul N.
Harisinghani, Mukesh G.
Gervais, Debra A.
TI Imaging-Guided Percutaneous Renal Biopsy: Rationale and Approach
SO AMERICAN JOURNAL OF ROENTGENOLOGY
LA English
DT Review
DE imaging-guided interventions; kidney; kidney biopsy; renal biopsy; renal
cell carcinoma
ID TRANSJUGULAR KIDNEY BIOPSY; FINE-NEEDLE ASPIRATION; BOSNIAK
CATEGORY-III; REAL-TIME ULTRASOUND; CELL-CARCINOMA;
COMPUTERIZED-TOMOGRAPHY; LIVER-DISEASE; MASS LESIONS; CORE BIOPSY;
DIAGNOSIS
AB OBJECTIVE. The purpose of this article is to discuss the history of, indications and rationale for, and approach to imaging-guided percutaneous renal biopsies.
CONCLUSION. With the progressive increase in the number of incidentally discovered renal masses, increased use of percutaneous ablation as a treatment alternative for the management of renal cell carcinoma and improvements in immunohistochemistry techniques, imaging-guided renal biopsy will continue to serve as a useful tool for the evaluation and management of renal diseases.
C1 [Uppot, Raul N.; Harisinghani, Mukesh G.; Gervais, Debra A.] Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA.
[Uppot, Raul N.; Harisinghani, Mukesh G.; Gervais, Debra A.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Uppot, RN (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, 55 Fruit St,White 270, Boston, MA 02114 USA.
EM ruppot@partners.org
NR 71
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Z9 20
U1 0
U2 2
PU AMER ROENTGEN RAY SOC
PI RESTON
PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA
SN 0361-803X
J9 AM J ROENTGENOL
JI Am. J. Roentgenol.
PD JUN
PY 2010
VL 194
IS 6
BP 1443
EP 1449
DI 10.2214/AJR.10.4427
PG 7
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 599XU
UT WOS:000277948400005
PM 20489082
ER
PT J
AU Blake, MA
Cronin, CG
Boland, GW
AF Blake, Michael A.
Cronin, Carmel G.
Boland, Giles W.
TI Adrenal Imaging
SO AMERICAN JOURNAL OF ROENTGENOLOGY
LA English
DT Review
DE adrenal cortical carcinoma imaging; adrenal CT; adrenal imaging; adrenal
lymphoma imaging; adrenal MRI; adrenal PET/CT; pheochromocytoma imaging
ID CHEMICAL-SHIFT MR; POSITRON-EMISSION-TOMOGRAPHY; CONTRAST-ENHANCED CT;
HISTOGRAM ANALYSIS; INITIAL-EXPERIENCE; F-18-FDG PET/CT; UNENHANCED CT;
ADRENOCORTICAL CARCINOMA; BRONCHOGENIC-CARCINOMA; FDG-PET
AB OBJECTIVE. Adrenal nodules are frequently encountered on current high-resolution imaging, and accurate characterization of such lesions is critical for appropriate patient care. Our article highlights how imaging techniques such as CT densitometry, CT washout characteristics, chemical shift MRI, PET, and PET/CT help characterize most adrenal lesions. We focus on these techniques as well as specifically, because of space constraints, the varied imaging appearances of adrenocortical carcinoma, pheochromocytoma, and lymphoma on these techniques.
CONCLUSION. The imaging characterization of adrenal lesions has continued to advance over the past decade as new technologies have evolved. CT, MRI, PET, and PET/CT are now established clinical techniques capable of differentiating benign from malignant adrenal lesions.
C1 [Blake, Michael A.; Cronin, Carmel G.; Boland, Giles W.] Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA.
[Blake, Michael A.; Cronin, Carmel G.; Boland, Giles W.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Blake, MA (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, 55 Fruit St, Boston, MA 02114 USA.
EM mblake2@partners.org
NR 75
TC 72
Z9 78
U1 0
U2 1
PU AMER ROENTGEN RAY SOC
PI RESTON
PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA
SN 0361-803X
J9 AM J ROENTGENOL
JI Am. J. Roentgenol.
PD JUN
PY 2010
VL 194
IS 6
BP 1450
EP 1460
DI 10.2214/AJR.10.4547
PG 11
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 599XU
UT WOS:000277948400006
PM 20489083
ER
PT J
AU Arellano, RS
Flanders, VL
Lee, SI
Mueller, PR
Gervais, DA
AF Arellano, Ronald S.
Flanders, Vincent L.
Lee, Susanna I.
Mueller, Peter R.
Gervais, Debra A.
TI Imaging-Guided Percutaneous Radiofrequency Ablation of Retroperitoneal
Metastatic Disease in Patients With Gynecologic Malignancies: Clinical
Experience With Eight Patients
SO AMERICAN JOURNAL OF ROENTGENOLOGY
LA English
DT Article
DE endometrial carcinoma; radiofrequency ablation
ID ENDOMETRIAL CARCINOMA; PROGNOSTIC FACTORS; RECURRENCE; RADIATION;
CREATION; LESIONS; CANCER
AB OBJECTIVE. The purpose of this study was to evaluate the efficacy of imaging-guided percutaneous radiofrequency ablation to treat metastatic retroperitoneal disease in patients with gynecologic malignancies.
MATERIALS AND METHODS. Patients with retroperitoneal metastatic disease due to gynecologic malignancies were evaluated for imaging-guided percutaneous radiofrequency ablation in this study. Efficacy of treatment was assessed by post-radiofrequency ablation activity on PET/CT scans.
RESULTS. Eight patients were considered for imaging-guided percutaneous radiofrequency ablation of retroperitoneal metastatic disease. Radiofrequency ablation was successfully completed in five patients with six metastatic tumors. All procedures were performed with the use of hydrodissection as an adjunct maneuver to displace adjacent structures. All patients showed absence of FDG activity on post-radiofrequency ablation PET/CT scans. Three (60%) of the five patients showed absence of FDG activity of the treated disease at 23.5 months after radiofrequency ablation.
CONCLUSION. Imaging-guided percutaneous radiofrequency ablation may be considered as an alternative to currently available therapies to treat recurrent metastatic disease due to endometrial carcinoma.
C1 [Arellano, Ronald S.; Flanders, Vincent L.; Lee, Susanna I.; Mueller, Peter R.; Gervais, Debra A.] Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA.
RP Arellano, RS (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, 55 Fruit St,White 270, Boston, MA 02114 USA.
EM rarellano@partners.org
NR 15
TC 9
Z9 11
U1 0
U2 0
PU AMER ROENTGEN RAY SOC
PI RESTON
PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA
SN 0361-803X
J9 AM J ROENTGENOL
JI Am. J. Roentgenol.
PD JUN
PY 2010
VL 194
IS 6
BP 1635
EP 1638
DI 10.2214/AJR.09.3561
PG 4
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 599XU
UT WOS:000277948400030
PM 20489107
ER
PT J
AU Prakash, P
Cronin, CG
Blake, MA
AF Prakash, Priyanka
Cronin, Carmel G.
Blake, Michael A.
TI Role of PET/CT in Ovarian Cancer
SO AMERICAN JOURNAL OF ROENTGENOLOGY
LA English
DT Review
DE ovarian cancer; PET/CT
ID DIAGNOSTIC-ACCURACY; F-18-FDG PET/CT; FDG-PET/CT; CT; STATISTICS;
RECURRENCE; CARCINOMA
AB OBJECTIVE. The purpose of this article is to review the role of FDG PET/CT in ovarian cancer, which is the leading cause of death among gynecologic cancers.
CONCLUSION. FDG PET/CT can significantly modify the assessment of the extent of primary and recurrent ovarian cancer and, hence, often alters patient management substantially. FDG PET/CT has thus become a critical tool for the preoperative evaluation of women with primary ovarian cancer and for postoperative follow-up assessment for evidence of recurrence in these patients.
C1 [Prakash, Priyanka; Cronin, Carmel G.; Blake, Michael A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Prakash, Priyanka; Cronin, Carmel G.; Blake, Michael A.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Blake, MA (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA.
EM mblake2@partners.org
NR 15
TC 24
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U1 0
U2 1
PU AMER ROENTGEN RAY SOC
PI RESTON
PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA
SN 0361-803X
J9 AM J ROENTGENOL
JI Am. J. Roentgenol.
PD JUN
PY 2010
VL 194
IS 6
BP W464
EP W470
DI 10.2214/AJR.09.3843
PG 7
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 599XU
UT WOS:000277948400037
PM 20489063
ER
PT J
AU Itani, KMF
Dryden, MS
Bhattacharyya, H
Kunkel, MJ
Baruch, AM
Weigelt, JA
AF Itani, Kamal M. F.
Dryden, Matthew S.
Bhattacharyya, Helen
Kunkel, Mark J.
Baruch, Alice M.
Weigelt, John A.
TI Efficacy and safety of linezolid versus vancomycin for the treatment of
complicated skin and soft-tissue infections proven to be caused by
methicillin-resistant Staphylococcus aureus
SO AMERICAN JOURNAL OF SURGERY
LA English
DT Article
DE Complicated skin and soft-tissue infection; Linezolid;
Methicillin-resistant Staphylococcus aureus; Vancomycin
ID LENGTH-OF-STAY; ECONOMIC OUTCOMES; INTRAVENOUS VANCOMYCIN; FOOT
INFECTIONS; MRSA; PHARMACOKINETICS; PENETRATION; TRIAL; COSTS; CARE
AB BACKGROUND: This open-label study compared oral or intravenous linezolid with intravenous vancomycin for treatment of complicated skin and soft-tissue infections (cSSTIs) caused by methicillin-resistant Staphylococcus aureus (MRSA).
METHODS: Patients with proven MRSA cSSTI were randomized to receive linezolid or vancomycin. Clinical and microbiologic outcomes, duration of antimicrobial therapy, length of hospital stay, and safety were assessed.
RESULTS: In the per-protocol population, the rate of clinical success was similar in linezolid- and vancomycin-treated patients (P = .249). The rate of success was significantly higher in linezolid-treated patients in the modified intent-to-treat population (P = .048). The microbiologic success rate was higher for linezolid at the end of treatment (P < .001) and was similar at the end of the study (P = .127). Patients receiving linezolid had a significantly shorter length of stay and duration of intravenous therapy than patients receiving vancomycin. Both agents were well tolerated. Adverse events were similar to each drug's established safety profile.
CONCLUSIONS: Linezolid is an effective alternative to vancomycin for the treatment of cSSTI caused by MRSA. Published by Elsevier Inc.
C1 [Itani, Kamal M. F.] VA Boston Healthcare Syst, Boston, MA 02132 USA.
[Itani, Kamal M. F.] Boston Univ, Boston, MA 02132 USA.
[Dryden, Matthew S.] Royal Hampshire Cty Hosp, Winchester, Hants, England.
[Bhattacharyya, Helen; Kunkel, Mark J.; Baruch, Alice M.] Pfizer Inc, New York, NY USA.
[Weigelt, John A.] Med Coll Wisconsin, Milwaukee, WI 53226 USA.
RP Itani, KMF (reprint author), VA Boston Healthcare Syst, 1400 VFW Pkwy, Boston, MA 02132 USA.
EM kitani@va.gov
FU Pfizer, Inc
FX This study was funded by Pfizer, Inc; editorial support was provided by
Elizabeth Melby Wells and Jean Turner of PAREXEL, Stamford, CT, and was
funded by Pfizer, Inc; Kamal Itani has been a consultant and speaker for
Pfizer; Matthew Dryden has been a member of advisory boards and has been
a speaker for Pfizer, Wyeth, Bayer, and Jansen Cilag; Helen
Bhattacharyya, Mark Kunkel, and Alice Baruch are employees of Pfizer;
John Weigelt is a consultant to Pfizer, Ortho McNeil, and
Schering-Plough.
NR 24
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U1 0
U2 15
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9610
J9 AM J SURG
JI Am. J. Surg.
PD JUN
PY 2010
VL 199
IS 6
BP 804
EP 816
DI 10.1016/j.amjsurg.2009.08.045
PG 13
WC Surgery
SC Surgery
GA 623ZH
UT WOS:000279785400017
PM 20227056
ER
PT J
AU Kougias, P
AF Kougias, Panos
TI Endoscopically unmanageable bleeding from duodenal ulcers: a job for the
vascular surgeon or the interventional radiologist? Response
SO AMERICAN JOURNAL OF SURGERY
LA English
DT Letter
ID ARTERIAL EMBOLIZATION; GASTROINTESTINAL HEMORRHAGE; EMBOLOTHERAPY
C1 [Kougias, Panos] Baylor Coll Med, Div Vasc Surg & Endovasc Therapy, Michael E DeBakey Dept Surg, Houston, TX 77030 USA.
[Kougias, Panos] Baylor Coll Med, Div Vasc Surg & Endovasc Therapy, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA.
RP Kougias, P (reprint author), Baylor Coll Med, Div Vasc Surg & Endovasc Therapy, Michael E DeBakey Dept Surg, Houston, TX 77030 USA.
NR 9
TC 0
Z9 0
U1 0
U2 1
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9610
J9 AM J SURG
JI Am. J. Surg.
PD JUN
PY 2010
VL 199
IS 6
BP 865
EP 866
DI 10.1016/j.amjsurg.2009.05.015
PG 2
WC Surgery
SC Surgery
GA 623ZH
UT WOS:000279785400027
ER
PT J
AU Long, KB
Butrynski, JE
Blank, SD
Ebrahim, KS
Dressel, DM
Heinrich, MC
Corless, CL
Hornick, JL
AF Long, Kevin B.
Butrynski, James E.
Blank, Seth D.
Ebrahim, Kurt S.
Dressel, Douglas M.
Heinrich, Michael C.
Corless, Christopher L.
Hornick, Jason L.
TI Primary Extragastrointestinal Stromal Tumor of the Pleura: Report of a
Unique Case With Genetic Confirmation
SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY
LA English
DT Article
DE gastrointestinal stromal tumor; KIT; DOG1; interstitial cells of Cajal
ID MONOCLONAL-ANTIBODY; INTERSTITIAL-CELLS; KIT MUTATIONS; SOFT-TISSUE;
CAJAL; DOG1; DIAGNOSIS; SUBTYPES; MARKER
AB Gastrointestinal stromal tumors (GISTs), the most common mesenchymal neoplasms of the tubular gastrointestinal tract, usually originate in the wall of the stomach or small intestine. Most GISTs harbor oncogenic mutations in either the KIT or platelet-derived growth factor receptor alpha (PDGFRA) tyrosine kinase receptor genes and show differentiation along the lines of the interstitial cells of Cajal. Rarely, GISTs arise primarily in the omentum, mesentery, or retroperitoneum, at which sites they are referred to as "extragastrointestinal stromal tumors'' (EGISTs). However, primary intrathoracic GIST arising in the pleura or lung has not been previously reported. We describe herein, a 62-year-old male who presented with a pleural-based mass unrelated to the esophagus that was morphologically typical of a spindle-cell GIST, showing strong immunoreactivity for KIT and DOG1, and harboring an exon 11 mutation in KIT. Ten years after resection, the tumor recurred as multiple masses in the pleura and mediastinum and was marginally reexcised. The patient was then treated with adjuvant imatinib mesylate with no evidence of further recurrences 13 months later. This seems to be the first EGIST arising above the diaphragm. This case shows a potential diagnostic pitfall with therapeutic consequences.
C1 [Long, Kevin B.; Hornick, Jason L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Long, Kevin B.; Butrynski, James E.; Hornick, Jason L.] Harvard Univ, Sch Med, Boston, MA USA.
[Butrynski, James E.] Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA.
[Blank, Seth D.] Maine Med Ctr, Maine Heart Surg Associates, Scarborough, ME USA.
[Dressel, Douglas M.] Maine Med Ctr, Spectrum Med Grp, Scarborough, ME USA.
[Ebrahim, Kurt S.] Maine Med Ctr, Maine Ctr Canc Med, Scarborough, ME USA.
[Heinrich, Michael C.] Oregon Hlth & Sci Univ, Div Hematol & Oncol, Portland VA Med Ctr, Portland, OR 97201 USA.
[Heinrich, Michael C.; Corless, Christopher L.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA.
[Corless, Christopher L.] Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97201 USA.
RP Hornick, JL (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA.
EM jhornick@partners.org
FU Veterans Affairs Merit Review Grant; GIST Cancer Research Fund
FX Funded in part from a Veterans Affairs Merit Review Grant (MCH) and
funding from the GIST Cancer Research Fund (CLC, MCH).
NR 21
TC 17
Z9 18
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0147-5185
J9 AM J SURG PATHOL
JI Am. J. Surg. Pathol.
PD JUN
PY 2010
VL 34
IS 6
BP 907
EP 912
DI 10.1097/PAS.0b013e3181d9f18f
PG 6
WC Pathology; Surgery
SC Pathology; Surgery
GA 601YK
UT WOS:000278104000020
PM 20442644
ER
PT J
AU Nadazdin, O
Boskovic, S
Murakami, T
O'Connor, DH
Wiseman, RW
Karl, JA
Tuscher, JJ
Sachs, DH
Madsen, JC
Tocco, G
Kawai, T
Cosimi, AB
Benichou, G
AF Nadazdin, Ognjenka
Boskovic, Svjetlan
Murakami, Toru
O'Connor, D. H.
Wiseman, Roger W.
Karl, J. A.
Tuscher, J. J.
Sachs, D. H.
Madsen, J. C.
Tocco, Georges
Kawai, Tatsuo
Cosimi, A. B.
Benichou, Gilles
TI Phenotype, Distribution and Alloreactive Properties of Memory T Cells
from Cynomolgus Monkeys
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Article
DE Alloreactivity; memory T cells; MHC genes; nonhuman primates
ID MAJOR HISTOCOMPATIBILITY COMPLEX; ALLOGRAFT-REJECTION; GRAFT-REJECTION;
IN-VIVO; EFFECTOR; TRANSPLANTATION; ALLORECOGNITION; GENERATION;
TOLERANCE; SUBSETS
AB The high frequency of memory T cells present in primates is thought to represent a major barrier to tolerance induction in transplantation. Therefore, it is crucial to characterize these memory T cells and determine their functional properties. High numbers of memory T cells were detected in peripheral blood and all lymphoid tissues except lymph nodes, which were essentially the site of naive T cells. The majority of CD8+ memory T cells were effector memory cells located in the blood and bone marrow while most CD4+ memory T cells were central memory cells present in the spleen. Next, memory T cells from over 100 monkeys were tested for their response to alloantigens by ELISPOT. Memory alloreactivity mediated via direct but not indirect allorecognition was detected in all animals. The frequency of allospecific memory T cells varied dramatically depending upon the nature of the responder/stimulator monkey combination tested. MHC gene matching was generally associated with a low-memory alloreactivity. Nevertheless, low anamnestic alloresponses were also found in a significant number of fully MHC-mismatched monkey combinations. These results show that selected donor/recipient combinations displaying a low memory alloresponsiveness can be found. These combinations may be more favorable for transplant tolerance induction.
C1 [Nadazdin, Ognjenka; Boskovic, Svjetlan; Murakami, Toru; Sachs, D. H.; Madsen, J. C.; Tocco, Georges; Kawai, Tatsuo; Cosimi, A. B.; Benichou, Gilles] Massachusetts Gen Hosp, Dept Surg, Transplantat Ctr, Boston, MA 02114 USA.
[Nadazdin, Ognjenka; Boskovic, Svjetlan; Murakami, Toru; Sachs, D. H.; Madsen, J. C.; Tocco, Georges; Kawai, Tatsuo; Cosimi, A. B.; Benichou, Gilles] Harvard Univ, Sch Med, Boston, MA USA.
[O'Connor, D. H.; Wiseman, Roger W.; Karl, J. A.; Tuscher, J. J.] Univ Wisconsin, Dept Pathol & Lab Med, Wisconsin Primate Res Ctr, Madison, WI USA.
RP Benichou, G (reprint author), Massachusetts Gen Hosp, Dept Surg, Transplantat Ctr, Boston, MA 02114 USA.
EM gbenichou@partners.org
OI o'connor, david/0000-0003-2139-470X
FU MGH ECOR; NIAID [U19 AI066705]; NIH [U191066705, PO1HL18646]
FX This work was supported by grants from the MGH ECOR and NIAID U19
AI066705 grants to GB NIH 19 DK080652 and HL018446 To ABC and NIH
U191066705 and PO1HL18646 to JCM.
NR 38
TC 39
Z9 39
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1600-6135
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD JUN
PY 2010
VL 10
IS 6
BP 1375
EP 1384
DI 10.1111/j.1600-6143.2010.03119.x
PG 10
WC Surgery; Transplantation
SC Surgery; Transplantation
GA 603FY
UT WOS:000278195300011
PM 20486921
ER
PT J
AU Sabin, LL
Rizal, A
Brooks, MI
Singh, MP
Tuchman, J
Wylie, BJ
Joyce, KM
Yeboah-Antwi, K
Singh, N
Hamer, DH
AF Sabin, Lora L.
Rizal, Abanish
Brooks, Mohamad I.
Singh, Mrigendra P.
Tuchman, Jordan
Wylie, Blair J.
Joyce, Katherine M.
Yeboah-Antwi, Kojo
Singh, Neeru
Hamer, Davidson H.
TI Attitudes, Knowledge, and Practices Regarding Malaria Prevention and
Treatment among Pregnant Women in Eastern India
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Article
ID MUKONO DISTRICT; EPIDEMIOLOGY; BURDEN; UGANDA
AB We explored views toward and use of malaria prevention and treatment measures among pregnant women in Jharkhand, India. We conducted 32 in-depth interviews and six focus group discussions (total = 73 respondents) with pregnant women in urban, semi-urban, and rural locations in a region with moderate intensity malaria transmission. Most respondents ranked malaria as an important health issue affecting pregnant women, had partially correct understanding of malaria transmission and prevention, and reported using potentially effective prevention methods, usually untreated bed nets. However, most conveyed misinformation and described using unproven prevention and/or treatment methods. Many described using different ineffective traditional malaria remedies. The majority also showed willingness to try new prevention methods and take medications if doctor-prescribed. Misconceptions and use of unproven prevention and treatment methods are common among pregnant women in eastern India. Policy makers should focus on improving knowledge and availability of effective malaria control strategies in this population.
C1 [Sabin, Lora L.] Boston Univ, Sch Publ Hlth, Ctr Global Hlth & Dev, Dept Int Hlth, Boston, MA 02118 USA.
Boston Univ, Sch Med, Dept Med, Infect Dis Sect, Boston, MA 02118 USA.
[Singh, Mrigendra P.; Singh, Neeru] Natl Inst Malaria Res Field Stn, Jabalpur, Madhya Pradesh, India.
[Tuchman, Jordan] Ctr Leadership & Management, Cambridge, MA USA.
[Wylie, Blair J.] Massachusetts Gen Hosp, Div Maternal Fetal Med, Dept Obstet & Gynecol, Boston, MA 02114 USA.
[Joyce, Katherine M.] Boston Med Ctr, Boston, MA USA.
RP Sabin, LL (reprint author), Boston Univ, Sch Publ Hlth, Ctr Global Hlth & Dev, Dept Int Hlth, 801 Massachusetts Ave,3rd Floor, Boston, MA 02118 USA.
EM lsabin@bu.edu; abanishr@bu.edu; mib@bu.edu; mrigendrapal@gmail.com;
jtuchman@msh.org; bwylie@partners.org; katherine.joyce@gmail.com;
kyantwi@bu.edu; neeru.singh@gmail.com; dhamer@bu.edu
OI Hamer, Davidson/0000-0002-4700-1495
FU G/PHN/HN/CS, Global Bureau; India Mission; U.S. Agency for International
Development (USAID) [GHS-A-00-03-00020-00]
FX This study was supported by the G/PHN/HN/CS, Global Bureau and the India
Mission, and the U.S. Agency for International Development (USA ID)
under the terms of Cooperative Agreement GHS-A-00-03-00020-00.
NR 24
TC 10
Z9 11
U1 0
U2 2
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD JUN
PY 2010
VL 82
IS 6
BP 1010
EP 1016
DI 10.4269/ajtmh.2010.09-0339
PG 7
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 606XP
UT WOS:000278462600008
PM 20519593
ER
PT J
AU Kendall, EA
LaRocque, RC
Bui, DM
Galloway, R
Ari, MD
Goswami, D
Breiman, RF
Luby, S
Brooks, WA
AF Kendall, Emily A.
LaRocque, Regina C.
Bui, Duy M.
Galloway, Renee
Ari, Mary D.
Goswami, Doli
Breiman, Robert F.
Luby, Stephen
Brooks, W. Abdullah
TI Short Report: Leptospirosis as a Cause of Fever in Urban Bangladesh
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Article
ID LINKED-IMMUNOSORBENT-ASSAY; AGGLUTINATION-TEST MAT; CONFIRMED
LEPTOSPIROSIS; RISK-FACTORS; SURVEILLANCE; INFECTION; DIAGNOSIS;
OUTBREAK; HAWAII; INDIA
AB We tested paired sera from 584 febrile persons in an low-income urban community in Bangladesh for evidence of Leptospira infection. A total of 8.4% of the persons met criteria for definite or probable infection. Persons with leptospirosis were older than those with undifferentiated fever in this population. The dominant infecting serogroups in Bangladesh differed from serogroups commonly reported in nearby regions.
C1 [LaRocque, Regina C.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[Bui, Duy M.; Galloway, Renee] Ctr Dis Control & Prevent, Zoonot & Select Agent Lab, Atlanta, GA USA.
[Kendall, Emily A.] Vanderbilt Univ, Sch Med, Nashville, TN 37232 USA.
[Luby, Stephen] Int Ctr Diarrhoeal Dis Res, Programme Infect Dis & Vaccine Sci, Dhaka 1000, Bangladesh.
[Breiman, Robert F.] Ctr Dis Control & Prevent, Kenya Med Res Inst, Nairobi, Kenya.
[Brooks, W. Abdullah] Int Ctr Diarrhoeal Dis Res, Hlth Syst Infect Dis Div, Dhaka 1000, Bangladesh.
RP Kendall, EA (reprint author), Vanderbilt Univ, Sch Med, 201 Light Hall, Nashville, TN 37232 USA.
EM e.a.kendall@vanderbilt.edu; rclarocque@partners.org; gum8@cdc.gov;
zul0@cdc.gov; mari@cdc.gov; drdolly@icddrb.org; sluby@icddrb.org;
abrooks@icddrb.org
OI Kendall, Emily/0000-0002-0083-422X
FU National Institutes of Health [U01-A158935, GR-00100, K01 TW07144, R24
TW007988]; U.S. Agency for International Development
[HRN-A-00-96-90005-00]; International Centre for Diarrhoeal Disease
Research Bangladesh: Centre for Health and Population Research
FX This study was supported by the National Institutes of Health
(U01-A158935 and GR-00100, K01 TW07144 to Regina C. LaRocque, and R24
TW007988 to Emily A. Kendall), by a cooperative agreement from the U.S.
Agency for International Development (HRN-A-00-96-90005-00), and by core
donors to the International Centre for Diarrhoeal Disease Research,
Bangladesh: Centre for Health and Population Research. The funding
sources had no involvement in the study design, interpretation, or
decision to publish.
NR 33
TC 9
Z9 10
U1 0
U2 6
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD JUN
PY 2010
VL 82
IS 6
BP 1127
EP 1130
DI 10.4269/ajtmh.2010.09-0574
PG 4
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 606XP
UT WOS:000278462600027
PM 20519612
ER
PT J
AU Bakaeen, FG
Chow, M
Ghadir, M
Albo, D
Berger, DH
Chu, D
AF Bakaeen, Faisal G.
Chow, Michael
Ghadir, Mued
Albo, Daniel
Berger, David H.
Chu, Danny
TI Ruptured Colonic Intramural Hematoma with Massive Hemorrhage after
Aortic Valve Replacement
SO AMERICAN SURGEON
LA English
DT Letter
ID ANTICOAGULANT-THERAPY
C1 [Bakaeen, Faisal G.] Michael E DeBakey VA Med Ctr, Dept Cardiothorac Surg, Houston, TX 77030 USA.
[Chu, Danny] Baylor Coll Med, Michael E DeBakey Dept Surg, Div Cardiothorac Surg, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA.
[Albo, Daniel; Berger, David H.] Baylor Coll Med, Michael E DeBakey Dept Surg, Div Gen Surg, Houston, TX 77030 USA.
RP Bakaeen, FG (reprint author), Michael E DeBakey VA Med Ctr, Dept Cardiothorac Surg, OCL 112 2002 Holcombe Blvd, Houston, TX 77030 USA.
EM fbakaeen@bcm.edu
NR 4
TC 1
Z9 1
U1 0
U2 0
PU SOUTHEASTERN SURGICAL CONGRESS
PI ATLANTA
PA 141 WEST WIEUCA RD, STE B100, ATLANTA, GA 30342 USA
SN 0003-1348
J9 AM SURGEON
JI Am. Surg.
PD JUN
PY 2010
VL 76
IS 6
BP 647
EP 648
PG 2
WC Surgery
SC Surgery
GA 602YG
UT WOS:000278174400018
PM 20583525
ER
PT J
AU Soncini, JA
Kanasi, E
Lu, SC
Nunn, ME
Henshaw, MM
Tanner, ACR
AF Soncini, Jennifer A.
Kanasi, Eleni
Lu, Shulin C.
Nunn, Martha E.
Henshaw, Michelle M.
Tanner, Anne C. R.
TI Oral microbiota of children in a school-based dental clinic
SO ANAEROBE
LA English
DT Article
DE Dental caries; School children; Hispanic; Streptococcus mutans;
Prevotella intermedia
ID EARLY-CHILDHOOD CARIES; MUTANS STREPTOCOCCI; RISK INDICATORS; PERMANENT
TEETH; NHANES-III; HEALTH; DENTITION; BACTERIA
AB Objectives: Dental caries disproportionately affects disadvantaged subjects. This study hypothesized that there were greater caries extent and higher levels of caries-associated and anaerobic subgingival bacterial species in oral samples of Hispanic and immigrant children compared with non-Hispanic and US born children.
Methods: Children from a school-based dental clinic serving a community with a large Hispanic component were examined, and the extent of caries was recorded. Microbial samples were taken from teeth and the tongues of children. Samples were analyzed using DNA probes to 18 oral bacterial species.
Results: Seventy five children were examined. Extent of caries increased with child age in immigrant, but not in US born or Hispanic children. There were no differences in the microbiota based on ethnicity or whether the child was born in US or not. There was a higher species detection frequency from teeth than tongue samples. Levels of Streptococcus mutans and other Streptococcus spp increased with caries extent. Prevotella intermedia, Tannerella forsythia and Selenomonas spp were detected at low levels in these children.
Conclusions: We conclude that, while there was a high rate of dental caries in disadvantaged school children, there were no differences in the caries-associated microbiota, including S. mutans, based on ethnicity or immigration status. Furthermore, while anaerobic subgingival, periodontal pathogens were also detected in children, there was no difference in species detection based on ethnicity or immigration status. Increased levels of streptococci, including S. mutans, however, were detected with high caries levels. This suggested that while it is beneficial to target preventive and treatment programs to disadvantaged populations, there is likely no additional benefit to focus on subgroups within a population already at high risk for dental disease. (C) 2009 Elsevier Ltd. All rights reserved.
C1 [Kanasi, Eleni; Lu, Shulin C.; Tanner, Anne C. R.] Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA.
[Soncini, Jennifer A.] Boston Univ, Dept Pediat Dent, Boston, MA 02215 USA.
[Nunn, Martha E.; Henshaw, Michelle M.] Boston Univ, Dept Dent Publ Hlth, Boston, MA 02215 USA.
[Tanner, Anne C. R.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Cambridge, MA 02138 USA.
RP Tanner, ACR (reprint author), Forsyth Inst, Dept Mol Genet, 140 Fenway, Boston, MA 02115 USA.
EM annetanner@forsyth.org
FU NIH/NIDCR [DE-014264, DE-015847, T32 DE-007151]
FX We would like to thank Marissa Puccio for assistance with sampling.
Research supported by NIH/NIDCR Grants DE-014264, DE-015847, and T32
Training Grant DE-007151 to E. Kanasi.
NR 27
TC 6
Z9 6
U1 0
U2 2
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1075-9964
J9 ANAEROBE
JI Anaerobe
PD JUN
PY 2010
VL 16
IS 3
BP 278
EP 282
DI 10.1016/j.anaerobe.2009.10.007
PG 5
WC Microbiology
SC Microbiology
GA 613AZ
UT WOS:000278949500019
PM 19879369
ER
PT J
AU Warren, L
Weinberg, G
AF Warren, Lisa
Weinberg, Guy
TI Lipid Emulsion and Recovery from Local Anesthetic-Induced "Cardiac
Arrest": Misleading Interpretations
SO ANESTHESIA AND ANALGESIA
LA English
DT Letter
ID SUCCESSFUL RESUSCITATION; INDUCED ASYSTOLE; PLEXUS BLOCK; BUPIVACAINE;
INFUSION; ROPIVACAINE; TOXICITY; INTOXICATION; LIDOCAINE; HEART
C1 [Warren, Lisa] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
[Weinberg, Guy] Univ Illinois, Jesse Brown VA Med Ctr, Dept Anesthesiol, Chicago, IL USA.
RP Warren, L (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
EM lwarren2@partners.org
NR 10
TC 2
Z9 2
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0003-2999
J9 ANESTH ANALG
JI Anesth. Analg.
PD JUN
PY 2010
VL 110
IS 6
BP 1750
EP 1751
DI 10.1213/ANE.0b013e3181d7af2b
PG 2
WC Anesthesiology
SC Anesthesiology
GA 604FW
UT WOS:000278263700042
PM 20501817
ER
PT J
AU Lu, Y
Wu, X
Dong, YL
Xu, ZP
Zhang, YY
Xie, ZC
AF Lu, Yan
Wu, Xu
Dong, Yuanlin
Xu, Zhipeng
Zhang, Yiying
Xie, Zhongcong
TI Anesthetic Sevoflurane Causes Neurotoxicity Differently in Neonatal
Naive and Alzheimer Disease Transgenic Mice
SO ANESTHESIOLOGY
LA English
DT Article
ID AMYLOID PRECURSOR PROTEIN; NECROSIS-FACTOR-ALPHA; CASPASE-3 ACTIVATION;
INTERFERON-GAMMA; 7-DAY-OLD RATS; BETA-APP; ISOFLURANE; DEPOSITION;
PRESENILIN; NICASTRIN
AB Background: Recent studies have suggested that children undergoing surgery under anesthesia could be at an increased risk for the development of learning disabilities, but whether anesthetics contribute to this learning disability is unclear. Therefore, the authors set out to assess the effects of sevoflurane, the most commonly used inhalation anesthetic, on caspase activation, apoptosis, beta-amyloid protein levels, and neuroinflammation in the brain tissues of neonatal naive and Alzheimer disease (AD) transgenic mice.
Methods: Six-day-old naive and AD transgenic (B6.Cg-Tg[amyloid precursor protein swe, PSEN1dE9]85Dbo/J) mice were treated with sevoflurane. The mice were killed at the end of the anesthesia, and the brain tissues were harvested and then subjected to Western blot, immunocytochemistry, enzyme-linked immunosorbent assay, and real-time polymerase chain reaction.
Results: Herein, the authors show for the first time that sevoflurane anesthesia induced caspase activation and apoptosis, altered amyloid precursor protein processing, and increased beta-amyloid protein levels in the brain tissues of neonatal mice. Furthermore, sevoflurane anesthesia led to a greater degree of neurotoxicity in the brain tissues of the AD transgenic mice when compared with naive mice and increased tumor necrosis factor-alpha levels in the brain tissues of only the AD transgenic mice. Finally, inositol 1,4,5-trisphosphate receptor antagonist 2-aminoethoxydiphenyl borate attenuated sevoflurane-induced caspase-3 activation and beta-amyloid protein accumulation in vivo.
Conclusion: These results suggest that sevoflurane may induce neurotoxicity in neonatal mice. AD transgenic mice could be more vulnerable to such neurotoxicity. These findings should promote more studies to determine the potential neurotoxicity of anesthesia in animals and humans, especially in children.
C1 [Xie, Zhongcong] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Geriatr Anesthesia Res Unit, Charlestown, MA 02129 USA.
Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA.
Harvard Univ, Sch Med, Charlestown, MA USA.
RP Xie, ZC (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Geriatr Anesthesia Res Unit, 114,16th St,3750, Charlestown, MA 02129 USA.
EM zxie@partners.org
FU National Institutes of Health (Bethesda, Maryland) [K08 NS048140, R21
AG029856, R01 GM088801]; American Geriatrics Society Jahnigen Award (New
York, New York); Alzheimer's Association (Chicago, Illinois)
FX Received from Departments of Anesthesia, Critical Care and Pain
Medicine, and Neurology, Massachusetts General Hospital and Harvard
Medical School, Charlestown, Massachusetts. Submitted for publication
October 8, 2009. Accepted for publication February 4, 2010. Supported by
grants K08 NS048140, R21 AG029856, and R01 GM088801 from the National
Institutes of Health (Bethesda, Maryland); the American Geriatrics
Society Jahnigen Award (New York, New York); and the
Investigator-Initiated Research Grant from the Alzheimer's Association
(Chicago, Illinois) (to Dr. Xie). The cost of anesthetic sevoflurane was
provided by the Department of Anesthesia, Critical Care and Pain
Medicine, Massachusetts General Hospital and Harvard Medical School.
Drs. Lu and Wu contributed equally to this work. The authors thank
Chuxiong Pan, M. D., M. S., and Jun Zhang, M. D., Ph. D., Research
Fellows, Department of Anesthesia, Critical Care and Pain Medicine,
Massachusetts General Hospital and Harvard Medical School, Charlestown,
Massachusetts, for technical support and scientific discussion.
NR 37
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U1 0
U2 16
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0003-3022
J9 ANESTHESIOLOGY
JI Anesthesiology
PD JUN
PY 2010
VL 112
IS 6
BP 1404
EP 1416
DI 10.1097/ALN.0b013e3181d94de1
PG 13
WC Anesthesiology
SC Anesthesiology
GA 605HT
UT WOS:000278339200016
PM 20460993
ER
PT J
AU Edlow, BL
Wainger, BJ
Frosch, MP
Copen, WA
Rathmell, JP
Rost, NS
AF Edlow, Brian L.
Wainger, Brian J.
Frosch, Matthew P.
Copen, William A.
Rathmell, James P.
Rost, Natalia S.
TI Posterior Circulation Stroke after C1-C2 Intraarticular Facet Steroid
Injection: Evidence for Diffuse Microvascular Injury
SO ANESTHESIOLOGY
LA English
DT Article
ID EPIDURAL INJECTIONS; ARTERY; ROOT
C1 [Edlow, Brian L.; Rost, Natalia S.] Massachusetts Gen Hosp, J Philip Kistler Stroke Res Ctr, Dept Neurol, Boston, MA 02114 USA.
[Wainger, Brian J.; Rathmell, James P.] Massachusetts Gen Hosp, J Philip Kistler Stroke Res Ctr, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
[Frosch, Matthew P.] Massachusetts Gen Hosp, J Philip Kistler Stroke Res Ctr, CS Kubik Lab Neuropathol, Boston, MA 02114 USA.
[Copen, William A.] Massachusetts Gen Hosp, J Philip Kistler Stroke Res Ctr, Dept Radiol, Boston, MA 02114 USA.
[Rathmell, James P.] Massachusetts Gen Hosp, J Philip Kistler Stroke Res Ctr, Div Pain Med, Boston, MA 02114 USA.
RP Rost, NS (reprint author), Massachusetts Gen Hosp, J Philip Kistler Stroke Res Ctr, Dept Neurol, 175 Cambridge St,Suite 300, Boston, MA 02114 USA.
EM nrost@partners.org
NR 14
TC 12
Z9 13
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0003-3022
J9 ANESTHESIOLOGY
JI Anesthesiology
PD JUN
PY 2010
VL 112
IS 6
BP 1532
EP 1535
DI 10.1097/ALN.0b013e3181d7b15a
PG 4
WC Anesthesiology
SC Anesthesiology
GA 605HT
UT WOS:000278339200030
PM 20460995
ER
PT J
AU Liao, MM
Ginde, AA
Clark, S
Camargo, CA
AF Liao, Michael M.
Ginde, Adit A.
Clark, Sunday
Camargo, Carlos A., Jr.
TI Salmeterol use and risk of hospitalization among emergency department
patients with acute asthma
SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY
LA English
DT Article
ID ACTING BETA-AGONISTS; INHALED CORTICOSTEROIDS; SAFETY; EXACERBATIONS;
METAANALYSIS; MULTICENTER; PHENOTYPE; VALUES; ADULTS
AB Background: The safety of inhaled long-acting beta(2)-agonists (LABAs) in the treatment of chronic asthma remains controversial and has not been evaluated in emergency department (ED) patients with acute asthma.
Objective: To determine whether ED patients undergoing long-term LABA therapy would have increased risk of asthma-related hospitalization compared with those not undergoing LABA therapy and whether concurrent long-term inhaled corticosteroid (ICS) therapy would mitigate this risk.
Methods: Prospective cohort study of patients aged 12 to 54 years with acute asthma in 115 EDs. Four patient groups were created based on their asthma regimen: no ICS or salmeterol (group A), salmeterol monotherapy (group B), ICS monotherapy (group C), and combination ICS and salmeterol (group D).
Results: Of the 2,236 included patients, group A had 1,221 patients (55%), group B had 48 patients (2%), group C had 787 patients (35%), and group D had 180 patients (8%); 489 patients (22%) required hospitalization. In a multivariable model controlling for 20 factors and using group A as the reference, group B had an increased risk of hospitalization (odds ratio [OR], 2.2; 95% confidence interval [CI], 1.0-4.9), whereas groups C (OR, 1.1; 95% CI, 0.8-1.5) and D (OR, 1.2; 95% CI, 0.8-1.9) did not.
Conclusion: Among ED patients with acute asthma, those undergoing salmeterol monotherapy had an increased risk of hospitalization; however, this risk was not seen among patients undergoing combination ICS-salmeterol therapy. Our findings provide data from a unique ED population on clinical response to acute asthma treatment among patients undergoing long-term LABA therapy. Ann Allergy Asthma Immunol. 2010; 104: 478-484.
C1 [Camargo, Carlos A., Jr.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, EMNet Coordinating Ctr,Dept Emergency Med, Boston, MA 02114 USA.
[Liao, Michael M.] Denver Hlth Med Ctr, Dept Emergency Med, Denver, CO USA.
[Liao, Michael M.; Ginde, Adit A.] Univ Colorado, Denver Sch Med, Dept Emergency Med, Aurora, CO USA.
[Clark, Sunday] Univ Pittsburgh, Div Gen Internal Med, Pittsburgh, PA USA.
RP Camargo, CA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, EMNet Coordinating Ctr,Dept Emergency Med, 326 Cambridge St,Suite 410, Boston, MA 02114 USA.
EM ccamargo@partners.org
RI Siry, Bonnie/D-7189-2017
FU Agency for Healthcare Research and Quality [F32-HS018123]; National
Institutes of Health (NIH) [KL2-RR025779, AI-52338]
FX Dr Liao was supported by Agency for Healthcare Research and Quality
grant F32-HS018123, Dr. Ginde by National Institutes of Health (NIH)
grant KL2-RR025779, and Dr. Camargo by NIH grant AI-52338.
NR 33
TC 7
Z9 7
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1081-1206
J9 ANN ALLERG ASTHMA IM
JI Ann. Allergy Asthma Immunol.
PD JUN
PY 2010
VL 104
IS 6
BP 478
EP 484
DI 10.1016/j.anai.2010.04.014
PG 7
WC Allergy; Immunology
SC Allergy; Immunology
GA 701OY
UT WOS:000285831500005
PM 20568379
ER
PT J
AU Merchant, RM
Abella, BS
Abotsi, EJ
Smith, TM
Long, JA
Trudeau, ME
Leary, M
Groeneveld, PW
Becker, LB
Asch, DA
AF Merchant, Raina M.
Abella, Benjamin S.
Abotsi, Edem J.
Smith, Thomas M.
Long, Judith A.
Trudeau, Martha E.
Leary, Marion
Groeneveld, Peter W.
Becker, Lance B.
Asch, David A.
TI Cell Phone Cardiopulmonary Resuscitation: Audio Instructions When Needed
by Lay Rescuers: A Randomized, Controlled Trial
SO ANNALS OF EMERGENCY MEDICINE
LA English
DT Article
ID HOSPITAL CARDIAC-ARREST; QUALITY
AB Study objective: Given the ubiquitous presence of cellular telephones, we seek to evaluate the extent to which prerecorded audio cardiopulmonary resuscitation (CPR) instructions delivered by a cell telephone will improve the quality of CPR provided by untrained and trained lay rescuers
Methods: We randomly assigned both previously CPR trained and untrained volunteers to perform CPR on a manikin for 3 minutes with or without audio assistance from a cell telephone programmed to provide CPR instructions. We measured CPR quality metrics-pauses (ie, no flow time), compression rate (minute), depth (millimeters), and hand placement (percentage correct) across the 4 groups defined by being either CPR trained or untrained and receiving or not receiving cell telephone CPR instructions.
Results: There was no difference in CPR measures for participants who had or had not received previous CPR training. Participants using the cell telephone aid performed better compression rate (100/minute [95% confidence interval (Cl) 97 to 103/minute] versus 44/minute [95% Cl 38 to 50/minute]), compression depth (41 mm [95% Cl 38 to 44 mm] versus 31 mm [95% Cl 28 to 34 mm]), hand placement (97% [95% Cl 94% to 100%] versus 75% [95% Cl 68% to 83%] correct), and fewer pauses (74 seconds [95% Cl 72 to 76 seconds] versus 89 seconds [95% Cl 80 to 98 seconds]) compared with participants without the cell telephone aid.
Conclusion: A simple audio program that can be made available for cell telephones increases the quality of bystander CPR in a manikin simulation. [Ann Emerg Med 2010,55-538-543.]
C1 [Merchant, Raina M.] Univ Penn, Sch Med, Robert Wood Johnson Fdn, Clin Scholars Program, Philadelphia, PA 19104 USA.
[Merchant, Raina M.; Abella, Benjamin S.; Abotsi, Edem J.; Smith, Thomas M.; Leary, Marion; Becker, Lance B.] Univ Penn, Sch Med, Ctr Resuscitat Sci, Philadelphia, PA 19104 USA.
[Merchant, Raina M.; Abella, Benjamin S.; Abotsi, Edem J.; Smith, Thomas M.; Leary, Marion; Becker, Lance B.] Univ Penn, Sch Med, Dept Emergency Med, Philadelphia, PA 19104 USA.
[Long, Judith A.; Trudeau, Martha E.; Groeneveld, Peter W.; Asch, David A.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA.
RP Merchant, RM (reprint author), Univ Penn, Sch Med, Robert Wood Johnson Fdn, Clin Scholars Program, 13th Floor Blockley Hall,423 Guardian St, Philadelphia, PA 19104 USA.
EM raina.merchant@uphs.upenn.edu
RI Abella, Benjamin/G-3579-2010;
OI Asch, David/0000-0002-7970-286X; Abella, Benjamin/0000-0003-2521-0891
FU Philadelphia Veterans Affairs Medical Center; Robert Wood Johnson
Foundation at University of Pennsylvania
FX By Annals policy, all authors are required to disclose any and all
commercial, financial, and other relationships in any way related to the
subject of this article that might create any potential conflict of
interest. See the Manuscript Submission Agreement in this issue for
examples of specific conflicts covered by this statement. This research
was supported by funding from the Philadelphia Veterans Affairs Medical
Center for Health Equity Research and Promotion pilot grant and the
Robert Wood Johnson Foundation Clinical Scholars program at the
University of Pennsylvania. The contents do not reflect the views of the
Department of Veterans Affairs or the United States Government
NR 10
TC 27
Z9 28
U1 0
U2 5
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0196-0644
J9 ANN EMERG MED
JI Ann. Emerg. Med.
PD JUN
PY 2010
VL 55
IS 6
BP 538
EP 543
DI 10.1016/j.annemergmed.2010.01.020
PG 6
WC Emergency Medicine
SC Emergency Medicine
GA 609RC
UT WOS:000278673800010
PM 20202719
ER
PT J
AU Goodson, JD
AF Goodson, John D.
TI Patient Protection and Affordable Care Act: Promise and Peril for
Primary Care
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Editorial Material
ID MEDICAL HOME
AB The Patient Protection and Affordable Care Act (PPACA) of 2010 brings both promise and peril for primary care. This Act has the potential to reestablish primary care as the foundation of U. S. health care delivery. The legislation authorizes specific programs to stabilize and expand the primary care physician workforce, provides an immediate 10% increase in primary care physician payment, creates an opportunity to correct the skewed resource-based relative value scale, and supports innovation in primary care practice. Nevertheless, the peril is that the PPACA initiatives may not alter the current trend toward an increasingly specialized physician workforce. To realize the potential for the PPACA to achieve a more equitable balance between generalist and specialist physicians, all primary care advocates must actively engage in the long rebuilding process.
C1 [Goodson, John D.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RP Goodson, JD (reprint author), Massachusetts Gen Hosp, 15 Parkman St, Boston, MA 02114 USA.
NR 8
TC 39
Z9 39
U1 0
U2 9
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
EI 1539-3704
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD JUN 1
PY 2010
VL 152
IS 11
BP 742
EP 744
DI 10.7326/0003-4819-152-11-201006010-00249
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 608CT
UT WOS:000278560000009
PM 20404263
ER
PT J
AU Tariman, JD
Berry, DL
Cochrane, B
Doorenbos, A
Schepp, K
AF Tariman, J. D.
Berry, D. L.
Cochrane, B.
Doorenbos, A.
Schepp, K.
TI Preferred and actual participation roles during health care decision
making in persons with cancer: a systematic review
SO ANNALS OF ONCOLOGY
LA English
DT Review
DE cancer; decision making; health care participation; patient preferences;
systematic review
ID QUALITY-OF-LIFE; BREAST-CANCER; PROSTATE-CANCER; INFORMATION NEEDS;
PATIENTS PREFERENCES; SURGICAL-TREATMENT; COLORECTAL-CANCER; FOLLOW-UP;
WOMEN; INVOLVEMENT
AB The preferred and actual participation roles during decision making have been studied over the past two decades; however, there is a lack of evidence on the degree of match between patients' preferred and actual participation roles during decision making. A systematic review was carried out to identify published studies that examined preferred and actual participation roles and the match between preferred and actual roles in decision making among patients with cancer. PubMed (1966 to January 2009), PsycINFO (1967 to January 2009), and CINAHL (1982 to January 2009) databases were searched to access relevant medical, psychological, and nursing literature. Twenty-two studies involving patients with breast, prostate, colorectal, lung, gynecological, and other cancers showed discrepancies between preferred and actual roles in decision making. These groups of patients wanted a more shared or an active role versus a less passive role. Across all cancer types, patients wanted more participation than what actually occurred. Research to date documents a pervasive mismatch between patients' preferred and actual roles during decision making. Yet, there is lack of innovative interventions that can potentially increase matching of patients' preferred and actual role during decision making. Role preferences are dynamic and vary greatly during decision making, requiring regular clinical assessment to meet patients' expectations and improve satisfaction with treatment decisions.
C1 [Tariman, J. D.; Berry, D. L.; Doorenbos, A.; Schepp, K.] Univ Washington, Seattle, WA 98195 USA.
[Berry, D. L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Cantor Ctr Res Nursing & Patient Care Serv, Boston, MA 02115 USA.
RP Tariman, JD (reprint author), Univ Washington, Seattle, WA 98195 USA.
EM jtariman@u.washington.edu
FU NINR NIH HHS [F31 NR011124]
NR 41
TC 101
Z9 105
U1 5
U2 17
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0923-7534
J9 ANN ONCOL
JI Ann. Oncol.
PD JUN
PY 2010
VL 21
IS 6
BP 1145
EP 1151
DI 10.1093/annonc/mdp534
PG 7
WC Oncology
SC Oncology
GA 603QS
UT WOS:000278223700003
PM 19940010
ER
PT J
AU Poon, LH
Kang, GA
Lee, AJ
AF Poon, Linda H.
Kang, Gail A.
Lee, Audrey J.
TI Role of Tetrabenazine for Huntington's Disease-Associated Chorea
SO ANNALS OF PHARMACOTHERAPY
LA English
DT Article
DE chorea; Huntington's disease; tetrabenazine
ID HYPERKINETIC MOVEMENT-DISORDERS; NEUROLEPTIC MALIGNANT SYNDROME; BASAL
GANGLIA; THERAPY; BRAIN; DEPRESSION; MANAGEMENT; SYMPTOMS; DRUGS; SCALE
AB OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and safety of tetrabenazine for the treatment of Huntington's disease (HD) associated chorea.
DATA SOURCES: Primary literature and review articles were obtained through a PubMed search (1959 November 2009) using the terms tetrabenazine, HD, chorea, and hyperkinetic movement disorders. A bibliographic search was performed on selected articles.
STUDY SELECTION AND DATA EXTRACTION: All English-language articles identified from the data sources were reviewed. Studies including greater than 10 patients and a direct comparative study with primarily HD-associated chorea were included in the review.
DATA SYNTHESIS: Tetrabenazine is the first drug approved by the Food and Drug Administration (FDA) for the management of HD-associated chorea. Tetrabenazine binds reversibly to the type 2 vesicular monoamine transporters and has been shown to inhibit monoamine uptake in presynaptic vesicles, resulting in monoamine depletion. The duration of the antichorea effect of tetrabenazine has been reported to be approximately 5.5 hours. Tetrabenazine is extensively metabolized hepatically by the CYP2D6 enzyme to its primary active metabolite, alpha-dihydrotetrabenazine. The half-life of alpha-dihydrotetrabenazine is 4-8 hours. Clinical trials demonstrated that tetrabenazine reduces chorea, on average, by 5 units based upon the chorea score from the Unified Huntington's Disease Rating Scale. The most common adverse effects reported include sedation, drowsiness, parkinsonism, and depression. Rarely, corrected QT interval prolongation, orthostatic hypotension, and hyperprolactinemia have been reported. Tetrabenazine also has a black box warning for increasing the risk of depression and suicidality.
CONCLUSIONS: Tetrabenazine can provide significant benefit in the treatment of chorea associated with HD. Given the potential adverse effects of tetrabenazine, health-care providers need to screen patients carefully prior to initiating treatment with this medication. In the future, additional long-term and comparative studies would be useful for further clarification of the role of tetrabenazine in the treatment of HD-associated chorea.
C1 [Poon, Linda H.] San Francisco VA Med Ctr, Pharm Serv 119, San Francisco, CA 94121 USA.
[Kang, Gail A.] Univ Calif San Francisco, Memory & Aging Ctr, San Francisco, CA 94143 USA.
[Poon, Linda H.; Lee, Audrey J.] Univ Pacific, Thomas J Long Sch Pharm, Stockton, CA 95211 USA.
RP Poon, LH (reprint author), San Francisco VA Med Ctr, Pharm Serv 119, 4150 Clement St, San Francisco, CA 94121 USA.
EM Linda.poon@va.gov
NR 53
TC 17
Z9 19
U1 3
U2 15
PU HARVEY WHITNEY BOOKS CO
PI CINCINNATI
PA PO BOX 42696, CINCINNATI, OH 45242 USA
SN 1060-0280
J9 ANN PHARMACOTHER
JI Ann. Pharmacother.
PD JUN
PY 2010
VL 44
IS 6
BP 1080
EP 1089
DI 10.1345/aph.1M582
PG 10
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 603DQ
UT WOS:000278189100015
PM 20442355
ER
PT J
AU Conrad, MF
AF Conrad, Mark F.
TI Renal Failure After Endovascular Abdominal Aortic Aneurysm Repair Reply
SO ANNALS OF SURGERY
LA English
DT Letter
C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
RP Conrad, MF (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
EM mconrad@partners.org
NR 2
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0003-4932
J9 ANN SURG
JI Ann. Surg.
PD JUN
PY 2010
VL 251
IS 6
BP 1190
EP 1190
DI 10.1097/SLA.0b013e3181e01560
PG 1
WC Surgery
SC Surgery
GA 608DE
UT WOS:000278561700033
ER
PT J
AU Raut, CP
Swallow, CJ
AF Raut, Chandrajit P.
Swallow, Carol J.
TI Are Radical Compartmental Resections for Retroperitoneal Sarcomas
Justified?
SO ANNALS OF SURGICAL ONCOLOGY
LA English
DT Editorial Material
ID SOFT-TISSUE SARCOMA; RADIATION-THERAPY; PROGNOSTIC-FACTORS;
PANCREATIC-CANCER; BEAM RADIOTHERAPY; SURVIVAL; SURGERY; MARGIN;
PANCREATICODUODENECTOMY; CLASSIFICATION
C1 [Raut, Chandrajit P.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Surg, Boston, MA 02115 USA.
[Raut, Chandrajit P.] Harvard Univ, Sch Med, Boston, MA USA.
[Swallow, Carol J.] Univ Toronto, Mt Sinai Hosp, Dept Surg, Toronto, ON, Canada.
RP Raut, CP (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Surg, 75 Francis St, Boston, MA 02115 USA.
EM craut@partners.org
NR 29
TC 19
Z9 20
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1068-9265
J9 ANN SURG ONCOL
JI Ann. Surg. Oncol.
PD JUN
PY 2010
VL 17
IS 6
BP 1481
EP 1484
DI 10.1245/s10434-010-1061-9
PG 4
WC Oncology; Surgery
SC Oncology; Surgery
GA 595EU
UT WOS:000277594300004
PM 20401636
ER
PT J
AU Yoon, SS
Chen, YL
Kirsch, DG
Maduekwe, UN
Rosenberg, AE
Nielsen, GP
Sahani, DV
Choy, E
Harmon, DC
DeLaney, TF
AF Yoon, Sam S.
Chen, Yen-Lin
Kirsch, David G.
Maduekwe, Ugwuji N.
Rosenberg, Andrew E.
Nielsen, G. Petur
Sahani, Dushyant V.
Choy, Edwin
Harmon, David C.
DeLaney, Thomas F.
TI Proton-Beam, Intensity-Modulated, and/or Intraoperative Electron
Radiation Therapy Combined with Aggressive Anterior Surgical Resection
for Retroperitoneal Sarcomas
SO ANNALS OF SURGICAL ONCOLOGY
LA English
DT Article
ID SOFT-TISSUE SARCOMA; PROGNOSTIC FACTORS; DOSE-ESCALATION; RADIOTHERAPY;
MANAGEMENT
AB We sought to reduce local recurrence for retroperitoneal sarcomas by using a coordinated strategy of advanced radiation techniques and aggressive en-bloc surgical resection.
Proton-beam radiation therapy (PBRT) and/or intensity-modulated radiation therapy (IMRT) were delivered to improve tumor target coverage and spare selected adjacent organs. Surgical resection of tumor and adjacent organs was performed to obtain a disease-free anterior margin. Intraoperative electron radiation therapy (IOERT) was delivered to any close posterior margin.
Twenty patients had primary tumors and eight had recurrent tumors. Tumors were large (median size 9.75 cm), primarily liposarcomas and leiomyosarcomas (71%), and were mostly of intermediate or high grade (81%). PBRT and/or IMRT were delivered to all patients, preferably preoperatively (75%), to a median dose of 50 Gy. Surgical resection included up to five adjacent organs, most commonly the colon (n = 7) and kidney (n = 7). Margins were positive for disease, usually posteriorly, in 15 patients (54%). IOERT was delivered to the posterior margin in 12 patients (43%) to a median dose of 11 Gy. Surgical complications occurred in eight patients (28.6%), and radiation-related complications occurred in four patients (14%). After a median follow-up of 33 months, only two patients (10%) with primary disease experienced local recurrence, while three patients (37.5%) with recurrent disease experienced local recurrence.
Aggressive resection of retroperitoneal sarcomas can achieve a disease-negative anterior margin. PBRT and/or IMRT with IOERT may possibly deliver sufficient radiation dose to the posterior margin to control microscopic residual disease. This strategy may minimize radiation-related morbidity and reduce local recurrence, especially in patients with primary disease.
C1 [Yoon, Sam S.; Maduekwe, Ugwuji N.] Massachusetts Gen Hosp, Dept Surg, Div Surg Oncol, Boston, MA 02114 USA.
[Yoon, Sam S.; Chen, Yen-Lin; Maduekwe, Ugwuji N.; Rosenberg, Andrew E.; Nielsen, G. Petur; Sahani, Dushyant V.; Choy, Edwin; Harmon, David C.; DeLaney, Thomas F.] Harvard Univ, Sch Med, Boston, MA USA.
[Chen, Yen-Lin; DeLaney, Thomas F.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Rosenberg, Andrew E.; Nielsen, G. Petur] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Sahani, Dushyant V.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Choy, Edwin; Harmon, David C.] Massachusetts Gen Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02114 USA.
[Kirsch, David G.] Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC USA.
[Kirsch, David G.] Duke Univ, Med Ctr, Dept Radiat Oncol, Durham, NC USA.
[Yoon, Sam S.] Univ Penn, Sch Med, Dept Canc Biol, Philadelphia, PA 19104 USA.
[Yoon, Sam S.] Univ Penn, Sch Med, Dept Surg, Philadelphia, PA 19104 USA.
RP Yoon, SS (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Surg Oncol, Boston, MA 02114 USA.
EM sam.yoon@uphs.upenn.edu
OI Choy, Edwin/0000-0001-9896-8084
FU NCI NIH HHS [R21 CA117128-01A1, R21 CA117128]
NR 32
TC 42
Z9 44
U1 1
U2 6
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1068-9265
J9 ANN SURG ONCOL
JI Ann. Surg. Oncol.
PD JUN
PY 2010
VL 17
IS 6
BP 1515
EP 1529
DI 10.1245/s10434-010-0935-1
PG 15
WC Oncology; Surgery
SC Oncology; Surgery
GA 595EU
UT WOS:000277594300010
PM 20151216
ER
PT J
AU Rogers, SO
Gray, SW
Landrum, MB
Klabunde, CN
Kahn, KL
Fletcher, RH
Clauser, S
Tisnado, D
Doucette, W
Keating, NL
AF Rogers, Selwyn O., Jr.
Gray, Stacy W.
Landrum, Mary Beth
Klabunde, Carrie N.
Kahn, Katherine L.
Fletcher, Robert H.
Clauser, Steven
Tisnado, Diana
Doucette, William
Keating, Nancy L.
TI Variations in Surgeon Treatment Recommendations for Lobectomy in
Early-Stage Non-Small-Cell Lung Cancer by Patient Age and Comorbidity
SO ANNALS OF SURGICAL ONCOLOGY
LA English
DT Article
ID MINIMALLY INVASIVE LOBECTOMY; PULMONARY RESECTION; SURGICAL RESECTION;
ELDERLY-PATIENTS; COMPLICATIONS; SURVEILLANCE; MANAGEMENT; MORTALITY;
SURVIVAL; DATABASE
AB Prior research suggests that older patients are less likely to undergo resection of early-stage non-small-cell lung carcinomas (NSCLCs). We surveyed surgeons to understand how their recommendations for lobectomy were influenced by age, the presence and severity of smoking-related lung disease, or by characteristics of the surgeons and their practices.
We surveyed surgeons caring for NSCLC patients regarding whether they would recommend lobectomy for hypothetical patients with early-stage NSCLC who varied by age (55 vs. 80 years) and comorbid illness (none, moderate, severe chronic obstructive pulmonary disease [COPD]). Ordinal logistic regression was used to identify the importance of patient, surgeon, and practice characteristics on surgery recommendations.
Surgeons recommended lobectomy for nearly all patients who were 55 years old with no comorbidity (adjusted proportion 98.6%), 55 years old with moderate COPD (adjusted proportion 97.8%), or 80 years old with no comorbidity (adjusted proportion 98.1%). Fewer recommended lobectomy for 80-year-old patients with moderate COPD (adjusted proportion 82.3%), and far fewer recommended lobectomy for severe COPD, irrespective of age (adjusted rate 18.7% for the 55-year-old patient and 6.1% for the 80-year-old patient) (P < 0.002). Surgeons who enroll patients onto clinical trials (P = 0.03) were more likely than others to recommend lobectomy, but no other surgeon characteristic predicted recommendations.
Lower rates of lobectomy among older patients do not seem to be explained by age-related biases among surgeons for otherwise healthy patients.
C1 [Rogers, Selwyn O., Jr.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA.
[Rogers, Selwyn O., Jr.] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA 02115 USA.
[Gray, Stacy W.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Gray, Stacy W.] Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA.
[Landrum, Mary Beth; Keating, Nancy L.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
[Klabunde, Carrie N.; Clauser, Steven] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Kahn, Katherine L.] RAND Corp, Santa Monica, CA USA.
[Kahn, Katherine L.; Tisnado, Diana] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Fletcher, Robert H.] Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA.
[Doucette, William] Univ Iowa, Coll Pharm, Iowa City, IA 52242 USA.
[Keating, Nancy L.] Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA.
RP Rogers, SO (reprint author), Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA.
EM srogers@partners.org
FU National Cancer Institute (NCI) [U01 CA093344, U01 CA093332, U01
CA093324, U01 CA093348, U01 CA093329, U01 CA01013, U01 CA093326];
Department of Veteran's Affairs [CRS 02-164]
FX This work of the Cancer Care Outcomes Research and Surveillance
(CanCORS) Consortium was supported by grants from the National Cancer
Institute (NCI) to the Statistical Coordinating Center (U01 CA093344)
and the NCI-supported Primary Data Collection and Research Centers (Dana
Farber Cancer Institute/Cancer Research Network U01 CA093332, Harvard
Medical School/Northern California Cancer Center U01 CA093324, RAND/UCLA
U01 CA093348, University of Alabama at Birmingham U01 CA093329,
University of Iowa U01 CA01013, University of North Carolina U01
CA093326) and by a Department of Veteran's Affairs grant to the Durham
VA Medical Center CRS 02-164.
NR 31
TC 10
Z9 10
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1068-9265
J9 ANN SURG ONCOL
JI Ann. Surg. Oncol.
PD JUN
PY 2010
VL 17
IS 6
BP 1581
EP 1588
DI 10.1245/s10434-010-0946-y
PG 8
WC Oncology; Surgery
SC Oncology; Surgery
GA 595EU
UT WOS:000277594300017
PM 20162461
ER
PT J
AU Maduekwe, UN
Yoon, SS
AF Maduekwe, Ugwuji N.
Yoon, Sam S.
TI In Reply: Does Metastatic Lymph Node Ratio Really Suit for Prognostic
Prediction of the D1 Lymphadenectomy?
SO ANNALS OF SURGICAL ONCOLOGY
LA English
DT Letter
C1 [Maduekwe, Ugwuji N.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Yoon, Sam S.] Hosp Univ Penn, Dept Surg, Philadelphia, PA 19104 USA.
RP Maduekwe, UN (reprint author), Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA.
EM sam.yoon@uphs.upenn.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1068-9265
J9 ANN SURG ONCOL
JI Ann. Surg. Oncol.
PD JUN
PY 2010
VL 17
IS 6
BP 1719
EP 1719
DI 10.1245/s10434-010-1065-5
PG 1
WC Oncology; Surgery
SC Oncology; Surgery
GA 595EU
UT WOS:000277594300040
ER
PT J
AU Hsia, TY
McQuinn, TC
Mukherjee, R
Deardorff, RL
Squires, JE
Stroud, RE
Crawford, FA
Bradley, SM
Reeves, ST
Spinale, FG
AF Hsia, Tain-Yen
McQuinn, Tim C.
Mukherjee, Rupak
Deardorff, Rachael L.
Squires, Jerry E.
Stroud, Robert E.
Crawford, Fred A.
Bradley, Scott M.
Reeves, Scott T.
Spinale, Francis G.
TI Effects of Aprotinin or Tranexamic Acid on Proteolytic/Cytokine Profiles
in Infants After Cardiac Surgery
SO ANNALS OF THORACIC SURGERY
LA English
DT Article; Proceedings Paper
CT 56th Annual Meeting of the Southern-Thoracic-Surgical-Association
CY NOV 04-07, 2009
CL Marco Isl, FL
SP So Thorac Surg Assoc
ID EPSILON-AMINOCAPROIC ACID; SYSTEMIC INFLAMMATORY RESPONSE;
CARDIOPULMONARY BYPASS; MATRIX METALLOPROTEINASES; RENAL DYSFUNCTION;
COLLAGENASE-2 MMP-8; PEDIATRIC-PATIENTS; TISSUE INHIBITORS; CHILDREN;
ACTIVATION
AB Background. After cardiopulmonary bypass (CPB), elaboration of cytokines, and subsequent induction of interstitial proteases, such as matrix metalloproteinases (MMPs), can result in a complex postoperative course. The serine protease inhibitor, aprotinin, which has been used in congenital heart surgery putatively for modulating fibrinolysis is now unavailable, necessitating the use of lysine analogues such as tranexamic acid (TXA). The present study tested the hypothesis that distinctly different plasma profiles of signaling molecules and proteases would be differentially affected after the administration of aprotinin or TXA in the context of congenital cardiac surgery and CPB.
Methods. Thirty-seven patients (age, 4.8 +/- 0.3 months) undergoing corrective surgery for ventricular septal defect and tetralogy of Fallot received either aprotinin (n = 22) or TXA (n = 15). Using a high throughput multiplex suspension immunoassay, plasma was serially quantified for cytokines and MMPs: before aprotinin or TXA (baseline), after separation from CPB, and 4, 12, 24, and 48 hours post-CPB.
Results. Tumor necrosis factor-alpha increased initially after CPB in both the aprotinin and TXA groups, but at 24 and 48 hours post-CPB was approximately 50% lower in the aprotinin group (p < 0.05). The IL-10 levels were threefold higher in the TXA group compared with the aprotinin group immediately post-CBP (p < 0.05). Plasma levels of MMP types associated with inflammation, MMP-8, and MMP-9, were twofold higher in the late post-CPB period in the TXA group when compared with the aprotinin group.
Conclusions. After ventricular septal defect or tetralogy of Fallot repair in children, cytokine induction occurs, which is temporally related to the emergence of a specific MMP profile. Moreover, these unique findings demonstrated differential effects between the serine protease inhibitor aprotinin and the lysine analogue TXA with respect to cytokine and MMP induction in the early postoperative period. The different cytokine-proteolytic profile between these antifibrinolytics may in turn influence biologic processes in the postoperative period. (Ann Thorac Surg 2010; 89: 1843-52) (C) 2010 by The Society of Thoracic Surgeons
C1 [Spinale, Francis G.] Med Univ S Carolina, Div Cardiothorac Surg, Strom Thurmond Res Ctr, Dept Pathol & Lab Med, Charleston, SC 29425 USA.
Med Univ S Carolina, Dept Anesthesia Perioperat Med, Charleston, SC 29425 USA.
Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA.
Univ Washington, Dept Pediat, Seattle, WA 98195 USA.
RP Spinale, FG (reprint author), Med Univ S Carolina, Div Cardiothorac Surg, Strom Thurmond Res Ctr, Dept Pathol & Lab Med, 114 Doughty St,Ste 625, Charleston, SC 29425 USA.
EM wilburnm@musc.edu
FU NHLBI NIH HHS [R01 HL057952-12, R01 HL059165-12, HL057952-08, R01
HL059165, R01 HL057952, HL059165-09]
NR 35
TC 10
Z9 10
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0003-4975
J9 ANN THORAC SURG
JI Ann. Thorac. Surg.
PD JUN
PY 2010
VL 89
IS 6
BP 1843
EP 1852
DI 10.1016/j.athoracsur.2010.02.069
PG 10
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA 599ST
UT WOS:000277934200019
PM 20494037
ER
PT J
AU Matthews, PB
Azadani, AN
Jhun, CS
Ge, L
Guy, TS
Guccione, JM
Tseng, EE
AF Matthews, Peter B.
Azadani, Ali N.
Jhun, Choon-Sik
Ge, Liang
Guy, T. Sloane
Guccione, Julius M.
Tseng, Elaine E.
TI Comparison of Porcine Pulmonary and Aortic Root Material Properties
SO ANNALS OF THORACIC SURGERY
LA English
DT Article
ID ROSS PROCEDURE; AUTOGRAFT DILATATION; OPERATION; VALVE; MECHANICS;
PRESSURE; DYNAMICS; IMPACT; FLOW
AB Background. The pulmonary autograft remodels when subjected to systemic pressure and subsequent dilation can lead to reoperation. Inherent material property differences between pulmonary and aortic roots may influence remodeling but are currently unknown. The objective of this study was to determine stiffness across a wide range of strain and compare nonlinear material properties of corresponding regions of native aortic and pulmonary roots.
Methods. Tissue samples from porcine aortic and pulmonary roots-sinuses and supravalvular artery distal to the sinotubular junction-were subjected to displacement-controlled equibiaxial stretch testing. Stress-strain data recorded were used to derive strain energy functions for each region. Stiffness from low to high strains at 0.15, 0.3, and 0.5 strain were determined for comparisons.
Results. Aortic and pulmonary roots exhibited qualitatively similar material properties; both had greater non-linearity in the sinus than supravalvular artery. The pulmonary artery was significantly more compliant than the ascending aorta both circumferentially and longitudinally throughout the strain range (p < 0.03), except at high strain circumferentially (p = 0.06). However, no differences in stiffness were seen circumferentially or longitudinally between pulmonary and aortic sinuses (p >= 0.3) until high strain, when the pulmonary sinuses were significantly stiffer (p < 0.05) in both directions.
Conclusions. Differences in stiffness between porcine aortic and pulmonary roots are regionally specific, supravalvular artery versus sinus. These regional differences may impact the mode of remodeling to influence late autograft dilation. (Ann Thorac Surg 2010; 89: 1981-9) (C) 2010 by The Society of Thoracic Surgeons
C1 [Tseng, Elaine E.] Univ Calif San Francisco, Med Ctr, Dept Surg, Div Cardiothorac Surg, San Francisco, CA 94143 USA.
San Francisco VA Med Ctr, San Francisco, CA USA.
RP Tseng, EE (reprint author), Univ Calif San Francisco, Med Ctr, Dept Surg, Div Cardiothorac Surg, 500 Parnassus Ave,Ste W405,Box 0118, San Francisco, CA 94143 USA.
EM elaine.tseng@ucsfmedctr.org
NR 31
TC 18
Z9 18
U1 0
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0003-4975
J9 ANN THORAC SURG
JI Ann. Thorac. Surg.
PD JUN
PY 2010
VL 89
IS 6
BP 1981
EP 1989
DI 10.1016/j.athoracsur.2010.03.002
PG 10
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA 599ST
UT WOS:000277934200038
PM 20494060
ER
PT J
AU Kratz, JR
Yagui-Beltran, A
Jablons, DM
AF Kratz, Johannes R.
Yagui-Beltran, Adam
Jablons, David M.
TI Cancer Stem Cells in Lung Tumorigenesis
SO ANNALS OF THORACIC SURGERY
LA English
DT Article; Proceedings Paper
CT 2nd International Biannual Minimally Invasive Thoracic Surgery Summit
CY OCT 09-10, 2009
CL Harvard Med Sch, Boston, MA
SP Cine Med
HO Harvard Med Sch
ID ONCOGENIC K-RAS; BASAL-CELLS; CLARA CELL; PROGENITOR CELLS; BRONCHIOLAR
EPITHELIUM; PTEN EXPRESSION; SIDE-POPULATION; IDENTIFICATION; TUMORS;
DIFFERENTIATION
AB Although stem cells were discovered more than 50 years ago, we have only recently begun to understand their potential importance in cancer biology. Recent advances in our ability to describe, isolate, and study lung stem cell populations has led to a growing recognition of the central importance cells with stem cell-like properties may have in lung tumorigenesis. This article reviews the major studies supporting the existence and importance of cancer stem cells in lung tumorigenesis. Continued research in the field of lung cancer stem cell biology is vital, as ongoing efforts promise to yield new prognostic and therapeutic targets. (Ann Thorac Surg 2010; 89: S2090-5) (C) 2010 by The Society of Thoracic Surgeons
C1 Univ Calif San Francisco, Dept Surg, Ctr Canc, San Francisco, CA 94115 USA.
Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
RP Kratz, JR (reprint author), Univ Calif San Francisco, Dept Surg, UCSF Helen Diller Family Comprehens Canc Ctr, 2340 Sutter St,Rm N261, San Francisco, CA 94115 USA.
EM johannes.kratz@ucsfmedctr.org
FU NCI NIH HHS [R01 CA093708, R011R01CA093708-01A3, R01 CA132566-04, R01
CA132566]
NR 64
TC 7
Z9 9
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0003-4975
J9 ANN THORAC SURG
JI Ann. Thorac. Surg.
PD JUN
PY 2010
VL 89
IS 6
BP S2090
EP S2095
DI 10.1016/j.athoracsur.2010.03.038
PG 6
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA 599ST
UT WOS:000277934200087
PM 20493987
ER
PT J
AU Seidman, LJ
Giuliano, AJ
Meyer, EC
Addington, J
Cadenhead, KS
Cannon, TD
McGlashan, TH
Perkins, DO
Tsuang, MT
Walker, EF
Woods, SW
Bearden, CE
Christensen, BK
Hawkins, K
Heaton, R
Keefe, RSE
Heinssen, R
Cornblatt, BA
AF Seidman, Larry J.
Giuliano, Anthony J.
Meyer, Eric C.
Addington, Jean
Cadenhead, Kristin S.
Cannon, Tyrone D.
McGlashan, Thomas H.
Perkins, Diana O.
Tsuang, Ming T.
Walker, Elaine F.
Woods, Scott W.
Bearden, Carrie E.
Christensen, Bruce K.
Hawkins, Keith
Heaton, Robert
Keefe, Richard S. E.
Heinssen, Robert
Cornblatt, Barbara A.
CA N Amer Prodrome Longitudinal Study
TI Neuropsychology of the Prodrome to Psychosis in the NAPLS Consortium
Relationship to Family History and Conversion to Psychosis
SO ARCHIVES OF GENERAL PSYCHIATRY
LA English
DT Article
ID ULTRA-HIGH-RISK; CLINICAL HIGH-RISK; NEUROCOGNITIVE DEFICITS;
WORKING-MEMORY; 1ST EPISODE; 1ST-DEGREE RELATIVES; PREDICTIVE-VALIDITY;
INTERRATER RELIABILITY; SCHIZOPHRENIA-PATIENTS; COGNITIVE PERFORMANCE
AB Context: Early detection and prospective evaluation of clinical high-risk (CHR) individuals who may develop schizophrenia or other psychotic disorders is critical for predicting psychosis onset and for testing preventive interventions.
Objectives: To elucidate the neuropsychology of the CHR syndrome, to determine the association of neuropsychological function with conversion to psychosis and family history of psychosis, and to examine whether baseline neuropsychological functioning predicts subsequent psychosis.
Design: Longitudinal study with 2 1/2 years of follow-up.
Setting: Eight centers participating in the North American Prodrome Longitudinal Study.
Participants: Three hundred four prospectively identified CHR individuals meeting Structured Interview for Prodromal Syndromes criteria, 52 non-CHR persons with a family history of psychosis in first- or second-degree relatives (family high-risk group), and 193 normal controls with neither a family history of psychosis nor a CHR syndrome, all of whom underwent baseline neuropsychological evaluations.
Main Outcome Measures: A neurocognitive composite score, 8 individual neuropsychological measures, an IQ estimate, and high-risk status.
Results: Global ("composite") neuropsychological functioning was comparably impaired in the CHR and family high-risk groups compared with controls, but profiles differed significantly between groups. Neuropsychological functioning in the CHR group was significantly lower in persons who progressed to psychosis than in those who did not and was worst in the subgroup with a family history of psychosis. Tests of processing speed and verbal learning and memory were most sensitive in discriminating CHR individuals from controls, although reductions were less severe than in established schizophrenia. Neuropsychological functioning did not contribute uniquely to the prediction of psychosis beyond clinical criteria, but worse verbal memory predicted more rapid conversion.
Conclusions: These findings document that CHR individuals have significant neuropsychological difficulties, particularly those who later develop psychosis. This dysfunction is generally of moderate severity but less than in first-episode schizophrenia, suggesting that further decline may occur after baseline CHR assessment.
C1 [Seidman, Larry J.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr,Publ Psychiat Div, Massachusetts Mental Hlth Ctr,Dept Psychiat, Boston, MA 02215 USA.
[Seidman, Larry J.; Tsuang, Ming T.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Meyer, Eric C.] Texas A&M Hlth Sci Ctr, Coll Med, Dept Psychiat & Behav Sci, Waco, TX USA.
[Addington, Jean] Univ Calgary, Dept Psychiat, Calgary, AB, Canada.
[Cadenhead, Kristin S.; Tsuang, Ming T.; Heaton, Robert] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA.
[Cannon, Tyrone D.; Bearden, Carrie E.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA.
[Cannon, Tyrone D.; Bearden, Carrie E.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA.
[McGlashan, Thomas H.; Woods, Scott W.; Hawkins, Keith] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA.
[Perkins, Diana O.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA.
[Walker, Elaine F.] Emory Univ, Dept Psychol, Atlanta, GA 30322 USA.
[Walker, Elaine F.] Emory Univ, Dept Psychiat, Atlanta, GA 30322 USA.
[Christensen, Bruce K.] McMaster Univ, Dept Psychiat & Behav Neurosci, Hamilton, ON, Canada.
[Keefe, Richard S. E.] Duke Univ, Dept Psychiat & Behav Sci & Psychol, Chapel Hill, NC USA.
[Heinssen, Robert] NIMH, Schizophrenia Spectrum Res Program, Div Adult Translat Res, Bethesda, MD 20892 USA.
[Cornblatt, Barbara A.] Zucker Hillside Hosp, Dept Psychiat, Long Isl City, NY USA.
RP Seidman, LJ (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr,Publ Psychiat Div, Massachusetts Mental Hlth Ctr,Dept Psychiat, 401 Pk Dr, Boston, MA 02215 USA.
EM lseidman@bidmc.harvard.edu
FU National Institute of Mental Health [R18 MH 43518, U01 MH081928, P50
M11080272]; [U01 MH066134]; [RO1 MH60720]; [K24 MH76191]; [R01
MH65079]; [K05MH01654]; [U01 MH066069]; [P50 MH064065];
[RO1MH062066]; [5 U01 MH081988]; [U01 MH74356]; [U01 MH082022]; [R41
MH083436]; [RO1 MH061523]
FX This study was supported by the National Institute of Mental Health
(grants R18 MH 43518, U01 MH081928, and P50 M11080272 to Dr Seidman;
grant U01 MH066134 to Dr Addington; grants RO1 MH60720 and K24 MH76191
to Dr Cadenhead; grant R01 MH65079 to Dr Cannon; grant K05MH01654 to Dr
McGlashan; grants U01 MH066069 and P50 MH064065 to Dr Perkins; grant R18
MH 43518 to Dr Tsuang; grants RO1MH062066 and 5 U01 MH081988 to Dr
Walker; grants U01 MH74356, U01 MH082022, and R41 MH083436 to Dr Woods;
and grant RO1 MH061523 to Dr Cornblatt).
NR 88
TC 195
Z9 202
U1 7
U2 27
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0003-990X
J9 ARCH GEN PSYCHIAT
JI Arch. Gen. Psychiatry
PD JUN
PY 2010
VL 67
IS 6
BP 578
EP 588
PG 11
WC Psychiatry
SC Psychiatry
GA 605CD
UT WOS:000278324000006
PM 20530007
ER
PT J
AU Yaffe, K
Vittinghoff, E
Lindquist, K
Barnes, D
Covinsky, KE
Neylan, T
Kluse, M
Marmar, C
AF Yaffe, Kristine
Vittinghoff, Eric
Lindquist, Karla
Barnes, Deborah
Covinsky, Kenneth E.
Neylan, Thomas
Kluse, Molly
Marmar, Charles
TI Posttraumatic Stress Disorder and Risk of Dementia Among US Veterans
SO ARCHIVES OF GENERAL PSYCHIATRY
LA English
DT Article
ID HOLOCAUST SURVIVORS; ALZHEIMERS-DISEASE; COGNITIVE DECLINE; PTSD
SYMPTOMS; HIPPOCAMPAL; BRAIN; IRAQ; CORTISOL; OUTCOMES; VIETNAM
AB Context: Posttraumatic stress disorder (PTSD) is highly prevalent among US veterans because of combat and may impair cognition.
Objective: To determine whether PTSD is associated with the risk of developing dementia among older US veterans receiving treatment in the Department of Veterans Affairs medical centers.
Design: A stratified, retrospective cohort study conducted using the Department of Veterans Affairs National Patient Care Database.
Setting: Department of Veterans Affairs medical centers in the United States.
Participants: A total of 181 093 veterans 55 years or older without dementia from fiscal years 1997 through 2000 (53 155 veterans with and 127 938 veterans without PTSD).
Main Outcome Measures: During the follow-up period between October 1, 2000, and December 31, 2007, 31 107 (17.2%) veterans were ascertained to have newly diagnosed dementia according to International Classification of Diseases, Ninth Revision, Clinical Modification codes.
Results: The mean baseline age of the veterans was 68.8 years, and 174 806 (96.5%) were men. Veterans with PTSD had a 7-year cumulative incident dementia rate of 10.6%, whereas those without had a rate of 6.6% (P<.001). With age as the time scale, Cox proportional hazards models indicated that patients with PTSD were more than twice as likely to develop incident dementia compared with those without PTSD (hazard ratio, 2.31; 95% confidence interval, 2.24-2.39). After multivariable adjustment, patients with PTSD were still more likely to develop dementia (hazard ratio, 1.77; 95% confidence interval, 1.70-1.85). Results were similar when we excluded those with a history of head injury, substance abuse, or clinical depression.
Conclusions: In a predominantly male veteran cohort, those diagnosed as having PTSD were at a nearly 2-fold-higher risk of developing dementia compared with those without PTSD. Mechanisms linking these important disorders need to be identified with the hope of finding ways to reduce the increased risk of dementia associated with PTSD.
C1 [Yaffe, Kristine; Covinsky, Kenneth E.; Neylan, Thomas; Marmar, Charles] San Francisco VA Med Ctr, San Francisco, CA 94121 USA.
[Yaffe, Kristine; Barnes, Deborah; Neylan, Thomas; Kluse, Molly; Marmar, Charles] Univ Calif San Francisco, Sch Med, Dept Psychiat, San Francisco, CA 94143 USA.
[Yaffe, Kristine] Univ Calif San Francisco, Sch Med, Dept Neurol, San Francisco, CA 94143 USA.
[Yaffe, Kristine; Vittinghoff, Eric] Univ Calif San Francisco, Sch Med, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Lindquist, Karla; Covinsky, Kenneth E.] Univ Calif San Francisco, Sch Med, Dept Med, San Francisco, CA 94143 USA.
RP Yaffe, K (reprint author), San Francisco VA Med Ctr, 4150 Clement St,Box 181, San Francisco, CA 94121 USA.
EM kristine.yaffe@ucsf.edu
FU US Department of Defense [W81XWH-05-2-0094]; National Institute on Aging
[AG031155]
FX This study was funded by US Department of Defense grant W81XWH-05-2-0094
(principal investigator: Dr Yaffe). Dr Yaffe was supported in part by
the National Institute on Aging (grant AG031155) and an anonymous
foundation.
NR 38
TC 131
Z9 133
U1 5
U2 19
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0003-990X
J9 ARCH GEN PSYCHIAT
JI Arch. Gen. Psychiatry
PD JUN
PY 2010
VL 67
IS 6
BP 608
EP 613
PG 6
WC Psychiatry
SC Psychiatry
GA 605CD
UT WOS:000278324000009
PM 20530010
ER
PT J
AU Biffi, A
Anderson, CD
Desikan, RS
Sabuncu, M
Cortellini, L
Schmansky, N
Salat, D
Rosand, J
AF Biffi, Alessandro
Anderson, Christopher D.
Desikan, Rahul S.
Sabuncu, Mert
Cortellini, Lynelle
Schmansky, Nick
Salat, David
Rosand, Jonathan
CA ADNI
TI Genetic Variation and Neuroimaging Measures in Alzheimer Disease
SO ARCHIVES OF NEUROLOGY
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; SURFACE-BASED ANALYSIS; IDENTIFIES VARIANTS;
HIPPOCAMPAL ATROPHY; HUMAN BRAIN; SEGMENTATION; VOLUME; BIN1; CLU
AB Objective: To investigate whether genome-wide association study (GWAS) validated and GWAS-promising candidate loci influence magnetic resonance imaging measures and clinical Alzheimer's disease (AD) status.
Design: Multicenter case-control study of genetic and neuroimaging data from the Alzheimer's Disease Neuroimaging Initiative.
Setting: Multicenter GWAS.
Patients: A total of 168 individuals with probable AD, 357 with mild cognitive impairment, and 215 cognitively normal control individuals recruited from more than 50 Alzheimer's Disease Neuroimaging Initiative centers in the United States and Canada. All study participants had APOE and genome-wide genetic data available.
Main Outcome Measures: We investigated the influence of GWAS-validated and GWAS-promising novel AD loci on hippocampal volume, amygdala volume, white matter lesion volume, entorhinal cortex thickness, parahippocampal gyrus thickness, and temporal pole cortex thickness.
Results: Markers at the APOE locus were associated with all phenotypes except white matter lesion volume (all false discovery rate corrected P values < .001). Novel and established AD loci identified by prior GWASs showed a significant cumulative score based effect (false discovery rate P = .04) on all analyzed neuroimaging measures. The GWAS-validated variants at the CR1 and PICALM loci and markers at 2 novel loci (BIN1 and CNTN5) showed association with multiple magnetic resonance imaging characteristics (false discovery rate P < .05).
Conclusions: Loci associated with AD also influence neuroimaging correlates of this disease. Furthermore, neuroimaging analysis identified 2 additional loci of high interest for further study.
C1 [Biffi, Alessandro; Anderson, Christopher D.; Cortellini, Lynelle; Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, Dept Neurol, Boston, MA 02114 USA.
[Desikan, Rahul S.; Sabuncu, Mert; Cortellini, Lynelle; Schmansky, Nick; Salat, David] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA USA.
[Biffi, Alessandro; Anderson, Christopher D.; Cortellini, Lynelle; Rosand, Jonathan] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
RP Rosand, J (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Dept Neurol, 185 Cambridge St,Ste CPZN 6818, Boston, MA 02114 USA.
EM jrosand@partners.org
RI Scharre, Douglas/E-4030-2011
FU Alzheimer's Disease Neuroimaging Initiative (ADNI); National Institutes
of Health (NIH) [U01 AG024904, P30 AG010129, K01 AG030514, R01
AG028676-01A1, R01 NS042861-06A1, 5P41 RR14075-11, R21 DA026104, R01
AG026484-02, R01 NS052585, R01 NS059727]; National Institute on Aging
(NIA) [AG02238, P50 AG05681, P01AG03991, AG021910]; National Institute
of Biomedical Imaging and Bioengineering [R01 EB006758, R01 EB001550];
Dana Foundation; American Heart Association/Bugher Foundation Centers
for Stroke Prevention Research [0775010N]; National Center for Research
Resources (NCRR) [P41-RR14075, U54 RR020278, R01 RR 16594-01A1, BIRN002,
U24 RR021382]; National Institute for Neurological Disorders and Stroke
[R01 NS059727, R01 NS052585-01]; Ellison Medical Foundation; Deane
Institute for Integrative Study of Atrial Fibrillation and Stroke
[P41-RR14075]; Mental Illness and Neuroscience Discovery Institute;
ADNI/NIH [U01 AG024904]; Howard Hughes Medical Institute
FX Data collection and sharing for this project was funded by the
Alzheimer's Disease Neuroimaging Initiative (ADNI) and the National
Institutes of Health (NIH) (grant U01 AG024904). The ADNI is funded by
the National Institute on Aging (NIA), the National Institute of
Biomedical Imaging and Bioengineering, and through generous
contributions from the following: Abbott Laboratories, AstraZeneca AB,
Bayer Schering Pharma AG, Bristol-Myers Squibb, Eisai Global Clinical
Development, Elan Corporation Plc, Genentech Inc, GE Healthcare,
GlaxoSmithKline, Innogenetics, Johnson and Johnson Services Inc, Eli
Lilly and Company, Medpace Inc, Merck and Co Inc, Novartis International
AG, Pfizer Inc, F. Hoffman-La Roche Ltd, Schering-Plough Corporation,
CCBR-SYNARC Inc, and Wyeth Pharmaceuticals, as well as nonprofit
partners the Alzheimer's Association and Alzheimer's Drug Discovery
Foundation, with participation from the US Food and Drug Administration.
Private sector contributions to the ADNI are facilitated by the
Foundation for the NIH. The grantee organization is the Northern
California Institute for Research and Education Inc, and the study is
coordinated by the Alzheimer's Disease Cooperative Study at the
University of California, San Diego. The ADNI data are disseminated by
the Laboratory for Neuro Imaging at the University of California, Los
Angeles. This research was also supported by the NIH (grants P30
AG010129 and K01 AG030514) and the Dana Foundation. Drs Biffi and
Anderson receive research support from the American Heart
Association/Bugher Foundation Centers for Stroke Prevention Research
(grant 0775010N). Dr Desikan receives research support from the National
Center for Research Resources (NCRR) (grant P41-RR14075), the National
Institute of Biomedical Imaging and Bioengineering (grant R01 EB006758),
the NIA (grant AG02238), and the National Institute for Neurological
Disorders and Stroke (grant R01 NS052585-01). Dr Sabuncu receives
research support from the NCRR (grant P41-RR14075), the National
Institute of Biomedical Imaging and Bioengineering (grant R01EB006758),
the NIA (grant AG02238), and the National Institute for Neurological
Disorders and Stroke (grant R01 NS052585-01). Mr Schmansky receives
research support from the NCRR (grant P41-RR14075), the National
Institute of Biomedical Imaging and Bioengineering (grant R01EB006758),
the NIA (grant AG02238), the National Institute for Neurological
Disorders and Stroke (grant R01 NS052585-01), and The Autism and
Dyslexia Project, funded by the Ellison Medical Foundation. Dr Salat is
funded by and receives research support from the NIH (grants R01
AG028676-01A1, R01 NS042861-06A1, 5P41 RR14075-11, R21 DA026104, and R01
AG026484-02). Dr Rosand is funded by the NIH (grants R01 NS052585 and
R01 NS059727), the American Heart Association/Bugher Foundation Centers
for Stroke Prevention Research (grant 0775010N), the Deane Institute for
Integrative Study of Atrial Fibrillation and Stroke, and the NCRR (grant
U54 RR020278). This work was supported by the National Center for
Research Resources (grants P41-RR14075 and R01 RR 16594-01A1); the NCRR
Biomedical Informatics Research Network Morphometric Project (grants
BIRN002 and U24 RR021382); the National Institute of Biomedical Imaging
and Bioengineering (grant R01 EB001550); the Mental Illness and
Neuroscience Discovery Institute; and the NIA (grants P50 AG05681,
P01AG03991, and AG021910).; Data collection and sharing for this project
were funded by the the ADNI/NIH (principal investigator: Michael Weiner;
grant U01 AG024904]) and the Howard Hughe Medical Institute (Open Access
Series of Imaging Studies project). The ADNI is funded by the NIA, the
National Institute of Biomedical Imaging and Bioengineering, 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 International AG, Alzheimer's Association,
Eisai Global Clinical Development, Elan Corporation Plc, Forest
Laboratories Inc, and the Institute for the Study of Aging, with
participation from the US Food and Drug Administration. Industry
partnerships are coordinated through the Foundation for the NIH. 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. This research was also supported by the
American Heart Association/Bugher Foundation Centers for Stroke
Prevention Research (grant 0774010N); the Deane Institute for
Integrative Study of Atrial Fibrillation and Stroke (grant P41-RR14075);
the National Center for Research Resources; the National Institute for
Biomedical Imaging and Bioengineering (grant R01 EB006758); the NIA
(grant AG02238); and the National Institute for Neurological Disorders
and Stroke (grants R01 NS052585-01 and R01 NS059727).
NR 35
TC 103
Z9 104
U1 2
U2 6
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0003-9942
J9 ARCH NEUROL-CHICAGO
JI Arch. Neurol.
PD JUN
PY 2010
VL 67
IS 6
BP 677
EP 685
PG 9
WC Clinical Neurology
SC Neurosciences & Neurology
GA 607OJ
UT WOS:000278513400005
PM 20558387
ER
PT J
AU Sano, M
AF Sano, Mary
TI Tarenflurbil Mechanisms and Myths
SO ARCHIVES OF NEUROLOGY
LA English
DT Editorial Material
ID GAMMA-SECRETASE INHIBITOR; ALZHEIMER-DISEASE; AMYLOID-BETA; SAFETY;
TRIAL; FLURBIPROFEN
C1 James J Peters Vet Affairs Med Ctr, Alzheimer Dis Res Ctr, Dept Psychiat, Mt Sinai Sch Med, Bronx, NY 10468 USA.
RP Sano, M (reprint author), James J Peters Vet Affairs Med Ctr, Alzheimer Dis Res Ctr, Dept Psychiat, Mt Sinai Sch Med, 130 Kingsbridge Rd,Code 150,Room 1F01, Bronx, NY 10468 USA.
EM mary.sano@mssm.edu
FU NIA NIH HHS [P50 AG005138-21A1, 2P50 AG005138-26, P50 AG005138]
NR 9
TC 4
Z9 4
U1 0
U2 4
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0003-9942
J9 ARCH NEUROL-CHICAGO
JI Arch. Neurol.
PD JUN
PY 2010
VL 67
IS 6
BP 750
EP 752
PG 3
WC Clinical Neurology
SC Neurosciences & Neurology
GA 607OJ
UT WOS:000278513400015
PM 20558395
ER
PT J
AU Yeung, HH
Walton, DS
AF Yeung, Helen H.
Walton, David S.
TI Clinical Classification of Childhood Glaucomas
SO ARCHIVES OF OPHTHALMOLOGY
LA English
DT Article
ID ANGLE-CLOSURE GLAUCOMA; RUBINSTEIN-TAYBI-SYNDROME; OF-THE-LITERATURE;
IRIDOCORNEAL ENDOTHELIAL SYNDROME; PRIMARY CONGENITAL GLAUCOMA;
ROTHMUND-THOMSON-SYNDROME; WEILL-MARCHESANI-SYNDROME;
WALKER-WARBURG-SYNDROME; STURGE-WEBER-SYNDROME; NAIL-PATELLA SYNDROME
AB Objective: An updated classification of the primary and secondary childhood glaucomas is offered for clinical use, and associated systemic diseases are included to enable their early recognition in children with known glaucoma.
Methods: Approximately 650 clinical records of patients with pediatric glaucoma were reviewed for type of glaucoma and associated systemic disease. A literature search was done for additional reported causes of childhood glaucoma. Previous classifications of pediatric glaucomas were also reviewed. Pertinent references to support inclusion of each clinical entity in the updated classification are included.
Results: A comprehensive and referenced classification of the pediatric glaucomas was enabled by this review.
Conclusion: A comprehensive, etiologically based classification of the pediatric glaucomas is now available to assist with the recognition of the many causes of primary and secondary glaucoma in childhood and to support the selection of specific treatment choices.
C1 [Walton, David S.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA USA.
[Yeung, Helen H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat, Boston, MA USA.
RP Walton, DS (reprint author), 2 Longfellow Pl,Ste 201, Boston, MA 02114 USA.
EM walton.blackeye@gmail.com
NR 170
TC 16
Z9 16
U1 0
U2 7
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0003-9950
J9 ARCH OPHTHALMOL-CHIC
JI Arch. Ophthalmol.
PD JUN
PY 2010
VL 128
IS 6
BP 680
EP 684
PG 5
WC Ophthalmology
SC Ophthalmology
GA 610QA
UT WOS:000278747900003
PM 20547943
ER
PT J
AU Ament, JD
Tilahun, Y
Mudawi, E
Pineda, R
AF Ament, Jared D.
Tilahun, Yonas
Mudawi, Eiman
Pineda, Roberto
TI Role for Ipsilateral Autologous Corneas as a Carrier for the Boston
Keratoprosthesis: The Africa Experience
SO ARCHIVES OF OPHTHALMOLOGY
LA English
DT Letter
ID INDEX
C1 [Ament, Jared D.; Pineda, Roberto] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA.
[Tilahun, Yonas] Univ Addis Ababa, Menelick Hosp 2, Addis Ababa, Ethiopia.
[Mudawi, Eiman] Makkah Ophthalm Tech Coll, Khartoum, Sudan.
RP Ament, JD (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA.
EM jaredament@post.harvard.edu
NR 6
TC 8
Z9 8
U1 4
U2 4
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0003-9950
J9 ARCH OPHTHALMOL-CHIC
JI Arch. Ophthalmol.
PD JUN
PY 2010
VL 128
IS 6
BP 795
EP 797
PG 5
WC Ophthalmology
SC Ophthalmology
GA 610QA
UT WOS:000278747900024
PM 20547962
ER
PT J
AU Maturo, S
Hartnick, CJ
AF Maturo, Stephen
Hartnick, Christopher J.
TI Use of 532-nm Pulsed Potassium Titanyl Phosphate Laser and Adjuvant
Intralesional Bevacizumab for Aggressive Respiratory Papillomatosis in
Children
SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY
LA English
DT Article
ID CARBON-DIOXIDE LASER; DYE-LASER; GLOTTAL PAPILLOMATOSIS; LARYNGEAL
PAPILLOMAS; PHOTODYNAMIC THERAPY; NATIONAL REGISTRY; CLINICAL-COURSE;
CIDOFOVIR; DYSPLASIA; INDOLE-3-CARBINOL
AB Objective: To describe the initial pediatric experience with intralesional bevacizumab (Austin) treatment for children with severe, recurrent respiratory papilloma (RRP).
Design: Retrospective medical chart review.
Setting: Tertiary care multidisciplinary aerodigestive center.
Patients: Three children, aged 3 to 6 years, with severe RRP requiring more than 4 operative interventions in 1 year whose parents (or legal guardians) consented to adjuvant treatment with intralesional bevacizumab.
Intervention: All 3 children were treated as follows: surgical debridement with a microdebrider, pulsed potassium titanyl phosphate laser treatments, and adjuvant intralesional injections with bevacizumab (1.25 mg total).
Main Outcome Measures: Time interval between operative interventions, Derkay severity scale for RRP, and pediatric voice-related quality of life (PVRQOL) scores.
Results: All 3 children demonstrated increased time between operative interventions. Two children had a substantial decrease in their Derkay score and improved PVRQOL scores. One child, although time between operative interventions improved, did not have any change in Derkay score and required further adjuvant therapy.
Conclusions: Injectable bevacizumab appears to show some efficacy in prolonging the time between treatments and therefore reducing the number of treatments per year in children with severe RRP. However, before any meaningful conclusions can be drawn, further studies must be conducted in the form of head-to-head trials looking specifically at the issues of time between treatment intervals, efficacy of one adjunct over another, vocal outcomes, and whether several adjunctive treatments confer advantage over 1 treatment. In-depth and careful informed consent is mandatory for these studies so that parents are aware of the risks and benefits (known and unknown) before such individualized decisions are made.
C1 [Maturo, Stephen; Hartnick, Christopher J.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA.
RP Hartnick, CJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA.
EM Christopher_hartnick@meei.harvard.edu
NR 41
TC 13
Z9 13
U1 1
U2 3
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0886-4470
J9 ARCH OTOLARYNGOL
JI Arch. Otolaryngol. Head Neck Surg.
PD JUN
PY 2010
VL 136
IS 6
BP 561
EP 565
PG 5
WC Otorhinolaryngology; Surgery
SC Otorhinolaryngology; Surgery
GA 610XZ
UT WOS:000278774900004
PM 20566906
ER
PT J
AU Reh, DD
Lewis, CM
Metson, R
AF Reh, Douglas D.
Lewis, Carol M.
Metson, Ralph
TI Frontal Bullosa Diagnosis and Management of a New Variant of Frontal
Mucocele
SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY
LA English
DT Article
ID PARANASAL SINUS MUCOCELE; ORBIT
C1 [Reh, Douglas D.] Johns Hopkins Univ, Dept Otolaryngol Head & Neck Surg, Johns Hopkins Sch Med, Johns Hopkins Sinus Ctr, Baltimore, MD 21093 USA.
[Lewis, Carol M.] Univ Texas MD Anderson Canc Ctr, Dept Head & Neck Surg, Houston, TX 77030 USA.
[Metson, Ralph] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA.
[Metson, Ralph] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA.
RP Reh, DD (reprint author), Johns Hopkins Univ, Dept Otolaryngol Head & Neck Surg, Johns Hopkins Sch Med, Johns Hopkins Sinus Ctr, 601 N Caroline St,6th Floor, Baltimore, MD 21093 USA.
EM dreh1@jhmi.edu
NR 13
TC 1
Z9 1
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0886-4470
J9 ARCH OTOLARYNGOL
JI Arch. Otolaryngol. Head Neck Surg.
PD JUN
PY 2010
VL 136
IS 6
BP 625
EP 628
PG 4
WC Otorhinolaryngology; Surgery
SC Otorhinolaryngology; Surgery
GA 610XZ
UT WOS:000278774900015
PM 20566916
ER
PT J
AU Geboes, K
Lauwers, GY
AF Geboes, Karel
Lauwers, Gregory Y.
TI Gastrointestinal Pathology A Continuing Challenge
SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE
LA English
DT Editorial Material
C1 [Geboes, Karel] Katholieke Univ Leuven, Univ Hosp, Dept Pathol, B-3000 Louvain, Belgium.
[Lauwers, Gregory Y.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Lauwers, Gregory Y.] Harvard Univ, Sch Med, Boston, MA USA.
RP Geboes, K (reprint author), Katholieke Univ Leuven, Univ Hosp, Dept Pathol, Minderbroedersstr 12, B-3000 Louvain, Belgium.
EM Karel.geboes@uz.kuleuven.ac.be
NR 7
TC 0
Z9 0
U1 0
U2 2
PU COLLEGE AMER PATHOLOGISTS
PI NORTHFIELD
PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA
SN 0003-9985
J9 ARCH PATHOL LAB MED
JI Arch. Pathol. Lab. Med.
PD JUN
PY 2010
VL 134
IS 6
BP 812
EP 814
PG 3
WC Medical Laboratory Technology; Medicine, Research & Experimental;
Pathology
SC Medical Laboratory Technology; Research & Experimental Medicine;
Pathology
GA 609FT
UT WOS:000278642000005
PM 20524859
ER
PT J
AU Misdraji, J
AF Misdraji, Joseph
TI Appendiceal Mucinous Neoplasms Controversial Issues
SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE
LA English
DT Article
ID DISSEMINATED PERITONEAL ADENOMUCINOSIS; PSEUDOMYXOMA-PERITONEI;
CLINICOPATHOLOGICAL ANALYSIS; VERMIFORM APPENDIX; OVARIAN-TUMORS;
ORIGIN; PROGNOSIS; CARCINOMATOSIS; CYSTADENOMA; EMPHASIS
AB Low grade appendiceal mucinous neoplasms can spread to the peritoneum as pseudomyxoma peritonei even though they are not obviously invasive in the appendix. During the past several decades, several problematic issues surrounding this enigmatic tumor have been debated in the literature, including appropriate nomenclature for the appendiceal tumors and their peritoneal metastases. In this article, the most contentious issues in the area of appendiceal mucinous tumors are examined. First, the classification systems that have been proposed for these tumors are compared in the context of whether the appendiceal mucinous tumors are ruptured adenomas or invasive carcinomas. The controversy about the nature of pseudomyxoma peritonei and its classification systems is discussed in the following section. A brief discussion follows that examines the issue of localized pseudomyxoma peritonei and its clinical significance. Next reviewed is the largely resolved controversy about whether ovarian mucinous tumors in this setting are separate primaries or are metastases from the appendiceal tumor. Finally, the controversy about the most effective treatment of patients with pseudomyxoma peritonei is discussed. (Arch Pathol Lab Med. 2010;134:864-870)
C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
RP Misdraji, J (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Warren Bldg 105F, Boston, MA 02114 USA.
EM jmisdraji@partners.org
NR 36
TC 46
Z9 52
U1 0
U2 1
PU COLLEGE AMER PATHOLOGISTS
PI NORTHFIELD
PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA
SN 0003-9985
J9 ARCH PATHOL LAB MED
JI Arch. Pathol. Lab. Med.
PD JUN
PY 2010
VL 134
IS 6
BP 864
EP 870
PG 7
WC Medical Laboratory Technology; Medicine, Research & Experimental;
Pathology
SC Medical Laboratory Technology; Research & Experimental Medicine;
Pathology
GA 609FT
UT WOS:000278642000010
PM 20524864
ER
PT J
AU Korenstein, D
Keyhani, S
Ross, JS
AF Korenstein, Deborah
Keyhani, Salomeh
Ross, Joseph S.
TI Physician Attitudes Toward Industry A View Across the Specialties
SO ARCHIVES OF SURGERY
LA English
DT Article
ID MEDICAL-STUDENTS EXPOSURE; CONFLICTS-OF-INTEREST;
PHARMACEUTICAL-INDUSTRY; EDUCATIONAL INTERVENTION; NATIONAL-SURVEY;
RESIDENTS; GIFTS; REPRESENTATIVES; PAYMENTS; PROPOSAL
AB Objectives: To explore attitudes of physicians from all specialties toward gifts from and interactions with the pharmaceutical and medical device industries.
Design: Anonymous, cross-sectional survey distributed and collected between June 1 and September 1, 2008.
Setting: Hospitals in the Mount Sinai School of Medicine consortium in the New York, New York, metropolitan area.
Participants: Faculty and trainee physicians from all clinical departments.
Main Outcome Measures: Attitudes toward industry interactions and gifts and their appropriateness measured on 4-point Likert scales.
Results: A total of 590 physicians and medical students completed the survey (response rate, 67.0%); 351 (59.5%) were male, 230 (39.0%) were attending physicians, and 131 (23.7%) of 553 (excluding medical students) were from surgical specialties. Attitudes toward industry and gifts were generally positive: 72.2% found sponsored lunches appropriate, whereas 25.4% considered large gifts appropriate. Surgeons, trainees, and those unfamiliar with institutional policies on industry interactions held more positive attitudes than others and were more likely to deem some gifts appropriate, including industry funding of residency programs and, among surgeons, receiving meals, travel expenses, and payments for attending lectures. Nonattending physicians held more positive attitudes toward receiving meals in clinical settings, textbooks, and samples.
Conclusions: Physicians continue to hold positive attitudes toward marketing-oriented activities of the pharmaceutical and device industries. Changes in medical culture and physician education focused on surgeons and trainees may align physician attitudes with current policy trends.
C1 [Korenstein, Deborah] Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA.
[Keyhani, Salomeh] Mt Sinai Sch Med, Dept Hlth Policy, New York, NY 10029 USA.
[Ross, Joseph S.] Mt Sinai Sch Med, Dept Geriatr & Adult Dev, New York, NY 10029 USA.
[Keyhani, Salomeh; Ross, Joseph S.] James J Peters Vet Affairs Med Ctr, Hlth Serv Res & Dev Res Enhancement Award Program, Bronx, NY USA.
[Keyhani, Salomeh; Ross, Joseph S.] James J Peters Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, Bronx, NY USA.
RP Korenstein, D (reprint author), Mt Sinai Sch Med, Dept Med, 1 Gustave Levy Pl,Campus Box 1087, New York, NY 10029 USA.
EM deborah.korenstein@mssm.edu
FU Attorney General Prescriber Education; National Institute on Aging [K08
AG032886]; American Federation of Aging Research
FX Data collection for this work was partially supported by the Attorney
General Prescriber Education Grant Program administered by the state of
Oregon. Dr Ross is supported by the National Institute on Aging grant
K08 AG032886 and by the American Federation of Aging Research through
the Paul B. Beeson Career Development Award Program.
NR 29
TC 24
Z9 24
U1 2
U2 3
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0004-0010
J9 ARCH SURG-CHICAGO
JI Arch. Surg.
PD JUN
PY 2010
VL 145
IS 6
BP 570
EP 577
PG 8
WC Surgery
SC Surgery
GA 610XY
UT WOS:000278774800013
PM 20566978
ER
PT J
AU Khosroshahi, A
Bloch, DB
Deshpande, V
Stone, JH
AF Khosroshahi, Arezou
Bloch, Donald B.
Deshpande, Vikram
Stone, John H.
TI Rituximab Therapy Leads to Rapid Decline of Serum IgG4 Levels and Prompt
Clinical Improvement in IgG4-Related Systemic Disease
SO ARTHRITIS AND RHEUMATISM
LA English
DT Article
ID AUTOIMMUNE PANCREATITIS; SCLEROSING PANCREATITIS; RHEUMATOID-ARTHRITIS;
LUPUS-ERYTHEMATOSUS; IMMUNOTHERAPY; AUTOANTIBODY; RESPONSES; IL-10
AB Objective. Patients with IgG4-related systemic disease (IgG4-RSD) frequently show an incomplete response to treatment with glucocorticoids and traditional disease-modifying antirheumatic drugs (DMARDs). B lymphocyte depletion is a therapeutic strategy known to be effective for pemphigus vulgaris, an autoimmune condition mediated by IgG4 autoantibodies. This study was performed to assess the clinical and serologic responses to B lymphocyte depletion therapy with rituximab in patients with IgG4-RSD.
Methods. Four patients with IgG4-RSD were treated with 2 intravenous doses (1 gram each) of rituximab. Clinical improvement was assessed by monitoring the tapering/discontinuation of prednisone and DMARDs, and by measuring the serum concentrations of B lymphocytes, immunoglobulins, and IgG subclasses before and after therapy.
Results. Clinical features of IgG4-RSD in these 4 patients included autoimmune pancreatitis, sclerosing cholangitis, lymphoplasmacytic aortitis, salivary gland involvement, orbital pseudotumor, and lacrimal gland enlargement. The 3 patients with elevated serum IgG and IgG4 levels at baseline had a mean IgG concentration of 2,003 mg/dl (normal range 600-1,500 mg/dl) and a mean IgG4 concentration of 2,160 mg/dl (normal range 8-140 mg/dl). Among these patients, the serum IgG4 concentrations declined by a mean of 65% within 2 months of rituximab administration. All 4 patients demonstrated striking clinical improvement within 1 month of the initiation of rituximab therapy, and tapering or discontinuation of their treatment with prednisone and DMARDs was achieved in all 4 patients. A decrease in IgG concentration was observed for the IgG4 subclass only.
Conclusion. Treatment with rituximab led to prompt clinical and serologic improvement in these patients with refractory IgG4-RSD, and is a viable treatment option for this condition. The decline in serum IgG4 concentrations was substantially steeper than that of the autoantibody concentrations in immune-mediated conditions in which rituximab is effective, such as in rheumatoid arthritis. In addition, the reduction in IgG-subclass levels appeared to be specific for IgG4. The swift improvement of IgG4-RSD suggests that rituximab achieves its effects in IgG4-RSD by depleting the pool of B lymphocytes that replenish short-lived IgG4-secreting plasma cells.
C1 [Stone, John H.] Massachusetts Gen Hosp, Rheumatol Unit, Boston, MA 02114 USA.
[Khosroshahi, Arezou; Bloch, Donald B.; Deshpande, Vikram; Stone, John H.] Harvard Univ, Sch Med, Boston, MA USA.
RP Stone, JH (reprint author), Massachusetts Gen Hosp, Rheumatol Unit, Yawkey 2,55 Fruit St, Boston, MA 02114 USA.
EM jhstone@partners.org
NR 30
TC 210
Z9 237
U1 2
U2 19
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD JUN
PY 2010
VL 62
IS 6
BP 1755
EP 1762
DI 10.1002/art.27435
PG 8
WC Rheumatology
SC Rheumatology
GA 619LU
UT WOS:000279432500026
PM 20191576
ER
PT J
AU Elhassan, B
Warner, JJP
AF Elhassan, Bassem
Warner, Jon J. P.
TI Open Versus Arthroscopic Acromioclavicular Joint Resection Reply
SO ARTHROSCOPY-THE JOURNAL OF ARTHROSCOPIC AND RELATED SURGERY
LA English
DT Letter
C1 [Elhassan, Bassem] Mayo Clin, Dept Orthoped, Rochester, MN 55905 USA.
[Warner, Jon J. P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg,Harvard Shoulder Serv, Boston, MA USA.
RP Elhassan, B (reprint author), Mayo Clin, Dept Orthoped, Rochester, MN 55905 USA.
NR 0
TC 0
Z9 0
U1 1
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 0749-8063
J9 ARTHROSCOPY
JI Arthroscopy
PD JUN
PY 2010
VL 26
IS 6
BP 727
EP 728
DI 10.1016/j.arthro.2009.12.002
PG 3
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA 613AI
UT WOS:000278947600007
ER
PT J
AU Lehman, SJ
Massaro, JM
Schlett, CL
O'Donnell, CJ
Hoffmann, U
Fox, CS
AF Lehman, Sam J.
Massaro, Joseph M.
Schlett, Christopher L.
O'Donnell, Christopher J.
Hoffmann, Udo
Fox, Caroline S.
TI Peri-aortic fat, cardiovascular disease risk factors, and aortic
calcification: The Framingham Heart Study
SO ATHEROSCLEROSIS
LA English
DT Article
DE Obesity; Atherosclerosis; Calcium; Risk factors
ID VISCERAL ADIPOSE-TISSUE; COMPUTED-TOMOGRAPHY; VASCULAR-DISEASE;
PERICARDIAL FAT; ASSOCIATION; MEN; ATHEROSCLEROSIS; ADIPOCYTES;
COMMUNITY; OBESITY
AB Objective: Perivascular fat through the secretion of paracrine and pro-inflammatory mediators may play a role in obesity-mediated vascular disease. We sought to examine associations between adipose tissue depots immediately surrounding the thoracic aorta, metabolic risk factors, and vascular calcification.
Methods: In participants free of cardiovascular disease (CVD) from the Framingham Heart Study Offspring cohort who underwent computed tomography (n = 1067, mean age 59 years, 56.1% women), thoracic periaortic fat depots were quantified. Visceral abdominal tissue (VAT) and calcification of the thoracic and abdominal aorta were also measured.
Results: Peri-aortic fat depots were correlated with body mass index, waist circumference (WC), VAT (all p < 0.0001), hypertension (p = 0.007), low HDL (p < 0.0001), serum triglycerides (p < 0.0001), impaired fasting glucose (p = 0.005), and diabetes (p = 0.02). These associations generally remained significant after adjustment for BMI and WC (all p-values < 0.05), but not after VAT adjustment. Thoracic aortic fat was associated with thoracic calcification in models containing VAT (OR 1.31, 95% CI 1.01-1.71, p = 0.04), but was not significant after adjustment for CVD risk factors (OR 1.16, 95% CI 0.88-1.51, p = 0.30). Thoracic aortic fat, however, was associated with abdominal aortic calcification (OR 1.48, 95% CI 1.11-1.98, p = 0.008) and coronary artery calcification (OR 1.47, 95% CI 1.09-1.98, p = 0.001) even in models including CVD risk factors and VAT.
Conclusions: Thoracic peri-aortic fat is associated with measures of adiposity, metabolic risk factors, and coronary and abdominal aortic calcification. Published by Elsevier Ireland Ltd.
C1 [Lehman, Sam J.; Schlett, Christopher L.; Hoffmann, Udo] Massachusetts Gen Hosp, Dept Cardiac MR PET CT, Boston, MA 02114 USA.
[Lehman, Sam J.] Flinders Univ S Australia, Dept Cardiol, Adelaide, SA 5001, Australia.
[Massaro, Joseph M.] Boston Univ, Dept Math, Boston, MA 02215 USA.
[O'Donnell, Christopher J.; Fox, Caroline S.] Natl Heart Lung & Bloods Framingham Heart Study, Bethesda, MD USA.
[O'Donnell, Christopher J.; Fox, Caroline S.] Natl Heart Lung & Bloods Framingham Heart Study, Framingham, MA USA.
[Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol, Boston, MA 02115 USA.
[Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA.
RP Fox, CS (reprint author), 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA.
EM foxca@nhlbi.nih.gov
OI Massaro, Joseph/0000-0002-2682-4812
FU National Heart, Lung and Blood Institute's Framingham Heart Study
[N01-HC-25195]; National Heart Foundation of Australia; Royal Australian
College of Physicians Research and Education Committee
FX This work was supported by the National Heart, Lung and Blood
Institute's Framingham Heart Study (N01-HC-25195). Dr. Lehman is
supported by grants from the National Heart Foundation of Australia and
Royal Australian College of Physicians Research and Education Committee.
NR 26
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U2 1
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0021-9150
J9 ATHEROSCLEROSIS
JI Atherosclerosis
PD JUN
PY 2010
VL 210
IS 2
BP 656
EP 661
DI 10.1016/j.atherosclerosis.2010.01.007
PG 6
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 601CY
UT WOS:000278036800056
PM 20152980
ER
PT J
AU van Diepen, JA
Wong, MC
Guigas, B
Bos, J
Shoelson, SE
Rensen, PCN
Havekes, LM
Romijn, JA
Voshol, PJ
AF van Diepen, J. A.
Wong, M. C.
Guigas, B.
Bos, J.
Shoelson, S. E.
Rensen, P. C. N.
Havekes, L. M.
Romijn, J. A.
Voshol, P. J.
TI Hepatocyte-specific Inflammation Directly Enhances VLDL-triglyceride
Production in Mice
SO ATHEROSCLEROSIS SUPPLEMENTS
LA English
DT Meeting Abstract
CT 2nd International Symposium of Chylomicrons in Disease
CY JUN 02-05, 2010
CL Rotterdam, NETHERLANDS
SP BMS, Novo Nordisk, MSD, AMT
C1 [van Diepen, J. A.; Bos, J.; Rensen, P. C. N.; Havekes, L. M.; Romijn, J. A.; Voshol, P. J.] Leiden Univ, Dept Gen Internal Med Endocrinol & Metab Dis, Med Ctr, NL-2300 RA Leiden, Netherlands.
[Wong, M. C.] Leiden Univ, Dept Pulmonol, Med Ctr, NL-2300 RA Leiden, Netherlands.
[Guigas, B.] Leiden Univ, Dept Mol Cell Biol, Med Ctr, NL-2300 RA Leiden, Netherlands.
[Shoelson, S. E.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA.
[Shoelson, S. E.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
[Havekes, L. M.] TNO Qual Life, Dept Biomed Res, Leiden, Netherlands.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 1567-5688
J9 ATHEROSCLEROSIS SUPP
JI Atheroscler. Suppl.
PD JUN
PY 2010
VL 11
IS 1
MA 10
BP 69
EP 70
DI 10.1016/j.atherosclerosissup.2010.04.016
PG 4
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 599SI
UT WOS:000277933000023
ER
PT J
AU Lin, HW
Tierney, HT
Richmon, JD
Mark, EJ
Deschler, DG
AF Lin, Harrison W.
Tierney, Hien T.
Richmon, Jeremy D.
Mark, Eugene J.
Deschler, Daniel G.
TI Extrusion of embolization coils through the carotid artery in a radiated
neck
SO AURIS NASUS LARYNX
LA English
DT Article
DE Extrusion; Embolization; Radiation therapy; Head and neck cancer;
Carotid artery
ID MIGRATION; PSEUDOANEURYSM; ANEURYSM; STOMACH
AB Extrusion of embolization coils is an exceedingly rare event. We present and discuss a unique case of coil extrusion through the carotid artery into the pharyngeal soli tissue in the setting of soft tissue radionecrosis (STRN). A 55-year-old man with previous chemoradiation therapy presented with massive transoral hemorrhage. Control of the bleeding was accomplished by coil embolization of the right carotid artery system. The patient subsequently developed spiking fevers, and an exploration of the neck revealed coil extrusion through the common carotid artery and into the neck and pharynx. Although the incidence of coil extrusion in the head and neck is remarkably low, this complication must be considered in the heavily radiated neck and a high index of suspicion should be maintained in the setting of radionecrosis and signs and symptoms of systemic infection. Appropriate management requires early recognition and removal of foreign material with wound stabilization. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
C1 [Lin, Harrison W.; Tierney, Hien T.; Deschler, Daniel G.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA.
[Lin, Harrison W.; Tierney, Hien T.; Deschler, Daniel G.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA.
[Richmon, Jeremy D.] Johns Hopkins Univ Hosp, Dept Otolaryngol Head & Neck Surg, Baltimore, MD 21287 USA.
[Mark, Eugene J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
RP Lin, HW (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, 243 Charles St, Boston, MA 02114 USA.
EM harrison_lin@meei.harvard.edu
NR 15
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Z9 6
U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0385-8146
J9 AURIS NASUS LARYNX
JI Auris Nasus Larynx
PD JUN
PY 2010
VL 37
IS 3
BP 390
EP 393
DI 10.1016/j.anl.2009.07.001
PG 4
WC Otorhinolaryngology
SC Otorhinolaryngology
GA 581RV
UT WOS:000276542900024
PM 19709831
ER
PT J
AU Tsang, HWH
Leung, AY
Chung, RCK
Bell, M
Cheung, WM
AF Tsang, Hector W. H.
Leung, Ada Y.
Chung, Raymond C. K.
Bell, Morris
Cheung, Wai-Ming
TI Review on vocational predictors: a systematic review of predictors of
vocational outcomes among individuals with schizophrenia: an update
since 1998
SO AUSTRALIAN AND NEW ZEALAND JOURNAL OF PSYCHIATRY
LA English
DT Review
DE employment outcome; frequency; meta-analysis; rehabilitation;
schizophrenia
ID SEVERE MENTAL-ILLNESS; NEUROCOGNITIVE ENHANCEMENT THERAPY; RANDOMIZED
CONTROLLED-TRIAL; COGNITIVE-BEHAVIORAL THERAPY; OF-THE-LITERATURE;
SUPPORTED EMPLOYMENT; PSYCHIATRIC DISABILITIES; WORK THERAPY; FOLLOW-UP;
CLINICAL PREDICTORS
AB Objective: Predictors of employment outcomes of individuals with schizophrenia have continued to be studied over the past decade with implications for the development of vocational interventions to help the mentally ill get and keep jobs.
Methods: A total of 62 relevant studies since 1998 were systematically reviewed by means of meta-analysis and frequency counts. Frequency count allowed all 62 studies to be included, whereas the meta-analysis excluded studies with inadequate information but made it possible to estimate the magnitude of effects.
Results: Both methods resulted in similar findings. In contrast to an earlier review, cognitive functioning received overwhelming support as a significant predictor. Other significant predictors included education, negative symptoms, social support and skills, age, work history (previous history of successful employment), and rehabilitation service to restore community functioning and well-being by occupational therapists, psychiatrists, psychologists, social workers and other mental health professionals. Positive symptoms, substance abuse, gender and hospitalization history were found to be non-significant predictors. The frequency count did not support marital status as a significant predictor but the meta-analysis did.
Conclusions: This review highlights increasing sophistication in understanding the links between individual characteristics and functional impairments. It also suggests that more research is needed into other potentially important predictors that may be changeable and relate to recovery. These include attitudes and beliefs about disability payments and psychological processes such as self-stigmatization, negative beliefs, and social skills deficits for which intervention may be possible.
C1 [Tsang, Hector W. H.; Leung, Ada Y.; Chung, Raymond C. K.] Hong Kong Polytech Univ, Dept Rehabil Sci, Neuropsychiat Rehabil Lab, Hong Kong, Hong Kong, Peoples R China.
[Cheung, Wai-Ming] Univ Hong Kong, Fac Educ, Hong Kong, Hong Kong, Peoples R China.
[Bell, Morris] US Dept Vet Affairs, Rehabil Res & Dev Serv, New Haven, CT USA.
[Bell, Morris] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA.
RP Tsang, HWH (reprint author), Hong Kong Polytech Univ, Dept Rehabil Sci, Neuropsychiat Rehabil Lab, Hong Kong, Hong Kong, Peoples R China.
EM rshtsang@inet.polyu.edu.hk
NR 84
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U1 6
U2 33
PU INFORMA HEALTHCARE
PI NEW YORK
PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA
SN 0004-8674
J9 AUST NZ J PSYCHIAT
JI Aust. N. Z. J. Psych.
PD JUN
PY 2010
VL 44
IS 6
BP 495
EP 504
PG 10
WC Psychiatry
SC Psychiatry
GA 612MK
UT WOS:000278902600001
PM 20482409
ER
PT J
AU Gurcan, HM
Keskin, DB
Ahmed, AR
AF Gurcan, Hakan M.
Keskin, Derin B.
Ahmed, A. Razzaque
TI Information for healthcare providers on general features of IGIV with
emphasis on differences between commercially available products
SO AUTOIMMUNITY REVIEWS
LA English
DT Review
DE Intravenous immunoglobulin; Biologic properties
ID INTRAVENOUS IMMUNOGLOBULIN THERAPY; ACUTE-RENAL-FAILURE;
OF-THE-LITERATURE; IMMUNE GLOBULIN; AUTOIMMUNE-DISEASES; GAMMA-GLOBULIN;
NATURAL AUTOANTIBODIES; INFECTIOUS-DISEASES; PEMPHIGUS-VULGARIS; PRION
REDUCTION
AB Objective: Intravenous immunoglobulin (IGIV) has provided an essential replacement therapy for primary and secondary immunodeficiencies patients and prophylaxis of infectious diseases in them. It is also used in several autoimmune and chronic inflammatory disorders. An overview of IGIV with information on several commercially available IGIV products is discussed.
Data Sources: Medline databases and literature provided by the manufacturer for each product presented in the manuscript.
Study Selection: From the vast body of information on IGIV, only those studies were selected that were pertinent to general features of IGIV (as presented below) or information provided by the manufacturer that facilitated comparing one product to the other.
Data Extraction: Data was extracted on production, and purification procedures, removal of infectious agents, physical and biochemical properties and issues of safety. Data was extracted only for products available in the US.
Data Synthesis: IGIV is prepared using pooled plasma. The purification of IGIV is a complex and multi-step process. There is a reciprocal relationship between the purity of IgG in the product and the recovery rate from the total plasma. It is quite possible that some of the biological mediators of the inflammatory and immune systems may be present in trace amounts. Screening and removal of blood borne pathogens is necessary and there are several different techniques available. The specifics of the administration are often variable and no consistent pattern or protocol has been used. When limited dosages are required IGIV may be administered subcutaneously. The side effects associated with IGIV are usually mild and self-limiting.
Conclusion: There are differences in products produced by different manufacturers. The current data does not provide sufficient detail or information to be able to make specific recommendations for the use of a given commercial preparation in a specific disease state. The use of IGIV is associated with certain common and uncommon side effects. The identification of risk factors that might predispose a patient to developing them have been studied and reported. In choosing a IGIV preparation the user may avoid features that may predispose to certain side effects. Equally important is monitoring of patients during and after the IGIV therapy. (C) 2010 Elsevier B.V. All rights reserved.
C1 [Gurcan, Hakan M.; Ahmed, A. Razzaque] New England Baptist Hosp, Dept Med, Ctr Blistering Dis, Boston, MA USA.
[Keskin, Derin B.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Ahmed, AR (reprint author), 70 Parker Hill Ave,Suite 208, Boston, MA 02120 USA.
EM aramanuscript@msn.com
NR 83
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U1 0
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1568-9972
J9 AUTOIMMUN REV
JI Autoimmun. Rev.
PD JUN
PY 2010
VL 9
IS 8
BP 553
EP 559
DI 10.1016/j.autrev.2010.03.003
PG 7
WC Immunology
SC Immunology
GA 621DP
UT WOS:000279554600006
PM 20346419
ER
PT J
AU Nappi, CM
Nappi, CM
Drummond, SPA
Thorp, SR
McQuaid, JR
AF Nappi, Carla M.
Nappi, Carla M.
Drummond, Sean P. A.
Thorp, Steven R.
McQuaid, John R.
TI Effectiveness of Imagery Rehearsal Therapy for the Treatment of
Combat-Related Nightmares in Veterans
SO BEHAVIOR THERAPY
LA English
DT Article
ID POSTTRAUMATIC-STRESS-DISORDER; SEXUAL ASSAULT SURVIVORS; SLEEP
DISTURBANCES; FOLLOW-UP; PTSD; TRIAL; SAMPLE
AB Imagery Rehearsal Therapy (IRT) has been shown to be efficacious in reducing nightmares, but the treatment has not been well-studied in veterans. The effectiveness of IRT was assessed from a chart review of veterans seeking outpatient treatment for chronic, trauma-related nightmares. Of those offered IRT, veterans who completed a full course of treatment for PTSD in the past year were more likely to initiate treatment. However, completion of IRT was not related to previous treatment, demographic variables, or nightmare severity reported at the first treatment session. Treatment completers reported significant reductions in nightmare frequency and intensity, severity of insomnia, and subjective daytime PTSD symptoms. Insomnia and PTSD symptoms, on average, were below clinical cutoffs following treatment, and 23% of patients showed a complete treatment response (<= 1 nightmare/week). Findings suggest IRT may be an effective short-term treatment for nighttime and daytime PTSD symptoms among veterans who complete a full course of treatment.
C1 [Drummond, Sean P. A.] Univ Calif San Diego, Lab Sleep & Behav Neurosci, San Diego, CA 92161 USA.
[Nappi, Carla M.; Nappi, Carla M.; Drummond, Sean P. A.; Thorp, Steven R.] Vet Affairs San Diego Healthcare Syst, San Diego, CA 92161 USA.
[McQuaid, John R.] San Francisco VA Med Ctr, San Francisco, CA USA.
RP Drummond, SPA (reprint author), Univ Calif San Diego, Lab Sleep & Behav Neurosci, 3350 La Jolla Village Dr,MC 151B,Bldg 13,3rd Floo, San Diego, CA 92161 USA.
EM drummond@ucsd.edu
NR 26
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U1 3
U2 13
PU ASSOC ADV BEHAVIOR THERAPY
PI NEW YORK
PA 305 7TH AVE #16A, NEW YORK, NY 10001-6008 USA
SN 0005-7894
J9 BEHAV THER
JI Behav. Therapy
PD JUN
PY 2010
VL 41
IS 2
BP 237
EP 244
PG 8
WC Psychology, Clinical
SC Psychology
GA 594PI
UT WOS:000277549200008
PM 20412888
ER
PT J
AU Delaney, M
Ballen, KK
AF Delaney, Meghan
Ballen, Karen K.
TI The role of HLA in umbilical cord blood transplantation
SO BEST PRACTICE & RESEARCH CLINICAL HAEMATOLOGY
LA English
DT Article
DE umbilical cord blood; transplantation; FBA
ID VERSUS-HOST-DISEASE; HEMATOPOIETIC-CELL TRANSPLANTATION; DONOR
BONE-MARROW; UNRELATED DONORS; CLASS-I; HEMATOLOGIC MALIGNANCIES;
PLACENTAL-BLOOD; ACUTE-LEUKEMIA; OUTCOMES; RECIPIENTS
AB Transplantation with umbilical cord blood for haematological malignancy and other diseases has increased over the last two decades. The parameters that affect clinical outcome have been intensely studied in this relatively new clinical setting. Although originally thought to not be critical for transplant success, human leucocyte antigen (HLA) matching of the patient and cord blood donor is now considered one of the most important indicators of outcome. Because clinical studies of cord-blood transplantation are often not large enough to detect subtle differences, the HLA matching algorithm in cord blood transplantation (CBT) is not clearly defined. This article will focus on HLA matching in CBT in relation to engraftment, graft versus host disease, relapse and survival. Outstanding questions in the field, such as the contribution of HLA-C, -DQ as well as the appropriate level of HLA matching and cord unit selection will be discussed. (C)10 Elsevier Ltd. All rights reserved.
C1 [Delaney, Meghan] Puget Sound Blood Ctr, Seattle, WA 98104 USA.
[Ballen, Karen K.] Massachusetts Gen Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02114 USA.
RP Delaney, M (reprint author), Puget Sound Blood Ctr, 921 Terry Ave, Seattle, WA 98104 USA.
EM meghand@psbc.org; kballen@partners.org
NR 42
TC 8
Z9 8
U1 0
U2 1
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1521-6926
J9 BEST PRACT RES CL HA
JI Best Pract. Res. Clin. Haematol.
PD JUN
PY 2010
VL 23
IS 2
BP 179
EP 187
DI 10.1016/j.beha.2010.05.003
PG 9
WC Hematology
SC Hematology
GA 659II
UT WOS:000282559800003
PM 20837329
ER
PT J
AU Schwab, P
Lipton, S
Kerr, GS
AF Schwab, Pascale
Lipton, Sarah
Kerr, Gail S.
TI Rheumatologic sequelae and challenges in organ transplantation
SO BEST PRACTICE & RESEARCH IN CLINICAL RHEUMATOLOGY
LA English
DT Article
DE transplant; gout; osteoporosis; avascular necrosis; graft-versus-host
disease; calcineurin inhibitor pain syndrome
ID VERSUS-HOST-DISEASE; STEM-CELL TRANSPLANTATION; CARPAL-TUNNEL-SYNDROME;
CHRONIC-RENAL-FAILURE; DISTAL LIMB SYNDROME; BONE LOSS;
LIVER-TRANSPLANTATION; KIDNEY-TRANSPLANT; CARDIAC TRANSPLANTATION; LUNG
TRANSPLANTATION
AB Despite the increasing success of transplantation, graft recipients experience a high burden of musculoskeletal symptoms that may hinder quality of life. Post-transplant musculoskeletal problems may result from sequelae of the organ dysfunction that indicated the transplant or from the subsequent anti-rejection therapy. Rheumatology consultants need to be familiar with the spectrum of musculoskeletal syndromes presenting in these unique patients and their appropriate treatment in the context of complex drug regimens and immunosuppression. Published by Elsevier Ltd.
C1 [Schwab, Pascale] Oregon Hlth & Sci Univ, Portland Vet Affairs Med Ctr, Div Arthrit & Rheumat Dis, Portland, OR 97239 USA.
[Lipton, Sarah] Portland VA Med Ctr, Dept Hosp & Specialty Med, Portland, OR 97239 USA.
[Kerr, Gail S.] Georgetown Univ, Vet Affairs Med Ctr, Rheumatol Sect, Washington, DC 20422 USA.
[Kerr, Gail S.] Howard Univ Hosp, Washington, DC 20422 USA.
RP Schwab, P (reprint author), Oregon Hlth & Sci Univ, Portland Vet Affairs Med Ctr, Div Arthrit & Rheumat Dis, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA.
EM schwabp@ohsu.edu; sarah.lipton@va.gov; Gail.kerr@va.gov
NR 95
TC 0
Z9 1
U1 1
U2 6
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1521-6942
J9 BEST PRACT RES CL RH
JI Best Pract. Res. Clin. Rheumatol.
PD JUN
PY 2010
VL 24
IS 3
BP 329
EP 340
DI 10.1016/j.berh.2009.12.011
PG 12
WC Rheumatology
SC Rheumatology
GA 618QM
UT WOS:000279370800004
PM 20534367
ER
EF