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 TC 27 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 TC 11 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 TC 23 Z9 27 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 TC 5 Z9 5 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 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 TC 27 Z9 27 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 TC 18 Z9 18 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 TC 7 Z9 11 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 TC 3 Z9 3 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 TC 32 Z9 34 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 TC 24 Z9 25 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 TC 1 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 TC 24 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 TC 11 Z9 11 U1 0 U2 1 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD 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 TC 16 Z9 17 U1 0 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 TC 26 Z9 28 U1 0 U2 7 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 TC 21 Z9 21 U1 0 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 TC 22 Z9 23 U1 3 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 TC 1 Z9 1 U1 2 U2 2 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 TC 10 Z9 10 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 Z9 76 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. 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[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 TC 111 Z9 112 U1 0 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 TC 135 Z9 142 U1 0 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 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 TC 194 Z9 199 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 Z9 7 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 TC 489 Z9 522 U1 25 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 TC 156 Z9 157 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 TC 31 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 TC 20 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 TC 8 Z9 8 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 TC 4 Z9 4 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 TC 20 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 TC 32 Z9 36 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 TC 21 Z9 21 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 TC 19 Z9 19 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 TC 4 Z9 4 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 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 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 TC 5 Z9 5 U1 1 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. NR 28 TC 72 Z9 79 U1 1 U2 10 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). NR 24 TC 19 Z9 20 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD 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 TC 39 Z9 41 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD 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 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD 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 TC 10 Z9 10 U1 1 U2 4 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. NR 5 TC 2 Z9 2 U1 0 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 TC 11 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 TC 140 Z9 142 U1 2 U2 8 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 Z9 17 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 TC 34 Z9 34 U1 1 U2 14 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 TC 12 Z9 12 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). NR 63 TC 32 Z9 33 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD 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 TC 128 Z9 133 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 TC 104 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 Z9 85 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 TC 20 Z9 21 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 TC 63 Z9 65 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 Z9 33 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 TC 159 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 TC 23 Z9 24 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 TC 18 Z9 18 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 TC 11 Z9 11 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] NR 12 TC 22 Z9 25 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 TC 20 Z9 20 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. NR 39 TC 8 Z9 8 U1 0 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. NR 92 TC 35 Z9 37 U1 2 U2 11 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). NR 61 TC 24 Z9 24 U1 0 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). NR 47 TC 23 Z9 24 U1 0 U2 0 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 TC 42 Z9 44 U1 0 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 TC 9 Z9 9 U1 0 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 TC 15 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 TC 23 Z9 24 U1 0 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 TC 82 Z9 83 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 TC 346 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 TC 8 Z9 8 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 TC 20 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 Z9 26 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 TC 57 Z9 63 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 TC 79 Z9 96 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 TC 75 Z9 79 U1 0 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 TC 6 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 TC 81 Z9 81 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 TC 23 Z9 24 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 TC 22 Z9 22 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